Using myelin water imaging to link underlying pathology to clinical function in multiple sclerosis: A scoping review

Background: Multiple sclerosis (MS) symptoms and pathology are heterogenous and complex. Identifying links between MS-related pathology (i.e., myelin damage) and associated clinical symptoms is critical for developing targeted therapeutics. Conventional MRI, commonly used for MS diagnosis and disease monitoring, lacks specificity with functional performance. Myelin water imaging (MWI) demonstrates increased specificity to myelin and is viewed as the gold standard for imaging myelin content in vivo. Yet, there is a paucity of MWI studies in MS and only a limited number also examine clinical function. Thus, it remains unknown whether MWI corresponds to functional performance in MS. This scoping review aimed to examine relations between MWI and functional domains relevant to MS to inform and guide future research. Methods: Seven databases were searched from their inception to September 1, 2021. Studies of adults with MS that included both brain MWI and either a measure of physical function, a measure of cognitive function, or a measure of disease severity were included. Thirteen studies (11 observational, 2 intervention) met the inclusion criteria. Results: The most commonly investigated MWI metric is the myelin water fraction (MWF). Persons with MS demonstrated markedly decreased MWF compared to healthy controls globally and across brain regions of interest (ROIs). Decreased MWF was associated with higher disability, worse motor and cognitive performance and decreased intervention response. Only five studies examined structure-function relationships in brain areas related to walking and cognitive function and only six studies extracted MWI metrics from explicit brain ROIs. Conclusions: MWI is a neuroimaging technique with increased specificity to myelin and offers greater insight to MS-driven pathology and its clinical manifestations, including motor and cognitive dysfunction and rehabilitation response. This scoping review identified critical gaps in MWI research in MS to offer future perspectives including ROI-based studies, inclusion of multi-domain functional assessment and examining MWI to provide evidence of neuroplasticity following training.