OBJECTIVE: To investigate the pathophysiological characteristics of cerebral blood flow (CBF) in patients with narcolepsy type 1 (NT1) via the arterial spin labeling (ASL) technique. METHODS: Thirty patients with diagnostic NT1 (PTs) and 34 age- and sex-matched healthy controls (HCs) were recruited for this study. Basic information was collected, and clinical evaluation and neuroimaging, including ASL and T1-3DBRAVO, was performed. The z-normalized CBF (zCBF) and spatial coefficient of variation (sCoV) were calculated, and the changes in NT1 were compared via analysis of covariate (ANCOVA). Furthermore, spearman's correlation analysis between impaired regional perfusion and clinical features was performed. Age, sex, and normalized grey matter volume were included as covariates. RESULTS: Compared with that of HCs, the zCBF of PTs significantly differed in regions of fronto-temporal-occipital cortex, right insula and posterior insula, and left rostral/dorsal anterior cingulate gyrus (ACG) (P <
0.006). Moreover, the sCoV was significantly altered in the frontotemporal cortex, rostral ACG, right hippocampus, and posterior insula (P <
0.003). In PTs, positive correlations were identified between the zCBF of the right superior/middle frontal gyrus (SFG/MFG) and mean sleep latency, and between the zCBF of the left SFG of the frontal pole and sleep hallucination severity. Moreover, the sCoV of the right MFG/hippocampus were positively associated with Rapid Eye Movement efficiency and negatively associated with Hamilton Anxiety Scale score, respectively. CONCLUSION: PTs exhibited abnormal regional perfusion in the frontal-temporal-occipital cortex and limbic system regions, which may serve as patient-specific imaging markers. Alterations in perfusion may lead to the clinical manifestations of underlying psychological and sleep disorders in PTs.