%0 Journal Article
%T Histological Validation and Clinical Application of 3D MR Fingerprinting-Derived Myelin Water Fraction in Brain Development and Leukodystrophy
%A Wei Jian Zhang
%A Liang Chen
%A Hao Ming Zhou
%A Qiang Sun
%A Bo Liu
%A Yifan Wang
%J Journal of Medical Sciences and Interdisciplinary Research
%@ 3108-4826
%D 2025
%V 5
%N 1
%R 10.51847/RaQVGlUyfR
%P 43-56
%X Magnetic resonance fingerprinting (MRF) allows rapid, noninvasive estimation of myelin content through the myelin water fraction (MWF), providing a tool for monitoring brain maturation and pathological changes. Despite this potential, MRF-derived MWF has not been systematically validated against histology, and its application in leukodystrophy remains unexplored. The present study aimed to confirm the histological basis of MRF-derived MWF in mice and to investigate how MWF relates to myelin, developmental stage, and leukodystrophy in both murine models and pediatric populations, demonstrating its translational potential. We performed 3D MRF on normal C57BL/6 mice at multiple ages, on megalencephalic leukoencephalopathy with subcortical cyst 1 wild type (MLC1 WT) mice, and on MLC1 knock-out (MLC1 KO) mice using a 3 T MRI system. MWF maps were extracted from the 3D MRF datasets, and myelin content was quantified histologically using anti-proteolipid protein (PLP) staining in the corpus callosum and cortex. Relationships between ‘MWF and PLP’ and between ‘MWF and age’ were evaluated in C57BL/6 mice. Differences in MWF were compared between MLC1 WT and KO mice. Retrospective data from 81 normally developing children were analyzed to assess age-dependent changes in MWF. In 35 C57BL/6 mice (ages 3–48 weeks), MWF showed significant positive associations with PLP immunoreactivity in both the corpus callosum (β = 0.0006, P = 0.04) and cortex (β = 0.0005, P = 0.006). In 12-week-old C57BL/6 mice, MWF correlated strongly with PLP (β = 0.0009, P = 0.003, R² = 0.54). Age-dependent increases in MWF were observed in the corpus callosum (β = 0.0022, P < 0.001) and cortex (β = 0.0010, P < 0.001). Seven MLC1 WT and nine MLC1 KO mice displayed significantly different MWF values in both regions (P < 0.001 for corpus callosum and cortex). In 81 children (median age 126 months, range 0–199 months), MWF changes with age were best described by a third-order polynomial regression (adjusted R² = 0.44–0.94, P < 0.001). MWF closely reflected histologically measured myelin, age-related maturation, and the presence of leukodystrophy, supporting 3D MRF-derived MWF as a rapid, noninvasive quantitative marker of myelin in both animal models and humans.
%U https://smerpub.com/article/histological-validation-and-clinical-application-of-3d-mr-fingerprinting-derived-myelin-water-fracti-5psv5isrncs2ryh