In vivo restricted diffusion imaging (RDI) is sensitive to differences in axonal density in typical children and adults.

The ability to dissociate axonal density in vivo from other microstructural properties is important for the diagnosis and treatment of neurologic disease, and new methods to do so are being developed. We investigated one such method-restricted diffusion imaging (RDI)-to see whether it can more accurately replicate histological axonal density patterns in the corpus callosum (CC) of adults and children compared to diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and generalized q-sampling imaging (GQI) methods. To do so, we compared known axonal density patterns defined by histology to diffusion-weighted imaging (DWI) scans of 840 healthy 20- to 40-year-old adults, and to DWI scans of 129 typically developing 7-month-old to 18-year-old children and adolescents. Contrast analyses were used to compare pattern similarities between the in vivo metric and previously published histological density models. We found that RDI was effective at mapping axonal density of small (Cohen's d = 2.60) and large fiber sizes (Cohen's d = 2.84) in adults. The same pattern was observed in the developing sample (Cohen's d = 3.09 and 3.78, respectively). Other metrics, notably NODDI's intracellular volume fraction in adults and GQI generalized fractional anisotropy in children, were also sensitive metrics. In conclusion, the study showed that the novel RDI metric is sensitive to density of small and large axons in adults and children, with both single- and multi-shell acquisition DWI data. Its effectiveness and availability to be used on standard as well as advanced DWI acquisitions makes it a promising method in clinical settings.