Myelin Water Imaging in Central Nervous System Disorders

Myelin water imaging is a quantitative MRI approach that isolates the signal arising from water trapped between the lipid bilayers of the myelin sheath, yielding a myelin water fraction (MWF) as an in vivo biomarker of myelin content. By acquiring multi-echo T2 relaxometry data and decomposing the decay into short, intermediate and long T2 components, this technique provides high specificity for myelin relative to other tissue compartments. Its sensitivity to demyelination and remyelination has been demonstrated in multiple sclerosis, leukodystrophies, traumatic brain injury and neurodevelopmental disorders. Beyond focal lesions, myelin water imaging enables whole-brain mapping of myelination patterns across ageing and in response to therapeutic interventions. Advances in acquisition speed, model regularisation and post-processing have improved spatial resolution and reduced scan times, facilitating translation into clinical research. The ability to quantify subtle alterations in myelin integrity supports early diagnosis, monitoring of disease progression and evaluation of remyelinating therapies, with global applicability across centres equipped with high-field and clinical-strength MRI scanners.

Research from Nature Portfolio

Comparative studies of multi-component myelin water fraction, T1w/T2w ratio and diffusion tensor imaging measures in healthy volunteers have revealed significant but region-dependent correlations among these metrics, underscoring that each modality offers unique microstructural insights. Myelin water fraction showed strong associations with diffusion anisotropy measures across white matter tracts, yet T1w/T2w and MWF exhibited only moderate concordance in cortical regions, highlighting the complementary nature of relaxometry and diffusion contrast. These findings inform the design of multi-modal protocols that integrate myelin water imaging with standard clinical sequences to enhance diagnostic specificity.

Deep learning–based segmentation of axons and myelin sheaths in microscopy data has provided quantitative benchmarks for validation of myelin water imaging. Convolutional neural network architectures trained on electron and light microscopy have achieved high pixel-wise accuracy in delineating myelinated fibres, enabling systematic comparison between histological ground truth and in vivo MWF measures. This synergy between advanced image analysis and relaxometry has accelerated the calibration of myelin water fraction as a tissue-specific biomarker in both preclinical models and human studies.

Myelin Water Imaging in Central Nervous System Disorders publication trend

The graph below shows the total number of articles in myelin water imaging in central nervous system disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Myelin water fraction (MWF): proportion of the MRI signal arising from water trapped between the layers of the myelin sheath, extracted via multi-echo T2 relaxometry.

T2 relaxometry: quantitative MRI technique that decomposes the decay of transverse magnetisation into multiple exponential components to characterise tissue microenvironments.

Diffusion tensor imaging (DTI): MRI method that measures the directionality and magnitude of water diffusion to infer microstructural architecture and integrity of white matter tracts.

Magnetic resonance fingerprinting (MRF): framework that acquires sequences with varying parameters to generate unique signal evolutions for simultaneous estimation of multiple tissue properties.

Magnetization transfer ratio (MTR): quantitative index of the exchange of magnetisation between free water protons and macromolecular-bound protons, often used as a surrogate for myelin density.

References

1. Comparisons between multi-component myelin water fraction, T1w/T2w ratio, and diffusion tensor imaging measures in healthy human brain structures. Scientific Reports (2019).
2. AxonDeepSeg: automatic axon and myelin segmentation from microscopy data using convolutional neural networks. Scientific Reports (2018).
3. 3D MR fingerprinting-derived myelin water fraction characterizing brain development and leukodystrophy. Journal of Translational Medicine (2023).
4. Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology. NeuroImage (2021).