Gabriel Mangeat^1,2, Russell Ouellette^2,3, Constantina Andrada Treaba^2,3, Tobias Granberg^2,3, Elena Herranz^2,3, Celine Louapre^2,3, Nikola Stikov^1,4, Jacob A. Sloane^3,5, Eric C. Klawiter^2,3,6, Caterina Mainero^2,3, and Julien Cohen-Adad^1,7
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.

Giovanni Savini^1,2, Matteo Pardini³, Alessandro Lascialfari^1,4, Declan Chard⁵, David Miller⁵, Egidio D'Angelo^2,6, and Claudia Angela Michela Gandini Wheeler-Kingshott^2,5
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.

Rebecca Sara Samson¹, Manuel Jorge Cardoso^2,3, Wallace J Brownlee¹, J William Brown^1,4, Matteo Pardini⁵, Sebastian Ourselin^2,3, Claudia Angela Michela Gandini Wheeler-Kingshott^1,6, David H Miller^1,7, and Declan T Chard^1,7
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.

Se-Hong Oh¹, Wanyong Shin¹, Jongho Lee², and Mark J. Lowe^1
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.

Elena Herranz^1,2, Costanza Giannì^1,2, Céline Louapre^1,2, Constantina Andrada Treaba^1,2, Sindhuja T Govindarajan¹, Gabriel Mangeat^1,3, Russell Ouellette¹, Marco L Loggia^1,2, Noreen Ward¹, Eric C Klawiter^1,2,4, Ciprian Catana^1,2, Jacob A Sloane^2,5, Jacob M Hooker^1,2, Revere P. Kinkel⁶, and Caterina Mainero^1,2
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.

Ferdinand Schweser^1,2, Jesper Hagemeier¹, Paul Polak¹, Michael G Dwyer¹, Niels P Bergsland^1,3, Nicola Bertolino¹, Bianca Weinstock-Guttman⁴, Andreas Deistung⁵, Jürgen R Reichenbach^5,6, and Robert Zivadinov^1,2
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. 

Yi-Ching Lynn Ho^1,2, Fiftarina Puspitasari¹, Way-Cherng Chen¹, and Kai-Hsiang Chuang^1
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.

Caroline Guglielmetti^1,2, Chloe Najac¹, Annemie Van der Linden², Sabrina M Ronen¹, and Myriam M Chaumeil^1
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.

Tsen-Hsuan Lin¹, Mitchell Hallman^1,2, Mattew F. Cusick³, Jane E. Libbey³, Peng Sun¹, Yong Wang^1,4,5,6, Robert S. Fujinami³, and Sheng-Kwei Song^1,5,6
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.  

Wei Bian¹, Eric Tranvinh¹, Thomas Tourdias², May Han³, Tian Liu⁴, Yi Wang⁴, Brian Rutt¹, and Michael Zeineh^1
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.