Arterial spin labeling reveals disordered cerebral perfusion and cerebral blood flow-based functional connectivity in primary open-angle glaucoma

Abstract

Abstract Purpose Primary open-angle glaucoma (POAG) is a widespread neurodegenerative condition affecting brain regions involved in visual processing, somatosensory processing, motor control, emotional regulation and cognitive functions. Cerebral hemodynamic dysfunction contributes to the pathogenesis of glaucomatous neurodegeneration. We aimed to investigate cerebral blood flow (CBF) redistributed patterns in visual and higher-order cognitive cortices and its relationship with clinical parameters in POAG, and we hypothesized that CBF changes together across regions within the same functional network. Methods Forty-five POAG patients and 23 normal controls underwent three-dimensional pseudocontinuous arterial spin labeling MRI to measure the resting-state CBF. Group comparisons of CBF and correlations between CBF changes and ophthalmological and neuropsychological indices were assessed. We determined CBF-based functional connectivity (CBFC) by calculating the correlations between specific regions and all other brain voxels and compared CBFC differences between groups. Results The patients exhibited decreased CBF in visual cortices, postcentral gyrus, inferior parietal lobule and cerebellum and increased CBF in medial, middle, and superior frontal gyri, as well as the insula. The reduced CBF in the visual cortices positively correlated with visual field defect (r = 0.498, p = 0.001) in POAG patients, while the increased CBF in the right medial frontal gyrus was negatively associated with the visual field defect (r = −0.438, p = 0.004) and positively associated with the cup-to-disc ratio (r = 0.469, p = 0.002). POAG patients showed negative connections weakening or converting to mild positive connections, as well as positive connections converting to negative connections. Conclusions Regional and interregional CBF properties confirmed that the aberrant brain regions extend beyond the visual pathway, including the somatosensory, emotional and cognitive networks, which highlights the importance of cerebral hemodynamic dysfunction in the pathophysiology of spreading neurodegeneration in POAG.