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

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 seconds/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.

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 4 groups: healthy controls (HCs) (n=42), patients with Parkinson disease (n=119), patients with Parkinson disease dementia (PDD) (n=16), and patients with progressive supranuclear palsy (PSP) (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.

In vivo, ALPS indices were higher at a b-value of 500 and 250 seconds/mm² compared with a b-value of 1000 seconds/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 seconds/mm²). In vivo, ALPS indices were lower in patients with PDD and PSP compared with HCs, though differences varied across b-values.

Both simulations and in vivo results suggest that the commonly used b-value of 1000 seconds/mm² is not optimal for assessing diffusion in the perivascular spaces. Intermediate b-values at approximately 700 seconds/mm² appear more suitable. However, further optimization of acquisition parameters is needed.