Imaging Study On Neurovascular Coupling In Neuromyelitis Optica

Objectives: Neurovascular coupling reflects the close relationship between neuronal activity and cerebral blood flow(CBF),providing a new mechanistic insight into health and disease.Neuromyelitis optica(NMO)is an autoimmune inflammatory demyelinating disease of the central nervous system.Abnormalities in grey matter and cognitive decline have been reported in patients with NMO.We aimed to investigate neurovascular coupling alteration and its clinical significance in NMO by using regional homogeneity(Re Ho)to measure neuronal activity and CBF to measure vascular response.Methods: A total of 56 patients with NMO(48 women and 8 men)who met the 2006 Wingerchuk diagnostic criteria and 63 sex-,age-and education-matched healthy controls(53 women and 10 men)were recruited in our study.MR imaging data were acquired using a 3.0-Tesla MR scanner(Discovery MR750,General Electric,Milwaukee,WI,USA),including resting-state functional magnetic resonance imaging(f MRI)and resting-state perfusion imaging(arterial spin labeling,ASL).Re Ho was calculated from f MRI and CBF was computed from ASL.The disease severity was assessed by the Expanded Disability Status Scale(EDSS)scores for each patient and a series of neuropsychological tests were performed for all participants.1.To quantitatively evaluate the global neurovascular coupling,across-voxel CBF-Re Ho correlations were calculated for each participant and then compared between the two groups.2.To quantify the regional neurovascular coupling,CBF/Re Ho ratio of each voxel was computed and then compared between the two groups.And voxel-wise comparisons were performed to identify the CBF or Re Ho differences between the two groups.3.Correlations between CBF/Re Ho ratio of each significant region and clinical variables were explored in patients with NMO.4.To at least partially reduce the effects of grey matter volume(GMV)changes,we repeated comparisons of global and regional neurovascular coupling after controlling for GMV.We also used the amplitude flow frequency fluctuation(ALFF)replacing the Re Ho to validate the reproducibility of our main findings.Results: 1.The global CBF-Re Ho coupling was decreased in patients with NMO relative to healthy controls(P=0.009).2.Patients with NMO showed decreased CBF/Re Ho ratio(10.9-17.3% reduction)in the parietal and occipital regions and increased CBF/Re Ho ratio(8.0-13.3% increase)in the insular,sensorimotor,temporal and prefrontal regions(P<0.05,FDR-corrected).Some of these abnormalities cannot be identified by a single CBF or Re Ho analysis.3.Cognitive dysfunction was found in NMO patients including deficits in attention,information processing speed,learning and memory.Both abnormally decreased and increased CBF/Re Ho ratios were related to clinical impairments and cognitive decline in patients with NMO(r=0.265-0.533 for positive correlations and-0.303--0.428 for negative correlations,P<0.05).4.After controlling for the global GMV of each subject,there was still a significant difference(P=0.011)in the global CBF-Re Ho coupling between patients and healthy controls.And the spatial distribution of brain regions with altered CBF/Re Ho ratio after GMV correction was similar to that without GMV correction,indicating that the altered neurovascular coupling in NMO is independent of GMV changes.The results using ALFF replacing Re Ho to reflect neuronal activity also suggested that the reported neurovascular coupling alterations in NMO are reproducible.Conclusions: Patients with NMO show abnormal neurovascular coupling,which is associated with disease severity and cognitive impairments.These findings may improve our understanding of the neural mechanisms of NMO from the perspective of neurovascular coupling.