Coupling between cerebral blood flow and cerebral blood volume: Contributions of different vascular compartments

Abstract

A better understanding of the coupling between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is vital for furthering our understanding of the BOLD response. The aim of this study was to measure CBF-CBV coupling in different vascular compartments during neural activation. Three haemodynamic parameters were measured during a visual stimulus. Look-Locker flow-sensitive alternating inversion recovery was used to measure changes in CBF and arterial CBV (CBV_a ) using sequence parameters optimized for each contrast. Changes in total CBV (CBV_tot ) were measured using a gadolinium-based contrast agent technique. Haemodynamic changes were extracted from a region of interest based on voxels that were activated in the CBF experiments. The CBF-CBV_tot coupling constant α_tot was measured as 0.16 ± 0.14 and the CBF-CBV_a coupling constant α_a was measured as 0.65 ± 0.24. Using a two-compartment model of the vasculature (arterial and venous), the change in venous CBV (CBV_v ) was predicted for an assumed value of baseline arterial and venous blood volume. These results will enhance the accuracy and reliability of applications that rely on models of the BOLD response, such as calibrated BOLD.

Keywords: BOLD; CBF-CBV coupling; arterial spin labelling; cerebral blood volume; fMRI.

Figure 1

A, overview of the experimental protocol including visual stimulus blocks (red lines), contrast agent injections (arrow Gd) and experimental details. B, example pulse sequence diagram of LL‐FAIR scheme used for CBF quantification with FAIR labelling followed by five EPI readouts. The initial four flip angles have θ = 35°, with a final readout pulse of flip angle of 90°. The first readout pulse occurs following an initial inversion delay (T _I = 600 ms) with subsequent readouts separated by a time interval (T _A = 350 ms). Data are collected with vascular crushing (VENC = 7.8 mm/s). the sequence is then repeated with repetition time T _R. C, CBV_a quantification with FAIR labelling followed by 19 EPI readouts. The first 18 flip angles are θ = 50°, with a final readout pulse of flip angle of 90°. The first readout pulse occurs following an initial inversion delay (T _I = 150 ms), with subsequent readouts separated by a time interval (T _A = 100 ms). The sequence is then repeated with repetition time T _R

Figure 2

Example LL‐FAIR difference images from a single subject as a function of post‐label delay time averaged over all experimental time points. A, CBF‐weighted images were acquired using five EPI readouts with the first four flip angles of θ = 35° and a final excitation pulse of θ = 90°. B, CBV_a‐weighted images were acquired using 19 EPI readouts with flip angles of θ = 50° and a final excitation pulse of θ = 90°

Figure 3

Example time courses of the raw signal for each modality from a single subject averaged over the CBF‐based region of interest. A, CBV_a‐weighted LL‐FAIR difference data were acquired over eight stimulus cycles. B, CBF‐weighted LL‐FAIR difference data were acquired over 12 stimulus cycles. C, CBV_tot‐weighted gradient echo (GE) EPI data were acquired over a period of 16 min. Two single‐dose boluses of a GBCA were injected at the beginning of minutes 4 and 5. The visual stimulus was presented for the remaining cycles

Figure 4

Haemodynamic changes during visual stimulation extracted from an ROI defined based on changes in CBF in response to the stimulus: Fractional change in arterial CBV (δCBV_a) (a), fractional change in CBF (δCBF) (B) and fractional change in total CBV (δCBV_tot) (C). time courses are displayed for all subjects (grey lines) and group mean weighted by the number of voxels in each subject's ROI (black solid line). The visual stimulus period is denoted by a solid black bar and averaging windows highlighted for on (pink; 9.6–19.2 s) and off (blue; 40.8–60 s) conditions