A team of magnetic imaging scientists led by Dr. Ravi Menon, PhD, at the University of Western Ontario’s Robarts Research Institute have developed a better way to track the progression of Multiple Sclerosis (MS) from its very early stages. The Robarts researchers used a technique called Quantitative Susceptibility (QS) Magnetic Resonance Imaging (MRI), to measure a sort of damage in specific areas of the brain which the study showed to be common to all patients. The findings are published in advance online, in the journal Radiology.
Entitled “Multiple Sclerosis: Improved Identification of Disease-relevant Changes in Gray and White Matter Using Susceptibility-based MR Imaging” (DOI: http://dx.doi.org/10.1148/radiol.14132475) the paper is coauthored by Dr. Menon with David A. Rudko , PhD; Igor Solovey , MSc; Joseph S. Gati , MSc; and Marcelo Kremenchutzky , MD variously associated with the Department of Physics (D.A.R., R.S.M.), Center for Functional and Metabolic Mapping, Robarts Research Institute (D.A.R., I.S., J.S.G., R.S.M.), and the Department of Neurology, University Hospital (M.K.), University of Western Ontario London, Ontario, Canada.
The coauthors describe their research as an evaluation of the potential of quantitative susceptibility (QS) and R2* mapping as surrogate biomarkers of clinically relevant, age-adjusted demyelination and iron deposition in multiple sclerosis. All study participants gave written informed consent, and the study was approved by the institutional review board. Quantitative maps of the magnetic resonance imaging susceptibility parameters (R2* and QS) were computed for 25 patients with either clinically isolated syndrome (CIS) or relapsing-remitting MS, as well as for 15 age and sex-matched control subjects imaged at 7 T. The candidate MR imaging biomarkers were correlated with Extended Disability Status Scale (EDSS), time since CIS diagnosis, time since MS diagnosis, and age.
The process employed used a standard Siemens 3T MRI so it could be reproduced in any hospital, using the technique, called QS. The researchers mapped this MRI parameter in 25 patients with relapsing-remitting MS or clinically isolated syndrome (CIS half of those diagnosed with CIS will go on to be diagnosed with MS) measuring both demyelination and iron deposition. Fifteen age and sex-matched control subjects were also scanned. While brain and spine lesions visualized with normal MRI tend to appear and disappear over time, QS shows common areas of damage in all patients that correlated very well with the Extended Disability Status Score (EDSS) which is a standard tool used to measure MS progression, as well as with age and time since diagnosis.
The researchers report that QS maps aided identification of significant, voxel-level increases in iron deposition in subcortical gray matter (GM) of patients with MS compared with control subjects, and that Voxelwise QS also supported a significant contribution of age to demyelination in patients with MS, suggesting that age-adjusted clinical scores may provide more robust measures of MS disease severity compared with non age-adjusted scores. They conclude that using QS and R2* mapping, evidence of both significant increases in iron deposition in subcortical GM and myelin degeneration along the WM skeleton of patients with MS was identified. Both effects correlated strongly with EDSS.
“In MS research, there is something we call a clinical-radiological paradox,” says Dr. Menon in a Robarts Institute release. “When you do conventional MRIs on these patients you see lesions in the brain very clearly, but the number or volume of their lesions do not correlate with the patients disabilities. This paradox has been recognized since the MRI was introduced to clinical practice in the early 80s, and yet this is the only imaging tool we have for assessing MS. Our research provides a quantitative tool using a relatively conventional imaging sequence but with novel analysis. This tool shows that there is considerable damage occurring in common areas of all patients in both the white matter and in the deep brain structures the gray matter. Those quantitative measures what we call quantitative susceptibility, correlate with disease symptoms.”
“Significantly, in white matter, even where we see no lesions whatsoever, we’re able to measure damage in the same area of all patients using QS mapping. So even at the very earliest stages of the disease when the disability score is very low, or when the person hasn’t yet been diagnosed with MS, theres already significant damage,” added Dr. Menon, who holds the Canada Research Chair in Functional and Metabolic Mapping, and is a Professor of Medical Biophysics, Diagnostic Radiology & Nuclear Medicine, Neuroscience, Biomedical Engineering, and Psychiatry At UWO’s Robarts Research Institute. “This could have important diagnostic and prognostic implications, as there are drugs available to slow or stop the progression of MS, if started early enough.”
The Robarts Research Institute’s Centre for Functional and Metabolic Mapping (CFMM) at UWO houses Canada’s only collection of high-field (3T human) and ultra-high field (7T human and 9.4T animal) MR systems.
The Centre is dedicated to establishing the anatomical, metabolic and functional characteristics of normal brain development and healthy aging across the lifespan; as well as establishing the brain basis of developmental, neuropsychiatric and neurodegenerative deficits. The Laboratory for Functional Magnetic Resonance Research (LfMRR) is located in a purpose built addition to the Robarts Research Institute on the UWO Campus.
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