Amide proton transfer–weighted MRI can detect tissue acidosis and monitor recovery in a transient middle cerebral artery occlusion model compared with a permanent occlusion model in rats Abstract Objectives To assess whether increases in amide proton transfer (APT)–weighted signal reflect the effects of tissue recovery from acidosis using transient rat middle cerebral artery occlusion (MCAO) models, compared to permanent occlusion models. Materials and methods Twenty-four rats with MCAO (17 transient and seven permanent occlusions) were prepared. APT-weighted signal (APTw), apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and MR spectroscopy were evaluated at three stages in each group (occlusion, reperfusion/1 h post-occlusion, and 3 h post-reperfusion/4 h post-occlusion). Deficit areas showing 30% reduction to the contralateral side were measured. Temporal changes were compared with repeated measures of analysis of variance. Relationship between APTw and lactate concentration was calculated. Results Both APTw and CBF values increased and APTw deficit area reduced at reperfusion (largest p = .002) in transient occlusion models, but this was not demonstrated in permanent occlusion. No significant temporal change was demonstrated with ADC at reperfusion. APTw deficit area was between ADC and CBF deficit areas in transient occlusion model. APTw correlated with lactate concentration at occlusion (r = − 0.49, p = .04) and reperfusion (r = − 0.32, p = .02). Conclusions APTw values increased after reperfusion and correlated with lactate content, which suggests that APT-weighted MRI could become a useful imaging technique to reflect tissue acidosis and its reversal. Key Points • APT-weighted signal increases in the tissue reperfusion, while remains stable in the permanent occlusion. • APTw deficit area was between ADC and CBF deficit areas in transient occlusion model, possibly demonstrating metabolic penumbra. • APTw correlated with lactate concentration during ischemia and reperfusion, indicating tissue acidosis.