Background: Nonarteritic anterior ischemic optic neuropathy (NAION) patients experience hypo perfusion in the short posterior ciliary arteries (SPCAs), however, the cause of hypo-perfusion is unclear. Real-time dynamic hemodynamic observations may provide clues into specific NAION pathogenic mechanisms. We aim to analyze hemodynamic changes occurring in NAION using multimodality imaging. Our specific focus is identifying pathogenic mechanisms underlying SPCA insufficiency in NAION. Methods: Three-dimensional arterial spin labeling (3D ASL) magnetic resonance imaging (MRI) and three-dimensional time-of-flight (3D-TOF) magnetic resonance angiography (MRA) were performed on 25 NAION patients (50 eyes) and 22 (44 eyes) normal cases were recruited. The diameter of the initial part of the ophthalmic artery and internal carotid artery siphon were measured using MRA. Blood vessel identification and blood flow (BF) were detected using 3D ASL MRI. We measured BF values of the optic nerve head (ONH) region of the retina/choroid complex, optic nerve (ON), temporal lobe, and occipital lobe. Results: We studied 32 NAION affected eyes, 18 NAION uninvolved eyes, and 44 normal eyes. Diameter of the initial part of ophthalmic artery in the NAION affected eyes was significantly larger than the uninvolved eyes (P=0.026). Diameter of the NAION eyes was 1.33 +/- 0.19 mm [mean standard deviation (SD)], uninvolved eyes were 1.15 +/- 0.21 mm. At a photolabeling delay times (PLD) of 1,500 and 2,500 ms, BF of the ONH and ON in NAION affected eyes was significantly less than uninvolved and normal eyes (pONH<0.001 both at 1,500 and 2,500 ms, pON<0.001 and pON=0.001 at 1,500 and 2,500 ms, respectively). ONH of uninvolved eyes was also significantly less than normal eyes. Additionally, BF of the ONH region correlated with temporal lobe BF, with an R-2=0.3231 and 0.2397 at 1,500 and 2,500 ms, respectively. BF of the ONH region also correlated with occipital lobe BF, with an R-2=0.2534 and 0.4397 at 1,500 and 2,500 ms, respectively. ON and temporal lobe BF also correlated, with an R-2=0.226 and 0.1504 at 1,500 and 2,500 ms, respectively. Conclusions: Abnormal hemodynamics of small cerebral vessels existed prior to the onset of NAION. A candidate mechanism underlying NAION appears to be transient insufficiency of blood supply and of ocular vascular regulation.