Background: Proton exchange rate (k(ex)) magnetic resonance imaging (MRI) has recently been developed, with preliminary results demonstrating its potential for evaluating reactive oxygen species. This prospective cohort study investigated the k(ex) in different stroke stages and its correlation with stroke severity and prognosis. Methods: In all, 96 ischemic stroke patients were included in the study. Patients were divided into 3 groups based on stroke phase (acute, subacute, and chronic). A spin echo-echo planar imaging sequence with presaturation powers of 1.5, 2.5, and 3.5 mu T was implemented to obtain Z-spectra, and k(ex) maps were constructed from direct saturation-removed omega plots. Relative k(ex) (r(kex)) and the relative apparent diffusion coefficient (rADC) were calculated as the ratio of k(ex) or ADC in the infarcts to values in contralateral tissue, respectively. Correlations between both k(ex) and r(kex) and National Institute of Health Stroke Scale (NIHSS) scores were evaluated. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of k(ex), r(kex), rADC, and lesion volume for predicting acute stroke outcome. Results: The k(ex) was significantly higher in ischemic lesions than in contralateral tissue at all stages. In addition, the k(ex) of acute lesions was higher than that of subacute and chronic lesions [mean (+/- SD) 935.1 +/- 81.5 vs. 881.4 +/- 55.7 and 866.9 +/- 76.7 s-1, respectively; P < 0.05 and P < 0.01, respectively]. The difference in kex between subacute and chronic lesions was not significant. In acute stroke, there was a limited correlation between a lesion's kex and NIHSS score (R2=0.16; P=0.01) and between rkex and NIHSS score (R2=0.28; P=0.001). Acute stroke patients with poor prognosis had significantly higher lesion k(ex) and rkex than did those with good prognosis (kex: 991.1 +/- 78.2 vs. 893.1 +/- 55.1 s-1, P < 0.001; rkex: 1.28 +/- 0.09 vs. 1.15 +/- 0.06, P < 0.001). In ROC analyses, kex and rkex showed favorable predictive performance for acute stroke outcome, with areas under the curve (AUC) of 0.837 and 0.880, respectively, which were slightly but not significantly higher than the AUCs for lesion volume (0.730) and rADC (0.673). Conclusions: This study indicates that kex MRI is promising for the diagnosis and management of ischemic stroke because it can reflect the oxidative stress of lesions and predict prognosis.