Multiple Sclerosis Human Studies Neuro
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Thursday May 12th
Room 710B  13:30 - 15:30 Moderators: Douglas L. Arnold and Maria Rocca

13:30 601.   Characterizing Brain Oxygen Metabolism in Patients with Multiple Sclerosis with T2-Relaxation-Under-Spin-Tagging (TRUST) MRI 
Yulin Ge1, Zhongwei Zhang1, Hanzhang Lu2, Lin Tang1, Hina Jaggi1, James Babb1, Joseph Herbert3, and Robert I Grossman1
1Department of Radiology, New York University Langone Medical Center, New York City, NY, United States, 2Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 3Department of Neurology, New York University Langone Medical Center, New York City, NY, United States

Using a newly developed T2-relaxation-under-spin-tagging (TRUST) MRI, a novel noninvasive technique for measuring brain venous sinus blood oxygenation (Yv), we have investigated the global oxygen metabolism changes in patients with relapsing remitting multiple sclerosis (MS). We found significantly increased Yv in patients (mean/SD: 64.2/5.1%) as compared to control subjects (mean/SD: 59.6/4.8%), and Yv has significant correlation with the total lesion load (r=0.44, P=0.03), but not with brain atrophy. Our findings suggest that significant underutilization of oxygen in MS might reflect the diffuse neuronal cells inactive state due to chronic and diffuse nature of the disease rather than parenchyma tissue loss.

13:40 602.   Evolution of Multiple Sclerosis Ring Lesions: a Serial Phase Imaging Study at 7T 
Wei Bian1,2, Kristin Harter3, Kathryn Hammond Rosenbluth4, Duan Xu2, Douglas AC Kelley2, Daniel Vigneron2, Sarah J Nelson2,5, and Daniel Pelletier6
1Joint Graduate Program in BioEngineering at UCSF & UCB, University of California San Francisco, San Francisco, CA, United States, 2Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 3School of Pharmacy, University of California San Francisco, San Francisco, CA, United States, 4Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States, 5Department of BioEngineeing and Therapeutic Sciences, Unviersity of California San Francisco, San Francisco, CA, United States, 6Department of Neurology, University of California San Francisco, San Francisco, CA, United States

MRI at 7 Tesla can produce high-resolution phase images of MS lesions that quantify the local field shifts sensitive to iron. A subset of MS lesions visible with phase imaging shows a distinct peripheral ring. The purpose of this serial in vivo 7T study was to follow the evolution of MS lesions showing a phase contrast ring for up to 2.5 years. Our results support the concept that once they have been formed, the peripheral rings in MS white lesions remain stable with time. The biological source of this phase contrast signal remains to be elucidated.

13:50 603.   Quantitative characterization of cortical pathology in multiple sclerosis using surface-based analysis of T2* relaxation at 7T 
Julien Cohen-Adad1,2, Karl G Helmer1,2, Allen Scott Nielsen3, Doug Greve1,2, Thomas Benner1,2, Rip Philip Kinkel2,3, Bruce R Rosen1,2, and Caterina Mainero1,2
1A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, 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. We combined ultra high field MRI (7T) with surface-based analysis to achieve quantitative assessment of cortical changes in MS. Results show a significant T2* increase in MS patients versus controls. This increase may reflect disseminated cortical pathology described in post-mortem examination. Surface-based analysis combined with quantitative measures has the potential to improve our understanding of the disease phenotypes via the discovery of specific quantitative biomarkers of cortical pathology in MS.

14:00 604.   Multiple Sclerosis alters Intra-cellular Sodium Concentration and Intra-cellular Volume Fraction: an in-vivo 7T MRI study. 
Lazar Fleysher1, Niels Oesingmann2, Ryan Brown1, Hina Jaggi1, Graham Wiggins1, Daniel Sodickson1, Joseph Herbert3, and Matilde Inglese1,4
1Radiology, NYU School of Medicine, New York, New York, United States, 2Siemens Medical Solutions USA, Malvern, PA, United States, 3Neurology, NYU School of Medicine, New York, New York, United States, 4Neurology, NYU School of Medicine, New York, New York

Intracellular Sodium Concentration (ISC) and Intracellular Sodium Volume Fraction (ISVF) are often used as operational measures of tissue viability. Elevated brain tissue sodium concentration (TSC) has been reported previously in MS patients. However, TSC is sensitive but not specific to variations in ISC and ISVF. In this work, we employ single- (SQ) and triple-quantum-filtered (TQF) sodium MRI at 7T to evaluate ISC and ISVF in MS patients. We found that ISCs in the MS patients are higher than in healthy controls indicating accumulation of intracellular sodium. In addition, we observed that the patientsí ISFVs are lower than those of healthy controls indicating loss of the intracellular volume.

14:10 605.   Atlas-based Quantification of Brain Normal-Appearing White and Gray Matter Volume, Relaxation Time and Diffusion Tensor Metrics in Multiple Sclerosis 
Khader M Hasan1, Indika S Walimuni1, Sushmita Datta1, Flavia Nelson2, Jerry S Wolinsky3, and Ponnada A Narayana4
1Radiology, UTHSCH, Houston, Texas, United States, 2Neurology, UTHSCH, Houston, Texas, 3Neurology, UTHSCH, Houston, Texasa, United States, 4Radiology, UTHSCH, Houston, Uexasa, United States

There have been a plethora of reports on the MS atrophic brain using whole brain or regional metrics combined with voxel-based and fiber tracking approaches. To date there has been no comprehensive report of the simultaneous fusion and application of standardized brain atlas and multimodal quantitative MRI methods on both normal-appearing white matter (NAWM) and norma-appearing subcortical and cortical gray matter (NAGM) of the MS brain relative to healthy controls with account of late development, natural aging and lesion effects. We used lesion spatial mapping methods and FreeSurfer volumetry in combination with relaxation and diffusion tensor imaging methods to obtain regional volumetry of both deep and lobar NAWM and cortical and subcortical NAGM in a cohort of relapsing and remitting (RRMS) patients and healthy adult controls. We demonstrate the utility of this approach by showing strong correlations of regional metrics with the expanded disability status score (EDSS). Our results consolidate published literature and offer a window to model the pathogensis of MS using a brain system level.

14:20 606.   Ten-year brain atrophy rate and its relevance to disability in multiple sclerosis 
Antonio Giorgio1, Maria Laura Stromillo1, Maria Letizia Bartolozzi2, Francesca Rossi1, Marco Battaglini1, Anita Blandino1, Leonello Guidi2, Patrizia Maritato2, Antonio Federico1, and Nicola De Stefano1
1Department of Neurological and Behavioral Sciences, University of Siena, Siena, Siena, Italy, 2Neurology Unit, Hospital of Empoli, Italy

This ongoing study is the first report of a long-term (10 years) follow-up on brain atrophy in MS. Brain volume loss is, on average, -5% in MS patients and -3% in normal controls. It seems to be a global process, involving all tissue compartments. Brain atrophy rate, both global and in the grey matter, was associated to clinical worsening, particularly in subject with higher frequency of clinical relapses and progressing disability. This suggests that long-term global and grey matter brain atrophy change may provide a valuable outcome of longstanding disability and progression in patients with MS

14:30 607.   Reversible NAA decreases in active MS lesions are not due solely to water content changes 
Irene Vavasour1, Cornelia Laule1,2, Madeleine Hodgson3, David Li1, Anthony Traboulsee4, Burkhard Maedler5, and Alexander MacKay1,3
1Radiology, University of British Columbia, Vancouver, British Columbia, Canada, 2Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada, 3Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada, 4Medicine (Neurology), University of British Columbia, Vancouver, British Columbia, Canada, 5Neurosurgery, University of Bonn, Germany

Previous magnetic resonance spectroscopy studies have shown a decrease in N-acetyl-aspartate (NAA) concentration when a new MS lesion appears followed by a subsequent rise. The most plausible explanation is that dilution from increased water content (WC) related to edema causes NAA to decrease while edema resolution leads to an NAA increase. Scanning monthly over 6 months, NAA concentrations of twelve new lesions were extracted using LCModel and corrected for relaxation and WC. Even after taking into account WC changes, NAA showed a reversible decrease in new lesions. The reversible NAA changes in new lesions are not a simple dilution effect.

14:40 608.   Quantitative assessment of iron in multiple sclerosis lesions 
Christian Langkammer1, Michael Khalil1, Christian Enzinger1, Mirja Wallner-Blazek1, Margit Jehna1, Siegried Fuchs1, Franz Fazekas1, and Stefan Ropele1
1Department of Neurology, Medical University of Graz, Graz, Austria

This study assessed iron accumulation in white matter lesions of 116 MS patients using R2* relaxometry. Intralesional R2* rates were compared to normal white matter of age matched controls and were related to clinical parameters. They showed a negative correlation with T2 lesion load and a positive correlation with brain atrophy and were significantly decreased in MS patients compared to white matter R2* rates of controls. The results of this work do not support expectations of increased iron accumulation in MS lesions, but rather indicate lower levels compared to normal white matter.

14:50 609.   Longitudinal Tract-Based Spatial Statistics Analysis Reveals Left and Right Asymmetric DTI Alterations in Relapsing Remitting Multiple Sclerosis 
Salem Hannoun1, Francoise Durand-Dubief1,2, Christian Confavreux2, Francois Cotton1, and Dominique Sappey-Marinier1,3
1CREATIS, University of Lyon, Lyon, Rhone-Alpes, France, 2Neurological Hospital, Lyon, Rhone-Alpes, France, 3CERMEP-Imagerie du Vivant, Lyon, Rhone-Alpes, France

This study aims to characterize longitudinal alterations of white matter (WM) over a period of 2 years in different clinical forms of multiple sclerosis (MS) using tract-based spatial statistics (TBSS). Significant alterations of diffusivity including FA decrease, and λ1, λ2 and λ3 increases were mostly found in the right hemisphere of relapsing-remitting (RR) patients, particularly in the external capsule (EC). Region of interest (ROI) analysis of this region confirmed these results and allowed the quantification of these changes over time. The comparison between left and right EC of DTI metrics variations over time showed significant decreases of FA and increases of λ1, λ2 and λ3 in the right ROI. This finding probably reflects an evolving process spreading from the left to the right hemisphere that may result from demyelination and/or remyelination processes in the right and left hemispheres, respectively.

15:00 610.   Axonal damage in the making: neurofilament phosphorylation and magnetization transfer in MS non-lesional white matter 
Klaus Schmierer1,2, Dan Tozer2, and Axel Petzold2,3
1Barts and The London School of Medicine & Dentistry, London, England, United Kingdom, 2Neuroinflammation, UCL Institute of Neurology, London, United Kingdom, 3Free University Medical Centre, Amsterdam, Netherlands

Multiple sclerosis (MS) affects the phosphorylation and thus the proton binding capacity of axonal neurofilament (Nf) proteins. Macromolecules can be quantified using magnetization transfer ratio (MTR). We explored in post mortem brain of 12 patients with MS whether in non-lesional white matter (NLWM) MTR is associated with Nf phosphoforms, as a biomarker of axonal phosphorylation in NLWM. Indeed, the concentration of hyperphosphorylated Nf correlated with T1 (r=0.7; p= 0.01) and (inversely) with MTR (r=-0.76 p<0.01) (fig 3) suggesting that both MTR and T1may be markers of axonal integrity in NLWM.