Mismatch between diffusion- and perfusion-weighted MRI was used to indicate a treatable area following focal ischemia, called the penumbra. Activity-induced manganese contrast MRI has been reported as a new visualization method for neural activation using manganese ions as a depolarization-dependent contrast agent. It is well known that energy failure induced by cerebral ischemia produces anoxic depolarization. The purpose of this study was to detect manganese accumulation caused by permanent middle cerebral artery occlusion (MCAO) of rat brain and to compare regional differences between manganese accumulation and decreased apparent diffusion coefficient (ADC). The ratios of signal intensity of manganese-enhanced MRI in the ipsilateral cortex to that in the contralateral cortex were 171.0 +/- 17.5% in MCAO group and 108.4 +/- 13.2% in the sham group. In addition, the enhanced region was much smaller than the area which was detected as having a reduced ADC. Magn Reson Med 50:7-12,2003. (C) 2003 Wiley-Liss, Inc.