The Role of Iron in T₂* Contrast and Transverse Relaxation of Beta-Amyloid Plaques in Alzheimer’s Disease
Mark David Meadowcroft^1,2, James R. Connor³, Qing X. Yang^1,3
1Radiology - Center for NMR Research, Pennsylvania State University - College of Medicine, Hershey, PA, United States; ²Neural and Behavioral Sciences, Pennsylvania State University - College of Medicine, Hershey, PA, United States; ³Neurosurgery, Pennsylvania State University - College of Medicine, Hershey, PA, United States

Conventional belief is that iron associated with beta-amyloid (Aβ) plaques is the underlying mechanism for plaque contrast in transverse imaging.  Through detailed histological MR examination in comparison to traditional histology methods utilizing iron chelation of plaques, this body of work has determined that there is a dual relaxation associated with human (Aβ)  plaques. Removal of iron from human (Aβ)  plaques still results in plaque MR imaging and relaxation.  The data indicate that iron content alone is not responsible for the hypo-intensities seen on the MR images and that there is a synergy between iron and plaque morphology on transverse relaxation.

Optimization of Susceptibility Weighted Imaging at 7T for Improved Detection of Alzheimer’s Amyloid Plaques Associated with Iron in Human Postmortem Brain
Yulin Ge¹, Tang Lin¹, Daniel K. Sodickson¹, Edward Lin¹, Jing Yang¹, E Mark Haacke², Mony de Leon¹, Robert I. Grossman¹, Thomas Wisniewski^1
1New York University School of Medicine, New York City, NY, United States; ²Wayne State University, Detroit, MI, United States

Due to markedly enhanced susceptibility contrast and signal-to-noise ratio at ultra-high-field MR, it is possible to detect amyloid plaques associated with iron deposition using susceptibility weighted imaging in patients with AD.

Quantitative Cerebral Blood Flow Changes in Huntington's Disease Measured Using Pulsed Arterial Spin Labeling - not available
J. Jean Chen¹, David H. Salat¹, H. Diana Rosas,^12
1A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States; ²Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

Huntington's disease (HD) has been associated with wide-spread cortical and subcortical grey matter atrophy, in which the role of cerebral blood flow (CBF) abnormalities is potentially significant. However, low spatial resolution erodes the ability of conventional techniques to reveal spatially-specific CBF changes. In this work, we present, for the first time, HD-related quantitative CBF changes measured using pulsed arterial-spin labelling (PASL). Regressing out the effect of cortical thinning, our results still show significant underlying CBF reduction across the cortex. CBF also decreased in the striatum and hippocampus. CBF reduction patterns were found to be partially independent of structural atrophy.

Dynamic Changes in Brain Metabolites and Tissue Water Diffusion Following Oral Amino Acid Challenge in Cirrhotics with Hepatic Encephalopathy
Fiona Smith¹, Hanan Mardini, Christopher Record, Andrew M. Blamire^1
1Newcastle MR Centre & Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

Liver cirrhosis kills more than 750,000 people worldwide each year.  Almost 30% of patients with cirrhosis experience hepatic encephalopathy (HE), a neuropsychiatric complication potentially linked to formation of cerebral edema driven by elevated blood ammonia. We used DTI and proton MRS to monitor edema and metabolite changes during induced hyperammonaemia by amino acid challenge in HE patients.  Elevated blood ammonia was accompanied by increased ADC and decreased myo-Inositol.  Absolute increase in blood ammonia significantly correlated with ADC and inversely correlated with myo-Inositol in the individual patients strongly supporting ammonia driven brain edema as a neurochemical mechanism for HE in cirrhosis. 

Joint Contribution of Structural and Perfusion MR Images for the Classification of Alzheimer’s Disease
Duygu Tosun¹, Pouria Mojabi¹¹, Mike W. Weiner¹, Norbert Schuff^1
1Center for Imaging Neurodegenerative Diseases, San Francisco, CA, United States

To determine the joint contribution of structural and arterial spin labeling MR imaging for the classification of Alzheimer’s disease (AD), we analyzed the cortical thickness and cerebral blood flow (CBF) measures jointly in a cross-sectional study of 24 AD and 38 healthy elderly controls using an integrated multimodality MRI processing framework and a cortical surface-based analysis approach. From the joint analysis, we infer that cortical atrophy dominates prediction of AD while CBF adds no significant value. One interpretation of the results is that CBF is diminished proportionately to brain tissue loss and therefore provides no additional information to structural alterations.

Neuroprotective Mechanism of Minocycline in an Accelerated Macaque Model of NeuroAIDS
Eva-Maria Ratai^1,2, Chan-Gyu Joo^1,2, Jeffrey Bombardier¹, Robert Fell¹, Julian He^1,2, Reza Hakimelahi^1,2, Tricia Burdo³, Jennifer Campbell³, Patrick Autissier³, Lakshmanan Annamalai⁴, Eliezer Masliah⁵, Susan Westmoreland, ^2,4, Kenneth Williams³, Ramon Gilberto Gonzalez^1,2
1Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States; ²Harvard Medical School, Boston, MA, United States; ³Biology Department, Boston College, Boston, MA, United States; ⁴Division of Comparative Pathology, New England Primate Research Center, Southborough, MA, United States; ⁵Department of Neurosciences, University of California at San Diego, La Jolla, CA, United States

HIV-associated neurocognitive disorders continue to be a significant problem.  Using the accelerated macaque model of neuroAIDS in combination with in vivo MR spectroscopy minocycline was found to be neuroprotective and able to reverse increased high energy metabolism, most likely localized to glia. Evaluating our observations, clues into the mechanisms underlying neuroprotection included reduction of microglial activation, reductions of CSF and plasma viral loads during treatment, and a reduction in a subset of circulating monocytes considered to be responsible for viral infection of the CNS by cell trafficking mechanisms.

The Role of the Uncinate Fasciculus in the Development of Dementia: A DTI-Tractography Study
Laura Serraa¹, Mara Cercignani¹, Roberta Perri², Barbara Spanò¹, Lucia Fadda^2,3, Camillo Marra⁴, Franco Giubilei⁵, Carlo Caltagirone^2,6, Marco Bozzali^1
1Neuroimaging laboratory, Fondazione IRCCS Santa Lucia, Roma, Italy; ²Department of Clinical and Behavioural Neurology, Fondazione IRCCS Santa Lucia, Roma, Italy; ³Department of Neuroscience, University of Rome ‘Tor Vergata’, Rome, Italy; ⁴Institute of Neurology, Università Cattolica, Roma, Italy; ⁵Department of Neurology, II Faculty of Medicine University of Rome, ‘Sapienza’, Rome, Italy; ⁶Department of Neuroscience, University of Rome ‘Tor Vergata’, Rome, Italy

The uncinate fasciculus (UF) connects temporal and frontal regions, traditionally implicated by pathological damage in dementia. We aimed at assessing, using DTI and tractography, the role of UF damage in the progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD), and whether its involvement could distinguish between patients with AD and patients with dementia with Lewy Bodies (DLB). Fractional anisotropy was significantly reduced only in the UF of demented patients as compared to both, HS and a-MCI patients. This suggests that UF involvement is relevant for the development dementia, but it does not distinguish between AD and DLB.

Cerebral Microbleeds Are Predictive of Mortality in the Elderly
Irmhild Schneider¹, Stella Trompet¹, Anton J.M. de Craen¹, Adriaan C.G.M. van Es¹, Mark A. van Buchem¹, Jeroen van der Grond^1
1Leiden University Medical Center, Leiden, Netherlands

Cerebral microbleeds are commonly found in patients with ischemic stroke, intracerebral hemorrhage (ICH) and Alzheimer disease. In this study we investigated the prognostic value of microbleeds in terms of all-cause mortality and cardiovascular mortality in a population suffering from vascular disease or at high risk for developing this condition. We found that the presence of two or more microbleeds implicates an increased risk of overall death. Furthermore, only “non-CAA” type microbleeds were associated with increased risk of cardiovascular death. Therefore, CAA type small vessel disease cannot be considered as risk factor for (cardiovascular) mortality.

Tract Atrophy in Alzheimer’S Disease Measured Using Probabilistic Tractography
Hojjatollah Azadbakht^1,2, Hamied A. Haroon^1,2, David M. Morris^1,2, Karl V. Embleton, ^2,3, Stephen F. Carter⁴, Brandon Whitcher⁵, Julie Snowden⁶, Geoff J.M. Parker^2,7
1Imaging Science and Biomedical Engineering, , School of Cancer and Imaging Sciences,, University of Manchester, Manchester, United Kingdom; ²The University of Manchester Biomedical Imaging Institute, University of Manchester, Manchester, United Kingdom; ³School of Psychological Science, University of Manchester, Manchester, United Kingdom; ⁴Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom; ⁵Clinical Imaging Centre, GlaxoSmithKline, London, United Kingdom; ⁶Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, Salford, United Kingdom; ⁷Imaging Science and Biomedical Engineering, School of Cancer and Imaging Sciences,, University of Manchester, Manchester, United Kingdom

The quantitative characterisation of atrophy can provide useful biomarkers for assessing the evolution of neurological conditions such as Alzheimer’s disease (AD). It is likely that atrophy caused by such conditions also affects white matter (WM) tracts via degenerative processes. If specific tract systems are more prone to atrophy than others, then tractography-guided atrophy measurements may be more sensitive than less targeted methods which focus on global gray and/or white matter. In this work we apply a novel method for quantifying the width of WM tracts to look for evidence of tract atrophy in mild cognitive impairment (MCI) and AD subjects.

Increases in CBF by Donepezil Treatment Enhance Cingulate Functional Network Activity in Mild Alzheimer's Disease
Wenjun Li¹, Chunming Xie^1,2, Jennifer Jones³, Malgorzata Franczak³, Piero Antuono³, Shi-jiang Li^1
1Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States; ²Neurology, Southeast University, Nanjing, Jiansu, China, People's Republic of; ³Neurology, Medical College of Wisconsin, Milwaukee, WI, United States

Cholinergic inhibitor (Aricept®) has been shown to improve cognitive function in adults with Alzheimer's disease (AD). Also, it has an effect on improving the cerebral blood flow (CBF) perfusion detected by PET technology. Previously we have found increased CBF in cingulate and posterior cingulated regions using a Pseudo-Continuous Arterial Spin Labeling (pCASL) MR technique. It is hypothesized that the increase in CBF after treatment could alter functional connectivity in related neural networks. The aim of the current study is to determine the changes in the functional connectivity in networks with significantly increased CBF after the drug treatment.