Related Experiment Video
Updated: Aug 7, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
3D MR fingerprinting-derived myelin water fraction characterizing brain development and leukodystrophy
Hyun Gi Kim1, Dongyeob Han2, Jimin Kim1
1Department of Radiology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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 (β = 0.0006, P = 0.04) and cortex (β = 0.0005, P = 0.006). In 12-week-old C57BL/6 mice MWF showed positive relations with PLP immunoreactivity (β = 0.0009, P = 0.003, R2 = 0.54). MWF in the corpus callosum (β = 0.0022, P < 0.001) and cortex (β = 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 R2 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.
Insights
Magnetic resonance fingerprinting (MRF) provides fast myelin water fraction (MWF) measurements. This study validates MRF-derived MWF against histology, showing its potential for assessing myelin in mouse models and human leukodystrophy.
Area of Science:
- Neuroimaging
- Biophysics
- Developmental Neuroscience
Background:
- Magnetic Resonance Fingerprinting (MRF) allows rapid myelin quantification through Myelin Water Fraction (MWF).
- MRF-derived MWF is a noninvasive tool for assessing brain development and disease.
- Histological validation of MRF-derived MWF and its relation to leukodystrophy are underexplored.
Purpose of the Study:
- To validate MRF-derived MWF using histology in mice.
- To establish the relationship between myelin, development, and leukodystrophy in mice and children.
- To demonstrate the potential applicability of 3D MRF in animal and human studies.
Main Methods:
- 3D MRF was performed on mice (C57BL/6, MLC1 WT, MLC1 KO) and children.
- Myelin Water Fraction (MWF) values were analyzed and compared with histological myelin quantification (PLP immunoreactivity).
- Associations between MWF, myelin markers, age, and leukodystrophy were evaluated.
Main Results:
- MRF-derived MWF positively correlated with myelin markers (PLP) and age in mice.
- Significant differences in MWF were observed between wild-type and leukodystrophy model mice.
- MWF in children showed a strong age-dependent relationship, fitting a third-order regression model.
Conclusions:
- MRF-derived MWF correlates with histological myelin content and developmental age.
- MRF-derived MWF effectively differentiates between healthy and leukodystrophy models.
- 3D MRF is a promising rapid, noninvasive method for quantifying brain myelin in both animal models and humans.
