Matthias Weigel^1,2,3, Peter Dechent⁴, Riccardo Galbusera^1,2, Rene Mueller⁵, Govind Nair⁶, Ludwig Kappos², Wolfgang Brück⁵, and Cristina Granziera^1,2
1Translational Imaging in Neurology (ThINk) Basel, Department of Medicine and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland, ²Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland, ³Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland, ⁴Department of Cognitive Neurology, MR-Research in Neurology and Psychiatry, University Medical Center Göttingen, Göttingen, Germany, ⁵Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany, ⁶Translational Neuroradiology Section, Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States

MR imaging is an indispensable tool for the depiction of human brain anatomy and pathology. Besides in vivo acquisitions, MRI of the fixated human brain is highly interesting: Very long scan times basically allow unprecedented MRI resolutions on clinical scanners. The present work describes an MRI approach that was developed for standard clinical 3T systems and tests for the viable boundaries: Within scan times between a few hours up to a weekend, acquisitions of high soft tissue contrast with isotropic resolutions up to 200μm can be achieved; revealing fine structure details and allowing an impressing lesion detection and characterization.

Jiaen Liu¹, Erin S. Beck¹, Peter van Gelderen¹, Pascal Sati¹, Jacco A. de Zwart¹, Hadar Kolb¹, Omar Al-Louzi¹, Mark Morrison¹, Daniel S. Reich¹, and Jeff H. Duyn^1
1National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States

T₂*-weighted MRI at high field is a promising tool to detect and characterize multiple sclerosis (MS) lesions. However, its high sensitivity to motion-induced B₀ field changes limits the successful application of this technique in routine clinical use. In this study, we evaluated our recently developed motion and B₀ correction method using a navigator-based 3D GRE acquisition for imaging MS lesions at 7 T.

Jinhee Jang¹, Hyeong-geol Shin², Yoonho Nam^1,3, Jingu Lee², Jongho Lee², and Woojun Kim^4
1Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, ²Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea, ³Radiology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, ⁴Neurology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

While susceptibility contrast gives details for MS lesions, two major changes – iron deposition and de-myelination had same contribution on QSM, increasing bulk magnetic susceptibility. In this work, we applied separation of positive and negative sources in clinical MS patients, and had a closer look of in-vivo MS lesions. We demonstrate variable appearances of MS lesions on separation maps as well as conventional imaging and QSM, and complex distribution and dynamic changes of positive (i.e. iron) and negative (i.e. myelin) in MS lesions, in cross-sectional and longitudinal observations.

Reza Rahmanzadeh^1,2, Po-Jui Lu^1,2, Muhamed Barakovic^1,2, Riccardo Galbusera^1,2, Matthias Weigel^1,2,3, Pietro Maggi⁴, Thanh D. Nguyen ⁵, Simona Schiavi⁶, Francesco La Rosa ^7,8, Daniel S. Reich⁹, Pascal Sati⁹, Yi Wang⁵, Meritxell Bach-Cuadra^7,8, Ernst-Wilhelm Radue¹, Jens Kuhle², Ludwig Kappos², and Cristina Granziera^1,2
1Translational Imaging in Neurology (ThINk) Basel, Department of Medicine and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland, ²Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland, ³Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland, ⁴Department of Neurology, Lausanne University Hospital, Lausanne, Switzerland, ⁵Department of Radiology, Weill Cornell Medical College, New York, NY, United States, ⁶Department of Computer Science, University of Verona, Verona, Italy, ⁷Signal Processing Laboratory (LTSS), Ecole polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland, ⁸Radiology Department, Center for Biomedical Imaging, Lausanne University and University Hospital, Lausanne, Switzerland, ⁹National Institute of Neurological Disorders and Stroke, Translational Neuroradiology Section, Division of Neuroimmunology and Neurovirology, Bethesda, MD, United States

The interplay between axonal and myelin damage in multiple sclerosis (MS) is poorly understood. This study aimed to evaluate the concomitant presence of axonal and myelin injury in living MS patients by using myelin and multi-shell diffusion MRI. Confirming neuropathological findings, our results show that (i) axonal and myelin damage exists in MS lesions and spreads out from the lesions in a centrifugal way, (ii) the extent of myelin and axonal damage differs among lesion subtypes and according to lesion anatomical locations and (iii) axonal (and not myelin) damage differs between relapsing-remitting and progressive MS patients.

Manoj K. Sammi¹, Elizabeth Silbermann², Greg Zarelli³, Dennis Bourdette², Michael Lane², Vijayshree Yadav², Caroline Butler⁴, Katherine Powers¹, Katherine Powers¹, Ian Tagge¹, Susan Goelz⁵, and William D Rooney^1,2,6,7
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, ²Department of Neurology, Oregon Health & Science University, Portland, OR, United States, ³Kaiser Sunnyside Medical Center, Clackamas, OR, United States, ⁴Oregon Health & Science University, Portland, OR, United States, ⁵Myelin Repair Foundation, Saratoga, CA, United States, ⁶Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States, ⁷Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, United States

A novel MRI T₁ relaxometry technique is used to monitor myelin water fraction (MWF) in normal appearing white matter and multiple sclerosis lesions in subjects with newly formed white matter lesions at baseline and a follow-up study after six months.  MWF was consistently low in new lesions at baseline and recovery over 6 months was highly variable.  T₁ relaxometry provides a promising quantitative and non-invasive tool for studying myelin repair in human brain.

Irene Margaret Vavasour^1,2, Carina Graf^2,3, Shannon H Kolind^1,2,3,4,5, Peng Sun⁶, Robert Carruthers⁴, Anthony Traboulsee^4,5, GR Wayne Moore^2,7, David KB Li^1,4,5, and Cornelia Laule^1,2,3,7
1Radiology, University of British Columbia, Vancouver, BC, Canada, ²International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada, ³Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ⁴Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada, ⁵MS/MRI Research Group, University of British Columbia, Vancouver, BC, Canada, ⁶Radiology, Washington University, St. Louis, MO, United States, ⁷Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Diffusely abnormal white matter (DAWM) is a non-focal area of mildly increased signal on proton density and T₂-weighted images. Advanced imaging techniques (T₁ and T₂ relaxation and diffusion basis spectrum imaging) compared measures of myelin, axons, oedema and inflammation between males and females with multiple sclerosis in normal appearing white matter (NAWM) and areas of DAWM. In NAWM, males had higher axial diffusivity indicative of axonal damage. In DAWM, MRI measures suggested demyelination in females whereas axonal damage was suggested in males. Both sexes show increased T₁, GMT₂ and water content in DAWM likely related to oedema.

Johann Malte Enno Jende¹, Felix Tobias Kurz¹, Mirjam Korporal-Kuhnke², Markus Weiler², Brigitte Wildemann², Andrea Viehöver², Sabine Heiland¹, Wolfgang Wick², Martin Bendszus¹, and Jennifer Kollmer^1
1Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany, ²Neurology, Heidelberg University Hospital, Heidelberg, Germany

This study investigated the correlation between T2w-hyperintense lesions to the peripheral nervous system (PNS) and the central nervous system (CNS) in multiple sclerosis (MS) by combining 3 Tesla magnetic resonance neurography (MRN) and 3 Tesla CNS MRI. It was found that CNS lesions and PNS lesions were inversely correlated (r=-0.432; p=0.0002). This finding might help to elucidate the underlying pathomechanism of PNS involvement in MS by indicating that PNS demyelination in MS does not occur secondary to CNS lesions in the sense of Wallerian degeneration.

Weiwei Chen¹, Mehran Shaghaghi², Haiqi Ye¹, Qianlan Chen¹, Yan Zhang¹, and Kejia Cai^2,3,4
1Radiology, Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ²Radiology, University of Illinois at Chicago, Chicago, IL, United States, ³Center for MR Research, University of Illinois at Chicago, Chicago, IL, United States, ⁴Bioengieering, University of Illinois at Chicago, Chicago, IL, United States

In this study, at the first time, we performed in vivo k_ex MRI of MS patients and evaluated its potential value for staging clinical MS lesions. In vivo proton exchange rate mapping was found to be highly correlated with Gadolinium enhancement for determining lesion activity. With further validation, k_ex may be an alternative endogenous MRI contrast for the clinical determination of dissemination in time (DIT) of MS lesions. 

Mohamed Mounir El Mendili¹, Ben Ridley¹, Bertrand Audoin^1,2, Soraya Gherib¹, Lauriane Pini¹, Françoise Reuter^1,2, Maxime Guye^1,3, Armin Nagel⁴, Audrey Rico², Clémence Boutière², Jean Pelletier^1,2, Jean-Philippe Ranjeva¹, Adil Maarouf^1,2, and Wafaa Zaaraoui^1
1Aix-Marseille Université, CNRS, CRMBM, Marseille, France, ²APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France, ³APHM, Hôpital de la Timone, Pôle d’Imagerie Médicale, CEMEREM, Marseille, France, ⁴Institute of Radiology, University Hospital Erlangen, Erlangen, Germany

Alteration of sodium homeostasis was previously evidenced in multiple sclerosis with total sodium concentration (TSC) found to be related to disability. However, the correlations found were moderate, maybe due to the fact that measured sodium accumulation combined intra and extra cellular sodium signal while only intra-cellular sodium concentration is relevant to assess neurodegeneration. One may suppose that developing reliable sequences able to assess only the intra-cellular signal may lead to a better estimation of neurodegeneration in multiple sclerosis and better correlations with irreversible disability. The present study proposes an original multi-TE sequence at 7T to reach this goal.

Junghun Cho¹, Thanh D. Nguyen², Weiyuan Huang², Shun Zhang², Xianfu Luo², Susan A. Gauthier³, Pascal Spincemaille², Ajay Gupta², and Yi Wang^1,2
1Biomedical Engineering, Cornell University, New York, NY, United States, ²Radiology, Weill Cornell Medical College, New York, NY, United States, ³Neurology, Weill Cornell Medical College, New York, NY, United States

Impaired energy metabolism is a major contributor to the ongoing inflammation and neurodegeneration in multiple sclerosis (MS) brains, particularly MS lesions. Cerebral regional oxygen extraction fraction mapping (rOEF) obtained from challenge-free multiecho gradient echo data demonstrates that lesions identified on quantitative susceptibility mapping (QSM) without rim (QSM rim-) have heterogenous OEF that is higher than that in other type of lesions. rOEF may offer insight into MS lesion remylination viability.

Adil Maarouf^1,2, Hanna Bou Ali¹, Pierre Besson¹, Jan Patrick Stellman^1,3, Soraya Gherib¹, Fanelly Pariollaud¹, Arnaud Le Troter¹, Maxime Guye^1,3, Patrick Viout¹, Jean Pelletier^1,2, Jean-Philippe Ranjeva¹, Bertrand Audoin^1,2, and Wafaa Zaaraoui^1
1Aix-Marseille Université, CNRS, CRMBM, Marseille, France, ²APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France, ³APHM, Hôpital de la Timone, Pôle d’Imagerie Médicale, CEMEREM, Marseille, France

Virtual hypoxia is a key factor in the induction of pathological processes in multiple sclerosis. ²³Na-MRI is an emerging technique in virtual hypoxia exploration, with previous studies showing relevance of grey matter sodium accumulation in MS. In the present study, we showed that grey matter sodium accumulation is mainly driven by accumulation in the most connected cortical regions (called hubs) and correlate with disability. This study provides an insight in several processes of energy failure and brain reorganization in MS.

Dinesh K Sivakolundu¹, Kathryn L West¹, Gayathri B Maruthy¹, Mark Zuppichini¹, Monroe P Turner¹, Dema Abdelkarim¹, Yuguang Zhao¹, Jeffrey Spence¹, Hanzhang Lu², Darin T Okuda³, and Bart Rypma^1
1The University of Texas at Dallas, Dallas, TX, United States, ²Johns Hopkins University, Baltimore, MD, United States, ³University of Texas Southwestern Medical Center, Dallas, TX, United States

Cognitive impairment occurs in ~70% of multiple sclerosis patients (MSP). The neural mechanism of this slowing is unknown. Vascular compliance reductions along the cerebrovascular tree would result in suboptimal vasodilation upon neural stimulation (i.e., neural-vascular uncoupling) and thus cognitive slowing. We tested arterial and venous cerebrovascular reactivity (CVR) along the cerebrovascular tree in nested cerebral cortical layers. Arterial CVR reduced exponentially along the cortical layers in controls and cognitively-normal MSP, but not in slower MSP. The exponential decay-constant was associated with individual subjects’ reaction-time. Such associations implicate neural-vascular uncoupling as a mechanism of cognitive slowing in MS. 

Marco Muccio¹, Peidong He¹, Claire S. Choi², Lillian Walton Masters², Lauren Krupp², Oded Gonen¹, Leigh Charvet², and Yulin Ge^1
1Department of Radiology, New York University School of Medicine, New York, NY, United States, ²Department of Neurology, New York University School of Medicine, New York, NY, United States

Transcranial direct current stimulation (tDCS) is an innovative, non-invasive, brain stimulation technique that modulates cortical excitability by applying weak electrical currents. Despite cognitive improvements in multiple sclerosis (MS) subjects have been recently reported, the underlying in-vivo physiological mechanism of tDCS remains largely unclear. The purpose of this study is therefore to firstly address the real time tDCS effect (with simultaneous MRI scans) on the functional connectivity of both controls and MS patients. Secondly, we want to investigate whether such changes are altered in MS subjects following 20 tDCS treatment sessions.