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

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.

Keywords: Arterial spin labeling; Cerebral blood flow; Connectivity; Magnetic resonance imaging; Primary open-angle glaucoma.

Fig. 1

Brain regions with altered CBF values in POAG patients compared with NCs. The cold color represents the decreased CBF in POAG patients are located in the bilateral LG and Cal; a region centered in the right PostCG and extending to the right IFG, SMG and IPL; a region extending from the IPL to the left SMG; the left cerebellar crus I; and the right cerebellar lobule VI. The warm color denotes the increased CBF values in POAG patients are set in the right medial FG; a region extending from the left MFG to the left medial prefrontal cortex; the bilateral MFG; the right SFG; and the right insula. (GRF-corrected voxel p value < 0.001 and cluster p value < 0.05). Abbreviations: CBF, cerebral blood flow; NCs, normal controls; POAG, primary open-angle glaucoma; LG, lingual gyri; Cal, calcarine gyri; PostCG, postcentral gyrus; IFG, inferior frontal gyrus; SMG, supramarginal gyrus; IPL, inferior parietal lobule; Medial FG, Medial frontal gyrus; MFG, middle frontal gyrus; SFG, superior frontal gyrus; GRF, Gaussian Random Field Theory

Fig. 2

The CBF connectivity maps of eleven ROIs from NCs and POAG patients. The The warm color indicated positive connections, and cold color indicated negative connections (AlphaSim correction with a voxel-level p < 0.001, AlphaSim value < 0.05). Abbreviations: POAG, primary open angle glaucoma; NCs, normal controls; GRF, Gaussian Random Field Theory. R, right; L, left; B, bilateral; LG, lingual gyri; Cal, calcarine gyri; PostCG, postcentral gyrus; IPL, inferior parietal lobule; Cere, cerebellar; Ins, insula; Medial FG, Medial frontal gyrus; MFG, middle frontal gyrus; SFG, superior frontal gyrus

Fig. 3

Brain regions with significant CBF connectivity differences between NCs and POAG patients. Compared with the NCs (dashed line), the POAG patients (solid line) showed decreased negative CBF connectivity between right Medial FG and right ITG as well as right MOG. Besides, contrary to the NCs, the POAG patients showed negative CBF connectivity between right PostCG and right Cal as well as right SOG, between right SFG and right ITG, and left IPL and right STG, and showed positive CBF connectivity between left MFG and right CPL as well as right ITG and between right MFG and right CPL as well as right MTG. Abbreviations: CBF, cerebral blood flow; POAG, primary open angle glaucoma; NCs, normal controls; R, right; L, left; Medial FG, Medial frontal gyrus; ITG, inferior temporal gyrus; MOG, middle occipital gyrus; PostCG, postcentral gyrus; Cal, Calcarine; SOG, superior occipital gyrus; SFG, superior frontal gyrus; STG, superior temporal gyrus; IPL, inferior parietal lobule; MFG, middle frontal gyrus; CPL, cerebellar posterior lobe; MTG, middle temporal gyrus