Quantification of Myelin Content Using Synthetic MRI in Demyelinating Disorders

Abstract

Myelin is essential for efficient neural conduction and axonal integrity, and its loss underlies a wide range of central nervous system (CNS) disorders. Accurate in vivo quantification of myelin content remains a longstanding challenge due to the complex biophysical properties of myelin and the limitations of conventional MRI techniques. Synthetic MRI (SyMRI) has recently emerged as a practical and quantitative method for assessing myelin by simultaneously measuring relaxation parameters R1, R2, and proton density from a single acquisition. Using these data, SyMRI generates myelin volume fraction (myelin VF) maps that provide voxel-wise and volumetric estimates of myelin content.

SyMRI offers significant advantages, including short acquisition times, automated segmentation, and robust reproducibility across scanners. Its clinical utility has been demonstrated in multiple sclerosis (MS), where myelin VF correlates with lesion burden, disability scores, and treatment-related remyelination. Beyond MS, SyMRI has shown potential in amyotrophic lateral sclerosis (ALS), tuberous sclerosis complex, and acute ischemic stroke, highlighting its versatility across demyelinating and neurodegenerative conditions. Validation studies reveal strong correlations between SyMRI metrics, histopathology, and other imaging biomarkers such as magnetization transfer saturation and diffusion parameters.
Despite promising results, standardization of acquisition protocols, segmentation algorithms, and normative databases is needed for wider clinical adoption. Continued refinement and integration with complementary imaging modalities could establish SyMRI as a cornerstone technique for quantitative myelin imaging, improving diagnostic precision, monitoring of disease progression, and evaluation of therapeutic response in demyelinating disorders.