3D MRI of whole-brain water permeability with intrinsic diffusivity encoding of arterial labeled spin (IDEALS)

This work proposes a novel MRI method - Intrinsic Diffusivity Encoding of Arterial Labeled Spin (IDEALS) - for the whole-brain mapping of water permeability in the human brain without an exogenous contrast agent. Quantitative separation of the intravascular and extravascular labeled water MRI signal was achieved in arterial spin labeling experiments with segmented 3D-GRASE acquisition by modulating the relative sensitivity between relaxation, true diffusion, and pseudodiffusion. The intrinsic diffusivity encoding in k-space created different broadening of the image-domain point spread functions for intravascular and extravascular labeled spins, from which blood-brain barrier (BBB) water extraction fraction (E_w) and water permeability surface area product (PS_w) were estimated. The feasibility and sensitivity of this method was evaluated in healthy subjects at baseline and after caffeine challenge. The estimated baseline E_w and PS_w maps showed contrast among gray matter (GM) and white matter (WM). GM E_w was significantly lower than that of WM (78.8% ± 3.3% in GM vs. 83.9% ± 4.6% in WM; p < 0.05) and GM PS_w was significantly higher than that of WM (131.7 ± 29.5 mL/100  g/min in GM vs. 76.2 ± 18.4 mL/100  g/min in WM; p < 0.05). BBB E_w was significantly lower for females than males (74.9% ± 3.7% for females vs. 81.3% ± 3.3% for males in GM; 80.5% ± 4.7% for females vs. 86.1 ± 3.0 for males in WM; p < 0.05 for both), while significant PS_w differences were only observed in WM (143.8 ± 34.4 mL/100  g/min for females vs. 123.6 ± 24.4 mL/100  g/min for males in GM; 91.6 ± 15.0 mL/100  g/min for females vs. 65.9 ± 12.5 mL/100  g/min for males in WM; p = 0.20 and p < 0.05 for GM and WM respectively). Significant correlations between E_w and CBF (r = -0.32, p < 0.05) and between PS_w and CBF (r = 0.89, p < 0.05) were observed, consistent with ¹⁵O-H₂O PET findings. After caffeine challenge, reduced CBF, E_w and PS_w were observed, demonstrating the sensitivity of IDEALS approach.