ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Scientific Session: Multiple Sclerosis: Novel Techniques & Studies

Monday, May 9, 2016
Hall 606
16:30 - 18:30
Moderators: Roland Henry, Jongho Lee

Association between cortical demyelination and structural connectomics in early multiple sclerosis
Gabriel Mangeat1,2, Russell Ouellette2,3, Constantina Andrada Treaba2,3, Tobias Granberg2,3, Elena Herranz2,3, Celine Louapre2,3, Nikola Stikov1,4, Jacob A. Sloane3,5, Eric C. Klawiter2,3,6, Caterina Mainero2,3, and Julien Cohen-Adad1,7
1Polytechnique Montreal, Montreal, QC, Canada, 2Athinoula A. Martinos Center for Biomedical Imaging, MGH, Charlestown, MA, United States, 3Harvard Medical School, Boston, MA, United States, 4Montreal Health Institute, Montreal, QC, Canada, 5Beth Israel Deaconess Medical Center, Boston, MA, United States, 6Department of Neurology, MGH, Boston, MA, United States, 7CRIUGM, Functional Neuroimaging Unit, Universite´ de Montre´al, Montreal, QC, United States
Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by diffuse abnormalities along white matter tracts and demyelination, including cortical lesions. In this study, we explored the interplay between cortical and brain structural networks integrity in a cohort of early MS subjects by combining quantitative mapping of T2* and T1 relaxation rates from 7T MRI acquisitions to measure cortical demyelination with diffusion imaging and graph theory to assess the structural brain architecture. Results suggest that motor, premotor and anterior cingulate cortices are affected simultaneously by cortical demyelination and connectomics alterations, at a very early stage of MS.

Cerebellar-cerebral connections with the default mode network influence working memory performance in MS
Giovanni Savini1,2, Matteo Pardini3, Alessandro Lascialfari1,4, Declan Chard5, David Miller5, Egidio D'Angelo2,6, and Claudia Angela Michela Gandini Wheeler-Kingshott2,5
1Department of Physics, University of Milan, Milan, Italy, 2Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia, Italy, 3Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy, 4Department of Physics, University of Pavia, Pavia, Italy, 5NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL, Institute of Neurology, University College London, London, United Kingdom, 6Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
The cerebellum is linked to the default mode network (DMN) and its contribution to non-motor functions is now increasingly recognized. In Multiple Sclerosis (MS) motor and cognitive functions are both impaired. Here we aimed at assessing a possible link between cognition and cerebellar-cerebral fibers disruption in MS. Probabilistic tractography and graph theory derived metrics were compared to Symbol Digit Modalities Test (SDMT) scores in MS. We found that accounting for cerebellar-cerebral connections when calculating DMN graph metrics yielded a stronger correlation between network efficiency and SDMT scores, suggesting that disruption of the cerebellar-cerebral connections has significant cognitive consequences in MS.

Outer and inner cortical MTR abnormalities observed in clinically isolated syndromes
Rebecca Sara Samson1, Manuel Jorge Cardoso2,3, Wallace J Brownlee1, J William Brown1,4, Matteo Pardini5, Sebastian Ourselin2,3, Claudia Angela Michela Gandini Wheeler-Kingshott1,6, David H Miller1,7, and Declan T Chard1,7
1NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London, London, United Kingdom, 2Translational Imaging Group, Centre for Medical Image Computing, Department of Medical Physics and Bioengineering, University College London, London, United Kingdom, 3Dementia Research Centre, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, United Kingdom, 4Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, 5Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy, 6Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia, Italy, 7National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, London, United Kingdom
Cortical magnetization transfer ratio (cMTR) is potentially a sensitive measure of pathology linked with disease progression in relapse-onset multiple sclerosis (MS). We investigated outer cMTR changes in people following a clinically isolated syndrome (CIS), and compared those who later developed MS with those who did not. Compared with controls, the outer-to-inner cMTR ratio was significantly lower in patients who developed MS after 15 years but not in those who remained CIS. This suggests that the pathological processes underlying preferential reductions in outer cMTR start early in the clinical course of MS, and may be relevant to conversion to MS.

Variable Density Magnetization Transfer (vdMT) imaging for 7 T MR Imaging
Se-Hong Oh1, Wanyong Shin1, Jongho Lee2, and Mark J. Lowe1
1Imaging Institute, Cleveland Clinic Foundation, Cleveland, OH, United States, 2Laboratory for Imaging Science and Technology, Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea, Republic of
Because of the much higher SAR and longer acquisition time, in-vivo studies using MT at UHF have not been clinically feasible. In this work, we demonstrated a new approach (variable density MT [vdMT])for acquiring whole brain covered 7T MT data in a clinically reasonable time. vdMT provides similar image quality to that obtained with conventional MT imaging, and shortens the scan time by avoiding from SAR limitation. The proposed method generates high-resolution MT data in reasonable scan time and it exhibits high similarity with the conventional method. Moreover, it maintains sensitivity to MS lesions.

The neuroinflammatory component of gray matter pathology in multiple sclerosis by in vivo combined 11C-PBR28 MR-PET and 7T imaging
Elena Herranz1,2, Costanza Giannì1,2, Céline Louapre1,2, Constantina Andrada Treaba1,2, Sindhuja T Govindarajan1, Gabriel Mangeat1,3, Russell Ouellette1, Marco L Loggia1,2, Noreen Ward1, Eric C Klawiter1,2,4, Ciprian Catana1,2, Jacob A Sloane2,5, Jacob M Hooker1,2, Revere P. Kinkel6, and Caterina Mainero1,2
1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States, 2Harvard Medical School, Boston, MA, United States, 3Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada, 4Department of Neurology, Massachusetts General Hospital, Boston, MA, United States, 5Beth Israel Deaconess Medical Center, Boston, MA, United States, 6University of California, San Diego, CA, United States
In multiple sclerosis (MS) histopathological investigations implicated neuroinflammation through microglia and/or macrophages activation in the pathogenesis of cortical and subcortical diffuse damage. By combining 11C-PBR28 positron emission tomography (PET) imaging with anatomical 7T and 3T MRI, we investigated the presence and correlates of neuroinflammation in cortex and gray matter of subjects with MS. We found that neuroinflammation was present in thalamus, hippocampus, basal ganglia as well as cortex, particularly cortical lesions, and associated with structural damage, increased neurological disability and impaired information processing speed. Our data indicate that neuroinflammation is closely associated with neurodegeneration.

Quantitative Susceptibility Mapping (QSM) in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) - a large cohort study
Ferdinand Schweser1,2, Jesper Hagemeier1, Paul Polak1, Michael G Dwyer1, Niels P Bergsland1,3, Nicola Bertolino1, Bianca Weinstock-Guttman4, Andreas Deistung5, Jürgen R Reichenbach5,6, and Robert Zivadinov1,2
1Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States, 2MRI Molecular and Translational Research Center, Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States, 3MR Research Laboratory, IRCCS Don Gnocchi Foundation ONLUS, Milan, Italy, 4Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States, 5Medical Physics Group, Department of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany, 6Michael Stifel Center for Data-driven and Simulation Science Jena, Friedrich Schiller University Jena, Jena, Germany
Quantitative susceptibility mapping (QSM) is the most sensitive technique available for studying tissue iron in vivo. In this work, we applied QSM to more than 1000 patients with multiple sclerosis (MS) and almost 250 patients with clinically isolated syndrome (CIS). Our results provide strong support for changed deep gray matter iron concentrations in MS and CIS. 

Dissociated longitudinal patterns of neural activation, functional connectivity and structural connectivity in a mouse model of de- and re-myelination
Yi-Ching Lynn Ho1,2, Fiftarina Puspitasari1, Way-Cherng Chen1, and Kai-Hsiang Chuang1
1Singapore Bioimaging Consortium, Agency for Science, Technology & Research (A*STAR), Singapore, Singapore, 2Interdisciplinary Institute of Neuroscience & Technology (ZIINT), Zhejiang University, Hangzhou, China, People's Republic of
We hypothesized that structure and functional responses do not demonstrate the same pattern of impairment across time. Using the cuprizone mouse model of reversible demyelination, we show different longitudinal patterns of neural activation and functional connectivity, compared to healthy mice and also to the extent of cuprizone demyelination.

Hyperpolarized 13C MRSI can detect neuroinflammation in vivo in a Multiple Sclerosis murine model
Caroline Guglielmetti1,2, Chloe Najac1, Annemie Van der Linden2, Sabrina M Ronen1, and Myriam M Chaumeil1
1University of California San Francisco, San Francisco, CA, United States, 2University of Antwerp, Antwerp, Belgium
This study demonstrates that 13C MRS of hyperpolarized pyruvate can be used to detect increased lactate production from pro-inflammatory macrophages, mechanism mediated by pyruvate dehydrogenase kinase-1 upregulation and pyruvate dehydrogenase inhibition,  in a preclinical model of multiple sclerosis, hence providing a novel tool for in-vivo detection of neuroinflammation.

Axon Loss as an Outcome Measure for Assessing Therapeutic Efficacy
Tsen-Hsuan Lin1, Mitchell Hallman1,2, Mattew F. Cusick3, Jane E. Libbey3, Peng Sun1, Yong Wang1,4,5,6, Robert S. Fujinami3, and Sheng-Kwei Song1,5,6
1Radiology, Washington University School of Medicine, St. Louis, MO, United States, 2Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, 3Pathology, University of Utah School of Medicine, Salt Lake City, UT, United States, 4Obstertic and Gynecology, Washington University School of Medicine, St. Louis, MO, United States, 5The Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States, 6Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
Diffusion basis spectrum imaging (DBSI) has successfully distinguished co-existing pathologies in CNS, such as MS. The utility of DBSI derived “axon volume” has not been explored previously. In this study, we demonstrated the use of axon loss, reflecting irreversible tissue damage, as an outcome measure for assessing therapeutic efficacy in a mouse model of multiple sclerosis.  

In vivo 7T Quantitative Susceptibility Mapping of Cortical Lesions in Multiple Sclerosis
Wei Bian1, Eric Tranvinh1, Thomas Tourdias2, May Han3, Tian Liu4, Yi Wang4, Brian Rutt1, and Michael Zeineh1
1Department of Radiology, Stanford University, Stanford, CA, United States, 2Service de NeuroImagerie Diagnostique et Thérapeutique, CHU de Bordeaux, Bordeaux, France, 3Department of Neurology, Stanford University, Stanford, CA, United States, 4Department of Radiology, Weill Medical College of Cornell University, New York, NY, United States
Magnetic susceptibility measured with quantitative susceptibility mapping (QSM) has been proposed as a biomarker for inflammation in multiple sclerosis (MS) white matter (WM) lesions. However, a detailed in vivo characterization of cortical lesions has not been performed. In this study, the susceptibility in both cortical and WM lesions relative to adjacent normal-appearing parenchyma was measured and compared for 14 MS patients using QSM at 7T. Our results showed that relative susceptibility was negative for cortical lesions but positive for WM lesions. The opposite pattern of relative susceptibility suggests that iron loss dominates the susceptibility contrast in cortical lesions.

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