|MRI of Multiple Sclerosis|
Pathological Basis of Dirty Appearing White Matter in
Multiple Sclerosis: Insights from MRI and Histology
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.
Addressing the Enigma of Invisible Pathology in MS: A
Multimodal Approach to Characterize Diffusely Abnormal and
Normal-Appearing White Matter
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.
MRI of Multiple Sclerosis with High
Contrast Susceptibility-Weighting and Extreme Resolution T2-Weighting
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.
Phase Imaging of Multiple Sclerosis at 7T
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.
In Vivo Characterization of Cortical Lesions in
Multiple Sclerosis by 7T MRI
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.
Indication of Oxidative Stress in Multiple Sclerosis
Using Proton MR Spectroscopic Imaging at 7T
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.
High Field MRI for Lesion
Characterisation in Multiple Sclerosis
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.
7 Tesla Sodium MRI of Patients with Multiple
Sclerosis: A Preliminary Study
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.
Magnetization Transfer Ratio Imaging in Multiple
Sclerosis – a Comparison of 3D Balanced Steady-State Free Precession and
2D Gradient Echo Sequences in Clinical Studies
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.
Tract-Based Spatial Statistics Shows Lower FA in the
Fornices of Early MS Patients
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.