Combined arterial spin labeling and diffusion-weighted imaging for noninvasive estimation of capillary volume fraction and permeability-surface product in the human brain

A number of two-compartment models have been developed for the analysis of arterial spin labeling (ASL) data, from which both cerebral blood flow (CBF) and capillary permeability-surface product (PS) can be estimated. To derive values of PS, the volume fraction of the ASL signal arising from the intravascular space (v(bw)) must be known a priori. We examined the use of diffusion-weighted imaging (DWI) and subsequent analysis using the intravoxel incoherent motion model to determine v(bw) in the human brain. These data were then used in a two-compartment ASL model to estimate PS. Imaging was performed in 10 healthy adult subjects, and repeated in five subjects to test reproducibility. In gray matter (excluding large arteries), mean voxel-wise v(bw) was 2.3 +/- 0.2 mL blood/100 g tissue (all subjects mean +/- s.d.), and CBF and PS were 44 +/- 5 and 108 +/- 2 mL per 100 g per minute, respectively. After spatial smoothing using a 6-mm full width at half maximum Gaussian kernel, the coefficient of repeatability of CBF, v(bw), and PS were 8 mL per 100 g per minute, 0.4 mL blood/10 g tissue, and 13 mL per 100 g per minute, respectively. Our results show that the combined use of ASL and DWI can provide a new, noninvasive methodology for estimating v(bw) and PS directly, with reproducibility that is sufficient for clinical use. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 67-75; doi:10.1038/jcbfm.2012.125; published online 19 September 2012