Identifying Diagnostic Thresholds for the Assessment of Cerebrovascular Reserve Impairment in Moyamoya Disease: CO2-Triggered BOLD-MRI and [15O]water-PET with Acetazolamide Challenge

Background: Assessment of cerebrovascular reserve capacity (CVRC) is central to treatment planning in adult Moyamoya disease. [15O]-water-PET with acetazolamide challenge (PET-ACZ) serves as the reference standard but is resource-intensive and not universally available, whereas breathhold BOLD MRI (bh-fMRI) may offer a practical noninvasive alternative for screening and triage. Methods: This retrospective diagnostic accuracy study compared bh-fMRI and PET-ACZ in 67 adult MMD patients (1072 ROIs across 402 supratentorial vascular territories) to determine correlation and clinically useful MRI thresholds for impaired cerebrovascular reserve. Data were analyzed using Pearson’s correlation and ROC curves (STARD-compliant). Cerebellum-normalized percent signal change (CN-PSC) was referenced against PET-ACZ < 66% for pathological CVRC. Results: Supratentorial territories showed strong correlation (r = 0.71, 95%CI 0.62–0.80). Optimal diagnostic threshold was <28.2% CN-PSC on bh-fMRI (Youden index; sensitivity 83.8%, specificity 80.9%, AUROC = 0.87); screening threshold < 60% CN-PSC yielded sensitivity 94.6% and NPV 91.1%. No patient factors (age, Suzuki stage, etc.) influenced agreement (univariate/multivariate analyses). Conclusions: Bh-fMRI supplements PET-ACZ as a screening and diagnostic tool for cerebrovascular reserve impairment in adult MMD. PET remains the reference standard for confirmation, especially in intermediate or discordant cases, and the proposed thresholds (<30% CN-PSC: impaired CVRC; 30–60%: confirm with PET-ACZ; >60%: monitor) require prospective validation before routine decision-making use.