  Diffusion magnetic resonance imaging offers unique in vivo sensitivity to
tissue microstructure in brain white matter, which undergoes significant
changes during development and is compromised in virtually every neurological
disorder. Yet, the challenge is to develop biomarkers that are specific to
micrometer-scale cellular features in a human MRI scan of a few minutes. Here
we quantify the sensitivity and specificity of a multicompartment diffusion
modeling framework to the density, orientation and integrity of axons. We
demonstrate that using a machine learning based estimator, our biophysical
model captures the morphological changes of axons in early development, acute
ischemia and multiple sclerosis (total N=821). The methodology of
microstructure mapping is widely applicable in clinical settings and in large
imaging consortium data to study development, aging and pathology.
