Optimizing the intrinsic parallel diffusivity in NODDI: An extensive empirical evaluation

PURPOSE: NODDI is widely used in parameterizing microstructural brain properties. The model includes three signal compartments: intracellular, extracellular, and free water. The neurite compartment intrinsic parallel diffusivity (d(∥)) is set to 1.7 μm(2)⋅ms(−1), though the effects of this assumption have not been extensively explored. This work investigates the optimality of d(∥) = 1.7 μm(2)⋅ms(−1) under varying imaging protocol, age groups, sex, and tissue type in comparison to other biologically plausible values of d(∥). METHODS: Model residuals were used as the optimality criterion. The model residuals were evaluated in function of d(∥) over the range from 0.5 to 3.0 μm(2)⋅ms(−1). This was done with respect to tissue type (i.e., white matter versus gray matter), sex, age (infancy to late adulthood), and diffusion-weighting protocol (maximum b-value). Variation in the estimated parameters with respect to d(∥) was also explored. RESULTS: Results show d(∥) = 1.7 μm(2)⋅ms(−1) is appropriate for adult brain white matter but it is suboptimal for gray matter with optimal values being significantly lower. d(∥) = 1.7 μm(2)⋅ms(−1) was also suboptimal in the infant brain for both white and gray matter with optimal values being significantly lower. Minor optimum d(∥) differences were observed versus diffusion protocol. No significant sex effects were observed. Additionally, changes in d(∥) resulted in significant changes to the estimated NODDI parameters. CONCLUSION: The default (d(∥)) of 1.7 μm(2)⋅ms(−1) is suboptimal in gray matter and infant brains.