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The aims of the study were to analyze the conventional and diffusion-weighted MRI (DWI) of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and to investigate underlying mechanisms.Features of 58 acute and 68 chronic stroke-like lesions as well as global brain abnormalities of 40 Chinese MELAS patients were analyzed.Gyriform DWI hyperintensity with decreased apparent diffusion coefficient (ADC) and patchy DWI hyperintensity with normal ADC were noted in 56 of 58 and 2 of 58 cortical regions of acute lesions, respectively. High ADC and mix of low and high ADC were observed in 51 of 58 and 5 of 58 affected subcortical white matters, respectively. Lacunar infarcts existed in 23 of 40 patients. Among 17 patients who have been followed, recurrence, progression, and progressive atrophy were noted in 8, 9, and 4 cases, respectively.This study demonstrates the conventional and diffusional MRI features of MELAS, suggesting a model of acute stroke-like lesions in which the cortex manifest with cytotoxic edema and the subcortical area with vasogenic edema.