MS in Gray Matter

Friday 16 May 2014

Stefano Tambalo¹, Silvia Fiorini¹, Roberta Rigolio², Pietro Bontempi¹, Andrea Sbarbati³, Guido Cavaletti², Paola Marmiroli², Stefano Pluchino⁴, and Pasquina Marzola^5
1Dept. of Neuological and Movement Science, Università di Verona, Verona, Verona, Italy, ²Dept. of Surgery and Translational Medicine, Università Milano-Bicocca, Milano, Italy, ³Dept. of Neuological and Movement Science, INSTM Firenze, Verona, Italy, ⁴Dept of Clinical Neurosciences, John Van Geest Centre for Brain Repair, Stem Cell Institute and NIHR, University of Cambridge, Cambridge, United Kingdom, ⁵Dept. of Informatics, University of Verona, Verona, Italy

Experimental Autoimmune Encephalomyelitis (EAE) is a good model of Multiple Sclerosis in rodents. We have applied fMRI to invesigate the alteration in functional response in rats induced with EAE. Cortical activation is altered in EAE rat brain, compared to controls. fMRI showed an increase in the activated volume involving also the cortex ipsilateral and some extra-cortical areas at the observed time points. These results demonstrate brain cortex remodeling in EAE, a remakable feature of MS. The present model seems to be a relevant tool in preclinical MS studies.

Nabeela Nathoo¹, James A. Rogers², V. Wee Yong², and Jeff F. Dunn^1,3
1Radiology, University of Calgary, Calgary, Alberta, Canada, ²Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada, ³Experimental Imaging Centre, University of Calgary, Calgary, Alberta, Canada

We showed previously that susceptibility weighted imaging (SWI) detects two types of lesions in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis: 1) vascular lesions, due to intravascular deoxyhemoglobin, and 2) parenchymal white matter lesions, due to iron deposition/demyelination. To identify vascular lesions in vivo, high oxygen was used during SWI MRI in EAE mice. High oxygen changed the appearance of vascular lesions, making them either disappear, become less dark, or become bright. As hyperoxygenation is well tolerated and safe, this method could be translated to MS patients to help differentiate between sources of lesions seen with SWI.

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

Double inversion recovery (DIR) is a powerful imaging technique for detecting cortical lesions in multiple sclerosis. Yet, the number of lesions detected by DIR is significantly lower than number of lesions identified on histology. Here we propose using magnetization transfer to enhance the suppression of white matter to improve the depiction of cortical lesions. Experiments on 14 patients show that magnetization transfer DIR (MT-DIR) doubles the number of detected lesions and improves the lesion contrast by ~30%.

Celine Louapre¹, Sindhuja T Govindarajan², Costanza Giannì², Julien Cohen-Adad³, Revere Philip Kinkel⁴, and Caterina Mainero^2
1AA Martinos Center for Biomedical Imaging, Charlestown, MA, United States, ²AA Martinos Center for Biomedical Imaging, MA, United States, ³Institute of Biomedical Engineering Ecole Polytechnique de Montreal, QC, Canada, ⁴Beth Israel Deaconess Medical Center, MA, United States

The relationship between diffuse cortical and underlying white matter (WM) injury in multiple sclerosis (MS) is not well understood. We used cortical thickness and intracortical laminar T2* relaxation decay to assess cortical injury, and to analyse its relationship with underlying WM pathology as assessed by diffusion tensor imaging. We found a spatial relationship between cortex and subcortical WM pathology at the overall brain level, and as a function of the depth from the white matter surface within WM tracts.

Martijn D. Steenwijk¹, Marita Daams^1,2, Lisanne J. Balk³, Prejaas K. Tewarie³, Jeroen J.G. Geurts², Frederik Barkhof¹, Hugo Vrenken^1,4, and Petra Pouwels^4
1Department of Radiology and Nuclear Medicine, VU University medical center, Amsterdam, Noord-Holland, Netherlands, ²Department of Anatomy and Neurosciences, VU University medical center, Amsterdam, Noord-Holland, Netherlands, ³Department of Neurology, VU University medical center, Amsterdam, Noord-Holland, Netherlands, ⁴Department of Physics and Medical Technology, VU University medical center, Amsterdam, Noord-Holland, Netherlands

Gray matter (GM) atrophy is common in multiple sclerosis (MS), but the spatial relation with white matter (WM) pathology is largely unknown. Studies investigating this topic are often limited to early patients or specific tracts. We present a new method using an advanced tractography-based approach to obtain ‘lesion connectivity’ maps at the cortical surface. Group-level vertex-wise statistics in a large cohort (n=208) of long-standing MS patients revealed large areas with negative associations between lesion connectivity and cortical thickness, indicating that cortical atrophy in MS can –at least partly– be explained by axonal damage or disconnection due to WM lesions.

Niels Bergsland^1,2, Marcella Laganà¹, Eleonora Tavazzi¹, Matteo Caffini², Paola Tortorella¹, Marco Rovaris¹, and Giuseppe Baselli^2
1Istituto IRCCS Santa Maria Nascente, Fondazione Don Gnocchi, Milan, Italy, ²Dipartimento di Elettronica, Informatica e Bioingegneria, Politecnico di Milano, Milan, Italy

The study of the relationship between grey matter (GM) and white matter damage in multiple sclerosis (MS) is relevant. This was a cross-sectional MRI study of 30 MS patients. Probabilistic tractography data and lesion load of the cortico-spinal tract (CST) were obtained. Measures of motor cortex (MC) thickness and area were obtained with Freesurfer. MC thickness correlated with CST mean diffusivity and lesion volume, and EDSS. MC surface area correlated with EDSS. Our findings further characterize the GM damage and confirm its impact of on disability. CST damage correlated with cortical thickness supporting the link between GM and WM damage.

Marco Battaglini¹, Mark Jenkinson², Antonio Giorgio¹, Maria Assunta Rocca³, Maria Laura Stromillo¹, Massimo Filippi³, jacqueline Palace⁴, and Nicola De Stefano^1
1Medicine, Surgery and Neurosciences, University of Siena, Siena, Tuscany, Italy, ²Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), University of Oxford, Oxford, United Kingdom, ³Neuroimaging Research Unit, Vita-Salute S.Raffaele University, Milano, Italy, ⁴Clinical Neurology, University of Oxford, Oxford, United Kingdom

This work provides a new SIENAX (SIENAX2.0) pipeline for the assessment of grey matter (GM) and white matter (WM) volume changes as measured on MR images of Multiple Sclerosis patients. Multisite datasets were analyzed and the results compared with those obtained by the SIENAX and the SPM8. New inhomogeneity correction and method for relabeling of potentially mislabeled GM clusters were introduced in SIENAX2.0 In isotropic high-quality dataset the new SIENAX2.0 allows robust GM and WM volume assessment halving the error when compared with SIENAX . In non-isotropic dataset, SIENAX2.0 significantly improves the robustness of GM and WM volume assessment.

Vanessa Lippolis¹, Daniel Altmann², Nils Muhlert³, Egidio Ugo D'Angelo⁴, Lucia Della Croce⁵, Matteo Pardini^6,7, Declan Chard⁷, David H. Miller⁷, Maria Ron⁷, Fulvia Palesi^8,9, and Claudia A.M. Wheeler-Kingshott^7
1Mathematics, University of Pavia, Pavia, Pavia, Italy, ²Department of Medical Statistics, LSHTM, London, London, United Kingdom, ³School of Psychology, Cardiff University, Cardiff, Wales, United Kingdom, ⁴Dept of Brain and Behavioral Sciences, University of Pavia, Pavia, Pavia, Italy,⁵Mathematics, University of Pavia, Pavia, Italy, ⁶Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Genoa, Italy, ⁷NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, London, United Kingdom, ⁸Department of Physics, University of Pavia, Pavia, Pavia, Italy, ⁹Brain Connectivity Center, National Neurological Institute C. Mondino, Pavia, Pavia, Italy

We present a statistical model in the GLM framework to relate cognitive scores to MRI-based cortical parameters, using a cohort of patients with MS and healthy controls. The model determined that patients were significantly worse in the Stroop test and presented a significant loss of cortical thickness; indeed variables that best predict MS status are the Right Medial Thickness and Right and Left Lateral Area. Cortical parameters are associated with cognitive scores, but there is no evidence that pathology of MS has an effect on these associations. In further works models can be expanded designing therapeutic interventions.

Elisabetta Pagani¹, Maria A. Rocca¹, Paolo Preziosa¹, Matteo Atzori², Frederik Barkhof³, Nicola De Stefano⁴, Christian Enzinger⁵, Franz Fazekas⁶, Antonio Gallo⁷, Hanneke Hulst³, Laura Mancini², Xavier Montalban⁸, Alex Rovira⁹, Maria Laura Stromillo⁴, Gioacchino Tedeschi⁷, Giancarlo Comi¹⁰, and Massimo Filippi^1
1Neuroimaging Research Unit, Institute of Experimental Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy,²Dept. Brain Repair and Rehabilitation, Institute of Neurology, UCL, London, GB, United Kingdom, ³Department of Radiology, Free University Medical Centre, Amsterdam, NL, Netherlands, ⁴Department of Neurological and Behavioral Sciences, University of Siena, Siena, SI, Italy, ⁵Division of Neuroradiology, Medical University of Graz, Graz, AT, Austria, ⁶Department of Neurology, Medical University of Graz, Graz, AT, Austria, ⁷Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, NA, Italy, ⁸Department of Neurology-Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, CT, Spain, ⁹Department of Radiology, Vall d’Hebron University Hospital, Barcelona, CT, Spain, ¹⁰Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, MI, Italy

Voxel-wise analysis to high-resolution 3DT1-weighted and diffusion tensor (DT)-MRI scans were applied to assess the structural correlates of cognitive dysfunction in multiple sclerosis (MS) patients and their validity in a multicenter setting. Twenty-three (37%) MS patients were classified as cognitively impaired (CI). Compared to cognitively preserved and controls, CI patients had atrophy of several deep gray matter nuclei, fronto-parietal regions and the corpus callosum (CC). Voxel-based approaches to define the regional distribution of brain damage in a multicenter setting in MS patients is feasible, contributing to better characterize disease clinical manifestations, including cognitive impairment.

Kiran K Seunarine¹, Kshitij Mankad², Michael Eyre², Cheryl Hemingway², and Christopher A Clark^1
1Imaging and Biophysics, UCL Institute of Child Health, London, London, United Kingdom, ²Great Ormond Street Hospital, London, United Kingdom

Paediatric onset multiple sclerosis (POMS) is known to result in a slower accumulation of physical disability over time despite the higher relapse rate than adult-onset MS. However, the mechanisms associated with POMS remain unclear. In this study we investigate microstructural differences between POMS patients and healthy control children using tract-space spatial statistics (TBSS). Results show widespread differences throughout the TBSS skeleton in paediatric MS compared to controls for all tensor metrics. These differences are consistent with severe demyelination. In addition to this, we observe correlations between tensor metrics and several clinical scores in the POMS patient group.