mcDESPOT-Derived Demyelination Volume in Multiple Sclerosis Patients Correlates with Clinical Disability and Senses Early Myelin Loss
Hagen H. Kitzler¹, Jason Su², Michael Zeineh², Sean C. Deoni³, Cyndi Harper-Little⁴, Andrew Leung⁵, Marcelo Kremenchutzky⁶, Brian K. Rutt^2
1Dept. of Neuroradiology, Technische Universitaet Dresden, Dresden, SN, Germany; ²Department of Radiology, Stanford University, Palo Alto, CA, United States; ³Department of Engineering, Brown University, Providence, RI, United States; ⁴Imaging Laboratories, Robarts Research Institute, London, ON, Canada; ⁵Department of Diagnostic Radiology and Nuclear Medicine, University of Western Ontario, London, ON; ⁶Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada

We applied the multi-component Driven Equilibrium Single Pulse Observation of T1 and T2 (mcDESPOT) method to a population of Multiple Sclerosis patients and normal controls, to assess its ability to characterize brain tissue demyelination across a spectrum of MS disease severity. We found strong correlations between Demyelinated Volume and EDSS (clinical disability score), as well as with Normalized Brain Volume (measure of total brain atrophy). We also found a significant difference between Demyelinated Volume in normal controls vs the subset of Clinical Isolated Syndrome patients, demonstrating the ability of mcDESPOT to sensitively detect early pre-MS changes.

Decrease of Brain Stiffness Compared to Loss of Brain Volume in Multiple Sclerosis Patients
Kaspar Josche Streitberger¹, Friedemann Paul², Dagmar Krefting³, Dieter Klatt¹, Sebastian Papazoglou¹, Sebastian Hirsch¹, Jürgen Braun³, Ingolf Sack^1
1Institute of Radiology, Charité - University Medicine Berlin, Berlin, Germany; ²Neurocure, Charité - University Medicine Berlin, Berlin, Germany; ³Institute of Medical Informatics, Charité - University Medicine Berlin, Berlin, Germany

Chronic inflammatory diseases of the CNS such as Multiple Sclerosis (MS) lead to demyelinization and to widespread degradation of neurons and axons – processes which alter the mechanical consistency of the brain. In this study MR elastography and MRI volumetry is used to investigate the alteration of brain mechanics and brain geometry due to MS. A decrease in brain stiffness of 17% accompanied by a loss of brain volume of 5% was measured in 17 MS patients and 42 healthy volunteers.

Surface-Based Techniques Reveal Regions of Reduced Cortical Magnetization Transfer Ratio in Patients with MS
Mishkin Derakhshan¹, Zografos Caramanos¹, Sridar Narayanan¹, Douglas L. Arnold¹, D. Louis Collins^1
1Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada

Novel imaging methods are essential to accurately detect and quantify the GM pathology that is increasingly being recognized in multiple sclerosis (MS). In this study, we measured the extent of subpial decreases in magnetization transfer ratios using a novel surface-based method. When comparing individual MS patients to a group of normal controls, we detected regions of significant MTR differences, which may include regions of cortical demyelination. Group-wise analysis revealed significant differences between the  group with secondary progressive MS and normal controls, but not between the relapsing-remitting patients and normal controls. We assessed the sensitivity of our method using simulations.

Altered Structural Architecture of the Striatum Is Associated with Impaired Motor Learning in Multiple Sclerosis
Valentina Tomassini^1,2, Rose Gelineau-Kattner^1,3, Mark Jenkinson¹, Jacqueline Palace¹, Carlo Pozzilli², Heidi Johansen-Berg¹, Paul M. Matthews^1,4
1FMRIB Centre, Dept of Clinical Neurology, The University of Oxford, Oxford, United Kingdom; ²Dept of Neurological Sciences, "La Sapienza" University, Rome, Italy; ³Baylor College of Medicine, Houston, TX, United States; ⁴GSK Clinical Imaging Centre, GlaxoSmithKline, London, United Kingdom

The behavioural evidence for altered motor skill learning in Multiple Sclerosis (MS) suggests that MS pathology may impair mechanisms of adaptive plasticity required for learning. The striatum is functionally relevant for both higher motor control and learning. The evidence for localized MS-related pathology within the striatum and disease-related disruption of its neocortical connections suggests a role of the striatum in impairing motor learning in MS. Here we tested whether impaired learning performance in MS was associated with localized changes in the striatal structural architecture and assessed the functional consequences of these behaviourally relevant structural changes.

Contribution of Subpial Pathology to Cortical Thinning in Multiple Sclerosis: A Combined 7T - 3T MRI Study
Caterina Mainero¹, Thomas Benner¹, Amy Radding¹, Andre van der Kouwe¹, R. Philip Kinkel², Bruce R. Rosen^1
1A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States; ²Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States

In multiple sclerosis (MS) it is unclear whether cortical atrophy is secondary to white matter (WM) damage, or underlies a primary neuronal process. Here, we investigate the contribution of different cortical lesions types at 7T and WM lesion load (WMLL) to cortical thinning in 14 MS patients. The higher the number of all cortical lesions, and of type III/IV lesions (subpial lesions extending partly or completely through the cortical width) the thinner the cortex was. There was only a trend to significance for WMLL. Thinning in frontal cortical areas showed the highest correlation with type III/IV lesions. Subpial pathology is a major determinant of cortical atrophy in MS.

Grey Matter Perfusion Is Inversely Correlated to T2 Lesion Load in MS Patients - A 3D GRASE Arterial Spin Labeling Study at 1.5T
Michael Amann¹, Jochen Gunther Hirsch¹, Lutz Achtnichts², Yvonne Naegelin², Johannes Gregori³, Martin Schaellebaum², Katrin Weier², Alain Thöni, Ernst Wilhelm Radue, Matthias Günther³, Ludwig Kappos², Achim Gass^1
1Neurology/Neuroradiology, University Hospital, Basel, BS, Switzerland; ²Neurology, University Hospital, Basel, BS, Switzerland; ³MR Research Neurology, University Hospital, Mannheim, BW, Germany

We investigated the influence of different clinical and MRI factors onto grey matter (GM) perfusion in MS patients (123 RRMS, 42 SPMS, 7 PPMS, and 5 CIS). To assess cerebral blood flow (CBF), we applied a pulsed arterial spin labeling technique combined with single-shot 3D-GRASE readout. The mean GM-CBF in each patient was calculated for 10 supratentorial slices. Multiple linear regression models were calculated to investigate the relationship between different factor sets and mean GM-CBF. Post-hoc Spearman rank correlation revealed significant correlation of GM-CBF with T2 lesion load (p=2*10^-6) and with age (p=0.002), but neither with GM-atrophy nor disease onset.

Early Adaptation in Resting State Networks in Multiple Sclerosis Is Found Using Independent Component Analysis and Dual Regression
Stefan D. Roosendaal¹, Menno M. Schoonheim¹, Hanneke E. Hulst¹, Ernesto Sanz-Arigita¹, Stephen M. Smith², Jeroen J.G. Geurts¹, Frederik Barkhof^1
1Radiology, VU University Medical Center, Amsterdam, Noord-Holland, Netherlands; ²FMRIB, John Radcliffe Hospital, Oxford, United Kingdom

We questioned whether functional changes can be found in rest in the early phase of MS. Resting state fMRI networks were compared between 14 patients with symptoms suggestive of MS (clinically isolated syndrome; CIS), 31 relapsing remitting (RR) MS patients and 41 healthy controls using independent component analysis and dual regression. CIS patients showed increased co activation in six of the eight networks found. No significant resting state network differences were found between RR patients and controls. Network-specific resting state changes can be already found in CIS, and are lost in MS patients with increasing brain damage and advancing disability.

T₂^*-Weighted Images Discriminate Multiple Sclerosis from Ischaemic Lesions
Jennifer Elizabeth Dixon¹, Emma C. Tallantyre², Ian Donaldson², Trudy Owens³, Nikos Evangelou², Peter G. Morris^1
1Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom; ²Department of Clinical Neurology, Nottingham University Hospital NHS Trust, Nottingham, Nottinghamshire, United Kingdom; ³Department of Economics, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

The detection of demyelinating lesions using MRI plays an important role in the diagnosis of MS. However, demyelinating brain lesions can be difficult to distinguish from small foci of cerebral ischaemia on MR images. Here we show that using ultra-high-field MRI we can reliably demonstrate the perivenous orientation of MS lesions and in doing so distinguish them from ischaemic brain lesions. The observation that T2* image contrast can be employed to differentiate between ischaemic and demyelinating lesions at ultra-high field offers hope that similar techniques could be adapted for application on clinically available systems.

Impaired Motor Performance in MS Is Associated with Increased GABA Level in Sensorimotor Cortex
Pallab Bhattacharyya¹, Micheal Phillips¹, Robert Bermel¹, Lael Stone¹, Mark Lowe^1
1Cleveland Clinic, Cleveland, OH, United States

In vivo GABA level is measured at sensorimotor cortex in healthy controls and MS patients using ¹H spectroscopy. The measured GABA level was correlated with clinical measure of MS as determined by Multiple Sclerosis Functional Composite (MSFC) scores. A strong inverse correlation was observed between the GABA level and motor performance (as measured by the 9 hole peg component of MSFC) in patients, while no such correlation was observed in the controls. No other component of MSFC showed any correlation with the GABA level in either patients or controls. The findings indicate motor impairment with increased GABA level in MS.

Assessing Neuronal Metabolism in MS by Modelling Imaging Measures
Olga Ciccarelli¹, Ahmed Toosy¹, Nicola De Stefano², Claudia Angela Michela Wheeler-Kingshott³, David H. Miller³, Alan J. Thompson^1
1NMR Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom; ²Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy; ³NMR Unit, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom

Mitochondrial dysfunction is central to the pathogenesis of many neurological diseases, including MS. We propose a methodology to estimate in-vivo neuronal mitochondrial metabolism and its relatice contribution to disability. We modelled N-acetyl-aspartate (NAA), measured by spinal cord 1H-MR spectroscopy, which reflects axonal integrity and mitochondrial metabolism, together with measures of axonal integrity, such as axial diffusivity and cord area, in patients with MS studied six months after a spinal cord relapse. The residual variance in NAA concentration after accounting for the structural measures should reflect mitochondrial metabolism. A lower mitochondrial metabolism was associated with greater disability indipendent of structural damage.