Rapid and efficient transmission of electric signals among neurons of vertebrates is ensured by myelin‐insulating sheaths surrounding axons. Human cognition, sensation, and motor functions rely on the integrity of these layers, and demyelinating diseases often entail serious cognitive and physical impairments. Magnetic resonance imaging radically transformed the way these disorders are monitored, offering an irreplaceable tool to noninvasively examine the brain structure. Several advanced techniques based on MRI have been developed to provide myelin‐specific contrasts and a quantitative estimation of myelin density in vivo. Here, the vast offer of acquisition strategies developed to date for this task is reviewed. Advantages and pitfalls of the different approaches are compared and discussed.

Recovering the T2 distribution from multi-echo T2 magnetic resonance (MR) signals is challenging but has high potential as it provides biomarkers characterizing the tissue micro-structure, such as the myelin water fraction (MWF). In this work, we propose to combine machine learning and aspects of parametric (fitting from the MRI signal using biophysical models) and non-parametric (model-free fitting of the T2 distribution from the signal) approaches to T2 relaxometry in brain tissue by using a multi-layer perceptron (MLP) for the distribution reconstruction. For training our network, we construct an extensive synthetic dataset derived from biophysical models in order to constrain the outputs with a priori knowledge of in vivo distributions. The proposed approach, called Model-Informed Machine Learning (MIML), takes as input the MR signal and directly outputs the associated T2 distribution. We evaluate MIML in comparison to a Gaussian Mixture Fitting (parametric) and Regularized Non-Negative Least Squares algorithms (non-parametric) on synthetic data, an ex vivo scan, and high-resolution scans of healthy subjects and a subject with Multiple Sclerosis. In synthetic data, MIML provides more accurate and noise-robust distributions. In real data, MWF maps derived from MIML exhibit the greatest conformity to anatomical scans, have the highest correlation to a histological map of myelin volume, and the best unambiguous lesion visualization and localization, with superior contrast between lesions and normal appearing tissue. In whole-brain analysis, MIML is 22 to 4980 times faster than the non-parametric and parametric methods, respectively.