Balancing Accuracy and Precision: Optimal b-Values for Diffusion Tensor Imaging along the Perivascular Space

Background and Purpose: The glymphatic system facilitates perivascular clearance, and its dysfunction has been implicated in neurodegenerative diseases. Diffusion Tensor Imaging Along the Perivascular Space (DTI-ALPS) has been proposed as an indirect approach to assess glymphatic function, but its reliability is debated. The choice of b-value is an aspect of possible improvement. While a b-value of 1000 s/mm2 is commonly used, the optimal b-value for DTI-ALPS remains unknown. This study aims to determine the optimal b-value for DTI-ALPS. Methods: Simulations were conducted to examine how the choice of maximum b-value influences bias, precision, and effect size of the ALPS index. DTI-ALPS was applied in a cohort of 194 participants divided into four groups: healthy controls (n=42), Parkinson’s disease patients (n=119), Parkinson’s disease dementia patients (n=16), and progressive supranuclear palsy patients (n=17). ALPS indices were calculated by manually placing regions of interest on projection and association fibers in each hemisphere. Group differences in ALPS indices across b-values were analyzed using mixed models. Results: In vivo, ALPS indices were higher at a b-value of 500 and 250 s/mm2 compared to a b-value of 1000 s/mm2 in both hemispheres. Simulations indicated a bias-variance trade-off: very low b-values reduced sensitivity and compromised precision, while high b-values improved precision but reduced accuracy. The simulated effect size of the ALPS index peaked at intermediate b-values (≈700 s/mm2). In vivo, ALPS indices were lower in Parkinson’s disease dementia and Progressive supranuclear palsy patients compared to healthy controls, though differences varied across b-values. Conclusions: Both simulations and in vivo results suggest that the commonly used b-value of 1000 s/mm2 is not optimal for assessing diffusion in the perivascular spaces. Intermediate b-values at approximately 700 s/mm2 appear more suitable. However, further optimization of acquisition parameters is needed.