Olayinka Adeoluwa Oladosu¹, Cayden Murray², Syed Rizvi², Mariana Bento^3,4, G Bruce Pike^3,4, and Yunyan Zhang^3,4
1Neuroscience, University of Calgary, Calgary, AB, Canada, ²University of Calgary, Calgary, AB, Canada, ³Radiology, University of Calgary, Calgary, AB, Canada, ⁴Clinical Neurosciences, University of Calgary, Calgary, AB, Canada

Sex difference in multiple sclerosis (MS) prevalence is well recognized but impacts on tissue microstructure and its variations with respect to disease modifying therapies (DMTs) remains unclear. Here we investigated sex-based differences in lesion microstructure and its variations with therapeutic approaches in 52 relapsing-remitting MS patients using diffusion tensor, compartment, and orientation models. We found that men had greater myelin and axonal damage than women in MS lesions, and there was less axonal damage in women taking oral versus injectable DMTs. These results may support further investigations of sex-driven differences in disease monitoring and treatment choices to promote personalized medicine.

Pallab K Bhattacharyya¹, Robert Fox¹, Jian Lin¹, Paola Raska¹, Ken Sakaie¹, and Mark J Lowe^1
1Cleveland Clinic Foundation, CLEVELAND, OH, United States

It has been reported that structural and functional connectivity impairment of motor and cognitive network in multiple sclerosis (MS), as measured by diffusion tensor imaging (DTI) and functional connectivity (fcMRI) respectively, stabilize after one year of fingolimod treatment. Structural and functional connectivity index (SFCI), a combined metric of DTI and fcMRI has previously been demonstrated as a sensitive imaging-based measure of progression of MS. Change of (i) motor (ii) cognitive and (iii) pathway combined SFCI were tracked over 2-year fingolimod therapy of MS. SFCI stabilized after one year, which shows its effectiveness to measure disease progression following therapy .    

Lily Zexter¹, Thanh D. Nguyen², Elizabeth M. Sweeney³, Yi Wang², and Susan A. Gauthier^1
1Department of Neurology, Weill Cornell Medicine, New York, NY, United States, ²Department of Radiology, Weill Cornell Medicine, New York, NY, United States, ³Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, United States

Quantitative susceptibility mapping (QSM) provides an effective means to directly map the distribution of magnetic susceptibility sources, such as brain iron. In this study, we examined the relationship between initial QSM change and short-term myelin recovery, measured by myelin water fraction (MWF). The results showed that change in lesion susceptibility at three months was significantly and negatively associated with change in MWF at one year. This significant association provides evidence of the damaging effect of brain iron during early stages of lesion development.

Katherine A Koenig¹, Jian Lin¹, Daniel Ontaneda¹, Kedar Mahajan¹, Jenny Feng¹, Stephen Rao¹, Sanghoon Kim¹, Stephen Jones¹, and Mark J Lowe^1
1The Cleveland Clinic, Cleveland, OH, United States

Cognitive dysfunction is a common symptom of Multiple Sclerosis (MS), and patients would benefit from a measure that estimates their risk of future decline. Previous work suggests that hippocampal subfield volumes may have value as a predictive measure. Using 7 tesla MRI, we measured hippocampal volumes in 77 participants with MS. We found relationships between subfield volumes and future cognitive performance. These relationships were driven by relapse remitting MS patients, although the secondary progressive MS group did not show clear differences in the relationship patterns.

Irene Margaret Vavasour¹, Jackie T Yik^2,3, Pierre Becquart⁴, Jasmine Gill⁴, Shannon H Kolind^1,2,3,5, Alice J Schabas⁵, Ana-Luiza Sayao⁵, Virginia Devonshire⁵, Robert Carruthers⁵, Anthony Traboulsee⁵, GR Wayne Moore^3,4,5, Sophie Stukas⁴, Cheryl Wellington⁴, Jacqueline Quandt⁴, David KB Li¹, and Cornelia Laule^1,2,3,4
1Radiology, University of British Columbia, Vancouver, BC, Canada, ²Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ³International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada, ⁴Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, ⁵Medicine, University of British Columbia, Vancouver, BC, Canada

We characterized the frequency of diffusely abnormal white matter (DAWM) in a broad cohort of multiple sclerosis (MS) participants. 35% of clinically isolated syndrome (CIS) and ~60% of MS participants had DAWM. CIS with DAWM had smaller cortical thickness, higher lesion load and higher concentration of neurofilament light chain compared to CIS without DAWM. DAWM may be useful in identifying brains at risk of injury but only in the CIS population when lesion load is low. Longitudinal studies are warranted.

Gian Franco Piredda^1,2,3, Tom Hilbert^1,2,3, Manuela Vaneckova⁴, Jan Krasensky⁴, Michaela Andelova⁵, Tomas Uher⁵, Barbora Srpova⁵, Eva Kubala Havrdova⁵, Karolina Vodehnalova⁵, Dana Horakova⁵, Veronica Ravano^1,2,3, Bénédicte Maréchal^1,2,3, Jean-Philippe Thiran^2,3, and Tobias Kober^1,2,3
1Advanced Clinical Imaging Technology, Siemens Healthcare AG, Lausanne, Switzerland, ²Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, ³LTS5, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ⁴Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Poland, ⁵Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Poland

In multiple sclerosis, gradients of tissue damage severity were found in periventricular areas and proved to change in response to treatment. This work investigates whether these gradual microstructural changes can be detected with high-resolution, whole-brain quantitative T₁ mapping and how they compare between two cohorts of early and progressive multiple sclerosis patients. T₁ deviations were computed in patients from normative atlases established in a healthy cohort and corrected for age and gender. Results show that a periventricular gradient of abnormal T₁ values in normal-appearing white matter is indeed present and increases from early to progressive stages of the disease. 

Veronica Ravano^1,2,3, Gian Franco Piredda^1,2,3, Manuela Vaneckova⁴, Jan Krasensky⁴, Michaela Andelova⁵, Tomas Uher⁵, Barbora Srpova⁵, Eva Kubala Havrdova⁵, Karolina Vodehnalova⁵, Dana Horakova⁵, Tom Hilbert^1,2,3, Bénédicte Maréchal^1,2,3, Reto Meuli², Jean-Philippe Thiran^2,3, Tobias Kober^1,2,3, and Jonas Richiardi^2
1Advanced Clinical Imaging Technology, Siemens Healthineers, Lausanne, Switzerland, ²Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, ³LTS5, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ⁴Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic, ⁵Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

In multiple sclerosis, standard radiological metrics (i.e. lesion load) correlate poorly with clinical outcomes. To overcome this limitation, we propose a novel method to evaluate T₁ relaxometry abnormalities along thirty-seven major white matter pathways extracted from a tractography atlas, i.e. without needing a diffusion scan. Evaluating T₁ z-scores along WM tracts strongly improved correlation with disability compared to lesion load. The strongest correlations were found for T₁ abnormalities in normal-appearing white matter, especially in infratentorial tracts. These results suggest that diffuse pathological changes in normal-appearing WM measured along atlas-based tracts using T₁ relaxometry could aid clinical evaluation of multiple sclerosis.

Jason Michael Millward¹, Claudia Chien², Joseph Kuchling², Friedemann Paul², Thoralf Niendorf¹, and Sonia Waiczies^1
1Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, ²NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany

We used clinical high resolution 3T MRI to investigate brain ventricle changes over time in patients with clinically isolated syndrome (CIS) who are at the early stages of disease, which may eventually become multiple sclerosis. While most patients showed an overall increase in ventricle volume, 23% also showed contractions greater than the range of variation in healthy subjects, even over a period of years. Patients with contracting ventricles were significantly younger than those without. This suggests that, in addition to neurodegeneration, other processes are implicated that lead to a transient enlargement of the ventricles, which then later resolves.

Arzu Ceylan Has Silemek¹, Guido Nolte², Jana Pöttgen^1,3, Andreas K. Engel⁴, Christoph Heesen^1,3, Stefan M. Gold^1,5, and Jan-Patrick Stellmann^6,7
1Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center Eppendorf, Hamburg, Germany, ²Department of Neurophysiology and Pathophysiology, University Medical Center Eppendorf, Hamburg, Germany, ³Department of Neurology, University Medical Center Eppendorf, Hamburg, Germany, ⁴Institute of Neurophysiology and Pathophysiology, University Medical Center Eppendorf, Hamburg, Germany, ⁵Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany, ⁶CRMBM AMU-CNRS, Aix-Marseille Université, Marseille, France, ⁷CEMEREM, APHM, CHU Timone, Marseille, France

There is still substantial inconsistency between clinical disabilities and findings on brain networks and lack of longitudinal study in Multiple Sclerosis (MS). We aimed to elucidate how topology alters and how disability progression affects the structural and functional organizations over 2-years using graph theory approach in relapsing-remitting MS (RRMS). RRMS patients have encountered with lack of improvement in PASAT over 2-years. Structural connectivity was more sensitive to show a relationship with a cognitive function over 2-years than the rs-fMRI and MEG functional metrics in RRMS patients. These findings underline the difficulties associated with functional imaging studies in MS.

Maria Højberg Knudsen^1,2, Helle Juhl Simonsen¹, Jette Lautrup Battistini Frederiksen^2,3, Ulrich Lindberg¹, Mark Bitsch Vestergaard¹, Henrik Bo Wiberg Larsson^1,2, and Stig Præstekjær Cramer^1
1Dept. Clinical Physiology, Rigshospitalet, Glostrup, Denmark, ²Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark, ³Dept. of Neurology, Rigshospitalet, Glostrup, Denmark

Ineffective disease control in multiple sclerosis leads to permanent disability, and biomarkers for early detection of inadequate treatment response are needed. The potential of the patlak derived influx constant (Ki) as a biomarker was investigated in fifteen relapsing-remitting multiple sclerosis patients undergoing alemtuzumab treatment. The subjects underwent dynamic contrast enhanced MRI and 3DT1-weighted scans to assess Ki in grey and white matter before and after treatment. The treatment associated change in Ki in grey matter predicted disease activity within two years. Treatment associated changes in Ki may be used as a biomarker of treatment efficacy.

Kyle Jeong¹, You-Jung Lee¹, Suk-Keu Yeom², Noel Carlson³, Lubdha Shah⁴, John Rose⁵, and Eun-Kee Jeong^4
1Utah Center for Advanced Imaging research, University of Utah, Salt Lake City, UT, United States, ²Radiology, Korea University Ansan Hospital, Ansan, Korea, Republic of, ³GRECC, Veteran Affairs, Salt Lake City, UT, United States, ⁴Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, United States, ⁵Neuroimmunology Division, University of Utah, Salt Lake City, UT, United States

Ultrahigh-b radial DWI (UHb-rDWI) is an MRI technique that can quantitatively evaluate the MS lesions with respect to degrees of demyelination and axonal damage and/or loss. With the current lack of sensitive diagnostic imaging for grading cervical spinal cord (CSC) injury and repair, our UHb-rDWI can potentially serve as a powerful tool to observe cervical spinal cord once validated through animal studies. Therefore, the main objective of this study was to evaluate mouse spinal cords with and without demyelination using UHb-rDWI and immunohistochemical analyses to authenticate the reliability and reproducibility of UHb-rDWI.

Cristian Andrés Montalba^1,2,3, Tomás Labbe^4,5, Marcelo Andia^1,2,3, Miguel Guevara⁶, Jean-François Mangin⁷, Juan Pablo Cruz², Ethel Ciampi^8,9, Claudia Carcamo^5,8, Pamela Guevara⁶, and Sergio Uribe^1,2,3
1Biomedical Imaging Center, Pontificia Universidad Católica de Chile, Santiago, Chile, ²Radiology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile, ³Millennium Nucleus for Cardiovascular Magnetic Resonance, Santiago, Chile, ⁴School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile, ⁵Interdisciplinary Center of Neurosciences, Pontificia Universidad Católica de Chile, Santiago, Chile, ⁶Faculty of Engineering, Universidad de Concepción, Concepción, Chile, ⁷UNATI, Neurospin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France, ⁸Neurology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile, ⁹Neurology Service, Hospital Dr. Sótero del Río, Santiago, Chile

Multiple Sclerosis patients develop cognitive impairment at the earliest stages of the disease, with changes in cortical recruitment related to cognitive tasks. We evaluated the relation between information-processing speed performance with different diffusivity measurements in subcortical regions between healthy subjects and RRMS patients. We evaluated the FA, MD, RD, and AD diffusivity maps of U-fibers with PASAT test scores in healthy subjects and RRMS patients. PASAT test scores are significantly linear related to Frontal, Temporal, and Parietal cortical areas in healthy subjects. There is no linear relationship between PASAT test scores and diffusivity maps in RRMS patients.

Lucas Soustelle^1,2, Andreea Hertanu^1,2, Arnaud Le Troter^1,2, Soraya Gherib^1,2, Samira Mchinda^1,2, Patrick Viout^1,2, Lauriane Pini^1,2, Claire Costes^1,2, Sylviane Confort-Gouny^1,2, Adil Maarouf^1,2,3, Bertrand Audoin^1,2,3, Audrey Rico^1,2,3, Clémence Boutière^1,2,3, Maxime Guye^1,2, Jean-Philippe Ranjeva^1,2, Gopal Varma⁴, David C. Alsop⁴, Jean Pelletier^1,2,3, Guillaume Duhamel^1,2, and Olivier M. Girard^1,2
1Aix Marseille Univ, CNRS, CRMBM, Marseille, France, ²APHM, Hôpital Universitaire Timone, CEMEREM, Marseille, France, ³APHM, Hôpital Universitaire Timone, Service de neurologie, Marseille, France, ⁴Division of MR Research, Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

Characterization of Multiple Sclerosis (MS) is of paramount importance for patient care. In this work, we compare inhomogeneous (ihMT) and conventional magnetization transfer (MT) MRI techniques for white matter (WM) evaluation in a group comparison analysis after normalization in a standard space (templates of MS patients and healthy controls). Regions of interest, voxel-based morphometry and histogram analyses revealed that signal changes in pathological WM are not equivalent for ihMT and MT, highlighting that both metrics provide complementary information.

Marios C. Yiannakas¹, Ratthaporn Boonsuth¹, Carmen Tur^1,2, Marco Battiston¹, Francesco Grussu^1,3, Rebecca S. Samson¹, Torben Schneider⁴, Masami Yoneyama⁵, Ferran Prados^1,6,7, Sara Collorone¹, Rosanna Cortese¹, Olga Ciccarelli¹, and Claudia A. M. Gandini Wheeler-Kingshott^1,8,9
1NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Fuculty of Brain Sciences, University College London, London, United Kingdom, ²Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron Institute of Research, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain, ³Radiomics Group, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, ⁴Philips Healthcare, Surrey, Guildford, United Kingdom, ⁵Philips Japan, Minatoku, Tokyo, Japan, ⁶Centre for Medical Image Computing, Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, ⁷Universitat Oberta de Catalunya, Barcelona, Spain, ⁸Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy, ⁹Brain Connectivity Research Centre, IRCCS Mondino Foundation, Pavia, Italy

Whilst multiple sclerosis (MS) is thought to be a disease of the central nervous system, evidence from neuropathological investigations has demonstrated that the peripheral nervous system (PNS) can also be affected in MS, with demyelination and axonal degeneration being the main pathophysiological mechanisms involved. In this study, PNS damage is assessed in vivo at proximal (lumbar plexus) and distal (sciatic nerve) anatomical locations in people with relapsing-remitting MS and healthy controls using magnetisation transfer ratio (MTR). Results demonstrate significantly reduced MTR values at distal anatomical locations, however no relationship is identified between these changes and clinical scores of disability.

Refaat E Gabr¹ and Ponnada A Narayana^1
1Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, Houston, TX, United States

Deep neural network was used to automatically segment diffusely abnormal white matter (DAWM) in 100 relapsing remitting multiple sclerosis patients (RRMS). Our calculated DAWM prevalence of 32% is comparable to ~ 25% reported elsewhere.  Based on our studies, only 13% of T2 lesions at baseline converted into DAWM by 60 months. Of the DAWM detected at baseline, only 15% converted to lesions, 45% persisted, and 40% resolved (converted to NAWM). These initial results suggest that DAWM may present a significant disease burden by itself.

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

This study investigates the temporal evolution of iron content and concentration in thalamic nuclei of patients with multiple sclerosis over two years. Both metrics declined significantly relative to controls in the pulvinar. Pulvinar iron may potentially serve as an imaging biomarker for oligodendroglial vitality in MS.

Fedel Machado-Rivas^1,2, Camilo Jaimes^1,2, Benoit Scherrer^1,2, Mark Gorman^1,2, Simon K Warfield^1,2, and Onur Afacan^1,2
1Radiology, Boston Children's Hospital, Boston, MA, United States, ²Radiology, Harvard Medical School, Boston, MA, United States

DTI has been used to evaluate brain microstructure in MS lesions and normal appearing white matter (NAWM). A DIAMOND model with an isotropic compartment + an anisotropic compartment may help disentangle the individual contribution of the compartments arising within a voxel, more accurately reflecting changes in the WM microstructure. In addition to finding differences in cAD, cRD, cMD and cFA, compartment diffusion model heterogeneity index was found to be significantly different in lesions. Our results support that a DIAMOND analysis can provide insights to MS lesion microstructure beyond conventional DTI metrics.

Øystein Bech Gadmar¹, Anne-Hilde Farstad², Berit Elstad², Piotr Sowa², and Wibeke Nordhøy^1
1Diagnostic Physics, Oslo University Hospital, Oslo, Norway, ²Radiology, Oslo University Hospital, Oslo, Norway

A MatLab-based inversion recovery sequence simulator/calculator was developed with the purpose of determining and testing optimal parameters for 3D IR acquisitions with the purpose of detecting Multiple Sclerosis lesions in brains. Single inversion FLAIR and dual inversion DIR sequences were studied including a “True-T2” DIR sequence removing the undesired T1 weighting inherent in IR sequences to improve lesion-WM contrast. A T2 preparation phase further helps facilitate T1 suppression. Optimized IR sequences were tested on healthy volunteers and some MS patients, on 1.5 T and 3.0 T MR scanners. Good lesion contrast efficiency with high SNR was found for True-T2 DIR.

Ivan Jambor¹, Aida Steiner², Marko Pesola³, Timo Liimatainen⁴, Marcus Sucksdorff³, Eero Rissanen ², Laura Airas², Hannu Aronen³, and Harri Merisaari^3
1Icahn School of Medicine at Mount Sinai, New York, NY, United States, ²Turku University Hospital, Turku, Finland, ³University of Turku, Turku, Finland, ⁴University of Oulu, Oulu, Finland

In this single center prospective clinical trial, we have shown feasibility of whole brain of T1ρadiab and TRAFF2 at 3T. Both of these methods provided higher lesion-to-normal appearing white matter contrast compared with conventional used T1-weighted imaging, and demonstrated potential to predict multiple sclerosis disease severity scores (EDSS, MSSS) at the time of imaging and 1-year follow-up. These encouraging findings stimulate further application of T1ρadiab and TRAFF2 at 3T in patients with multiple sclerosis.

Alina Lopatina^1,2, Stefan Ropele³, Renat Sibgatulin¹, Jürgen R Reichenbach^1,2,4, and Daniel Güllmar^1
1Medical Physics Group / IDIR, Jena University Hospital, Jena, Germany, ²Michael-Stifel-Center for Data-Driven and Simulation Science, Jena, Germany, ³Department of Neurology, Medical University of Graz, Graz, Austria, ⁴Center of Medical Optics and Photonics Jena, Jena, Germany

To analyze the classification procedure of identifying multiple sclerosis (MS) based on diffusion-weighted imaging data by using convolutional neural networks (CNNs), we generated relevance maps. The relevance maps indicate the contribution of each input voxel to the final classification score and may facilitate new findings regarding MS-specific biomarkers. The study showed that voxels in the central brain area including some of the lesion voxels are important for correct classification. This information may be used in the future to perform a more detailed analysis in order to classify different MS-phenotypes or predict disease progression.