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