Assessment of cerebrovascular reactivity in middle cerebral artery stenosis using non-hypercapnic resting-state fMRI: a potential biomarker for hemodynamic alterations

Cerebrovascular reactivity(CVR), a key indicator of cerebrovascular reserve, is crucial for evaluating cerebrovascular pathophysiology. This study employed resting-state MRI (rs-MRI) to assess CVR alteration in patients with unilateral middle cerebral artery stenosis or occlusion (MCA-S) under non-hypercapnic conditions, comparing them with healthy controls. A total of 41 patients with unilateral MCA-S and 50 age-, sex-, and education-matched normal controls (NC). All underwent rs-MRI and neuropsychological assessments. CVR was derived from rs-fMRI frequency band signals, and t -test was conducted to obtain the CVR-differentiated brain regions. Exploratory seed-based FC analysis was further performed to characterize the network context of regions showing altered CVR. Partial correlation analyses explored relationships between these differential brain regions and both neuropsychological assessments and clinical indicators. Discriminative performance of the CVR-related metric between MCA-S and controls was evaluated using receiver operating characteristic (ROC) curves. Compared with the NC group, patients with MCA-S exhibited increased CVR in the contralesional Cerebellum Crus1 (CC1) and decreased iCVR in the ipsilesional postcentral gyrus (PoCG). When contralesional CC1 served as regions of interest (ROIs), increased FC was observed in the ipsilesional middle frontal gyrus (MFG) and the contralesional precuneus of MCA-S patients. The partial correlation analysis indicated a positive correlation between the FC of the ipsilesional MFG and anxiety scores ( r = 0.404, (95% CI : 0.106, 0.631), P = 0.012, P -FDR = 0.030). Using ipsilesional PoCG as the ROI, MCA-S patients showed significantly decreased FC in ipsilesional PoCG, contralesional precentral gyrus (PreCG), and ipsilesional supplementary motor area. The FC of the contralesional PreCG showed a positive correlation with anxiety scores ( r = 0.436, (95% CI : 0.142, 0.658), P = 0.006, P -FDR = 0.030). ROC analysis demonstrated strong diagnostic accuracy for CVR in CC1 (AUC = 0.809) and PoCG (AUC = 0.787), with a combined AUC of 0.866. Non-hypercapnic rs-MRI effectively evaluates CVR alterations in MCA-S patients and may serve as a complementary physiological biomarker for characterizing hemodynamic alteration.