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

Abstract

BackgroundCoupling 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.PurposeTo investigate NVC changes and potential neural basis in MELAS by combining resting‐state functional MRI (rs‐fMRI) and arterial spin labeling (ASL).Study TypeProspective.SubjectsTwenty‐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/Sequence3.0 T, resting‐state gradient‐recalled echo‐planar imaging and pseudo‐continuous 3D ASL sequences.AssessmentAmplitude 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 TestsTwo‐sample t‐test, paired‐sample t‐test, Gaussian random fields correction. A P value <0.05 was considered statistically significant.ResultsCompared 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 ConclusionsThis 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.Evidence Level2Technical EfficacyStage 1