Novel calibrated short TR recovery (CaSTRR) method for brain-blood partition coefficient correction enhances gray-white matter contrast in blood flow measurements in mice

The goal of the study was to develop a novel, rapid Calibrated Short TR Recovery (CaSTRR) method to measure the brain-blood partition coefficient (BBPC) in mice. The BBPC is necessary for quantifying cerebral blood flow (CBF) using tracer-based techniques like arterial spin labeling (ASL), but previous techniques required prohibitively long acquisition times so a constant BBPC equal to 0.9 mL/g is typically used regardless of studied species, condition, or disease. An accelerated method of BBPC correction could improve regional specificity in CBF maps particularly in white matter. Male C57Bl/6N mice (n = 8) were scanned at 7T using CaSTRR to measure BBPC determine regional variability. This technique employs phase-spoiled gradient echo acquisitions with varying repetition times (TRs) to estimate proton density in the brain and a blood sample. Proton density weighted images are then calibrated to a series of phantoms with known concentrations of deuterium to determine BBPC. Pseudo-continuous ASL was also acquired to quantify CBF with and without empirical BBPC correction. Using the CaSTRR technique we demonstrate that, in mice, white matter has a significantly lower BBPC (BBPCwhite = 0.93 ± 0.05 mL/g) than cortical gray matter (BBPCgray = 0.99 ± 0.04 mL/g, p = 0.03), and that when voxel-wise BBPC correction is performed on CBF maps the observed difference in perfusion between gray and white matter is improved by as much as 14%. Our results suggest that BBPC correction is feasible and could be particularly important in future studies of perfusion in white matter pathologies.