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Cornelia Laule¹, Irene M. Vavasour¹, Esther Leung¹, David K. B. Li¹, Piotr Kozlowski¹, Anthony L. Traboulsee¹, Joel Oger¹, Alex L. MacKay¹, G.R. Wayne Moore¹

¹University of British Columbia, Vancouver, Canada

The pathological basis of dirty-appearing white matter (DAWM) in MS is not known. 53 MS subjects were examined with T₁, multi-echo T₂ and magnetisation transfer (MT). 23 samples of formalin-fixed MS tissue were examined with multi-echo T₂ and a wide variety of histological stains for axons, myelin lipids and proteins. DAWM in-vivo had reduced myelin water and MT ratio, and increased T₂ and water content. Histological analysis suggests DAWM is the MRI equivalent of a region with selective reduction of myelin phospholipids detected by the MWF, but with a relative preservation of myelin proteins, as well as axons.

Alexandra Seewann¹, Hugo Vrenken², Erwin Blezer³, Lars Boe², Jonas Castelijns², Chris Polman², Petra Pouwels², Frederik Barkhof², Jeroen Geurts²

¹VU University Medical center, Amsterdam, Netherlands; ²VU University Medical Center, Amsterdam, Netherlands; ³University Medical Center Utrecht, Utrecht, Netherlands

Extralesional, diffusely affected white matter (DAWM), as detected on conventional MRI, may also contribute to lesion  burden and hence disability in multiple sclerosis patients (MS) patients. As the histopathological correlates of DAWM are unknown, the aim of this post-mortem study was to radiologically and histologically characterize tissue changes in DAWM as compared to normal-appearing WM (NAWM). Seventeen brain slices from 10 chronic MS patients were imaged with qualitative MRI at two different field strengths and with quantitative MRI. Regions of interest (ROIs) were correlated with histopathology.DAWM represents a separate pathological process, reflecting significantly abnormal  quantitative MRI and histopathology measures.

Amir Eissa¹, Robert Marc Lebel¹, Jeff Robert Korzan, Anna Edith Zavodni, Kenneth Gary Warren, Derek James Emery, Alan H. Wilman¹

¹University of Alberta, Edmonton, Canada

Patients with multiple sclerosis are imaged at 4.7 Tesla using T2-weighted fast spin echo with 0.19 cubic millimetre voxels, and susceptibility-weighted imaging with increased contrast.  The phase images from susceptibility weighting reveal increased iron content in some lesions, while the T2-images show precise lesion boundaries.

Kathryn E. Hammond¹, Daniel Pelletier, Meredith Metcalf, Radhika Srinivasan, Duan Xu, Doug A. Kelley, Daniel B. Vigneron, ¹, Sarah J. Nelson, ¹

¹University of California San Francisco (UCSF) / Berkeley Joint Graduate Group in Bioengineering, San Francisco, California , USA

The phase of the MR signal is sensitive to magnetic susceptibility-shifted compounds such as iron and provides a new contrast mechanism for studying neurodegeneration. Gradient echo images of seventeen RRMS patients were acquired at 7T at a resolution of 195x260 microns. The phase images showed novel contrast in lesions in the deep medullary veins. The phase contrast was often focused at the lesion periphery, a region known to have iron-laden macrophages in acute plaques and non-heme iron deposits in chronic plaques. MS patients had significantly higher phase contrast in the basal ganglia than controls, suggesting increased iron deposition.

Caterina Mainero¹, Andre van der Kouwe¹, Thomas Benner¹, Graham Wiggins¹, Bruce R. Rosen¹, R Philip Kinkel²

¹Massachusetts General Hospital, Charlestown, Massachusetts, USA; ²Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

Although the development of cortical lesions has emerged as a major component of disease progression in multiple sclerosis (MS), the study of such lesions is constrained by the technical limitations of currently available MR techniques. Recent data at ultra-high field (7 T) indicate the ability to visualize cortical structure in great detail, potentially improving the detection of cortical MS lesions. Our preliminary data show the ability of high field 7T MRI not only to detect but also to characterize cortical lesions heterogeneity in MS patients. Different type of cortical lesions might have different pathogenesis and impact on disease outcome.

Radhika Srinivasan¹, Sarah Nelson¹, Kathyrn Hammond¹, Duan Xu¹, Douglas Kelley², Daniel B. Vigneron¹, Daniel Pelletier¹

¹University of california, San Francisco, California , USA; ²GE Medical Systems, USA

Oxidative stress is believed to be one of the causes that can trigger neurodegeneration in MS. The GST supergene family that encodes for enzymes involved in GSH metabolism were differentially expressed in plaques and shown to affect long term prognosis in MS. Glutathione (GSH) is accessible for measurement using non-invasive proton spectroscopic imaging techniques. It is therefore possible to provide a metric for oxidative state and phenotype in MS. However, since GSH is present in low concentrations in the brain and overlaps with stronger resonances it is not visible at lower field strengths such as 3T. In this study we use the benefit of improved SNR and chemical shift dispersion at 7T to develop a spectral editing scheme for the unobstructed detection of GSH. Using this technique the concentration of GSH is evaluated in white and gray matter in MS and compared to normal subjects.

Klaus Schmierer¹, Po-Wah So², David H. Miller¹, Sebastian Brandner¹, Harold G. Parkes¹, Tarek A. Yousry¹

¹Institute of Neurology, UCL, London, UK; ²Imperial College London, Hammersmith Hospital Campus, London, UK

Multiple sclerosis (MS) affects central nervous system white matter (WM) and grey matter (GM). Unlike WM lesions (WML), GM lesions (GML) are rarely detected at 1.5T. In order to better characterise GML multimodal MRI (T1, T2, MTR, diffusion) was performed on post mortem MS brain at 9.4T. In seven formalin fixed tissue blocks 11 GML and 9 WML were detected. All MR modalities provided useful measures to assess MS pathology. Contrast-to-noise was highest for both GML and WML at TE=24ms in T2 weighted acquisition. Formalin fixation (start, duration) were confounders of some MRI indices.

Guillaume Madelin¹, Niels Oesingmann², Glyn Johnson¹, Sonia Nielles-Vallespin³, Bernd Stoeckel², Enzo Barberi⁴, Robert Pinkerton⁴, Daniel Sodickson¹, Robert I. Grossman¹, Matilde Inglese¹

¹New York University, New York, New York, USA; ²Siemens Medical Solutions, New York, New York, USA; ³Siemens AG, Erlangen, Germany; ⁴XLR imaging Inc, London, Canada

Multiple Sclerosis (MS) is a multi-focal, demyelinating disease with involvement of neurons and axons. Pathological and imaging studies have shown that neuro-axonal loss occurs from disease onset, and that it correlates with disability. There is increasing evidence that the intra-axonal accumulation of sodium ions may contribute to degeneration. Sodium MRI (23Na MRI) provides an indicator of cellular and metabolic integrity. The low sensitivity and spatial resolution of 23Na MRI make higher field strengths desirable to improve this imaging modality. The aim of this study was to optimize 23Na MRI at 7T and investigate its feasibility to study patients with MS.

Jochen G. Hirsch¹, ², Oliver Bieri¹, Klaus Scheffler¹, Alain Thoeni¹, Ernst-Wilhelm Radue¹, Ludwig Kappos¹, Achim Gass¹

¹University Hospital Basel, Basel, Switzerland

There is great need for techniques, that quantitatively assess subtle tissue changes beyond the gross pathology in multiple sclerosis. We evaluated a new 3D-bSSFP MTR protocol yielding maximal sensitivity to MT in human brain. We compared this 3D-bSSFP with the commonly used 2D-GRE approach in a clinical setup, and evaluated the advantages of bSSFP in a quantitative study on 20 MS patients. Protocols were adjusted to similar acquisition times while using optimized sequence settings for both approaches. Higher, and esp. isotropic resolution, whole brain coverage, and stronger grey-white matter MTR contrast turned out to be the important advantages of 3D-bSSFP.

Stefan Dirk Roosendaal¹, Jeroen J.G. Geurts¹, Hugo Vrenken, Keith S. Cover, Jonas A. Castelijns¹, Petra J.W. Pouwels, Frederik Barkhof¹

¹MS Center, Amsterdam, Netherlands

With the recently developed method Tract-Based Spatial Statistics, DTI measures of white matter can be compared voxelwise. This tool was used on DTI data of 31 patients with Multiple Slerosis and 31 age-matched healthy controls. In our study, which is one of the first to use TBSS in MS, we found that MS patients have areas of lower FA, not only in the WM commonly affected by lesions, but also more specifically in structures involved in memory processing, like the fornices and the hippocampus. These areas were found to be already affected in the early stages of the disease.