Imaging of Dementia & Neurodegeneration

                  1938.     Degeneration of Subcortical White Matter in Alzheimer's Disease: Atlas-Based Automated Mapping and Its Diagnostic Utility Based on Multi-Variate Model

Takashi Yoshiura¹, Akio Hiwatashi¹, Koji Yamashita¹, Hironori Kamano¹, Yukihisa Takayama¹, Eiki Nagao¹, Tuvshinjargal Dashjamts¹, Hiroshi Honda¹

¹Department of Clinical Radiology, Kyushu University, Fukuoka, Japan

We measured mean diffusivities (MD) in subcortical white matter (WM) in 78 different cortical regions using an atlas-based mapping method in 33 patients with Alzheimer�fs disease (AD) and 28 healthy control subjects to determine whether the topographical pattern of the diffusion abnormalities can be used to diagnose AD. Uni-variate analysis in which discrimination was attempted based on MD in the single region resulted in the accuracy of 88.5 %. Multi-variate analysis in which a linear discriminant function based on MDs from multiple cortical regions increased the accuracy up to 96.7 %.

                  1939.     Deterioration of Abstract Reasoning Ability in MCI and Alzheimer's Disease: Correlation with Local Gray Matter Volume Loss Using DARTEL VBM Analysis

Takashi Yoshiura¹, Akio Hiwatashi¹, Koji Yamashita¹, Hironori Kamano¹, Yukihisa Takayama¹, Eiki Nagao¹, Tuvshinjargal Dashjamts¹, Hiroshi Honda¹

¹Department of Clinical Radiology, Kyushu University, Fukuoka, Japan

We estimated brain regions whose damages are responsible for the deterioration in abstract reasoning ability measured by Raven�fs colored progressive matrices (CPM) in 37 patients with Alzheimer�fs disease (AD) (n=19) and mild cognitive impairment (MCI) (n=18) using VBM with non-linear registration based on DARTEL algorithm. A multiple regression analysis was used to map the regions where gray matter volumes were correlated with CPM scores. Significant correlations were seen in 14 regions with the strongest correlation in the left middle frontal gyrus. Results suggested that damages of multiple regions are responsible for deterioration of abstract reasoning ability in AD and MCI.

                  1940.     MRI Shape Analysis Predicts Progression from Mild Cognitive Impairment to Alzheimer's Disease

Donald Louis Collins¹, Vladimir Fonov¹, Simon Duchesne^2,3

¹McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, QC, Canada; ²Centre de Recherche Université Laval - Robert Giffard, Quebec, Canada; ³Dépt. de Radiologie, Faculté de Médecine, Université Laval, Quebec, Canada

A method is presented to predict conversion from mild cognitive impairment to Alzheimer’s disease using shape analysis of baseline T1w MRI data.  Using 100 MCI subjects from the ADNI database, PCA analysis of deformation fields required to register to a minimum deformation template is used to build a shape model of the aging brain. LDA of the eigenvalues is used to build a classifier to identify converters and non-converters.  Testing with 100 additional MCI subjects demonstrates accuracies of 65% at 12 months and 64% at 24 months. Adding baseline HC volume increases accuracy to 73% and 69%, respectively.

                  1941.     Ultra-High Field MRS in Healthy Aging and Early Cognitive Impairment

Mary Charlotte Stephenson¹, Mirjam I. Schubert², Maryam Abaei², Antonio Napolitano², Rob G. Jones³, Peter G. Morris¹, Dorothee P. Auer²

¹SPMMRC, School of Physics and Astronomy, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom; ²Academic Radiology, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom; ³School of Community Healthy Sciences, University of Nottingham, Nottingham, Nottinghamshire

Metabolic profiles in the posterior cingulate cortex (PCC) have been found to be altered due to healthy aging and in many neurodegenerative diseases. The purpose of this study was to use increased spectral resolution and signal, available at higher field, to measure changes in the PCC metabolic profile due to healthy aging and cognitive impairment. Atrophy corrected levels of N-acetyl aspartate, glutamate and aspartate were found to significantly decrease with healthy aging. Levels of phosphocreatine were greatly reduced in patients with cognitive impairment, supporting a crucial role for Creatine Kinase dysfunction in dementia.

                  1942.     Cerebral Blood Flow in Alzheimer's Disease by Arterial Spin Labeling QUASAR

HKF Mak¹, Queenie Chan², Zhipeng Zhang¹, Esben Petersen³, Deqiang Qiu¹, Xavier Golay⁴, Leung-Wing Chu⁵

¹Diagnostic Radiology, University of Hong Kong, Hong Kong, Hong Kong; ²Philips Healthcare; ³Clinical Imaging Research Centre, National University of Singapore, Singapore, Singapore; ⁴UCL Institute of Neurology, Univeristy College of London, United Kingdom; ⁵Medicine, University of Hong Kong, Hong Kong

Arterial Spin Labeling MRI is a non-invasive method in studying cerebral blood flow, which can be used as an indirect marker of glucose metabolism. In our local Chinese cohort of 13 Alzheimer's disease (mean age- 76.3, MMSE- 16.3) and 15 cognitively normal elderly adults (mean age- 70.8, MMSE- 28.4), QUASAR sequence showed impaired cerebral blood flow in middle & posterior cingulate, bilateral inferior frontal, bilateral superior frontal, right inferior parietal and left superior temporal gyri in AD as compared to controls. This distribution of perfusion impairment is characteristic of moderate Alzheimer’s disease, analogous to regional hypometabolism in Positron Emission Tomography.

                  1943.     Co-Analysis of Structural Imaging and DTI in Alzheimer's Disease

Valerie A. Cardenas^1,2, Duygu Tosun^1,2, Kristine Yaffe, ^2,3, Bruce Miller⁴, Norbert Schuff^1,2, Michael W. Weiner^1,2

¹Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States; ²San Francisco VA, San Francisco, CA, United States; ³Neurology and Psychiatry, UCSF, San Francisco, CA, United States; ⁴Memory and Aging Clinic, UCSF, San Francisco, CA, United States

A voxel-wise co-analysis of structural imaging and DTI is presented and compared to analyses with a single modality only, to determine whether a multi-modality analysis detects effects due to Alzheimer's disease with greater sensitivity. Results show that co-analysis with FA does not detect greater AD-related disease than structural analysis alone.

                  1944.     Parental History of Alzheimer Disease Predicts Abnormal White Matter in Cognitively Normal Elderly Individuals

Joseph Mettenburg¹, David N. Daniels¹, Beau Ances², Huiling Peng², Joshua Shimony¹, Abraham Z. Snyder¹, John C. Morris², Mark A. Mintun¹, Tammie L.S. Benzinger³

¹Mallinckrodt Institute of Radiology, Washington University in Saint Louis; ²Neurology, Washington University in Saint Louis; ³Mallinckrodt Institute of Radiology, Washington University in Saint Louis, St. Louis, MO, United States

DT-MRI was performed on cognitively normal adults with and without a family history of dementia of the Alzheimer’s type (DAT).  Regional differences were identified in the corpus callosum and parietal white matter in those individuals with confirmed parental history of DAT.  These findings support the hypothesis that white matter abnormalities precede the clinically apparent onset of dementia, representing either early pathophysiological changes or fundamental differences in white matter integrity which may place individuals at risk for subsequent development of Alzheimer Disease.

                  1945.     Discrimination of Alzheimer’s Disease from Cognitively Healthy Individuals: An Arterial Spin Labeling MRI Study

Mike P. Wattjes¹, Nelleke Tolboom², Menno Schoonheim¹, Jose Maria Garcia-Santos¹, Joost P. Kuijer¹, Bart N. M. van Berckel³, Philip Scheltens², Frederik Barkhof¹, Ernesto J. Sanz-Arigita¹

¹Dept. of Radiology, VU University Medical Center, Amsterdam, Netherlands; ²Dept. of Neurology, VU University Medical Center; ³Dept. of Nuclear Medicine, VU University Medical Center

These specific perfusion patterns measured by ASL-MRI suggest fundamental differences in the brain perfusion between AD patients and cognitively healthy subjects and could contribution to the diagnoses of AD-related dementia.

                  1946.     Resting State Functional Patterns in AD and Their Correlation with Regional Amyloid-β Distribution.

Ernesto Sanz-Arigita¹, Nelleke Tolboom², Jolanda Boverhoff², A.A. Lammertsma², R. Boellaard², M. Yaqub², A.D. Windhorst², Cornelius S. Stam³, Philip Scheltens⁴, Frederik Barkhof⁵, Bart van Berckel²

¹Radiology, VUmc, Amsterdam, North Holland, Netherlands; ²Nuclear Medicine and PET Research, VUmc, Amsterdam, Netherlands; ³Neurophysiology, VUmc, Amsterdam, Netherlands; ⁴Neurology, VUmc, Amsterdam, Netherlands; ⁵Radiology, VUmc, Amsterdam, Netherlands

Alzheimer-related differences in basal functional brain networks are likely be related to the regional distribution of neuropathology. To explore this relationship, we have scanned the same population of AD patients and age-matched controls both with fMRI in resting state condition and PET, employing two different amyloid-b tracers: 11C-PIB reveals the distribution of neurofibrillary tangles and 18F-FDDNP binds predominantly to amyloid plaques. The functional networks affected in AD, and the distribution of neuropathology largely overlaps. We will demonstrate the specific relationship between either type of amyloid pathology and particular functional networks.

                  1947.     Pulsed Arterial Spin Labeling Perfusion in Healthy Aging and Early Dementia

Christine Preibisch¹, Annette Förschler¹, Afra Wohlschläger¹, Christian Sorg², Timo Grimmer², Hans Förstl², Alexander Kurz², Claus Zimmer¹, Panagiotis Alexopoulos²

¹Abteilung für Neuroradiologie, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; ²Klinik und Poliklinik für Psychiatrie und Psychotherapie, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany

Problem: PASL was used to study cerebral perfusion changes in patients with MCI and AD. Methods: Resting CBF maps were obtained from 16 young (30±10a) and 15 elderly (65±5a) cognitively normal controls, 13 patients with MCI (69±9a) and 7 patients with mild dementia in AD (70.9±11.2a). Results: Hypoperfusion was detected in parietal cortex and right angular gyrus when patients were compared to controls. A significant perfusion decrease in parietal cortex and left caudate was also detected in elderly compared to young controls. Conclusion: This suggests that PASL is capable to investigate the transition from normal ageing to dementia.

                  1948.     Fully-Automated MRI Quantification of Lateral-Ventricle Volume and Volume-Change in Patients with Alzheimer’s Disease

Zografos Caramanos^1,2, Vladimir S. Fonov³, Jacqueline T. Chen, ^2,3, Simon J. Francis, ^2,3, Alexandre Carmel-Veilleux^3,4, Sridar Narayanan, ^2,3, D Louis Collins³, Douglas L. Arnold, ^2,3

¹McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec , Canada; ²NeuroRx Research, Montreal, Quebec, Canada; ³McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; ⁴NeuroRx Research, Montreal, Quebec , Canada

Precise and accurate quantification of the volume, and longitudinal change in volume, of the lateral ventricles (LV) based on MRI data is an important goal in understanding the natural progression of neurodegenerative disorders such as Alzheimer’s disease (AD) and multiple sclerosis.  In the present study, we provide evidence from 270 AD patients for the accuracy of a novel, fully-automated, MRI-based technique for LV segmentation.  Furthermore, we provide preliminary evidence (from a subset of 33 of these patients) for the validity and precision of two novel, fully-automated, MRI-based techniques for the estimation of longitudinal change in LV volume.

                  1949.     A Study of APOE and Cerebral Perfusion in Adult Offspring of Patients with Alzheimer's Dementia Using Dynamic Susceptibility Contrast MRI

Rachel DiAnne McKinsey¹, Zhifei Wen¹, Alan McMillian¹, Beth Meyerand¹, Sterling Johnson², Sean Fain^1,3, Cindy Carlsson²

¹Medical Physics, University of Wisconsin-Madison, Madison, WI, United States; ²GRECC, Veteran Administration Hospital, Madison, WI, United States; ³Radiology, University of Wisconsin-Madison, Madison, WI, United States

APOE and vascular dysfunction are associated with increased risk of AD.  Changes in perfusion have been identified in APOE carriers verse non-carriers. The application of DSC perfusion with intravenous gadolinium contrast injection to investigate perfusion changes in AD has the ability to provide  CBF, CBV, and MTT perfusion maps. We investigated the ability of DSC MRI to measure CBV, CBF, and MTT changes in non-demented children with increased risk for AD due to one or more risk factors: APOE and/or family history. 

                  1950.     Alteration of Integrity and Patterns of the Memory Modules in Mild Cognitive Impairment and Alzheimer's Disease

Guangyu Chen¹, Piero Antuono², Shi-Jiang Li¹

¹Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States; ²Neurology, Medical College of Wisconsin, Milwaukee, WI, United States

We tested a hypothesis that the integrity and organization patterns of specific modules (HIP-TP) responsible for memory processing are altered in Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) subjects, in comparison with cognitively normal (CN) subjects. HIP-TP in CN is very well organized and has highly directed connected bilateral symmetric regions, but the MCI and AD HIP-TP module have fewer directed left and right connections, and the modules are hardly symmetric and organized. There is a potential that patterns of the HIP-TP modules could be employed to distinguish MCI subjects from CN subjects.

                  1951.     Dynamic Changes in Causal Strength in Memory Encoding Networks in Alzheimer’s Disease  Detected by Granger Causality Analysis

Guangyu Chen¹, B. Douglas Ward¹, Shi-Jiang Li¹

¹Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States

A quantitative Granger causality analysis, which can measure the causal strength among different time series, was employed to identify and quantify the directional hippocampus and default model network in cognitively normal subjects, and detect the changes in the directional network in AD patients. Interestingly in AD subjects, the functional afferents of parahippocampal gyrus is significantly decreased but the efferents of that are increased. And the abnormal network are correlated with abnormal behaviors.

                  1952.     Diffusion Tensor Imaging in Patients with Alzheimer’s Disease and Mild Cognitive Impairment

Sidy Fall¹, Souraya El Sankari², Roger Bouzerar³, Bertille Perin⁴, Marc-Etienne Meyer⁵, Olivier Baledent³

¹Imaging and Biophysics, University Hospital , Amiens, Picardie, France; ²Institute of Neuroscience, Cliniques Universitaires Saint-Luc, Brussels, Belgium; ³Imaging and Biophysics, University Hospital, Amiens, Picardie, France; ⁴Neurology , University Hospital, Amiens, Picardie, France; ⁵Nuclear Medicine, University Hospital, Amiens, Picardie, France

We used DTI to investigate inferior fronto-occipital fasciculus (IFO) alterations in patients with Alzheimer’s disease and Mild Cognitive Impairment (MCI). Within each group, we compared DTI parameters between the two hemispheres in IFO. We found no differences in DTI parameters between the two patients groups. Our results reveal that the longitudinal and radial diffusivities, fractional anisotropy and apparent diffusion coefficient were significantly higher on the right lobe than on the left lobe in AD group. While, Within the MCI group, only FA and radial diffusivity were higher on the right lobe than on the left lobe.

                  1953.     Association of White Matter Hyperintensities with White Matter Changes in Alzheimer's Disease as Studied by DTI

Liya Wang¹, Felicia C. Goldstein², Hui Mao¹

¹Radiology and Emory Center for Systems Imaging, Emory University School of Medicine, Atlanta, GA, United States; ²Neurology, Emory University School of Medicine, Atlanta, GA, United States

White matter hyperintensities (WMH) provide an additive effect is considered to be a risk factor of Alzheimer¡¯s disease (AD).  We investigated which DTI indices: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (DR) and axial diffusivity (DX) values were more sensitive to differentiate AD from normal control and how different levels of WMH may contribute to AD in specific areas of the white matter. FA and DR were helpful to discriminate AD with different grade of WMH.  Different level WMH contributed AD in different regions and extent. The increased DR may provide measurement of demyelination of AD in pathology.

                  1954.     Reduced Regional Fractional Anisotropy in Cognitively Normal Individuals with Biochemical and Imaging Evidence of Cerebral Amyloid Deposition

Joseph Mettenburg¹, David N. Daniels¹, Yvette I. Sheline, ¹², Beau Ances³, Huiling Peng³, Abraham Z. Snyder¹, John C. Morris³, Mark A. Mintun¹, Tammie L.S. Benzinger⁴

¹Mallinckrodt Institute of Radiology, Washington University in Saint Louis; ²Psychiatry, Washington University in Saint Louis; ³Neurology, Washington University in Saint Louis; ⁴Mallinckrodt Institute of Radiology, Washington University in Saint Louis, St. Louis, MO, United States

Amyloid plaque deposition in the brain is one of the key pathological hallmarks of Alzheimer’s disease.  Recently, CSF amyloid beta42 peptide levels and PET scans using C-11 Pittsburgh Compound B (PIB) have been established as potential biomarkers for dementia of the Alzheimer’s type (DAT).  Using DTI, we evaluated white matter microstructure in subjects with and without established DAT and identified differences in both the corpus callosum and precuneus.  The same white matter findings were identified in non-demented subjects with positive CSF and PIB-PET, suggesting that microstructural abnormalities in white matter integrity may precede cognitive changes in DAT.

                  1955.     White Matter Disruption and Its Relationship with Cognitive Function and Cortical Atrophy in Alzheimer’s Disease

Hao Huang¹, Xin Fan¹, Kristin Martin-Cook², Guanghua Xiao³, Laura Lacritz⁴, Myron Weiner⁴, Roger Rosenberg²

¹Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States; ²Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, United States; ³Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States; ⁴Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States

The purpose of this study is to find an effective white matter biomarker of Alzheimer’s disease (AD) which may indicate disease severity and progression. In this study, DTI and T1 weighted images were acquired from 38 subjects (20 AD, 18 controls). We surveyed all white matter tracts by labeling of the ICBM-DTI-81 digital atlas and correlated FA values of individual white matter tracts with cognitive testing score and cortical atrophy map respectively. The correlation analyses show that tracts in the limbic system, namely fornix and cingulum, are the most sensitive tract to cognitive testing scores and cortical atrophy.

                  1956.     Quantitative 7T Relaxographic, Volumetric and DCE Assessment of Thalamic Changes in Early Alzheimer’s Disease

Valerie C. Anderson¹, David P. Lenar¹, Joseph F. Quinn², William J. Woodward³, Jeffrey A. Kaye², William D. Rooney³

¹Neurological Surgery, Oregon Health & Science University, Portland, OR, United States; ²Neurology, Oregon Health & Science University, Portland, OR, United States; ³Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States

Longitudinal water proton (¹H₂O) relaxation time constants (T₁) are strongly associated with macromolecular volume fraction. Here, we report that ¹H₂O T₁ values are increased in the thalamus of subjects with early AD compared to age-matched, cognitively normal controls. Further, we find that the increased ¹H₂O T₁ values in early AD reflect, at least in part, neurodegenerative (macromolecular loss)  processes and that contributions to the increased ¹H₂O T₁ values from altered blood water content (via dilation or increased vessel density) are small.

                  1957.     Dementia Induces Correlated Reductions in White Matter Integrity and  Cortical Thickness: A Multivariate Neuroimaging Study with Sparse  Canonical Correlation Analysis

Brian Avants¹, Phil Cook¹, Lyle Ungar¹, James Gee¹, Murray Grossman¹

¹University of Pennsylvania, philadelphia, PA, United States

We present a novel, unsupervised method, sparse canonical correlation analysis for neuroimaging (SCCAN), that automatically locates correlated sets of voxels in complementary imaging modalities. The method reveals significant and syndrome-specific cortical thickness-diffusion tensor imaging networks in two neurodegenerative diseases, AD and FTD. Subject diagnosis was confirmed by autopsy or CSF-biomarker ratios. The SCCAN summary correlates, in AD, with MMSE reduction and, in FTD, with reduced verbal fluency. Thus, SCCAN identifies disease-specific networks of effects in white matter and cortical thickness that appear in anatomy suspected to be involved in these diseases and that relate specifically to impaired cognitive processes.

                  1958.     Resting-State FMRI Contributes to Differentiate Patients with Dementia with Lewy Bodies from Those with Alzheimer's Disease

Barbara Basile¹, Mara Cercignani¹, Laura Serra², Roberta Perri³, Camillo Marra⁴, Lucia Fadda³, Carlo Caltagirone^3,5, Marco Bozzali²

¹Neuroimaging Laboratory, Santa Lucia Foundation, Rome , Italy, Italy; ²Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy, Italy; ³Clinical and Behavioural Neurology Laboratory, Santa Lucia Foundation, Rome, Italy, Italy; ⁴Department of Neurosciences, Catholic University of Rome, Roma, Italy, Italy; ⁵Department of Neurosciences , University of Torvergata, Rome, Italy, Italy

Resting-state fMRI was used to investigate changes of functional connectivity (FC) within specific resting-state networks (RSNs) in the presence of Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB) as compared to normal aging. Using ICA analysis, we identified 10 RSNs across subjects. AD patients revealed reduced FC in the posterior cingulate, within the default-mode-network. Conversely, DLB patients showed reduced FC in occipital areas, within the visual network. These findings respectively account for brain disconnection between medial temporal lobes and other association cortexes in the development of AD symptoms, and for occipital abnormalities potentially responsible for visual hallucinations in DLB.

                  1959.     On Using Optimized MRS Acquisitions for Improved Mild Cognitive Impairment Diagnosis

Ileana Hancu¹, John Cowan², Earl Zimmerman²

¹GE Global Research Center, Niskayuna, NY, United States; ²Albany Medical Center, Albany, NY, United States

Accurate and repeatable mI measurements may offer a simple means for diagnosing or monitoring treatment in mild cognitive impairment (MCI) patients. Unfortunately, such repeatable measurements are difficult to obtain in vivo. The current report investigates the capability of CPRESS to better separate MCI subjects from normal controls (NC’s). With only 12 subjects in each of the MCI and NC categories, p-values separating the two classes decrease from 0.03 to 0.002 when using CPRESS instead of a short TE PRESS sequence. The impact of more repeatable mI concentration measurements in diagnosing or monitoring MCI evolution or treatment is discussed.

                  1960.     Classification of AD, MCI and Controls Using Large-Scale Network Analysis

Gang Chen¹, Barney Douglas Ward¹, Chunming Xie¹, Zhilin Wu¹, Wenjun Li¹, Jennifer Jones², Malgorzata Franczak², Piero Antuono², Shi-Jiang Li¹

¹Department of Biophysics,, Medical College of Wisconsin, Milwaukee, WI, United States; ²Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, United States

There has been great interest in developing objective biologically based markers that can be used to predict risk, diagnose, stage, or track the course and treatment of dementia and other neurodegenerative diseases. Alzheimer disease (AD) is the most common form of dementia. Mild cognitive impairment (MCI) is a transitional state between normal aging and dementia, and is often considered a risk factor for AD. In this study, we employed resting-state MRI connectivity methods and the large-scale network analyses to discriminate between AD, MCI and healthy control subjects.

                  1961.     Investigating Parkinson’s Disease Using Rotating Frame MRI

Silvia Mangia¹, Timo Liimatainen², Igor Nestrasil³, Michael Garwood¹, Paul Tuite³, Dennis Sorce¹, Shalom Michaeli¹

¹CMRR - Dept. of Radiology, University of Minnesota, Minneapolis, MN, United States; ²Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for molecular Medicine, University of Kuopio, Kuopio, Finland; ³Dept. of Neurology, University of Minnesota, Minneapolis, MN, United States

Rotating frame relaxation (T1rho and T2rho) were measured under a variety of RF pulses (namely continuous-wave, and frequency swept pulses in the adiabatic and subadiabatic regime) on twenty one Parkinson's disease (PD) subjects at 4T. Results demonstrate that different RF pulses significantly modulate the rotating frame relaxations in the substantia nigra (SN), providing the opportunity to extract fundamental parameters of the system based on theoretical modeling of the relaxation channels. The greatest sensitivity to identify sub-regions of the SN was achieved by the so-called RAFF pulse, which combines T1rho and T2rho relaxation mechanisms. Measurements from ferritin samples were additionally performed.

                  1962.     Parkinson's Disease and Imaging of the Substantia Nigra Structure with 7.0T MRI

Dae-Hyuk Kwon¹, Hye-Jin Jeong¹, Se-Hong Oh¹, Jong-Min Kim², Syung-Yeon Park¹, Young-Bo Kim¹, Beom-Seok Jeon², Zang-Hee Cho¹

¹Neuroscience Research Institute, Gachon University of Medicine and Science, Incheon, Korea, Republic of; ²Movement Disorder Center, Seoul National University Hospital, Seoul, Korea, Republic of

T2* weighted MR image is influenced by iron deposition, so that SN shows up iron-related MRI contrast for all that SN is gray matter. Therefore T2* MR imaging shows great potential in PD study using ultra high field (UHF) 7.0T. And 3D T2* Gradient Echo (GE) sequence makes it possible to study a volumetric analysis and a structural morphometry for SN. This method is validated, despite the reduced SNR associated with fast imaging techniques. And 3D model of the SN shows quite well structural changes in PD case.

                  1963.     Perfusion Networks in Parkinson’s Disease Revealed Using Arterial Spin Labeling

Tracy R. Melzer^1,2, Richard Watts, ^1,3, Michael R. MacAskill^1,2, Ross Keenan⁴, Ajit Shankaranarayanan⁵, David C. Alsop⁶, Charlotte Graham^1,2, Leslie Livingston¹, John C. Dalrymple-Alford, ^1,7, Tim J. Anderson^1,2

¹Van der Veer Institute for Parkinson's and Brain Research, Christchurch, New Zealand; ²Medicine, University of Otago, Christchurch, New Zealand; ³Physics and Astronomy, University of Canterbury, Christchurch, New Zealand; ⁴Christchurch Radiology Group, Christchurch, New Zealand; ⁵GE Healthcare, Menlo Park, CA, United States; ⁶Beth Israel Deaconess Medical Center, Boston, MA, United States; ⁷Pyschology, University of Canterbury, Christchurch, New Zealand

Pseudo-continuous ASL was used to investigate cerebral blood flow in 44 Parkinson’s disease (PD) patients and 26 controls.  Principal component analysis produced a set of covariance patterns which were used to form a perfusion network that successfully distinguished PD from control.  The PD-related network was characterized by decreased perfusion in PD versus controls in bilateral posterior parietal-occipital regions, posterior medial cortices, precentral and bilateral middle frontal gyri, and left caudate.  Preserved perfusion occurred in bilateral globus pallidus.  This ASL-derived PD network provides a marker to objectively gauge disease severity and serves as a potential method to longitudinally track disease progression.

                  1964.     Abnormal Spontaneous Brain Activity in Early Parkinson's Disease Revealed by ALFF Analysis

Hong Yang¹, Xu-ning Zheng², Yu-feng Zang³, Yi-lei Zhao¹, Jue Wang³, Min-ming Zhang¹

¹Department of Radiology, First Affiliated Hospital of College of Medical Science, Zhejiang University, Hangzhou, Zhejiang, China; ²Department of Neurology, First Affiliated Hospital of College of Medical Science, Zhejiang University, Hangzhou, Zhejiang, China; ³State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China

Using a new biomarker, the amplitude of the low frequency fluct uation (ALFF), the current study is to explore the abnormal spontaneous neural activity of resting state in early PD. Ten early PD patients were compared with eleven gender- and age-matched controls. Data processing was performed using DPARS software. In this study, abnormal ALFF demonstrate that spontaneous neural activity in the resting state is changed in patients with early PD, furthermore, those abnormal neuronal activity should be considered in explaining findings in behavior deficits in early PD. This method is a potential tool to monitor the progression of PD.

                  1965.     Investigation of Brain Iron Content in Patients with Parkinson's Disease Using Phase and R₂^* Obtained with Multi Echo Susceptibility Weighted Imaging

Christian Denk¹, Samantha Palmer², Martin J. McKeown³, Alexander Rauscher¹

¹UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada; ²Brain Research Centre, Vancouver, BC, Canada; ³Pacific Parkinson's Research Centre, Vancouver, BC, Canada

The main pathologic feature of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra pars compacta (Snc). There is increasing evidence that iron-mediated oxidative stress via the Fenton reaction is responsible for this loss of neurons. Iron's paramagnetism leads to changes in the relaxation rates R1, R2 and R2* and the phase of susceptibility weighted images (SWI). The aim of this study was therefore to use multi echo SWI for the investigation of both phase and R2* relaxation in deep brain structures of patients with PD. The strongest correlation with phase to the UPDRS score of -0.5 was found in the medial SN pars compacta as well as the largest phase differences between PD patients and controls. A smaller correlation was found with R2*, which is in agreement with previous studies of cerebral R2* in patients with PD.

                  1966.     Susceptibility Mapping of the Substantia Nigra in Parkinson Patients at 7T

Andreas Schäfer¹, Derek VM. Ott¹, Almut Focke², Johannes Schwarz², Robert Turner¹, Sonja A. Kotz¹

¹Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; ²University Hospital Leipzig, Leipzig, Germany

Parkinson’s disease is the second most common neurodegenerative disorder in humans. It has been previously demonstrated that transverse relaxation times change in Parkinson patients, supporting pathological findings of increased iron content in the substantia nigra. However, relaxation time is a quite indirect measure of changes in iron concentration, and hard to quantify. Recent studies have used phase images to study neurodegenerative diseases, but this method has the disadvantage that field perturbation maps derived from phase data are non-local. Our study demonstrates that local susceptibility maps, directly indexing iron concentration, can be calculated from phase image data in Parkinson patients.

                  1967.     A Single-Center, Phase 1, Open Label,  Dosage-Escalation Study of Creatine Monohydrate in Subject with Amyotrophic Lateral Sclerosis

Eva-Maria Ratai^1,2, Nazem Atassi, ^2,3, Stuart Wallace, ^2,4, Jeffery Bombardier¹, David Greenblatt⁵, Merit Cudkowicz, ^2,3, Allitia Dibernardo, ^2,3

¹Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States; ²Harvard Medical School, Boston, MA, United States; ³Neurology, Massachusetts General Hospital, Charlestown, MA, United States; ⁴Psychiatry, Massachusetts General Hospital, Charlestown, MA, United States; ⁵Pharmacology & Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, United States

The purpose of this study was to evaluate the serum pharmacokinetics of orally administered creatine in subjects with ALS and to assess whether oral intake produces increased concentrations of creatine in the brain utilizing in vivo MR Spectroscopy.  Six ALS patients were enrolled in this open-label pilot study. Patients escalated weekly through 3 different dose levels. Creatine serum levels increased with daily use of 5, 10, 15 gm BID. MR Spectroscopy results are suggestive that creatine crosses the blood brain barrier when given at a high dose of 15 gm BID.  Furthermore, glutamine and glutamate levels decreased post treatment.

                  1968.     Cross-Sectional and Longitudinal Voxel-Based Relaxometry Study in ALS

Don Charles Bigler¹, Claire Flaherty-Craig², Yaman Aksu³, Byeong-Yeul Lee⁴, Kevin R. Scott², Helen E. Stephens², Jeffrey J. Vesek⁵, Jianli Wang⁵, Michele L. Shaffer⁶, Paul J. Eslinger^2,5, Zachary Simmons², Qing X. Yang^5,7

¹Psychiatry, Penn State Hershey Medical Center, Hershey, PA, United States; ²Neurology, Penn State Hershey Medical Center, Hershey, PA, United States; ³Electrical Engineering, Penn State University, State College, PA, United States; ⁴Bioengineering, Penn State Hershey Medical Center, Hershey, PA, United States; ⁵Radiology, Penn State Hershey Medical Center, Hershey, PA, United States; ⁶Public Health Sciences, Penn State Hershey Medical Center, Hershey, PA, United States; ⁷Neurosurgery, Penn State Hershey Medical Center, Hershey, PA, United States

The objectives of this study were to identify regions of T2 change in ALS cross-sectionally using VBR and determine the relationship of T2 with time, disease duration, and disease severity longitudinally.  T1-weighted and multi spin-echo images were acquired from 12 control and 12 ALS at baseline, 7 at 6 months, and 6 at 12 months.  After post-processing clusters of significant T2 increase cross-sectionally were found in frontal and temporal areas.  Longitudinally, increased T2 was associated with disease duration mainly in frontal areas.  Increased T2 in ALS is likely due to atrophy in cortical areas and acute inflammation in subcortical regions.

                  1969.     Regional and Global Cerebral Blood Flow Is Reduced in Patients with Post-Stroke Dementia

Jiabao He¹, Michael J. Firbank², Rajesh N. Kalaria², Baldev Singh², Paul Danson², John O'Brien², Andrew M. Blamire¹

¹Newcastle MR Centre and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; ²Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom

Stroke is one of the most important risk factors for dementia.  In stroke survivors who do not have immediate, severe cognitive impairment, the risk of developing dementia is significantly increased.  Stroke may also exacerbate or trigger the development of neurodegenerative pathology.  Small vessel vascular effects may be an important factor in neurodegeneration.   We compared CBF in post-stroke patients with and without cognitive decline, patients with Alzheimer’s disease and healthy controls. Regional and global deficits in CBF were found in patients with post-stroke dementia resembling patterns of change in AD patients, while cognitively intact post-stroke patients had normal CBF.

                  1970.     The Effects of ApoE4 Allele and Age on Subcortical Brain Atrophy in HIV Positive Subjects

Linda Chang¹, Marilou Andres², Jeff Sadino¹, Caroline Jiang¹, Helenna Nakama³, Ute Feger¹, Thomas Ernst¹

¹Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States; ²Pacific Biomedical Research Center, University of Hawaii at Manoa, Honolulu, HI, United States; ³Department of Psychiatry, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States

The presence of apolipoprotein (Apo) E4 allele may accelerate the progression of HIV disease, and increase the risk for developing HIV associated neurocognitive disorder (HAND).  Whether Apo E4 allele and age may influence subcortical brain atrophy in HIV patients are unknown and were evaluated in this study.  Smaller subcortical structures were found in HIV patients with HAND, less so in those with normal cognition.  ApoE4 genotype was associated with greater atrophic effects in the younger but not older HIV patients, which suggests that ongoing neuro-inflammatory processes may be more robust and have stronger deleterious effects in the younger patients.

                  1971.     Increased Folding Complexity of the Left Temporal Pole in Temporal Lobe Epilepsy

Natalie L. Voets^1,2, Boris C. Bernhardt², Hosung Kim², Andrea Bernasconi²

¹University of Oxford FMRIB Centre, Oxford, Oxfordshire, United Kingdom; ²Montreal Neurological Institute and Hospital, McGill University, NeuroImaging of Epilepsy Laboratory and McConnell Brain Imaging Centre, Montreal, Quebec, Canada

Converging histological and radiological data suggest neurodevelopmental abnormalities may play a role in the pathogenesis of drug-resistant temporal lobe epilepsy (TLE). Using surface-based cortical curvature measures, we identified abnormally increased cortical folding in the left temporal pole of patients with both left and right TLE as compared to healthy controls. Increased left temporopolar folding was associated with abnormal positioning of the ipsilateral hippocampus in left TLE patients, and associated with unfavourable surgical outcome in patients with a right-sided seizure focus. These results suggest abnormalities in global limbic network connectivity may play an important role in temporal lobe epileptogenesis.

                  1972.     1H NMR Metabolomics Study of Cerebrospinal Fluid (CSF) in Amyotrophic Lateral Sclerosis (ALS) Patients

Lydie Nadal-Desbarats¹, Helène Blasco², Segolene Veau², Patrick Vourc'h², Caroline Moreau³, David Devos³, Philippe Corcia⁴, Christian R. Andres²

¹Laboratoire de RMN, INSERM U930 - CNRS 2448 - Université François Rabelais, Tours, France; ²Laboratoire de Biochimie et Biologie moleculaire, Inserm U930-CNRS 2448 - Université François Rabelais, Tours, France; ³Service de Neurologie et Pathologie du Mouvement, EA2683, Hopital R. Salengro - CHRU Lille, Lille, France; ⁴Centre SLA, CHRU Bretonneau, Tours, France

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease. Pathophysiological mechanisms involved in this disease are complex but remain for the most part unknown. This lack of knowledge might explain the absence of reliable biological marker. CSF could be a source of biomarkers. The aim of this study was to analyze CSF of patients with ALS by 1H NMR in order to identify biomarkers in the early stage of the disease, and to evaluate the biochemical factors involved in this disease. We quantified 18 metabolites like amino-acids, organic acids and ketonic bodies. Higher concentrations of metabolites such as ketone bodies contribute to the PCA separation between the two populations.

                  1973.     T₁-Weighted Images Detect Motor Neuron Degeneration in ALS

Govind Nair¹, John D. Carew^2,3, Sharon Usher⁴, Michael Benatar^4,5, Xiaoping P. Hu¹

¹Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, United States; ²Institute for Health Studies, Carolinas HealthCare System, Charlotte, NC, United States; ³School of Public Health, Emory University, Atlanta, GA, United States; ⁴Department of Neurology, Emory University, Atlanta, GA, United States; ⁵Department of Epidemiology, Emory University, Atlanta, GA, United States

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease affecting the motor neurons in the brain and spinal cord. VBM analysis performed on T1-weighted images of the brain revealed significant changes in the motor cortex and supporting white matter of ALS patients compared with age-matched healthy control subjects. ROI analysis revealed a significant decrease in signal intensity from these regions, with signal intensity of ALS group showing significant correlation with clinical measures of disease severity. These findings suggest that T1-weighted images may have utility as an imaging biomarker of disease progression in ALS.

                  1974.     31P and 1H MR Spectroscopic Studies on Changes of Cerebral Brain Metabolism Induced by Alcoholism and Detoxification

Ulrich Pilatus¹, Joerg Magerkurth¹, Nicole Schwan², Tilmann Wetterling², Barbara Schneider²

¹Institute of Neuroradiology, University Hospital, Goethe-University, Frankfurt, Germany; ²Department of Psychiatry, University Hospital, Goethe-University

Cerebral metabolites at day 1 and day 7 of alcohol detoxification therapy were studied using 1H and 31P spectroscopic imaging. Particularly for prefrontal brain, metabolite concentrations correlated with the withdrawal syndrome. The results suggest that less severe symptoms support neuronal recovery while a less pronounced deviation from control values for energy or membrane related compounds  is correlated with more severe symptoms.

                  1975.     Schizophrenia Impact on Perfusion Parameters: A Dynamic Susceptibility Contrast Magnetic Resonance Imaging Study.

Denis Peruzzo¹, Gianluca Rambaldelli^2,3, Alessandra Bertoldo¹, Marcella Bellani^2,3, Roberto Cerini⁴, Sivlia Marini⁵, Roberto Pozzi Mucelli⁵, Michele Tansella^2,3, Paolo Brambilla^6,7

¹Department of Information Engineering, University of Padova, Padova, Italy; ²Inter-University Center for Behavioural Neurosciences, University of Verona, Verona, Italy; ³Department of Medicine and Public Health, University of Verona, Verona, Italy; ⁴Service of Radiology, Policlinico GB Rossi Hospital, Verona, Italy; ⁵Department of Morphological and Biomedical Sciences, University of Verona, Verona, Italy; ⁶Inter-University Center for Behavioural Neurosciences, University of Udine, Udine, Italy; ⁷Scientific Institute, IRCCS “E. Medea”, Udine, Italy

Abnormalities of Cerebral Blood Flow (CBF) and Volume (CBV) have been observed in schizophrenia patients, suggesting that a disruption of the vascular system may occur in this disease. However, cerebral perfusion is also influenced by several physiologic parameters, not necessarily connected to the pathology. We performed a DSC-MRI analysis to study the role of the demographic information on perfusion parameter estimates between patients with schizophrenia and normal control subjects. We found that differences (i.e. between-subject variability) in CBF and CBV are partially explained by the age and/or by a difference in the subject health conditions.

                  1976.     Early Magnetic Resonance Spectroscopy Renormalized of Prefrontal Cortex and Anterior Cingulated Cortex Metabolites in Hepatic Encephalopathy After Liver Transplantation

Haiyan Lou¹, Desheng Shang², Minming Zhang³

¹Department of Radiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang , China; ²Department of Radiology, The First Affiliated Hospital, Hangzhou, Zhejiang, China; ³Department of Radiology, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou, Zhejiang, China

                  1977.     ARV-Mediated Changes in Viral Levels and Neuroaxonal Function Precede Improvements in Cognition in Chronically HIV-Infected Subjects.

Margaret R. Lentz¹, Mona A. Mohamed^2,3, Hyun Kim¹, Jennifer A. Short¹, Mahaveer N. Degaonkar², Elkan Halpern¹, Katherine Conant⁴, Ned Sacktor⁵, Ola Selnes⁵, Peter B. Barker^2,3, Martin G. Pomper²

¹Department of Neuroradiology/A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, United States; ²Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, United States; ³F. M. Kirby Center for Functional Brain Imaging/Kennedy Krieger Institute, Johns Hopkins Medical Institutions, Baltimore, MD, United States; ⁴Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States; ⁵Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, United States

The application of combined antiretroviral (ARV) therapy has been shown to change viral and immune signaling kinetics, indicating that correlations between these and MR measures observed in cross-sectional studies may not last.  MRSI, global deficit scorings (GDS) and CSF HIV RNA levels of 51 chronically HIV-infected subjects examined over 10 months of a new ARV administration were included in this study.  Mixed model regression analysis indicated that later improvements in subjects’ GDS were associated with earlier improvements in neuroaxonal function and CSF viral load, suggesting that ARV-mediated decreases in CSF viral levels and neuroaxonal recovery precede improvements in cognitive functioning.

                  1978.     Hippocampus Perfusion Studies of Gulf War Veterans Using OPTIMAL FAIR

Xiufeng Li¹, Subhendra N. Sarkar², David E. Purdy³, Qihua Lin^4,5, David M. Buhner⁵, Robert W. Haley⁵, Richard W. Briggs^1,5

¹Radiology, UT Southwestern, Dallas, TX, United States; ²Radiology, Beth Israel Deaconess Medical Center, Boston, MA, United States; ³Siemens Healthcare, Malvern, PA, United States; ⁴Clinical Sciences, UT Southwestern Medical Center, Dallas, TX, United States; ⁵Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States

To verify the previous findings and facilitate futher investigation of the pathological characteristics of Gulf War Illness, a semi-blind hippocampus perfusion study with physostigmine challenge was performed for veterans with Gulf War Syndromes 1, 2 and 3 and healthy veterans in two sessions two days apart: the first session with saline infusion and the second session with physostigmine infusion. New study results are similar to those found in the SPECT studies performed in 1997-1998, indicating that the physiological effects upon hippocampal blood flow still persist a decade later.

                  1979.     White Matter Abnormalities in Tourette Syndrome Extend Beyond Motor Pathways

Irene Neuner^1,2, Yuliya Kupriyanova³, Tony Stöcker^2,4, Oleg Posnansky², Marc Tittgemeyer³, Frank Schneider^1,4, N. J. Shah^2,5

¹Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany; ²Medical Imaging Physics, Institute of Neuroscience and Medicine - 4, Forschungszentrum Juelich, Juelich, Germany; ³Max-Planck-Institut für Neurologische Forschung, Cologne, Germany; ⁴JARA – Translational Brain Medicine, Germany; ⁵Department of Neurology,Faculty of Medicine, RWTH Aachen University, Aachen, Germany

White matter abnormalities in patients with Tourette syndrome are investigated using diffusion tensor imaging, Tract-Based Spatial Statistics and correlation analysis. Our results indicate that TS is not restricted to motor pathways alone but affects association fibres such as the inferior fronto-occipital fascicle, the superior longitudinal fascicle and fascicle uncinatus as well.  The detected abnormalities in Tourette patients complement the idea of the developmental character of the disorder. They show a pathological pattern reaching beyond the corticospinal tract. The alteration pattern of decreased fractional anisotropy and increased radial diffusivity might indicate a deficit myelination as one pathophysiologic factor in Tourette.

                  1980.     Persistent Basal Ganglia NAA/Cr Ratio Differences in Gulf War Illness

Sergey Cheshkov^1,2, Audrey Chang¹, Hyeon-Man Baek¹, Sandeep Ganji¹, Evelyn Babcock¹, Richard Briggs^1,2, Robert Haley²

¹Radiology, UT Southwestern Medical Center, Dallas, TX, United States; ²Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States

Decrease in the N-acetylaspartate to creatine ratio (NAA/Cr) was previously measured via magnetic resonance spectroscopy at 1.5T in bilateral basal ganglia, pons, and in left hippocampus of Gulf War Illness patients.  The Seabees cohort veterans (controls, Syndrome 1, 2, and 3 patients) studied in 1997-1998 recently participated in a follow-up study at 3T. The group comparison of this new spectroscopic data indicates reduced NAA/Cr ratio in all three Syndrome groups compared to the control group, the decrease is significant in the left and nearly significant in the right basal ganglia. This finding indicates possible neuronal damage in the affected population.

                  1981.     Quantitative Sensory Testing FMRI: Differences Between Gulf War Illness Patients and Deployed Controls

Aman Ish Goyal¹, Parina Gandhi¹, Yan Fang¹, Lei Jiang¹, Luo Ouyang¹, Sandeep Ganji¹, David Buhner², Wendy Ringe³, Kaundinya Gopinath^1,2, Richard Briggs^1,2, Robert Haley²

¹Department of Radiology, UT Southwestern Medical Center, Dallas, TX, United States; ²Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States; ³Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, United States

Previous studies have shown higher cooling and warming thresholds in hands and feet of Gulf War (GWI) veterans. In this study, brain activation to warm sensation stimuli and hot pain stimuli was measured with a quantitative sensory testing (QST) fMRI paradigm, in GWI veterans with Syndromes1 (Syn1), Syn2 and Syn3, as well as age-matched controls. Syn2 and Syn1 groups exhibited significantly decreased brain activation during warm sensation compared to controls. On the other hand, Syn2 and Syn1 groups evoked significantly higher activation to hot pain stimuli in a number of pain processing areas.

                  1982.     Advanced Mr Imaging of Active Duty Military Personnel Following Acute Blast-Related Tbi

Christine Louise MacDonald¹, Dana Cooper¹, John Witherow², Abraham Snyder³, Joshua Shimony³, Marcus Raichle³, Stephen Flaherty², Raymond Fang², David Brody¹

¹Neurology, Washington University, Saint Louis, MO, United States; ²Landstuhl Regional Medical Center, Landstuhl, Germany; ³Radiological Sciences, Washington University, Saint Louis, MO, United States

Military personnel have a higher rate than civilians of Traumatic Brain Injury (TBI) even during times of peace.  TBI has been called the signature injury of the wars in Iraq and Afghanistan . Many of these injuries occur as the result of blast exposure, but little is known about the characteristics of blast-related TBI. Diffusion tensor imaging (DTI) was employed for this study of 85 active duty military personnel (20 control, 65 TBI).  Abnormalities were found on DTI that were not apparent on conventional imaging.  This is the first time this has been observed in this particular population.

                  1983.     Transverse Relaxation Measurements of Brain Metabolites in Gulf War Illness

Audrey Jennifer Chang¹, Sergey Cheshkov^1,2, Richard Briggs^1,2, Robert Haley²

¹Radiology, UT Southwestern Medical Center, Dallas, TX, United States; ²Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States

Relaxation times are often an assumed value in spectroscopy studies, despite their potential diagnostic value and usefulness in quantifying metabolite concentrations.  The purpose of this study was to measure the transverse (T2) relaxation times of the major brain metabolites (NAA, Crt, and Chot) in left and right basal ganglia of veterans with Gulf War Illness (GWI) and age-matched veteran controls to determine if the T2 values differ between ill veterans and controls or  among the three syndrome variants of GWI.

                  1984.     Reduced Hippocampal Body Functional Connectivity in Gulf War Illness

Yan Fang¹, Luo Ouyang¹, Cybeles Onuegbulem², Aman Goyal¹, Lei Jiang¹, Parina Gandhi¹, Sandeep Ganji¹, Wendy Ringe², Kaundinya Gopinath^1,3, Richard Briggs^1,3, Robert Haley³

¹Department of Radiology, UT Southwestern Medical Center, Dallas, TX, United States; ²Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, United States; ³Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States

Memory loss is a common complaint among veterans with Gulf War Illness (GWI), and preliminary studies have documented hippocampal dysfunction in GWI. Abnormal functional connectivity to hippocampus has also been observed in various other diseased populations. This study used resting state or functional connectivity MRI (fcMRI) to examine functional connectivity of the hippocampus in GWI subjects. GWI veterans exhibited significantly reduced connectivity to left and right hippocampal body in a number of brain regions, indicating disruption of hippocampal networks and/or damage to hippocampus in GWI.

                  1985.     neuGRID: A GRID-Based E-Infratructure for Data Archiving, Communication and Computationally Intensive Applications in the Medical Sciences

Keith S. Cover¹, Frederik Barkhof¹, Alex Zijdenbos², Christian Spenger², Richard McClatchey³, David Manset⁴, Lars-Olof Wahlund⁵, Yannick Legre⁶, Tony Solomonides⁶, Giovanni B. Frisoni⁷

¹VU University Medical Center, Amsterdam, Netherlands; ²Prodema Medical; ³University of the West of England; ⁴MAAT G Knowledge SL; ⁵Karolinska Institutet; ⁶HealthGrid; ⁷Fatebenefratelli

neuGRID is developing a new user-friendly Grid-based research e-Infrastructure enabling the European neuroscience community to carry out computer intensive research required for the pressing study of degenerative brain diseases (for example, the Alzheimer disease). In neuGRID, the archiving of large amounts of imaging data is paired with hundreds of CPU’s and a variety of software packages. Neuroscientists will be able to identify neurodegenerative disease markers through the analysis of 3D magnetic resonance brain images via the provision of sets of distributed medical and GRID services. The infrastructure is designed to be expandable to services for other medical applications and is compliant with EU and international standards regarding data collection, data management, and Grid construction.

                  1986.     Accurate Mapping of Brains with Severe Atrophy Based on Multi-Channel Non-Linear Transformation

Aigerim Djamanakova¹, Andreia V. Faria², Kenichi Oishi², Xin Li², Kazi Akhter², Laurent Younes^3,4, Peter van Zijl^2,5, Michael Ira Miller³, Susumu Mori²

¹Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, United States; ²Radiology, Johns Hopkins University, Baltimore, MD, United States; ³Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, United States; ⁴Applied Mathematics & Statistics, Johns Hopkins University, Baltimore, MD, United States; ⁵F.M. Kirby Center for Functional Magnetic Resonance Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

We used Large Deformation Diffeomorphic Metric Mapping in order to improve the registration of brains with enlarged ventricles from patients with Alzheimer's disease .  By employing a second channel of information comprised of the lateral ventricle segmentation maps, obtained semi-automatically and automatically, we were able to increase the accuracy of the mappings.  The degree of accuracy was calculated by comparing the results of the manual segmentation of lateral ventricles and a neighboring structure, lingual gyrus, with the single and dual-channel registration-based segmentation.  This approach can be a powerful tool for improving registration of images.

                  1987.     Optimization of the MPRAGE Sequence for Fully Automatic Brain Volumetry and a Comparison of Reproducibility Between Two Different Phased Array Receiver Head Coils at 3 T

Love Erlandsson Nordin^1,2, Leif Svensson^1,2, Per Julin^3,4, Susanne Müller⁵, Terri Louise Lindholm^1,2

¹Medical Physics, Karolinska University Hospital Huddinge, Stockholm, Sweden; ²SMILE Image Laboratory, Karolinska University Hospital Huddinge, Stockholm, Sweden; ³AstraZeneca R&D Neuroscience, Södertälje, Sweden; ⁴Clinical Geriatrics, Karolinska University Hospital Huddinge, Stockholm, Sweden; ⁵Radiology, Karolinska University Hospital Huddinge, Stockholm, Sweden

The aim of this study has been to optimize the contrast parameters of the MPRAGE sequence for fully automatic brain tissue segmentation. The goal has been to achieve as reliable and reproducible volumetric measurements of the human brain as possible. The optimization was carried out on a 3 T MRI unit using 2 different multi array head coils (12 and 32 channels) and 9 healthy young volunteers. The study also includes a comparison of the reproducibility in measurement between the two head coils. The results show that it is possible to achieve good reproducibility in measurement for the total brain volume and the 12 channel head coil gives slightly more reproducible results.

                  1988.     A Population-Based Template for High-Dimensional Normalization of Postmortem Human Brains from Elderly Subjects

Robert John Dawe¹, David A. Bennett², Julie A. Schneider², Konstantinos Arfanakis¹

¹Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States; ²Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States

Postmortem MRI of the human brain offers several advantages over in vivo imaging. For example, histological analysis can be performed following the MR scan, allowing for verification of imaging findings and testing of new MRI diagnostic techniques. Spatial transformation of individual postmortem brain MRI volumes to a common reference would facilitate voxel-based investigations, which would provide information throughout the brain in a timely manner and without user bias, in contrast to ROI-based analyses. In this work, population-based methods were used to create an MRI template that is suitable for high dimensional spatial normalization of postmortem human cerebral hemispheres.

                  1989.     In Vivo 3D Imaging of Human Lateral Geniculate Nucleus Using Optimized Inversion Recovery Sequence at 3T and 7T

Chan Hong Moon¹, Jung-Hwan Kim¹, JinHong Wang¹, Kyongtae Ty Bae¹

¹University of Pittsburgh, Pittsburgh, PA, United States

We demonstrated excellent tissue contrast of the lateral geniculate nucleus (LGN) with suppression of signals from the surrounding white matters, such as optic radiation using an (inversion-recovery) MPRAGE sequence with appropriate TI at 3T and 7T. The LGN was superiorly delineated with a high SNR at 7T, as compared to 3T. An imaging method that allows for accurate and reliable volume measurement of LGN is essential for the investigation of the association between LGN atrophy in vivo and neurodegenerative glaucoma.

                  1990.     Semi-Automatic Brain Ventricle Segmentation Using Partial Volume Fraction Calculation of CSF Based on Quantitative MRI

J. B.M. Warntjes^1,2, J. West^1,3, R. Birgander⁴, P. Lundberg⁵

¹Center for Medical Imaging Science and Visualization (CMIV), Linköping, Sweden; ²Department of Medicine and Health, Division of Clinical Physiology, Linköping, Sweden; ³, Department of Medicine and Health, Division of Radiation Physics, Linköping, Sweden; ⁴Department of Radiology (NUS), Department of Radiation Sciences, Umeå, Sweden; ⁵Department of Medicine and Health, Division of radiation physics, Linköping, Sweden

A method is described to measure the partial volume fraction of cerebrospinal fluid for each voxel in a complete brain volume within a scan time of 5 to 6 minutes, based on quantification of the relaxation rates R1 and R2 and proton density. This measurement allows to accurately segment the brains ventricular system independent of image resolution and without user-dependent image thresholding.

                  1991.     Quantitative MR at 3.0 T of Patients with Non-Symptomatic Localization-Related Epilepsy: Association with Generalized and Partial Seizures

Jacobus FA Jansen¹, Marielle Vlooswijk², H Majoie², Paul Hofman², Marc De Krom², Albert Aldenkamp², Walter H. Backes²

¹Medical Physics, MSKCC, NY, United States; ²MUMC, Maastricht, Netherlands

Although cognitive dysfunction is a prevalent co-morbidity in patients with chronic epilepsy, it is not clear whether these patients display cerebral abnormalities that are related to the cognitive impairment that can be detected with in vivo magnetic resonance (MR) techniques. This report study aims to determine neuronal determinants of cognitive impairment in patients with chronic epilepsy. Quantitative MR, comprising T2 relaxometry, diffusion tensor imaging, and spectroscopic imaging, was applied to detect possible neuronal correlates in terms of micro-structural and metabolic abnormalities.

                  1992.     Deformation Based Morphometry (DBM) in Temporal Lobe Epilepsy with and Without Mesial Temporal Sclerosis

Cathy Scanlon¹, Susanne G. Mueller², Duygu Tosun², Ian Cheong², Michael W. Weiner², Ken D. Laxer³

¹Center for Imaging of Neurodegenerative Diseases , Dept. of Radiology and Biomedical Imaging, University of California,, San Francisco, CA, United States; ²Center for Imaging of Neurodegenerative Diseases, Dept. of Radiology and Biomedical Imaging, University of California,, San Francisco, CA, United States; ³Pacific Epilepsy Program, California Pacific Medical Center, San Francisco, CA, United States

Deformation-based morphometry (DBM) was applied to 2 sub-groups of temporal lobe epilepsy (TLE); 15 patients with mesial temporal sclerosis (TLE-mts) and 14 with normal MRI on visual inspection (TLE-no). TLE-mts demonstrated extensive extra-hippocampal abnormalities when compared with controls (n=33). TLE-no demonstrated more subtle but significant findings not previously reported with a similar analysis in voxel based morphometry (VBM). This may suggest DBM to be a more sensitive approach to detect subtle volume changes in this group.

                  1993.     Quantification of Microtubule Stabilizing Drug Treatment Effect on Axonal Transport Rate in a Transgenic Mouse Model of Alzheimers Disease

Jieun Kim¹, In-Young Choi^1,2, Mary L. Michaelis³, Sang-Pil Lee^1,4

¹Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States; ²Neurology, University of Kansas Medical Center, Kansas City, KS, United States; ³Pharmacology & Toxicology, University of Kansas, Lawrence, KS, United States; ⁴Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States

Axonal transport impairment has been implicated as a common mechanism of Alzheimer’s disease progression. A newly developed microtubule stabilizing agent, TH237-A, is known for protecting neurons against A_β toxicity, decreasing abnormal tau phosphorylation in cultured neurons, and permeating the blood-brain barrier. We have investigated the efficacy of TH237-A in preserving axonal transport integrity in an animal model of AD, 3xTg-AD mice, over one year by measuring axonal transport rates in olfactory bulbs using manganese enhanced MRI. Results show that the drug does not reverse axonal transport deficits but may be effective in preventing further axonal transport impairment.

                  1994.     Imaging Correlates of Neuropsychological Tests in Minimal Hepatic Encephalopathy Due to Extrahepatic Portal Vein Obstruction

Santosh Kumar Yadav¹, Amit Goel², Vivek A. Saraswat³, Arti Srivastava¹, Sanjay Verma⁴, Ram Kishore S. Rathore⁵, Michael A. Thomas⁶, Chandra M. Pandey⁷, Kashi N. Prasad⁴, Rakesh K. Gupta¹

¹Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ²Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences Lucknow India, Lucknow, UP, India; ³Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ⁴Mathematics and Statistics, Indian Institute of technology, Kanpur, UP, India; ⁵Mathematics and Statistics, Indian Institute of technology Kanpur, Kanpur, Uttar Pradesh, India; ⁶Radiological Sciences, UCLA School of Medicine, Los Angeles, CA, Los Angeles, CA, United States; ⁷Biostatistics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India

Thirty-one EHPVO patients along with 23 controls were included in this study. All subjects underwent for neuropsychological tests, measurement of blood ammonia, MR imaging, 1H-MR spectroscopy. Serum cytokines were measured only in 10 patients and 8 controls. MHE was present in 45% patients. Significantly increased ammonia, Glx/Cr, and cytokines and MD with decrease in mI/Cr and MTR with no change in Cho/Cr were noted in patients with MHE compared to controls. Significantly increased Glx/Cr and blood ammonia indicates its central role in the pathogenesis of EHPVO related MHE. The presence of significant increased serum cytokines in these patients suggest that inflammation also pay an important role in the pathogenesis of MHE.

                  1995.     Understanding Difference in Biochemical, Neuropsychological and Brain MR Imaging Profile of Minimal Hepatic Encephalopathy Secondary to Cirrhosis and Extrahepatic Portal Vein Obstruction

Santosh Kumar Yadav¹, Amit Goel², Vivek A. Saraswat², R KS Rathore³, M A. Thomas⁴, A Yadav¹, K N. Prasad⁵, C M. Pandey⁶, Rakesh Kumar Gupta¹

¹Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ²Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ³Mathematics and Statistics, Indian Institute of technology Kanpur, Kanpur, Uttar Pradesh, India; ⁴Radiological Sciences, UCLA School of Medicine, Los Angeles, CA, Los Angeles, CA, United States; ⁵Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ⁶Biostatistics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Thirty-three cirrhotic MHE and 14 EHPVO MHE with 23 age/sex matched control were included in final analysis. Liver function test, NPT, CFF, blood ammonia, proinflammatory molecules, MR imaging and 1H MR spectroscopy were recorded in all patients. MHE was significantly higher in cirrhosis than EHPVO. Significantly increased blood ammonia, proinflammatory molecules, Glx/Cr and MD with decreased mIns/Cr was observed in both form of MHE as compared to controls, however Cho/Cr significantly decreased only in cirrhotic MHE as compared to EHPVO MHE and controls. Increased blood ammonia, proinflammatory molecules, Glx/Cr and MD with decreased mIns/Cr is common in both form of MHE and involved the pathogenesis of MHE, however Cho/Cr depletion was observed only in cirrhotic MHE, confirms that Cho/Cr depletion is related to liver dysfunction and is unrelated to MHE. Our study confirms that there are differences in biochemical, proinflammatory molecules and MR profile in MHE of cirrhosis and EHPVO.

                  1996.     Amygdala Network Dysfunction Links Depressive Symptom and Memory Deficit in Elderly with Amnesic Mild Cognitive Impairment

Chunming Xie^1,2, Wenjun Li¹, Joseph Goveas¹, Piero Antuono¹, Jennifer Jones¹, Guangyu Chen¹, Malgorzata Franczak¹, Zhilin Wu¹, Shi-Jiang Li¹

¹Medical College of Wisconsin, Milwaukee, WI, United States; ²Neurology, School of Clinical Medicine, Southeast University, Nanjing, Jiangsu, China

The purpose of this study was to identify neural correlates of depressive symptoms and memory deficits in the amygdala functional connectivity network (AFCN) in elderly with or without amnesic mild cognitive impairment (aMCI) using the resting state functional connectivity MRI technique. aMCI subjects showed abnormal AFCN activity and the significant different correlation patterns in the distinct nodes within the AFCN correlated to depressive symptoms and memory deficits. This suggests the AFCN has dual effects that link depressive symptoms and memory deficits. The altered neural substrates of the AFCN underlying the emotional and cognitive functions mediation were associated with disease state.

                  1997.     Assessing the Effect of Age on Voxel-Based Relaxometry of Epileptic Patients

Rachel Sharkey^1,2, Robert Karl Kosior, ^1,3, Paolo Federico^1,2, Richard Frayne, ¹²

¹Seaman Family MR Research Centre, Foothills Medical Centre, Calgary, AB, Canada; ²Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; ³Biomedical Engineering, University of Calgary, Calgary, AB, Canada

Our objective was to assess the effect of age on T2 for voxel-based relaxometry (VBR) analysis. Regressions of T2 versus age were run on data from healthy controls with a voxel-based analysis and with regions of interest. For controls and epileptic patients, VBR was performed once with age included as a nuisance variable, and once without. The correlation was variable across the brain, and significant (p < 0.05) in four regions, including the hippocampus (decreasing T2 with age). Without adjusting for age, discrepancies in VBR findings are found in younger and older patients.

Normal Aging Brain

                  1998.     A Multiparametric Study of White Matter Integrity and Cognition in Old Age

Susana Muñoz Maniega¹, Lars Penke², María C. Valdés Hernández¹, Catherine Murray², Natalie A. Royle¹, Alan J. Gow², Jonathan D. Clayden³, John M. Starr⁴, Mark E. Bastin⁵, Ian J. Deary², Joanna M. Wardlaw¹

¹Clinical Neurosciences, University of Edinburgh, Edinburgh, United Kingdom; ²Psychology, University of Edinburgh, Edinburgh, United Kingdom; ³Institute of Child Health, University College London, London, United Kingdom; ⁴Geriatric Medicine, University of Edinburgh, Edinburgh, United Kingdom; ⁵Medical Physics, University of Edinburgh, Edinburgh, United Kingdom

Using diffusion MRI tractography we segmented white matter tracts thought to be related with cognition in a cohort of healthy older people. We registered the tract segmentations to parametric maps of magnetization ratios and T1 relaxation times and used these parameters, as well as fractional anisotropy and mean diffusivity, to characterise the white matter integrity of the tracts. The study of how tract integrity relates to cognition in old age revealed new relationships not shown by diffusion parameters only. This work suggests that a multi-parameter approach could unravel the effects of ageing on the brain and cognition better than the lone use of diffusion MRI.

                  1999.     Rates of Brain Tissue Changes in the General Population of Elderly - The AGES-Reykjavik Study

Sigurdur Sigurdsson¹, Thor Aspelund^1,2, Lars Forsberg³, Jesper Fredriksson³, Olafur Kjartansson, ^1,4, Palmi V. Jonsson, ^1,4, Gudny Eiriksdottir¹, Tamara B. Harris⁵, Alex Zijdenbos⁶, Mark A. van Buchem⁷, Lenore J. Launer⁵, Vilmundur Gudnason^1,2

¹The Icelandic Heart Association, Kopavogur, Iceland; ²The University of Iceland, Reykjavik, Iceland; ³Raforninn Inc, Reykjavik, Iceland; ⁴The University Hospital of Iceland, Reykjavik, Iceland; ⁵The National Institute on Aging, Bethesda, United States; ⁶Biospective Inc, Montreal, Canada; ⁷Leiden University Medical Center, Leiden, Netherlands

Estimations on age-related rate of changes of brain tissues have mostly been gathered from cross-sectional MRI studies. A limitation of cross-sectional design is the inability to directly assess intra-individual change. Longitudinal studies on brain tissues and age in large population cohorts are lacking. We compared estimated rates of cross-sectional and longitudinal changes with age in brain tissues in a population-based cohort of 4614 older persons. The longitudinal data show a substantially higher age-related rate of change in tissue volumes when compared to the cross-sectional estimates and show that the cross-sectional data underestimates the rate of change in brain tissues.

                  2000.     Effects of Sex and Age on Regional Frontal Lobe Gray Matter Distribution

Vanessa Anne Sluming^1,2, Andrew Mayes³, Iain D. Wilkinson⁴, Charles Romanowski⁴, Enis Cezayirli⁵, Patricia E. Cowell⁶

¹School of Health Sciences, University of Liverpool, Liverpool, Merseyside, United Kingdom; ²Magnetic Resonance and Image Analysis Research Centre, University of Liverpool, Liverpool, Merseyside, United Kingdom; ³School of Psychology, University of Manchester, Manchester, United Kingdom; ⁴Academic Department of Radiology, University of Sheffield, United Kingdom; ⁵Department of Anatomy, University of Celal Bayar , Turkey; ⁶Department of Human Communication Sciences, University of Sheffield, United Kingdom

VBM analysis of grey matter distribution within the healthy adult brain was undertaken, in a sample of 31 males and 35 females (age range: 20-72 years) to investigate sex differences in the effect of brain ageing. Data were analysed using a full factorial analysis (2x2x2). There were no significant sex by age effects. Within sex regression analyses revealed that females showed age related GM decrements within several frontal regions tending medially, whereas males sowed age related decrements in bilateral structures including IFG (BA44/45). These findings are discussed.

                  2001.     White Matter Lesion Intensity and Cognitive Ability: Relationships in Youth and Old Age

Maria Valdés Hernandez¹, Lars Penke², Susana Muñoz Maniega¹, Catherine Murray², Natalie Royle¹, Alan J. Gow², John M. Starr³, Mark E. Bastin⁴, Ian J. Deary², Joanna M. Wardlaw¹

¹Clinical Neurosciences, University of Edinburgh, Edinburgh, United Kingdom; ²Psychology, University of Edinburgh, Edinburgh, United Kingdom; ³Geriatric Medicine, University of Edinburgh, Edinburgh, United Kingdom; ⁴Medical Physics, University of Edinburgh, Edinburgh, United Kingdom

Intensity of white matter lesions (WMLs) on structural MRI may be linked to the severity of underlying white matter damage, and hence to old age cognitive decline. Here we investigate relationships between the volumes of intense (i) and less-intense (Li) WMLs in a unique cohort of ? subjects in whom cognitive ability is available in both youth (11 years) and old age (72-73 years). iWMLs were predominant located in frontal areas, while LiWMLs were mainly located posteriorly. iWMLs had a stronger relationship with cognition than LiWMLs in both youth and old age. These findings support the frontal ageing hypothesis.

                  2002.     Investigation of Cerebral Ischemic Disease in the Aged with Aortic Stenosis

Ping Wang¹, Elizabeth Strambrook², Michel Bilello¹, Thomas Floyd³

¹Radiology, University of Pennsylvania, Philadelphia, PA, United States; ²Anesthesiology & Critical Care, University of Pennsylvania, Philadelphia, PA, United States; ³Anesthesiology & Critical Care, and Neurology, University of Pennsylvania, Philadelphia, PA, United States

To test the correlations of aging, sex, and aortic stenosis (AS) degree with the severity of pre-existing white matter and ischemia-like lesions.  Aging was associated with rapidly progressive cerebral ischemic disease; female sex accounted for a 56% increased in lesion volume over men; while the severity of AS did not demonstrate statistical significance in influencing lesion volume, univariate analysis demonstrated an important trend of increasing lesion volume with increasing severity of AS.

                  2003.     Novel Atlas-Based Technique for Longitudinal Investigation of Diffusion Tensor Tractography Data: Application to Healthy Ageing

Ai Wern Chung¹, Rebecca A. Charlton¹, Nigel C. Lawes², Robin G. Morris³, Hugh S. Markus¹, Thomas R. Barrick¹

¹Centre for Clinical Neuroscience, Saint George's University of London, London, United Kingdom; ²Graduate Medical School, University of Limerick, Limerick, Ireland; ³Department of Psychology, Institute of Psychiatry, King's College University of London, London, United Kingdom

We present a novel technique applying probabilistic diffusion tensor tractography on longitudinal data to assess white matter structural integrity in ageing subjects over a period of two years. Our method was able to consistently extract white matter tracts associated with working memory over time and between two ageing cohorts (middle-aged and elderly). Tract connections were found between the fronto-temporal, fronto-parietal and temporo-parietal lobes. Our study suggests a decrease in white matter structural integrity of these tracts with age could be related to the decline in working memory performance.

                  2004.     Magnetization Transfer and Spin-Lattice Relaxation Time Measurements of White Matter Lesions in Normal Aging

Mark E. Bastin¹, Maria Valdés Hernandez², Susana Muñoz Maniega², Catherine Murray³, Alan J. Gow³, Paul A. Armitage², Joanna M. Wardlaw², Ian J. Deary³

¹Medical Physics, University of Edinburgh, Edinburgh, United Kingdom; ²Clinical Neurosciences, University of Edinburgh, Edinburgh, United Kingdom; ³Psychology, University of Edinburgh, Edinburgh, United Kingdom

White matter lesions are a common finding on T2- and FLAIR-weighted MRI scans of older subjects, but their etiology and relationship to cognitive function remains unclear. The aim of this pilot study was to characterize differences in magnetization transfer ratio and spin-lattice relaxation time between macroscopically normal-appearing white matter and white matter lesions in a subset of a unique cohort of aging subjects, the Lothian Birth Cohort 1936.

                  2005.     Hypertension, Arterial Health and Neuronal Integrity in Midlife

Andreana P. Haley^1,2, Tarumi Takashi³, Jun Sugawara³, Hirofumi Tanaka³

¹Psychology, The University of Texas at Austin, Austin, TX, United States; ²UT Imaging Research Center, Austin, TX, United States; ³Kinesiology, The University of Texas at Austin, Austin, TX, United States

The present study bridges the gap between midlife hypertension and late-life cognitive impairment, a relationship that has long been documented but remains poorly understood. We demonstrate that midlife hypertension and associated arterial thickening relate to cerebral measures of neuronal health and viability in middle-aged adults with intact cognitive performance.

                  2006.     Comparison of Brain Metabolites Changes Associated with Visual Sexual Arousal in Premenopausal and Menopausal Women: Functional MR Spectroscopy

Tae-Hoon Kim¹, Gwang-Woo Jeong^1,2, Han-Su Baek¹, Gwang-Won Kim¹, Heoung-Keun Kang², Jong-Chul Yang³, Kwangsung Park⁴

¹Interdisplinary Program of Biomedical Engineering, Chonnam National University Medical School, Gwangju, Korea, Republic of; ²Radiology, Chonnam National University Medical School, Gwangju, Korea, Republic of; ³Psychiatry, Chonbuk National University Hospital, Chonbuk, Korea, Republic of; ⁴Urology, Chonnam National University Medical School, Gwangju, Korea, Republic of

With menopause, women underwent changes of overall hormones, leading to functional changes of organs. A majority of menopausal women experience some exchanges in sexual function. Using fMRI technique, menopausal a few papers concerning differential brain activation patterns between premenopausal and menopausal women were published. However, it is unclear how brain metabolite change in menopause affects sexual arousal.

  The purpose of this study was to investigate the brain metabolic changes associated with visual sexual arousal in premenopausal and menopausal women using functional MR spectroscopy (fMRS).

                  2007.     Motion Detection in Healthy Young, Middle-Aged, and Elderly Adults Using  a Water Signal Based Navigator Echo: A  ¹H MRS Study

Sarah Andrea Wijtenburg¹, Kathleen L. Fuchs², Virginia I. Simnad³, Jack Knight-Scott¹

¹Radiology, Children's Healthcare of Atlanta, Atlanta, GA, United States; ²Neurology, University of Virginia, Charlottesville, VA, United States; ³Neurology, Evergreen Hospital Medical Center, Kirkland, WA, United States

Here, we build upon our earlier work incorporating a CHESS pulse into a STEAM sequence by presenting a new method for analyzing and interpreting motion data collected from three age groups: healthy young (HY), healthy middle-aged (HM), and healthy elderly (HE). Our results show that listed in increasing order of motion during a ¹H MRS STEAM spectroscopy examination: HY, HM, and HE.

                  2008.     Cross-Site Reproducibility of ¹H-MRS

Irene Margaret Vavasour¹, Cornelia Laule¹, Burkhard Maedler², Trudy Harris¹, David K.B. Li¹, Anthony L. Traboulsee³, Alex L. MacKay¹

¹Radiology, University of British Columbia, Vancouver, BC, Canada; ²Physics and Astronomy, University of British Columbia; ³Medicine, Univeristy of British Columbia

Quantitative assessment of ¹H-MRS metabolite concentrations has the potential to be an in-vivo marker for disease progression and treatment efficacy in pharmaceutical trials. The present study examines cross-site reproducibility of ¹H-MRS metabolite concentrations measured on the same 5 people at 6 sites. Average percent differences of inter and intra-site reproducibility was <10% for n-acetyl-aspartate and myo-Inositol, <7% for creatine, <8% for choline and <21% for glutamate and glutamine. All percent differences between sites were of a similar magnitude increasing confidence in comparing results from across the sites.

                  2009.     Aging Effects on the Functional Connectivity in the Resting Brain

Zhengjun Li^1,2, Aniseh Kadivar³, John Pluta³, Holly D. Soares⁴, Murray Grossman³, John Detre³, Ze Wang⁵

¹Dept. of Biomedical Engineering, Shanghai Jiao Tong University, China; ²Dept of Psychiatry, University of Pennsylvania, United States; ³Dept of Neurology, University of Pennsylvania, United States; ⁴Pfizer Inc, United States; ⁵Dept of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States

Functional connectivity (FC) and the default mode network represents two recent active research directions in fMRI. Previous studies have shown the aging effect in resting FC based on independent component analysis or concurrent task involved fMRI defined region-of-interests (ROIs). No published work has assessed the aging effects on resting FC in the DMN using the seed region based method. To meet this gap, we here report some preliminary results of the aging inter-region FC in the normal brain using resting fMRI and found age-dependent FC decrease in anterior cingulate cortex and posterior cingulate cortex.

                  2010.     Correlation Between Venous Blood T1 and BOLD FMRI in Young and Elderly Subjects

Lirong Yan¹, Yan Zhuo¹, Bo Wang¹, Cheng Li², Jiongjiong Wang²

¹Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; ²Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

We investigated the relationship between in vivo measurement of venous blood T1 and BOLD signal changes during visual stimulation in two groups of young and elderly subjects. There was a significant negative correlation between venous blood T1 and BOLD activation across subjects. Upon including venous blood T1 as a covariate, the differences in BOLD activation between the two age groups weakened, suggesting that aging effects on BOLD fMRI may be partly attributed to baseline hematocrit variations.

                  2011.     Increased Resting State Connectivity Between Left and Right Hemispheres with Increasing Age

Daniel Joshua Cox^1,2, Rafat S. Mohtasib³, Daniela Montaldi⁴, Laura M. Parkes^1,2

¹Imaging Sciences and Biomedical Engineering, School of Cancer and Imaging Sciences, The University of Manchester, Manchester, Lancashire, United Kingdom; ²Biomedical Imaging Institute (BII), The University of Manchester, Manchester, Lancashire, United Kingdom; ³Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool, United Kingdom; ⁴School of Psychological Sciences, The University of Manchester, Manchester, Lancashire, United Kingdom

This study aims to investigate changes in resting state functional connectivity with increasing age. 40 healthy subjects (aged 20 – 76) participated. Gradient echo EPI images were collected during a Stroop task and active regions were found across the group. The BOLD amplitude in the right middle frontal gyrus (MFG) increased with age, reducing laterality of activation. Partial correlation was used to investigate functional connectivity between bilateral MFG, which was found to increase with age between bilateral MFG in adults aged 40yrs+. Increased connectivity was also associated with improved accuracy, suggesting alterations in functional connectivity may be important for performance.

                  2012.     Age-Related Effects on Resting State Default, Executive and Salience Networks Reveal Different Pruning Mechanisms – a Resting State FMRI Study.

Vesa Kiviniemi¹, Harri Littow¹, Ahmed Abou-elseoud¹, Katariina Mankinen², Jukka Rahko³, Jukka Remes¹, Juha Nikkinen¹, Tuomo Starck¹, Juha Veijola⁴, Christian Beckmann⁵, Osmo Tervonen¹

¹Diagnostic Radiology, Oulu University Hospital, Oulu, Finland; ²Pediatric department, Oulu University Hospital, Oulu, Finland; ³Child Psychiatry, Oulu University Hospital, Oulu, Finland; ⁴Psychiatry, Oulu University, Oulu, Finland; ⁵Clinical Neuroscience, Imperial College, London, United Kingdom

Resting state networks undergo various age related changes both in strength and spatial distribution. Some occur in adolescence while many changes also occur later in adulthood. A salience network splits without much strength in any age group. These different findings reflect multiple normal ageing processes of the central nervous system.

                  2013.     Age-Related Differences of Brain Activation Patterns Upon Imaginary Walking

Ekkehard Küstermann^1,2, Markus Ebke³, Katja Dolge⁴, Natascha Lohr¹, Dieter Leibfritz², Manfred Herrmann¹

¹ZKW/Neuropsychologie, Universität Bremen, Bremen, Germany; ²Organische Chemie, Universität Bremen, Bremen, Germany; ³Neurologie, Klinikum Bremen-Mitte, Bremen, Germany; ⁴JCLLaID, Jacobs University Bremen, Bremen, Germany

The steadiness of walking decreases in elderly with advancing age. This study was designed to explore changes in the activation pattern during walking. Healthy young and elderly subjects performed imaginated walking tasks while being scanned. Elderly subjects exhibited stronger and larger activations as compared to younger subjects with a marked increase in the IPL. During imaginated walking, negative BOLD signal changes were only observed in younger, but not in elderly subjects.

                  2014.     Naming Errors and Gray Matter Structural Variations

Katie McMahon¹, Anna Holmes², Shiree Heath², Anthony Angwin³, Lindsey Nickels⁴, Eril McKinnon², Sophie Van Hees², David Copland^2,3

¹Centre for Magnetic Resonance, University of Queensland, Brisbane, Queensland, Australia; ²UQ Centre for Clinical Research, University of Queensland, Australia; ³School of Health and Rehabilitation Sciences, University of Queensland, Australia; ⁴Macquarie Centre for Cognitive Science (MACCS), Macquarie University, Sydney, NSW, Australia

The frequency of naming errors increases in normal aging.  In this study we examined an elderly cohort of subjects; classified their naming difficulties and correlated this with high resolution structural MRI images.  Different regions were structurally correlated for reduced semantic, phonological and visual perception errors, including the inferior temporal lobe, middle temporal lobe, and occipital-parietal regions.

                  2015.     Correlations Between Semantic Priming, Word Recognition and Gray Matter Density

Katie McMahon¹, Anthony Angwin², Anna Holmes³, Shiree Heath³, Sophie Van Hees³, David Copland, ^2,3

¹Centre for Magnetic Resonance, University of Queensland, Brisbane, Queensland, Australia; ²School of Health and Rehabilitation Sciences, University of Queensland, Australia; ³UQ Centre for Clinical Research, University of Queensland, Australia

A normal elderly cohort was examined with MRI and a lexical access/semantic priming task.  The priming effect (semantically related vs unrelated prime-target pairs), and the word (semantic + unrelated response times) versus non-word targets were calculated. These variables were covaried with the individual subjects’ high resolution MRI images, to investigate any possible structural dependencies.  Structures of areas associated with attentional and semantic priming networks were significant when compared against non-word responses, and areas of conceptual object knowledge and familiarity when compared with the priming effect.

                  2016.     The Hemodynamic Response Characteristics Underlying the Age-Related Change of Brain Activation During Motor Execution

Toshiharu Nakai¹, Makoto Miyakoshi¹, Epifanio Bagarinao¹, Chikako Nakai², Kayako Matsuo³

¹Functional Brain Imaging Lab, National Center for Geriatrics and Gerontology, Ohbu, Aichi, Japan; ²School of Health Sciences, Toyoshashi Sozo University, Toyohashi, Aichi; ³Psychology, National Taiwan University, Taipei, Taiwan

The characteristics of the hemodynamic response function underlying the age-related change was investigated to estimate its contribution to the statistical evaluation of fMRI by using motor tasks. It was suggested that the neuronal demanded was augmented to support cognitive processing for motor regulation rather than motor execution itself. Augmented activation in the elderly subjects mostly depended on the increased BOLD signal amplitude between the initial and post-stimulus peaks. It will be recommended to consider the potential bias induced by the non-linear dynamics of HRF to assess the age-related change of brain activation.

                  2017.     Differences in GABA to Creatine Ratio Between the Occipital and the Medial Pre-Frontal Cortices

Jan Willem W. van der Veen¹, Paul J. Carlson¹, Jun Shen¹

¹NIH, NIMH, MAP, Bethesda, MD, United States

GABA and Glx were measured in 28 volunteers using a PRESS-based two step J editing sequence. Two voxels located in the medial prefrontal cortex (MPFC) and the occipital lobe (OCC) were studied. The GABA/Cre ratio was significantly higher (P<0.001) in the OCC (0.115 +/- 0.008) than in the MPFC (0.102 +/- 0.009). Co-edited Glx/Cre ratio was significantly (P<0.001) lower in the OCC (0.0806 +/- 0.006) than in the MPFC (0.0974 +/- 0.009). Our results, combined with previously reported Cre distribution in brain, show that there are significant differences in GABA and Glx between MPFC and OCC.

Developing Brain & TTS Abnormalities

                  2018.     Optimizing a 3D Double Inversion Recovery (DIR) Protocol to Obtain Optimal Grey/White Matter Contrast in the Pediatric Brain

Amy Louise Kotsenas¹, David W. Stanley², Dan W. Rettmann³, John D. Port¹

¹Dept. of Radiology, Mayo Clinic, Rochester, MN, United States; ²GE Healthcare, Proctor, MN, United States; ³GE Healthcare, Rochester, MN, United States

The double inversion recovery (DIR) sequence supresses both cerebrospinal fluid and white matter signal which is of benefit in detecting subtle malformations of cortical development. Using the TI parameters from our adult DIR protocol did not provide optimum white matter signal suppression in pediatric patients as the T1 of the white matter varies with the degree of myelination. We were able to determine approximate TIwm values for use in DIR sequence to optimize the grey-white matter contrast in patients aged 1 year to 7.5 years. We were unable to optimize white matter suppression in children under 1 year of age.

                  2019.     An Optimized, 3D, High-Resolution MR Imaging Protocol to Study In-Utero Gyrification and Myelination of the Brain of Non-Human Primate.

Peter Kochunov¹, David Purdy², Duff Davis¹

¹Reseach Imaging Institute, UTHSCSA, san antonio, TX, United States; ²Siemens Healthcare USA, Malvern, PA , United States

Because non-human primates (NHPs) and humans share a highly orchestrated pattern of cerebral development, imaging of fetal brain maturation in NHPs provides an excellent opportunity to validate theories regarding gyrification of the cortex. Compared to human studies, structural imaging in NHPs is challenging because of the small brain size, and spatial sampling comparable to human studies (~1.0 mm3) requires brain-size-adjusted sampling volumes of ~150 microns3. Longitudinal studies of in utero NHP brain were accomplished with a true FISP isotropic 3D protocol having superior signal-to-noise ratio, low SAR, and good contrast among gray matter, white matter, CSF, and amniotic fluid.

                  2020.     Diffusion Spectrum Tractography and Histology: Developing Connectivity in the Cat Brain

Emi Takahashi¹, Guangping Dai², Ruopeng Wang², Kenichi Ohki³, Glenn D. Rosen⁴, Albert M. Galaburda⁴, Rebecca D. Folkerth⁵, Van J. Wedeen², P. Ellen Grant^1,6

¹Department of Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, United States; ²Department of Radiology, Massachusetts General Hospital; ³Department of Neurobiology, Harvard Medical School; ⁴Department of Neurology, Beth Israel Deaconess Hospital, Harvard Medical School; ⁵Department of Pathology, Childrens Hospital Boston; ⁶Department of Radiology, Children's Hospital Boston

The transient subplate (SP), located just below the immature cortex, is crucial for the formation of neuronal circuits, but it has been challenging to image abundant crossings running through the SP.  Using high-resolution diffusion spectrum imaging (DSI) tractography, we successfully imaged 3-dimensional cortical/subcortical pathways in P0 (newborn), P35 (pediatric), and P100 (adult) cats and compared the findings to histology.  In some regions, perpendicular to the projecting pathways, emergence of long association fibers was also imaged. These results show the potential of DSI in fixed pathological specimens at any stage of myelination to provide information on developing organization and connectivity.

                  2021.     Diffusion MRI of in Utero Mouse Embryos

Lin Zhao¹, Scott E. Fraser¹, J. Michael Tyszka¹

¹California Institute of Technology, Pasadena, CA, United States

In utero MR microscopy of developing mouse embryos is complicated by maternal respiratory motion and by the general lack of tissue contrast between embryonic tissues, particularly in the CNS. We explore here the use of volumetric diffusion-weighted MR microscopy to visualize the embryonic brain in utero at later development stages.

                  2022.     Prenatal MR Imaging of Focal Cortical Gyration Anomalies at Early Stage of Development

Andrea Righini¹, Cecilia Parazzini¹, Chiara Doneda¹, Laura Avagliano², Filippo Arrigoni¹, Mariangela Rustico¹, Gaetano Bulfamante², Fabio Triulzi¹

¹Radiology and Neuroradiology, Children's Hospital V. Buzzi, Milan, Italy, Italy; ²Pathology, San Paolo Hospital, Milan, Italy, Italy

We report the MRI patterns of focal cortical gyration anomalies, as they appear at a very early stage of the sulcation process (when fetal brain is almost “lyssencephalic”).  22 cases (gestational age between 21 and 24 weeks) showed focal gyration anomalies, which could be divided in four basic patterns of cortical  rim distortion: “wart-like”, “saw-tooth”, major aberrant invaginating sulucs/i, single or multiple bumps. Most of these cases presented similarities to the rat model of experimentally induced polymicrogyria. The present cohort shows how focal cortical gyration anomalies can be detected even at very early sulcation process stage

                  2023.     Fetal Imaging with Multitransmit MR at 3.0T: Preliminary Findings

Christopher G. Filippi¹, Alisa Johnson², Joshua P. Nickerson³, Betsy Sussman⁴, Jay Gonyea⁵, Trevor Andrews⁶

¹Radiology, University of Vermont School of Medicine-Fletcher Allen Health Care, Burlington, VT, United States; ²radiology, fletcher allen health care, burlington, VT, United States; ³Radiology, Fletcher Allen Health Care, Burlington, VT, United States; ⁴Radiology, Fletcher Allen Health Care-University of Vermont School of Medicine, Burlington, VT, United States; ⁵Radiology, University of Vermont School of Medicine, Burlington, VT, United States; ⁶Radiology, Philips Health Care, Cleveland, OH, United States

Multitransmit MR corrects B1 inhomogeneity which lessens dielectric shading, and a more uniform flip angle reduces focal SAR hot spots and allows for safe fetal MR imaging at 3.0 T for brain anomalies, and using multitransmit MR with SENSE allows for faster scan times and better signal to noise.  We present 3 cases comparing 3.0T fetal MR imaging with and without multitransmit to follow-up MR imaging in the perinatal period to assess the accuracy, image quality, and clinical feasibility of multitransmit MR imaging of the fetus at 3.0T

                  2024.     Fetal Cortex Extraction Using Subject Specific Priors

Paul Aljabar¹, Mellisa S. Damodaram², Mary A. Rutherford³, Daniel Rueckert¹, Joseph V. Hajnal³

¹Visual Information Processing group, Department of Computing, Imperial College London, London, United Kingdom; ²     Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Imperial College London, London, United Kingdom; ³Robert Steiner MR Unit, Imaging Sciences Department, MRC Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, United Kingdom

Automatic segmentation of the cortex from fetal brain MRI has potential as a significant tool in developmental neuroscience. We developed an accurate and robust method for extracting the cortex based on creating subject specific cortical priors using label propagation from automatically produced neonatal atlases. The method was tested on 12 fetal subjects with gestational age range from 20 -30 weeks, imaged using single shot Fast Spin Echo sequences with Slice to Volume (SVR) 3D reconstruction. The method was validated against manual segmentation and found to yield a mean error of 1.15±1.03mm.

                  2025.     White Matter Maturation of Normal Human Fetal Brain-An in Vivo Diffusion Tensor Imaging Tractography Study

Emilie ZANIN¹, Jean-Philippe Ranjeva¹, Sylviane Confort-Gouny¹, Maxime Guye¹, Danielle Denis², Patrick J. Cozzone¹, Nadine GIRARD¹

¹CRMBM UMR CNRS 6612, Marseille, France; ²CHU Nord, Marseille, France

Objective of this study was to demonstrate the ability of DTI tractography, to assess in vivo and in utero a crucial stage of human fetal brain development: the white matter maturation. We observed that evolution of diffusion characteristics during gestation were different for cortical spinal tract, optic radiations, anterior, middle and posterior part of corpus callosum reflecting the presence of structural heterogeneity between these large WM tracts during gestation. Non-linear curve fittings of normalized longitudinal and radial water diffusivities as a function of age identify 3 different phases of maturation with specific dynamics for each WM bundle type.

                  2026.     Birth the Hardest Journey in Life and a Brain Warping Experience. a Deformation Field Morphology Study of Fetal Brain During Labor

Peter Kochunov¹, Carlos Castro², Gerald Schatten³, David Purdy⁴, Duff Davis¹

¹Reseach Imaging Institute, UTHSCSA, san antonio, TX, United States; ²Ob / Gyn and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; ³Pittsburgh Development Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; ⁴Siemens Medical Solutions, Malvern, PA , United States

Neonates of Old World monkeys have the longest gestational development phase among comparably sized mammals, and as a consequence, neonatal heads approach the size of the birthing canal. This can lead to cephalo-pelvic limitation, a situation in which the size of the birthing canal presents a physical limit on the size and shape of neonate during parturition. An unexpected labor provided a rare opportunity to map deformations experienced by the neonatal brain during these normal contractions. A deformation field analysis produced a 3-D array of 3-D displacement vectors, showing dramatic regional deformation of the fetal brain during normal labor.

                  2027.     Mapping the Development of the Human Connectome

Patric Hagmann¹, Olaf Sporns², Stephan Gerhard³, Rudolph Pienaar^4,5, Jean-Philippe Thiran³, Leila Cammoun³, Neel Madan⁶, P Ellen Grant^4,5

¹Department of Radiology, CHUV-UNIL, Lausanne, VD, Switzerland; ²Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States; ³Signal Processing Laboratory 5, EPFL, Lausanne, VD, Switzerland; ⁴Division of Newborn Medicine and Department of Radiology, Children’s Hospital Boston, Boston, MA, United States; ⁵Athinoula A. Martinos Center for Biomedical Imaging, MGH-Harvard, Boston, MA, United States; ⁶Department of Radiology, MGH-Harvard, Boston, MA, United States

From birth to early adulthood the brain undergoes dramatic modifications resulting in network development and optimization. In the present study we investigate the development of the human connectome but measuring myelination trajectories of individual connections over the entire brain structural network using high b-value diffusion imaging and tractography. We found significant changes in several network measures that support increased integration and efficiency. We also observe that the network doesn’t myelinate at a uniform rate but with different myelination speeds dependant on the type of cortex.

                  2028.     Mapping Primary Gyrogenesis. In-Utero, High-Resolution Structural MRI Study of Brain Development in Fetal Baboons

Peter Kochunov¹, Carlos Castro², David Purdy³, Yi Zhang¹, Duff Davis¹

¹Reseach Imaging Institute, UTHSCSA, san antonio, TX, United States; ²Ob / Gyn and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; ³Siemens Medical Solutions, Malvern, PA , United States

Primary gyrogenesis is a poorly-understood developmental process that transforms the lissencephalic cortex of a maturing mammalian brain toward its mature, gyrencephalic state by sculpting an intricate pattern of folds (gyri) and burrows (sulci).  A novel in utero MRI protocol developed specifically for high-resolution imaging of fetal brain was used for precise tracking of global and regional gyrification in fetuses of baboons, information that would otherwise be difficult to obtain. These studies revealed a disparity in the growth rates of revealed a disparity of the growth rates in sulcal length and depth.

                  2029.     Central and Cortical Gray Mater Segmentation of Magnetic Resonance Images of the Fetal Brain

Meritxell Bach Cuadra¹, Marie Schaer², Gabriele Bonano¹, Anouk André¹, Laurent Guibaud³, Stephan Eliez², Jean-Philippe Thiran¹

¹Signal Processing Laboratory (LTS5), Ecole Polytechnique Federale de Lausanne (EPFL), Ecublens, Vaud, Switzerland; ²Service Médico-Pédagogique, Psychiatry Department, University of Geneva School of Medicine, Switzerland; ³Imagerie pédiatrique et fœtale, Hôpital Debrousse, Lyon, France

In this work we present our methodology to segment central (basal ganglia) and cortical gray mater of brain in magnetic resonance fetal imaging. This is a key step in the study of early human brain development. The results for basal ganglia segmentation are quantitatively validated in 4 cases from 29 to 32 gestational weeks. Cortical brain surface is evaluated qualitatively in a case study. Our efforts are now in testing such approach on a wider range of gestational ages that we will include in the final version of this work and studying as well its generalization to different scanners and different type of MRI sequences.

                  2030.     Correction Strategy for Infants’ Diffusion-Weighted Images Corrupted with Motion

Jessica Dubois^1,2, Ghislaine Dehaene-Lambertz^1,3, Lucie Hertz-Pannier^2,4, Giovanna Santoro¹, Jean-François Mangin, ^3,5, Cyril Poupon, ^3,5

¹U562, Inserm, Gif-sur-Yvette, France; ²LBIOM, CEA, Gif-sur-Yvette, France; ³IFR49, Paris, France; ⁴U663, Inserm, Paris, France; ⁵LNAO, CEA, Gif-sur-Yvette, France

Diffusion Tensor Imaging (DTI) offers the possibility to study the developing white matter non-invasively. However, diffusion-weighted images obtained in non-sedated infants are often corrupted with motion artifacts. We propose a post-processing methodology which takes advantage of the high diffusion orientation count and corrects these images before the computation of diffusion maps. The strategy relies on three successive steps: two steps of correction of corrupted slices (using decomposition on a spherical harmonics basis), separated by a step of 3D motion registration. This approach was validated on DTI data from 15 infants, by reliably evaluating the corpus callosum maturation with tractography-based quantification.

                  2031.     Characterization of the Pig Brain as a Neuroimaging Model for Early Human Brain Development: A Combined Structural MRI and DTI Study

Jeff D. Winter¹, Jelena Lukovic¹, Andrea Kassner^1,2

¹Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada; ²Medical Imaging, University of Toronto, Toronto, Ontario, Canada

In this study, we explored the potential of the swine brain for neurodevelopmental imaging by MRI characterization of structural and microstructural changes. We collected anatomical and diffusion tensor images from 11 juvenile (1-12 wk) pigs. A significant positive logarithmic relationship existed between body weight and tissue brain volumes, as well as the surface folding index, a measure of cortical folding. Similar to humans, fractional anisotropy exhibited a logarithmic increase with body weight for all regions investigated. No mean diffusivity changes existed. These results suggest the swine brain may provide an informative model for translational studies of early human brain development.

                  2032.     Quantitative Fiber Tracking in the Premature at Term Age Shows a Correlation with MRI Findings, Gestational Age and Head Circumference

Carola van Pul^1,2, Britt van Kooij³, Gijs Hoskam⁴, Linda de Vries³, Manon Benders³, Anna Vilanova⁴, Floris Groenendaal³

¹Clinical Physics, Maxima Medical Center, Veldhoven, Noord-Brabant, Netherlands; ²School of Medical Physics and Engineering, Eindhoven University of Technology, Eindhoven, Noord-Brabant, Netherlands; ³Neonatology, Wilhemina Children's Hospital, Utrecht, Netherlands; ⁴Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Noord-Brabant, Netherlands

We studied 92 prematurely born neonates (<31 weeks) at term equivalent age using quantitative Fiber Tracking (FT), generated on 3.0T MRI. Patients were divided into three groups, based on scoring of the conventional MRI’s. Using a general linear model, the effects of factor (group) and variables (gestational age, birth weight and head circumference) were tested. For the FA and ADC in corpus callosum fiber bundle, a significant relation with MR group was observed.  Furthermore, for the corpus callosum, volume, Cl and length depended significantly on the gestational age, suggesting an influence of age at birth on brain maturation.

                  2033.     High Angular Resolution Diffusion Imaging (HARDI) Analysis of the Motor Pathway in Infants

Jeffrey I. Berman¹, Sonia L. Bonifacio², Roland G. Henry¹, Donna M. Ferriero^2,3, Hannah C. Glass², A James Barkovich¹, Duan Xu¹

¹Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States; ²Pediatrics, University of California San Francisco, San Francisco, CA, United States; ³Neurology, University of California San Francisco, San Francisco, CA, United States

High angular resolution diffusion imaging (HARDI) was used to examine white matter microstructre in 3 and 6 month old infants with a history of birth asphyxia.  Residual-bootstrap probabilistic q-ball tractography was used to delineate the motor pathway. As in adults, the motor tract intersects other white matter tracts in the centrum semiovale and q-ball fiber tractography could traverse these regions.  Diffusion parameters were measured in the 3D region defined by fiber tractography. This study demonstrates the feasibility of using in-vivo HARDI to discriminate complex white matter architecture in infants within a reasonable exam time.

                  2034.     Vein Quantification of SWI in Infants with Hypoxic-Ischemic Encephalopathy (HIE)

Samuel Barnes^1,2, Chantal Lunderville², Gene Kitamura², Stephen Ashwal², Andre Obenaus²

¹Wayne State University, Detroit, MI, United States; ²Loma Linda University, Loma Linda, CA, United States

The use of susceptibility weighted imaging (SWI) in hypoxic-ischemic encephalopathy (HIE) can give additional information about the varying amounts of deoxyhemoglobin in cerebral veins as an indicator of metabolic stress. Abnormal levels of deoxyhemoglobin (low or high) are correlated with poor clinical outcome. This work compares different qualitative and quantitative measures of venous visibility as an indicator of deoxyhemoglobin levels and how it correlates with clinical outcome.

                  2035.     Gender Differences in the Rate of White Matter Microstructural Development During Late Childhood and Adolescence

Jonathan D. Clayden¹, Sebastian Jentschke¹, Monica Muñoz¹, Janine Cooper¹, Tina Banks², Faraneh Vargha-Khadem¹, Chris A. Clark¹

¹Institute of Child Health, University College London, London, Greater London, United Kingdom; ²Radiology Department, Great Ormond Street Hospital, London, Greater London, United Kingdom

There is evidence for various changes in white matter microstructure during development, in some cases specific to certain pathways. In this study we report what we believe to be the first evidence of gender differences in the rates of change of diffusion MRI parameters, in a healthy group of 8-17 year old children.

                  2036.     Clinical Application of Readout-Segmented (RS)-EPI for Diffusion-Weighted Imaging in Pediatric Brain

Samantha J. Holdsworth¹, Kristen Yeom¹, Stefan Skare¹, Patrick David Barnes¹, Roland Bammer¹

¹Radiology, Stanford University, Palo Alto, CA, United States

Readout-segmented (RS)-EPI has been suggested as an alternative approach to EPI for high resolution diffusion-weighted imaging (DWI) with reduced distortions. Here we implemented GRAPPA-accelerated RS-EPI DWI on 35 pediatric patients at 3T. We compared these images with standard accelerated (ASSET) EPI DWI used routinely for pediatric clinical studies. Images were categorized by resolution, distortion level, SNR, lesion conspicuity, and diagnostic confidence. RS-EPI out-performed ASSET EPI and demonstrated that it may be a useful method for DWI for evaluating lesions such as hypoxic-ischemic brain injury, diffuse axonal injury, tumors, dermoid/epidermoid, and skull base/orbital pathology.

                  2037.     Assessment of Structural Maturation of the Optic Radiation in Children with Probalistic Tractography

Michael Dayan¹, Chris A. Clark¹

¹Radiology & Physics, UCL Institute of Child Health, London, United Kingdom

The optic radiation (OR) is a component of the visual pathway assumed to mature before 3 years old. This study aimed at evaluating diffusion tensor (DT) metrics within this tract, notably fractional anisotropy (FA) and radial diffusivity (RD), as a function of age, hemisphere and gender in children aged from 7 to 18. DT probabilistic tractography based on 10000 iterations was carried out for this purpose. A one sample t-test demonstrated a hemispheric dependence for RD (p < 0.01) but not for FA (p > 0.96). A multiple regression analysis did not show any gender effect for any DT indices. A significant age dependence was found for FA (p < 0.001) and RD (p < 0.04). These findings suggest an age-related effect from 7 to 18 years well after the OR is myelin mature, which suggests that maturational and/or developmental changes occur in the OR long after myelination.

                  2038.     Anatomical Assessment of the Optic Radiation in Children with Probabilistic Tractography

Michael Dayan¹, Chris A. Clark¹

¹Radiology & Physics, UCL Institute of Child Health, London, United Kingdom

Temporal lobectomy, a surgical procedure notably carried out in children affected by intractable epilepsy, may be associated with visual field defects if the optic radiation (OR) is damaged. The lack of data in children on the spatial dimensions and location of this pathway with highly variable anterior aspect, Meyer’s loop (ML), lead us to reconstruct the OR in children in the age range 7 to 18 with probabilistic tractography. The segmentation was assessed by computing two reference anatomical distances, the distance from ML to the temporal pole (ML-TP) and to the occipital pole (ML-OP), and comparing them with other tractography and dissection studies in adults. A one sample t-test showed a hemispheric dependence for ML-TP and ML-OP (p < 0.02) and a multiple regression analysis demonstrated a gender dependence but no age effect. The distances reported in this study were similar to tractography and dissection studies in adults. These data and the statistically significant dependence on gender and hemisphere are envisaged to be relevant when considering neurosurgical planning for temporal lobectomy in children.

                  2039.     White Matter Properties Predict the Speed of Neural Processing and Cortical Maturation in Children

Colleen Dockstader^1,2, William Gaetz³, Conrad Rockel¹, Donald Mabbott¹

¹Dept of Psychology/Division of Haemotology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; ²Dept of Anaesthesia and Pain Medicine, The Hospital for Sick Children, Toronto, ON, Canada; ³Biomagnetic Imaging Laboratory, Children's Hospital of Phiadelphia, Philadelphia, PA, United States

We investigated age-related changes in the latency of the P100m visual response in occipital cortex and the biophysical properties of white matter in eleven healthy children to determine the impact of white matter growth on the maturation of neuronal signaling. Using TBSS, we found a significant relationship between FA and P100m latency in the dorsal processing stream. The latency of the P100m was inversely related to FA and positively related to age.  Our findings suggest that simple measures of evoked latency on a visuomotor-attention task reflects dorsal stream integrity that is related to stage of cortical maturation in healthy children.

                  2040.     Precision and Accuracy of Arterial Spin Labeling Perfusion MRI in the Pediatric Population

Varsha Jain¹, Mariel Giannetta¹, Michael Langham¹, Sharon Xie¹, Daniel Licht¹, Joan Giannetta¹, Timothy Roberts², John Detre¹, Hallam Hurt², Felix Wehrli¹, Jiongjiong Wang¹

¹University of Pennsylvania, Philadelphia, PA, United States; ²Children's Hospital of Philadelphia, Philadelphia, PA, United States

We evaluated the precision and accuracy of absolute CBF measurements using two arterial spin labeling (ASL) techniques, pulsed ASL (PASL) and pseudo-continuous ASL (pCASL) in a typical developing cohort of 18 healthy children 7 to 17 years old. Longitudinal reproducibility (precision) was assessed by repeated scans 2-4 weeks apart, while accuracy was assessed by comparison with total blood flow volume measured by phase-contrast (PC) MRI at the labeling plane. The results demonstrate excellent precision (ICC=0.62) and accuracy (ICC=0.77) of quantitative CBF measured by pCASL.

                  2041.     Optimisation of Fast Quantitative T2 Imaging of the Premature Brain: A Fantom Study

Laetitia Maurin^1,2, Dominique Sirinelli², Jean Philippe Cottier, ^1,3, Laurent Barantin^1,2

¹NMR Department, UMR Inserm U 930 - CNRS ERL 3106 - Université François Rabelais de Tours, TOURS, France; ²Pediatric Radiology, CHRU de TOURS, TOURS, France; ³Neuroradiology, CHRU de TOURS, TOURS, France

The aim of this work was to optimize and compare different T2 sequences so we could find one suitable for quantitative study of premature newborn brain. Four sequences were tested. After mathematical correction, T2 values found for each sequence were comparable to those calculated by the reference sequence. We choose the SSFSE sequence for premature T2 maps due to its duration. This sequence was optimized in order to decrease final acquisition time. This work allowed us to create a sequence, SSFSE 4 echoes, reliable and reproducible to calculate pediatric neurologic T2 maps with duration suitable for routine clinical practice.

                  2042.     Investigating the Need and Feasibility of Cardiac Triggering for Diffusion Imaging Data in Neonatal Subjects

Lajos R. Kozak¹, Gábor Rudas¹, Zoltán Vidnyánszky^1,2, Zoltán Nagy³

¹MR Research Center, Semmelweis University, Budapest, Hungary; ²Neurobionics Research Group, Hungarian Academy of Sciences - Pázmány Péter Catholic University - Semmelweis University, Budapest, Hungary; ³Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, United Kingdom

The feasibility of cardiac triggered diffusion data acquisition in a pediatric population was investigated. Data was collected with and without cardiac triggering either along the z gradient direction and then subjected to bootstrap statistics (3 subjects) or in 15 non-collinear directions and fitted to a tensor model (3 subjects). We found that cardiac triggering decreases the variability in the data without a significant increase in acquisition time in the investigated pediatric population.

                  2043.     RF Shield Coat for Mother to Be in the Magnet with Her Child.

Shin-ichi Urayama¹, Naozo Sugimoto², Hidenao Fukuyama¹

¹Human Brain Research Center, Kyoto University, Kyoto, Japan; ²School of Health Sciences, Faculty of Medicine, Kyoto University, Kyoto, Japan

For pediatric imaging, accompanying scan, in which an accompanying person wearing an RF shield coat is in the magnet with the child, was examined. Although there are two problems, peripheral nerve stimulation and SNR reduction, this technique is proved to be a feasible solution to avoid risks in pediatric imaging.

                  2044.     Young Adults Born with Very Low Birth Weight Demonstrate Widespread White Matter Abnormalities on Brain DTI

Live Eikenes¹, Jon Skranes², Ann-Mari Brubakk², Asta Håberg³

¹Department of circulation and medical imaging, Norwegian University of Science and Technology, Trondheim, Norway; ²Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway; ³Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway

Preterm birth with very low birth weight (VLBW, ≤ 1500 g) is associated with reduced white matter integrity and connectivity in childhood and adolescence. These changes in white matter are correlated to motor, sensory and neuropsychological impairments. This study demonstrates that preterm birth with VLBW results in significant and long-term irreversible changes in white matter microstructure that may interfere with neuropsychological functioning. Lower birth weight and perinatal problems requiring prolonged treatment on mechanical ventilator and/or intensive care have permanent negative effects on white matter integrity.

                  2045.     Fractional Anisotropy Correlates with Total IQ and Visual Perception in Young Adults Born with Very Low Birth Weight

Live Eikenes¹, Gro Løhaugen², Kjerstin Bjørlykke², Ann-Mari Brubakk², Jon Skranes², Asta Håberg³

¹Department of circulation and medical imaging, Norwegian University of Science and Technology, Trondheim, Norway; ²Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway; ³Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway

Perinatal brain injury caused by very preterm birth with very low birth weight (VLBW, ≤ 1500 g) is associated with changes in white matter integrity and connectivity, and to a variety of neurodevelopmental problems including cognitive impairments and visual perceptual deficits in childhood and adolescence. Widespread correlations between fractional anisotropy and total IQ and visual perception scores was detected in a young adult VLBW group, demonstrating the pervasive nature of the reduction in cognition and perception in this group. The results demonstrate that the neuroimpairments persist into adulthood.

                  2046.     The Rate of Reduction in Cerebral Cortical Diffusion Anisotropy Reflects the Rate of Brain Development

Lindsey A. Leigland¹, Christopher D. Kroenke¹

¹Oregon Health & Science University, Portland, OR, United States

Throughout the human gestational period, morphological differentiation of cortical neurons and glial cells cause water diffusion anisotropy within the developing cerebral cortex to decrease with age.  Herein, the loss of cortical fractional anisotropy (FA) reported by several research groups in five different species is referenced against a systematic comparative study of the timing of several milestones in brain development. It is found that, when the loss of cortical FA is approximated as an exponential decay with age, the time constant reflecting the rate of FA change is in agreement with independent estimates of the rate in which developmental events occur.

                  2047.     MRI Characterization of Cleft Lip and Palate Resulting from Hedgehog Signaling Antagonism in Mice

Rob Lipinski¹, Chihwa Song², Jerry Gipp³, Wade Bushman³, Ian Rowland⁴

¹Bowles Center for Alcohol Research, University of North Carolina, Chapel Hill, NC, United States; ²Medical Physics, University of Wisconsin, Madison, WI, United States; ³Urology Department, University of Wisconsin, Madison, WI, United States; ⁴Department of Radiology, University of Wisconsin, Madison, WI, United States

In utero Hedgehog (Hh) signaling antagonist exposure causes a spectrum of birth defects including holoprosencephaly (HPE) and cleft lip and palate (CLP).  High resolution MRI and standard histological methodologies were used to characterize the CNS phenotype of GD16.5 mouse fetuses exposed to Hh antagonists.  HPE fetuses exhibited incompletely separated cerebral hemispheres and complete pituitary and olfactory bulb agenesis.  Those with CLP exhibited olfactory bulb hypoplasia and anterior pituitary aplasia.  These results demonstrate phenotypic fidelity of the mouse model to known clinical phenotypes and highlight subtle CNS abnormalities as are expected to occur in a subset of clinical CLP populations.

                  2048.     Impaired Neurodevelopmental Outcome Associated with Increased White Matter Chol/Cr in Preterm Infants

David Price¹, Giles Simon Kendall², Alan Bainbridge¹, Samantha Johnson², Cornelia Hagmann², Roxanna Gunny³, Xavier Golay⁴, Ernest B. Cady¹, Nicola Jane Robertson², Enrico De Vita⁵

¹Medical Physics & Bio-Engineering, UCL Hospitals NHS Foundation Trust, London, United Kingdom; ²Academic Neonatology, EGA UCL Institute for Women's Health, London, United Kingdom; ³Neuroradiology, Great Ormond Street Hospital for Children; ⁴Institute of Neurology, University College London; ⁵Lysholm Department of Neuroradiology, UCL Hospitals NHS Foundation Trust, London, United Kingdom

Infants born prematurely have a higher incidence of neurodevelopmental disorders. Diffuse white matter injury is the commonest MR finding in preterm infants, and has been described qualitatively and quantitatively; the clinical correlate of diffuse white matter injury is currently unknown.  In the current study raised Cho/Cr and Lac/Cr, and reduced Naa/Cho were significantly associated with composite motor outcome at 12 months corrected age, and accounted for by significant associations with gross motor development. The raised choline could be attributed to delayed myelination, astrogliosis; the raised Lac/Cr suggests impaired oxidative phosphorylation, and the reduced Naa is in keeping with neuronal loss.

                  2049.     Developmental Coordination Disorder: A Voxel-Based MRI Study of Neural Correlates

William Lloyd¹, Mark Mon-Williams², Gordon D. Waiter³, Justin H. G. Williams⁴

¹Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, AB25 2ZD, United Kingdom; ²Institute of Physiological Sciences, University of Leeds, Leeds, United Kingdom; ³Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, United Kingdom; ⁴Department of Child Health, University of Aberdeen, Aberdeen, United Kingdom

Developmental Coordination Disorder (DCD) is a common childhood disease that affects roughly 6% of the population and can have a long-term impact for sufferers. The role of specific brain areas in DCD has long been postulated from behavioural studies, yet the underlying aetiology of the disease remains poorly understood. We used MRI to investigate correlations between regional brain volumes and psychometric measures in a DCD population. The research presented here provides, to the best of our knowledge, the first structural neuroimaging evidence of the role of regional brain structure in DCD.

                  2050.     Diffusion Tensor Imaging Study of Adolescents with Spina Bifida

Xiawei Ou^1,2, John J. Hall³, Charles M. Glasier^1,2, Jeffrey H. Snow³

¹Radiology Department, Arkansas Children's Hospital, Little Rock, AR, United States; ²Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, United States; ³Psychology Section, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States

Diffusion tensor imaging study was performed on adolescents with spina bifida and age matched controls. The study was aimed to detect the abnormalities in cerebral white matter microstructures in spina bifida patients. We found significantly elevated mean diffusivity of water in major white matter tracts, as well as decreased fractional anisotropy in the corpus callosum and callosal fibers. In addition, significant changes of white matter DTI parameters were observed in the cerebral hemisphere with ventricular shunt in spina bifida patients. Our study provides useful information of brain development affected by spina bifida.

                  2051.     Ornithine Transcarbamylase Deficiency with Persistent Abnormality in Cerebral Glutamate Metabolism

Napapon Sailasuta¹, Andrea L. Gropman², Kent Harris¹, Osama Abulseoud³, Brian D. Ross^1,4

¹Clinical MR Spectroscopy, Huntington Medical Research Institutes, Pasadena, CA, United States; ²Neurology, Children's National Medical Center, Washington D.C., United States; ³University of Southern California, Keck School of Medicine, Los Angeles, CA, United States; ⁴Rudi Schulte Research Institute, Santa Barbara , CA, United States

Despite effective treatment of hyperammonemia, children and adult survivors of ornithine transcarbamlyase deficiency (OTCD) a frequent enzyme defect of the hepatic urea cycle, exhibit a wide variety of neurological, neuropsychological, neuroimaging and neurochemical abnormalities.  Most recently, in addition to proton MRS abnormalities o sub-clinical hepatic encephalopathy, residual deficits in glutamate neurotransmission have been identified by non-invasive 13C MRS studies after ‘loading’ tests with 1-13C and 2-13C glucose.  The results point to a hitherto unrecognized defect in cerebral glucose metabolism.  Successful therapies of this new lesion may improve long term neurological outcome for this and other defects of urea synthesis.

                  2052.     Diffusion MRI Detects Different Developmental Trajectory in the Thalamus of Adolescents with Attention-Deficit Hyperactivity Disorder (ADHD) Compared with Typically Developing Controls

Maria Fatima Falangola^1,2, Vitria Adisetiyo¹, Wende R. Gelb¹, Jens H. Jensen¹, Caixia Hu¹, Ali Tabesh¹, Francisco X. Castellanos³, Adriana DiMartino³, Joseph A. Helpern^1,2

¹Radiology, New York University Langone Medical Center, New York, NY, United States; ²Center for Advanced Brain Imaging, Nathan Kline Institute, Orangeburg, NY, United States; ³Child Study Center, New York University Langone Medical Center, New York, NY, United States

Since the neuroanatomical basis of attention deficit-hyperactivity disorder (ADHD) is postulated to involve the frontal cortical-basal ganglia-thalamic-cerebellar circuits, we decided to examine the microstructural integrity of the thalamus in adolescents with ADHD using diffusion MRI, including a new technique called diffusional kurtosis imaging (DKI). We report that for a typically developing adolescent (12-18 yr), there are age-related diffusion changes in the thalamus, but no diffusion changes in the ADHD group, which suggest that there may be a difference in the trajectories of structural development in the thalamus between typically developing and ADHD adolescents.

                  2053.     Cerebellar Vermis Impairment in Children Treated for Brain Malignancies

Alena Horska¹, Ashley LaClair², Mona Mohamed¹, Carolyn T. Wells³, Todd McNutt¹, Moody Wharam¹, E Mark Mahone⁴, Wendy Kates²

¹Johns Hopkins University, Baltimore, MD, United States; ²SUNY Upstate Medical University, Syracuse, NY, United States; ³Children's National Medical Center, Rockville, MD, United States; ⁴Kennedy Krieger Institute, Baltimore, MD, United States

The goal of this prospective longitudinal study in children receiving brain radiation involving the cerebellum was to evaluate vermal volumes and performance on neuropsychological tests associated with cerebellar function. In patients, lower mean vermal volumes and impaired performance on visual-spatial and fine motor tasks were detected at baseline. At 6-months post-radiation, further decrease in vermal volumes was detected in medulloblastoma patients; the vermal volumes decrease was not associated with reduction in neuropsychological performance compared to baseline.  Regression analyses of the 6-months follow-up data from all subjects revealed better performance on the Purdue Pegboard tests with larger vermal volumes.

                  2054.     Susceptibility-Weighted Imaging in Pediatric Epilepsy

Masahiro Ida¹, Hisashi Yoshizawa¹, Shunsuke Sugawara¹, Yuko Kubo¹, Keiko Hino¹, Naoya Yorozu¹

¹Department of Radiology, Tokyo Metropolitan Ebara Hospital, Tokyo, Japan

Susceptibility-weighted imaging (SWI) exploits phase shift itself to enhance contrast caused by the susceptibility differences between tissues. SWI provides high-spatial resolution, blood-oxygen-dependent contrast without requiring contrast media. We present two pediatric patients who showed prominent cortical veins with marked hypointensity on SWI in the acute stage after onset of generalized seizure. SWI findings reflect transient misery perfusion secondary to hyperexcitation in status epilpticus. SWI directly detect impaired oxygen metabolism caused by increased oxygen demand of the cerebral tissue in pediatric patients with epileptic seizures. SWI has the possibility to diagnose acute postictal encephalopathy, before cytotoxic edema occurs on DWI.

                  2055.     Changes of Fractional Anisotropy in Ischemic White Matter in Childhood Moyamoya Disease: Correlation with Perfusion MRI.

Hyeon Tae Jeong¹, Jinna Kim , Hyeon Seok Choi, Eun Soo Kim, Seung-Koo Lee

¹Department of Radiology, Yonsei University College of Medicine, Seoul, 250 Seongsanno, Seodaemun-gu, Korea, Republic of

The purpose of this study is to evaluate the clinical relevance to FA measurement in white matter suffering from decreased perfusion in moyamoya disease, through the correlation between FA value and perfusion MRI. 

 In the areas of chronic hypoperfusion in Moyamoya disease, FA was decreased significantly although overt infarct was not demonstrated. Diffusion tensor imaging can be used in the assessment of intergrity of white matter suffering from chronic ischemia.

                  2056.     Measurement of Brain Water in Children During and After Treatment for Diabetic Ketoacidosis

Michael H. Buonocore¹, Sandra L. Wootton-Gorges², Nathan Kuppermann³, Ryan Caltagirone, Nicole S. Glaser

¹Radiology, UC Davis Imaging Research Center, Sacramento, CA, United States; ²Radiology, UC Davis Medical Center, Sacramento, CA, United States; ³Emergency Medicine and Pediatrics, UC Davis Medical Center, Sacramento, CA, United States

The purpose of this study was to measure brain water in children undergoing treatment for DKA to assess cerebral edema. Brain water was measured on a 3T system using FSPGR scans with five different flip angles, followed by non-linear curve fitting to derive proton density (M0) maps, and calibrating regional M0 map values with the values from 100% water reference vials placed within the imaged volume. Results from seven children suggest that regional brain water is elevated early in the course of treatment, confirming a degree of cerebral edema. Edema increases during the course of treatment with fluids and insulin, and then resolves after the child recovers.

                  2057.     Regional Grey-White Matter Volume Abnormalities in Children with Histories of Early Deprivation

Jeong-Won Jeong^1,2, Michael Behen^1,2, Piti Sinsoongsud^1,2, Otto Muzik, ^2,3, Benjamin Wilson^1,2, Harry T. Chugani, ^2,3

¹Pediatrics and Neurology, Wayne State University, Detroit, MI, United States; ²PET center, Children's Hospital of Michigan, Detroit, MI, United States; ³Pediatrics,  Neurology, and Radiology, Wayne State University, Detroit, MI, United States

A previous 18FDG-PET study revealed that children with histories of institutional rearing showed significantly decreased glucose metabolism in neumerous brain regions.  Dysfunction in these regions may result from severe stress of early deprivation. This study presents an atlas-based analysis to assess specific volumetric changes in predefined brain regions of the children with histories of early deprivation and examines associations between regional findings and cognitive, socioemotional, and behavioral difficulties that commonly are observed in the orphans. Significant bilateral volume reduction in grey-white matter was observed in the orphan group. It was highly correlated with their externalizing behavioral deficit and perceptual functioning.

                  2058.     Aberrant Change of Arcuate Fasciculus Geometry in Children with Angelman Syndrome: Diffusion Tensor MRI Study

Jeong-Won Jeong^1,2, Senthil Sundaram^1,2, Benjamin Wilson^1,2, Harry T. Chugani, ^2,3

¹Pediatrics and  Neurology, Wayne State University, Detroit, MI, United States; ²PET center, Children's Hospital of Michigan, Detroit, MI, United States; ³Pediatrics,  Neurology, and Radiology, Wayne State University, Detroit, MI, United States

Angelman syndrome (AS) is a genetic disorder characterized by mental retardation, speech impairment, and gait apraxia. Speech impairment is universal but severity differs, which can be characterized by myelination delay or deficits of white matter associated with language production and conception, especially of arcuate fasciculus (AF) bridging Broca¡¯s and Wernicke¡¯s areas. This study presents new DT-MRI methodology to identify aberrant shapes of arcuate fibers and quantify abnormal tracts in terms of their geometry. We found that the AF of AS patients have steeper lateral-curvatures cauisng them not to reach Wernicke¡¯ area and also their FA values were significantly reduced.

                  2059.     DTI Evaluation of Language Tracts in Autistic Patients with and Without Language Impairment Compared to Typically Developing Children

Lidia M. Nagae¹, John Dell¹, Robert A. Zimmerman¹, Timothy P.L. Roberts¹

¹Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, United States

The superior longitudinal fasciculus (SLF), related to language, was evaluated using diffusion tensor imaging in autistic patients, in particular in a specific group of autistics patients with language impairment (ASD/+LI), compared to autistic patients without language impairment (ASD/-LI), and typically developing children and adolescents (TD). Mean diffusivity, along with axial diffusivity were found to be increased in ASD/+LI when compared to TD. Intermediate values were obtained in ASD/-LI. These findings might reflect reported microstructural abnormalities of the brain, thought to be related to immature white matter development.

                  2060.     Asymmetric Interhemispheric Fiber Tracts in Patients with Hemimegalencephaly on Difusion Tensor MRI

Noriko Sato¹, Tomoyuki Takahashi, Miho Ota, Nakata Yasuhiro, Masayuki Sasaki

¹National Center Hospital of Neurology and Psychiatry, Kodaira, Tokyo, Japan

Asymmetrical fiber tract distributions passing through the corpus callosum in hemimegalencephaly patients.

                  2061.     Diffusion Tensor Imaging of Rostral Brain Areas in Patients with Congenital Central Hypoventilation Syndrome

Rajesh Kumar¹, Paul M. Macey^2,3, Mary A. Woo², Ronald M. Harper^1,3

¹Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; ²School of Nursing, UCLA, Los Angeles, CA, United States; ³Brain Research Institute, UCLA, Los Angeles, CA, United States

Congenital central hypoventilation syndrome (CCHS) patients show respiratory and autonomic deficits likely resulting from PHOX2B mutations affecting autonomic development, or from hypoxic injury. We evaluated axial- and radial-diffusivity, indicating axonal and myelin deficits, respectively, in rostral brain of CCHS. Increased radial-diffusivity emerged in the corona-radiata, internal-capsule, and corpus-callosum, suggesting myelin injury. Axial-diffusivity changes appeared in the thalamus, internal-capsule, corona-radiate, occipital, and temporal lobes, suggesting axonal deficits. Increased axial- and radial-diffusivity appeared in basal forebrain, limbic, occipital, and temporal areas, indicating myelin and axonal deficits. The mechanisms of brain injury are unknown, but likely include both hypoxic and genetic processes.

                  2062.     Surface Deformation-Based Analysis of Regional Shape Variations of Hippocampus in Children with FAS

Jesu Christopher Joseph¹, Anton Eicher², Christopher Warton¹, Sandra W Jacobson³, Joseph L Jacobson³, Christopher D Molteno, Patrick Marais², Ernesta M Meintjes¹

¹Human Biology, University of Cape Town, Cape Town, Western Cape, South Africa; ²Computer Science, University of Cape Town, Cape Town, Western Cape, South Africa; ³Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, United States

The main objective of this work is to assess the shape variations of the hippocampus structure between control and FAS affected children. For this High-resolution structural MRI images were acquired of 12 children aged 9-12 years on a 3T Siemens Allegra Scanner (6 controls and 6 FAS). Hippocampi were manually delineated. The entire structure of the hippocampus was divided into three regions, namely head, body and tail. A point distribution model, which represents the mean geometry of a shape using landmark points, was used to capture the true geometry of the hippocampus. Approximately 2366 landmark points were used. Principal Component Analysis (PCA) was used to study correlations of movement between groups of landmark points among the control children who were used as the training set and to assess the geometric variations between the healthy and exposed subjects.

                  2063.     A Realistic Model of Brain Tissue in Case of Hydrocephalus: Application of MRI, DTI and MRE

Kamal Shahim¹, Ralph Sinkus², Jean-Marie Drezet¹, Shahan Momjian³, jean-francois Molinari⁴

¹LSMX, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland; ²Laboratoire Ondes et Acoustique, ESPCI, Paris, France; ³University Hospitals of Geneva and University of Geneva, Switzerland; ⁴LSMS, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland

Hydrocephalus is a cerebral disease wherein the brain ventricles dilate and the parenchyma is stressed. In order to study this condition, a finite element model is built using the geometries of the ventricles and the skull measured by MRI. DTI is used to establish the fiber direction and the local frame. Indeed, elasticity data based on MRE is incorporated into the constitutive equation. The brain parenchyma is modeled as a porous medium. Under an applied pressure gradient, Isotropic and Transverse Isotropic models are tested and compared together. The transmission of the applied pressure is substantially influenced by the anisotropy and inhomogeneity of brain parenchyma.

                  2064.     Abnormal Brain Tissue Sodium Metabolism on MRI After Cardiac Arrest in Children

Ericka L. Fink^1,2, Patrick M. Kochanek^1,2, Ashok Panigrahy³, Fernando E. Boada^4,5

¹Critical Care Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States; ²Safar Center for Resuscitation Research, Pittsburgh, PA, United States; ³Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States; ⁴Radiology, UPMC, Pittsburgh, PA, United States; ⁵Magnetic Resonance Research Center, Pittsburgh, PA, United States

In two children with cardiac arrest, tissue sodium concentration was increased in regions of the brain that are most vulnerable to hypoxia-ischemia and reperfusion (basal ganglia and occipitoparietal cortex), representing prolonged or delayed deranged brain tissue Na metabolism.

                  2065.     Diffusional Kurtosis Imaging Assessment of Tuberous Sclerosis Complex

Vitria Adisetiyo¹, Sarah S. Milla², Howard Weiner³, Caixia Hu², Ali Tabesh², Jens H. Jensen^1,2, Joseph A. Helpern^1,2

¹Neuroscience and Physiology, New York University School of Medicine, New York, NY, United States; ²Radiology, New York University School of Medicine, New York, NY, United States; ³Neurosurgery, New York University School of Medicine, New York, NY, United States

Tuberous Sclerosis Complex (TSC) is a rare genetic disease that manifests in the CNS as cortical/subcortical tuber lesions consisting of abnormal dysplastic neurons. Tubers are presumed to contribute to epileptogenesis and to developmental delays in TSC. Given several reports of “silent” tubers with active surrounding perilesion tissue, we applied Diffusional Kurtosis Imaging (DKI) to quantitatively characterize the microstructure of tubers as compared to surrounding perilesion and normal appearing contralateral tissue in TSC patients aged 2-10 years and age-matched controls. Region of interest analysis found that only tubers are associated with significant increase in diffusivity and substantial decrease in microstructural heterogeneity.

                  2066.     Fetal Brain During a Binge Drinking Episode.  a Dynamic Susceptibility Contrast Fetal Brain Perfusion Study.

Peter Kochunov¹, Carlos Castro², Gerald Schatten³, David Purdy⁴, Hsiao-Ying Wey¹, Duff Davis¹

¹Reseach Imaging Institute, UTHSCSA, san antonio, TX, United States; ²Ob / Gyn and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; ³Pittsburgh Development Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; ⁴Siemens Healthcare USA, Malvern, PA , United States

While the teratogenic properties of alcohol are well known, the mechanisms by which alcohol-induced damage is produced in the CNS are still largely unknown. We present findings of changes in dynamic susceptibility contrast (DSC) in fetal brain of a non-human primate (baboon) during a protocol designed to approximate a binge drinking episode. Signal changes in the brain and uterus/placenta were compared using a pulse sequence protocol with high temporal and spatial resolution, showing that gadodiamide entered fetal cerebral circulation following alcohol administration.

Multiple Sclerosis

                  2067.     7 Tesla 3D-FLAIR and 3D-DIR: High Sensitivity in Cortical Regions in Multiple Sclerosis

Wolter L. de Graaf¹, F. Visser^2,3, M. P. Wattjes¹, J. Geurts⁴, P. Pouwels⁵, C. H. Polman⁶, F. Barkhof¹, P. R. Luijten², J. A. Castelijns¹

¹Radiology, VU University Medical Center, Amsterdam, Netherlands; ²Image Science Institute, University Medical Center Utrecht, Utrecht, Netherlands; ³PHILIPS Healthcare; ⁴Pathology, VU University Medical Center, Amsterdam, Netherlands; ⁵Physics and Medical Technology, VU University Medical Center, Amsterdam, Netherlands; ⁶Neurology, VU University Medical Center, Amsterdam, Netherlands

MR diagnostics in Multiple Sclerosis have benefited from sequences like fluid attenuated inversion recovery (FLAIR) and double inversion recovery (DIR), that increase sensitivity especially in cortical regions. We demonstrate use of 3D (isotropic) FLAIR, DIR and T1-weighted clinically feasible imaging at 7 Tesla. Images were read for the number of lesions visible in the regular classifications for the several sequences. Results were also compared with images obtained from the same patients at 3 Tesla. A large sensitivity increase especially in cortical regions was found at 7 Tesla for all 3D sequences. 3D-FLAIR however, proofed to be the most sensitive.

                  2068.     3D Magnetization Prepared Double Inversion Recovery (3D MP-DIR) at 7 Tesla

Frederik Visser^1,2, Jaco J M Zwanenburg¹, Wolter L. de Graaf³, J A. Castelijns³, Peter R. Luijten¹

¹UMC, Utrecht, Netherlands; ²PHILIPS Healthcare; ³VU UMC Amsterdam

Dedicated magnetization preparation pre-pulses (MP) have been designed to acquire high resolution 3D DIR images covering the whole brain at 7-Tesla.The ability to detect sub-millimeter  cortical and/or sub cortical lesions has great potential for future clinical studies.

                  2069.     Cortical Lesions in MS:  Assessment  at 7T

Kathrine T. Bluestein¹, Cherian Renil Zachariah¹, Steffen Sammet¹, Devin Elizabeth Prior¹, David Pitt², Aaron Boster², Amir Abduljalil¹, Michael V. Knopp¹, Petra Schmalbrock¹

¹Department of Radiology, The Ohio State University, Columbus, OH, United States; ²Department of Neurology, The Ohio State University, Columbus, OH, United States

Assessment of cortical lesions in MS is of significant interest, because correlation of conventional MRI with clinical findings is limited. However, detection of cortical lesions has been hampered by their small size and low contrast. In this study, we assessed cortical lesion detection in 7 MS patients and healthy controls at 7T using high resolution 3D T2* weighted, white matter attenuated (WHAT) turbo field echo and T1-weighted IR-TFE imaging. Cortical lesions were best seen with the WHAT sequence, and there was little reader variability.

                  2070.     High Resolution Magnetization Transfer Imaging at 7T : Detection of Cortical Lesions in MS Patient

Olivier E. Mougin¹, Jennifer Dixon¹, Ian Donaldson², Emma Tallantyre², Nikos Evangelou², Penny A. Gowland¹

¹Sir Peter Mansfield Magnetic Resonance Centre, School of Physics & Astronomy,University of Nottingham, Nottingham, Nottinghamshire, United Kingdom; ²Institute of Neuroscience, Nottingham, Nottinghamshire, United Kingdom

This study aims to detect cortical lesions in MS patients. High resolution MTR scans (0.5mm isotropic, as well as 0.35mm in plane resolution) have been acquired at 7T using a novel imaging sequence. The MTR contrast has been compared between white matter and grey matter, showing a greater grey matter (GM) / white matter (WM) contrast to noise ratio at 7T, providing a good delineation of WM and GM lesions at high resolution with the MTR contrast. The sequence is being used to study changes in the cortex of MS patients.

                  2071.     Surface-Based Analysis of Subpial T2*signal Changes at 7T in Multiple Sclerosis

Julien Cohen-Adad^1,2, Douglas Greve^1,2, Thomas Benner^1,2, Amy Radding^1,2, R Philip Kinkel, ^2,3, Bruce R. Rosen^1,2, Bruce Fischl^1,2, Caterina Mainero^1,2

¹A. A. Martinos Center for Biomedical Imaging, Dept. of Radiology, MGH, Charlestown, MA, United States; ²Harvard Medical School, Boston, MA, United States; ³Beth Israel Deaconess Medical Center, Boston, MA, United States

The ability to detect and to classify in vivo gray matter (GM) lesions in multiple sclerosis (MS) is required to better understand pathological processes associated with disease progression and disability. In this paper we combined ultra high field MRI (7T) with surface-based analysis to achieve quantitative assessment of subtle and diffuse cortical changes in multiple sclerosis (MS). Results show a significant increase of the T2* signal in MS patients versus controls. This increase may reflect the diffuse subpial pathology that has been described in autopsy cases of MS. Surface-based analysis facilitates the characterization of cortical lesions in vivo.

                  2072.     What Does (Quantitative) MRI of the MS Cortical Gray Matter Measure? a Post Mortem Imaging Exploration.

Alexandra Marion Seewann^1,2, Hugo Vrenken^3,4, Evert-Jan Kooi⁵, Paul van der Valk⁵, Dirk Knol⁶, Chris Polman¹, Petra Pouwels⁴, Frederik Barkhof³, Jeroen Geurts, ^3,5

¹Neurology, VU University medical center, Amsterdam, Netherlands; ²Neurology, Medical University Graz, Graz, Austria; ³Radiology, VU University medical center, Amsterdam, Netherlands; ⁴Physics and Medical Technology, VU University medical center, Amsterdam, Netherlands; ⁵Pathology, VU University medical center, Amsterdam, Netherlands; ⁶Epidemiology and Biostatistics, VU University medical center, Amsterdam, Netherlands

Only few lesions in cortical gray matter (CGM) of multiple sclerosis (MS) patients can be visualized with conventional MRI. Quantitative MRI techniques are more sensitive to cortical damage, but the histopathological correlates of quantitative MRI changes in the MS CGM are unclear. We aimed to define the underlying pathology of cortical quantitative MRI changes, and to compare MRI visible and invisible lesions by histopathology. 16 brain slices from 10 chronic MS patients were imaged with qualitative and quantitative MRI at 1.5T. Regions of interests were correlated with histopathology. 

Quantitative MRI measurements reflect the extent of cortical demyelination. Conspicuity of cortical GM lesions on conventional MRI is determined by lesional size.

                  2073.     Quantification of Formalin-Fixed MS Brain Tissue Parameters T1, T2*, PD and Phase at 7T and Comparison with Histopathology

Cherian Renil Zachariah¹, David Pitt², Peter Wassenar¹, Bradley D. Clymer¹, Amir Abduljalil¹, Michael V. Knopp¹, Petra Schmalbrock¹

¹Radiology, The Ohio State University, Columbus, OH, United States; ²Neurology, The Ohio State University, Columbus, OH, United States

Depiction of cortical demyelination in MS is still hampered by low contrast, spatial resolution and specificity.This study applies T2*-gradient echo and inversion recovery turbo field echo (IR-TFE) sequences 7T to image formalin-fixed tissue specimen  and measure T1,T2*,PD and phase differences. We notice that PD maps and phase maps may be promising for enhancing cortical lesion depiction . Following MRI, specimen were cut and labeled with anti-myelin basic protein antibodies to detect myelin and with anti-CD68 antibodies to detect activated macrophages/microglia. Scanned histology slides were scored for cortical lesions  and compared to MRI

                  2074.     MRI Texture Correlates of Pathological Findings in Post-Mortem Multiple Sclerosis Brain

Yunyan Zhang^1,2, GR Wayne Moore¹, Cornelia Laule¹, Thorarin A. Bjarnason², Piotr Kozlowski¹, Alex L. Mackay¹, Anthony L. Traboulsee¹, David K. B. Li¹

¹University of British Columbia, Vancouver, BC, Canada; ²University of Calgary, Calgary, AB, Canada

Ten post-mortem brain samples from 3 MS subjects were imaged at 7T. Regions of interest were marked on histological sections staining for myelin and axon, then were matched on MR images including lesions (14), normal appearing white matter (NAWM, 12) and regions of reduced myelin and axon (rLrB). MRI texture analysis based on polar Stockwell Transform (PST) was performed. Texture was highest in lesions, intermediate in rLrB and lowest in NAWM (p < 0.01) providing evidence that texture abnormality associates with tissue pathology. PST analysis may be a potential tool to quantify tissue integrity in MS or other neurological disorders.

                  2075.     Evaluating MACC for Improved MS Rater Agreement

David S. Wack¹, Michael G. Dwyer¹, Niels Bergsland¹, Sara Hussein¹, Robert Zivadinov¹

¹University at Buffalo, Buffalo Neuroimaging Analysis Center, Buffalo, NY, United States

The software method of Minimum Area Contour Change (MACC) is evaluated for use to improve same scan inter-rater agreement for the delineation of T2 hyper-intense MS lesions; and for the application of ROIs to follow up time points.  The MACC method improves inter-rater agreement, and performs about on par with another rater for the purpose of drawing lesion ROIs on a follow-up scan.

                  2076.     Lesion Recognition in Multiple Sclerosis: A Sequence Comparison and Quantification Study at 3T

Tobias Kober^1,2, Cristina Granziera^3,4, Delphine Ribes^1,2, Patrick Browaeys⁵, Myriam Schluep⁶, Katrin Wohlfarth⁷, Reto Meuli⁵, Gunnar Krueger²

¹Laboratory for functional and metabolic imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; ²Advanced Clinical Imaging Technology, Siemens Suisse SA - CIBM, Lausanne, Switzerland; ³Department of Neurology, Hôpitaux Universitaires de Genève, Lausanne, Switzerland; ⁴Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; ⁵Department of Radiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; ⁶Department of Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; ⁷H IM MR PLM AW Neurology, Siemens AG, Erlangen, Germany

Detection and radiological characterisation of multiple sclerosis (MS) lesions is an essential part both of clinical diagnosis and MS research. Ten early-stage MS patients and ten controls were included in this study aiming at (i) comparing five different high-resolution imaging sequences (FLAIR, MP-RAGE, DIR, SPACE, MP2RAGE) and (ii) quantifying T1 relaxation times of lesions with respect to their location in the brain. Results suggest that the DIR sequence is the most sensitive for total lesion count, followed by the MP2RAGE. Confirming previous studies, T1 relaxation times were found to be overall prolonged.

                  2077.     Pre-Filling MS Lesions on T1 and T2-Weighted Images for Improved Tissue Segmentation

Jonathan S. Jackson^1,2, Declan Chard², Antonia Ceccarelli¹, Elisa Dell'Oglio¹, Ashish Arora¹, Mohit Neema¹, Rohit Bakshi¹, David Miller², Claudia Angela Michela Wheeler-Kingshott²

¹Laboratory for Neuroimaging Research, Brigham & Women's Hospital, Harvard Medical School, Brookline, MA, United States; ²Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom

Robust lesion in-painting has been demonstrated on T1 and T2-weighted images. Many automated algorithms rely on accurate histograms for segmentation; therefore this approach to lesion WM correction based on the global histogram is appropriate and strongly recommended as a pre-processing step for MS images.

                  2078.     A New MRI Analysis Method for Lesional Heterogeneity Characterisation in Multiple Sclerosis as Demonstrated by Quantitative MRI.

Marios C. Yiannakas¹, Daniel J. Tozer¹, Declan T. Chard¹, David H. Miller¹, Claudia A.M Wheeler-Kingshott¹

¹UCL - Institute of Neurology, London, United Kingdom

In this work a new MR analysis method is presented which utilises conventional FSE dual echo data sets with the use of advanced images algebra (ADIMA) in order to enhance the dynamic range in the image with a consequent enhancement of lesional heterogeneity in MS lesions. It is found that the images show bright and dark lesions indicating heterogeneity of pathological process. Masks of these bright and dark lesions are applied to MRI parameter maps and it is found that the corresponding areas on MTR, T1 and T2 maps show different values, corresponding to the two lesion types.

                  2079.     Characterization of Multiple Sclerosis Lesions Through a Quantitative Study of Perfusion Using a Gadolinium Contrast Agent

Ryan Griffin¹, Adam Brandenberry¹, Jiachao Liang¹, Christopher Murphy¹, Trenton Rink¹, Joe Konrad¹, Xiangyu Yang¹, Michael Knopp¹, Steffen Sammet¹

¹Radiology, The Ohio State University, Columbus, OH, United States

The purpose of this study was to use Dynamic Contrast Enhanced MRI at 3T to quantitatively study the perfusion of MS lesions. Using Brix’s two compartment model, we found statistically significant differences in the mean extracted values of the pharmacokinetic values Amp and k_el of enhancing lesions with respect to those from normal appearing brain tissue, as well as a statistically significant difference in the mean extracted value of Amp from hypointense lesions with respect to normal appearing brain tissue.  Rising enhancement after the initial uptake of gadolinium (indicated by a negative k_el value) was observed for every enhancing lesion.

                  2080.     Altered Brain Perfusion and Tissue Injury in Early Multiple Sclerosis Assessed by ASL and MTR Statistical Mapping Analyses

Wafaa Zaaraoui¹, Françoise Reuter¹, Mathias Lemaire¹, Audrey Rico¹, Anthony Faivre¹, Virginie Callot¹, Irina Malikova¹, Elisabeth Soulier¹, Sylviane Confort-Gouny¹, Patrick J. Cozzone¹, Jean Pelletier¹, Bertrand Audoin¹, Jean-Philippe Ranjeva¹

¹Faculté de Médecine, CRMBM UMR CNRS 6612, Marseille, France

Recent studies have evidenced the crucial role of perfusion alteration in multiple sclerosis (MS). However, little is known about the relationships between hemodynamical parameters and local tissue damage encountered at all stages of the disease, and especially at the early phase. To investigate the putative relationships between perfusion alterations and structural local white matter and grey matter impairments in early MS, we designed a MR protocol combining statistical mapping analyses of arterial spin labeling (ASL) data and magnetization transfer ratio (MTR) data obtained in 12 patients with clinically isolated syndromes (CIS) and 12 matched controls.

                  2081.     Identifying the Start of Multiple Sclerosis Tissue Injury: A Longitudinal DTI Study

Robert J. Fox¹, Daniel Ontaneda¹, Xiofeng Wang², Ken Sakaie³, Jian Lin³, Mark J. Lowe³, Michael D. Phillips³

¹Mellen Center for MS, Cleveland Clinic, Cleveland, OH, United States; ²Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, United States; ³Radiology, Cleveland Clinic, Cleveland, OH, United States

We used HARDI DTI in a longitudinal study of multiple sclerosis patients to identify changes in brain tissue prior to the development of acute inflammation (gadolinium enhancement).  We found significantly decreased fractional anisotropy (FA) up to 10 months prior to the development of gadolinium-enhancing lesions.  Changes in FA were driven an increase in transverse diffusivity, while longitudinal diffusivity remained unchanged.  This study provides evidence for impaired myelin integrity up to 10 months prior to development of gadolinium enhancement.

                  2082.     Corpus Callosum Atrophy and Diffusion Abnormalities in Clinically Isolated Syndrome Revealed by Diffusion Tensor Tractography

Fuchun Lin¹, Chunshui Yu², Yaou Liu², Hao Lei¹

¹Wuhan Institute of Physics & Mathematics, The Chinese Academy of Sciences, Wuhan, Hubei, China; ²Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing, China

Diffusion tensor based group tractography was used to determine the corpus callosum (CC) integrity in clinically isolated syndrome (CIS). Compared to the healthy subjects, the CIS patients had significantly reduced midsagittal CC area, and significantly higher MD, λ ₁, λ ₂₃ and significantly lower FA in the entire CC. Moreover, the average FA of the normal-appearing CC of the CIS patients correlated negatively with the whole-brain lesion load while the other three diffusion indices correlated with the lesion load positively. These results suggested that both the morphology and the microstructure of the CC appear to be damaged at the stage of CIS.

                  2083.     Characterization of Early White Matter Damages in Multiple Sclerosis Patients with a Clinically Isolated Syndrome: A Tract Based Spatial Statistics Study

Salem Hannoun^1,2, Françoise Durand-Dubief, ^1,3, Christian Confavreux³, Dominique Sappey-Marinier^1,2

¹CREATIS-LRMN, University of Lyon 1, Lyon, Rhone-Alpes, France; ²CERMEP-Imagerie du Vivant, Bron, Rhone-Alpes, France; ³Neurological Hospital, Lyon, Rhone-Alpes, France

This study aims to characterize early pathological processes occurring in twelve multiple sclerosis (MS) patients with a clinically isolated syndrome (CIS) compared to relapsing remitting (RR) patients and control subjects using tract-based spatial statistics (TBSS). Significant alterations of diffusivity including FA decrease, and axial (ëa) and radial (ër) diffusivities increases, were found in extensive white matter regions of CIS patients, with ër being the most affected. If ër alterations may reflect the demyelinating processes occurring in MS, ëa can be more evocative of late appearing axonal damage as confirmed by the increase of ëa in RR compared to CIS patients.

                  2084.     Correlation of Clinical Parameters and DTI Imaging Features in Multiple Sclerosis

Carli Jessica Lehr¹, Mustafa Okan Irfanoglu¹, Firdaus Janoos, Steffen Sammet¹, Michael V. Knopp²

¹Department of Radiology, The Ohio State University, Columbus, OH, United States; ²Department of Radiology, OSU, Columbus, OH, United States

Diffusion Tensor Imaging plays an important role in the quantitative analysis of Multiple Sclerosis lesions. This study investigates the correlation between clinical parameters and DTI imaging features such as FA, ADC, lesion volumes, and tract connectivity. DTI derived features provide better correlations to clinical scores than conventional MRI-based characteristics.  The strongest correlations were found when all DTI imaging features were analyzed together against clinical data values. This illustrates the usefulness of comprehensive DTI imaging features in analyzing clinical deficits in Multiple Sclerosis.

                  2085.     Effect of Gradient Resolution in Diffusion Tensor Imaging on the Appearance of Multiple Sclerosis Lesions at 3T

Mustafa Okan Irfanoglu¹, Raghu Machiraju¹, Michael V. Knopp¹, Steffen Sammet¹

¹Department of Radiology, The Ohio State University, Columbus, OH, United States

Diffusion Tensor Imaging proved to be a useful modality for the diagnosis of Multiple Sclerosis. However, the quality of the DTI-derived scalar maps and tractography is directly dependent on experimental design. In clinical settings, scan time is a major constraint and not many diffusion weighted volumes can be acquired. In this work, we analyze the effects of gradient resolution on the appearance of multiple sclerosis regions. Results indicate that with increasing number of gradients, statistics based on lesion scalar map distributions becomes more stable and spending extra minutes might be beneficial if DTI is to be assessed for diagnosis.

                  2086.     Radial Diffusivity in Remote Optic Neuritis Discriminates Visual Outcomes

Junqian Xu¹, Robert T. Naismith¹, Nhial Tutlam¹, Kathryn M. Trinkaus², Sheng-Kwei Song³, Anne Cross¹

¹Neurology, Washington University in St. Louis, St. Louis, MO, United States; ²Biostatistics, Washington University in St. Louis, St. Louis, MO, United States; ³Radiology, Washington University in St. Louis, St. Louis, MO, United States

We studied 70 remote optic neuritis (ON) patients using the previously described high-resolution reduced field-of-view optic nerve diffusion tensor imaging protocol at 3 T.  Radial diffusivity (RD) strongly correlated with visual functional assessments, retinal nerve fiber layer thickness, and visual evoked potential.  RD also discriminated nerves with normal recovery from those with mild visual impairment, and those with mild impairment from profound visual loss.  In addition, RD differentiated healthy controls from both the clinically affected nerves and unaffected fellow nerves after ON. RD differentiated all categories of 5% contrast  sensitivity (CS) outcomes, and all categories of Pelli-Robson CS with the exception of normal recovery from mildly affected.

                  2087.     Low Contrast Visual Stimuli Yield Differential Volumes of Functional MRI Activation in Affected and Unaffected Eyes Following Recovery from Optic Neuritis

Robert A. Bermel¹, Jeffrey A. Cohen¹, Lael A. Stone¹, Blessy Mathew², Mark J. Lowe², Michael D. Phillips²

¹Neurological Institute, Cleveland Clinic, Cleveland, OH, United States; ²Imaging Institute, Cleveland Clinic, Cleveland, OH, United States

Optic neuritis (ON) is caused by inflammatory demyelination in the optic nerve, commonly as an early component of multiple sclerosis (MS). Recovery from ON is variable, facilitated by mechanisms which may include remyelination and cortical reorganization. We used visual fMRI with stimuli at three different contrast levels to investigate cortical activation following ON in 6 patients with MS and remote unilateral ON. Differences in cortical activation between affected and unaffected eyes were most apparent when utilizing the lower contrast visual stimulus. We conclude that low-contrast visual fMRI may be sensitive to detect cortical changes following ON.

                  2088.     Quantitative Fast T1 Mapping at 7 Tesla: Initial Results in Multiple Sclerosis Patients and Healthy Controls

Wolter L. de Graaf¹, J. M. Hoogduin², F. Visser^2,3, P. Pouwels⁴, H. Vrenken⁴, C. H. Polman⁵, F. Barkhof¹, P. R. Luijten², J. A. Castelijns¹

¹Radiology, VU University Medical Center, Amsterdam, Netherlands; ²Image Science Institute, University Medical Center Utrecht, Utrecht, Netherlands; ³PHILIPS Healthcare; ⁴Physics and Medical Technology, VU University Medical Center, Amsterdam, Netherlands; ⁵Neurology, VU University Medical Center, Amsterdam, Netherlands

In Multiple Sclerosis, T1 mapping has shown to be able to differentiate normal from normal appearing grey and white matter. At high field, T1 relaxation times increase and therefore it is expected that changes in brain tissue due to multiple sclerosis become more pronounced. A fast T1 mapping sequence of 4.5 minutes with an in-plane resolution of 1x1 mm2 and slice thickness of 1.5 mm is applied at 7 Tesla to assess the sensitivity of the method at high field. Patients as well as healthy controls are examined and whole brain histograms and analysis of specific brain regions are made.

                  2089.     In Vivo Quantitative Evaluation of Multiple Sclerosis Progression Using Gradient Echo Plural Contrast Imaging Technique

Jie Luo¹, Pascal Sati², Anne H. Cross³, Dmitriy A. Yablonskiy²

¹Chemistriy, Washington University in St.Louis, St. Louis, MO, United States; ²Radiology, Washington University in St. Louis, St. Louis, MO, United States; ³Neurology, Washington University in St. Louis, St. Louis, MO, United States

One reason for the weak correlation between conventional MRI (based on T1/T2 weighted images) and clinical findings is the inability of conventional MRI to quantify the extent of tissue damage. In this study, we demonstrated that an efficient method based on GEPCI technique not only depicts MS lesions similar to conventional T1w and FLAIR images, but also allows quantitative evaluation of disease progression. Combining characteristics of main peak in R2* histograms and quantitative score assigned to MS lesions, allows the evaluation not only of the volume of cerebral MS lesions, but incorporates the degree of tissue damage as well.

                  2090.     Absolute Quantification of Myelin Related Volume in the Brain

J. B.M. Warntjes¹, J. West^1,2, A. M. Landtblom^1,3, P. Lundberg²

¹Center for Medical Imaging Science and Visualization (CMIV), Linköping, Sweden; ²Department of Medicine and Health, Division of radiation physics, Linköping, Sweden; ³Department of Clinical Neuroscience, Linköping, Sweden

A method is described to measure the myelin related volume fraction for each voxel for a complete brain within a scan time of 5 to 6 minutes, based on absolute quantification of the relaxation rates R1 and R2 and proton density. The absolute decrease of visible PD with a simultaneous increase of R1 and R2 corresponds to an increase of myelin. Myelin related volume is correlated with Fractional Anisotropy maps and conventional T1W, T2W and FLAIR images. Repeated measurements show a standard deviation of 1-2% in myelin volume for the whole brain.

                  2091.     Changes in Multiple Sclerosis Over 6 Months as Seen with T2 Relaxation and Diffusion Histograms

Irene Margaret Vavasour¹, Shannon Heather Kolind², Cornelia Laule¹, Burkhard Maedler³, David K.B. Li¹, Anthony L. Traboulsee⁴, Alex L. MacKay^1,3

¹Radiology, University of British Columbia, Vancouver, BC, Canada; ²FMRIB Centre, University of Oxford, Oxford, United Kingdom; ³Physics and Astronomy, University of British Columbia; ⁴Medicine, Univeristy of British Columbia

Twelve multiple sclerosis subjects and 12 healthy age and gender matched controls were scanned twice at a 6 month interval to compare histograms derived from normal white matter (NWM), normal appearing white matter (NAWM) and multiple sclerosis lesions. Myelin water fraction (MWF), geometric mean T₂ (GMT₂), fractional anisotropy, mean diffusivity and the eigenvalues were measured. Mean MWF and GMT₂ histograms did not differ between the two time points although histograms from NWM, NAWM and lesions were different. Histograms from the diffusion metrics differed slightly between month 0 and 6. T₂ relaxation and diffusion metrics give complementary information about MS tissue.

                  2092.     Myelin Water Fraction Reduction in Multiple Sclerosis Normal Appearing White Matter: Where Are All the Zeroes?

Cornelia Laule^1,2, Shannon H. Kolind³, Irene M. Vavasour¹, Burkhard Mädler², Joel Oger⁴, Anthony L. Traboulsee⁴, Wayne Moore⁵, David KB Li¹, Alex L. MacKay¹

¹Radiology, University of British Columbia, Vancouver, BC, Canada; ²Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada; ³FMRIB Centre, University of Oxford, Oxford, United Kingdom; ⁴Medicine, University of British Columbia, Vancouver, BC, Canada; ⁵Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Using T₂ relaxation it is possible to measure myelin water fraction in multiple sclerosis (MS) normal appearing white matter (NAWM). Previous work employing a region of interest based approach found reduced myelin water fraction (MWF) in MS NAWM relative to normal white matter in controls. Using an improved 3D T2 relaxation sequence at higher field strength, we also found reduced MWF in MS NAWM which correlated with EDSS. Voxels with lowest MWF values were not uniformly distributed throughout the NAWM, but rather tended to arise near grey/white matter interfaces in the periphery of the brain.

                  2093.     Individual Voxel Based Analysis of Brain Magnetization Transfer Maps Evidences High Variability of Grey Matter Injury in Patients at the First Stage of Multiple Sclerosis

Lorena Jure¹, Wafaa Zaaraoui¹, Celia Rousseau¹, Françoise Reuter¹, Audrey Rico¹, Irina Malikova¹, Sylviane Confort-Gouny¹, Patrick J. Cozzone¹, Jean Pelletier¹, Bertrand Audoin¹, Jean-Philippe Ranjeva¹

¹CRMBM UMR CNRS 6612, Marseille, France

Various MR studies, based on group comparison have demonstrated a common pattern of grey matter (GM) injury in patients since the early stage of multiple sclerosis (MS). However, little is know about the potential variability of this early GM involvement which may determine the high variability of the functional prognosis. We propose an optimized method to obtain from statistical mapping analyses applied on MTR data, the GM MTR abnormalities of subjects at the individual level. Feasibility is demonstrated in early MS patients showing variable individual patterns of GM injury that could explain heterogeneity of clinical progression for this disease.

                  2094.     Definition of Regional Distribution of Gray Matter Loss in MS Patients with Fatigue: A Voxel-Based Morphometry Study

Maria A. Rocca¹, Gianna Riccitelli¹, Cristina Forn¹, Bruno Colombo², Giancarlo Comi², Massimo Filippi¹

¹Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Hospital San Raffaele, Milan, Italy; ²Department of Neurology, Scientific Institute and University Hospital San Raffaele, Milan, Italy

Using voxel-based morphometry, we defined the topographical distribution of  gray matter (GM) atrophy in multiple sclerosis (MS) patients with fatigue. Compared to healthy volunteers and to MS patients without fatigue, patients with fatigue had reduced GM volume in several areas of the left frontal lobe, including the middle frontal gyrus (MFG), the precentral gyrus, the superior and inferior frontal gyrus, and the cingulate gyrus. Fatigue severity was significantly correlated with atrophy of the precentral gyrus, suggesting that structural damage in areas that are part of the sensorimotor network might be among the mechanisms responsible for the presence of MS-related fatigue.

                  2095.     Evidence of Subcortical Grey Matter Atrophy and Surface Morphology Differences in Primary Progressive Multiple Sclerosis

Rose Gelineau-Kattner^1,2, Tarunya Arun¹, Damian Jenkins¹, Morgan Hough¹, Jacqueline Palace³, Mark Jenkinson¹

¹FMRIB Centre, University of Oxford, Oxford, United Kingdom; ²Baylor College of Medicine, Houston, TX, United States; ³Clinical Neurology, Oxford University and Oxford Radcliffe Hospitals NHS Trust, United Kingdom

Grey matter damage is important in the pathology of Primary Progressive Multiple Sclerosis (PPMS).  We scanned 22 patients and 7 controls at baseline, and 2, 50, and 52 weeks. FreeSurfer was used to segment subcortical grey matter and vertex analysis was performed with FSL’s FIRST to identify differences in surface morphology between groups. Significant atrophy and correlations with EDSS and/or disease duration were seen in some structures at baseline and all structures showed volume reduction over one year. Surface morphology differences were found in the thalamus and pallidum. Results highlight importance of subcortical atrophy and structural morphology differences in PPMS.

                  2096.     Regional Gray Matter Volumes Changes in Relapsing-Remitting and Secondary Progressive Multiple Sclerosis – a Longitudinal Comparative Voxel-Based Morphometry Study

Kerstin Bendfeldt¹, Louis Hofstetter, Pascal Kuster, Stefan Traud, Nicole Müller-Lenke, Yvonne Naegelin, Ludwig Kappos, Achim Gass, Thomas E. Nichols², Frederik Barkhof³, Stephan Roosendaal³, Jeroen Geurts³, Hugo Vrenken³, Ernst-Wilhelm Radue, Stefan J. Borgwardt⁴

¹University Hospital Basel, Basel, Basel-Stadt, Switzerland; ²University of Warwick; ³University of Amsterdam; ⁴Medical Image Analysis Centre, University Hospital Basel, Basel, Basel-Stadt, Switzerland

We used optimized voxel-based morphometry to study similarities and differences of regional gray matter volume development in relapsing remitting and secondary progressive MS. Although regional gray matter volume measures reveal areas of significant gray matter volume loss in RRMS, the results from this study suggest, that there is no marked acceleration in the progressive phase of the disease. This implies that the more pronounced impact of gray matter pathology in the secondary progressive phase is a result of longer linear accrual of such damage, rather than a phase-specific acceleration.

                  2097.     Gender Effects on Atrophy in MS: Cognitive Implications

Menno M. Schoonheim¹, Doriana Landi², Jeroen JG Geurts^1,3, Hugo Vrenken^1,4, Ernesto J. Sanz-Arigita¹, Linda Douw⁵, Chris H. Polman⁵, Frederik Barkhof¹

¹Radiology, VU University Medical Center, Amsterdam, Noord Holland, Netherlands; ²Università Campus Biomedico, Rome, Italy; ³Pathology, VU University Medical Center, Amsterdam, Noord Holland, Netherlands; ⁴Physics & Medical Technology, VU University Medical Center, Amsterdam, Noord Holland, Netherlands; ⁵Neurology, VU University Medical Center, Amsterdam, Noord Holland, Netherlands

Multiple sclerosis displays clear gender effects in female predisposition, as well as male negative clinical prognosis. To investigate gender effects of atrophy and cognition in MS, we acquired brain volumes and neuropsychological assessments in 32 RRMS patients (14 male, 17 female) and 22 healthy controls (10 male, 12 female). Atrophy and cognitive impairment were present in male patients only. An interaction between group and gender was present for whole-brain volume and verbal memory. These were correlated in the patient group only. This underlines the need for future research to investigate gender effects in MS more thoroughly, with possible therapeutic implications.

                  2098.     Memory Impairment in MS Correlates to Hemodynamic Response in Event-Related FMRI of Episodic Memory

Katherine A. Koenig¹, Blessy Mathew¹, Jian Lin¹, Lael Stone², Stephen Rao³, Michael Phillips¹, Mark J. Lowe¹

¹Imaging Institute, The Cleveland Clinic, Cleveland, OH, United States; ²Mellen Center, The Cleveland Clinic, Cleveland, OH, United States; ³Schey Center, The Cleveland Clinic, Cleveland, OH, United States

Nineteen patients with MS performed a verbal incidental encoding task, followed by a word recognition task (WR). Stimuli from the WR task were split into “encoded” and “non-encoded” based on performance of each subject. The encoded stimuli of the five highest performers were used to create an average t-map to select regions of interest for a correlation analysis. Areas involved in semantic encoding, including the DLPFC and the inferior frontal gyrus, showed a significant positive correlation between the fit hemodynamic response amplitude during encoded stimuli on the WR task and a test of verbal memory.

                  2099.     Corpus Callosum Fractional Anisotropy Predicts Clinical Progression and Cognitive Dysfunction in Early Primary-Progressive MS: A 5 Year Follow-Up Study

Benedetta Bodini¹, Mara Cercignani², Zhaleh Khaleeli¹, Sophie Penny^3,4, Maria Ron⁵, David H. Miller⁵, Alan J. Thompson¹, Olga Ciccarelli¹

¹NMR Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom; ²Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; ³NMR Unit, Department of Neuroinflammation, UCL Institute of Neurology , London, United Kingdom; ⁴Department of Psychology, National Hospital for Neurology and Neurosurgery, London, United Kingdom; ⁵NMR Unit, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom

The aim of this study was to identify which brain area predicts the development of disability over five years and cognitive dysfunction after five years in 32 patients with early primary-progressive multiple sclerosis. Employing tract-based spatial statistics and voxel-based morphometry, we found that lower fractional anisotropy in the corpus callosum at study entry predicted a greater progression of disability, as measured by the EDSS, over the follow-up, and worse verbal memory, attention and speed of information processing, and  executive functions, after five years.  Our findings highlight the importance of damage to the inter-hemispheric callosal pathways in determining disability in MS.

                  2100.     A Voxel Based Diffusion Tensor Image Analysis on Cognitive Decline in Mildly and Moderately Impaired Multiple Sclerosis Patients

Wim Van Hecke¹, Jan Sijbers², Alexander Leemans³, Guy Nagels⁴, Evert Vandervliet¹, Paul M. Parizel¹

¹Department of Radiology, Antwerp University Hospital, Antwerp, Belgium; ²VisionLab, University of Antwerp, Antwerp, Belgium; ³Image Sciences Institute, Utrecht, Netherlands; ⁴MS centrum, Melsbroek, Belgium

The aim of this study was to examine the relationship between the Paced Auditory Serial Addition Test and the diffusion properties that are related to microstructural white matter breakdown in patients with mild and moderate Multiple Sclerosis.

                  2101.     Early Compensatory Changes Within the Memory Network of Multiple Sclerosis Patients

Hanneke E. Hulst¹, Stefan D. Roosendaal¹, Menno M. Schoonheim¹, Lizanne J. Schweren¹, Ysbrand D. van der Werf², Chris H. Polman³, Frederik Barkhof¹, Jeroen J. Geurts^1,4

¹Radiology, VU University Medical Center, Amsterdam, Noord-Holland, Netherlands; ²Clinical Neurophysiology, VU University Medical Center, Amsterdam, Noord-Holland, Netherlands; ³Neurology, VU University Medical Center, Amsterdam, Noord-Holland, Netherlands; ⁴Pathology, VU University Medical Center , Amsterdam, Noord-Holland, Netherlands

Cognitive decline is frequently seen in multiple sclerosis (MS). This study investigates the changes in hippocampal activation patterns in MS. Functional MRI, an encoding- and retrieval paradigm, was acquired of 24 cognitively preserved (CP) and 10 cognitively impaired (CI) MS patients and 15 healthy controls (HC). Where CP patients only showed increased brain activation in the dorsal streams of the memory system, CI patients showed reduced brain activation in the (para)hippocampal areas and the ventral stream of the memory system. Our findings indicate that functional reorganization takes place early in the disease course and is a finite phenomenon in MS.

                  2102.     Memory Impairment in MS Correlates to Hemodynamic Response in Event-Related FMRI of Incidental Encoding

Katherine A. Koenig¹, Blessy Mathew¹, Jian Lin¹, Lael Stone², Stephen Rao³, Michael Phillips¹, Mark J. Lowe¹

¹Imaging Institute, The Cleveland Clinic, Cleveland, OH, United States; ²Mellen Center, The Cleveland Clinic, Cleveland, OH, United States; ³Schey Center, The Cleveland Clinic, Cleveland, OH, United States

Eighteen patients with MS performed a verbal incidental encoding task, followed by a word recognition task. Performance on the WR task was used to split incidental encoding stimuli into “encoded” and “non-encoded” maps. The fit hemodynamic response amplitude during encoded and non-encoded stimuli on the encoding task was correlated with a test of verbal memory. Against expectation, the non-encoded words showed only positive correlations, while the encoded words showed only negative correlations with verbal memory performance. It is unclear if this result is due to disease processes in MS, or due to compensatory strategies.

                  2103.     Cognitive Impairment in Early Multiple Sclerosis Related to Metabolic Impairment in Cerebellum

Wafaa Zaaraoui¹, Françoise Reuter¹, Audrey Rico¹, Irina Malikova¹, Elisabeth Soulier¹, Patrick Viout¹, Yann Le Fur¹, Sylviane Confort-Gouny¹, Patrick J. Cozzone¹, Jean Pelletier¹, Jean-Philippe Ranjeva¹, Bertrand Audoin¹

¹Faculté de Médecine, CRMBM UMR CNRS 6612, Marseille, France

While metabolic changes and cognitive impairment are known to be present in multiple sclerosis (MS) from the earliest stage of the disease, no exhaustive examinations have been performed to assess potential relationships between metabolite levels and cognitive status. Our study aimed to investigate whether magnetic resonance spectroscopic markers in normal appearing brain tissues are related to cognitive status in multiple sclerosis.

                  2104.     Is Myelin Water Fraction a Clinically Viable Biomarker of Disease in Primary Progressive Multiple Sclerosis?

Shannon Kolind^1,2, Lucy Matthews^1,3, Heidi Johansen-Berg¹, Rose Gelineau-Kattner^1,4, M Isabel Leite³, Jacqueline Palace³, Sean Deoni²

¹FMRIB Centre, University of Oxford, Oxford, United Kingdom; ²Centre for Neuroimaging Sciences, King's College London, London, United Kingdom; ³Clinical Neurology, Oxford University and Oxford Radcliffe Hospitals NHS Trust, Oxford, United Kingdom; ⁴Baylor College of Medicine, Houston, TX, United States

Critical need exists for a sensitive and specific biomarker in primary progressive multiple sclerosis (PPMS), which features diffuse neuronal and myelin damage. This study explored estimates of myelin water fraction (MWF) as such a biomarker. Sixteen PPMS patients were imaged using the mcDESPOT multi-component relaxometry technique, and correlations between MWF estimates and clinical disability scores were investigated. We found significant negative correlation between MWF and EDSS scores across diffuse brain regions. Correlations between MWF and specific scores of bladder/bowel, mental and sensory functions were found in appropriate brain regions. Findings support the emerging relevance of MWF changes to clinical manifestations.

                  2105.     Preparation for Multi-Site Myelin Water Relaxation Studies: Inter and Intra-Site Reproducibility in Normal Controls

Cornelia Laule^1,2, Irene M. Vavasour¹, Burkhard Mädler², Trudy Harris³, David KB Li¹, Anthony L. Traboulsee⁴, Alex L. MacKay^1,2

¹Radiology, University of British Columbia, Vancouver, BC, Canada; ²Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada; ³UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada; ⁴Medicine, University of British Columbia, Vancouver, BC, Canada

Quantitative assessment of T₁ and T₂ relaxation has the potential to provide important in-vivo markers for disease progression and treatment efficacy in pharmaceutical trials. The present study examine cross-site reproducibility of mean T₁, geometric mean T₂ (GMT₂) and myelin water fraction (MWF) measured on the same 5 people at 6 sites. Average percent differences of inter and intra-site reproducibility was <1% for GMT₂, ~3% for T₁ and ~6% for MWF. While mean T₁ and GMT₂ have slightly better reproducibility, MWF provides a specific measure of brain myelin content, and is hence ideal for assessing neuroprotective and remyelination strategies.

                  2106.     1H-MRS and Water Proton T1 Investigations of New Lesions in Relapse Remitting Multiple Sclerosis

Madeleine Hodgson¹, Cornelia Laule^1,2, Irene Vavasour^1,2, Burkhard Mädler¹, Alex MacKay^1,2

¹Physics, University of British Columbia, Vancouver, British Columbia, Canada; ²Radiology, University of British Columbia, Vancouver, British Columbia, Canada

Little is known about the pathological evolution of acute MS lesions. Using 1H-MRS one can measure changes in metabolites such as n-acetyl-aspartate (NAA), which may become altered in MS.  We used 1H-MRS and water proton T1 measurements to investigate the time-course of biochemical changes occurring in new MS lesions. Multi-voxel 1H-MRS data was acquired monthly from 20 Relapsing-Remitting MS subjects.  Metabolite and water proton T1 changes for the same volume were investigated  Lesions exhibited a significant decrease in NAA and a significant increase in mean T1, compared to normal appearing white matter, 2 months before lesion appearance on conventional imaging.

                  2107.     1H-MRS Study of Secondary Progressive MS Patients Followed Over 2 Years in the Dirucotide (MBP8298) Placebo Controlled Study

Madeleine Hodgson¹, Cornelia Laule^1,2, Irene Vavasour^1,2, David Li², Yinshan Zhao³, Tony Traboulsee³, Joel Oger³, Alex MacKay^1,2

¹Physics, University of British Columbia, Vancouver, British Columbia, Canada; ²Radiology, University of British Columbia, Vancouver, British Columbia, Canada; ³Medicine, University of British Columbia, Vancouver, British Columbia, Canada

1H-MRS is a useful technique for evaluating demyelination and axonal integrity and thus can be used to monitor disease progression in Multiple Sclerosis (MS).  Dirucotide (MBP8298) has exhibited potential as a treatment for Secondary Progressive MS (SPMS) to slow disease progression.  The effects of Dirucotide were investigated using 1H-MRS in a single centre, double-blinded MRI substudy with a placebo control.  There is no change observed in important metabolites in either of the cohorts over a two-year period, which is perhaps not surprising given that Dirucotide did not meet primary endpoints in the MAESTRO-01 Phase III trial.

                  2108.     In Vivo Measurement of Glutathione (GSH) in the Human Brain with Secondary Progressive Multiple Sclerosis Using Selective Multiple Quantum Chemical Shift Imaging of GSH

In-Young Choi^1,2, Sang-Pil Lee^1,3, Sharon G. Lynch⁴

¹Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States; ²Department of Neurology, Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States; ³Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States; ⁴Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States

Oxidative stress has been implicated in multiple sclerosis (MS), a chronic inflammatory disease with the presence of a neurodegenerative process particularly in progressive MS.  However, the effects of oxidative stress in MS have not been well described in the living human brain. In this study, we measured the cerebral GSH levels in the patients with secondary progressive MS (SPMS) using doubly selective multiple quantum GSH CSI. The GSH levels were significantly lower in the SPMS patients compared with those in the age- and gender-matched healthy controls, indicating the presence of increased oxidative stress in the absence of measurable inflammation.

                  2109.     Quantitative Venous Vasculature Assessment on Susceptibility-Weighted Imaging Reflects Presence of Severe Chronic Venous Insufficiency in the Brain Parenchyma of Multiple Sclerosis Patients. a Case-Control Study

Guy U. Poloni¹, Paolo Zamboni², E. Mark Haacke³, Stefano Bastianello⁴, Michael G. Dwyer¹, Niels Bergsland⁵, Claudiu V. Schirda¹, David Wack¹, Christopher R. Magnano¹, Bianca Weinstock-Guttman⁶, Fabrizio Salvi², David Hojnacki⁶, Robert Zivadinov¹

¹University at Buffalo, Buffalo Neuroimaging Analysis Center, Buffalo, NY, United States; ²University of Ferrera- Bellaria Neurosciences, Vascular Diseases Center, Ferrera, Italy; ³Radiology, Wayne State University, Detroit, MI, United States; ⁴Institu Neurologico Casimiro Mondino, Neuroradiology Unit, Pavia, Italy; ⁵University at Buffalo, Buffalo Neuroimaging Analysis Center, Buffalo, United States; ⁶University at Buffalo, The Jacobs Neurological Institute, Buffalo, NY, United States

To develop an objective method for quantifying venous vasculature in brain parenchyma on susceptibility-weighted imaging (SWI). To apply this technique in multiple sclerosis (MS) patients and in healthy controls (HC).

                  2110.     A Semi-Automated Analysis Pipeline for Reproducible SWI Analysis of Multiple Sclerosis Pathology

Michael G. Dwyer¹, Niels Bergsland², Claudiu Schirda², Mari Heininen-Brown, Ellen Carl, David Wack, Guy U. Poloni, Robert Zivadinov³

¹Buffalo  Neuroimaging Analysis Center; ²University at Buffalo, Buffalo Neuroimaging Analysis Center, Buffalo, NY, United States; ³Neurology, Buffalo Neuroimaging Analysis Center, Buffalo , NY , United States

Susceptibility-weighted imaging (SWI) has gained much interest recently as a sensitive means for detecting iron deposition in a variety of diseases, including multiple sclerosis (SM). We propose a fast and reproducible analysis pipeline to extract detailed quantitative SWI data and to combine it with other established indicators of disease state (including magnetization transfer and perfusion imaging).

                  2111.     Chronic Cerebrospinal Venous Insufficiency and Iron Deposition on Susceptibility-Weighted Imaging in Patients with Multiple Sclerosis

Robert Zivadinov¹, Paolo Zamboni², E. Mark Haacke³, Erica Menegatti⁴, Bianca Weinstock-Guttman⁵, Claudiu Schirda¹, Anna M. Malagoni², David Hojnacki⁵, Cheryl Kennedy¹, Ellen Carl¹, Niels Bergsland¹, Sara Hussein¹, Mari Heininen-Brown¹, Ilaria Bartolomei⁶, Fabrizio Salvi², Michael G. Dwyer¹

¹University at Buffalo, Buffalo Neuroimaging Analysis Center, Buffalo, NY, United States; ²University of Ferrera- Bellaria Neurosciences, Vascular Diseases Center, Ferrera, Italy; ³MR Research Facility, Wayne State University, Detroit, MI, United States; ⁴University of Ferrera- Bellaria Neurosciences, Vascular Diseases Center, Buffalo, NY, United States; ⁵University at Buffalo, The Jacobs Neurological Institute, Buffalo, NY, United States; ⁶University of Ferrera- Bellaria Neurosciences, Vascular Diseases Center, Ferrera, NY, United States

Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture in multiple sclerosis patients characterized by stenoses affecting the main extracranial venous outflow pathways and by a high rate of cerebral venous reflux that may lead to increased iron deposition in the brain. We explored relationship between venous hemodynamic (VH) parameters and disability and iron concentration in deep-gray matter (DGM) structures and lesions on susceptibility-weighted imaging. There was a significant association between higher number of VH criteria and higher iron concentration in T2 and T1 lesion volumes. Higher iron concentration in DGM structures was strongly associated with higher disability status.

                  2112.     Cine Cerebrospinal Fluid Imaging in Multiple Sclerosis. a Case-Control Study

Robert Zivadinov¹, Christopher Magnano², Bianca Weinstock-Guttman³, David Wack², Eric Lindzen³, David Hojnacki³, Niels Bergsland², Cheryl Kennedy², Justine Reuther², Michael G. Dwyer², Claudiu Schirda²

¹Neurology, Buffalo Neuroimaging Analysis Center, Buffalo , NY , United States; ²University at Buffalo, Buffalo Neuroimaging Analysis Center, Buffalo, NY, United States; ³University at Buffalo, The Jacobs Neurological Institute, Buffalo, NY, United States

To investigate the cerebrospinal fluid (CSF) dynamics in Sylvius aqueduct in multiple sclerosis (MS) patients versus healthy controls (HC) and to define correlates with other specific disease metrics.

                  2113.     An Objective Quantification Technique of the Cerebrospinal Fluid (CSF) Flow in the Cerebral Aqueduct, in Patients with Multiple Sclerosis

Claudiu Schirda¹, Paolo Zamboni², Christopher Magnano¹, Eric Lindzen³, David Wack¹, Bianca Weinstock-Guttman³, Deepa Ramasamy¹, Ellen Carl¹, David Hojnacki³, Cheryl Kennedy¹, Michael Dwyer¹, Niels Bergsland¹, Jennifer Cox¹, Fabrizio Salvi², Robert Zivadinov^1,3

¹Buffalo Neuroimaging Analysis Center, University at Buffalo, Buffalo, NY, United States; ²University of Ferrara, Ferrara, Italy; ³The Jacobs Neurological Institute, University at Buffalo, Buffalo, NY, United States

When compared to white matter or gray matter, the involvement of the cerebrospinal fluid (CSF) in the Multiple Sclerosis (MS) disease has scarcely been explored until now and typically a lumbar puncture is required. We investigate the flow properties of the CSF in the aqueduct of Sylvius and how they relate to other MS disease metrics, by using non-invasive MRI in a pilot study with MS patients and healthy controls. An objective flow quantification technique using automatic segmentation of the aqueduct was developed and was validated on a flow phantom and scan-rescanning 4 subjects within a week.

                  2114.     Effects of Temporal Resolution on Blood-Brain Barrier Permeability Measurement with Dynamic Contrast Enhanced MRI in Multiple Sclerosis Enhancing Lesions

Ileana Ozana Jelescu¹, Ilana Ruth Leppert¹, Sridar Narayanan¹, Douglas L. Arnold¹, G Bruce Pike¹

¹Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

Accurate and reproducible measurements of blood-brain barrier permeability in MS enhancing lesions would benefit follow-ups of lesion activity and comparison of detection sensitivity between different Gd-enhanced protocols. We propose a Dynamic Contrast Enhanced MRI protocol that allows sampling of the arterial input function with high temporal resolution in the first minute post-injection, followed by a lower temporal resolution but high spatial resolution acquisition of enhancement in lesions. This “dual temporal resolution” method was tested experimentally and through simulations and, compared to previous methods, has proven to yield more accurate and precise estimates over a wide range of permeability values.

                  2115.     Relative Recirculation (RR): A Potential Tool for Monitoring Blood-Brain Barrier Disruption in Secondary Progressive Multiple Sclerosis

Andrea Kassner^1,2, Igor Sitartchouk¹, Rebecca E. Thornhill^1,2, Timothy J. Carroll³, Chaitali Mulay⁴, Richard Aviv^1,4

¹Medical Imaging, University of Toronto, Toronto, Ontario, Canada; ²Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; ³Radiology, Northwestern University, Chicago, IL, United States; ⁴Neuroradiology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. While blood-brain barrier (BBB) disruption associated with relapsing-remitting MS is readily identified using gadolinium-enhanced T1-weighted MRI, these MRI markers lack the sensitivity required for monitoring secondary progressive MS. Relative recirculation (rR), a parameter extracted from dynamic susceptibility contrast (DSC) data, can delineate BBB disruption in patients with acute ischemic stroke. Relative recirculation was measured from DSC perfusion data obtained from 19 patients with secondary progressive MS. The average lesion rR was significantly greater than in normal appearing white matter and shows potential for monitoring secondary progressive MS.

                  2116.     A Three-Dimensional Multi-Scale Line Filter Algorithm for Segmentation of Vein Vessels in Susceptibility Weighted Images

Guy U. Poloni^1,2, Michael G. Dwyer¹, Niels Bergsland¹, Claudiu V. Schirda¹, Stefano Bastianello², Robert Zivadinov^3,4

¹Buffalo Neuroimaging Analysis Center, Buffalo, NY, United States; ²Neuroradiology Unit, Fondazione “Istituto Neurologico Casimiro Mondino” IRCCS, Pavia, Italy; ³Buffalo Neuroimaging Analysis Center, Buffalo , NY , United States; ⁴The Jacobs Neurological Institute, University at Buffalo, Buffalo, NY, United States

SWI is a MRI application that can directly image cerebral veins through the use of phase information to enhance local susceptibility. The present work introduces an algorithm, based on a 3-dimensional linear filter, for segmenting and measuring vein vessels in the brain and for classifying vessels according to their diameter. The resultant multi-scale line-filtered images provide significantly improved segmentation and visualization of curvilinear structures, in particular with respect to small vessels, contributing to the quantitative investigation of vascular impairment in the pathologies of the central nervous system.

White Matter Diseases

                  2117.     MR Relaxometry and Diffusion Tensor Imaging of Normal Appearing White Matter in Mild Traumatic Brain Injury.

Christopher James Andrew Cowie^1,2, Benjamin S. Aribisala¹, Jiabao He¹, Joshua Wood¹, Alexander David Mendelow², Patrick Mitchell², Andrew M. Blamire¹

¹Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, Tyne & Wear, United Kingdom; ²Department of Neurosurgery, Newcastle General Hospital, Newcastle upon Tyne, Tyne & Wear, United Kingdom

Mild traumatic brain injury (mTBI) is associated with long term cognitive and affective symptoms. Findings on conventional MRI often do not account for the duration and severity of these symptoms. The aim of this study was to ascertain whether MR relaxometry and diffusion tensor imaging would reveal abnormalities in normal appearing white matter (NAWM) in patients with mTBI. Whole group analysis showed no significant differences, but after grouping the patients according to the side of the visible lesion, a significant increase in the mean diffusivity (MD) of ipsilateral frontal lobe NAWM was demonstrated.

                  2118.     Quantification of DTT Metrics in Various Fiber Bundle in Patients with Frontal Lobe Injury and Its Correlation with Neuropsychological Tests

Manoj Kumar¹, Deepa Pal¹, Ram KS Rathore², Bal K. Ojha³, Anil Chandra³, Raj Kumar³, Rakesh Kumar Gupta¹

¹Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ²Mathematics and Statistics, Indian Institute of Technology, , Kanpur, Uttar Pradesh, India; ³Neurosurgery, Chhatrapati Shahuji Maharaj Medical University,, Lucknow, Uttar Pradesh, India

Diffusion tensor imaging (DTI) was performed within 7 days and after 6 months of injury in 21 traumatic brain injury (TBI) patients with frontal lobe injury and 21 age/sex matched controls. Diffusion tensor tractography (DTT) was proposed for quantification of various white matter (WM) tracts in patients with frontal lobe injury to assess diffuse axonal injury (DAI) and to look for correlation of these fiber bundles measures with various neuropsychological tests (NPT). We found reduced fractional anisotropy (FA) and increased mean diffusivity (MD) values in all WM tracts in TBI patients compared to controls, NPT scores were found to be significantly impaired in follow-up patients compare to controls and some of these tests showed significant correlation with DTI indices with different WM tracts. WM tracts which show significant difference on DTT were also correlated with those NPT which are associated with main function of frontal lobe such as memory, attention, visual and motor function. It appears more realistic methods for DAI quantification in TBI patients and provides information about structural integrity and connectivity of whole fiber tracts.

                  2119.     White Matter Degradation in Fornix After Mild Traumatic Brain Injury: Cross-Sectional and Longitudinal MRI Investigations

Wang Zhan¹, Grant Gauger², Lauren Boreta¹, Gary Abrams², Karl Young¹, Yu Zhang¹, Marzieh Nezamzadeh¹, Norbert Schuff¹, Michael W. Weiner¹

¹Radiology and Medical Imaging, University of California, San Francisco, San Francisco, CA, United States; ²VA Medical Center, San Francisco

Fornix is one of the primary white matter structures of the limbic system, and its damage in mild traumatic brain injury (TBI) may explain the memory and learning dysfunctions in the post-concussion syndrome. N=24 TBI patients were longitudinally studied in two time points using T1 anatomical imaging and diffusion tensor imaging (DTI) to measure the fornix-to-brain ratio (FBR) and WM integrity of fornix, and compared with matched healthy controls. Our data show that the WM degradation in fornix onset in the acute stage after mild TBI, and that this degradation continued during the following 6-month period of recovery.

                  2120.     Detection of Tissue Changes in Traumatic Brain Injury Patients Using Automatic Regional Analysis of Quantitative MR Scans

Benjamin Segun Aribisala¹, Christopher J.A. Cowie^1,2, Jiabao He¹, Joshua Wood¹, David A. Mendelow², Patrick Mitchell², Andrew M. Blamire¹

¹Institute of Cellular Medicine, Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, England, United Kingdom; ²Department of Neurosurgery, Newcastle General Hospital, Newcastle University, Newcastle upon Tyne, England, United Kingdom

Traumatic head injury is one of the major causes of neurological morbidity and mortality in the UK with more than 0.1 million admissions per year with primary diagnosis of head injury. This constitutes a huge drain on medical resources. Majority of these patients have ongoing symptoms which do not correlate with MRI or CT findings.  Here we investigated a cohort of patients with mild TBI using multi-parametric real space analysis. Our results show that a fully automatic real space method of analysing quantitative MR parameters can be used to detect changes in normal appearing tissues in patients suffering mild TBI.

                  2121.     Using Jacobean Determinants to Map Within-Subject Serial Changes in Brain Volume in Difficult Contexts: Implementation in Traumatic Brain Injury with Decompressive Craniectomy

Steve Sawiak¹, Virginia FJ Newcombe², M G. Abate², Jo G. Outtrim², John D. Pickard¹, T A. Carpenter¹, Guy B. Williams¹, David K. Menon²

¹Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom; ²Division of Anaesthesia, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom

Atrophy is common post traumatic brain injury (TBI) and may correlate with outcome. We hypothesised that quantification of Jacobian determinants could assess progressive changes in brain volume in within subject analyses, even in contexts that produce major problems with comparative analyses.  We show implementation of the approach in a single TBI subject with serial scans before and up to 12 months after decompressive craniectomy, compared to results from healthy controls.  The results indicate it is possible to monitor the changes in brain volume over time post TBI in an individual.

                  2122.     The Relationship of White Matter Lesion and Contract Enhanced Lesion Development Courses in Radiation Induced Brain Injury: An MRI Based Study

H Huang^1,2, M Deng¹, S F. Leung³, Y L. Chan¹, D K. Yeung¹, H C. Chan¹, A T. Ahuja¹, Y X. Wang¹

¹Department of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong; ²Department of Radiology, The Shenzhen Third People’s Hospital, Shenzhen, China; ³Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital

The natural course of radiation induced brain injury still remains poorly understood. Among the abnormalities white matter edema-like lesions (WML) and contrast enhanced necrotic lesions (CEL) have been most commonly reported. It was recently reported that radiation induced brain injury was not always an irreversible and progressive process, but one that could show regression and resolution. In total 22 nasopharyngeal carcinoma patients with 36 lobes displaying WML and CEL were analysed in this study. The preliminary results of this study suggest the development of WML and CEL tend to follow the same pattern, and not develop in the opposite direction.

                  2123.     Dynamic Susceptibility Contrast Mr Perfusion Imaging of the Brain  in X-Linked Adrenoleukodystrophy

Otto Rapalino¹, Mara Kunst¹, Patricia Musolino², Florian Eichler^2,3

¹Radiology, Massachusetts General Hospital, Boston, MA, United States; ²Neurology, Massachusetts General Hospital, Boston, MA, United States; ³Martinos Center for Biomedical Imaging, Charlestown, MA, United States

Dynamic Susceptibility Contrast (DSC) MR perfusion was used to characterize the perfusion abnormalities in patients with adrenoleukodystrophy and adrenomyeloneuropathy.  This study demonstrates that the combination of conventional MR and DSC perfusion MR techniques allows the definition of five different zones with characteristic profiles of abnormal signal and perfusion in patients with adrenoleukodystrophy that correspond to the zonal anatomy previously described on pathological studies.  These findings can be helpful in predicting disease progression, selecting patients for therapeutic interventions and elucidating the pathophysiology of this disorder.

                  2124.     Diffusion Tensor Imaging Detects Abnormalities in the Corticospinal Tract of the Brain in Patients with Adrenomyeloneuropathy

Aliya Gifford¹, Anna Binstock², Joseph Wang³, Kathy Zackowski^3,4, Jonathan Farrell^5,6, Peter C.M. van Zijl^5,6, Gerald Raymond^1,4, Seth Smith^7,8

¹Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, United States; ²University of Maryland School of Medicine, Baltimore, MD; ³Motion Analysis Laboratory, Kennedy Krieger Institute, Baltimore, MD; ⁴Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD; ⁵Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD; ⁶F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD; ⁷Vanderbilt University Institute of Imaging Science, United States; ⁸Department of Radiology, Vanderbilt University, Nashville, TN

Adrenomyeloneuropathy (AMN) is characterized by primary distal axonopathy with secondary demyelination.  In this study we performed diffusion tensor imaging (DTI) at 1.5T on 29 healthy volunteers and 39 AMN patients.  Tractography of the left and right corticospinal tracts (CST) were performed and diffusion anisotropy and diffusivity were computed.  A significant change in FA and perpendicular diffusivity was found from the pons to mid-brain (p<0.01) and mid-brain to thalamus (p<0.001) regions in AMN patients.  This suggests that DTI can quantify the pathway-specific abnormalities in AMN, and results are in corroboration with knowledge that cerebral damage is present in AMN.

                  2125.     A Seven Years Quantitative MRI and MRS Follow-Up Study on Successful Bone Marrow Transplantation for Presymptomatic Juvenile Metachromatic Leukodystrophy

Xiao-Qi Ding¹, Annette Bley², Alfried Kohlschütter², Jens Fiehler³, Heinrich Lanfermann¹

¹Institute of  Diagnostic and Interventional Neuroradiology , Hannover Medical School, Hannover, Germany; ²Department of Paediatrics, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; ³Department of Neuroradiology, University Medical Centre Hamburg-Eppend, Hamburg, Germany

Bone marrow transplantation (BMT) has been advocated as treatment of juvenile metachromatic leukodystrophy (MLD). The effectiveness of this high-risk treatment is still questionable due to the rarity of follow-up reports. We carried out a 7 years MRI follow-up on a boy with juvenile MLD who had received BMT treatment in the presymptomatic phase and remained free of MLD symptoms during the observation. Conventional morphological MRI showed minor stable white matter lesions while quantitative T2-mapping and MR spectroscopy evidenced a stagnancy of the demyelination process and an ongoing maturation of the brain.

                  2126.     Voxelwise Analysis of Pelizeaus-Merzbacher Disease in 17 Genetically Proven Cases Using Diffusion Tensor Imaging

Onur Ozyurt¹, Alp Dincer², Zuhal Yapici³, Cengiz Yalcinkaya⁴, Mefkure Eraksoy³, Cengizhan Ozturk¹

¹Bogazici University, Biomedical Engineering Institute, Istanbul, Turkey; ²Acibadem University, School of Medicine, Department of Radiology; ³Istanbul University, Istanbul Faculty of Medicine, Department of Neurology; ⁴Istanbul University, Cerrahpasa Medical Faculty, Department of Neurology

In this study, tract based spatial statistics (TBSS) approach is used for the investigation of Pelizeaus-Merzbacher Disease (PMD), which is a rare X-linked disease characterized by defective central nervous system myelination due to a mutation in the proteolipid protein 1 gene.

                  2127.     In Vivo Proton MR Spectroscopy Findings Specific for Adenylosuccinate Lyase Deficiency

Steffi Dreha-Kulaczewski¹, Marco Henneke¹, Knut Brockmann¹, Marinette van der Graaf^2,3, Michel Willemsen⁴, Udo Engelke⁵, Peter Dechent⁶, Arend Heerschap³, Gunther Helms⁶, Ron Wevers⁵, Jutta Gaertner¹

¹Department of Pediatrics and Pediatric Neurology, Georg August University, Goettingen, Germany; ²Clinical Physics Laboratory in the Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; ³Department of Radiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; ⁴Department of Pediatric Neurology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; ⁵Laboratory of Genetic, Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; ⁶MR-Research in Neurology and Psychiatry, Georg August University, Goettingen, Germany

Adenylosuccinate lyase (ADSL) deficiency is an inherited metabolic disorder and characterized by the accumulation of succinylaminoimidazolecarboxamide riboside and succinyladenosine (S-Ado) in tissue and body fluids. In three children, presenting with psychomotor delay, autistic features, and white matter changes on brain MRI, screening for inborn errors of metabolism included in vitro proton MRS. It revealed resonances at 8.27 and 8.29ppm that correspond to S-Ado. In vivo proton MRS showed a signal at 8.3ppm in gray and white matter brain regions of all three patients, which was undetectable in controls. In vivo proton MRS provides a conclusive finding in ADSL deficiency.

                  2128.     Cerebral Accumulation of 3-Hydroxyisovaleric Acid in Adults Until Recently Unaware of Having 3-Methylcrotonyl-CoA Carboxylase (MCC) Deficiency

Marinette van der Graaf^1,2, Udo F.H. Engelke³, Eva Morava⁴, Mirian C.H. Janssen⁵, Maaike C. de Vries⁴, Leo AJ Kluijtmans³, Bozena Goraj¹, Arend Heerschap¹, Ron A. Wevers³

¹Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; ²Clinical Physics Laboratory, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; ³Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; ⁴Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; ⁵General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

Recently, our group showed for the first time cerebral accumulation of 3-hydroxyisovaleric acid (3HIVA) in a pediatric patient with 3-Methylcrotonyl-CoA Carboxylase deficiency (MCCD). 3HIVA has been considered to have neurotoxic effects, but this is under debate. The present study reports on cerebral accumulation of 3HIVA detected by 3T proton MRS in two adult women with MCCD, whom deficiency was  discovered by a positive neonatal screening of their healthy new-born babies. As the women had not been  aware of having this disorder before and they have no or limited complaints, 3HIVA is postulated to have no or minor neurotoxic effect.

                  2129.     White Matter Lesion Load in Type 2 Diabetes - A VBM Study

Lars Eric Forsberg^1,2, Sigurdur Sigurdsson³, Thor Aspelund^3,4, Jesper Fredriksson², Smári Kristinsson², Ólafur Kjartansson³, Bryndís Óskarsdóttir³, Pálmi V. Jónsson^3,4, Gudný Eiríksdóttir³, Tamara B. Harris⁵, Mark A. van Buchem⁶, Alex Zijdenbos⁷, Lenore J. Launer⁵, Vilmundur Gudnason^3,4

¹Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; ²Raförninn ehf, Reykjavik, Iceland; ³Icelandic Heart Association, Kopavogur, Iceland; ⁴The University of Iceland, Reykjavik, Iceland; ⁵Laboratory of Epidemiology, Demography, and Biometry, National Institute of Aging, Bethesda, MD, United States; ⁶Department of Radiology, Leiden University Medical Center, Leiden, Netherlands; ⁷Biospective Inc., Montreal, Canada

Type 2 diabetes (DM2) is a known risk factor for white matter lesions (WML) in elderly subjects. In this study, we used voxel-based morphometry (VBM) to analyse the common distribution of WML in 215 subjects with DM2 (average age 76.1 years) compared to 1675 non-diabetic controls (average age 75.8 years). Our main finding is that DM2 subjects have commonly large WML areas in the brain that extend from the frontal lobe to the parietal lobe.

                  2130.     Relationship Between Serum Inflammatory Markers, Regional Brain Volumes, and Perfusion in Older Diabetic Subjects

Peng Zhao¹, Vera Novak¹, Kun Hu¹, Medha Munshi¹, David Alsop², Amir Abduljalil³, Peter Novak⁴

¹Gerontology, Beth Israel Deaconess Medical Center, Boston, MA, United States; ²Radiology, Beth Israel Deaconess Medical Center, Boston, MA, United States; ³Radiology, Ohio State University, Columbus, OH, United States; ⁴Neurolgoy, University of Massachusetts Medical School, Worcester, MA, United States

Type 2 DM is a major risk factor for both large and small vessel atherosclerosis, stroke, and vascular dementia. Hyperglycemia is a common mechanism of endothelial dysfunction and neuronal cell damage. Microvascular disease manifests as white matter hyperintesities on MRI, regional atrophy and functional decline. Inflammation further affects microcirculatory regulation and contributes to arteriolosclerosis. We investigated the effects of inflammation on regional perfusion and neurodegenerative changes in grey and white matter on MRI. Inflammatory markers had different effects on regional brain volumes. sICAM was associated with atrophy across all regions in the DM group, with the most significant effects in the frontal and parietal regions. In the control group, regional perfusion on both sides in the parietal lobe is positively correlated with sICAM, and perfusion in the right occipital lobe is positive with sVCAM. Associations between regional brain volumes and other inflammatory markers were not prominent. Frontal and parietal regions with high energy demands are more vulnerable to the effects of DM in the brain.

                  2131.     Quantification of Frontal Glutamate Neurotranmission in Human HIV

Napapon Sailasuta¹, Kimbery Shriner², Kent Harris¹, Thao T. Tran^1,3, Osama Abulseoud⁴, Brian D. Ross^1,5

¹Clinical MR Spectroscopy, Huntington Medical Research Institutes, Pasadena, CA, United States; ²The Phil Simon Clinic, Huntington Memorial Hospital, Pasadena, CA, United States; ³Rudi Schulte Research Institute, Santa Barbara, CA, United States; ⁴University of Southern California, Keck School of Medicine, Los Angeles, CA, United States; ⁵Rudi Schulte Research Institute, Santa Barbara , CA, United States

Despite successful treatment of HIV and AIDS, neuroimaging and neurospectroscopy abnormalities persist suggesting residual viral effects or unwanted neurological side effects of effective therapies.  Elucidation of the recently described reduction in frontal lobe glutamate concentration in white matter of HIV-affected individuals requires independent 13C MRS measurement of glutamate turnover neurotransmitter rates in neurons and glia.  This study develops the necessary frontal lobe assay of neuronal and axonal glutamate turnover by infusion of 2-13C glucose followed by low-power nOe 13C MRS in HIV and normal control subjects.  Preliminary results indicate reduced 13C glutamate turnover in successfully treated HIV.

                  2132.     Proton MR Spectroscopy Findings in Chronic Neuroborreliosis

Caitlin Judith Hardy¹, Amit Gokhale², David Younger², Nissa Perry², Oded Gonen²

¹Radiology, NYU, New York, NY, United States; ²NYU School of Medicine

Abnormal metabolite levels were found in 3/3 patients with a diagnosis a post Lyme disease syndrome using 1H-MRS.

Animal Models of White Matter Disease

                  2133.     Vascular Endothelial Growth Factor - A Novel Player in SCI Pain

Laura Sundberg¹, Juan Herrera¹, Olivera Nesic², Ponnada Narayana¹

¹Diagnostic and Interventional Imaging, The University of Texas Medical School, Houston, TX, United States; ²Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, United States

Vascular endothelial growth factor (VEGF) has been investigated as a potential treatment for spinal cord injury (SCI) due to its vascular-promoting and neuroprotective effects; however, studies have provided conflicting information about the post-SCI effects of VEGF.  In this study, VEGF was delivered immediately after SCI and longitudinal MRI and behavioral studies were performed into the chronic phase of injury.  It was found that VEGF treatment results in tissue sparing and increased markers of neurofilament, but many animals also displayed a higher incidence of mechanical allodynia.  VEGF may spare tissue, but may also encourage non-specific sprouting of axons into pain pathways.

                  2134.     Viscoelastic Properties Change at an Early Stage of Cuprizone Induced Affection of Oligodendrocytes in the Corpus Callosum of C57/black6 Mice

Katharina Schregel¹, Eva Wuerfel¹, Jens Wuerfel¹, Dirk Petersen¹, Ralph Sinkus²

¹University of Luebeck, Luebeck, Germany; ²Institut Langevin, ESPCI, Paris, France

MRE is an innovative imaging technique developed to non-invasively map and quantify the viscoelastic properties of tissue in vivo. As pathological alterations cause changes in elasticity and viscosity, MRE might be applied to characterize the structural integrity of given tissues and could be employed for diagnosis and clinical monitoring of neurodegenerative diseases such as multiple sclerosis. Therefore it appears to be essential to evaluate the effect of pathological processes occurring in multiple sclerosis on the viscoelastic properties of cerebral tissue with the help of experimental rodent models. We introduced the cuprizone mouse-model (C57/black6) which depicts key features of multiple sclerosis.

                  2135.     Hybrid Diffusion Imaging in a Spinal Cord Model of Dysmyelination

A P. Hosseinbor¹, I D. Duncan², A L. Alexander, A A. Samsonov³, Y-C Wu⁴, S A. Hurley, R A. Fisher, A S. Field³

¹Medical Physics, University of Wisconsin-Madison, Madison, WI, United States; ²Medical Sciences, University of Wisconsin-Madison; ³Radiology, University of Wisconsin-Madison; ⁴Dartmouth College

The shaking pup (shp) is a canine mutant model of dysmyelination, and suffers from severe myelin deficiency. In a previous study of shp brain, Po was shown to differentiate between a control and diseased pup with respect to myelin content. In this study, WM integrity is examined in the spinal cord of shp using both DTI and DSI measurements acquired from a HYDI approach. Standard DTI measures and Po are compared to see if one or both are sensitive to changes in myelin content between shp and control, as well as to more subtle differences between two diseased pups.

                  2136.     Ex Vivo Visualization of Cortical Lesions in Non-Human Primates with MS Using Inversion Recovery Experiments

Erwin Lambert Blezer¹, Yolanda S. Kap², Jan Bauer³, Bert L. 't Hart²

¹Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands; ²Department of Immunobiology, Biomedical Primate Research Center, Rijswijk, Netherlands; ³Brain Research Institute, University of Vienna, Vienna, Austria

Cortical pathology is an important feature of MS. However visualization with MRI is poor although sensitivity is increased using FLAIR and Double Inversion Recovery (suppression of CSF and white matter) experiments. Various inversion recovery experiments were tested ex vivo on brains of marmoset with MS, which develop cortical lesions, in their ability to improve cortical lesion detection. Experiments included settings of inversion times in which CSF, white or grey matter was suppressed and a DIR experiment in which both white and grey matter was suppressed. Cortical lesions were best visualized after suppression of white matter or in the DIR experiment.

                  2137.     Increasing Diffusion Time Improves in Vivo DTI Sensitivity to White Matter Degeneration

Ying-Jr Chen¹, Joong Hee Kim¹, Jian Wang¹, Tsang-Wei Tu, ¹², Sheng-Kwei Song¹

¹Radiology, Washington University in St. Louis, Saint Louis, MO, United States; ²Mechanical, Aerospace and Structural Engineering, Washington University in St. Louis, Saint Louis, MO, United States

The sensitivities of detecting white matter injury using 6 ms and 38 ms diffusion time were examined in the present study. We demonstrated that increased diffusion time in diffusion tensor imaging measurements improves the sensitivity of detecting axonal injury and myelin damage  in cuprizone treated mice. In the cuprizone model of demyelination, axonal injury was seen as significantly decreased axial diffusivity at both 6 and 38 ms diffusion time with more significantly decreased axial diffusivity observed at longer diffusion time.

                  2138.     The Effect of Systemic Depletion of Natural Killer Cells in an EAE Mouse Model of Multiple Sclerosis Examined by Magnetic Resonance Imaging and Bioluminescence Imaging

Gregory Harrison Turner¹, Junwei Hao², Ruolan Liu², Wenhua Piao², Timothy L. Vollmer³, Rong Xiang⁴, Antonio La Cava⁵, Denise I. Campagnolo², Luc Van Kaer⁶, Fu-Dong Shi²

¹Keller Center for Imaging Innovation, Barrow Neurological Institute, Phoenix, AZ, United States; ²Neurology, Barrow Neurological Institute, Phoenix, AZ, United States; ³Neurology, University of Colorado Denver School of Medicine, Aurora, CO, United States; ⁴Medicine, Nankai University, Tianjin, China; ⁵Medicine, University of California Los Angeles, Los Angeles, CA, United States; ⁶Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States

Natural killer (NK) cells of the innate immune system can profoundly impact the development of adaptive immune responses against foreign invaders, as well as self-antigens.  In this study a combination of in vivo MRI and bioluminescence imaging was used to investigate effects of systemic depletion of NK cells on lesion development in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis.  The results of this study suggest organ-specific activity of NK cells on the magnitude of CNS inflammation.

Imaging of Psychiatric Disorders

                  2139.     Glutamate, Glutamine, NAA, and GABA Levels in Hippocampus in Schizophrenia as Measured by 1H-MRS at 3T

Ana Stan¹, Perry Mihalakos², Deborah Douglas³, Stephanie Morris², Changho Choi³, Carol Tamminga²

¹Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, United States; ²Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States; ³Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

We report a result of a 3T 1H-MRS study in schizophrenia. The concentrations of glutamate (Glu), glutamine (Gln), and N-acetylaspatate (NAA) in hippocampus (voxel 50x15x15 mm) were measured using a triple refocusing sequence. GABA was measured with a difference editing method. MRS scans were conducted on 13 schizophrenia volunteers (10 on medication (SV-ON) and 3 off-medication (SV-OFF)) and 14 normal volunteers (NV). LCModel fitting was used for spectral analysis. [Glu]/[Cr] was observed to be similar between NV and SV-ON (p = 0.4). However, [Glu]/[Cr] in SV-OFF was significantly lower (~30%) than in both NV and SV-ON (p = 0.02 and 0.04, respectively). For Gln, the concentrations were about the same between the three groups (p > 0.2). Compared to NV, [NAA]/[Cr] was reduced (by 10%) in SV-ON (p = 0.006), but not in SV-OFF (p = 0.55). The GABA data showed difference between SV-OFF and SV-ON (p = 0.05).

                  2140.     Asymmetry Patterns of Association Fibers in Schizophrenia: Preliminary Results Using Diffusion Spectrum Imaging Tractography

Yu-Chun Lo¹, Su-Chun Huang², Hai-Gwo Hwu³, Chih-Min Liu³, Chen-Chung Liu³, Wen-Yih Isaac Tseng^2,4

¹Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, Taiwan; ²Institute of Biomedical Engineering,  National Taiwan University, Taipei, Taiwan, Taiwan; ³Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; ⁴Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan

Three association fibers connecting the frontal and temporal lobes and three commissural fibers connecting the bilateral orbitofrontal lobes, inferior frontal gyri, and superior temporal gyri related to the social and language functions that might serve the neuropsychopathology of patients with schizophrenia inferred from diffusion spectrum imaging tractography. In neurotypical participants, a consistent leftward asymmetry in the three pairs of association fibers was found. However, adults with schizophrenia did not demonstrate such asymmetry. Lack of leftward asymmetry in schizophrenia may imply a disruption in the normal pattern of structural and functional connectivity in frontal-temporal brain regions.

                  2141.     White Matter Abnormalities Associated with Neurological Soft Signs in First-Episode Schizophrenia: A Diffusion Tensor Imaging Study.

Christine Rodriguez-Régent¹, Sabine Mouchet-Mages², Sebastian Rodrigo, Marie-Odile Krebs², Catherine Oppenheim, Jean-François Meder

¹Department of Morphologic and Functional Imaging, University Paris Descartes, Sainte Anne Hospital, PARIS, France; ²Pathophysiology of Psychiatric Diseases, University Paris Descartes, Sainte Anne Hospital, PARIS, France

Schizophrenic patients often present with neurological soft signs (NSS) but the cerebral changes underlying these signs are poorly understood. This study examines the microstructural changes associated with NSS using Diffusion Tensor Imaging. Forty-five patients with first-episode schizophrenia underwent DTI and a neurological examination. Fractional anisotropy (FA), calculated using a voxel based analysis, was analyzed with NSS scores.  FA was negatively correlated with NSS scores in the white matter of the right prefrontal, left occipital and right parietal areas. Thus, this is the first study which confirms that microstructural changes of white matter are associated with NSS in schizophrenia.

                  2142.     Interaction of Hippocampal Volume and N-Acetylaspartate Concentration Deficits in Schizophrenia: A Combined MRI and 1H-MRS Study at 3 T

Florian Schubert¹, Andreas Klaer², Martina Ballmaier², Karolina Leopold², Ines Haeke², Martin Schaefer³, Ruediger Bruehl¹, Juergen Gallinat²

¹Physikalisch-Technische Bundesanstalt, Berlin, Germany; ²Charite University Medicine, Berlin, Germany; ³Kliniken Essen, Essen, Germany

We used single voxel 1H-MRS at 3 Tesla to measure absolute NAA concentrations and, as a gold standard of CNS volumetry, a validated delineation protocol for the hippocampus to study the interaction between between hippocampal NAA reduction and volume deficits in 29 schizophrenic patients and 44 controls. The hippocampus of the patients exhibited a significantly smaller volume and lower NAA concentration than that of healthy controls. For schizophrenic patients a significant negative correlation between hippocampal NAA concentration and volume was observed. The results argue for a coexistent neurochemical and structural deficit in the hippocampus of schizophrenic patients.

                  2143.     An MRI Study of the Caudate Nucleus in Euthymic Bipolar I Disorder

Louise Emsell¹, Camilla Langan¹, Sarah Hehir¹, Helen Casey¹, Wil van der Putten¹, Peter McCarthy¹, Rachel Skinner¹, Dara M. Cannon¹, Colm McDonald¹

¹NUI Galway, Galway, Ireland

Bipolar disorder is a complex illness characterised by extremes of mood. It is likely that subtle changes in neuroanatomy contribute to the underlying aetiopathology of the disorder. This study sought to identify differences in the volume of the caudate nucleus in a prospectively confirmed sample of 59 remitted patients compared to 59 individually age and gender matched healthy controls to identify trait related anatomical changes. We did not find a main of effect of diagnosis. However,we did detect gender differences in caudate volume (F>M),age-related volumetric decrease across the study population and a main effect of family history in patients.

                  2144.     Brain Matter Corrected Quantification of  Phosphomono- And Phosphodiesters in the Brain of Patients with Schizophrenia

Wolfgang Weber-Fahr¹, Mathias Zink², Andreas Meyer-Lindenberg², Monika Uhrig¹, Nuran Tunc-Skarka¹, Mareen Hoerst¹, Helga Welzel-marquez¹, Alexander Sartorius², Gabriele Ende¹

¹Neuroimaging, Central Institute of Mental Health, Mannheim, NA, Germany; ²Dept. Psychiatry, Central Institute of Mental Health, Mannheim, NA, Germany

A 3D-whole head RINEPT sequence was used together with point-spread function corrected tissue segmentation for robust absolute quantification of spectral edited Phosphomono- and –diester-signals in the brains of schizophrenic patients and controls. The corrected metabolite concentrations show a significant reduction of Phosphocholine and Glycerophosphocholine (GPC) in the basal ganglia and thalamus of schizophrenic patients compared to controls. GPC was also significantly lower in the cerebellum while Phosphorylethanolamine showed a trend for lower concentration in patients in the frontal region.

                  2145.     Altered Fiber Radial Diffusivity in Schizophrenia Revealed by HARDI

Xin Hong^1,2, Lori R. Arlinghaus³, Herbert Y. Meltzer⁴, Sohee Park⁵, Adam W. Anderson, ^2,3

¹Institute of Imaging Science, Vanderbilt University , Nashville, TN, United States; ²Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States; ³Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States; ⁴Department of Psychiatry, Vanderbilt University, Nashville, TN, United States; ⁵Department of Psychology, Vanderbilt University, Nashville, TN, United States

We performed a group comparison of the diffusion properties and intravoxel fiber coherence estimated by FORECAST analysis. Significantly higher FA is found in schizophrenia patients compared to healthy controls in the left superior longitudinal fasciculus and bilateral internal capsules. In all three regions, strong negative correlation between FA and radial diffusivity is found at both voxel and cluster levels, even after controlling for coherence variation. Significantly lower coherence is found between the two groups at the cluster level, but not voxel level. Our results suggest the altered FA was mainly due to structural rather than organizational changes in these regions.

                  2146.     Comparison of Different CSF Correction Methods in a MRS Study of Depressed Psychiatric Patients

John DeWitt Port¹, Ileana Hancu², Heidi Alyssa Edmonson¹, Zhonghao Bao³, Mark A. Frye⁴

¹Radiology, Mayo Clinic, Rochester, MN, United States; ²GE Global Research Center, Niskayuna, NY, United States; ³Information Services, Mayo Clinic, Rochester, MN, United States; ⁴Psychiatry, Mayo Clinic, Rochester, MN, United States

Various methods have been used to correct for the amount of CSF within spectroscopic voxels.  However, it remains unclear which method is best.  We performed CSF correction on an MRS dataset comparing depressed psychiatric patients to normal controls, using the ratio to creatine as well as two anatomically-based CSF correction methods.  All three CSF correction methods yielded significant results for most statistical comparisons; ROC analysis demonstrated no single CSF correction technique to be better than the others.  If the metabolite value used in the denominator is stable, ratios may actually improve statistical sensitivity relative to anatomically-based CSF correction methods.

                  2147.     fMRI and Connectivity Effects of Electro-Convulsive Therapy (ECT) in Depressed Patients

Erik B. Beall¹, Mark J. Lowe¹, Michael D. Phillips¹, Steve Jones¹, Pallab K. Bhattacharyya¹, David Muzina²

¹Radiology, Cleveland Clinic, Cleveland, OH, United States; ²Psychiatry, Cleveland Clinic, Cleveland, OH, United States

ECT is a safe and effective treatment for depression. However its mechanisms have not been studied with the BOLD effect in a pre- and post-ECT fMRI and connectivity study. We present preliminary results that show reduced activation and connectivity in response to working memory and affective tasks.

                  2148.     Decreased Anterior Cingulate Cortex GABA in Depressed Adolescents Measured by Proton MRS at 3T

Vilma Gabbay¹, Xiangling Mao², Yisrael Katz¹, Aviva Pazner¹, James S. Babb¹, Dikoma C. Shungu²

¹NYU Child Study Center, NYU School of Medicine, New York, NY, United States; ²Radiology, Weill Cornell Medical College, New York, NY, United States

Adolescent major depressive disorder (MDD) is a serious public health concern as it often leads to suicide. However, limited research has been conducted to date in this clinical population. This is the first study to examine in vivo γ-aminobutyric acid (GABA) in adolescents with MDD. Using proton MRS, levels of GABA were measured in the anterior cingulate cortex of adolescents with MDD and found to be decreased compared to matched healthy control subjects. This finding supports the notion that GABA abnormalities may be involved early in the etiology of MDD.

                  2149.     Reduced Functional Connectivity in Major Depression: A Whole Brain Study of Multiple Resting-State Networks

Ilya M. Veer^1,2, Christian F. Beckmann^3,4, Evelinda Baerends^1,2, Marie J. van Tol^1,5, Luca Ferrarini⁶, Julien R. Milles⁶, Dick J. Veltman⁷, Andre Aleman⁸, Mark A. van Buchem^1,2, Nic J. van der Wee^1,5, Serge A. Rombouts^1,2

¹Leiden Institute for Brain and Cognition (LIBC), Leiden, Netherlands; ²Department of Radiology, Leiden University Medical Center (LUMC), Leiden, Netherlands; ³FMRIB, University of Oxford, Oxford, United Kingdom; ⁴Department of Clinical Neuroscience, Imperial College London, London, United Kingdom; ⁵Department of Psychiatry, Leiden University Medical Center (LUMC), Leiden, Netherlands; ⁶Department of Radiology, Division of Image Processing, Leiden University Medical Center (LUMC), Leiden, Netherlands; ⁷Department of Psychiatry, Free University Medical Center (VUMC), Amsterdam, Netherlands; ⁸BCN Neuroimaging Center, University of Groningen, Groningen, Netherlands

Major depression is associated with abnormal function of a large-scale mood processing and regulating brain circuit of interconnected regions. Therefore, resting-state (RS) functional connectivity networks were investigated in a group of 19 medication-free patients diagnosed with major depressive disorder without comorbidity, and 19 age- and gender-matched healthy controls. Using independent component, 13 relevant RS networks were found for the entire group. Adopting a dual regression method, subject specific maps were calculated and subsequently used for permutation analysis. We found decreased functional connectivity in three networks, which may relate to the affective and cognitive symptoms in major depression.

                  2150.     Investigating Transverse Relaxation Time Abnormalities in Autism

Yann Gagnon^1,2, N Rajakumar³, Neil Gelman^1,2, Peter Williamson³, Dick Drost^1,2, Jean Théberge^1,2, Rob Nicolson³

¹Imaging, Lawson Health Research Institute, London, Ontario, Canada; ²Medical Biophysics, University of Western Ontario, London, Ontario, Canada; ³Psychiatry, University of Western Ontario

Quantitative transverse relaxation time (T2) imaging offers a unique opportunity to evaluate the neurobiology of brain tissue.  In the current study, we further localize our previously reported overall white matter T2 increase in a sample of children with autism to developmentally relevant neuroanatomic white matter regions.

                  2151.     Aberrant Neurodevelopment of the Social Cognition Network  During Adolescence in Autism Spectrum Disorders

Chun-Wei Lan¹, Kun-Hsien Chou², I-Yun Chen³, Ya-wei Cheng³, Jean Decety⁴, Yang-Teng Fan³, Ching-Po Lin^1,3

¹Institute of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taipei, Taiwan; ²Institute of Biomedical Engineering, National Yang Ming University, Taipei, Taiwan; ³Institute of Neuroscience, National Yang Ming University, Taipei, Taiwan; ⁴Departments of Psychology and Psychiatry, The University of Chicago, Chicago, United States

The autism spectrum disorders (ASD), during childhood, undergoes precocious growth, followed by maturation deceleration. But how the ASD brain changed during adolescence is unclear. We enrolled 25 male adolescents with ASD and 25 controls for voxel-based morphometric analysis. Global brain volume enlargement of ASD did not persist into adolescence. The right inferior parietal lobule and posterior cingulate cortex, a role in social cognition, had a significant interaction of age by group as indicated by an accelerated age-related loss in the adolescents with ASD but an age-related gain in the controls. The findings provided evidence of aberrant neurodevelopment in ASD.

                  2152.     White Matter Abnormalities in Boys with Autism Spectrum Disorders: Preliminary Evidence from Diffusion Tensor Imaging

Sung-Yeon Park¹, Se-Hong Oh¹, Hyo-Woon Yoon¹, Young-Bo Kim¹, Zang-Hee Cho¹, Keun-Ah Cheon²

¹Neuroscience Research Institute, Gachon University of Medicine and Science, Incheon, Korea, Republic of; ²2Division of child and Adolescent Psychiatry, Department of Psychiatry, Kwandong University College of Medicine, Kyunggi-Do, Korea, Republic of

Autism spectrum disorders (ASD) are characterized by qualitative impairments of reciprocal social interaction and deficits in communication, and stereotyped or repetitive pattern of behavior. A few reports have shown the abnormalities of white matter in autism using diffusion tensor imaging (DTI), however there is still lack of evidence showing strong relation to abnormalities in white matter structural integrity with autism. We enrolled thirty four male subjects (17 ASD, 17 healthy controls, matched on age, IQ, handedness.). Our preliminary findings which showed significant reduction of FA in white matter structure related social cognition in ASD subjects compared control subjects support previous findings that social brain structure may be disrupted in ASD. These findings will help on understanding of more advanced neurobiological basis underlying the social deficits in ASD.

                  2153.     Imaging Myelin in Autism

Janneke Zinkstok¹, Eileen Daly¹, Christine Ecker¹, Patrick Johnston¹, Shannon Kolind², Declan Murphy¹, Sean Deoni²

¹Section of Brain Maturation, Institute of Psychiatry, London, United Kingdom; ²Centre of Neuroimaging Sciences, Institute of Psychiatry, London, United Kingdom

Using the novel Multi-Component Driven Equilibrium Single Pulsed Observation of T1 and T2 (mcDESPOT) method, we quantitatively compared myelin content between individuals with autism and healthy controls.  We found significantly reduced myelin content in adults with autism in brain regions previously implicated in autism, including the body of the corpus callosum, and in frontal, temporal, parietal and occipital regions; and in white matter tracts including the left and right uncinate, the left inferior occipitofrontal tract, the left inferior cerebellar peduncle, the left arcuate, the right anterior segment, the left inferior and superior longitudinal fasciculus, and the posterior segments bilaterally. 

                  2154.     Inter-Subject Comparison of Fractional Anisotropy in Attention-Deficit/hyperactivity Disorder

Tzu-Chao Chuang¹, Sheng-Po Huang¹, Pinchen Yang², Ming-Ting Wu^3,4

¹Electrical Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan, Taiwan; ²Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Taiwan; ³School of Medicine, National Yang-Ming University, Taipei, Taiwan, Taiwan; ⁴Radiology, Kaohsiung Veteran General Hospital, Kaohsiung, Taiwan, Taiwan

In this study, white matter abnormalities of attention-deficit hyperactivity disorder were investigated using diffusion tensor imaging. Two different algorithms, including the well-known voxel-based morphometry (VBM) method and recently proposed tract-based spatial statistics (TBSS), were applied for inter-subject comparison. 26 male adolescents (12 ADHD patients and 14 age-matching control subjects) were recruited in this study. Significant decrease of FA was observed on white matter tracts widespread in a scattering pattern by the use of both methods in patients compared to the control group.

                  2155.     MRS Measurement of GABA and Glutamate-Glutamine in Frontal Cortex in Obsessive-Compulsive Disorder

Lawrence Steven Kegeles^1,2, H. Blair Simpson¹, Xiangling Mao³, Rena Staub¹, Dikoma C. Shungu³

¹Psychiatry, Columbia University, New York, NY, United States; ²Radiology, Columbia University, New York, NY, United States; ³Radiology, Weill Cornell Medical Center, New York, NY, United States

This MRS study addressed GABA and glutamate-glutamine levels in a hypothesized abnormal neurochemical circuit in obsessive-compulsive disorder (OCD). Recent animal and human studies have implicated the glutamate system in OCD in these abnormalities.  We used the J edited spin echo difference method to evaluate glutamate-glutamine and GABA in two frontal cortical regions, the anterior cingulate and dorsolateral prefrontal cortex in OCD.  We found no differences between OCD subjects and controls in either measure in either brain region, suggesting that further studies are needed to fully characterize the neurochemistry of the hypothesized abnormal circuitry in OCD.

                  2156.     Impaired Default-Mode Networks of Affective Disorders: Evidences of Image-Guided Proton MRS

Tzu-chen Yeh^1,2, Chih-Ying Lin², Cheng-Wen Ko³, Ton-Ping Su⁴, Wan-Yuo Guo⁵, Jen-Chuen Hsieh², Low-Ton Ho¹

¹Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Taiwan; ²Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan, Taiwan; ³Department of Computer Science and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan, Taiwan; ⁴Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan, Taiwan; ⁵Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, Taiwan

The spatial template of default-mode network (DMN) has been constructed and shown precuneus/posterior cingulate areas (PC, Brodmann area 31) with highest reproducibility in 60 normal subjects. High resting metabolic rate of DMN was implied by previous deoxy-glucose positron emission tomography. In this study of affective disorders (bipolar and major depressive disorders), bioenergetics of Brodmann area 24 and DMN was probed by total creatine using real-time localized image-guided proton magnetic resonance spectroscopy (ig-HMRS) and LCModel quantification. As compared to affective disorders, higher metabolism of PC (representing DMN) in normal subjects was supported by higher total creatine concentration.

                  2157.     Glutamate Levels in the Anterior Cingulate Cortex Correlate with Self-Reported Impulsivity in Patients with Borderline Personality Disorder and Healthy Controls

Mareen Hoerst^1,2, Wofgang Weber-Fahr¹, Nuran Tunc-Skarka¹, Matthias Ruf¹, Martin Bohus², Christian Schmahl², Gabriele Ende¹

¹Department of Neuroimaging, Central Institute of Mental Health, Mannheim, Germany; ²Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany

Dysfunction and deficits in the structure of the anterior cingulate cortex (ACC) have been reported in borderline personality disorder (BPD). Impulsivity belongs to the key features of BPD and can be related to ACC function. In this study we found significantly increased self-reported impulsivity and higher levels of glutamate in the anterior cingulate cortex in subjects with BPD as compared to healthy controls. In both groups the ACC glutamate concentrations were positively correlated with self-reported impulsivity.

                  2158.     Grey Matter Abnormalities in Adult Attention Deficit/hyperactivity Disorder as Measured with Structural MRI

Natalia del Campo^1,2, Julio Acosta-Cabronero^3,4, Samuel R. Chamberlain, Dowson Jonathan⁵, Tim D. Fryer, ⁴, Trevor W. Robbins, Barbara J. Sahakian⁵, Ulrich Muller

¹Psychiatry, University of Cambridge, Cambridge, Cambs, United Kingdom; ²2Behavioural and Clinical Neuroscience Institute, Cambridge, Cambs, United Kingdom; ³Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; ⁴Wolfson Brain Imaging Centre; ⁵Department of Psychiatry

Attention deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children. To date, little is known about the persistence and stability of anatomical changes in ADHD across the lifespan. 16 adult ADHD patients and 17 healthy controls undertook structural magnetic resonance imaging. Using cluster-based permutation analysis we found that ADHD patients had reduced grey matter density in distributed circuitries including the right inferior and middle frontal cortex, as well as bilateral putamen, hippocampus, amygdala and cerebellum. These findings add to a growing body of evidence implicating abnormalities in fronto-striatal, fronto-cerebellar and limbic circuitries in ADHD.

                  2159.     A Systematic Analysis of Association Fiber Tracts in Chronic Alcoholics Found Significant Deficit of White Matter Integrity in Superior Longitudinal Fasciculus Using Diffusion Spectrum Imaging Tractography

Cheng-Liang Liu¹, I-Chao Liu², Wen-Yang Chiang³, Fang-Cheng Yeh⁴, Li-Wei Kuo¹, Wen-Yih Isaac Tseng^1,5

¹Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, Taipei, Taiwan; ²School of Medicine, Fu Jen Catholic University, Taipei, Taiwan; ³The Methodist Hospital Research Institute, Weill Medical College of Cornell University, Houston, TX, United States; ⁴Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States; ⁵Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

In this study, we investigated the relationship between the effect of alcoholic use and the microstructural alteration of seven association fiber tracts using diffusion spectrum imaging tractography and tract-specific analysis. The metric of generalized fractional anisotropy (GFA) was used to identify the difference between control and alcoholic groups. Among all the association fiber tracts, a significant GFA deficit was found in bilateral superior longitudinal fasciculus for chronic alcoholics. A future study to analyze the segmented parts of the tract is needed to further reveal the subtle change of microstructural alteration of association fiber tracts in alcoholism.

                  2160.     Frontal White Matter Choline-Containing Compounds Increase with Alcohol Consumption and Glutamate Decreases with Increasing Addiction Criteria

Gabriele Ende¹, Derik Hermann², Mareen Hoerst¹, Nuran Tunc-Skarka¹, Gunilla Oberthuer¹, Svenja Wichert², Juri Rabinstein², Wolfgang Weber-Fahr¹, Karl Mann², Sabine Vollstaedt-Klein²

¹Neuroimaging, Central Institute of Mental Health, Mannheim, Germany; ²Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany

With this 1H MRS study we aimed to investigate correlations between frontal white matter choline-containing compounds and glutamate with alcohol consumption and addictions scores in heavy drinking as well as in non-abstinent alcohol dependent patients. A positive correlation of choline-containing compounds and alcohol consumption could be replicated but the high variance could not be explained by addiction criteria (OCDS, ICD-10 and DSM IV). However, measures of addiction showed significant negative correlations with glutamate in the heavy drinking groups.

                  2161.     Test and Retest of the Emotional Responses in Adolescents Prenatally Exposed to Cocaine

Zhihao Li¹, Priya Santhanam¹, Claire D. Coles², Mary Ellen Lynch², Stephan Hamann³, Xiaoping Hu¹

¹Biomedical Engineering, Emory Univ. & Georgia Tech., Atlanta, GA, United States; ²Psychiatry and behavioral Science, Emory Univ., Atlanta, GA, United States; ³Psychology, Emory Univ., Atlanta, GA, United States

The present fMRI study examined the interaction effect of prenatal cocaine exposure (PCE) and development on brain activations associated with emotional arousal, in adolescents. Comparing age 17 to 15, cortical responses elicited by negative emotional stimuli are reduced in the controls but remain roughly the same in the PCE adolescents. The present results suggest a long-term and stable PCE effect on emotional arousal regulation.

                  2162.     Altered Cortical Thickness in Young Cannabis Abusers

Deborah Yurgelun-Todd^1,2, Piotr Bogorodzki³, Melissa Lopez-Larson^1,2, Robert Kurjata³, John Churchwell¹, Jadwiga Rogowska⁴

¹Brain Institute, University of Utah, Salt Lake City, UT, United States; ²VISN 19 MIRECC, Salt Lake City, UT, United States; ³Institute of Radioelectronics, Warsaw Technical University, Warsaw, Poland; ⁴Brain Imaging Center, McLean Hospital/Harvard Medical School, Belmont, MA, United States

It is unknown whether altered cortical thickness during adolescence is associated with marijuana (MJ) use. This investigation used cortical-surface based techniques to compare MJ using adolescents and healthy controls (HC). Eighteen adolescents with DSM-IV MJ Dependence and 18 HCs had an MRI scans using a 3T Siemens Trio scanner. Cortical reconstruction and volumetric segmentation was performed with the Freesurfer image analysis suite. Compared to HCs, MJ users had decreased cortical thickness in bilateral superior frontal cortex and bilateral and left insula. Furthermore, the average thickness of the right insula was found to negatively correlate with age of first MJ use.

                  2163.     Perfusion Deficit to Cholinergic Challenge in Veterans with Gulf War Illness

Peiying Liu Wang¹, Sina Aslan¹, Xiufeng Li², David Buhner³, Richard Briggs², Robert Haley³, Hanzhang Lu¹

¹Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States; ²Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States; ³Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States

A highly plausible etiology for the Gulf War Illness (GWI) is that the neural damage and cognitive deficits are associated with excessive exposure to cholinesterase-inhibiting cholinergic stimulants. Our previous SPECT study provided strong indication that cerebral blood flow of veterans with Syndrome 2 GWI has reduced responses to cholinergic challenge, compared to unaffected control veterans. The present study confirmed and extended previous findings that patients with Gulf War Illness have abnormal response to an inhibitory cholinergic challenge, physostigmine infusion, when compared to age-gender-education matched control veterans. This new technique may provide a cost-effective biomarker for characterization of Gulf war illness.

                  2164.     Cortical GABA and Glutamate Changes in Posttraumatic Stress Disorder

Anderson Mon^1,2, Thomas Neylan³, Dieter Meyerhoff^1,4

¹Radiology, University of California, San Francisco, San Francisco, CA, United States; ²Center for Imaging of Neurodegenerative Diseases, Veteran Administration Medical Center, San Francisco, CA; ³Psychiatry, University of California, San Francisco, San Francisco, CA, United States; ⁴Center for Imaging of Neurodegenerative Diseases, Veteran Administration Medical Center, San Francisco, CA, United States

We studied NAA, Glu and GABA levels in post traumatic stress disorder using magnetic resonance spectroscopy. We found lower NAA in the anterior cingulate, lower GABA in the posterior occipital cortex, and lower GABA and higher Glu in the medial temporal lobe as compared to control subjects. Metabolite levels related to PTSD symptomatology and suggest neuronal injury, perhaps associated with excitatory and inhibitory processes in cortical brain

Clinical Brain Tumor Imaging: Anatomic, MT, SWI & Perfusion MRI

                  2165.     Potential Utility of Quantitative Magnetisation Transfer Imaging for Detection of Lesion Extent in Glioblastoma Multiforme

Gerard Thompson^1,2, Sha Zhao^1,2, Samantha J. Mills^1,2, John R. Cain^1,2, Geoff J M Parker^1,2, Alan Jackson^1,2

¹Imaging Science and Biomedical Engineering, University of Manchester, Manchester, United Kingdom; ²Biomedical Imaging Institute, University of Manchester, Manchester, United Kingdom

Glioblastoma multiforme is an aggressive primary brain tumour, which invades preferentially along white matter tracts. Histopathological and PET evidence suggests that at the time of diagnosis, infiltrating tumour already exists at sites distant from the enhancing tumour visible on conventional anatomical MR imaging. Since MR is used to plan radiotherapy and surgery, there is concern that infiltrating tumour may be missed, and may therefore escape optimal treatment. We provide preliminary evidence in two cases that quantitative magnetisation transfer (qMT) imaging can detect changes in white matter adjacent to glioblastoma which appear otherwise normal on conventional MR imaging.

                  2166.     Perfusion MRI Fractional Tumor Bulk Mapping:  Correlation with Multiple Stereotactic Biopsies in Recurrent GBM

Leland S. Hu^1,2, Seban Liu³, Dilini S. Pinnaduwage⁴, Kris A. Smith⁵, Peter Nakaji⁵, Amylou C. Dueck⁶, Todd Jensen⁷, Jennifer M. Eschbacher⁸, Joseph E. Heiserman², John P. Karis², Josef Debbins³, Burt G. Feuerstein⁹, Kathleen M. Schmainda¹⁰, Leslie C. Baxter³

¹Radiology, Mayo Clinic, Arizona, Scottsdale, AZ, United States; ²Radiology, Neuroradiology Section, St. Joseph's Hospital - Barrow Neurological Institute, Phoenix, AZ, United States; ³Keller Center for Imaging Innovation, St. Joseph's Hospital - Barrow Neurological Institute, Phoenix, AZ, United States; ⁴Radiation Oncology, University of California - San Francisco, San Francisco, CA, United States; ⁵Neurosurgery, St. Joseph's Hosptial - Barrow Neurological Institute, Phoenix, AZ, United States; ⁶Biostatistics, Mayo Clinic, Arizona, Scottsdale, AZ, United States; ⁷Imaging Biometrics, LLC; ⁸Neuropathology, St. Joseph's Hospital - Barrow Neurological Institute, Phoenix, AZ, United States; ⁹Neuro-Oncology, St. Joseph's Hospital - Barrow Neurological Institute, Phoenix, AZ, United States; ¹⁰Radiology, Medical College of Wisconsin, Milwaukee, WI, United States

We present methods to calculate ‘Perfusion MRI (pMRI) fractional tumor bulk,’ which quantifies and spatially localizes areas of tumor recurrence within non-specific contrast enhanced (CE) MRI lesions.  We correlate these measures with the percentage, or fraction, of tissue samples histopathologically diagnosed as tumor, in a group of recurrent Glioblastoma Multiforme (GBM) patients undergoing multiple stereotactic biopsies.

                  2167.     Pseudo-Tumoral Response of Glioblastoma to Anti-Angiogenic Treatment Prematurely Revealed by Using Arterial Spin-Labeling (ASL) Perfusion MRI and Susceptibility Weighted Imaging (SWI).

Slim Fellah¹, Yann Lefur¹, Elisabeth Soulier¹, Céline Boucard², Sylviane Confort-Gouny¹, Olivier Chinot², Patrick J. Cozzone¹, Jean-Philippe Ranjeva¹, Virginie Callot¹

¹Centre de Résonance Magnétique Biologique et Médicale (CRMBM), CNRS UMR 6612, Faculté de Médecine, Marseille, France; ²Unité de Neuro-Oncologie, CHU Timone, Marseille, France

Anti-angiogenics have become part of Glioblastoma therapeutic protocol. However pseudo-response followed by a critical recurrence may be observed. Non-responders thus need to be prematurely identified. However current imaging criteria are insufficient or late, new MR markers should therefore be investigated. In this preliminary study, we used a multimodal protocol including particularly ASL and SWI, which provide vascular information. A few weeks after the beginning of the treatment, FLAIR and post-contrast T1-WI showed partial response whereas perfusion MRI and SWI demonstrated hyperperfusion and vascularization increase. The parameters derived from such sequences should thus be considered as early indicators of tumor evolution.

                  2168.     Longitudinal Monitoring of Low-Grade Glioma Transformation: A Fully-Automatic Method Using Quantitative DSC-MRI

Kyrre E. Emblem^1,2, Paulina Due-Tonnessen^1,3, Inge A. Rasmussen Jr¹, Atle Bjornerud^2,4

¹The Interventional Centre, Rikshospitalet, Oslo University Hospital, Oslo, Norway; ²Department of Medical Physics, Rikshospitalet, Oslo University Hospital, Oslo, Norway; ³Clinic for Imaging- and Intervention, Rikshospitalet, Oslo University Hospital, Oslo, Norway; ⁴Department of Physics, University of Oslo, Oslo, Norway

In this study, a fully-automatic method for longitudinal monitoring of low-grade glioma transformation by quantitative dynamic susceptibility contrast (DSC) MRI was evaluated and compared to conventional criteria for malignant glioma progression. Thirteen patients were imaged at least three times, with an average time between two consecutive MR exams of 283 days. Our results suggest that the fully-automatic method provides a sensitive marker for tumor progression at an early stage compared to conventional imaging criteria. Also, the quantitative tumor analysis and monitoring of baseline perfusion values in unaffected brain tissue, allows inter- and intra-patient comparisons across MR machines and institutions.

                  2169.     Can Susceptibility-Weighted Imaging Determine Response to Combined Anti-Angiogenic, Cytotoxic, and Radiation Therapy in GBM Patients?

Janine M. Lupo¹, Soonmee Cha¹, Emma Essock-Burns^1,2, Nicholas Butowski³, Sarah J. Nelson^1,2

¹Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States; ²Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States; ³Department of Neurosurgery, University of California, San Francisco, San Francisco, CA, United States

This study investigated whether the unique contrast provided by SWI, which highlights heterogeneity within the post-gadolinium contrast enhancing brain tumor lesion, can predict response to treatment. Nineteen patients with newly-diagnosed GBM were imaged prior to beginning anti-angiogenic, cytotoxic, and radiation therapy and followed until progression.   The volume of SWI hypointense signal within the contrast-enhancing lesion was dramatically higher in patients who progressed after 1 year post-therapy compared to patients who progressed within 6 months of initiating treatment. These findings suggest that SWI could be advantageous for determining which patients would be the best candidates for adjuvant anti-angiogenic therapeutic strategies.

                  2170.     Comparison of DSC-Derived Perfusion Parameters in Response to Conventional Therapy or Adjuvant Anti-Angiogenic Therapy in Patients Newly-Diagnosed with GBM

Emma Essock-Burns^1,2, Yan Li¹, Janine M. Lupo¹, Mei-Yin Polley³, Nicholas Butowski³, Susan M. Chang³, Soonmee Cha, ^1,3, Sarah J. Nelson^1,4

¹Department of Radiology and Biomedical Imaging, UC San Francisco, San Francisco, CA, United States; ²Joint Graduate Group in Bioengineering, UC San Francisco/UC Berkeley , San Francisco, CA, United States; ³Department of Neurological Surgery, UC San Francisco, San Francisco, CA, United States; ⁴Department of Bioengineering and Therapeutic Sciences, UC San Francisco, San Francisco, CA, United States

Adjuvant anti-angiogenic therapy may alter the presentation of contrast enhancement creating a clinical need for new methods of evaluating response. Dynamic susceptibility contrast enhanced imaging was used to assess vascular changes of patients newly diagnosed with GBM in response to either conventional (XRT+cytotoxic) or adjuvant anti-angiogenic therapy. A decrease in vascularization was observed early in adjuvant anti-angiogenic therapy. Progression-free survival status of patients receiving anti-angiogenic therapy may be dominated by an initial change in leakage, while PFS of patients receiving conventional therapy is not. This work highlights the need for further functional imaging techniques for the evaluation of response.

                  2171.     Parametric Response Map as an Imaging Biomarker to Distinguish Progression from Pseudoprogression in High Grade Gliomas

Christina Tsien¹, Craig J. Galban¹, Thomas L. Chenevert¹, Timothy D. Johnson¹, Daniel A. Hamstra¹, Pia C. Sundgren¹, Larry Junck¹, Charles R. Meyer¹, Alnawaz Rehemtulla¹, Theodore Lawrence¹, Brian D. Ross¹

¹University of Michigan, Ann Arbor, MI, United States

We have developed a reliable method for distinguishing true progression from pseudoprogression by quantifying on a voxel-wise basis therapeutic-associated hemodynamic alterations in patients with high grade glioma. The parametric response map of rCBV (PRM_rCBV) at week 3 during chemoradiation is shown to be a potential early imaging biomarker of response that may be helpful in distinguishing pseudoprogression from true progression in patients with high grade glioma.

                  2172.     Quantitative Metrics Derived from DCE MRI as a Biomarker for Early Response to Radiation Therapy in Brain Metastases

Yue Cao¹, Felix Y. Feng, Diana Gomez-Hassan², James A. Hayman, Theodore S. Lawrence, Christina I. Tsien

¹Radiology and Radiation Oncology, University of Michigan, Ann Arbor, MI, United States; ²Radiology, University of Michigan, Ann Arbor, MI, United States

The response of metastatic lesions to whole brain radiation therapy (WBRT) is highly heterogeneous.  In this study, we evaluated quantitative metrics derived from DCE MRI for early assessment of response of brain metastatic lesions to WBRT.  We found that changes in vascular volume and perfusion at the completion of WBRT differentiated responsive lesions from non-responsive ones.  These DCE metrics have the potential for early prediction of treatment response in brain metastases. This requires further validation, but may provide a means for individualizing therapy in patients with brain metastases by selecting patients requiring treatment intensification with stereotactic RT.

                  2173.     Dynamic Contrast Enhanced and Susceptibility Based CBV Measurements Perform Equally in Grading of Cerebral Gliomas

Muftah Ahmed Manita¹, Paul Morgan², Keith Robson³, Timothy Jaspan³, Dorothee P. Auer¹

¹Academic Radiology, University of Nottingham, Nottingham, United Kingdom; ²Radiology & Radiological Science, Medical University of South Carolina, United States; ³Nottingham University Hospital, United Kingdom

Perfusion MRI DSC (T2*) has shown added values in glioma tumour differentiation with rCBVmax is the best performing metrics obtained from dynamic susceptibility contrast technique (DSC). However, this technique is susceptible to blood leak that results in rCBV overestimation. T1 MRI perfusion (DCE) is not susceptible to vascular disruption. Nineteen patients with low and high grade glioma underwent MR perfusion (T1 and T2*) was analysed with Java image software. Significant difference (P=0.000) with excellent correlation (0.81) between the two tumour grades in both techniques with accuracy of 100%. T1 based DCE is robust technique to follow postoperative cases.

                  2174.     Enhancing Fraction and Survival in Glioblastoma Multiforme

Samantha Jane Mills^1,2, Calvin Soh², Gerard Thompson¹, Giovanni Buonaccorsi¹, Catherine McBain³, Sha Zhao¹, Geoff James Martin Parker¹, Alan Jackson^1,2

¹Imaging Science and Biomedical Engineering, University of Manchester, Manchester, Greater Manchester, United Kingdom; ²Department of Neuroradiology, Salford Royal Foundation Trust Hospital, Salford, Greater Manchester, United Kingdom; ³Department of Clinical Oncology, Christie Hospital, Manchester, Greater Manchester, United Kingdom

This study describes the relationship between the DCE-MRI derived measure, Enhancing Fraction, and overall survival in patients with Glioblastoma Multiforme, with the findings of increased survival in association with elevated Enhancing Fraction.

Imaging of Brain Tumors: Techniques & Contrast Media

                  2175.     Delta T1 Method: An Automatic Post-Contrast ROI Selection Technique for Brain Tumors

Devyani Bedekar^1,2, Todd Jensen³, Scott Rand^1,4, Mark Malkin, ^2,5, Jennifer Connelly, ^2,5, Kathleen Schmainda, ^2,6

¹Radiology, Medical College of Wisconsin, Milwaukee, WI, United States; ²Translational Brain Tumor Research Program, Medical College of Wisconsin, Milwaukee, WI, United States; ³Imaging Biometrics, Milwaukee, WI, United States; ⁴Translational Brain Tumor Research Program, Medical College of Wisconsin,  Milwaukee, WI, United States; ⁵Neurology, Medical College of Wisconsin, Milwaukee, WI, United States; ⁶Radiology & Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States

The primary approach to monitoring patients with brain tumors is to obtain pre and post-contrast T1-weighted images.  Bright areas on the pre-contrast images are suggestive of blood products, which may be a result or treatment, and are therefore not to be considered as enhancing lesions on the post-contrast images.  However, the difference between the brightness that exists on both the post and pre-contrast images can be quite subtle, a condition that is occurring more frequently now with the increasing use of anti-angiogenic agents. Therefore it is becoming increasingly difficult to monitor patients with brain tumors simply by visually comparing differences in enhancement.  As a solution in this report we propose an automatic method, the delta T1 method (dTM), which is capable of  detecting even subtle enhancing tumor free of blood products, thereby enabling the automatic creation of ROIs in a fast and reliable manner that avoids subjective variability.

                  2176.     Analysis of Brain Tumors and Metastases by Quantitative MT Imaging with BSSFP: Initial Experiences

Meritxell Garcia¹, Monika Gloor², Christoph Stippich¹, Felix Jax¹, Klaus Scheffler², Oliver Bieri²

¹Department of Neuroradiology, University of Basel Hospital, Basel, Switzerland; ²Radiological Physics, University of Basel Hospital, Basel, Switzerland

The efficacy of quantitative MT (qMT) imaging for characterization of benign and malignant brain lesions is analyzed with balanced steady-state free precession. Eleven patients with 3 different lesions (4 glioblastoma multiforme, 4 meningeomas and 3 metastases) were investigated on a clinical 1.5T MR-scanner. MT-effects are described in terms of MTR, relaxation times (T1, T2), MT exchange rate (kf) and the macromolecular content (F). Marked divergences between contrast-enhancing regions, edema and normal-appearing brain were found within and between the different lesions, which might be attributed to differences in edema, cell infiltration and myelin properties. Thus, qMT-imaging might play a major role in adding information for diagnostic tumor characterization.

                  2177.     Magnetic Resonance Imaging Contrast of Brain Tumors at 7 Tesla Compared to 3 Tesla

Iris-Melanie Noebauer-Huhmann¹, Pavol Szomolanyi^1,2, Claudia Kronnerwetter¹, Siegfried Trattnig¹

¹MR Centre - High field MR, Department of Radiology, Medical University of Vienna, Vienna, Austria; ²Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia

It is well known that the effect of MR contrast agents is influenced by the magnetic field strength. The aim of the study was to compare the diagnostic efficacy of a Gadolinium-based MRI contrast agent (gadobenate dimeglumine) in primary brain tumors at 7Tesla versus 3Tesla. Post contrast MP-RAGE sequences were evaluated by region of interest measurements. At 7Tesla, the tumor-to-brain-contrast after gadolinium administration was significantly higher (91.4) than at 3Tesla (37.3). Further studies will show if the higher tumor-to-brain-contrast post gadolinium administration at 7Tesla may be beneficial for tumors with minor contrast agent accumulation, or allow for a dose reduction.

                  2178.     Ultra-High Field MRI of Primary Brain Tumors: Contrast and Resolution

Fernando Emilio Boada¹, Yongxian Qian¹, Frank Lieberman², Denise Davis¹, Ronald Hamilton³

¹MR Research Center, University of Pittsburgh, Pittsburgh, PA, United States; ²Neurooncology, University of Pittsburgh, Pittsburgh, PA, United States; ³Department of Neuropathology, University of Pittsburgh, Pittsburgh, PA, United States

Imaging of primary brain tumors at Ultra-High Field (UHF) magnetic resonance imaging (MRI) has tremendous appeal due to the expected improvements in contrast at spatial resolution scales previously unpractical for in vivo human MRI. In this work we demonstrate the use of UHF for evaluating the microvascular structure of brain tumors and the improvements in signal quantification during sodium MRI

                  2179.     Combined ³¹P and ¹H Magnetic Resonance Spectroscopic Imaging of Phosphomono and -Diesters in Human Brain Tumors at 3T.

Jannie Petra Wijnen¹, Tom W.J. Scheenen¹, Arend Heerschap¹

¹Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands

We demonstrated the clinical feasibility of combined ¹H and ³¹P MRSI with sensitivity enhancement by polarisation transfer of ¹H to ³¹P spins of human brain tumours at 3T to uncover the composition of (phosphorylated)choline and phosphorylated ethanolamine compounds in the membrane. Preliminary results from 4 patients with different tumour types show potentially important differences among tumours. This opens a window on a detailed view of the levels of some key metabolites in membrane phospholipid metabolism of human tumours.

                  2180.     Multi-Echo Time Approach for Study of Metabolic Profiles in Brain Tumors at 3T

Changho Choi¹, Ivan Dimitrov^1,2, Deborah Douglas¹, Aditya Patel¹, Hao Huang¹, Ralph Deberardinis³, Juan Pascual⁴, Robert Bachoo⁵, Craig Malloy¹, Elizabeth Maher⁶

¹Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States; ²Philips Medical Systems, Cleveland, OH, United States; ³Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States; ⁴Neurology, Physiology and Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States; ⁵Neurology, University of Texas Southwestern Medical Center, Dallas, TX, United States; ⁶Internal Medicine and Neurology, University of Texas Southwestern Medical Center, Dallas, TX, United States

Echo time dependence of coupled-spin metabolites following point-resolved spectroscopy (PRESS) at 3T has been investigated with computer simulations. Three pairs of PRESS subecho times, (TE1, TE2) = (32, 22), (32, 80), and (32, 214) ms, were selected for optimum selectivity of glutamate and glutamine, and used for in vivo measurements of metabolites in brain tumors. We present preliminary in vivo results that show pronounced abnormalities of metabolic profiles, including elevated glutamine and glycine in glioblastoma multiforme and differentiation between lipids and lactate in low- and high-grade gliomas.

                  2181.     In Vivo MRI of MR-Labeled Neural Stem Cell Migration to Gliomas

Bensheng Qiu¹, Daohai Xie², Piotr Walczak³, Xubin Li, Jesus Ruiz-Cabello³, Satoshi Minoshima, Jeff W.M. Bulte³, Xiaoming Yang

¹University of Washington, Seattle, WA, United States; ²Radiology, Suzhou University School of Medicine; ³The Johns Hopkins University

Neural stem cells (NSC) have been recognized as cellular vehicles for treatment of invasive brain tumors. MRI is a unique non-invasive tool to monitor the migration of stem cells labeled with MR contrast agents, such as superparamagnetic iron oxide (SPIO) particles. Pervious studies have confirmed that magnetosonoporation (MSP) can instantly labeled SPIO into stem cells. The aim of this study was to validate the feasibility of MRI of MSP-labeled NSC migration to gliomas in vivo.

                  2182.     The Effect of Fiber Affinity on Predicted Cancer Cell Migration Based on MR-DTI

Anitha Priya Krishnan¹, Delphine Davis^2,3, Paul Okunieff³, Walter G. O'Dell, ^1,3

¹Biomedical Engineering, University of Rochester, Rochester, NY, United States; ²Imaging Sciences, University of Rochester, Rochester, NY, United States; ³Radiation Oncology, University of Rochester, Rochester, NY, United States

The current methods for determining the treatment margin for Stereotactic Radiotherapy of gliomas are inadequate as recurrences often occur at the boundary of the treatment margin. We developed a random walk model to determine the microscopic spread of tumor cells to facilitate in the development of anisotropic treatment margins. In this study we have shown that the affinity of cancer cells to fibers in the brain can be modeled better by the spread in the direction of migration about the Principal Diffusion Direction determined using DTI than by using a variable step-size in the random walk of cancer cells.

                  2183.     Correlating DTI-Based Cancer Cell Migration Model Predictions with the Location of Secondary Tumors

Anitha Priya Krishnan¹, Delphine Davis², Paul Okunieff³, Walter G. O'Dell³

¹Biomedical Engineering, University of Rochester, Rochester, NY, United States; ²Imaging Sciences, University of Rochester, Rochester, NY, United States; ³Radiation Oncology, University of Rochester, Rochester, NY, United States

The current methods for determining the treatment margins for stereotactic radiotherapy of gliomas is inadequate as the tumor often recurs at the boundary of the treatment margin. The areas of high normalized cell migration predicted by our random walk model coincide with the direction along which the tumor recurs. Here we have established that there is a statistically significant correlation between the model predictions and the recurrence site and the average normalized cell concentration in the recurrence site is higher than the normalized cell concentration in 78% of the voxels on a surface equidistant from the primary tumor surface.

                  2184.     Decreased Cerebral Oxygen Extraction Fraction (OEF) Measured by MR QBOLD Following Stereotactic Radiosurgery (SRS) in Patients with Metastatic Brain Tumors

Parinaz Massoumazdeh¹, Xiang He¹, Sarah Jost², Keith Rich³, Dmitriy Yablonskiy¹, Tammie Benzinger⁴

¹Mallinckrodt Institute of Radiology, Washington University in Saint Louis; ²Swedish Hospital, Seattle, WA, United States; ³Neurosurgery, Washington University in Saint Louis; ⁴Mallinckrodt Institute of Radiology, Washington University in Saint Louis, St. Louis, MO, United States

There is growing evidence that solid organ tumors with ability to grow in hypoxic conditions demonstrate resistance to conventional chemotherapy and radiation therapy.  Here, we used MR qBOLD technique to measure the OEF of metastatic brain tumors before and after SRS.  In this population, OEF of both the tumors and peritumoral edema prior to SRS was elevated.  Following SRS, OEF decreased in the areas of lesions.  This suggests that qBOLD OEF may provide a new method to monitor brain tumor response to therapy.

                  2185.     A Comparison of Signal Intensity & DCE-MRI Based Methods for Assessing Enhancing Fraction

Samantha Jane Mills^1,2, Gerard Thompson¹, Giovanni Buonacorrsi¹, Geoff James Parker¹, Alan Jackson^1,2

¹Imaging Science and Biomedical Engineering, University of Manchester, Manchester, United Kingdom; ²Department of Neuroradiology, Salford Royal Foundation Trust Hospital, Salford, Greater Manchester, United Kingdom

The established technique for measuring Enhancing Fraction utilises the initial area under the concentration curve derived from a DCE-MRI acquisition. This can be time consuming and requires complex post processing analysis. This study examines the feasibility of obtaining an measure of Enhancing Fraction from conventional, pre and post contrast T1weighted imaging and compares this to the established DCE-MRI derived technique. The two methods show good correlation but are not directly interchangeable methods of measuring Enhancing Fraction.

                  2186.     Simultaneous Resting State FMRI and FET-PET

Irene Neuner^1,2, Joachim Bernhard Maria Kaffanke¹, Cornelius Werner^1,2, Martina Reske^1,3, Karl-Joseph Langen¹, Hans Herzog¹, N. Jon Shah^1,2

¹Institute of Neurosciences and Medicine 4, Medical Imaging Physics, Forschungszentrum Jülich GmbH, 52425 Juelich, Germany; ²Faculty of Medicine, Department of Neurology, RWTH Aachen University, 52074 Aachen, Germany; ³Department of Psychiatry, University of California San Diego, San Diego, CA, United States

For the planning of surgical intervention in human brain tumour cases, it is important to know if critical brain areas might be affected by the surgical process itself. PET imaging using radiolabelled amino acids is a valuable technique for the diagnosis of cerebral gliomas. O-(2-[18F]Fluorethyl)-L-Tyrosin (FET) is a well established amino acid tracer that delivers information about tumour extent, the optimal biopsy site and detection of tumour recurrences. In this study, FET-PET and BOLD-fMRI data were acquired simultaneously; data from a representative human brain tumour case are presented. In contrast to task-based functional studies, resting state fMRI offers the opportunity to detect a variety of cortical networks in a single experiment.

                  2187.     Multi-Layer Appearance of Abscess Capsule on Post-Gd SWI Images: Effects of Filtering and Phase Mask

Ping-Hong Lai^1,2, Hing-Chiu Chang^3,4, Hsiao-Wen Chung⁴

¹Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; ²School of Medicine, National Yang-Ming University, Taipei, Taiwan; ³Applied Science Laboratory, GE Healthcare Taiwan, Taipei, Taiwan; ⁴Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan

SWI is a novel MR technique that exploits the magnetic susceptibility differences of various tissues, such as venous structure and iron deposition. When SWI was applied to patients with abscess, we found that, compared with homogeneous rim-enhancement on post-contrast magnitude images, the capsular portion of pyogenic brain abscess on post-contrast SWI images showed a multi-layer appearance. In this work, in order to clarify whether this multi-layer characteristic is physiological or technical in it origin, we investigate the causes of this multi-layer appearance, and use a theoretical model to simulate the multi-layer appearance upon the use of different SWI processing parameters.

                  2188.     When Does Brain Motion Interfere with the Accuracy of Stereotactic Radiosurgery? Investigation of Brain Motion in the Presence of Stereotactic Frame.

Dee H. Wu¹, Jesse Hatfield¹, Jignesh Modi¹, Genu Mathew¹

¹Radiological Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States

The aim of stereotactic radiosurgery is to provide accurate placement of radiation localized to targeted diseased tissues while minimizing placement of large doses of radiation into sensitive normal tissues (such as motor strip, brain stem, internal capsule, optic nerve, and other major nerve bundles).  It is well known that the brain moves during the cardiac cycle in which the action of pulsatile blood flow produces brain expansion and contraction.  Such movement provides a potential conflict with the objective of providing millimeter to submillimeter localization accuracy of radiation treatment.  This has led to recommendations for the use of electronic gating of radiosurgery placement.  While brain motion was extensively studied in the early 1990s(1, 2), and has been a source of debate for more recent studies for the degree of head fixation required for patients for presurgical planning with fMRI (3).  Such brain motion has been cited to be on the order of 0.5 mm for controlled studies over a short period of time (minutes), to 1-3 millimeters over the course of an fMRI experiment when standard to minimal head fixation is used (4).  None of these studies were performed with such stringent fixation as that provided during radiotherapy.  The frames such that include head fixation with the insertion of metal pins attached to the patient skull with metallic frames.

                  2189.     Image-Guided Tissue Validation of Combined Preload Dosing and Mathematical Modeling Correction of Perfusion MRI Measures

Leland S. Hu^1,2, Leslie C. Baxter³, Dilini S. Pinnaduwage⁴, Todd Jensen⁵, Amylou C. Dueck⁶, Jennifer M. Eschbacher⁷, Joseph E. Heiserman², John P. Karis², Josef Debbins³, Jonathan Placencia Placencia⁸, Seban Liu³, Burt G. Feuerstein⁹, Kathleen M. Schmainda¹⁰

¹Radiology, Mayo Clinic, Arizona, Scottsdale, AZ, United States; ²Radiology, Neuroradiology Section, St. Joseph's Hospital - Barrow Neurological Institute, Phoenix, AZ, United States; ³Keller Center for Imaging Innovation, St. Joseph's Hospital - Barrow Neurological Institute, Phoenix, AZ, United States; ⁴Radiation Oncology, University of California - San Francisco, San Francisco, CA, United States; ⁵Imaging Biometrics, LLC; ⁶Biostatistics, Mayo Clinic, Arizona, Scottsdale, AZ, United States; ⁷Neuropathology, St. Joseph's Hospital - Barrow Neurological Institute, Phoenix, AZ, United States; ⁸Biomedical Engineering, Arizona State University, Tempe, AZ, United States; ⁹Neuro-Oncology, St. Joseph's Hospital - Barrow Neurological Institute, Phoenix, AZ, United States; ¹⁰Radiology, Medical College of Wisconsin, Milwaukee, WI, United States

We validate mathematical modeling correction of relative cerebral blood volume (rCBV) in regards to effectiveness of 1) minimizing T1W leakage and 2) correcting T2/T2*W residual effects, by correlating localized measures with image-guided tissue histopathology and microvascular density from stereotactic biopsies in post-treatment high-grade gliomas.

                  2190.     Automatic Segmentation of Optic Pathway Gliomas Using  Multiparametric Mri Methods

Liat Ben Sira¹, Lior Weizman², Leo Joskowicz², Ronit Precel¹, Shlomi Constantini^3,4, Dafna Ben Bashat⁵

¹Department of Radiology , Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel; ²School of Eng and Computer Science, The Hebrew Univeristy of Jerusalem, Jerusalem, Israel; ³The Paediatric Neurosurgery Department, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel; ⁴Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel; ⁵The Wohl Institute for Advanced Imaging, Brain Imaging Center, Tel Aviv Sourasky Medical Center , Tel-Aviv, Israel

Accurate and consistent volumetric measurements of optic pathway gliomas (OPG), the most common tumor in the brain in patients with Neurofibromatosis, are clinically crucial. In this study we present an automatic method for segmentation of OPGs from multi-spectral MRI datasets. The method effectively incorporates prior location of the OPG, its shape and intensity and accurately identifies the boundaries in a consistent and repeatable manner. The method was tested on 15 data sets, the optimal threshold was derived from a receiver operating characteristic curve, and a significant correlation was obtained between the volume calculated using this method compared to manual measurements.

                  2191.     Translational Methods for Retrospective Long Term Evaluation of Cancer with MRS

Dee H. Wu¹, Levi Garrett¹, Jignesh Modi¹, Bowei Han¹, Hans Cao¹

¹Radiological Center, University of Oklahoma Health Sciences Center, Edmond, OK, United States

We have created a procedure for retrospective review of digitized MRS images  that permits fundamental baseline removal and frequency bracketing with the target of creating a user-friendly tool.  This newly created clinical workflow will improve long term care for patients that may require important decisions pertaining to whether the status of a tumor has changed (such as tumor reoccurrence or remission).   A central concept is that we have also conducted tolerance testing in which common confounds to artifacts that arise from shimming, electronic noise, field inhomogenity, coil sensitivities, relaxation.

                  2192.     MR Biomarkers of Tyrosine Kinase Inhibition in Mouse Gliomas

Paul A. Schornack¹, Jia-Jean Yiin, Bo Hu, Raghvendra S. Sengar, Ken-Wei Liu, Haizhong Feng, Frank S. Lieberman, Jann N. Sarkaria², Erik Wiener, Hsin-I Ma³, Shi-yuan Cheng

¹Radiology, University of Pittsburgh, Pittsburgh, PA, United States; ²Mayo Clinic; ³Taiwan National Defense Medical Center

We present a comparison of MR techniques sensitive to T2, T2*, & ADC to measure mouse gliomas & correlate with histology.  We compare untreated mice with mice treated with an anti-angiogenic agent, ZD6474 (Zactima, vandetanib), a dual inhibitor of VEGFR2 & EG.  ZD6474 significantly inhibited growth & angiogenesis of gliomas expressing EGFRvIII by specifically blocking signaling transducers in brain, which suggests a potential application in treatments for gliomas that overexpress this factor.  Our results indicate that susceptibility/T2* weighted MR along with ADC and T2 measurements can be used as a means of non-invasively quantifying the efficacy of such treatment protocols.

                  2193.     Characterization of Brain Tumor Using High Order Diffusion Imaging

Chu-Yu Lee¹, Chris Goettl², Leslie C. Baxter³, John P. Karis³, Josef P. Debbins, ^1,3

¹Electrical Engineering, Arizona State University, Tempe, AZ, United States; ²College of Medicine, University of Arizona, Phoenix; ³Barrow Neurological Institute, Phoenix

Brain neoplasms are typically characterized by contrast enhanced T1 imaging. Depending on the course of treatment, tumor reoccurrence remains a possibility, and can be difficult to distinguish from other enhancing areas, for example post-treatment radiation effects (PTRE), typically necrosis [1].  Further, detailed information about the tumor heterogeneity as detected by standard MR methods is not generally available, but can play a significant role in characterizing and grading the tumor.  In this work, a simple multi-b-value DWI sequence has been developed to better understand the heterogeneity and diffusion characteristics of different types of tumors, encountered during routine clinical scanning.  The signal decay is fitted with two recently developed diffusion models: a stretched exponential (£\-DWI) [2] and a cumulant expansion (DKI) [3] model, where fitted parameters £\ and Kapp were shown to correlate the diffusion heterogeneity.  We expected to see differences in alpha and K when the multi-b-value DWI sequence directed to the anatomy of interest, primarily due the heterogeneity of the more advanced tumors.

                  2194.     Tumor Enhancement in a Brain Glioma Model: An Intra-Individual Comparison of Half Dose Gadobenate Dimeglumine Vs Full Dose Gadopentetate Dimeglumine at 1.5 and 3 T

Ulrike I. Attenberger¹, Val M. Runge², Jonathan Williams³, Henrik J. Michaely

¹Department of Clinical Radiology and Nuclear Medicine, University Medical Center Manheim, Germany, Mannheim, Baden-Württemberg, Germany; ²Scott & White Clinic and Hospital, Texas A&M University Health Science Center, Department of Radiology , Temple, TX, United States; ³Department of Radiology, , Scott & White Clinic and Hospital, Texas A&M University Health Science Center, Temple, TX, United States

Regarding nephrogenic systemic fibrosis (NSF), the injected dose level becomes very important, since NSF is reported to be related to gadolinium chelate injection in patients with an impaired renal function, depending upon chelate stability and dose. With gadobenate dimeglumine, a chelate with transient protein binding and a higher r1 relaxivity became available. Combining a high relaxivity chelate and 3 T offers multiple opportunities for dose reduction without loss in image quality. This was proven in a rat brain glioma model at 1.5 and 3 T, comparing half dose gadobenate dimeglumine vs full dose gadopentetate dimeglumine, a standard extracellular gadolinium chelate.

                  2195.     MRI Acceptance Protocol for the Multicenter GO Glioblastoma Project

Sylvain Ollivro^1,2, Pierre Antoine Eliat³, Eric Hitti, ^2,3, Loan Tran¹, Jacques Donald de Certaines^1,4, Hervé Saint-Jalmes^2,4

¹Cancéropôle Grand Ouest, Rennes, France; ²LTSI, INSERM, U642, Université Rennes 1, Rennes, France; ³PRISM, IFR 140/Biogenouest, Université Rennes 1, Rennes, France; ⁴CRLCC, Rennes, France

We have verified thanks to a specific common quality control that 7 MRI devices included in a multicenter clinical project, had homogenous and acceptable characteristics to allow quantification and comparison between parameters extracted from different patient images acquired on different sites and to permit correlation with biopsies. This quality control was established with sequences from the MRI protocol. The studied parameters slightly varied depending on the different sites and MRI manufacturers and were in the awaiting of the project. This kind of quality control procedure should be included at the early beginning of any multicenter clinical projects involving quantitative MRI.

                  2196.     Large Scale Comparison of Gadobenate Dimeglumine and Comparator Agents

Matthew J. Kuhn¹, Howard A. Rowley², Michael V. Knopp³, Kenneth R. Maravilla⁴, Zoran Rumboldt⁵

¹Radiology, University of Illinois at Peoria, Peoria, IL, United States; ²Radiology, University of Wisconsin, Madison, WI, United States; ³Radiology, Ohio State University, Columbus, OH, United States; ⁴Radiology and Surgery, University of Washington, Seattle, WA, United States; ⁵Radiology, Medical University of South Carolina, Charleston, SC, United States

382 patients were randomized to receive 2 MR exams within 2 days to 2 weeks with equal 0.1mmo/kg doses of either gadobenate dimeglumine (N=382) or a comparator gadolinium agent. Blinded experts assessed post-contrast images for both qualitative (eg, global contrast enhancement, lesion-to-brain contrast, lesion delineation, internal lesion morphology and structure, tumor vascularization, and global image preference) and quantitative (eg, contrast-to-noise ratio [CNR]; percent lesion enhancement) efficacy parameters. In all six studies, images produced following administration of Gd-BOPTA demonstrated greater contrast enhancement, provided more diagnostic information including additional lesion detection, and were significantly preferred by experienced, blinded neuroradiologists.

Brain Tumor Imaging: Diffusion, MRS & High-Field Imaging

                  2197.     Assessment of Invasion and Recurrence in Glioblastoma Multiforme Using Diffusion Weighted MRI Edge Characteristics of Contrast Enhancing Tumor

Peter Sherman LaViolette^1,2, Benjamin M. Ellingson, ^2,3, Jennifer M. Connelly, ^2,4, Mark G. Malkin, ^2,4, Scott D. Rand, ^2,3, Kathleen M. Schmainda^1,2

¹Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States; ²Translational Brain Tumor Program, Medical College of Wisconsin, Milwaukee, WI, United States; ³Radiology, Medical College of Wisconsin, Milwaukee, WI, United States; ⁴Neurology, Medical College of Wisconsin, Milwaukee, WI, United States

Traditionally, brain tumor recurrence is defined as new MRI contrast enhancement apparent in follow-up imaging.  This study shows that diffusion weighted MRI edge characteristics of contrast enhancing tumors show measurable differences indicative of tumor invasion prior to contrast enhancing recurrence

                  2198.     Determination of Structural Differences Between Glioblastomas and Metastases by Diffusion Kurtosis Imaging

Peter Raab^1,2, Elke Hattingen², Kea Franz³, Friedhelm E. Zanella², Heinrich Lanfermann^1,2

¹Neuroradiology, Hannover Medical School, Hannover, Germany; ²Neuroradiology, JW Goethe University, Frankfurt/Main, Germany; ³Neurosurgery, JW Goethe University, Frankfurt/Main, Germany

Diffusion kurtosis imaging evaluates the non-Gaussian diffusion pattern of water and indicates tissue structure complexity. In this diffusion study we found differences between glioblastomas and cerebral metastases, that indicate more directed diffusion in glioblastomas and a higher structural complexity in metastases.

                  2199.     Fiber Density Mapping in Patients with Gliomas: Histopathologic Evaluation of a Novel Approach for Post-Processing of DTI Data

Andreas Stadlbauer^1,2, Michael Buchfelder², Oliver Ganslandt²

¹MR Physics Group, Department of Radiology, Landesklinikum St. Poelten, St. Poelten, Austria; ²Department of Neurosurgery, University of Erlangen-Nuremberg, Erlangen, Germany

To histopathological evaluate fiber density mapping (FDM) in glioma patients for assessment of the extent of destruction of white matter structures in the center, the transition zone and the border zone of gliomas. We correlated FDM-data and histopathological findings from 78 stereotactic biopsies of 20 glioma patients. We found a negative logarithmic correlation of fiber-density with both, % tumor infiltration and tumor cell number. For a tumor infiltration of >60% no fibers are remaining. In tumor regions with <16% tumor cells functional important fiber structures may still exists.  Our histopathology-fiber-density-model may be helpful for preoperative-planning to prevent post-therapeutic neurologic deficits.

                  2200.     Graded Functional Diffusion Maps (FDMs) Applied to the Whole Brain: A Sensitive Imaging Biomarker for Monitoring Brain Tumor Growth and Invasion

Benjamin M. Ellingson^1,2, Mark G. Malkin^1,3, Scott D. Rand^1,2, Jennifer M. Connelly^1,4, Pete S. LaViolette^1,5, Devyani P. Bedekar^1,2, Kathleen M. Schmainda^1,2

¹Translational Brain Tumor Program, Medical College of Wisconsin, Milwaukee, WI, United States; ²Dept. of Radiology, Medical College of Wisconsin, Milwaukee, WI, United States; ³Dept. of Neurology and Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States; ⁴Dept. of Neurology, Medical College of Wisconsin, Milwaukee, WI, United States; ⁵Dept. of Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States

Diffusion weighted imaging (DWI) measures of apparent diffusion coefficient (ADC) is believed to reflect the level of tumor cellularity in malignant gliomas. Functional diffusion maps (fDMs) were developed to examine voxel-wise changes in ADC, then stratify voxels as either increasing ADC (indicative of necrosis or "hypocellularity"), decreasing ADC (indicative of growing tumor or "hypercellularity"), or not changing within regions of contrast-enhancement or FLAIR signal abnormality. Because the particular threshold used for voxel classification dictates the sensitivity and specificity to changes in tumor cell density, we hypothesize that a graded fDM technique that stratifies voxels into varying degrees of change, applied to the whole brain, may be useful for visualizing invading and proliferating tumor with both high sensitivity and specificity. In the current study we examine graded fDMs in 120 patients and discuss how graded fDMs can be used to detect and monitor brain tumor growth and invasion beyond the traditional malignant boundary.

                  2201.     Differentiating Malignant Glioma from Metastasis Using Regions of Interest Generated by a Novel Diffusion Tensor Segmentation Algorithm

Timothy Lloyd Jones¹, Ai Wern Chung², Andrew John Lawrence², B Anthony Bell¹, Thomas Richard Barrick²

¹Academic Neurosurgery Unit, St George's University of London, London, United Kingdom; ²Centre for Clinical Neurosciences, St George's University of London, London, United Kingdom

Difficulties can arise in clinical practice in differentiating between primary malignant glioma and brain metastasis owing to their similar appearances on conventional MRI sequences. Although previous studies have identified differences in diffusion parameters between the tumour types, the diagnostic role of diffusion tensor imaging (DTI) has yet to be fully elucidated. We propose an application of a novel whole brain DTI segmentation algorithm in generating regions of interest (tumour and oedema) from Diffusion Colour Maps (DCMs) created using our technique. We identify differences in diffusion between tumour types, compare our method with conventional manually drawn regions of interest and propose potential clinical applications for our method.

                  2202.     Assessment of Diffusion Parameters in Scans Prior to Progression in GBM Patients Following Anti-Angiogenic Therapy

Laleh Jalilian¹, Emma Essock-Burns^1,2, Susan M. Chang³, Soonmee Cha^3,4, Sarah J. Nelson, ^1,4

¹Surbeck Laboratory of Advanced Imaging, Department of Radiology, University of California, San Francisco, San Francisco, CA, United States; ²UCSF/UCB Graduate Group in Bioengineering, University of California, San Francisco, San Francisco, CA, United States; ³Department of Neurological Surgery, University of California, San Francisco, University of California, San Francisco, San Francisco, CA, United States; ⁴Department of Radiology, University of California, San Francisco, University of California, San Francisco, San Francisco, CA, United States

Diffusion-weighted Imaging (DWI) is an important adjunct to standard imaging in the management of GBM patients receiving anti-angiogenic treatments. In this study, ADC values were obtained for a) areas on preprogression scans that ultimately progressed to new contrast-enhancement on progression scans (NEW_CEL), and b) new FLAIR abnormality on preprogression scans with exclusion of areas of contrast enhancement and areas that progress to new contrast-enhancement on progression scans (T2ALL_M).  Results demonstrated increasing ADC values in NEW_CEL but no change in T2ALL_M in scans prior to progression.  Clinical implications include interpreting new FLAIR abnormality as a consequence of anti-angiogenic treatment alone.

                  2203.     Comparison of Glioma Sub-Populations Using In-Vivo ADC Values and Ex-Vivo ¹H HR-MAS Spectroscopy

Adam Elkhaled¹, llewellyn Jalbert¹, Hikari Yoshihara¹, Gaby Bourne¹, Colleen Cloyd^1,2, Joanna Phillips³, Soonmee Cha¹, Susan M. Chang⁴, John Kurhanewicz^1,5, Radhika Srinivasan¹, Sarah J. Nelson^1,5

¹Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States; ²School of Pharmacy, University of California, San Francisco, United States; ³Department of Pathology, University of California, San Francisco, San Francisco, CA, United States; ⁴Department of Neurological Surgery, University of California, San Francisco; ⁵Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, United States

Characterization of glioma recurrence and grade transformation has remained elusive. Image-guided biopsies from glioma patients were evaluated using pathology, in-vivo ADC, and ex-vivo proton HR-MAS spectroscopy. Newly diagnosed and recurrent grade IV tissue samples were found indistinguishable from one another. A comparison of recurrent grade IV to recurrent low-grade glioma revealed a significant difference in [myo-inositol] and [creatine]; recurrent low-grades which had upgraded displayed higher total choline compared to non-upgraded and high-grade glioma; the [myo-I]/[total choline] ratio differentiated non-upgraded low-grades from all other cohorts. ADC values demonstrated an inverse relationship with tumor grade and negative correlation with glutathione.

                  2204.     Finding Early Prognostic Marker from 3D ¹H-MRSI and Diffusion Tensor Imaging for Newly-Diagnosed GBM Patients Receiving Radiation, Temozolomide and PKC Inhibitor

Ilwoo Park^1,2, Adam Elkhaled², Achuta Kadambi², Inas Khayal², Nicholas Butowski³, Susan M. Chang³, Sarah J. Nelson^1,2

¹Joint Graduate group in Bioengineering, University of California San Francisco/Berkeley, San Francisco, CA, United States; ²Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States; ³Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States

The purpose of this study was to use 3D ¹H MR Spectroscopic Imaging (MRSI) and diffusion tensor imaging (DTI) to develop early prognostic markers for GBM patients undergoing radiation, temozolomide and PKC inhibitor. Twenty-nine patients with newly diagnosed GBM were examined using a 3T MR scanner. Conventional anatomical imaging parameters could not distinguish between progression groups at baseline or 1 month. Parameters derived from MRSI and DTI provided information at baseline and early follow-up examinations that may be valuable in predicting the time-to-progression for patients with GBM.

                  2205.     Longitudinal MRSI Study in Newly Diagnosed Glioblastoma Multiforme

Yan Li¹, Janine M. Lupo¹, Soonmee Cha¹, Susan Chang², Sarah J. Nelson^1,3

¹Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States; ²Department of Neurological Surgery, University of California, San Francisco, CA, United States; ³Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, CA, United States

Glioblastoma Multiforme (GBM) is the most common and malignant type of primary brain tumor, resulting in a median survival of approximately one year. Our study of 18 patients with GBM indicated that metabolic abnormalities more accurately reflect the underlying tumor burden. We found that the Cho to NAA index (CNI) values in the contrast-enhancing lesion (CEL) are elevated at 2 months prior to progression while having less changes in CEL volume at that time. Patients who have a CEL volume with high CNI values are more likely to progress compared with those who have with smaller CEL volume and lower CNI values. We also observed that the regions with high CNI values outside the CEL region could subsequently become enhancing.

                  2206.     31P and 1H Spectroscopic Imaging of Recurrent Malignant Gliomas

Ulrich Pilatus¹, Joerg Magerkurth¹, Oliver Bähr², Joachim Steinbach², Elke Hattingen¹

¹Institute of Neuroradiology, University Hospital, Goethe-University, Frankfurt, Germany; ²Senckenbergisches Institute of Neurooncology, University Hospital, Goethe University

Proton and 31P MRSI was performed on human malignant recurrent gliomas in order to provide in vivo analysis of membrane metabolism and neuronal brain damage (tNAA). Phosphorylated components in the membrane metabolism showed clear changes indicating a shift to proliferating cell fractions.  While the increase in the phosphocholine/glycerophosphocholine ratio in tumor tissue did not reach significance (p=0.07) the respective ratio for the ethanolamine compound was clearly significant (p=0.02). Further, the significant increase in the inorganic-phosphate/phosphocreatine ratio hints to limited energy supply within the tumor.

                  2207.     Comparison of in Vivo MRS Glutamate/Glutamine Levels in Tumor-Associated Epilepsy

Christopher Steward¹, Bradford Moffat¹, Tanya Yuen², Terence O'Brien², Patricia Desmond¹, Andrew Morokoff³, Chris Kokkinos⁴

¹Radiology, University of Melbourne, Melbourne, VIC, Australia; ²Medicine, University of Melbourne, Melbourne, VIC, Australia; ³Surgery, University of Melbourne, Melbourne, VIC, Australia; ⁴Radiology, Royal Melbourne Hospital, Melbourne, VIC, Australia

The pathogenesis of tumour associated seizures (TAS), a common co-morbidity with brain tumors remains poorly understood. Glutomate has been implicated in many types of epilepsy. In a pilot study the concentration of glutamate/glutamine associated with gliomas using in vivo MRS was studied, and correlated with observed pre-operative seizures. Elevated glutamate/glutamine levels were found in the peritumoral area of tumours who experienced pre-operative seizures compared to those which did not. Due to the small sample size, we are in the process of acquiring a larger MRS and ex vivo prospective data set (N>100) to confirm these findings.

                  2208.     Interpreting Fractional Anisotropy in Gliomas: Correlation with 1H Spectroscopy and Consideration of SNR

Franklyn Arron Howe¹, Tom R. Barrick², Greg A. Fellows³, Alan J. Wright⁴

¹Cardiac & Vascular Sciences , St George's, University of London, London, United Kingdom; ²Clinical Neuroscience, St George's, University of London, London, United Kingdom; ³Academic Neurosurgery, St George's, University of London, London; ⁴Radiology, UMC st. Radboud University Hospital, Nijmegen, Netherlands

Metabolic information from 1H MRSI may aid image segmentation using DTI and so improve delineation of infiltrative brain tumours such as gliomas. NAA and fractional anisotropy (FA) are expected to decrease with tumour infiltration and loss of neuronal structure, but FA calculated from principal diffusion magnitude images is biased due to the contribution of noise. We have investigated the FA and NAA distribution in glioblastomas in comparison to simulated data that takes into account the effect of SNR on the measurement of low FA values. Our data provides evidence for diffusion anisotropy in glioblastomas in the absence of functional neurones.

                  2209.     5 Year Longitudinal Mri Follow-Up and 1H Single Voxel  Mrs in  13 Patients with Gliomatosis Treated with Temodal, Radiotherapy and  Antiangiogenic Therapy.

Jean-Marc Constans^1,2, François Kauffmann³, Gabriela Hossu⁴, Weibei Dou⁵, Jean-Michel Derlon⁶, Emmanuelle Lechapt-Zalcmann⁷, Samuel Valable⁸, Jean-Sebastien Guillamo^9,10

¹MR Unit, CHU de CAEN, CAEN, Normandy, France; ²CERVOxy, Cyceron- CI-NAPS- CNRS , CAEN, Normandy, France; ³LMNO- UMR 6139, CNRS, CAEN, France; ⁴UMR 947, CIC-IT et INSERM, Nancy, France; ⁵Electronic, Tsinghua University, Beijing, China; ⁶CHU de Caen, CAEN, France; ⁷CHU de Caen, Caen, France; ⁸Cyceron CINAPS CNRS UMR 6232, CAEN, France; ⁹CHU CAEN, France; ¹⁰CERVOxy, Cyceron CNRS CI-NAPS, CAEN, France

MRS with Cho/Cr, mI/Cr and NAA/Cr ratios, could be more sensitive than MRI and could, in some cases, be predictive of worsening in gliomatosis follow-up. These spectroscopic changes occurred well before clinical deterioration. There is a large variability, but repetition and modelisation of spectroscopic measurements during longitudinal follow-up could allow us to diminish it and to improve gliomatosis prognostic evaluation.

Studying the relationship between MRS measures, methionine PET, segmentation and perfusion parameters could lead to better understanding of therapeutic response, especially with regard to chemotherapy and antiangiogenic molecules and  in the future hypoxia modulators.

                  2210.     Prominent Citrate Predicts Malignant Progression of Low-Grade Astrocytomas in Children

Arabhi C. Nagasunder¹, Mikhail Laskov², Albert Joseph², Ashok Panigrahy^1,3, Girish Dhall², Jonathan L. Finlay², Ignacio Gonzalez-Gomez⁴, Mark D. Krieger⁵, Marvin D. Nelson¹, Stefan Bluml^1,6

¹Department of Radiology, Childrens Hospital Los Angeles, Los Angeles, CA, United States; ²Childrens Center for Cancer and Blood Diseases, Childrens Hospital Los Angeles, Los Angeles, CA, United States; ³Department of Radiology, Childrens Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States; ⁴Department of Neuropathology, Childrens Hospital Los Angeles, Los Angeles, CA, United States; ⁵Department of Neurosurgery, Childrens Hospital Los Angeles, Los Angeles, CA, United States; ⁶Rudi Schulte Research Institue, Santa Barbara, CA, United States

Pediatric low-grade gliomas can either progress to a high-grade lesion or remain dormant for long periods of time.  Currently, there is a need to identify markers that would allow pediatric neuro-oncologists to predict tumor progression. Our goal was to determine whether aggressive pediatric low-grade II astrocytoma have metabolic features that distinguishes them from stable grade II astrocytoma using in vivo MR Spectroscopy. We found that elevated citrate and low NAA may predict malignant progression of low-grade astrocytomas.

                  2211.     Brain MR Imaging and 1H-MR Spectroscopy Changes in Patients with Extra-Hepatic Portal Vein Obstruction from Early Childhood to Adulthood

Santosh Kumar Yadav¹, Sona Saksena¹, Anshu Srivastava², Arti Srivastava¹, Vivek A. Saraswat³, Michael A. Thomas⁴, Ram Kishore S. Rathore⁵, Rakesh K. Gupta¹

¹Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ²Pediatric gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ³Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; ⁴Radiological Sciences, UCLA School of Medicine, Los Angeles, CA, Los Angeles, CA, United States; ⁵Mathematics and Statistics, Indian Institute of technology Kanpur, Kanpur, Uttar Pradesh, India

Sixty-three patients with EHPVO having different age groups with 47 age/sex matched controls were studied. Neuropsychological tests, MR imaging, 1H-MR Spectroscopy and blood-ammonia estimation were performed in all subjects. 40% EHPVO patients had MHE who showed significantly increased Mean diffusivity, Glx/Cr, blood-ammonia and GP T1 H in all age groups; however, mIns/Cr was significantly lower only in adults when compared to controls. Mean diffusivity positively correlated with blood-ammonia and Glx/Cr in all age groups. A significant positive correlation was observed between Glx/Cr and blood-ammonia. Increases in Mean diffusivity, Glx/Cr, blood-ammonia and GP T1 H and decrease in mIns/Cr are associated with pathogenesis of MHE in adults with EHPVO. No change of cho/Cr in EHPVO may serve as a diagnostic marker for its differentiation from cirrhosis induced MHE. A significant positive correlation among blood ammonia, Glx/Cr and mean diffusivity indicates that hyperammonia contributes to the generalized low grade cerebral edema.

                  2212.     Repeatability of Measured Lactate and Other Metabolites in Patients with Astrocytoma

Mary McLean¹, Amy Sun², Radha Railkar², Andrea Schaeffer², Thomas Bradstreet², Haiying Liu², Rose-ann Blenman-Abange², Ilse Joubert³, Stephen Price³, Charlotte Hodgkin³, John Griffiths¹

¹Cambridge Research Institute, Cancer Research UK, Cambridge, England, United Kingdom; ²Merck & Co Inc, West Point, PA, United States; ³Addenbrooke's Hospital, Cambridge, United Kingdom

We implemented lactate editing at 3T using BASING pulses and assessed its repeatability in phantoms and in human brain tumours in vivo to estimate the level of lactate and other metabolites . In phantoms, a coefficient of variation of 11% was achieved for lactate with SNR similar to in vivo. In tumours, lactate was detected, and there was a non-significant trend of lower metabolite concentrations in scan 2 than scan 1. Lactate editing may provide a useful means of simultaneously monitoring lactate, choline and lipids in vivo, all of which are of interest in tumour progression and response to treatment.

                  2213.     Differentiation Between Low and High Grade in Non-Enhancing Cerebral Gliomas and Neuronal- Glial Tumors

Xiang Liu¹, Wei Tian¹, Sven Ekholm¹

¹Department of Imaging Science, University of Rochester Medical Center, Rochester, NY, United States

Grading of non-enhancing supratentorial gliomas and neuronal-glial tumors (NEGNGT) is a diagnostic dilemma on conventional MR imaging as 45% of these tumors could be malignant. We retrospectively compared diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI) and MR spectroscopic imaging in preoperative grading of 50 patients with histology confirmed non-enhancing supratentorial gliomas and neuronal-glial tumors. The imaging parameters, included mean FA, mean FA ratio, maximal FA, minimal ADC, maximal rCBV, Cho/Cr and Cho/NAA which all were evaluated for both tumor groups. There were significant differences of mean FA, mean FA ratio and maximal FA between low and high grade NEGNGT(p<0.05), but no significance was found for the other parameters. ROC analysis showed that the maximal FA value had a higher sensitivity and specificity than the other parameters to differentiate between low and high grade NEGNGT. This result indicates that maximal FA may be the best adjuvant tool to help differentiating between low and high grade in non-enhancing supratentorial gliomas and neuronal-glial tumors.

                  2214.     MR Biomarker Profile for Infiltrative Tumor Region in Malignant Glioma

Radhika Srinivasan¹, Joanna J. Phillips¹, Gabriela Bourne¹, Alvin Au¹, Soonmee Cha¹, Susan Chang¹, Sarah J. Nelson¹

¹University of California, San Francisco, San Francisco, CA, United States

This study addresses the inability of conventional imaging to delineate infiltrative tumor regions, which causes the tumor to recur within the treatment volume. These regions have normal cellularity due to diffusely infiltrating cells and cannot be located based on increased cellularity with choline and ADC. To define an MR profile of an infiltrative tumor region HR-MAS spectroscopy of image-guided biopsies in newly diagnosed and recurrent GBM were analyzed and evaluated relative their spatial location within the tumor, pathological measures of its paired sample and diffusion measures derived from the biopsy location. These results will be presented and discussed.

                  2215.     Assessment of Vascularity in Malignant Glioma: Development of an Imaging Protocol at 7 T

Lars Gerigk¹, Armin Nagel², Armin Biller¹, Julien Dinkel¹, Lydia Schuster¹, Thomas Hauser¹, Michael Puderbach¹, Marco Essig¹, Stefan Delorme¹, Michael Bock²

¹Radiology, German Cancer Research Institute, Heidelberg, Baden-Württemberg, Germany; ²Medical Physics in Radiology, German Cancer Research Institute, Heidelberg, Baden-Württemberg, Germany

Malignant gliomas are highly vascularized, which makes them a target for new anti-angiogenic agents. MRI therapy monitoring will require more sophisticated methods than measuring the extent of contrast enhancement, because these agents change the blood-brain-barrier. Using the advantage of 7 T, direct imaging of the tumor vasculature becomes feasible. In our newly developed clinical imaging protocol, high-resolution T2w and T1w images show the internal morphology of the lesion, whereas TOF-MRA and SWI visualize the arterial and venous intratumoral vasculature. Automatic co-registration of MRA and morphology proved to be a simple, fast and reliable method to evaluate tumor vascularization.

                  2216.     Initial Experience with Ferumoxytol Dynamic Susceptibility MRI in Human Brain at 3T and 7T

Jeffrey Moses Njus¹, Edit Dosa², Seymur Gahramanov², John W. Grinstead³, Xin Li¹, Charles S. Springer, Jr. ¹, Edward A. Neuwelt², William D. Rooney¹

¹Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States; ²Department of Neurology, Oregon Health & Science University, Portland, OR, United States; ³Siemens Medical Solutions, Portland, OR, United States

MRI DSC techniques offer an efficient way to characterize brain perfusion properties. However, the use of low-molecular weight gadolinium based contrast agents (Gd) can introduce a significant confound into standard DSC analysis if extravasation is extensive; as often is the case for brain tumors.  The purpose of this study was to investigate the use of an ultra-small paramagnetic iron oxide (USPIO) compound to estimate brain tumor blood volume in human subjects.  To accomplish this goal, DSC acquisitions were performed using both Gd and USPIO based contrast agents in eleven human subjects at 3T and 7T.

Clinical Stroke Imaging: DWI DKI, MTC MRS & Plaque Imaging

                  2217.     Identification of Early Onset Strokes Using Multiparametric MRI as a Witness

Ona Wu¹, Lee H. Schwamm², Priya Garg¹, Muhammed A. Pervez², Albert J. Yoo³, Aurauma Chutinet², Robert Irie¹, Byeongseo Yook¹, William A. Copen³, Pamela W. Schaefer³, Aneesh B. Singhal², Karen L. Furie², Alma Gregory Sorensen¹

¹Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States; ²Department of Neurology, Massachusetts General Hospital; ³Department of Radiology, Massachusetts General Hospital

Approximately 25% of ischemic stroke patients have unwitnessed strokes and therefore ineligible for on label thrombolytic therapy. We investigated whether multiparametric MRI can be used for identifying patients who have early stage strokes (<=4.5 h). Acute DWI, PWI and FLAIR images from acute stroke patients imaged within 12 h since last known to be well (N=175) were analyzed. In regions that were DWI abnormal, there were significant difference in relative T2WI and FLAIR between patients seen within 4.5 h and those seen later. Multivariate logistic regression showed that T2WI, ADC, and CBV were predictive of patients with early onsets.

                  2218.     Evolution of Fractional Anisotropy in Hyperacute Ischemic Stroke

Ashley D. Harris^1,2, Linda B. Andersen, ^2,3, Robert K. Kosior, ^2,4, Henry Chen, ^2,5, Marina Salluzzi, ^2,4, Randall B. Stafford, ^2,5, Bradley G. Goodyear, ^2,3, Richard Frayne, ^2,3

¹School of Psychology, CUBRIC, Cardiff University, Cardiff, United Kingdom; ²Seaman Family MR Research Centre, Foothills Medical Centre, Calgary, Alberta, Canada; ³Clinical Neurosciences and Radiology, Univerisity of Calgary, Calgary, Alberta, Canada; ⁴Biomedical Engineering, Univerisity of Calgary, Calgary, Alberta, Canada; ⁵Physics, Univerisity of Calgary, Calgary, Alberta, Canada

Diffusion-weighted images and apparent diffusion coefficient maps are widely used in ischemic stroke detection; however, additional information may be available from diffusion imaging in the assessment of hyperacute ischemic stroke. In this study, fractional anisotropy was examined during hyperacute ischemic stroke (0–6h from onset) in a canine model. White matter shows a biphasic FA response; an initial increase followed by a decrease. Grey matter showed FA increases. The timing and magnitude of these FA changes appears to be related to stroke severity. With thorough understanding of these changes, FA may be useful in treatment decisions for stroke patients.

                  2219.     Apparent Kurtosis and Fractional Anisotropy Potentially Predicts Tissue Outcome in Sub-Acute Stroke

Danielle van Westen^1,2, Markus Nilsson³, Håkan Sjunnesson^1,2, Freddy Ståhlberg, ^2,3, Sara Brockstedt⁴, Ronnie Wirestam³, Jimmy Lätt^1,3

¹Center for Medical Imaging and Physiology, Lund University Hospital, Lund, Sweden; ²Department of Diagnostic Radiology, Lund University, Lund, Sweden; ³Department of Medical Radiation Physics, Lund University, Lund, Sweden; ⁴Radiation Physics, Lund University Hospital, Lund, Sweden

Diffusion measurements were performed 2, 9 and 90 days after stroke onset, estimating the mean diffusivity (MD), the apparent diffusion kurtosis (ADK) and the fractional anisotropy (FA). Tissue outcome at day 90 was dependent on tissue type, i.e. white- or grey matter, as well as location. For instance, deep white matter developed gliosis, while subcortical U-fibres pseudonormalized. FA and ADK obtained at day 2 predicted the tissue outcome at day 90 in white matter.

                  2220.     Diffusion Weighted Imaging of Carotid Atherosclerotic Plaque in Symptomatic Patients at 3-Tesla: Correlation with MRI, CT & Histopathological Predictors of Plaque Vulnerability

N Jane Taylor¹, Vicky J. Goh¹, J James Stirling¹, Ian Simcock¹, Matthew Orton², David J. Collins², Ralph Strecker³, Leon Menezes⁴, Raymond Endozo⁴, Justin J. Cross⁵, Richard Harvey⁶, Carl W. Kotze⁶, Syed W. Yusuf⁶, Ashley Groves⁴

¹Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, United Kingdom; ²CRUK-EPSRC Cancer Imaging Centre, Institute of Cancer Research & Royal Marsden Hospital, Sutton, Surrey, SM2 5PT, United Kingdom; ³Healthcare Sector, Siemens AG, 91052 Erlangen, Germany; ⁴University College Hospital, London, United Kingdom; ⁵Addenbrookes Hospital, Cambridge, United Kingdom; ⁶Brighton and Sussex University Hospitals, Brighton, Sussex, United Kingdom

Accurate identification of vulnerable carotid plaque influences patient treatment. Diffusion weighted imaging at 3T may potentially contribute to the identification of active plaques. This feasibility study in 14 patients with symptomatic disease assesses the correlation between plaque apparent diffusion coefficient (ADC) and imaging/histopathological features of vulnerability (thin cap, lipid core, haemorrhage, angiogenesis (CD105 or VEGF) & inflammation (CD68).  Mean (SD) plaque ADC was 1.30 X10-3(0.29) mm2/s. There was no difference in ADC between patients with and without MRI features of plaque vulnerability. There was a positive trend between ADC & CD105/VEGF, markers of angiogenesis meriting further investigation.

                  2221.     Differing Fractional Anisotropy Changes in Grey Matter and White Matter in Early Ischemic Stroke

Mohamed Mustafa Hirji^1,2, Ashley D. Harris, ^2,3, Robert K. Kosior, ^2,4, Cheryl R. McCreary, ^2,5, Richard Frayne^2,5

¹University of Calgary, Calgary, Alberta, Canada; ²Seaman Family MR Research Centre, Alberta Health Services, Calgary, Alberta, Canada; ³School of Psychology & Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, Wales, United Kingdom; ⁴Biomedical Engineering, University of Calgary, Calgary, Alberta, Canada; ⁵Radiology & Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

We characterise the fractional anisotropy (FA) changes in ischemic stroke. Diffusion tensor images of 13 patients were obtained within 26 hours of stroke (acutely) and >21 days later (follow-up). FA and eigenvalues were measured in freehand regions of interest (ROIs); anatomically-matched contralateral ROIs were used for control. Acutely, FA increased in gray matter (GM) but not in white matter (WM); the eigenvalue reductions were unbalanced in GM, but balanced in WM. At follow-up, FA decreased in both GM and WM with the eigenvalue changes similar in both GM and WM. Our results give insight into microstructural changes in stroke.

                  2222.     Intensive Blood Pressure Lowering Increases Cerebral Blood Flow in Older Subjects with Hypertension

Jiabao He¹, Dinesh Tryambake¹, Michael J. Firbank², John T. O’Brien², Gary A. Ford¹, Andrew M. Blamire¹

¹Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom; ²Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom

CBF determines brain tissue metabolic supply and is compromised in chronic hypertension which alters autoregulatory function.  Blood pressure (BP) lowering therapy has clear clinical benefit but may risk inducing hypoperfusion.  Optimal target BP in older subjects with hypertension is unclear, although guidelines recommend target BP of <130/85 mmHg and <140/80 mmHg for patients with and without previous vascular events respectively. We used ASL to determine the effect of usual (<140/85 mmHg) and intensive (<130/80 mmHg) BP lowering on CBF in older hypertensive subjects and demonstrate that intensive BP lowering increases CBF compared to usual BP lowering therapy.

                  2223.     Correlation Study of Cerebral Blood Flow and EEG Feature Based on CO2 Stimulation

Jing Wang¹, Liu Chen¹, Bing Wu², Xiaoping Hu³, Xiaoying Wang, ¹², Jue Zhang^1,4, Jing Fang^1,4

¹Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China; ²Dept. of Radiology, Peking University First Hospital, Beijing, China; ³Dept. of Biomedical Engineering, Georgia Institute of Technology / Emory University, Atlanta, United States; ⁴College of Engineering, Peking University, Beijing, China

The MR based evaluation of cerebral blood flow (CBF) plays an important role in assessment of post-stroke rehabilitation, but limits by its inconvenient and high costs. In this study, the weighted average accuracy index (WAAI), as a novel electroencephalogram (EEG) feature related index was introduced to estimate effectively the change of EEG pattern with the gradual CBF improvement due to the increase of CO2 concentration. Group results of healthy subjects showed that there existed a strong relationship between WAAI and CBF, indicating that the proposed WAAI index could be helpful to evaluate the extent of brain perfusion recovery.

                  2224.     MRI Study of ASL, MRS and BOLD in Patients with Left Symptomatic Internal Carotid Artery

Jie Lu¹, KunCheng Li¹, Miao Zhang, XiaoYi Wang

¹Xuanwu Hospital, Capital Medical University, Beijing, China

Arterial Spin Labeling (ASL) can quantitatively measure perfusion without the need of contrast material. 1H spectroscopy (1H-MRS) can identify cerebral abnormal metabolism. Patients with symptomatic occlusion of the internal carotid artery (ICA) with compromised cerebral blood flow (CBF) and decrease N-acetyl aspartate (NAA) are at risk for future ischemic infarcts. These patients can have different degree of cognitive impairment, especially working memory impairment2. Blood oxygenation level dependent (BOLD) is best used for studying processes that can be rapidly turned on and off like memory. In this study, we characterized CBF, MRS and BOLD changes in patients with symptomatic ICA occlusion.

                  2225.     Is There a Relationship Between M1 Cortex Activation and Upper Extremity Motor Characteristics During Acute Stage After Stroke?

Urska Puh¹, Andrej Vovk², Igor Serša³, Dusan Suput⁴

¹University of Ljubljana, Faculty of Health Sciences, Ljubljana, Slovenia; ²Pathophysiology, Univ. of Ljubljana Faculty of Medicine, Ljubljana, Slovenia; ³Institut Jozef Stefan, Slovenia; ⁴Pathophysiology, Univ. of Ljubljana Faculty of Medicine, Slovenia

12 patients with partially impaired function of one upper extremity 2-8 days after first ischemic stroke participated in the study. A 1.5 T scanner was used for brain fMRI during upper extremity functional tasks in the first and third week and 3 months after the stroke. Muscle strength and dexterity of the HPE were measured concomitantly. Spearman correlation coefficient was calculated to compare the M1 activation of each brain hemisphere and the motor characteristics of the HPE. Recovery of HPE function correlated well with the intensity and/or area of M1 cortex activation mainly in the ipsilesional hemisphere.

                  2226.     Varied Vasomotor Responses Among Brain Territories in Unilateral ICA Stenosis Patients Studied Using Breath-Hold BOLD MRI

Wan Chun Kuan¹, Ting Yu Chang², Keh Shih Chuang¹, Ho Fai Wong³, Tsong Hai Lee², Ho Ling Liu^4,5

¹Dept. of Biomedical Engineering and Environmental Sciences, National Tsing Hua Univ., Hsinchu, Taiwan; ²Stroke Center, Department of Neurology, Chang Gung Memorial Hospital; ³Department of Neuroradiology, Chang Gung Memorial Hospital; ⁴Dept. of Medical Imaging and Radiological Sciences, Chang Gung Univ.; ⁵Dept. of Medical Imaging and Intervention, Chang Gung Memorial Hospital

Impaired cerebral vasoreactivity could be one of the predictors for hyperperfusion after carotid interventions for patients with internal carotid artery (ICA) stenosis. This study aimed to evaluate the differences of hemodynamic responses among blood-supply territories, induced by vasodilatation following a breath-holding task, in patients with unilateral ICA stenosis using BOLD MRI. The temporal correlation between bilateral vasomotor responses in the MCA territories was utilized as an index.  The results showed significantly impaired responses of the lesion side as compared to the normal side (p<0.05) for patients exhibited hyperperfusion after the stenting (sensitivity = 100%, specificity = 92.3%).

                  2227.     Quantitative Magnetization Transfer Imaging in Acute Stroke: A Follow Up Study Correlating Quantitative MRI with Respect of Severity of Stroke

Felix Jax¹, Monika Gloor², Oliver Bieri², Meritxell Garcia¹, Stefan Engelter³, Felix Fluri³, Klaus Scheffler², E.-W. Radue¹, SG Wetzel¹

¹Department of Neuroradiology, University of Basel Hospital, Basel, Switzerland; ²Department of Radiological Physics, University of Basel Hospital, Basel, Switzerland; ³Department of Neurology, University of Basel Hospital, Basel, Switzerland

Magnetisation transfer (MT) imaging can potentially serve as a marker for loss of tissue integrity. Moreover increased pathologic specificity is expected from quantitative MT (qMT) as compared to the assessment of the semi-quantitative MT ratio (MTR) images only. Here, we present an evaluation of qMTI data over three consecutive MRIs within the first 10 days for patients suffering from middle cerebral artery stroke with different progression of symptoms. Results seem to be superior to simple MTR measurements and possibly allow for early statement of prognosis and efficacy of therapeutic methods.

                  2228.     The Assessment of Vessel Size Index and Its Application in Patients with Ischemic Stroke

Chao Xu¹, Wolf Schmidt¹, Peter Brunecker¹, Valerij Kiselev², Peter Gall², Nils Bodammer³, Jochen Fiebach¹

¹Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin Berlin, Berlin, Germany; ²Medical Physics, Department of Diagnostic Radiology, University Hospital Freiburg, Freiburg, Germany; ³Max Planck Institute for Human Development, Berlin, Germany

This study aims at implementation and evaluation of vessel size imaging (VSI) in patients with ischemic stroke. Stable values of vessel diameter have been observed in healthy volunteers in a good agreement with anatomic knowledge. VSI measurement is shown to be feasible for the clinical examination in stroke patients. Given the limitations of small number of patients, hypointensities on VSI maps in acute and chronic stage have been observed in areas of the final infarction. The recovered tissue showed normal VSI in the acute phase.

                  2229.     Regional Delta-Diffusion Analysis of the Brain During Cardiac Cycle in Idiopathic Normal Pressure Hydrocephalus

Naoki Ohno^1,2, Tosiaki Miyati², Mitsuhito Mase³, Hirohito Kan², Harumasa Kasai⁴, Masaki Hara⁴, Yuta Shibamoto⁴, Kazuo Yamada³, Akihiro Kitanaka², Tomoyuki Yamamoto¹

¹Department of Radiological Technology, Kanazawa University Hospital, Kanazawa, Japan; ²Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan; ³Department of Neurosurgery and Restorative Neuroscience, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan; ⁴Department of Radiology, Nagoya City University Hospital, Nagoya, Japan

There have been many unsolved problems with this syndrome in terms of the diagnostic criteria and selection of appropriate patients for shunt surgery. To evaluate the intracranial condition of the brain in idiopathic normal-pressure hydrocephalus (I-NPH), we determined the change in the apparent diffusion coefficient of the brain during the cardiac cycle (delta-ADC). Delta-ADC analysis makes it possible to noninvasively obtain new and more detailed information on the intracranial condition in I-NPH and thereby assist in the diagnosis.

Stroke: Animal Models

                  2230.     Enhanced Functional and Structural Connectivity in the Contralesional Hemisphere After Unilateral Stroke in Rats: A Combined Resting-State FMRI and MEMRI Study

Maurits P.A. van Meer^1,2, Wim M. Otte^1,3, Kajo van der Marel¹, Jan W. Berkelbach van der Sprenkel², Rick M. Dijkhuizen¹

¹Biomedical MR Imaging and Spectroscopy group, Image Sciences Institute, Utrecht, Netherlands; ²Department of Neurosurgery, Rudolf Magnus Institute of Neuroscience, Utrecht, Netherlands; ³Department of Neurology, Rudolf Magnus Institute of Neuroscience, Utrecht, Netherlands

Reorganization of neuronal networks may effectively constitute spontaneous functional recovery after stroke. However, the association between structural and functional remodelling in post-stroke brain remains unclear. In this study we combined resting-state fMRI with manganese-enhanced MRI to elucidate the relationship between functional and structural brain connectivity in presumably reorganized contralesional brain tissue in rats that have recovered from experimental unilateral stroke. We detected increased uptake of the neuroanatomical tracer manganese in the contralesional sensorimotor cortex that was significantly correlated with enhanced functional connectivity within this region. Our data suggest that improved neuroanatomical connectivity underlies enhancement of functional connectivity in reorganizing neuronal networks after stroke.

                  2231.     Evolution of Functional Connectivity After Transient Stroke in Rats

Woo Shim^1,2, Kwangyeol Yeol Baek^1,2, Jeong Kon Kim³, Guangping Dai¹, Jaeseong Jeong², Bruce Rosen¹, Young Ro Kim¹

¹Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States; ²Bio and brain engineering, KAIST, Yuseong-gu, Daejeon, Korea, Republic of; ³Radiology, Asan Medical Center, Seoul, Korea, Republic of

We monitored changes of resting-states functional connectivity using cross-correlation technique over a period of 30 days after transient cerebral ischemic damage. Averaged correlation strengths among some ROIs in stroke rats monotonically increased within the contralesional hemisphere over time, eventually matching those in control group. Despite the slight recovery, cross-correlation values measured within ipsilesional hemisphere and between bilateral hemispheres show severely impaired functional connectivity over 30 days after stroke. Although highly speculative, the data demonstrated that the initial limb dysfunction is related to the loss of brain connectivity in both ipsi- and contra-lesonal brain regions and that the restoration of function may be associated more with the increase of functional connectivity within the contralesional than the ipsilesional hemisphere.

                  2232.     Multi-Parametric Stroke Imaging Protocol for Mice Using a 1H Cryo Probe at 9.4 T

Patrick Michael Heiler¹, Friederike Lara Vollmar², Melanie Heilmann¹, Andreas Lemke¹, Stephen Meairs², Marc Fatar², Lothar Rudi Schad¹

¹Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany; ²Experimental Neurology, Heidelberg University, Mannheim, Germany

The investigation of rt-PA therapy after MCAo in mice by means of MRI requires adequate resolution for the brain size of about 1 x 1 cm², in measurement times acceptable for follow-up studies. We present a protocol including t2-weighted imaging, diffusion weighted imaging and a TOF angiography using a 1H surface cryo coil at 9.4T. The results demonstrate that rt-PA therapy leads to reperfusion of the MCA and significantly reduces the extension of ischemia. The short measurement time makes the protocol suitable for both, detection of the MCAo success immediately after the surgery and temporal evolution studies after rt-PA therapy.

                  2233.     High-Resolution 31P Chemical Shift Imaging of Acute Stroke at 11.7T

Andrew Bresnen¹, Fang Du¹, Qiang Shen¹, Geoffrey Clarke², Timothy Q. Duong¹

¹Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Tx, United States; ²Radiological Sciences, University of Texas Health Science Center at San Antonio, San Antonio, Tx, United States

In vivo 31P chemical shift imaging allows direct measurements of the high energy phosphates. 31P NMR has proven useful for investigating the bioenergetics in normal brain. However, the low SNR, long scan time and low spatial resolution of 31P NMR have prevented its widespread use, particularly in the study of acute stroke. This study implemented and optimized 31P CSI on rat brain with high spatio-temporal resolution at 11.7T. This approach, along with 1H diffusion, perfusion and T2 MRI, was used to investigate changes of high energy phosphates in stroke rats at 1, 3 and 24 hrs after onset.

                  2234.     Diffusion Tensor Echo Planar Imaging of Mouse Brain After Brief Focal Middle Cerebral Artery Occlusion at 14T

Hongxia Lei^1,2, Yohan Van de Looij^1,3, Nicolas Kunz^1,3, Carole Berthet⁴, Lorenz Hirt⁴, Rolf Gruetter^1,5

¹LIFMET, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; ²Radiology, University of Lausanne, Lausanne, Switzerland; ³Pediatrics, University of Geneva, Geneva, Switzerland; ⁴Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; ⁵Radiology, University of Geneva, Geneva, Switzerland

Diffusion tensor imaging allowed accurately measuring ADC, which is very essential for stroke studies. We sought to establish feasibilities of EPI-version DTI of mouse brain after brief ischemia at 14T. The nearly artifact free DTI images allowed accurately measuring ADC maps and help localizing ischemic core more precisely when no abnormal T₂ contrast expressed.

                  2235.     Cerebral Blood Flow Autoregulation in Transient Ischemic Tissue Expressed Delayed Hyperperfusion Two Days After Middle Cerebral Arterial Occlusion

Kazuhiro Nakamura¹, Yasushi Kondoh¹, Shigenori Mizusawa¹, Junko Yoshida¹, Hajime Miyata¹, Toshibumi Kinoshita¹

¹Akita Research Institute for Brain and Blood Vessels, Akita, Japan

Strong hyperperfusion was observed in transient ischemic tissue 48-72 h after middle cerebral artery occlusion (MCAO). To investigate a physiological reason for the phenomena, we have performed experiments for revealing cerebral blood flow (CBF) autoregulation in transient ischemic tissue using a lower body negative pressure method. Using the lower body negative pressure method, we can avoid an estimation error in CASL from a blood oxygen dependent signal change. The results show CBF in ischemic tissue is higher than normal in all blood pressure range and it should indicate the autoregulatory failure of small pial artery in the ischemic tissue.

                  2236.     Incorporating ADC Temporal Profiles in Acute Stroke to Predict Ischemic Tissue Fate

Virendra R. Desai¹, Qiang Shen¹, Timothy Q. Duong¹

¹Research Imaging Institute, Ophthalmology/Radiology, UT Health Science San Antonio, San Antonio, TX, United States

Acute diffusion data has been used to predict ischemic tissue fate on a pixel-by-pixel basis. Previous predictions however were made based on acute MRI data from a single time point. This study proposes a novel approach to incorporate the temporal characteristics of acute ADC (apparent diffusion coefficient) changes to characterize tissue fate based on a pixel-by-pixel basis. This approach was tested on rat stroke models subjected to permanent and 60-min middle cerebral artery occlusion (MCAO). We concluded that there were distinct temporal patterns that determined tissue salvageability.

                  2237.     tPA-Induced Suppression of Cerebrovascular Parameters in Acute Rat Stroke Model: Dynamic MRI Study

Young Ro Kim¹, Xiang Fan², Guangping Dai¹, Jeong Kon Kim³, Bruce R. Rosen¹, xiaoying Wang²

¹Radiology, Martinos Center for Biomedical Imaging / Massachusetts General Hospital, Charlestown, MA, United States; ²Radiology, Neuroprotection Research laboratory / Massachusetts General Hospital, Charlestown, MA, United States; ³Radiology, Asan Medical Center, Seoul, Korea, Republic of

Tissue plasminogen activator (tPA) has been frequently used for treating acute ischemic stroke based on re-canalization, reopening of occluded vessels for the reinstitution of regional blood perfusion. Despite the promising clinical outcomes, exogenous tPA may worsen the ischemia-induced blood brain-barrier disruption, elevate risks of intracranial hemorrhage, and in part consequently reduces the therapeutic time window. Therefore, it is critically important to understand the overall effects of tPA treatment on cerebrohemodynamics. In this study, we investigated the vasoreactivity in response to intravenously administered tPA and to systemic hypercapnia before and after tPA using a permanent focal stroke rat model.

                  2238.     Validation of T2* Weight Signal Change of Oxygen Challenge as a Potential Better Penumbra Estimation

Fang Du¹, Shiliang Huang¹, Qiang Shen¹, Timothy Q. Duong¹

¹Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Mismatch of diffusion/perfusion by MRI has been used as an estimate of the ischemic penumbra, but there are large parts of the mismatch region appear not to at risk and it was also reported that some of the apparent diffusion coefficient reduction area can be salvaged by early reperfusion.  It was proposed that T2* weight signal change of oxygen challenge could be a better penumbra estimation.  This study applied OC technique to a group of transient ischemia rats and proved this hypothesis.

                  2239.     MRI of Emboli Localization and Lysis in an Embolic Model of Rat Middle Cerebral Artery Occlusion

Ronn Philip Walvick¹, Bernt Torre Bratane², James Bouley², Nills Henninger², Mitchell Albert¹, Marc Fisher¹

¹Radiology, University of Massachusetts Medical School, Worcester, MA, United States; ²Neurology, University of Massachusetts Medical School, Worcester, MA, United States

We present a novel technique to localize and observe the dynamics of clot lysis during tissue Plasminogen Activator (tPA).  Prior to fabrication of clots, blood was doped with Magnevist (Bayer, Wayne, NJ).  Clots were withdrawn tubing and injected into the left common carotid artery at the base of the skull causing a  middle cerebral artery occlusion.  MRI consisted of diffusion, perfusion, and T1 weighted imaging for clot localization, and MR angiography.  During tPA administration, serial T1 weighted and perfusion imaging was performed.  Our results demonstrate the ability of this method to detect clots in a preclinical model of embolic stroke.

                  2240.     Magnetic Resonance Imaging as an In-Vivo Tool for Evaluating Efficacy of Brain Edema Prevention Therapy in a Rat Stroke Model

Denise C. Welsh¹, Andrew Danziger², Theodore Detwiler², Hillary Regan², Joseph J. Lynch², Christopher P. Regan², Donald S. Williams¹, Alexandre Coimbra¹

¹Imaging, Merck, West Point, Pa, United States; ²Central Pharmacology, Merck, West Point, Pa, United States

While numerous studies have used MRI techniques for studying stroke pathology, there has been limited use of MR parameters as in vivo markers of novel treatment efficacy.  Here, Gd-enhanced T1-w and T2-w MR data were used to verify the efficacy of pre- and post-infarct treatment with a novel KDR kinase inhibitor (KDRi) known to reduce vascular permeability and therefore, BBB leakage.  In line with previously published ex-vivo data (1), in-vivo MRI results suggest efficacy of KDRi treatment in reducing BBB leakage and edema formation, as indicated by tissue water content.

                  2241.     Longitudinal Assessment of Brain Damage in Hypertension Rats Using Diffusion Tensor Imaging

Chien-Yuan Lin¹, Cheng-Di Chiu^2,3, Ming-Huang Lin¹, Wai-Mui Cheung¹, Teng-Nan Lin¹, Chen Chang¹

¹Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; ²Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; ³Department of Neurosurgery, Chang-Hua Hospital, Chang-Hua, Taiwan

The elevated blood pressure is considered to be the main risk factor of stroke and is highly associated with white matter lesions. This study aimed to investigate the change of white matter microstructure under various levels of blood pressures.

                  2242.     MRI Monitoring of Endogenous Stem Cell Therapies in Animal Models of Stroke

Voytek Gretka¹, Lisa Di Diodato¹, Amy Hoyles², Nancy J. Lobaugh³, Cindi Morshead², Greg J. Stanisz¹

¹Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; ²Department of Surgery, University of Toronto, Toronto, ON, Canada; ³Cognitive Neurology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

In animal models of stroke, endogenous neural precursor cells can be activated with growth factors such as epidermal growth factor (EGF) and erythropoietin (EPO) leading to increased neurogenesis and behavioural recovery. We demonstrated the feasibility of using MR to distinguish between regenerating and pathological tissues when using endogenous stem cell therapies in rats. Tissue growth in the lesion site has MR characteristics (T₁ and T₂) similar to that of normal brain tissue, and differs distinctly from the cavity present when animals are untreated. MRI is able to predict the outcome of the treatment as early as 2 weeks post stroke.

                  2243.     Identifying the Ischaemic Penumbra by Probing Tissue Metabolism and Imaging Changes in Tissue Lactate.

William Matthew Holmes¹, Maria Rosario Lopez Gonzalez², Lindsay Gallagher¹, Graeme A. Deuchar¹, I M. Macrae¹, Celestine Santosh³

¹GEMRIC, Wellcome Surgical Institute, Univeristy of Glasgow, Glasgow, United Kingdom; ²SINAPSE, Clinical Physics, University of Glasgow, Glasgow, United Kingdom; ³Institute of Neurological Sciences, Southern General Hospital, Glasgow, United Kingdom

One of the most important considerations when treating acute stroke patients is to establish whether potentially salvageable (penumbral) tissue is still present within the brain. Currently perfusion-diffusion mismatch MRI is used, which is an indirect measure lacking precision . Here we propose a new MRI method for imaging the ischaemic penumbra based on the brain’s capacity to use lactate as a metabolic substrate. Spectroscopic imaging is used to map the changes in tissue lactate induced by giving a challenge of 100% oxygen.

                  2244.     Estimation of the Onset Time of Cerebral Ischemia in Rats Using T_1ρ MRI

Kimmo T. Jokivarsi¹, Yrjö Hiltunen², Heidi I. Gröhn³, Olli H. Gröhn¹, Risto A. Kauppinen⁴

¹Department of Neurobiology, A.I.Virtanen -Institute, Kuopio, Finland; ²Department of Environmental Science, University of Kuopio, Kuopio, Finland; ³Department of Clinical Physiology, Nuclear Medicine and Neurophysiology, North Karelia Central Hospital, Joensuu, Finland; ⁴Department of Radiology, Dartmouth Medical School, Hanover, NH, United States

MRI parameters can be used to acquire information about stroke and its progression. We investigated the prediction potential of absolute T_1ρ in cerebral ischemia in a rat stroke model. Our results show that δT_1ρ can give an accurate estimate of ischemia time. Clinically this method provides an easy and fast MR method for ischemia time estimation that can be used in the absence of a priori knowledge or as an additional confirmation for the clinical estimate of stroke onset.

                  2245.     Artificial Neural-Network Prediction of Ischemic Tissue Fate in Acute Stroke Imaging

Shiliang Huang¹, Qiang Shen^1,2, Timothy Q. Duong^1,2

¹Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States; ²Department of Ophthalmology/Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

A flexible artificial neural network (ANN) algorithm was developed and applied to predict ischemic tissue fate on three stroke groups: 30-min, 60-min and permanent MCAO in rats. CBF, ADC and T2 were acquired during the acute phase up to 3hrs and again at 24hrs followed by histology. Infarct was predicted pixel-by-pixel using only acute (30-min) stroke data. Receiver-operating-characteristic analysis was used to quantify prediction accuracy. It was concluded that the ANN predictive model has the potential to serve as promising metrics for diagnosis, prognosis and therapeutic evaluation of acute stroke.

                  2246.     Prolonged Post-Ischemic Hyperperfusion: A Systematic Multimodal MRI Study

Qiang Shen^1,2, Fang Du¹, Shiliang Huang¹, Timothy Q. Duong^1,2

¹Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States; ²Ophthalmology/Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Regional hyperperfusion after stroke is a frequent, yet poorly understood, phenomenon. In this study, multimodal MRI (diffusion, perfusion, T2, T1, pH-weighted and dynamic contrast-enhanced imaging, and MRA) were acquired in a 30-min transient MCAO in rat. Significant hyperperfusion was observed 24hrs post-occlusion and peaked at 48hrs. Hyperperfusion areas were consistent with regions with T1 and T2 increases, and early-phase pH decrease, and late-phase permeability changes. MRA showed significant vasodilatation of distal small arteries. We conclude that hyperperfusion does not appear to salvage tissue. Multimodality MRI investigation helps to gain significant insights into the underlying physiological changes associated with hyperperfusion.

NRA & CSF Studies with Clinical Applications

                  2247.     Magnetic Resonance Angiography of the Mouse Cerebrovascular System at 17.6 T

Firat Kara¹, Alia Alia¹

¹Leiden Institude of Chemistry, Leiden University, Leiden, Netherlands

As magnetic field strength increase toward higher fields , it  allows significant improvements in  MRI techniques by enhancing contrast to noise and  signal to noise ratio. The use of magnetic resonance angiography (MRA) in ultra high magnetic field to visualize cerebrovascular structure of  animals,  promote development of early diagnosis and treatment of human neurodegenerative diseases.  In this study, an improved contrast-to-noise ratio at 17.6 T imaging contribute to visualization the smaller vessels of the mouse brain. Branches of  anterior cerebral artery (ACA)are better depicted  on maximum intensity projections(MIP) with  17.6 T imaging than MIPs obtained with 9.4.

                  2248.     Time of Flight Magnetic Resonance Angiography of the Canine Brain at 3T and at 7T - A Quantitative Comparison

Steffen Sammet¹, Paula Martin-Vaquero², Rita L. Echandi², Ronaldo C. da Costa², Christina L. Tosti¹, Michael V. Knopp³

¹Department of Radiology, The Ohio State University, Columbus, OH, United States; ²Veterinary Hospital, The Ohio State University, Columbus, OH, United States; ³Department of Radiolgy, The Ohio State University, Columbus, OH, United States

The purpose of this study was to evaluate the ability of 2D ToF-MRA to depict cerebral arteries in the canine brain and to compare the results obtained from a high field magnet (3T) with an ultrahigh field magnet (7T). ToF-MRA at high and ultra-high magnetic fields should be included in the MRI imaging protocol of dogs suspected of having cerebrovascular disease. 7T field ToF-MRA allows a better delineation of small vessels in the canine brain than 3T ToF-MRA.

                  2249.     Blood Contrast Agent Concentration Measured by Dynamic MRI in Intra- And Extracranial Mouse Vessels at 9.4 Tesla Using a Novel Cryogenic Probe

Melanie Heilmann¹, Hanne Boll², Sebastian J. Schambach², Christoph Groden², Marc A. Brockmann², Lothar R. Schad¹

¹Computer-Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany; ²Neuroradiology, University Medicine Mannheim, Germany

Quantitative dynamic MRI requires knowledge of contrast agent (CA) concentration in blood. Due to the small size of murine vessels, so far an arterial input function (AIF) has only been measured in mouse hearts. Using a novel cryogenic probe at 9.4 T, we measured CA kinetics in intra- and extracranial vessels. Although high inter-individual variations were observed, in average, kinetics of the superficial temporal vein provided good estimates for blood CA concentration. Smaller vessels suffered from partial volume effects but were less prone to inter-individual variations. Whether mouse perfusion studies benefit from vessel-based AIFs, remains to be studied in future.

                  2250.     Cerebral Blood Flow Change in One Hear Beat by CO2 Concentration Using Retrospective PC MRI Measurements

Yi-Jui Liu^1,2, Chun-Jung Juan³, Teng-Yi Huang⁴, Hsiao-Wen Chung⁵, Cheng-Yu Chen³

¹Department of Automatic Control, Feng Chia University, Taichung, Taiwan; ²Master's Program in Biomedical Informatics and Biomedical Engineering, Feng Chia University, Taichung, Taiwan; ³Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; ⁴Department of Electrical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; ⁵Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan

The purpose of this study was to evaluate the cerebral blood change in one cardiac cycle in different concentration of carbon dioxide inhalation. Using retrospectively gated 2D phase contrast MRI is suitable method for measuring the velocity of cerebral arteries and veins during one hear beat. It is noninvasive modality to quantify the blood flow and blood volume in one heart cycle with high spatial and temporal resolution. By this MR method, we proceeded the experiment that observe the blood flow change during the CO2 concentration change.

                  2251.     Quantification of Carotid Artery Blood Flow Before and After the Acetazolamide Challenge

Josephine Mary Reeve¹, Dinesh Selvarajah², Nyssa Craig¹, Paul David Griffiths¹, Solomon Tesfaye², Iain D. Wilkinson¹

¹Academic Radiology, University of Sheffield, Sheffield, S Yorkshire, United Kingdom; ²Diabetes, Royal Hallamshire Hospital, Sheffield, S Yorkshire, United Kingdom

Cerebrovascular reserve or the ability to vasodilate under stress may be a crucial physiological mechanism, providing increased arterial flux when necessary. This study quantified flow within the internal carotid artery (ICA) in 14 normal young adults before and after administration of a carbonic anhydrase inhibitor (acetazolamide). Quantitative flow assessment was based on a single-slice, multi-phase, fast-field echo sequence. Data was extracted via ROI analysis. Significant increases in velocity, flux, apparent vessel diameter but not heart rate were observed following acetazolamide. This assessment provides an objective in-vivo marker of the functional reserve of the macrovascular supply system.

                  2252.     Towards True Arterial Intracranial TOF-MRA at 7T: Protocol Optimization Using VERSE Pulses

Soeren Johst¹, Sebastian Schmitter², Armin Nagel¹, Wolfhard Semmler¹, Michael Bock¹

¹Medical Physics in Radiology, German Cancer Research Center (dkfz), Heidelberg, Germany; ²Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States

TOF MRA highly profits from high fields, however, SAR restrictions limit the use of high-resolution protocols. In particular, venous suppression with saturation pulses is difficult within clinically acceptable measurement times (TA ¡Ü 10min). Using the VERSE algorithm on the excitation pulses as well as on the energy-intensive saturation pulses permits an effective SAR reduction that can be used to shorten the acquisition time. With a modified TOF MRA pulse sequence high resolution intracranial MRA data sets with excellent venous suppression could be acquired in 10 min at 7 Tesla.

                  2253.     Fast Inversion Recovery Magnetic Resonance Angiography (FIR-MRA) of the Intracranial Arteries

Ek Tsoon Tan¹, John Huston III¹, Norbert G. Campeau¹, Stephen J. Riederer¹

¹Radiology, Mayo Clinic, Rochester, MN, United States

Spin-labeling-based FIR-MRA can provide high resolution 3D intracranial MRA. A detailed comparison of FIR-MRA (7.7 min) to standard 3D time-of-flight (TOF) MRA (6.5 min) was performed at 3 Tesla. Superior or equal vessel conspicuity, continuity, and venous suppression were demonstrated in eight normal subjects with FIR-MRA. Three clinical studies were performed. In two patients with coiled aneurysms, FIR-MRA provided superior depiction of aneurysm remnants to TOF. In one arteriovenous malformation (AVM) patient, FIR-MRA provided a clearer depiction of the AVM nidus than TOF and contrast-enhanced MRA, and could differentiate between the arterial and venous components of the AVM.

                  2254.     Assessment of the Supra-Aortic Vessels Using Time-Resolved Double-Bolus 3D TWIST-MRA

Andreas Korn¹, Till K. Hauser¹, Sören Danz¹, Benjamin Bender¹, Michael Fenchel¹, Thomas Nägele¹, Ulrike Ernemann¹, Uwe Klose¹

¹Department of Neuroradiology, University Hospital Tübingen, Tübingen, Germany

MRA of the supra-aortic vessels is usually performed in CARE bolus technique, which necessitates high operator experience and interaction with the control panel. TWIST requires less operator experience and interaction. Goal of the present work was to implement an automated and therefore robust protocol for the TWIST angiography of the supra-aortic vessels with high spatial resolution and increased likelihood of optimal arterial contrast by double bolus injection. The new double bolus injection protocol allowed for good separation of arterial vessels at least after one of the two bolus applications.

                  2255.     High Resolution 3D Intracranial Imaging at 3.0T

Yiu-Cho Chung¹, Steven Shea², Ye Qiao³, Orlando P. Simonetti⁴, Bruce Wasserman³

¹Siemens Medical Solutions USA, Inc., Columbus, OH, United States; ²Siemens Corporate Research, United States; ³Johns Hopkins University, United States; ⁴The Ohio State University, United States Minor Outlying Islands

Intracranial artery imaging is usually done by 2DTSE. However, the technique has long scan time, and has very limited anatomical coverage. We propose here the use of T1w-SPACE, a variant of TSE, for 3D imaging of the intracranial vessels. Using a 32 channel head coil at 3.0T, the technique achieves a spatial resolution of (0.5mm)3, comparable to CT, in less than 11minutes. The technique can cover both sides of the tortuous ICA and MCA in one scan. SNR comparison found that the 3D technique has consistently higher SNR than 2DTSE.

                  2256.     Utility of Susceptibility Weighted Imaging for the Detection of Arteriovenous Shunting in Vascular Malformations of the Brain

Bharathi Dasan Jagadeesan¹, Josser E. Delgado Almandoz², Tammie Benzinger², Christopher Moran²

¹Neuroradiology, Washington University School of Medicine , St Louis, MO, United States; ²Neuroradiology, Washington University School of Medicine, St Louis, MO, United States

We retrospectively evaluated the utility of susceptibility weighted imaging (SWI) in the detection of arterio-venous shunting (AVS) in 47 patients with 66 brain vascular malformations (BVM) identified on digital subtraction angiography (DSA). AVS was considered to be present if there was hyperintensity in a vein adjacent to the BVM. Overall, SWI had a sensitivity of 93%, specificity of 100% and accuracy of 97% for the detection of AVS. In the 13 BVMs associated with hemorrhage, SWI had sensitivity and specificity of 100%. In the 53 BVMs not associated with hemorrhage, SWI had a sensitivity of 92% and specificity of 100%.

                  2257.     Comparative Study of 3.0- And 1.5-T MR in the Follow-Up of Moyamoya Disease

Qianna Jin¹, Tomoyuki Noguchi¹, Hiroyuki Irie¹, Masashi Nishihara¹, Tetsuyoshi Hirai¹, Masatou Kawashima², Toshio Matsushima², Sho Kudo¹

¹Radiology, Saga University Hospital, Saga, Japan; ²Neurosurgery, Saga University Hospital, Saga, Japan

To retrospectively compare 3.0- and 1.5-T magnetic resonance (MR) findings in patients with moyamoya disease (MMD), and assess the relationship and difference between those two modalities in the follow-up of MMD. 60 (120 sides) MMD patients (15 male and 45 female patients, age range: 5 to 60 years, post/pre-operative patients: 44/ 16) were included. We got different upgrading rate among one-year interval follow-up with 1.5- and 3.0-T MR in different orders. Regardless of disease progressing, we should be careful about 1.5-T MR in evaluating steno-occlusive severity of intracranial vessels in MMD for its higher overestimating rate compared with 3.0-T MR.

                  2258.     Temporal Stability of Blood Flow Patterns in Cerebral Aneurysms Quantified with 2D Phase Contrast Magnetic Resonance Imaging In-Vivo

Christof Karmonik¹, Yi J. Zhang¹, Orlando Diaz², Richard Klucznik², David Purdy³, Robert G. Grossman¹

¹Neurosurgery, The Methodist Hospital Neurological Institute, Houston, TX, United States; ²Radiology, The Methodist Hospital Neurological Institute, Houston, TX, United States; ³Siemens Healthcare, Malvern, PA, United States

Complex flow patterns in cerebral aneurysms have been identified by computational fluid dynamics (CFD) studies to potentially be predictive of aneurysm rupture. Here, we quantified the stability of blood flow patterns in cerebral aneurysms in vivo based on flow features in  2D pcMRI images in seven aneurysms.  A stability index (SI) defined as the area fraction (in percent) exhibiting sign changes of the through-plane velocity was calculated. Average SI range was 1.3%-20.6%. Average SI and aneurysm size were linearly correlated (R=0.796). Further studies are warranted to explore the potential of the average SI as a marker for aneurysm rupture.

                  2259.     Measurement of Deep Gray Matter Perfusion in Acute Mild Traumatic Brain Injury Using Segmented True-FISP ASL

Elan J. Grossman¹, Yulin Ge¹, Matilde Inglese¹, Ke Zhang¹, Jing An², Ding Xia¹, Jian Xu³, Niels Oesingmann³, Kelly A. Mcgorty¹, Joseph Reaume¹, Robert I. Grossman¹, Qun Chen¹

¹Center for Biomedical Imaging, Department of Radiology, NYU School of Medicine, New York, United States; ²Siemens Medical Solutions, Beijing, China; ³Siemens Medical Solutions, Malvern, PA, United States

Conventional imaging fails to reveal evidence of damage in mild traumatic brain injury (MTBI) that accounts for its disabling impairments. The purpose of the current study is to examine if perfusion changes in thalamus and basal ganglia can be a possible indicator of pathology in acute MTBI. We have employed segmented True-FISP ASL, which we recently developed to measure perfusion in deep gray matter at high spatial resolution. Results indicate there are significant differences between patients and controls in thalamus and caudate. This suggests these regions may exhibit hypoperfusion in acute MTBI and could be biomarkers of persistent post-concussive syndrome.

                  2260.     Complex Flow Patterns in a Real-Size Intracranial Aneurysm Phantom: A PC-MRI Study Compared with PIV

Pim van Ooij¹, Annetje Guédon², Christian Poelma³, Joppe J. Schneiders⁴, Charles B. Majoie⁴, Jenny Dankelman², Ed vanBavel¹, Aart J. Nederveen⁴

¹Biomedical Engineering & Physics, Academic Medical Center, Amsterdam, Noord-Holland, Netherlands; ²Biomechanical Engineering, Delft University of Technology, Delft, Netherlands; ³Laboratory for Aero and Hydrodynamics, Delft University of Technology, Delft, Netherlands; ⁴Radiology, Academic Medical Center

To validate 4D blood flow velocity measurements in intracranial aneurysms using phase contrast MRI, a real-size glass phantom of an intracranial aneurysm was created and used for blood flow velocity measurements using PC-MRI and PIV. Resolution of PC-MRI was 0.5x0.5x0.5 mm and took 70 minutes to scan. Both steady and pulsatile flow measurements in MRI and PIV produced similar flow patterns of similar magnitude, although more noise was found in the MR results. Velocity to noise ratio will improve with more accurate velocity encoding settings. More importantly, to be able to apply the PC-MRI scan in patients, scan time needs to be shortened severely, for example by acceleration techniques.

                  2261.     Distribution of Cerebral Blood Flow in the Nucleus Caudatus, Nucleus Lentiformis, and Thalamus in Patients with a Carotid Artery Stenosis

Nolan S. Hartkamp¹, Reinoud P.H. Bokkers¹, H. B. van der Worp², L. J. Kappelle², M. P.J. van Osch³, Willem P.T.M. Mali¹, Jeroen Hendrikse¹

¹Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands; ²Department of Neurology, University Medical Center Utrecht, Utrecht, Netherlands; ³Department of Radiology, Leids University Medical Center, Leiden, Netherlands

For patients with a symptomatic internal carotid artery (ICA) stenosis, it is often difficult to identify the symptomatic artery for treatment due to the variability in perfusion territories of the major cerebral arteries. For the basal ganglia, this imposes an even greater difficulty. Using selective arterial spin-labeling MRI, this study found the nucleus caudatus in patients with a symptomatic ICA stenosis was more often fed by the contralateral ICA compared to healthy control subjects (p=0.03). This was accompanied by reversed blood flow through the ipsilateral anterior part of the circle of Willis (p<0.01).

                  2262.     Value of Three-Dimensional Contrasted-Enhanced MR Angiography Combined with MRI in Diagnosis and Treatment of Cerebral Arteriovenous Malformations

Qi Liu¹, Ping jian Lu¹, Fei Wang¹, li Wang¹

¹Radiology, Changhai Hospital, Second Military Medical University, Shanghai, China

Cerebral arteriovenous malformations are congenital vascular lesions with dilated feeding arteries and draining veins without an intervening capillary bed. Treatment is recommended for most patients because of the risk of hemorrhage, which largely dependent on the imaging information available before treatment. Three-dimensional contrasted-enhanced MR angiography combined with MRI, as a noninvasive technique with the advantages of arterial angiography, can depict the feeding arteries, venous drainage pattern, nidus, and provide more accurate localization of the nidus, adjacent brain anatomy. These data are important for the planning of surgical resection, endovascular embolization and radiotherapy.

                  2263.     Flow-Sensitive Black Blood Imaging : Clinical Intracranial Applications

Vijay Sawlani¹, J Spark², Faiza Admiraa-Behloul³

¹Radiology, Morriston and Singleton hospitals ABM university NHS trust, Swansea, United Kingdom; ²Morriston and Singleton hospitals ABM university NHS trust, Swansea,, United Kingdom; ³MR-BU, Toshiba Meidcal Systems Europe, Zoetermeer, Netherlands

Susceptibility-weighted imaging (SWI) is sensitive to venous vasculature and is a powerful tool for evaluating vascular malformations such as venous angiomas. To enhance the visibility of small vascular structures, especially at 1,5T systems,  a flow-sensitive black-blood (FS-BB) has been recently developed; The purpose of this study is to evaluate the utility of the FS-BB sequence in various intracranial lesions apart from vascular malformations.

                  2264.     Characterization of Carotid Plaque in-Vivo and ex-Vivo Using MRI, CTA and Histology

Maria Rosario Lopez Gonzalez¹, William Matthew Holmes², William Stewart³, Keith W. Muir⁴, Barrie Condon, George Welch⁵, Kirsten Forbes

¹SINAPSE, Clinical Physics, University of Glasgow, Glasgow, United Kingdom; ²GEMRIC, Wellcome Surgical Institute, Faculty of Medicine, University of  Glasgow, Glasgow, United Kingdom; ³Department of Neuropathology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, United Kingdom; ⁴Division of Clinical Neurosciences, University of Glasgow, Glasgow, United Kingdom; ⁵Vascular surgery, Southern General Hospital, Glasgow, United Kingdom

In-vivo 3T MR and CTA images were acquired of symptomatic stroke patients. These images show that most of the patients presented high degrees of atherosclerotic carotid plaque. To help to identify unstable and vulnerable plaques, segmentation of the different plaque components was carried out by using a semiautomatic thresholding method. Half of the patients underwent surgical excision of the carotid plaque. The specimens obtained were imaged in a 7T scanner. The specimens were sectioned and stained with heamatoxylin-eosin and Elastin van Gieson. Correlation of the MRI datasets and Histology was carried out.

                  2265.     Supraaortic MRA and Vessel Wall Enhancement with a Blood Pool Contrast Agent at 3.0T: Preliminary Results in Carotid Artery Disease and Intraindividual Comparision with Gd-DTPA

Dariusch Reza Hadizadeh¹, Guido Matthias Kukuk¹, Jürgen Gieseke¹, Arne Koscielny², Frauke Verrel², Jack Boschewitz¹, Ute Fahlenkamp¹, Hans Heinz Schild¹, Winfried Albert Willinek¹

¹Radiology, University of Bonn, Bonn, NRW, Germany; ²Vascular surgery, University of Bonn, Bonn, NRW, Germany

Vessel wall enhancement may serve as a potential marker for identification of high-risk atherosclerotic plaques. 3D-MRA and plaque enhancement at the level of the carotid bifurcation were assessed after application of the blood pool contrast agent gadofosveset trisodium and Gd-DTPA at 3.0 Tesla. 24h after injection of Gd-DTPA, no remaining vessel wall enhancement was observed, whereas remaining vessel wall enhancement (10% in atherosclerotic plaque and 2% in non-diseased vessel walls) was observed after injection of Gadofosveset Trisodium. Residual vessel wall enhancement 24h after injection of gadofosveset trisodium  may reflect neo-vessel density and be a predictor for future ischemic events.

                  2266.     A Comparative Study of 3D Time of Flight MRA and Contrast-Enhanced MRA :Clinical and Phantom Studies

Yoko Saito¹, Minoru Osanai², Kazuhiko Oyu², Keito Hamada², Hiraku Yodono³

¹Graduate School of Health Sciences, Hirosaki University , Hirosaki, Aomori, Japan; ²Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori, Japan; ³Radiology, Narumi Hospital, Hirosaki, Aomori, Japan

We evaluated the stenotic degree of arteries at the skull base level which are demonstrated on both 3D-TOF MRA and CE-MRA in 139 cases (659 vessels ). The discrepancy between these two technique in grading steotic degree occurred in 80 arteries. The stenotic grading were more severely estimated with CE MRA than with TOF MRA.We also performed phantom study. TOF-MRA tended to demonstrate the phantom more accurately than CE-MRA. On TOF-MRA with 1.6mm slice thickness, diameters were most accurately demonstrated. In CE-MRA, diameters of the tube were significantly more accurate with parallel imaging than with ZIP.

                  2267.     Direct Visualization and Quantitation of CSF Flow in Shunts

Noam Alperin^1,2, Sang H. Lee¹, Leonardo Macedo³, Daniele RigamontI⁴, Ari Blitz³

¹University of Miami, Miami, FL, United States; ²Radiology, University of Miami, United States; ³Radiology, Johns Hopkins, Baltimore, MD; ⁴Nuerosurgery, Johns Hopkins, Baltimore, MD

Diversion of excessive CSF from hydrocephalic brains by shunting is, in many cases, a life saving procedure. The down side of shunting is high failure rate. Consequently, about 40% of the shunting procedures performed annually in the US are for shunt replacement. The decision for shunt replacement is challenging as there is no reliable noninvasive test for shunt function. We present the first direct visualization and quantitation of CSF flow in ventricular shunts using high temporal and spatial resolution cine phase contrast MR and automated flow quantitation technique. Volumetric flow rate through in patent shunts were on the order of the CSF production rate.

Manganese - Enhanced MRI

                  2268.     Using Manganese-Enhanced MRI (MEMRI) to Detect the Order of Neuronal Connections in the Olfactory Pathway at the Level of Specific Layers

Der-Yow Chen¹, Stephen J. Dodd, Daniel R. Glen, Ziad S. Saad, Alan P. Koretsky

¹NINDS, National Institutes of Health, Bethesda, MD, United States

MEMRI can be used for neuronal tracing in the brain. Here it is demonstrated that MEMRI identifies the laminar connections of the olfactory system and traces layer-specific inputs to olfactory cortices. MnCl₂ was injected into nostrils or the olfactory bulb of rats, and they were imaged with this MRI technique at several time points. The dynamic changes of Mn²⁺ enhancement could be characterized by the arrival latency into each specific region. The olfactory pathway from olfactory bulb to higher-order cortex was labeled in proper, known laminar order. Mn²⁺ enhancement into the orbitofrontal cortex predicts that connections from olfactory cortex innervate superficial layer of the orbitofrontal cortex. This is a connection that has not been previously mapped.  Therefore, MEMRI neural tracing is specific at the level of cortical layers in the olfactory pathway.

                  2269.     Evaluation of the Applicability of Manganese-Enhanced and Dynamic Gadolinium-Enhanced Imaging to Study the Role of Caveolin-1 in Blood-Retinal Barrier Integrity

Philippe Garteiser¹, Bruce A. Berkowitz^2,3, Debbie Saunders¹, Rebecca Cranford¹, Rheal A. Towner¹, Michael H. Elliott⁴

¹Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States; ²Department of Anatomy and Cell Biology, Wayne State University, Detroit, MI, United States; ³Department of Ophthalmology, Wayne State University, Detroit, MI, United States; ⁴Department of Ophtalmology, Dean A McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States

Mn-enhanced MRI (MEMRI) has recently emerged as an important tool in retinal function studies. Caveolin-1 (Cav-1), the principal protein member of caveolar membrane domains, is believed to be essential to blood-retinal barrier integrity and ion homeostasis of the retina. Here, we evaluate how MEMRI and other MRI techniques may detect functional disruptions induced by cell type-specific knock out of the Cav-1 gene in mice. The MEMRI signature of light and dark adaptation and the dynamic gadolinium-enhanced signal behavior of iodate-induced retinal impairments indicate that both methods have sufficient sensitivity to warrant their application to cell-type specific Cav-1 ko mice.

                  2270.     Layer-Specific Anatomical MRI of the Retina with Balanced Steady State Free Precession with and Without Manganese Enhancement

Eric Raymond Muir^1,2, Bryan H. De La Garza², Sung-Hong Park³, Timothy Q. Duong²

¹Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States; ²Research Imaging Institute, Ophthalmology/Radiology, UT Health Science Center San Antonio, San Antonio, TX, United States; ³Research Imaging Institute, Radiology, UT Health Science Center San Antonio, San Antonio, TX, United States

Anatomical MRI of the retina has previously reported 3-4 layers in the rodent retina using conventional gradient echo (GE) and spin echo MRI. Following intraocular injection of manganese, seven layers were detected previously. This study explored balanced steady state free precession (bSSFP) MRI to image the mouse retina at 35x35x200 µm. Moreover, we compared GE and bSSFP with and without intraocular manganese injection. We demonstrated that bSSFP can reveal 7 layers without using contrast agent. Layers detected by bSSFP without manganese were consistent with those of manganese-enhanced MRI and histology.

                  2271.     Assessing in Vivo Axonal Transport Rates from Deep Brain Structures in Mouse Models of Human Disease

Taeko Inoue¹, Robia G. Pautler¹

¹Dept. of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, United States

Axonal transport is an important cellular mechanism necessary for the normal function and viability of a neuron. As a result, deficits in axonal transport have become associated with the development and progression of human diseases such as diabetes and neurodegenerative diseases such as Alzheimer’s disease. Here we demonstrate the potential of Manganese Enhanced MRI (MEMRI) for measuring in vivo deficits of axonal transport in two mouse models of human disease.

                  2272.     The Effect of Peripheral Administration of Monosodium Glutamate on  Ionotropic Glutamate Receptor Signalling in the Mouse Brain in Vivo Shown Through Manganese Enhanced MRI

Mohammed Khair Hankir^1,2, James R. Parkinson¹, Stephen R. Bloom³, Jimmy David Bell¹

¹Metabolic and Molecular Imaging Group, Imperial College, London, United Kingdom; ²Investigative Medicine, Imperial College , London, United Kingdom; ³Investigative Medicine, Imperial College, London, United Kingdom

Peripheral administration of monosodium glutamate (MSG) stimulates feeding in rodents. This may be due to the direct activation of glutamate receptors expressed in the arcuate nucleus (ARC) of the hypothalamus. We have used manganese enhanced MRI (MEMRI) to demonstrate that intraperitoneal administration of MSG dose dependently increases Mn2+ influx into the ARC and that this can be suppressed with a glutamate receptor subtype specific receptor antagonist. These results reveal that MEMRI is a sufficiently sensitive tool to detect glutamatergic signalling in vivo with high temporal and spatial resolution.

                  2273.     Reduced Manganese Enhancement and Flow in the Olfactory Pathway in Mice with Experimental Neuropsychiatric Lupus Demonstrated by Manganese Enhanced MRI

Tammar Kushnir¹, Shaye Kivity², Eli Konen¹, David Manor¹, Nancy Agmon-Levin², Miri Blank², Joab Chapman³, Yehuda Shoenfeld², Galia Tsarfaty¹

¹Dept. of Diagnostic Imaging, MRI Unit, The Chaim Sheba Medical Center, Tel Hashomer, Israel; ²Center of Autoimmune Diseases, The Chaim Sheba Medical Center, Tel Hashomer, Israel; ³Dept. of neurology, Sagol Neuroscience Center, The Chaim Sheba Medical Center, Tel Hashomer, Israel

Manganese enhanced MRI (MEMRI) allows in-vivo mapping of functional neuronal connections in the brain. The method was used to investigate the olfactory system in mice with experimental neuropsychiatric lupus (NPSLE), induced by intra-cerebro-ventricular injection of anti-ribosomal-P antibodies. MEMRI scans were performed before and 40 hours after intranasal MnCl2 administration. NPSLE induction resulted in a depression-like behavior accompanied with a significant deficit in olfactory function. MEMRI demonstrated impaired olfactory neuronal function expressed as a significant reduction in normalized manganese enhancement and flow throughout of the olfactory pathway, compared to healthy mice. Our results propose that autoimmune-CNS conditions may influence olfactory function.

                  2274.     Oral Manganese as an MRI Contrast Agent for the Detection of Nociceptive Activity

Kathleen Elizabeth Jacobs¹, Deepak Behera¹, Garry Gold¹, Michael Moseley¹, Jarrett Rosenberg¹, David Yeomans², Sandip Biswal¹

¹Radiology, Stanford University, Stanford, CA, United States; ²Anesthesia, Stanford University, Stanford, CA, United States

Manganese-enhanced magnetic resonance imaging (MEMRI) is a potentially powerful diagnostic method for identifying neural regions of pain processing for image-guided interventions.  Manganese can enter nerves via voltage-gated calcium channels, which are selectively upregulated in pain.  We gave manganese by oral gavage to two rat groups: one with spared injury of their sciatic nerves and a sham-operated group.  We found that rats with spared nerve injury have increased manganese ion uptake and retention in their nerves compared to the nerves of sham-operated rats as shown by increased MR signal and nerve concentrations.  Therefore, manganese can specifically enhance nerves associated with nociception.

MRI of Neural Plasticity

                  2275.     In Vivo Detection of Axonal Plasticity in Rat Hippocampus Using DTI

Teemu Laitinen¹, Alejandra Sierra¹, Asla Pitkänen¹, Olli Gröhn¹

¹A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland

The ability of in vivo diffusion tensor imaging to detect axonal plasticity in dentate gyrus sub region of hippocampus was studied in rats after kainic acid induced status epilepticus. Our results show that fractional anisotropy of dorsal dentate gurys is increased 17 months after the brain injury when compared to healthy control animals. Histological evaluation showed significant increase in the density of mossy fiber sprouting and myelinated axons the kainic acid treated animals, consistent with the DTI results. The results of this study suggest that axonal plasticity can be detected using in vivo DTI.

                  2276.     Short-Term Learning Induced Plasticity Visualized with Diffusion MRI

shimrit Tzur-Moryosef¹, tamar Blumenfeld-Katzir²

¹tel aviv university, tel aviv, Israel; ²neurobiology, tel aviv university, tel aviv, Israel

Plasticity in the adult brain following learning procedure is commonly attributed to functional plasticity and restricted to the hippocampus. This study we utilize Magnetic diffusion tensor imaging (DTI) in order to characterize microstructural plasticity induced by short-term learning paradigm. Analyses were done by ADC and FA parameters in order to characterize both white and gray matter changes. Rats were scanned before and one day after a one-day version of the Morris water maze task. Paired t-test comparisons demonstrate FA increase in the cingulum bundle and FA and ADC decrease in striatum-related gray matter, motor and sesorimotor cortex.

                  2277.     Investigation of Tissue Plasticity Following Low-Dose Amphetamine Treatment in Transient Ischemic Rat Stroke Model Using Diffusion Tensor Imaging

Hua-Shan Liu¹, Hui Shen¹, Hanbing Lu¹, Jenny Chou¹, April P. Zhu¹, William Rea¹, Yun Wang¹, Yihong Yang¹

¹National Institute on Drug Abuse, Baltimore, MD, United States

There is considerable evidence to suggest that amphetamine can improve functional outcome in animal model of stroke, which is involved in the mechanisms of induced axonal growth and reinnervation of brain tissues. In this study we used DTI to assess changes in perilesional tissue integrity after amphetamine treatment in a rat stroke model. We found that FA showed a significantly higher increase under the influence of amphetamine after 25 days.

                  2278.     Learning Is Necessary for Training Induced Brain Plasticity

Jason Philipp Lerch¹, Amanpreet Badhwar^2,3, Edith Hamel², John G. Sled¹

¹Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada; ²McGill University, Montreal, Quebec, Canada; ³ (contributed equally to this abstract)

Here we used a mouse model of Alzheimer’s Disease (AD) with impaired spatial learning to test whether a capacity to learn is necessary for training induced MRI detectable volume changes to occur. Mice were trained on two different versions of the Morris Water Maze, fixation perfused and scanned overnight at 32 µm isotropic resolution. As hypothesized, hippocampal based spatial learning was impaired in AD mice, whereas striatum dependent non-spatial learning was equivalent between AD and wild-type mice. The data presented herein thus indicates that learning is a requirement for MRI detectable plasticity.