3D MR fingerprinting-derived myelin water fraction characterizing brain development and leukodystrophy

Background Magnetic resonance fingerprinting (MRF) enables fast myelin quantification via the myelin water fraction (MWF), offering a noninvasive method to assess brain development and disease. However, MRF-derived MWF lacks histological evaluation and remains unexamined in relation to leukodystrophy. This study aimed to access MRF-derived MWF through histology in mice and establish links between myelin, development, and leukodystrophy in mice and children, demonstrating its potential applicability in animal and human studies.Methods 3D MRF was performed on normal C57BL/6 mice with different ages, megalencephalic leukoencephalopathy with subcortical cyst 1 wild type (MLC1 WT, control) mice, and MLC 1 knock-out (MLC1 KO, leukodystrophy) mice using a 3 T MRI. MWF values were analyzed from 3D MRF data, and histological myelin quantification was carried out using immunohistochemistry to anti-proteolipid protein (PLP) in the corpus callosum and cortex. The associations between 'MWF and PLP' and 'MWF and age' were evaluated in C57BL/6 mice. MWF values were compared between MLC1 WT and MLC1 KO mice. MWF of normal developing children were retrospectively collected and the association between MWF and age was assessed.Results In 35 C57BL/6 mice (age range; 3 weeks-48 weeks), MWF showed positive relations with PLP immunoreactivity in the corpus callosum (beta = 0.0006, P = 0.04) and cortex (beta = 0.0005, P = 0.006). In 12-week-old C57BL/6 mice MWF showed positive relations with PLP immunoreactivity (beta = 0.0009, P = 0.003, R2 = 0.54). MWF in the corpus callosum (beta = 0.0022, P < 0.001) and cortex (beta = 0.0010, P < 0.001) showed positive relations with age. Seven MLC1 WT and 9 MLC1 KO mice showed different MWF values in the corpus callous (P < 0.001) and cortex (P < 0.001). A total of 81 children (median age, 126 months; range, 0-199 months) were evaluated and their MWF values according to age showed the best fit for the third-order regression model (adjusted R-2 range, 0.44-0.94, P < 0.001).Conclusion MWF demonstrated associations with histologic myelin quantity, age, and the presence of leukodystrophy, underscoring the potential of 3D MRF-derived MWF as a rapid and noninvasive quantitative indicator of brain myelin content in both mice and humans.

Automated summary

This study investigated the potential of Magnetic Resonance Fingerprinting (MRF) as a noninvasive method for quantifying brain myelin content. The study found associations between MRF-derived myelin water fraction (MWF) and histological myelin quantity, age, and the presence of leukodystrophy in both mice and humans. These findings highlight the potential applicability of MRF-derived MWF in assessing brain development and disease.