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Diffusion magnetic resonance imaging offers unique in vivo sensitivity totissue microstructure in brain white matter, which undergoes significantchanges during development and is compromised in virtually every neurologicaldisorder. Yet, the challenge is to develop biomarkers that are specific tomicrometer-scale cellular features in a human MRI scan of a few minutes. Herewe quantify the sensitivity and specificity of a multicompartment diffusionmodeling framework to the density, orientation and integrity of axons. Wedemonstrate that using a machine learning based estimator, our biophysicalmodel captures the morphological changes of axons in early development, acuteischemia and multiple sclerosis (total N=821). The methodology ofmicrostructure mapping is widely applicable in clinical settings and in largeimaging consortium data to study development, aging and pathology.

Mapping tissue microstructure of brain white matter in vivo in health and disease using diffusion MRI