Nicholas John Eichner¹, Reza Rahmanzadeh¹, Matthias Weigel¹, Muhamed Barakovic¹, Po-Jui Lu¹, Ludwig Kappos¹, Pascal Sati², Daniel S. Reich², Yi Wang³, Jens Kuhle¹, and Cristina Granziera^1
1Department of Biomedical Engineering, University of Basel, Basel, Switzerland, ²National Institute of Neurological Disordes and Stroke, Bethesda, MD, United States, ³Cornell University, Ithaca, NY, United States

We assessed the presence and extent of cortical abnormalities in patients with relapsing remitting and progressive multiple sclerosis by using surface-based quantitative susceptibility mapping and T1 relaxometry analysis. Our results showed that QSM and T1 maps acquired at 3T MRI are sensitive to cortical damage in MS patients and reveal more extensive areas of alterations in progressive than in relapsing-remitting MS. Changes in cortical QSM and T1 suggest chronic demyelination and possibly iron accumulation.

Giuseppe Pontillo¹, Sirio Cocozza¹, Serena Monti², Maria Petracca³, Roberta Lanzillo³, Vincenzo Brescia Morra³, Arturo Brunetti¹, and Giuseppe Palma^2
1Department of Advances Biomedical Sciences, University of Naples "Federico II", Naples, Italy, ²Institute of Biostructures and Bioimaging, National Research Council, Napoli, Italy, ³Department of Neurosciences and Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples, Italy

Alterations of magnetic susceptibility are known to occur in the deep gray matter (DGM) of multiple sclerosis (MS) patients, reflecting a mixture of atrophy, iron and myelin changes. We combined the analysis of quantitative susceptibility mapping (QSM) and R1 relaxometry contrasts in order to obtain iron- and myelin-specific maps, from which we estimated mean iron and myelin concentrations as well as total iron and myelin contents for each DGM structure. We found increased mean iron in the basal ganglia of MS patients compared to healthy controls, probably reflecting atrophy-related concentration, along with actual atrophy-independent iron depletion phenomena in the thalamus.

Vanessa Wiggermann^1,2, Shawna Abel³, Irene M Vavasour⁴, Enedino Hernández-Torres³, Christian Kames^1,2, David KB Li^4,5, Roger Tam^4,5, Shannon H Kolind^1,3, Anthony Traboulsee³, and Alexander Rauscher^1,2
1Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ²Pediatrics, University of British Columbia, Vancouver, BC, Canada, ³Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada, ⁴Radiology, University of British Columbia, Vancouver, BC, Canada, ⁵MS/MRI Research (Neurology), University of British Columbia, Vancouver, BC, Canada

Abnormalities seen on clinical MRIs in the brain and spinal cord of multiple sclerosis (MS) patients lack specificity to myelin. Thus, efficacy of new treatments that aim to protect or remyelinate cannot be fully captured. Quantitative MR metrics, such as R₂* and quantitative susceptibility mapping (QSM), have demonstrated good sensitivity to myelin and iron-related tissue changes, but the clinical relevance of such changes has not yet been assessed. We showed that R₂* provides good group-wise distinction of MS patients and controls, while QSM values reflected clinically meaningful variations in upper and lower motor function as well as cognitive processing speed.

Jung-Jiin Hsu¹, Jung-Yu C. Hsu², and Roland G. Henry^1
1Department of Neurology, University of California San Francisco, San Francisco, CA, United States, ²Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan

Magnetization transfer (MT) is of great interest in clinical and pre-clinical imaging to probe tissue properties that cannot be visualized directly with conventional MRI. Current research and development of MT MRI is based on the chemical exchange mechanism. However, it has long been reported that, instead of chemical exchange, the cross-relaxation mechanism is responsible for MT in biological tissue. In this work, a fast MRI method is developed based on cross relaxation for the measurement of the spin–lattice relaxation rate and the MT rate and is applied to characterize multiple sclerosis lesions.

Fahad Salman¹, Robert Zivadinov^1,2, Niels Bergsland³, Michael G. Dwyer¹, Bianca Weinstock Guttman⁴, and Ferdinand Schweser^1,5
1Neuroimaging, Buffalo Neuroimaging Analysis Center, Buffalo, NY, United States, ²MRI Clinical and Translational Research Center, Buffalo, NY, United States, ³Neurology, Buffalo Neuroimaging Analysis Center, Buffalo, NY, United States, ⁴Neurology, Jacobs Comprehensive MS Center for Treatment & Research, Buffalo, NY, United States, ⁵Neurology, MRI Clinical and Translational Research Center, Buffalo, NY, United States

Several recent cross-sectional studies have observed decreasedmagnetic susceptibility in the thalamus of patients with multiple sclerosis (MS) using Quantitative Susceptibility Mapping (QSM).However, the concavity of the iron concentration trajectory in normal aging renders the interpretation of findings of the previous studies difficult. In the present work, we applied QSM longitudinally in conjunction with a dedicated analysis procedure to obtain optimal longitudinal measurement accuracy. Our longitudinal results confirm previous cross-sectional findings and suggest that thalamic QSM may serve as an imaging marker for disease progression in MS.

Gibran Manasseh¹, Mário João Fartaria^2,3,4, Tom Hilbert², Jérémy Deverdun⁵, Meritxell Bach Cuadra⁶, Philippe Maeder¹, Patric Hagmann¹, Tobias Kober², and Vincent Dunet^1
1Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, ²Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne; Siemens Healthcare AG; École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ³Advanced Clinical Imaging Technology, Siemens Healthcare AG, Lausanne, Switzerland, ⁴Signal Processing Laboratory (LTS 5), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ⁵I2FH, Institut d'Imagerie Fonctionnelle Humaine, Montpellier University Hospital Center, Gui de Chauliac Hospital, Montpellier, France, ⁶Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne; École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

Quantitative susceptibility mapping is an emerging MRI technique that may provide additional information on brain tissue with potential applications in multiple sclerosis characterization and monitoring. However, the link between tissue susceptibility and disease evolution is not well known. This study investigates the relationship between basal ganglia, thalamus and normal appearing white matter susceptibility and lesion load, based on a fully automated pipeline for lesion and brain segmentation. Significant correlations were found between lesion load and susceptibility in putamen, thalamus, and white matter, presumably due to myelin loss in basal ganglia and iron loss in normal appearing white matter and thalamus.

Jiahao Li¹, Weiyuan Huang², Xianfu Luo², Thanh D. Nguyen², Susan A. Gauthier², Pascal Spincemaille², and Yi Wang^1,2
1Biomedical Engineering, Cornell University, Ithaca, NY, United States, ²Radiology, Weill Cornell Medicine, New York, NY, United States

The central vein sign (CVS) has been suggested as a potential biomarker for multiple sclerosis (MS) lesion detection and differential diagnosis. A major hurdle for clinical investigation of CVS of MS lesion is the lack of high-quality visualization on current MRI. In this work, we propose a Susceptibility Relaxation based Optimization (SRO) method that uses routinely acquired multi-echo gradient echo magnitude and phase data to generate an image with optimal CVS contrast while preserving lesion signal. Preliminary qualitative and quantitative results demonstrate that SRO provides superior MS lesion and CVS detection compared to prior methods.

Elizabeth N. York¹, Rozanna Meijboom¹, Nicole White¹, Maria Valdes Hernandez¹, Michael J. Thrippleton¹, Peter Connick¹, and Adam Waldman^1
1Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom

Magnetization transfer saturation (MTsat) is a quantitative measure of white matter (WM) integrity with inherent correction for B₁ inhomogeneities and T₁ relaxation. MTsat is sensitive to pathological changes in axonal myelin in multiple sclerosis (MS) and may predict clinical disability. MTsat within normal-appearing WM and WM hyperintensities was measured in 76 patients with recently diagnosed relapsing-remitting MS. After accounting for age, MTsat in normal-appearing WM, but not WM hyperintensities, predicted clinical disability (as assessed by Multiple Sclerosis Functional Composite z-scores) in MS when central tendency and standard deviation were considered. This suggests MTsat is sensitive to early MS pathology.

Xixi Yang^1,2,3,4, Martina D Liechti^1,2, Baris Kanber^3,5, Carole H Sudre^5,6,7, Gloria Castellazzi^3,8, Jiaying Zhang^9,10,11, Marios C Yiannakas³, Gwen Gonzales², Ferran Prados Carrasco^3,5,12, Ahmed T Toosy³, Claudia A. M. G Wheeler-Kingshott^3,13,14, and Jalesh N Panicker^1,2
1Department of Brain Repair & Rehabilitation, UCL Queen Square Institute of Neurology, London, United Kingdom, ²Department of Uro-Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom, ³NMR Research Unit, UCL Queen Square MS Centre, London, United Kingdom, ⁴Department of Neurology, Xuan Wu Hospital of Capital Medical University, Beijing, China, ⁵Centre for Medical Image Computing, UCL Department of Medical Physics and Bioengineering, London, United Kingdom, ⁶School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom, ⁷Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom, ⁸Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy, ⁹Department of Perinatal Imaging & Health, School of Biomedical Engineering & Imaging Sciences, King’s College London, London, United Kingdom, ¹⁰King’s Health Partners, St Thomas’ Hospital, London, United Kingdom, ¹¹Department of Computer Science and Centre for Medical Image Computing, University College London, London, United Kingdom, ¹²Universitat Oberta de Catalunya, Barcelona, Spain, ¹³Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy, ¹⁴Brain MRI 3T Center, IRCCS Mondino Foundation, Pavia, Italy

White matter (WM) abnormalities subtending overactive bladder (OAB) symptoms in multiple sclerosis (MS) is poorly understood. MS patients with and without OAB symptoms were recruited to investigate the association between WM changes and OAB symptoms in MS. Lower FA were found in MS with OAB compared with MS without LUTS (p=0.072). An inverse correlation was found between FA and OAB severity (p=0.021) in MS. OAB symptoms are associated with WM anisotropy changes in MS as demonstrated by diffusion-weighted imging (DWI).

Muhamed Barakovic^1,2, Reza Rahmanzadeh^1,2, Po-Jui Lu^1,2,3, Pietro Maggi^4,5, Pascal Sati⁶, Daniel Reich⁶, Francesco La Rosa^7,8, Meritxell Bach Cuadra^7,9, Simona Schiavi¹⁰, Alessandro Daducci¹⁰, Jens Kuhle¹, Matthias Weigel^1,2,11, Ludwig Kappos¹, and Cristina Granziera^1,2
1Translational Imaging in Neurology (ThINk) Basel, Department of Medicine and Biomedical Engineering, University Hospital Basel and University of Basel, Neurologic Clinic and Policlinic, Basel, Switzerland, ²Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland, ³Digital Technology and Innovation Siemens Healthineers, Princeton, NJ, United States, ⁴Department of Neurology, Saint-Luc University Hospital,Université Catholique de Louvain, Bruxelles, Belgium, ⁵Department of Neurology, Lausanne University and University Hospital, Lausanne, Switzerland, ⁶Translational Neuroradiology Section, Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States, 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, Basel, Switzerland, ⁹Radiology Department, Center for Biomedical Imaging, Lausanne University and University Hospital Lausanne, Lausanne, Switzerland, ¹⁰Department of Computer Science, University of Verona, Verona, Italy, ¹¹Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland

In this study, we implemented seven microstructure models based on diffusion-weighted MRI data and investigated their sensitivity in assessing between-lesion differences in axonal content in multiple sclerosis lesions. The result of the analysis showed that all the models selected report lower intracellular volume fraction in white matter lesions compared to normal-appearing white matter. Few of the methods highlighted high sensitivity; however, they also show a different spectrum of ranges in terms of intracellular volume fraction. Whether one of the methods reflect a reliable assessment will be addressed in further studies using postmortem material.

Veronica Ravano^1,2,3, Michaela Andelova⁴, Mazen Fouad A-Wali Mahdi¹, Reto Meuli², Tomas Uher⁴, Jan Krasensky⁵, Manuela Vaneckova⁵, Dana Horakova⁴, Tobias Kober^1,2,6, and Jonas Richiardi^1,2
1Advanced Clinical Imaging Technology, Siemens Healthcare, Lausanne, Switzerland, ²Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, ³Medical Imaging Processing, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ⁴Department of Neurology and Center of Clinical Neuroscience First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic, ⁵MR unit, Department of Radiology First Facutly of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic, ⁶LTS5, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

In multiple sclerosis, the standard radiological metrics correlate poorly with clinical disability (‘clinico-radiological paradox’). To help filling this gap, we propose to map neurological impairments to white matter tract damage resulting from lesions. Because diffusion imaging is typically not part of multiple sclerosis clinical workups, quantitative tract damage metrics were extracted using a tractography atlas and an automated lesion segmentation algorithm.

We were able to successfully identify which functional system (EDSS sub-score) was affected by damage on given tracts. These findings suggest the usefulness of using our fully automated atlas-based approach to study mechanisms of neurological diseases.

Sean P Devan^1,2, Xiaoyu Jiang^1,3, Francesca Bagnato⁴, and Junzhong Xu^1,3,5,6
1Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United States, ²Chemical and Physical Biology Program, Vanderbilt University, Nashville, TN, United States, ³Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ⁴Neuroimaging Unit/Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States, ⁵Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, ⁶Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, United States

Multi-compartment diffusion imaging using the spherical mean technique (SMT) is a recently developed method that provides more specific information for probing axonal properties in e.g., multiple sclerosis (MS) patients. However, the accuracy and precision of SMT have not been comprehensively investigated to date. We used Cramér-Rao Lower Bound (CRLB) analysis and MS patient data to optimize an SMT acquisition protocol for practical MS imaging. Second, we used computer simulations to comprehensively evaluate the accuracy and precision of SMT for reporting axonal information under various pathologic conditions. The results support better implementation and interpretation of SMT imaging for MS patients.  

Xuemei Huang¹, Ken E. Sakaie¹, Jian Lin¹, Robert J. Fox¹, and Mark J. Lowe^1
1Imaging Institute, U-15, Cleveland Clinic, Cleveland, OH, United States

Diffusion Tensor Imaging (DTI) analysis was performed in the multi-site phase II trial of ibudilast in progressive multiple sclerosis. This study extends that analysis to three pathways to examine DTI measures in 31 progressive MS patients on treatment and 31 patients on placebo. Probabilistic tracking maps were generated. Mean pathway diffusion measures: longitudinal diffusivity (LD) and transverse diffusivity (TD) are reported. We report here that diffusion measures don’t significantly change over time in the treatment group but we observe a significant change over time in the placebo group.
 

Cristian Montalba^1,2,3, Mariana Zurita^1,4, Tomás Labbé^1,5, Marcelo Andia^1,2, Miguel Guevara⁶, Jean-François Mangin⁷, Juan Pablo Cruz², Ethel Ciampi^8,9, Claudia Cárcamo^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, ⁴Institute of Cognitive Neuroscience, University College London, London, UK., London, United Kingdom, ⁵Interdisciplinary Center of Neurosciences, Pontificia Universidad Católica de Chile, Santiago, Chile, ⁶Faculty of Engineering, Universidad de Concepción, Concepción, Chile, 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, Santiago, Chile

We evaluated different diffusivity measurements of subcortical regions that can be related with different test scores in FAS, SDMT and PASAT test. For this purpose, we evaluated the FA, MD, RD and AD diffusivity maps of U-fibers with the test scores in healthy subjects and RRMS patients. In our sample, FAS test scores are significant linear related with Postcentral gyrus with RD and MD maps in RRMS patients. PASAT test scores are significant linear related with Precentral gyrus with FA and RD maps in healthy subjects. There is no linear relationship between SDMT test score and diffusivity maps.

Daniel Güllmar¹, Renat Sibgatulin¹, Stefan Ropele², and Jürgen R Reichenbach^1,3
1Medical Physics Group / IDIR, Jena University Hospital, Jena, Germany, ²Department of Neurology, Medical University of Graz, Graz, Austria, ³Michael-Stifel-Center for Data driven sciences, Friedrich-Schiller-University Jena, Jena, Germany

Quantitative MR diffusion imaging in multiple sclerosis is a promising tool for deciphering the mechanisms and processes during the disease progression. We employed new MR diffusion acquisition techniques (like SMS) as well as advanced post-processing (like NODDI, SMT) in order to investigate the differences in normal appearing white matter of MS patients in contrast to healthy volunteers.

Pallab K Bhattacharyya^1,2, Robert Fox³, Jian Lin¹, Hong Li⁴, Ken Sakaie¹, and Mark Lowe^1
1Imaging Institute, Cleveland Clinic, Cleveland, OH, United States, ²Radiology, Cleveland Clinic Lerner College of Medicine, CLEVELAND, OH, United States, ³Neurological Institute, Cleveland Clinic, Cleveland, OH, United States, ⁴Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, United States

Paced auditory serial addition test (PASAT) and symbol digit modalities test (SDMT) are two most commonly used tests to evaluate cognitive performance in MS. The specificity of the two tests to cognitive network in brain was evaluated with diffusion tensor imaging and correlating transverse diffusivity (TD) along different functionally relevant pathways with PASAT/SDMT scores. While SDMT showed association with TD along all pathways (and whole brain white matter), PASAT was associated with only frontoparietal pathway, establishing its specificity to cognitive network.

Maria Teresa Cassiano¹, Roberta Lanzillo², Bruno Alfano³, Teresa Costabile², Marco Comerci³, Anna Prinster³, Marcello Moccia², Rosario Megna³, Vincenzo Brescia Morra², Arturo Brunetti¹, and Mario Quarantelli^3
1Department of Advanced Biomedical Sciences, University "Federico II", Naples, Italy, ²Department of Neurosciences, Reproductive Science and Odontostomatology, University "Federico II", Naples, Italy, ³Biostructure and Bioimaging Institute, National Research Council, Naples, Italy

To assess voxelwise in gray matter the correlation between relaxation rates and both physical and cognitive impairment in MS, R1 and R2 relaxation rate maps from 241 Relapsing-Remitting MS patients were assessed voxelwise for correlation with EDSS and the percentage of impaired cognitive test.

Inverse correlation between EDSS and R2 were detected throughout the brain, while inverse correlations with R1 were mostly limited to perirolandic and supramarginal cortices.

Cognitive impairment correlated negatively with R1, and to a lesser extent with R2, in the limbic system and dorsolateral prefrontal cortices.

Paola Valsasina¹, Maria A. Rocca^1,2, Milagros Hidalgo de la Cruz¹, Claudio Gobbi³, Antonio Gallo⁴, Chiara Zecca³, Alvino Bisecco⁴, and Massimo Filippi^1,2,5
1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy, ²Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy, ³Department of Neurology, Neurocenter of Southern Switzerland, Civic Hospital, Lugano, Switzerland, ⁴Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, University of Campania “Luigi Vanvitelli”, Naples, Italy, ⁵Vita-Salute San Raffaele University, Milan, Italy

In this study, we used cortical thickness analysis to investigate the evolution over time of cortical grey matter atrophy in a multicenter cohort of patients with multiple sclerosis (MS) acquired at 3 European sites. We detected a different susceptibility to cortical damage across the different clinical phenotypes of MS, with the involvement of temporal, parietal and occipital regions in relapsing-remitting MS, and an additional frontal involvement in progressive MS. Different annualized cortical thinning rates were found across MS clinical phenotypes. Cortical thinning in frontal and temporal areas was crucial for identifying patients with more severe disability at follow-up.

Fanny Munsch¹, Gopal Varma¹, Manuel Taso¹, Shahamat Tauhid², Olivier M. Girard³, Guillaume Duhamel³, Rob Bakshi⁴, and David Alsop^1
1Radiology, Division of MRI Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ²Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States, ³CRMBM, Aix Marseille Univ, CNRS, Marseille, France, ⁴Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

Inhomogeneous magnetization transfer (ihMT) and magnetization transfer (MT) have differential sensitivity to myelin and can be used to characterize cortical gray matter. We compared cortical surface-based analyses of ihMT and MT between multiple sclerosis (MS) patients and age-matched healthy volunteers. IhMT at mid-thickness decreased less than MT in most cortical regions of MS patients. Integrated signal across cortical depth showed less spatial variability and clear decrease of ihMT but less than MT. As ihMT is understood to be more specific to myelin than MT, these findings suggest loss of cortical nonmyelinated cells and structures exceed cortical myelin loss in MS. 

Vivek Shriram Murumkar¹, Jitender Saini¹, Nethravati Manjunath², Dhritiman Chakraborty³, and Rakesh Gupta^4
1Neuroimaging and interventional radiology, national institute of mental health and neuroscineces (NIMHANS) bangalore, india, Bangalore, India, Bangalore, India, ²Neurology, national institute of mental health and neuroscineces (NIMHANS) bangalore, india, Bangalore, India, Bangalore, India, ³Neuroanaesthesia, national institute of mental health and neuroscineces (NIMHANS) bangalore, india, Bangalore, India, Bangalore, India, ⁴radiology, Fortis Hospital, Gurugram, India

Optic neuritis is presenting feature in 15-20% cases of MS and 50% cases of MS have optic neuritis during course of illness. Signals from CSF and intraorbital fat are main hurdles in optic nerve imaging, 3D FLAIR and 3D DIR are used to study optic nerve pathologies as they suppress fat and CSF signals. DIR nulls signal from NAWM providing inherent contrast. 3D DIR and 3D FLAIR was done in 31 case of acute optic neuritis and 30 controls. We found higher contrast rates, sensitivity and negative predictive value for the 3D DIR than 3D FLAIR in acute optic neuritis

Marios C. Yiannakas¹, Marco Battiston¹, Francesco Grussu^1,2, Ratthaporn Boonsuth¹, Rebecca S. Samson¹, Torben Schneider³, Masami Yoneyama⁴, Ferran Prados^1,5,6, Carmen Tur¹, Sara Collorone¹, Rosanna Cortese¹, Olga Ciccarelli¹, and Claudia A.M. Gandini Wheeler-Kingshott^1,7,8
1Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, United Kingdom, ²Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom, ³Philips Healthcare, Guildford, Surrey, United Kingdom, ⁴Philips Japan, Minatoku, Tokyo, Japan, ⁵Centre for Medical Image Computing, Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, ⁶Universitat Oberta de Catalunya, Barcelona, Spain, ⁷Brain MRI 3T Research Centre, IRCCS Mondino Foundation, Pavia, Italy, ⁸Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy

Evidence from histopathological studies has demonstrated the involvement of the peripheral nervous system in multiple sclerosis (MS), specifically alteration in myelin content and, to a lesser extent, axonal degeneration. However, evidence from objective investigations in vivo is lacking. In this pilot study, the lumbar plexus and the sciatic nerve are investigated in people with MS using a previously optimised magnetisation transfer ratio (MTR) protocol developed in healthy controls. Results demonstrate reduced MTR values in both anatomical regions studied, consistent with histopathological data, and as such highlighting a need for further investigations in a larger sample population.

Marios C. Yiannakas¹, Francesco Grussu^1,2, Marco Battiston¹, Ratthaporn Boonsuth¹, Rebecca S. Samson¹, Torben Schneider³, Masami Yoneyama⁴, Ferran Prados^1,5,6, Carmen Tur¹, Sara Collorone¹, Rosanna Cortese¹, Olga Ciccarelli¹, and Claudia A. M. Gandini Wheeler-Kingshott^1,7,8
1Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, United Kingdom, ²Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom, ³Philips Healthcare, Guildford, Surrey, United Kingdom, ⁴Philips Japan, Minatoku, Tokyo, Japan, ⁵Centre for Medical Image Computing, Medical Physics and Biomedical Engineering, University College London, London, United Kingdom, ⁶Universitat Oberta de Catalunya, Barcelona, Spain, ⁷Brain MRI 3T Research Centre, IRCCS Mondino Foundation, Pavia, Italy, ⁸Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy

Ex vivo investigations have demonstrated the involvement of the peripheral nervous system in multiple sclerosis (MS). However, the use of advanced imaging methods to study individual peripheral nerves in vivo, such as the sciatic nerve, has been hindered by a number of technical challenges. In this pilot in vivo study, we explore the feasibility of acquiring multi-shell diffusion-weighted imaging (DWI) metrics in the sciatic nerve of people with relapsing-remitting MS (RRMS) using reduced field-of-view echo planar imaging. DWI metrics in people with RRMS display changes in comparison to healthy controls, suggesting that the structural integrity of the nerve is compromised.

Irene Margaret Vavasour^1,2, Lisa Eunyoung Lee³, Adam V Dvorak^2,4, Shawna Abel³, Poljanka Johnson³, Stephen Ristow³, Cornelia Laule^1,2,4,5, Roger Tam^1,6, David KB Li^1,3, Nathalie Ackermans³, Alice Schabas³, Jillian Chan³, Ana-Luiza Sayao³, Virginia Devonshire³, Robert Carruthers³, Anthony Traboulsee³, and Shannon H Kolind^1,2,3,4
1Radiology, University of British Columbia, Vancouver, BC, Canada, ²International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada, ³Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada, ⁴Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ⁵Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, ⁶School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada

Damage to the spinal cord is common in multiple sclerosis (MS) and is an important contributor to physical disability. While spinal cord cross sectional area (CSA) is correlated with disability, CSA is a non-specific measure of tissue damage. The addition of cervical cord myelin water imaging, which measures myelin-related abnormalities, to cord area resulted in better correlations with MS clinical disability than cord CSA alone. In particular, myelin abnormality + CSA was best correlated with 9-hole peg test which requires more fine motor skills and therefore could be strongly influenced by damage to white matter.

Kristin P. O'Grady^1,2, Kurt G. Schilling², Mereze Visagie², Sanjana Satish², Shekinah Malone³, Atlee Witt², Anna Combes², Richard Dylan Lawless^2,4, Colin D. McKnight¹, Francesca R. Bagnato⁵, and Seth A. Smith^1,2,4
1Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ²Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United States, ³Meharry School of Medicine, Meharry Medical College, Nashville, TN, United States, ⁴Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, ⁵Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States

Spinal cord pathology is integral to disease symptoms and progression in multiple sclerosis (MS), but imaging methods developed and optimized for studying the spinal cord in vivo with clinically relevant scan times are lacking. Here, we applied a clinically feasible diffusion tensor imaging (DTI) sequence to examine relationships between imaging measures of microstructural damage in the spinal cord and lower extremity functional deficits in low-disability, relapsing-remitting MS patients. Our results show significant correlations between gray matter radial diffusivity and measures of sensation and motor function.

Nico Papinutto¹, Shuiting Cheng¹, Mahir Khan¹, Jung-Jiin Hsu¹, and Roland G Henry^1
1UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, United States

Acquiring images on a phantom and 54 multiple sclerosis patients, we explored the feasibility of T₁ mapping using a fast 2D inversion recovery method based on a TrueFISP sequence. We also explored the relationship between T₁ values and the intensity of 2D PSIR images. The fast T₁ mapping method was shown to be precise, and PSIR intensities shown to have a strong correlation with T₁. PSIR has been extensively used to segment in-vivo gray and white matter tissues in the spinal cord, and this study suggests that it can simultaneously provide microscopic information related to the longitudinal relaxation time T₁.

Richard D Lawless^1,2, Kristin O'Grady^1,3, Mereze Visagie¹, Anna Combes¹, Haley Feiler¹, Francesca Bagnato⁴, and Seth A. Smith^1,2,3
1Vanderbilt University Institute of Imaging Sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ²Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, ³Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ⁴Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States

Spinal cord damage in multiple sclerosis often leads to the formation of inflammatory lesions. APT CEST has been proposed as an MRI biomarker capable of detecting the underlying biochemical changes associated with lesion formation, however, CEST findings are susceptible to confounding influences such as the macromolecular magnetization transfer contribution and changes to longitudinal relaxation. AREX is a proposed method which corrects for these contributors and may improve measurement of the CEST component in vivo. In this study we sought to compare MT- and T1-corrected AREX to an uncorrected CEST quantification method in SC lesions of MS patients.

Elisabetta Pagani¹, Raffaello Bonacchi^1,2, Alessandro Meani¹, Laura Cacciaguerra^1,2, Ermelinda De Meo^1,2, Paolo Preziosa^1,2, Maria A. Rocca^1,2, and Massimo Filippi^1,2,3
1Neuroimaging Research Unit, Institute of Experimental Neurology, 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

Cervical spinal cord involvement is common in multiple sclerosis (MS). We performed a comprehensive multiparametric MRI study to explore pathophysiological substrates of damage and to identify the most accurate imaging predictors of disability and disease course. We found that the processes contributing to disability differ according to the stage of the disease. In relapsing-remitting MS patients, lesions and microstructural damage to cervical spinal cord tracts have a prominent role, whereas in progressive MS patients, cervical cord grey matter atrophy becomes clinically meaningful.

Marco Battiston¹, Carmen Tur^1,2, Marios C. Yiannakas¹, Francesco Grussu^1,3, Torben Schneider⁴, Daniele Martinelli⁵, Baris Kanber⁶, Ferran Prados^1,6,7, Patrizia Pajak¹, Olga Ciccarelli¹, Rebecca S. Samson¹, and Claudia A.M. Gandini Wheeler-Kingshott^1,8,9
1NMR Research Unit, UCL Queen Square MS Centre, Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, United Kingdom, ²Neurology Department, , Luton and Dunstable University Hospital, Luton, United Kingdom, ³Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom, ⁴Philips Healthcare, Guilford, United Kingdom, ⁵IRCCS Mondino Foundation, Pavia, Italy, 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 MRI 3T Center, IRCCS Mondino Foundation, Pavia, Italy

Multiple Sclerosis (MS) is a complex disease whose mechanisms of progression still remain unclear. The use of quantitative MRI techniques in a multi-modal fashion, i.e. acquisition of more than one contrast type, can help to non-invasively measure changes in the tissue at a microstructural level during the disease course. Moreover, evidence of spinal cord involvement and its role in the diagnosis and prognosis is mounting. Here, we aim to address both needs by developing a multi-modal qMRI protocol for joint investigation of brain and spinal cord microstructure, and we report findings from a small cohort of people with MS.

Sanuji Gajamange¹, Frederique Boonstra², Gustavo Noffs^1,3, Thushara Perera^1,4, Vilija Jokubaitis², Adam Vogel^1,4,5, Andrew Evans^3,4, Helmut Butzkueven², Anneke van der Walt², and Scott Kolbe^2
1The University of Melbourne, Melbourne, Australia, ²Monash University, Melbourne, Australia, ³Royal Melbourne Hospital, Melbourne, Australia, ⁴The Bionics Institute, Melbourne, Australia, ⁵University of Tübingen, Tübingen, Germany

Cerebellar dysfunction is a common feature of multiple sclerosis (MS), leading to disabling symptoms such as tremor. In MS, brain atrophy is the most accepted correlate of neurodegeneration; however cerebellar atrophy does not seem to correlate with the degree of cerebellar dysfunction. Here we explore axonal degeneration, a key driver of disability, with a fibre-specific marker based on diffusion-weighted MRI – fibre density and fibre bundle cross-section. We found that loss of cerebellar fibre density and fibre cross-section was associated with increased clinical cerebellar dysfunction. Fibre-specific measures could provide a useful marker of cerebellar dysfunction in MS.  

Refaat E Gabr¹, Luning Wang², John A Lincoln³, and Ponnada A Narayana^1
1Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, Houston, TX, United States, ²Philips healthcare, Gainesville, FL, United States, ³Neurology, University of Texas Health Science Center at Houston, Houston, TX, United States

Detection of infratentorial lesions is important for diagnosis of multiple sclerosis. However, infratentorial lesions are hard to detect on conventional FLAIR protocols. In this work, we optimized the refocusing flip angle in the turbo spin echo readout of 3D FLAIR to enhance infratentorial lesion contrast in individual patients. T1, T2, and proton density measured in the brain stem and cortical gray matter were used to calculate the refocusing angle that maximizes the contrast-to-noise ratio. The patient-specific approach was assessed in 8 MS patients. Improved infratentorial lesion contrast was achieved in most of the cases.

Laleh Eskandarian^1,2, Bahadır Konuskan³, Hacer Dasgin², Ismail Solmaz³, Rahsan Gocmen⁴, Banu Anlar⁴, and Kader Karli Oguz^2,4
1Neuroscience Department, Bilkent University, Ankara, Turkey, ²National Magnetic Resonance Research Center (UMRAM), Bilkent University, Ankara, Turkey, ³Faculty of Medicine, Pediatric Neurology, Hacettepe University, Ankara, Turkey, ⁴Faculty of Medicine, Department of Radiology, Hacettepe University, Ankara, Turkey

Pediatric-onset-Multiple-Sclerosis (POMS) has been reported to have larger and higher number of T2 lesions as with more frequent posterior fossa involvement compared to adults. We aimed to analyze POMS patients morphological, microstructural alterations and their correlates with clinical characteristics with emphasis on posterior system. SUIT,Freesurfer and TBSS were used for spatialized parcellation, and analysis. Cerebellum except paramedian structures and cerebral cortices showed volume reductions, cerebral white matter and midbrain showed reduced FA and increased MD,AD,RD. Total and periventricular lesion loads, thalamic volumes showed correlations with special clinical metrics. Multiparametric brain MRI may reveal information on tissue changes and clinical correlates.

Alina Lopatina¹, Renat Sibgatulin¹, Stefan Ropele², Jürgen R Reichenbach^1,3, and Daniel Güllmar^1
1Medical Physics Group / IDIR, Jena University Hospital, Jena, Germany, ²Department of Neurology, Medical University of Graz, Graz, Austria, ³Michael Stifel Center for Data-driven Sciences, Friedrich-Schiller-University Jena, Jena, Germany

Convolutional neural network (CNN) was proposed to identify multiple sclerosis patients and healthy subjects while susceptibility-weighted imaging (SWI) was used for MRI scans preprocessing in order to disclose important features hidden in brain venograms.  Using only one two-dimensional slice for each subject makes the proposed algorithm easy-applied and useful for clinical practice.

François-Louis Collemiche¹, Céline Charroud², Aude Metzger³, Xavier Ayrignac⁴, Pierre Labauge⁴, Nicolas Menjot de Champfleur⁴, Emmanuelle Le Bars⁴, and Jérémy Deverdun^4
1Neuroradiology, Hospital Gui de Chauliac, MONTPELLIER, France, ²Center for Mind/Brain Science, Rovereto, Italy, ³Hospital Pierre Wertheimer, Lyon, France, ⁴Hospital Gui de Chauliac, MONTPELLIER, France

One hypothesis in physiopathological mechanisms of multiple sclerosis (MS) involves astrocyte metabolism disruption as a consequence of axonal dysfunction, leading to cerebral vasoreactivity alterations (CVR). The aim was to explore a possible link between axonal tracts alterations and CVR disruption. 35 MS patients underwent MR. We selected motor clinical symptoms, and compared cerebral vasoreactivity and DTI maps. Both poCVR and DTI maps showed vasoreactivity alterations in white matter regions. Maps outlined the Inferior Fronto-Occipital Fasciculus in patients with “difficulties using upper limbs”. Vasoreactivity could be a new biomarker for assessing the evolution of white matter tracts’ alterations in MS follow-up.

Refaat E Gabr¹, Ivan Coronado¹, and Ponnada A Narayana^1
1Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, Houston, TX, United States

Multiple sclerosis (MS), a demyelinating disease of the central nervous system, affects more than two million people worldwide. Contrast enhancing lesions are thought to reflect active disease state and play a key role in MS management. Deep learning (DL) based on convolutional neural networks has reached state-of-art performance on semantic segmentation tasks. Using annotated images for 398 MS patients, we evaluated DL performance on segmentation of enhancing lesions. Our approach yielded Dice similarity coefficient of 0.78, true positive rate of 0.91, and false positive rate of 0.28 for test data. Network performance was excellent for enhancement volumes ≥70 µl.

Refaat E Gabr¹, John A Lincoln², Arash Kamali¹, Xiaojun Sun¹, Khader M Hasan¹, and Ponnada A Narayana^1
1Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, Houston, TX, United States, ²Neurology, University of Texas Health Science Center at Houston, Houston, TX, United States

Infratentorial lesions play an important role in the diagnosis of multiple sclerosis (MS), but are challenging to detect on conventional FLAIR protocols. Synthetic FLAIR3 images were generated by combining FLAIR and T2-weighted images to improve lesion contrast while maintaining CSF suppression. We evaluated FLAIR3 for detecting infratentorial lesions in 10 patients with MS. Our results show 11-fold increase in the lesion contrast-to-noise ratio and 163% increase in the number of detected lesions using FLAIR3 as compared to FLAIR.

Carmen Tur^1,2, Francesco Grussu^1,3, Ferran Prados^1,4,5, Baris Kanber⁴, Thalis Charalambous^1,6, Declan T. Chard^1,7, Olga Ciccarelli^1,7, and Claudia A.M. Gandini Wheeler-Kingshott^1,8,9
1UCL Queen Square Institute of Neurology, University College London, London, United Kingdom, ²Neurology, Luton and Dunstable University Hospital, Luton, United Kingdom, ³Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom, ⁴Centre for Medical Image Computing, Medical Physics and Biomedical Engineering department, University College London, London, United Kingdom, ⁵e-Health center, Universitat Oberta de Catalunya, Barcelona, Spain, ⁶Department of Medicine, St. George’s University of London, London, United Kingdom, ⁷University College London Hospitals Biomedical Research Centre, National Institute for Health Research, London, United Kingdom, ⁸Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy, ⁹Brain MRI 3T Research Centre, IRCCS Mondino Foundation, Pavia, Italy

Lesion load is the main predictor of future disability in multiple sclerosis (MS) but its predictive power is limited possibly because key aspects of lesions, such as their spatial distribution, morphology or pathological substrate are not being considered. Here we demonstrate the relevance of shape and spatial features of white matter lesions in the development of disability in MS through a novel approach. This new methodological framework (SSPACE-MS) is based on the analysis of the covariance matrix defined by the spatial position of lesional voxels. It can be applied longitudinally and is easily implementable in clinical practice. 

Amalie Monberg Hindsholm¹, Claes Nøhr Ladefoged¹, Flemming Littrup Andersen¹, Stig Præstekjær Cramer¹, Liselotte Højgaard¹, and Ulrich Lindberg^1
1Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet University, Copenhagen, Denmark

Automatic segmentation of MRI-visible multiple sclerosis (MS) lesions could potentially reduce assessment time and inter- and intra-rater variability. Recently, automatic methods using deep convolutional neural networks (CNN) have obtained great results in image segmentation. This work implements a state-of-the-art 2D CNN-based segmentation method from literature and extends and recalibrates it to a local MS dataset of 91 patients. A clinical evaluation is performed on an independent MS dataset of 53 patients, where 94% of predicted segmentation masks were deemed valuable for clinical use.

Elisabetta Pagani¹, Loredana Storelli¹, Paolo Preziosa^1,2, Federica Esposito², Laura Cacciaguerra^1,2, Massimo Filippi^1,2,3, and Maria A. Rocca^1,2
1Neuroimaging Research Unit, Institute of Experimental Neurology, 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

Gray matter is more relevant than white matter (WM) atrophy in explaining clinical disability and cognitive impairment in multiple sclerosis (MS). However, WM is a complex structure whose fiber orientation should be considered when investigating its morphology. In a group of MS patients and healthy controls, we applied constrained spherical deconvolution and fixel-based morphometry to estimate the distribution of WM fiber bundles and  their cross-section area as a measure of atrophy. We found that the application of this approach in MS improved when accounting for the presence of lesions and that atrophy was specific of WM fiber bundles.

Ingo Hermann^1,2, Ralf Schmidt¹, Benedikt Rieger¹, Eloy Martinez-Heras³, Elisabeth Solona³, Sara Llufriu³, Achim Gass⁴, Lothar R. Schad¹, and Frank G. Zöllner^1
1Computer Assisted Clinical Medicine, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany, ²Magnetic Resonance Systems Lab, Department of Imaging Physics, Delft University of Technology, Delft, Netherlands, ³Center of Neuroimmunology, Laboratory of Advanced Imaging in Neuroimmunological Diseases, Hospital Clinic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Universitat de Barcelona, Barcelona, Spain, ⁴Department of Neurology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany

We evaluated an MRF-EPI sequence for simultaneous T₁ and T₂* quantification in 44 patients with multiple sclerosis (MS) lesions at two scanners. We found significantly increased T₁ and T₂* times in MS lesions with differences up to 100 %. MS lesions resulted in broad distribution in the T₁, T₂* space compared with dense, separated clusters for white and gray matter.

Caroline Köhler¹, Hannes Wahl¹, Paul Kuntke¹, Tjalf Ziemssen², Jennifer Linn¹, and Hagen H. Kitzler^1
1Institut und Poliklinik für Diagnostische und Interventionelle Neuroradiologie, University Hospital Carl Gustav Carus, Dresden, Germany, ²Neurology, University Hospital Carl Gustav Carus, Dresden, Germany

Myelin water imaging  allows the assessment of relative myelination by estimating the myelin water fraction (MWF). This work investigated if the degree of MWF loss in multiple sclerosis is associated with T1 hypointense and isointense lesions. Within n = 1668 FLAIR lesions of n = 63 MS patients, 79% had a hypointense correlate, and 21% of the lesions had an isointense appearance on non-enhanced T1-weighted images. Significant differences were found for hypointense (MWFmean = 0.126) and isointense (MWFmean = 0.185) lesions. These results show varying degrees of myelin reduction.

Carl Herrmann¹, Eckart Grönerwäller¹, Antje Els¹, Joseph Kuchling^2,3,4, Friedemann Paul^2,3,4, and Thoralf Niendorf^1,2
1Berlin Ultrahigh Field Facility (B.U.F.F.) Max Delbrück Center For Molecular Medicine in the Helmoltz Association, Berlin, Germany, ²Experimental und Clinical Research Center (ECRC), Charité-Campus Berlin-Buch, Berlin, Germany, ³NeuroCure Clinical Research Center, Charité – Universitätsmedizin, Berlin, Germany, ⁴Department of Neurology, Charité – Universitätsmedizin, Berlin, Germany

MRI examinations commonly involve a series of multiple imaging contrasts and MR-metrics, resulting in long examination times and propensity to motion and slice misregistration. Dual or multi-contrast techniques offer substantial scan time reduction. Recognizing this opportunity this work presents a dual contrast RARE-EPI hybrid, that provides T₂ (RARE module) and T₂* (EPI module) contrast and facilitates simultaneous T₂ and T₂* mapping in a single radially (under)sampled scan (2-in-1 RARE-EPI). The applicability of 2-in-1 RARE-EPI is demonstrated in an in vivo feasibility study involving patients suffering from multiple sclerosis and healthy controls and benchmarked versus conventional T₂ and T₂* weighted/mapping techniques.

Xianfu Luo^1,2, Elizabeth Sweeney³, Ulrike W. Kaunzner⁴, Weiyuan Huang¹, David Pitt⁵, Yi Wang¹, Susan Gauthier⁴, and Thanh D. Nguyen^1
1Department of Radiology, Weill Medical College of Cornell University, New York, NY, United States, ²Department of Radiology, Northern Jiangsu People's Hospital, Yangzhou, China, ³Department of Healthcare Policy and Research, Weill Medical College of Cornell University, New York, NY, United States, ⁴Department of Neurology, Weill Medical College of Cornell University, New York, NY, United States, ⁵Yale University, New Haven, CT, United States

Quantitative susceptibility mapping (QSM) has emerged as a sensitive MRI tool for in vivo monitoring inflammation in MS brain. Low-grade inflammation in chronic active lesions have been shown to contain iron-enriched, activated microglia and macrophages on histopathology  and have been linked to greater tissue damage. QSM can provide accurate in vivo quantification of  iron-laden inflammatory cells. It might be used to assess treatment response.

Arzu Ceylan Has Silemek¹, Jean-Philippe Ranjeva^2,3, Bertrand Audoin^2,3, Christoph Heesen^1,4, Stefan M. Gold^1,5, and Jan-Patrick Stellmann^2,3
1Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany, ²CRMBM AMU-CNRS , Marseille, France, Marseille, France, ³CEMEREM, APHM, CHU Timone, Marseille France, Marseille, France, ⁴Klinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany, ⁵Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health (BIH), Klinik für Psychiatrie & Psychotherapie und Medizinische Klinik m.S. Psychosomatik, Campus Benjamin Franklin (CBF), Berlin, Germany

Visual backward masking paradigm (VB) distinguishes between conscious and unconscious processes and evaluates fundamental brain functions and cognition. Delayed consciousness was shown as related with white matter damage in early Multiple Sclerosis (MS). However, it is unknown, if regional brain activity and structural connectivity are related to delayed consciousness in MS. We investigated the impaired access to consciousness in MS[25(MS)/37(controls)] using task-based-fMRI based on the VB and its relation with structural connectivity.  Lower activation was detected in unconscious-processing in MS vs controls. Strong relationship between VB-performance and lower structural connectivity in ventral-attention/visual/default-mode networks supports the sensitivity of VB in MS.  

Frederique Boonstra¹, Gustavo Noffs^2,3, Thushara Perera^2,4, Vilija Jokubaitis⁵, Adam Vogel^2,4,6, Andrew Evans^3,4, Helmut Butzkueven⁵, Anneke van der Walt⁵, and Scott Kolbe^5
1Neuroscience, Monash University, Melbourne, Australia, ²University of Melbourne, Melbourne, Australia, ³Royal Melbourne Hospital, Melbourne, Australia, ⁴Bionics Institute, Melbourne, Australia, ⁵Monash University, Melbourne, Australia, ⁶University of Tübingen, Tübingen, Germany

Almost half of patients with multiple sclerosis (MS) experience tremor, which significantly worsens disability. Pathophysiology studies of MS tremor have highlighted the importance of the cerebello-thalamo tract. This study aimed to use resting-state fMRI to identify brain networks that are dysfunctional in MS tremor. We found significantly higher connectivity within the motor network in tremor patients compared to controls, and the mean activation within the motor network was negatively correlated to tremor. Resting-state fMRI could provide useful markers for studying the pathophysiology of tremor in MS.

Ken Sakaie¹, Paola Raska², Nancy Obuchowski², Kunio Nakamura³, Mark J. Lowe¹, and Robert J. Fox^4
1Imaging Institute, The Cleveland Clinic, Cleveland, OH, United States, ²Quantitative Health Sciences, The Cleveland Clinic, Cleveland, OH, United States, ³Lerner Research Institute, The Cleveland Clinic, Cleveland, OH, United States, ⁴Neurological Institute, The Cleveland Clinic, Cleveland, OH, United States

In a clinical trial, it may be necessary to incorporate multiple centers to get a sufficiently large sample size. Trials that use imaging may suffer from heterogeneity among centers in terms of scanner platform. In the SPRINT-MS trial, diffusion tensor imaging (DTI) measures indicated a larger treatment effect than brain parenchymal fraction (BPF). However, the effect measured by DTI was not statistically significant. In this study, we examine the hypothesis that heterogeneity in scanner type contributed to variance in DTI measures, reducing the statistical power of the measurement.

Ho-Joon Lee¹, Yeonah Kang¹, Marc Lebel², Jae Eun Song³, and Sung-Min Gho^4
1Department of Radiology, Haeundae Paik Hospital, Busan, Republic of Korea, ²MR Collaboration and Development, GE Healthcare, Calagary, AB, Canada, ³Department of Electrical and Electronic Engineering, Yonsei University, Seoul, Republic of Korea, ⁴MR Collaboration and Development, GE Healthcare, Seoul, Republic of Korea

With advances in deep learning, feasibility has been investigated for myelin water fraction (MWF) reconstruction showing promising results, enabling fast reconstruction, however whether images denoised with deep learned reconstruction(DL) will improve MWF map quality has not been investigated. After denoising of multi-echo GRE magnitude images with a DL algorithm, data was fitted to a three-component magnitude model. Use of DL, shows better results as compared to conventionally generated maps (i.e. decreased NRMSE and mean fitting errors (WM), increased PSNR and SSIM). Gibb's ringing artifact was removed remarkably. 

Ana-Maria Oros-Peusquens¹, Dennis Thomas¹, Alexander L. MacKay², and N. Jon Shah^1
1Research Centre Juelich, Juelich, Germany, ²University of British Columbia, Vancouver, BC, Canada

The influence of steady state on myelin water fraction derived from mGRE data was investigated, with the aim of estimating myelin water T1. Myelin and tissue water were identified by their T2* properties following an NNLS analysis. PCA denoising reduced the variability (SD) of MWF by nearly a factor of 2. The residuals of the NNLS fit were found to be small (below 0.5%) but highly significant, and showed no dependence on TR. The derived T1 of myelin water was highly variable and shorter than that of tissue water. These findings are consistent with a reduced exchange between pools.

Jae Eun Song¹ and Dong-Hyun Kim^1
1Electrical and Electronic Engineering, Yonsei University, Seoul, Republic of Korea

In this study, we propose a model-based unsupervised learning algorithm to estimate three-component exponential model parameters. The proposed method, model-based T2* autoencoder, is composed of ANN encoder and three-component model decoder. Incorporation of ANN encoder and three-component model decoder provides noise robust estimation of MWF and physically meaningful information at deep latent space.

Noam Omer¹, Tamar Blumenfeld-Katzir¹, Natalie Bnaiahu¹, Meirav Galun², and Noam Ben-Eliezer^1,3,4
1Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel, ²Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel, ³Center for Advanced Imaging Innovation and Research (CAI2R), New-York University Langone Medical Center, New York, New York, NY, United States, ⁴Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel

Multicomponent T₂ analysis (mcT₂) can be highly valuable for probing tissue microstructure. However, it remains challenging due to its ill-conditioned nature, and due to inherent contamination of multi spin-echo signals by stimulated echoes. We present a novel mcT₂ algorithm that tackles the high-dimensionality of this problem, using correlations between local and global features of the anatomy in question. The accuracy of this tool is demonstrated on phantoms and in vivo. Our results suggest that the method can accurately identify microscopic compartments, operate at realistic scan times, and be used estimate to estimate myelin content in vivo.

Nikkita Khattar¹, Richard G. Spencer¹, and Mustapha Bouhrara^1
1NIA, NIH, Baltimore, MD, United States

Iron is known to play a central role in neuronal viability and pathophysiology. Although susceptibility weighted imaging (SWI) is highly sensitive to iron, few studies have investigated the effect of age and sex on iron deposition using SWI. Further, the potential association between iron deposition and myelination is unclear. It has been suggested that myelin breakdown releases iron, which further acts to potentiate myelin loss through oxidative mechanisms. Here, we investigate the association between local iron deposition and age, sex, and myelination, measured using an advanced myelin content imaging method, on a cohort of cognitively unimpaired participants.
 

Richard Wonjoong Kim¹, Nikkita Khattar¹, Wenshu Qian¹, Joseph Alisch¹, Richard G. Spencer¹, and Mustapha Bouhrara^1
1NIA, NIH, Baltimore, MD, United States

Emerging evidence indicates that myelination and axonal abnormalities could lead to alterations of brain connectivity, contributing to a myriad of neurological disorders.  Measurement of myelin to axonal volume, as defined by the g-ratio, has been shown to represent a sensitive and specific metric of neurodevelopment and neurodegeneration. However, only a single study to date has sought to evaluate age-related differences in g-ratio in the adult human brain. Here, we introduce and compare two novel approaches to g-ratio mapping. Both methods revealed a quadratic relationship between g-ratio and age in a large cohort of cognitively unimpaired participants.   
 

Mustapha Bouhrara¹, Luis E. Cortina¹, Abinand C. Rejimon¹, Nikkita Khattar¹, and Richard G. Spencer^1
1NIA, NIH, Baltimore, MD, United States

Very few MR investigations have been conducted to assess age-dependent myelination differences in the brainstem, in spite of the brainstem's central role in regulating vital functions. This is likely due to the small structural scale of the brainstem, necessitating accurate high spatial resolution imaging for quantitative studies. Here, we used our recently developed approach to myelin water fraction (MWF) mapping and found a decrease in myelination with age in different brainstem regions, with several regions exhibiting a quadratic association. We believe that this study is the first investigation of MWF changes with normative aging in the brainstem.
 

Stephen J Sawiak¹, M Arsalan Khan², Gemma Cockcroft³, Edward T Bullmore⁴, and Angela C Roberts^3
1Translational Neuroimaging Laboratory, PDN, University of Cambridge, Cambridge, United Kingdom, ²University of Cambridge, Cambridge, United Kingdom, ³Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom, ⁴Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom

Changes in myelination are prominent throughout brain development. Here, we assess MTsat as a measure of intracortical myelination in the developing marmoset brain with 38 subjects from infancy to adulthood. We find that the measure is consistent between brains and that across the cortex as a whole, adults differ in apparent myelination compared with infants and early adolescents particularly within central and deeper cortical layers. Regional analysis with this metric will facilitate differentiation between morphological and microstructural developmental changes that cannot be elucidated with conventional structural imaging. 

Wenwen Yu¹, Run Pu², Zhe Wu², Hongjian He², Yuequan Shi³, Zuofu Zhou³, Zheng Wang⁴, and Jianhui Zhong^2,5
1Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, CAS Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, Shanghai, China, ²Center for Brain Imaging Science and Technology, Key Laboratory for Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrumental Science, Zhejiang University, Hangzhou, China, ³Department of Radiology, Fujian Provincial Maternity and Children’s Hospital of Fujian Medical University, Fuzhou, China, ⁴Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China, ⁵Department of Imaging Sciences, University of Rochester, Rochester, NY, United States

A tight association between iron and myelin content has been demonstrated in the local brain regions. However, it remains unknown whether such relationship exists between adjacent brain regions. Using 8 young and 8 older macaque monkeys, we integrated MRI-based QSM and MWF imaging to examine the relation between iron deposition in components of BG and the myelin content of BG-connecting IC. Our results reveal that the iron of BG is positively correlated with the myelin of IC at different aging stages, and demonstrate that iron in BG also affects the myelin content of the anatomically distinguished yet connected WM structures.

Bretta Russell-Schulz¹, Irene M Vavasour^1,2,3, Hanwen Liu^2,4, Cornelia Laule^2,3,4,5, Erin L MacMillan^1,6,7, Alex L MacKay^1,3,4, Carolyn Sparrey^2,8, and Bonita Sawatzky^2,9
1UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada, ²International Collaboration on Repair and Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada, ³Radiology, University of British Columbia, Vancouver, BC, Canada, ⁴Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, ⁵Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, ⁶SFU ImageTech Lab, Simon Fraser University, Surrey, BC, Canada, ⁷Philips Canada, Marham, ON, Canada, ⁸School of Mechatronic Systems Engineering, Simon Fraser University, Surrey, BC, Canada, ⁹Orthopaedics, University of British Columbia, Vancouver, BC, Canada

Adults living with Amyoplasia report lower physical activity but no educational or cognitive impairment. Myelin water fraction (MWF) is a quantitative MRI metric useful for examining white matter myelin content. We expect brain MWF to be similar or higher between Amyoplasia and controls in most of the brain but lower in areas associated with physical ability. In 3 adults with Amyoplasia MWF maps were created using a 32-echo T2 GRASE compared to an open-source healthy control atlas. Small reductions in corticospinal tract myelin were observed, while the remainder of the brain examined was similar to the control atlas.

Ahmed M. Elkady¹, Zhe Wu^1,2, Dumitru Fetco¹, Ilana R. Leppert¹, Douglas L. Arnold¹, Sridar Narayanan¹, and David A. Rudko^1,3
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada, ²Techna Institute, University Health Network, Toronto, ON, Canada, ³Department of Biomedical Engineering, McGill University, Montreal, QC, Canada

We comparatively evaluated non-corrected Magnetization Saturation (MTSat), B1-corrected MTsat, wave-CAIPI direct Visualization of Short myelin Transverse component (wave-CAIPI ViSTa), and multi-atlas probabilistic tissue classification in multiple sclerosis (MS) lesions and white matter tracts of healthy and MS subjects. The relationship between ViSTa myelin water fraction (MWF) and MTSat myelin volume fraction (MVF) was altered in MS normal appearing white matter (NAWM) compared NAWM of controls. This may reflect specific alterations in the macromolecular and myelin water pool fractions observed in demyelinating tissue. ViSTa MWF was more sensitive in detecting pathological differences between the MS and control groups.

Richard Dortch¹ and Francesca Bagnato^2,3
1Barrow Neurological Institute, Phoenix, AZ, United States, ²Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States, ³Neuroimaging Unit/Neuroimmunology Division, Vanderbilt University Medical Center, Nashville, TN, United States

Quantitative magnetization transfer using the selective inversion recovery method yields indices [macromolecular-to-free water pool-size-ratio (PSR) and longitudinal spin-lattice relaxation rate (R_1f)] that report on myelin content in the brain. In this study, SIR indices were estimated in the corticospinal tract (CST) of patients with multiple sclerosis for comparison to clinical disability measures [Expanded Disability Status Scale (EDSS) and Timed 25-Foot Walk T25FW)]. Significant correlations were observed between SIR indices (PSR/R_1f) and disability scores (EDSS/T25FW). The strongest correlation was between PSR and EDSS, suggesting that measurements of PSR in the CST may report on myelin damage and/or repair in multiple sclerosis. 

Lucas Soustelle^1,2, Soraya Gherib^1,2, Samira Mchinda^1,2, Sylviane Confort-Gouny^1,2, Arnaud Le Troter^1,2, Maxime Guye^1,2, Jean-Philippe Ranjeva^1,2, Patrick Viout^1,2, Lauriane Pini^1,2, Claire Costes^1,2, Adil Maarouf^1,2,3, Bertrand Audoin^1,2,3, Audrey Rico^1,2,3, Clémence Boutière^1,2,3, Fanelly Pariollaud^1,2, Françoise Reuter^1,2, Victor Nunes Dourado de Carvalho^1,2, Véronique Gimenez^1,2, Andreea Hertanu^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

Assessment of lesion evolution in Multiple Sclerosis (MS) is critical to monitor the disease progression but remains challenging in clinical practice. Inhomogeneous magnetization transfer (ihMT) is a promising technique that has demonstrated sensitivity to demyelination in preclinical and clinical studies. In this work, a 3D ihMT technique was integrated as part of a multiparametric MRI protocol and applied to active MS lesion follow up over a period of six months. Variations of ihMT ratio were compared to those of conventional magnetization transfer imaging and diffusion tensor imaging often used in clinical research to assess demyelination.

Caroline Köhler¹, Hannes Wahl¹, Tjalf Ziemssen², Paul Kuntke¹, Jennifer Linn¹, and Hagen H. Kitzler^1
1Institut und Poliklinik für Diagnostische und Interventionelle Neuroradiologie, University Hospital Carl Gustav Carus, Dresden, Germany, ²Neurology, University Hospital Carl Gustav Carus, Dresden, Germany

Multiple Sclerosis lesions are pathologically heterogeneous. The Multi-component relaxation method (mcDESPOT) which allows the determination of relative myelination by estimating the myelin water fraction (MWF) could be valuable to capture the high variability of disease development. In a pilot study n=112 RRMS patients got MRI examination and MWF values were determined of white matter (WM) and individual lesions. The MWF of WM was 0.230 for healthy controls and 0.224 for RRMS patients. 2787 WM FLAIR lesions were examined. Patients with a higher degree of disability of EDSS ≥ 4 significantly have lower MWF values than patients with EDSS < 2.5.