Shannon Kolind

Myelin water imaging (MWI) is a quantitative magnetic resonance imaging (MRI) technique generally regarded as the most rigorous approach for non-invasive, in-vivo measurement of myelin content.Although MWI has proven valuable for the study of development, aging, disease, injury, genetics, and fundamental biology in the central nervous system, the power of its insights hinge on accurate characterization of normative values. To that end, we used MWI data from 100 adults (age 20-78) to create an optimized, unbiased myelin atlas and characterize how myelin content changes throughout the adult life span; an invaluable, openly available reference for future studies.In practice, lengthy acquisition times have limited the utility of MWI and often lead to alternative approaches being used to acquire surrogates for MWI. To compare the traditional multi-echo T2 relaxation and alternative steady-state MWI approaches, we created multivariate brain and spinal cord atlases and found an approximately linear relationship between myelin estimates, which broke down in the presence of unique relaxation times (spinal cord, tissue affected by disease pathology). This work will improve retrospective interpretation, and guide future design, of MWI studies.Next, we addressed lengthy MWI acquisition times using conventional compressed sensing before ultimately introducing the Constrained, Adaptive, Low-dimensional, Intrinsically Precise Reconstruction (CALIPR) framework. Drastically improved reconstruction performance allowed whole-brain MWI to be acquired using a previously unattainable sequence (fully sampled acquisition time 2h:57m:20s) in only 7m:26s with CALIPR (acceleration factor 23.9, 4.2% of the dataset). Reproducibility experiments demonstrated excellent precision, and CALIPR provided markedly increased sensitivity to demyelinating disease pathology (the hallmark application for myelin imaging). We implemented CALIPR for MWI of brain and spinal cord, and for two of the three largest MRI manufacturers. The CALIPR framework provides increased acceleration, precision, and sensitivity for MWI, and could be similarly transformative for other quantitative MRI applications.Finally, we implemented CALIPR on an ultra-low field (0.064T) portable, point-of-care MRI scanner to acquire accurate, quantitative T2 mapping data in
View record

Cognitive impairment is a common symptom in multiple sclerosis (MS) that presents in up to 70% of patients. Cognitive symptoms in MS typically manifest as deficits in attention, memory and/or processing speed, with processing speed being most frequently affected. MS-related cognitive impairment represents a major burden as it can significantly lower quality of life and is a main contributor to unemployment.Conventional magnetic resonance imaging (MRI) with T1-weighted and T2-weighted contrast is the mainstay of MS diagnosis and monitoring. However, conventional MRI is limited in that it is qualitative, lacks biological specificity and correlates poorly with clinical and cognitive status. In contrast, myelin water imaging (MWI) is an advanced MRI technique that measures the signal from water in the myelin bilayers, providing a quantitative myelin-specific measurement (myelin water fraction, MWF). The aim of this thesis is to investigate the relationship between myelin damage and cognitive performance in MS using MWI.First, we demonstrate that MWF in normal appearing white matter (NAWM) was significantly associated with processing speed performance in MS in 3 a priori selected white matter tracts associated with cognition. Next, we show that the relationship between NAWM MWF and cognitive performance extends to additional cognitive domains in a larger cohort. Finally, rather than selecting brain regions a priori, we employed an assumption-free data driven approach using permutation testing to show that myelin damage extent and anatomical location is unique to the cognitive domain being investigated, with greater myelin damage in these regions in cognitively impaired versus cognitively preserved patients. Further, we demonstrate that the severity and spatial extent of myelin damage in cognitive domain-specific white matter regions is strongly associated with cognitive performance.This thesis demonstrates that there is a strong relationship between the location and severity of myelin damage and MS-related cognitive impairment. As the treatment landscape for MS moves toward the development of remyelination therapies, understanding the role of myelin pathology in cognitive symptoms is critical for translating findings to clinical trials. These results also highlight the promise of MWI for monitoring myelin changes and their relationship to cognitive worsening and improvement when investigating new therapies.

View record