Magnetic resonance fingerprinting-based myelin water fraction mapping for the assessment of white matter maturation and integrity in typical development and leukodystrophies

Abstract

A quantitative biomarker for myelination, such as myelin water fraction (MWF), would boost the understanding of normative and pathological neurodevelopment, improving patients' diagnosis and follow-up. We quantified the fraction of a rapidly relaxing pool identified as MW using multicomponent three-dimensional (3D) magnetic resonance fingerprinting (MRF) to evaluate white matter (WM) maturation in typically developing (TD) children and alterations in leukodystrophies (LDs). We acquired DTI and 3D MRF-based R1, R2 and MWF data of 15 TD children and 17 LD patients (9 months-12.5 years old) at 1.5 T. We computed normative maturation curves in corpus callosum and corona radiata and performed WM tract profile analysis, comparing MWF with R1, R2 and fractional anisotropy (FA). Normative maturation curves demonstrated a steep increase for all tissue parameters in the first 3 years of age, followed by slower growth for MWF while R1, R2R₂ and FA reached a plateau. Unlike FA, MWF values were similar for regions of interest (ROIs) with different degrees of axonal packing, suggesting independence from fiber bundle macro-organization and higher myelin specificity. Tract profile analysis indicated a specific spatial pattern of myelination in the major fiber bundles, consistent across subjects. LD were better distinguished from TD by MWF rather than FA, showing reduced MWF with respect to age-matched controls in both ROI-based and tract analysis. In conclusion, MRF-based MWF provides myelin-specific WM maturation curves and is sensitive to alteration due to LDs, suggesting its potential as a biomarker for WM disorders. As MRF allows fast simultaneous acquisition of relaxometry and MWF, it can represent a valuable diagnostic tool to study and follow up developmental WM disorders in children.

Keywords: fractional anisotropy; imaging biomarker; leukodystrophies; magnetic resonance fingerprinting; myelin water fraction; neurodevelopment; relaxometry; white matter disorders.