Acetazolamide-augmented BOLD MRI to Assess Whole-Brain Cerebrovascular Reactivity in Chronic Steno-occlusive Disease Using Principal Component Analysis.

Background Exhaustion of cerebrovascular reactivity (CVR) portends increased stroke risk. Acetazolamide-augmented blood-oxygen-level-dependent (BOLD) MRI has been used to estimate CVR, but low signal-to-noise conditions relegate its use to terminal CVR measurements ( CVR end ) that neglect dynamic features of CVR. Purpose To demonstrate comprehensive characterization of acetazolamide-augmented BOLD MRI response in chronic steno-occlusive disease (SOD) using a computational framework to pre-condition signal time courses for dynamic whole-brain CVR analysis. Materials and Methods Retrospective analysis of consecutive patients with unilateral chronic SOD who underwent acetazolamide-augmented BOLD for recurrent minor stroke or transient ischemic attack at a single academic medical center between May 2017-October 2020. A custom principal component analysis-based denoising pipeline was used to correct spatially varying, non-signal bearing contributions obtained by a local principal component analysis of the MRI time series. Standard, voxel-wise CVR end maps representing terminal responses were produced and compared with the maximal CVR ( CVR max ) as isolated from binned (per-repetition time), denoised BOLD time course. A linear mixed effects model was used to compare CVR max and CVR end in healthy and diseased hemispheres. Results 23 patients (median age 51 years, IQR 42-61, 13 men) undergoing 32 BOLD examinations were included. Processed MRI data demonstrated two-fold improvement in signal-to-noise ratio, allowing improved isolation of dynamic characteristics in signal time course for sliding-window CVR max analysis to the level of each BOLD repetition time (~2s). Mean CVR max was significantly higher than mean CVR end in diseased (5.2% vs 3.8%, P<0.01) and healthy hemispheres (5.5% vs 4.0%, P<0.01). Several distinct time-signal signatures were observed, including non-responsive; delayed and/or blunted; brisk, and occasionally non-monotonic time courses with paradoxical features in normal and abnormal tissues (i.e., steal, reverse-steal). Conclusion A principal component analysis based computational framework for analysis of acetazolamide-augmented BOLD can measure unsustained CVR maxima through two-fold improvements in signal-to-noise ratio.