The purpose of this study was to measure cerebrovascular reactivity (CVR) in chronic steno-occlusive disease using a novel approach that couples BOLD imaging with acetazolamide (ACZ) vasoreactivity (aczBOLD), to evaluate dynamic effects of ACZ on BOLD and to establish the relationship between aczBOLD and dynamic susceptibility contrast (DSC) perfusion MRI. Eighteen patients with unilateral chronic steno-occlusive disease of the anterior circulation underwent a 20-min aczBOLD imaging protocol, with ACZ infusion starting at 5 min of scan initiation. AczBOLD reactivity was calculated on a voxel-by-voxel basis to generate CVR maps for subsequent quantitative analyses. Reduced CVR was observed in the diseased vs. the normal hemisphere both by qualitative and quantitative assessment (gray matter (GM): 4.13% ± 1.16% vs. 4.90% ± 0.98%, P = 0.002; white matter (WM): 2.83% ± 1.23% vs. 3.50% ± 0.94%, P = 0.005). In all cases BOLD signal began increasing immediately following ACZ infusion, approaching a plateau at ~ 8.5 min after infusion, with the tissue volume of reduced augmentation increasing progressively with time, peaking at 2.60 min (time range above 95% of the maximum value: 0-4.43 min) for the GM and 1.80 min (time range above 95% of the maximum value: 1.40-3.53 min) for the WM. In the diseased hemisphere, aczBOLD CVR significantly correlated with baseline DSC time-to-maximum of the residue function (Tmax) (P = 0.008 for the WM) and normalized cerebral blood flow (P = 0.003 for the GM, and P = 0.001 for the WM). AczBOLD provides a novel, safe, easily implementable approach to CVR measurement in the routine clinical environments. Further studies can establish quantitative thresholds from aczBOLD towards identification of patients at heightened risk of recurrent ischemia and cognitive decline.
Keywords: Acetazolamide; Blood-oxygen level dependence; Cerebrovascular disease; Cerebrovascular reserve; Cerebrovascular stenosis; MR perfusion.