Acetazolamide-augmented dynamic BOLD (aczBOLD) imaging for assessing cerebrovascular reactivity in chronic steno-occlusive disease of the anterior circulation: An initial experience

Abstract

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.

Cerebral MR oximetry during acetazolamide augmentation: Beyond cerebrovascular reactivity in hemodynamic failure

“…ACZ‐augmented dynamic BOLD fMRI can detect decreased CVR in the disease‐affected hemisphere of CVD. However, it may be insufficiently sensitized to the discrimination between areas of reduced CVR and Stage 2 hemodynamic failure . The subject data from our group's fMRI BOLD CVR study were compared with the QSM‐OEF maps derived in the current study from the same subjects.…”

“…The study was approved by the Institutional Review Board; retrospective review of patient data was performed and informed consent was obtained from healthy control (HC) subjects for undergoing a research magnetic resonance imaging (MRI) scan. CVD patients in this study were included in previous publications, in which their referral and inclusion status is outlined …”

“…Each subject also had a volumetric magnetization‐prepared rapid gradient echo (MPRAGE) T 1 ‐weighted image with 1 mm isotropic resolution, which was utilized for spatial normalization. ACZ‐challenged blood oxygenation level‐dependent (BOLD) functional (f)MRI was also acquired for the CVD patients pre‐ and post‐ACZ; these acquisition parameters were described in a previous study in which the data were also used . No ACZ administration was performed in the HC subjects.…”

“…Compromised CVR is associated with an increased risk of ischemic stroke among CVD patients . Reduction in CVR can be measured dynamically by utilizing a flow augmentation stimulus such as acetazolamide (ACZ) . Increased OEF (CVD Stage 2) is linked to a 5‐fold increase in the 2‐year rate of ischemic stroke in patients with carotid occlusion, and may therefore have utility in disease classification and prognosis …”

The Brain Thermal Response as a Potential Neuroimaging Biomarker of Cerebrovascular Impairment

“…It was recently reported that CVR BOLD increases continuously following ACZ administration, reaching a plateau at approximately 8.5 minutes which continues through the remainder of the acquisition. 40 While CVR delays beyond 20 minutes are difficult to exclude, we expect that the window of maximal augmentation is likely captured within this study design.…”