Elizabeth York¹, Rozanna Meijboom¹, Mark Bastin¹, Agniete Kampaite¹, Maria Valdes Hernandez¹, Michael J. Thrippleton¹, Peter Connick², Siddharthan Chandran^1,2, David P.J. Hunt¹, and Adam D. Waldman^1
1Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom, ²Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, United Kingdom

There is a pressing need for longitudinal in vivo biomarkers sensitive to heterogeneous pathology in relapsing-remitting multiple sclerosis (RRMS). The MR-g-ratio may be derived from myelin-sensitive magnetisation transfer saturation (MTsat) and multishell diffusion-weighted MRI but its relevance as a longitudinal biomarker and correlate of disability progression in RRMS is previously unexplored. Fifty-nine patients with recently diagnosed RRMS contributed g-ratio data at baseline and one year. G-ratio showed a significant decrease in normal-appearing white matter (NAWM) but not T2 FLAIR white matter lesions over one year. Both g-ratio in NAWM and lesions were, however, associated with clinical disability progression.

Ajay Nemani¹, Katherine Koenig², Xuemei Huang¹, and Mark J Lowe^2
1Imaging Institute, Cleveland Clinic, Cleveland, OH, United States, ²Cleveland Clinic, Cleveland, OH, United States

Multiple sclerosis (MS) is characterized by degenerative changes in white matter, resulting in motor and cognitive deficits.  The corresponding damage to functional brain networks is not well understood.  We studied several graph theoretic network features of multiple sclerosis patients imaged with rsfMRI.  Using a data-driven parcellation designed for optimal node-based representation as well as sex and age-matched controls, we find no significant differences.  This result was robust to individual and group parcellations, as well as paired and group comparisons.  This differs from previous studies based on standard parcellations and pooled group comparisons.  Methodologic reasons for the different observations are discussed.

Tigris S. Joseph^1,2, Hanwen Liu^2,3,4, Shannon H. Kolind^1,2,4,5, Guojun Zhao⁴, Peng Sun⁶, Robert Carruthers⁴, Alice Schabas⁴, Ana-Luiza Sayao⁴, Virginia Devonshire⁴, Roger Tam^5,7, G. R. Wayne Moore^2,4,8, David K. B. Li^4,5, Sheng-Kwei Song⁹, Anthony Traboulsee⁴, Irene M. Vavasour^2,5, and Cornelia Laule^1,2,5,8
1Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ²International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, BC, Canada, ³Montreal Neurological Institute - Hospital, McGill University, Montreal, QC, Canada, ⁴Medicine, University of British Columbia, Vancouver, BC, Canada, ⁵Radiology, University of British Columbia, Vancouver, BC, Canada, ⁶Imaging Physics, MD Anderson Cancer Center, Houston, TX, United States, ⁷School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada, ⁸Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, ⁹Radiology, Washington University, St. Louis, MO, United States

Inflammation is a key component in multiple sclerosis (MS) pathology. Quantitative MRI metrics reflecting inflammation are important for understanding disease processes in vivo. Metrics from multi-echo T₂ relaxation, Diffusion Basis Spectrum Imaging (DBSI) and Neurite Orientation Dispersion and Density Imaging (NODDI) were compared in participants with MS and healthy controls. NODDI neurite density index and DBSI restricted fraction were correlated and may be sensitive to similar pathology. GMT₂ correlated negatively with cellularity, but positively with oedema, suggesting oedema may be a key mechanism driving GMT₂ increases. Our findings support a complementary T₂ and diffusion approach to probe inflammation in MS.

Hang Zhang¹, Jinwei Zhang², Melanie Marcille³, Pascal Spincemaille⁴, Thanh D. Nguyen³, Susan A. Gauthier³, Yi Wang³, and Elizabeth M. Sweeney^5
1Electrical & Computer Engineering, Cornell University, New York, NY, United States, ²Biomedical Engineering, Cornell University, New York, NY, United States, ³Department of Radiology, Cornell University, New York, NY, United States, ⁴Cornell University, New York, NY, United States, ⁵Department of Population Health Sciences, Cornell University, New York, NY, United States

Chronic active multiple sclerosis (MS) lesions are characterized on Quantitative susceptibility mapping (QSM) by a paramagnetic rim (rim+) at the edge of the lesion. We present QSMRim-Net, a deep neural network that fuses lesion-level radiomic and convolutional image features together for automated identification of rim+ lesions on MRI. On the lesion-level, using five-fold cross validation, the proposed QSMRim-Net detected rim+ lesions with an area under the receiver operating characteristic curve of 0.965 and an area under the precision recall curve of 0.655.  QSMRim-Net out-performed other state-of-the-art methods on both metrics.

Fahad Salman¹, Niels Bergsland^1,2, Michael Dwyer^1,3, Bianca Weinstock-Guttman⁴, Robert Zivadinov^1,3, and Ferdinand Schweser^1,3
1Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, NY, United States, ²IRCCS, Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy, ³Center for Biomedical Imaging, Clinical and Translational Science Institute, The State University of New York, Buffalo, NY, United States, ⁴Jacobs Multiple Sclerosis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States

Most T1w imaging sequences produce only weak deep gray matter (DGM) contrast compared to iron-sensitive techniques such as QSM. In particular, using multi-modal information in both template generation and brain normalization steps has the potential to result in improved segmentation performance. In this study, we compared FIRST to a custom multi-contrast T1w-QSM atlas segmentation approach for estimating thalamic volumes and susceptibility. Our study suggested that an advanced atlas-based approach may result in better regional segmentations of regions with weak T1w contrast and result in more accurate parameter estimates.

Samantha Noteboom¹, Martijn D. Steenwijk¹, David R. van der Nederpelt², Eva M.M. Strijbis³, Bastiaan Moraal², Frederik Barkhof^2,4, Jeroen J.G. Geurts¹, Matthan W. A. Caan⁵, Hugo Vrenken², and Menno M Schoonheim^1
1Anatomy and Neurosciences, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, ²Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, ³Neurology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, ⁴Neurology and Healthcare Engineering, UCL London, Amsterdam, United Kingdom, ⁵Biomedical Engineering & Physics, Amsterdam UMC, location AMC, Amsterdam, Netherlands

Conventional brain segmentation approaches typically require high resolution 3D-T1 weighted images, which are often unavailable in clinical multiple sclerosis (MS) protocols. Recently, SynthSeg was released which allows 3D-FLAIR to be used for segmentations. This study compared segmentation on 3D-FLAIR with SynthSeg to segmentation in the same patients on 3D-T1 (SynthSeg, FastSurfer and SAMSEG). Brain segmentation was performed on 100 patients with 3D-T1 and 3D-FLAIR images from research and clinical datasets. ICC results showed good comparability for brain tissue, ventricle and grey matter assessments in research data. In clinical data only good comparability was found for ventricle segmentation.

Alessandro Cagol¹, Reza Rahmanzadeh¹, Muhamed Barakovic¹, Po-Jui Lu¹, Matthias Weigel², Lester Melie-Garcia¹, Antoine Lutti³, Than D. Nguyen⁴, Yi Wang⁴, Jens Kuhle⁵, Ludwig Kappos¹, and Cristina Granziera^1
1Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland. Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland, Basel, Switzerland, ²Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland. Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland. Division of Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland, Basel, Switzerland, ³Laboratory for Research in Neuroimaging, Department of Clinical Neuroscience, Lausanne University Hospital and University of Lausanne, Switzerland, Lausanne, Switzerland, ⁴Department of Radiology, Weill Cornell Medical College, New York, NY, USA, New York, NY, United States, ⁵Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland, Basel, Switzerland

Thalamus represents a pivotal structure to study MS-associated neurodegeneration. In this study we investigated the alterations in thalamic microstructure of MS patients by using magnetization transfer saturation (MTsat), T1-relaxometry, and myelin water fraction (MWF). Compared to healthy controls (HCs), MS patients presented significant modifications in the thalamic quantitative MRI metrics, suggesting ongoing microstructural and myelin loss. The thalamic quantitative MRI metrics explored showed variable degrees of association with MS lesion burden, brain atrophic changes, as well as with clinical and cognitive disability.

Wafaa Sweidan¹, Jenny Chen¹, Benjamin Ades-Aron¹, Tamar Bacon², Matthew Lee¹, Santiago Coelho¹, Dmitry S Novikov¹, Timothy Shepherd¹, Ilya Kister², and Els Fieremans^1
1Radiology, NYU, New York, NY, United States, ²Neurology, NYU, New York, NY, United States

In a cohort of 172 MS subjects, we identified thalamic atrophy as a significant gray matter correlate of patient-reported indices of motor disability.

Graziella Donatelli^1,2, Paolo Cecchi^1,2, Gianmichele Migaleddu¹, Matteo Cencini³, Claudio D'Amelio⁴, Guido Buonincontri³, Luca Peretti^2,3,4, Livia Pasquali⁴, Michela Tosetti^2,3, Mirco Cosottini⁴, and Mauro Costagli^3,5
1Azienda Ospedaliero Universitaria Pisana, Pisa, Italy, ²IMAGO 7 Research Foundation, Pisa, Italy, ³IRCCS Stella Maris, Pisa, Italy, ⁴University of Pisa, Pisa, Italy, ⁵Department of Neuroscience, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Sciences, University of Genoa, Genoa, Italy

Quantitative maps of T1-shortening (ΔT1) related to intra-venous contrast media administration are obtained in patients with Multiple Sclerosis by using 3D Quantitative Transient-state Imaging. Statistically significant ΔT1 is observed not only in enhancing lesions, but also in some non-enhancing lesions, suggesting a potential role of this method as a quantitative imaging biomarker to detect subtle blood-brain barrier damage.

Ronja C. Berg¹, Viola Pongratz², Markus Lauerer², Thomas Amthor³, Guillaume Gilbert⁴, Aurore Menegaux¹, Claus Zimmer¹, Christian Sorg¹, Mariya Doneva³, Irene Vavasour⁵, Mark Mühlau², and Christine Preibisch^1
1Department of Neuroradiology, School of Medicine, Technical University of Munich, Munich, Germany, ²Department of Neurology, School of Medicine, Technical University of Munich, Munich, Germany, ³Philips Research Europe, Hamburg, Germany, ⁴MR Clinical Science, Philips Healthcare, Mississauga, ON, Canada, ⁵Department of Radiology, University of British Columbia, Vancouver, BC, Canada

Measurement of myelin concentration could provide valuable information on the integrity of brain tissue. Several myelin-sensitive magnetic resonance imaging methods have been developed. Here, we compared myelin water fraction (MWF), inhomogeneous magnetization transfer ratio (ihMTR) and magnetization transfer saturation (MTsat) in healthy volunteers and patients with multiple sclerosis (MS). We found highest correlation between MWF and ihMTR but all three measures showed clearly reduced values in MS lesions compared to healthy or normal-appearing white matter. However, the measures varied in differentiating between various WM regions and between peri-lesional tissue and more distant normal-appearing WM.

Serge Didenko Vasylechko^1,2, Fedel Machado-Rivas^1,2, Camilo Jaimes^1,2, Mark P. Gorman^2,3, Leslie Benson^2,3, Simon K. Warfield^1,2, Sila Kurugol^1,2, and Onur Afacan^1,2
1Radiology, Boston Children's Hospital, Boston, MA, United States, ²Harvard Medical School, Boston, MA, United States, ³Neurology, Boston Children's Hospital, Boston, MA, United States

This study evaluated myelin water fraction (MWF) estimates in chronic MS lesions against contralateral normal appearing white matter (NAWM) of pediatric onset MS patients (POMS). Accelerated 2D multi-slice CPMG acquisitions provided near full brain coverage. Two methods were used to estimate the myelin fractions, as well as intra-/extra- axonal (IE) associated water and CSF water. Significant differences were found between the group measures. Further comparison of NAWM in POMS showed significant differences with whole-white matter in a control group. Our results support that a multi-component T2 analysis can provide quantitative insights into lesional and non-lesional disease burden in POMS.

Irene Margaret Vavasour¹, Colm Elliott², Doug Arnold^2,3, Laura Gaetano⁴, David Clayton⁵, Stefano Magon⁴, Ulrike Bonati⁴, Wei Wei⁴, Anthony Traboulsee¹, and Shannon Kolind^1
1University of British Columbia, Vancouver, BC, Canada, ²NeuroRX Research, Montreal, QC, Canada, ³McGill University, Montreal, QC, Canada, ⁴F Hoffmann-La Roche Ltd, Basel, Switzerland, ⁵Genentech Inc, San Francisco, CA, United States

Multiple sclerosis (MS) slowly evolving lesions (SELs) are defined on MRI as contiguous regions of pre-existing lesions with constant and concentric local expansion on conventional T1-weighted and T2-weighted images. Myelin-related changes using myelin water fraction (MWF) and magnetization transfer ratio (MTR) in SELs and non-SELs were measured over 192 weeks in patients with relapsing MS. SELs showed reduced myelin measures at baseline compared to non-SELs. Furthermore, over the 4 years, only SELs, and not non-SELs, showed a significant mean decrease in MWF and increase in T1. Both results are indicative of progressive demyelination in this subgroup of chronic lesions.

Paola Valsasina¹, Maria A. Rocca^1,2,3, Alessandro Meani¹, Loredana Storelli¹, Claudio Gobbi^4,5, Chiara Zecca^4,5, Frederik Barkhof^6,7, Menno M Schoonheim⁸, Eva Strijbis⁷, Hugo Vrenken^6,7, Antonio Gallo⁹, Alvino Bisecco⁹, Olga Ciccarelli¹⁰, Marios Yiannakas¹⁰, Alex Rovira¹¹, Jaume Sastre-Garriga¹², Jacqueline Palace¹³, Lucy Matthews¹³, Achim Gass¹⁴, Philipp Eisele¹⁴, Carsten Lukas¹⁵, Barbara Bellenberg¹⁵, Monica Margoni¹, Paolo Preziosa^1,2, and Massimo Filippi^{1,2,3,16,17
1}Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy, ²Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy, ³Vita-Salute San Raffaele University, Milan, Italy, ⁴Neurology Clinic, MS Center/ Headache Center, Neurocenter of Southern Switzerland, Lugano, Switzerland, ⁵Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland, ⁶Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam UMC, location Vumc, Amsterdam, Netherlands, ⁷Department of Neurology, MS Center Amsterdam, Amsterdam UMC, location Vumc, Amsterdam, Netherlands, ⁸Department of Anatomy and Neurosciences, MS Center Amsterdam, Amsterdam UMC, location Vumc, Amsterdam, Netherlands, ⁹Department of Advanced Medical and Surgical Sciences, and 3T MRI-Center, University of Campania “Luigi Vanvitelli”, Naples, Italy, ¹⁰NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom, ¹¹Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Barcelona, Spain, ¹²Department of Neurology/Neuroimmunology, Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain, ¹³Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ¹⁴Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany, ¹⁵Institute of Neuroradiology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany, ¹⁶Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy, ¹⁷Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy

Aim of this study was to evaluate the independent role of brain and cervical cord damage in predicting 5-year clinical disability worsening in a multicentre cohort of multiple sclerosis patients. Results showed that cortical atrophy and spinal cord damage, together with baseline disability and progressive disease phenotype, independently predicted 5-year disability worsening (C-index=0.81). Older age, higher clinical disability and cord lesion number independently predicted conversion to a progressive disease phenotype (C-index=0.91). Focal spinal cord lesions and cortical atrophy had also a role in predicting clinically-relevant disability milestones at 5 years.

Yan Xie¹, Yan Zhang¹, Weiyin Vivian Liu², and Wenzhen Zhu^1
1Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ²GE Healthcare, MR Research China, Beijing, China

The purpose of this study was to assess the differences in the patterns of NMOSD and MS-related optic nerve damage by DTI. In this study, the intraorbital optic nerve was divided anatomically in three equal parts. We found that NMOSD-related optic neuritis exhibited extensive optic nerve damage, particularly in the posterior segment of the optic nerve, whereas MS-related optic neuritis tended to be more anterior-middle optic nerve damage. In addition, the combination of FA with conventional MRI showed better differential diagnostic efficacy for NMOSD and MS-related optic neuritis.