Altered Neurovascular Coupling in Patients With Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS): A Combined Resting-State fMRI and Arterial Spin Labeling Study

Background: Coupling between neuronal activity and blood perfusion is termed neurovascular coupling (NVC), and it provides a potentially new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), whether anomalous NVC would be present is unclear.Purpose: To investigate NVC changes and potential neural basis in MELAS by combining resting-state functional MRI (rs-fMRI) and arterial spin labeling (ASL).Study Type: Prospective.Subjects: Twenty-four patients with MELAS (age: 29.8 +/- 7.3 years) in the acute stage and 24 healthy controls (HCs, age: 26.4 +/- 8.1 years). Additionally, 12 patients in the chronic stage were followed up.Field Strength/Sequence: 3.0 T, resting-state gradient-recalled echo-planar imaging and pseudo-continuous 3D ASL sequences.Assessment; Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity strength (FCS) were calculated from rs-fMRI, and cerebral blood flow (CBF) was computed from ASL. Global NVC was assessed by correlation coefficients of CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS. Regional NVC was also evaluated by voxel-wise and lesion-wise ratios of CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS.Statistical Tests: Two-sample t-test, paired-sample t-test, Gaussian random fields correction. A P value <0.05 was considered statistically significant.Results: Compared with HC, MELAS patients in acute stage showed significantly reduced global CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS coupling (P < 0.001). Altered CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS ratios were found mainly distributed in the middle cerebral artery territory in MELAS patients. In addition, significantly increased NVC ratios were found in the acute stroke-like lesions in acute stage (P < 0.001), with a recovery trend in chronic stage.Data Conclusions: This study showed dynamic alterations in NVC in MELAS patients from acute to chronic stage, which may provide a novel insight for understanding the pathogenesis of MELAS.