Diffusion‐derived intravoxel‐incoherent motion anisotropy relates to CSF and blood flow

Purpose 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.