Novel Calibrated Short TR Recovery (CaSTRR) Method for Brain-Blood Partition Coefficient Correction Enhances Gray-White Matter Contrast in Blood Flow Measurements in Mice

Abstract

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 (BBPC white = 0.93 ± 0.05 mL/g) than cortical gray matter (BBPC gray = 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.

Brain–Blood Partition Coefficient and Cerebral Blood Flow in Canines Using Calibrated Short TR Recovery (CaSTRR) Correction Method

“…In this study we were able to produce BBPC maps of sufficient quality to perform voxel-wise correction of CBF maps with coverage of the entire brain using a CaSTRR acquisition protocol that only required 4 min of scan time. This is an improvement over the reported CaSTRR technique in mice which required 17 min of scan time due to the much higher resolution requirement of scanning small animals at 7T (Thalman et al, 2019). A 4 min scan time is comparable to the acquisition time of the pCASL technique for CBF.…”

“…Another significant advantage of this study is the use of Bayesian bias field correction to account for inhomogeneities in the receiver coil sensitivity profile. The CaSTRR method described in mice assumed a sufficiently homogenous profile in the birdcage receive coil, but observed significant signal loss near the large ear canals of the mouse (Thalman et al, 2019). Other BBPC studies attempted to correct for bias field using a separate measurement on a uniform phantom (Roberts et al, 1996; Leithner et al, 2010), but it is unlikely that the receiver profile would be the same when measuring the non-uniform tissue of a live subject.…”

“…For the CaSTRR proton density measurements a series of 2-D image stacks were acquired using a phase-spoiled, fast low-angle shot gradient echo (FLASH-GRE) sequence with varying repetition times (TR = 125, 250, 500, 1000, and 2000 ms) (Thalman et al, 2019). The shortest possible echo time (TE = 1.9 ms) was used to minimize T2 ∗ decay.…”

“…Therefore, the M 0 maps were calibrated to absolute water content in two ways. The first follows the previously published CaSTRR technique which uses a series of five phantoms containing mixtures of deuterium oxide and distilled water at 40, 30, 20, 10, and 0% (Thalman et al, 2019). These phantoms were also doped with 0.18 mM gadobutrol (Gadavist, Bayer Healthcare Pharmaceuticals, Whippany, NJ, United States) to reduce the longitudinal relaxation rate (T1) to be similar to the T1 of brain tissue (≈ 1.2 s).…”

“…This assumption is made because the previously published MRI methods to experimentally determine BBPC required prohibitively long acquisition times and ASL studies were generally focused on gray matter perfusion where BBPC variability was assumed to be small (Roberts et al, 1996; Leithner et al, 2010). A recent study in mice at 7T reported an 87% reduction in the acquisition time for BBPC maps using an MRI technique called calibrated short TR recovery (CaSTRR) (Thalman et al, 2019). Like previous methods, CaSTRR determines relative proton density using a series of gradient echo acquisitions with varying repetition times (TR) and then calibrates the proton density map using a set of deuterium doped phantoms which provide an absolute scale of water content.…”