Audrey P Fan^1,2, Revere P Kinkel^3,4, Nancy K Madigan^3,4, A Scott Nielson³, Thomas Benner², Emanuele Tinelli⁵, Bruce R Rosen^2,4, Elfar Adalsteinsson^1,2, and Caterina Mainero^2,4
1Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, United States, ²Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, ³Beth Israel Deaconess Medical Center, Boston, MA, United States, ⁴Harvard Medical School, Boston, MA, United States, ⁵Neurology and Psychiatry, University of Rome "La Sapienza", Rome, Italy

This study directly quantified OEF in individual cortical veins from patients at different stages of multiple sclerosis (MS) disease using MRI magnetic susceptibility measurements at 7 Tesla. Patients with late disease exhibited 6.2% absolute reduction in OEF compared to controls (p=0.024). Cortical OEF negatively correlated with disease duration (p=0.02) and white matter lesion volume (p<0.01). Across all patients, decreased OEF strongly associated with reduced cognitive performance, and cortical OEF was the main independent predictor of processing speed (p=0.03, stepwise regression). This study implicates metabolic deficiency early in the development of cognitive dysfunction in MS, and highlights OEF as a useful new metric of cortical pathology.

Anna Blazejewska¹, Ali Al-Radaideh², Olivier Mougin², Su Yin Lin³, Richard W. Bowtell², Cris S. Constantinescu³, and Penny A. Gowland^2
1Magnetic Resonance Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ²Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, ³Department of Neurology, Clinical Sciences, University of Nottingham

A new method of characterizing peri-lesional changes in multiple sclerosis has been developed and tested on MTR and MPRAGE images from patients with Clinically Isolated Syndrome. It showed that all lesions display a proximal rim which is wider on MTR and MTRc than on T1w scans. More distally, most lesions show increases in MTR or T1w signal (negative S), but a significant fraction show a decrease (positive S) which indicates the presence of a ring around the lesion.

PALLAB K BHATTACHARYYA¹, ROBERT A BERMEL¹, MICHEAL D PHILLIPS¹, LAEL A STONE¹, BLESSY A MATHEW¹, and MARK J LOWE^1
1Cleveland Clinic, Cleveland, OH, United States

Multiple sclerosis (MS) is often associated with cortical reorganization that is manifested in an increase in the extent of functional cortical activation in MS patients versus controls during performance of specific tasks. Mechanism of this reorganization process is largely unknown. Since gamma amino butyric acid (GABA) has been suggested to play a role in MS, we examined the dependence of task specific fMRI activation on GABA levels in the sensorimotor and visual cortices. We observed increased cortical GABA level with increased activation in both the cortices in MS, which suggests a role of GABA in the cortical reorganization/adaptation process.

M. Lyksborg^1,2, R. Larsen¹, P. S. Sørensen³, M. Blinkenberg³, A. Dogonowski², E. Garde², G. J.M. Parker⁴, H. R. Siebner², and T. B. Dyrby^2
1Technical University Of Denmark, Kgs. Lyngby, Denmark, ²Danish Research Centre for Magnetic Resonance, Hvidovre Hospital, Hvidovre, Denmark,³Danish Multiple Sclerosis Research Center, Denmark, ⁴University Of Manchester, United Kingdom

Multiple sclerosis is a disease with a highly heterogeneous disease pattern where lesions along a given tract may have varying impact on the global anatomical connectivity of the underlying axons. In the following we demonstrate how the technique of Anatomical Connectivity Mapping is capable of quantifying anatomical connectivity differences between two patient groups with High/low EDSS disease scores. Strong group differences are seen along corticospinal tract, in cerebellar white matter and subcortical white matter in the visual cortex. Results show that such differences are not distinguishable with traditional diffusion measures.

Dmitriy A. Yablonskiy¹, Jie Luo¹, Aditi Iyer¹, Alexander L. Sukstanskii¹, and Anne H. Cross^2
1Radiology, Washington University, St. Louis, Missouri, United States, ²Neurology, Washington University, St. Louis, Missouri, United States

Phase images obtained by gradient echo MRI provide image contrast in multiple sclerosis distinct from T1W and T2W images. Herein we examine phase contrast in MS based on the Generalized Lorentzian Approach that relates MR signal phase to tissue microarchitechture. Our theory and experimental data show that the phase contrast can appear almost abruptly at the onset of a lesion. Also, contrary to common sense anticipation that phase contrast should grow with MS lesion progression (as it happens for other contrast mechanisms), we demonstrate that it can actually disappear as the tissue destruction progresses toward “black hole” phase.

Wafaa Zaaraoui¹, Simon Konstandin², Bertrand Audoin¹, Armin M. Nagel³, Audrey Rico¹, Irina Malikova¹, Elisabeth Soulier¹, Patrick Viout¹, Sylviane Confort-Gouny¹, Patrick J. Cozzone¹, Jean Pelletier¹, Lothar R. Schad², and Jean-Philippe Ranjeva^1
1CRMBM UMR CNRS 6612 - Aix-Marseille Université, Marseille, France, ²Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany,³German Cancer Research Center (DKFZ), Department of Medical Physics in Radiology, Heidelberg, Germany

The key role of sodium accumulation leading to neuronal injury in multiple sclerosis has recently been highlighted. Using in vivo sodium MRI at 3T, we have characterized for the first time the spatial spreading of brain sodium accumulation in two groups of relapsing remitting multiple sclerosis (RRMS) patients (13 early RRMS and 13 advanced RRMS) compared to 15 healthy controls. Brain sodium accumulation was present from the early stage of RRMS and dramatically spread during the course of the disease in the whole brain especially in the normal appearing tissues concomitantly to progression of disability and independently from atrophy.

Emily T. Wood^1,2, Itamar Ronen³, Aranee Techawiboonwong⁴, Craig K. Jones^5,6, Peter B. Barker^5,6, Daniel Harrison⁷, Peter Calabresi⁷, and Daniel S. Reich^1,6
1NINDS, National Institutes of Health, Bethesda, Maryland, United States, ²Dept of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³C.J. Gorter Center for High Field MRI, Dept of Radiology, Leiden University Medical Center, Leiden, Netherlands, ⁴Mahidol University, Nakhon Pathom, Thailand, ⁵F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ⁶Dept of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁷Dept of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

In this study, we compare the diffusion properties of N-acetylaspartate and water in the corpus callosum between multiple sclerosis patients and healthy controls at 7T. Diffusion tensor spectroscopy (DTS) combines features of both DTI and MRS, allowing measurement of the diffusion properties of intracellular metabolites. As such, it may be sensitive to disruption of tissue microstructure within neurons and might consequently serve as a useful marker of axonal integrity and reversible damage in MS. We find a negative correlation between NAA and water parallel diffusivity in normal appearing white matter suggesting that we are detecting axonopathy underlying inflammation and edema.

Maria A. Rocca¹, Paola Valsasina², Martina Absinta², Angelo Ghezzi³, Lucia Moiola⁴, Pierangelo Veggiotti⁵, Andrea Falini⁶, Giancarlo Comi⁴, Massimo Filippi², and the MS and Neuroimaging Study Groups of the Italian Neurological Society^7
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, Italy, ²Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, ³MS Centre, Ospedale di Gallarate, ⁴Department of Neurology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, ⁵Department of Child Neurology and Psychiatry, Fondazione IRCCS Istituto Neurologico C Mondino, Pavia, Italy, ⁶Department of Neuroradiology, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, ⁷.....

In this study, we assessed functional connectivity (FC) at resting state (RS) within and among networks with potential functional relevance in 38 patients with pediatric multiple sclerosis (MS) and 18 age- and sex-matched healthy controls. Decreased FC was found in the sensorimotor and primary visual networks, as well as in posterior and infratentorial regions of the default mode, salience, executive control, attention and working memory networks. Conversely, increased FC was found in frontal regions of the salience and of the default mode networks. Decreased FC was associated with a more severe clinical disability and a longer disease duration.

Souraya El Sankari¹, Olivier Balédent², Vincent van Pesch¹, Christian Sindic¹, and Thierry Duprez^3
1Neurology, Catholic University of Louvain, Brussels, Belgium, ²Imaging and Biophysics, Amiens University Hospital, Amiens, France, ³Neuroradiology, Catholic University of Louvain, Brussels, Belgium

Recent Doppler sonographic studies have hypothesized venous dysfunction implication in the pathogenesis of for multiple sclerosis (MS). Using Phase Contrast (PC) MRI non invasive technique, we have collected arterial (carotidian and vertebral), venous (jugular cervical veins and intracranial sinuses), and CSF (aqueductal and cervical subarachnoidian) flows, and analyzed them using a home-made software. We show in the present work, that intracranial and cervical venous flows are comparable in 12 MS patients and 12 aged-matched healthy controls paired for the arterial filling flows. The only difference consists of increased cervical CSF stroke volumes. Results are discussed as regards to literature data.

Yongxia Zhou¹, Joseph Herbert¹, Hina Jaggi¹, Robert I Grossman¹, and Yulin Ge^1
1Radiology/CBI, New York University Langone Medical Center, New York, NY, United States

Voxel-based whole brain analyses were used to assess spatial distribution of lesion probability (on FLAIR), regional atrophy (using voxel-based morphometry on MPRAGE), microstructural damage (tract-based spatial statistics using diffusion tensor imaging), and interhemispheric synchronization disruption (voxel mirrored homotopic correlation using resting state fMRI) in 16 MS patients and 16 controls. We demonstrated specific abnormality patterns underlying different pathological processes in both gray matter and white matter and their regional likelihood on each quantitative measure. The structural and functional measures are complementary to each other in understanding the complicated disease processes of MS.