Myelin water imaging as a quantitative diagnostic tool for neurodegenerative diseases: a systematic review

Introduction: Neurodegenerative diseases such as multiple sclerosis (MS), Alzheimer’s disease (AD), and Parkinson’s disease (PD) share overlapping clinical and pathological features, complicating early diagnosis and management. Demyelination, a key pathological hallmark, underscores the importance of accurately assessing white matter (WM) integrity. Content: Myelin water imaging (MWI), an advanced non-invasive MRI technique, quantifies the myelin water fraction (MWF) and offers high specificity for detecting myelin abnormalities. This systematic review explores the feasibility and diagnostic utility of MWI across MS, AD, and PD by analyzing 21 high-quality studies from major databases, following PRISMA guidelines. Summary: MWI consistently revealed reduced MWF in MS patients across various WM regions, lesion types, and disease stages, including responsiveness to early treatment. In AD, MWF decline correlated with disease progression and apolipoprotein E4 (APOE4) genotype, supporting its potential in early diagnosis. Findings in PD were inconsistent, reflecting secondary or minimal myelin involvement in its pathology. Outlook: MWI shows strong promise as a non-invasive imaging biomarker, particularly in MS and AD. Standardization of acquisition protocols, integration with multimodal imaging, and further longitudinal studies are essential to establish its clinical utility and support broader implementation in neurodegenerative disease diagnostics.