Abstract
This study investigates the feasibility of multi-b-value, multi-directional diffusion MRI for assessing the anisotropy of the cerebral pseudo-diffusion (D*)-tensor. We examine D*-tensor's potential to (1) reflect CSF and blood flow, and (2) detect microvascular architectural alterations in cerebral small vessel disease (cSVD) and aging. METHODS: Multi-b-value diffusion MRI was acquired in 32 gradient directions for 11 healthy volunteers, and in six directions for 29 patients with cSVD and 14 controls at 3 T. A physics-informed neural network was used to estimate intravoxel incoherent motion (IVIM)-DTI model parameters, including the parenchymal slow diffusion (D-)tensor and the pseudo-diffusion (D*)-tensor, from which the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were derived. Comparisons of D*-tensor metrics were made between lateral, third, and fourth ventricles and between the middle cerebral arteries and superior sagittal sinus. Group differences in D*-tensor metrics in normal-appearing white matter were analyzed using multivariable linear regression, correcting for age and sex. RESULTS: D*-anisotropy aligned well with CSF flow and arterial blood flow. FA(D*), MD(D*), AD(D*), and RD(D*) were highest in the third, moderate in the fourth, and lowest in the lateral ventricles. The arteries showed higher MD(D*), AD(D*), and RD(D*) than the sagittal sinus. Higher FA(D*) in the normal-appearing white matter was related to cSVD diagnosis and older age, suggesting microvascular architecture alterations. CONCLUSION: Multi-b-value, multi-directional diffusion analysis using the IVIM-DTI model enables assessment of the cerebral microstructure, fluid flow, and microvascular architecture, providing information on neurodegeneration, glymphatic waste clearance, and the vasculature in one measurement.