Advanced MRI in Multiple Sclerosis

Monday 22 April 2013

Maria A. Rocca¹, Martina Absinta¹, Maria Pia Amato², Angelo Ghezzi³, Lucia Moiola⁴, Agnese Fiorino⁴, Pierangelo Veggiotti⁵, Giancarlo Comi⁴, Massimo Filippi¹, and and the MS and Neuroimaging Study Groups of the Italian Neurological Society^6
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy, ²Department of Neurology, University of Florence, Florence, FI, Italy, ³MS Centre, Ospedale di Gallarate, Gallarate, VA, Italy, ⁴Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy, ⁵Child Neurology Unit, National Neurological Institute C. Mondino, Pavia, PV, Italy, ⁶SIN, Siena, SI, Italy

We combined structural and functional MRI techniques to improve our understanding of the mechanisms responsible for the presence and severity of cognitive impairment in 35 patients with pediatric multiple sclerosis (MS). We found that in pediatric MS patients, cognitive dysfunction is associated to structural and functional abnormalities of core regions of the default mode network located in the posterior brain, particularly the precuneus. Increased resting state functional connectivity of regions located in the frontal lobe might compensate for such a dysfunction and contribute to cognitive preservation.

Yulin Ge¹, Hanzhang Lu², Yongxia Zhou³, Feng Xu², Ilya Kister⁴, Hina Jaggi³, Joseph Herbert⁵, and Robert I. Grossman^6
1Radiology, New York University Langone Medical Center, New York, New York, United States, ²Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States, ³Radiology, NYU Langone Medical Center, New York, New York, United States, ⁴Neurology, NYU Langone Medical Center, New York, New York, United States, ⁵Neurology, New York University, New York, New York, United States, ⁶Radiology, New York University, New York, New York, United States

Normal neuronal activity is tightly linked to and critically depends on the increase of blood flow for instantaneous supply of oxygen and glucose. This study is to evaluate whether there is cerebrovascular reactivity (CVR) impairment in patients with multiple sclerosis (MS) using hypercapnia BOLD MRI. Our findings of significant decrease of CVR in MS patients suggest an impaired vascular regulation of blood flow supply or defect neurocoupling mechanism, which may affect effective oxygen delivery particularly to the previously healthy and normal neurons and lead to neurodegeneration over time.

Elisabetta Pagani¹, Maria A. Rocca¹, Giulia Longoni¹, Vittorio Martinelli², Bruno Colombo², Andrea Falini³, Giancarlo Comi², and Massimo Filippi^1
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy, ²Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy, ³Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy

The use of a regional approach for the study of hippocampal atrophy in a large cohort of patients with multiple sclerosis (MS) allowed us to detect differences in the regional pattern of damage distribution across the main disease clinical phenotypes. We found a selective and progressive CA1 atrophy in patients with MS as well as a substantial involvement of the subiculum, the major efferent of hippocampal pathways, even in the early phases of the disease. Primary progressive MS MS patients, in whom inflammation is relatively modest, showed a relative sparing of hippocampal formation.

Vasily L. Yarnykh¹, James D. Bowen², Alexey A. Samsonov³, Pavle Repovic², Angeli Mayadev², Bart P. Keogh², Beena Gangadharan², Hunter R. Underhill¹, Kenneth R. Maravilla¹, and Lily K. Jung Henson^2
1Radiology, University of Washington, Seattle, WA, United States, ²Swedish Medical Center, Seattle, WA, United States, ³Radiology, University of Wisconsin, Madison, WI, United States

Macromolecular proton fraction (MPF) is a key parameter determining magnetization transfer in tissues. Recent studies demonstrated close associations between MPF and myelin content in neural tissues. We present the first clinical evaluation of a recently published fast whole-brain MPF mapping method in multiple sclerosis (MS). MPF in both white and gray matter in MS demonstrated highly significant decrease compared to controls and strong correlations with disability. Notably, gray matter MPF showed the strongest correlations with clinical status, thus emphasizing a critical role of gray matter demyelination in MS. This study establishes MPF as a new quantitative imaging biomarker of demyelination.

Yaou Liu¹, Teng Xie², Ni Shu², Kuncheng Li¹, and Yong He^2
1Department of Radiology, Xuanwu hospital, Capital Medical University, Beijing, China, ²State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China

We analyzed the global and regional cortical thickness (CTh) in patients with neuromyelitis optica (NMO), and directly compared with multiple sclerosis (MS) and healthy controls (HCs). Different patterns of cortical thinning between MS and NMO were observed. MS showed a widespread cortical thinning in many brain regions predominantly in frontal and temporary lobes, while subtle cortical thinning in occipital lobe was observed compared with HCs. When directly compare MS and NMO, several brain regions in temporary lobe was found significantly thinner in MS. Furthermore a significant correlation was found between CTh in several brain regions and clinical variables. This study.

Mishkin Derakhshan¹, Gabriel Leonard¹, Daviad Araujo¹, D. Louis Collins¹, Douglas L. Arnold¹, and Sridar Narayanan^1
1Montreal Neurological Institute, McGill University, Montreal, QC, Canada

The hippocampi (HC) have been found to be demyelinated in postmortem studies of patients with multiple sclerosis (MS), and HC pathology has been shown to be responsible for memory impairment. Using magnetization transfer ratio (MTR) as a marker of demyelination, we examined HC demyelination and HC atrophy in 26 patients with MS and 15 controls matched for age, sex, and education level. We found that focal HC MTR values best explained memory performance, specifically working and visual immediate memory, better than volumetric measures.

Ponnada A. Narayana¹, Koushik Govindarajan¹, Priya Goel¹, Sushmita Datta², John A. Lincoln³, Stacy S. Cofield⁴, Gary R. Cutter⁴, Fred D. Lublin⁵, and Jerry S. Wolinsky^3
1Diagnostic and Interventional Imaging, University of Texas Hlth Sci Cntr Houston, Houston, Texas, United States, ²Diagnostic and Interventional Imaging, Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, United States, ³Neurology, University of Texas Hlth Sci Cntr Houston, Houston, Texas, United States,⁴3Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, United States, ⁵The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, New York, United States

Changes in regional and global cortical thickness and age- and gender dependence of these measures on a large MS cohort that is a part of a multi-center clinical trial were investigated. Changes in regional cortical thicknesses were larger in the left hemisphere compared to the right. Males showed stronger age dependent cortical thickness than females. Strongest reductions in the thickness were observed in the entorhinal cortex and temporal poles in MS, the structures implicated in several neurodegenerative diseases. Weaker age dependent changes in both global and regional cortical thicknesses were observed in MS patients compared to controls.

Rebecca S. Samson¹, Manuel Jorge Cardoso^2,3, Nils Muhlert⁴, Varun Sethi⁴, Claudia Angela M. Wheeler-Kingshott⁴, Maria A. Ron⁴, Sebastian Ourselin^2,3, David H. Miller⁴, and Declan T. Chard^4
1NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, England, United Kingdom, ²Centre for Medical Image Computing, UCL Department of Computer Sciences, London, United Kingdom, ³Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom, ⁴NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom

Histopathology has demonstrated extensive cortical demyelination in multiple sclerosis (MS), often in a subpial location. We subdivided the cortex into inner and outer ‘bands’, and investigated the relationship between inner and outer cortical abnormality (as measured by the magnetisation transfer ratio (MTR)) and clinical course in a large cohort of MS patients. Outer was lower than inner MTR in people with MS and controls, as expected due to the lower myelin content in the outer cortex. Outer cortical MTR reductions (consistent with subpial demyelination) were observed in relapse-onset MS and were most marked in people with secondary progressive MS.

Adil Maarouf^1,2, Jean Christophe Ferré^3,4, Wafaa Zaaraoui¹, Elise Bannier⁵, Christian Barillot⁴, Isabelle Berry⁶, Gilles Edan⁷, Damien Galanaud⁸, Jean Pelletier^1,9, Christophe Portefaix¹⁰, Ayman Tourbah¹¹, Jean-Philippe Ranjava¹, and Bertrand Audoin^1,9
1CRMBM, CNRS UMR 7339, Marseille, France, ²Dept. of Neurology, CHU REIMS, Reims, France, ³Dept. of Neuroradiology, CHU Rennes, RENNES cedex 9, France, ⁴Visages U746, INSERM INRIA IRISA, Rennes, France, ⁵Neurinfo, INSERM INRIA IRISA, Rennes, France, ⁶Dept. of Biophysics, CHU Toulouse, Toulouse, France, ⁷Dept. of Neurology, CHU Rennes, Rennes, France, ⁸Dept of Neuroradiology, Pitié Salpêtrière Hospital, Paris, France, ⁹Dept. of Neurology, CHU Marseille, Marseille, France, ¹⁰Dept. Radiology, CHU Reims, Reims, France, ¹¹Dept. of Neurology, CHU Reims, Reims, France

Macrophage infiltration is an important pattern in inflammatory processes associated to multiple sclerosis. The aim of this longitudinal and multicentric study was to determine the prevalence of USPIO enhancement in patients with early MS and the impact of macrophage activity at early and medium term on tissue integrity assessed by MTR. From the earliest stage of MS, we highlighted the presence in vivo of activated macrophages. Destructuration was higher and persistent in lesions with significant macrophages burden. The total T2-w lesion was significantly higher in the group of patient that had at baseline at least one USPIO-positive lesion.

Eric Y. Zhao¹, Irene Vavasour², Marjan Zakeri³, Michael Borich³, Cornelia Laule⁴, Anthony L. Traboulsee⁵, David K.B. Li², Lara Boyd³, and Alex L. Mackay^2,6
1Department of Cellular & Physiological Sciences, The University of British Columbia, Vancouver, BC, Canada, ²Department of Radiology, The University of British Columbia, Vancouver, BC, Canada, ³Brain Behavior Lab, Department of Physical Therapy, The University of British Columbia, Vancouver, BC, Canada, ⁴Department of Pathology & Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada, ⁵Division of Neurology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada, ⁶Department of Physics & Astronomy, The University of British Columbia, Vancouver, BC, Canada

Myelin water fraction (MWF) measured via the signal fraction of the short T₂ relaxation time can be used to monitor demyelination in MS over time. Transcallosal inhibition (TCI), measured via transcranial magnetic stimulation, is also indicative of neuronal health. This study aims to uncover correlations between callosal MWF and TCI parameters to better characterize MWF as a predictor of neurophysiologic function. We found that decreased MWF in the callosal region shown to carry motor information is correlated with delayed onset as well as decreased duration and magnitude of TCI. We attribute this to loss of spatiotemporal summation due to demyelination.