One diffusion acquisition and different white matter models: How does microstructure change in human early development based on WMTI and NODDI?

•We analyze the microstructural changes in human white matter tracts from ages 0 to 3.•We compare two biophysical models: White Matter Tract Integrity metrics and NODDI.•Both models reveal a large increase in axonal water fraction and tortuosity.•The changes are consistent with myelination, fiber asynchrony and classification.•The quantitative mismatch between models is explained by differences in assumptions.

White matter microstructural changes during the first three years of healthy brain development are characterized using two different models developed for limited clinical diffusion data: White Matter Tract Integrity (WMTI) metrics from Diffusional Kurtosis Imaging (DKI) and Neurite Orientation Dispersion and Density Imaging (NODDI). Both models reveal a non-linear increase in intra-axonal water fraction and in tortuosity of the extra-axonal space as a function of age, in the genu and splenium of the corpus callosum and the posterior limb of the internal capsule. The changes are consistent with expected behavior related to myelination and asynchrony of fiber development. The intra- and extracellular axial diffusivities as estimated with WMTI do not change appreciably in normal brain development. The quantitative differences in parameter estimates between models are examined and explained in the light of each model's assumptions and consequent biases, as highlighted in simulations. Finally, we discuss the feasibility of a model with fewer assumptions.