Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Ravi Menon

Abstract

Multiple sclerosis (MS) is the most common neurological disease in young Canadians, yet its etiology remains obscure. Two possibly related findings in MS are brain iron deposition and the presence of small veins in white matter lesions. This thesis concerns the development and application of 3 Tesla magnetic resonance imaging tools to image iron and veins in early multiple sclerosis.

To facilitate measurements of iron concentration as well as production of cerebral venograms, we first optimized multi-echo susceptibility weighted imaging (SWI), using numerical simulations and input from physicians. We validated measurements of R2*, an MRI parameter that scales linearly with iron concentration.

Subsequently, we proposed quantification of the caliber of the internal jugular veins (IJVs) from magnetic resonance venograms. IJVs are implicated in the chronic cerebrospinal venous insufficiency model of MS, an increasingly disputed theory that attributes iron deposition in MS to venous abnormalities. We report that the coefficient of variation of measurements of average cross-sectional area of the IJVs is on the order of 7%.

We performed quantitative investigations of iron concentration in a cohort of patients at risk of MS diagnosis, compared to healthy controls. We report increased R2* (putative iron) in deep as well as cortical grey matter in patients. We subsequently measured IJV area, finding a trend for reduced total IJV caliber in patients; however, we found no correlation between R2* changes and IJV area.

We investigated the ability of multi-echo SWI to detect central veins within white matter hyperintensities (WMHs). We found that patients who converted from clinically isolated syndrome (CIS) to MS had a larger fraction of lesions with central veins compared to patients with non-converted CIS and healthy controls. Moreover, all patients who received a diagnosis of MS within the study window had >40% lesions with central veins at their CIS baselines, suggesting there may be predictive value in this biomarker.

The subjects from these last two studies represent a subset of our cohort in an ongoing longitudinal study. Using methodology described herein, we are equipped to further investigate different biomarkers of disease to better understand early pathology in MS.


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