This study aimed to noninvasively characterize the metabolic alterations in ischemic brain tissues using Z-spectrum-fitted multiparametric chemical exchange saturation transfer-weighted magnetic resonance imaging (CEST-MRI).Three sets of Z-spectrum data with saturation power (B1) values of 1.5, 2.5, and 3.5 µT, respectively, were acquired from 17 patients with ischemic stroke. Multiple contrasts contributing to the Z-spectrum, including fitted amide proton transfer (APTfitted), +2 ppm peak (CEST@2ppm), concomitantly fitted APTfitted and CEST@2ppm (APT&CEST@2ppm), semisolid magnetization transfer contrast (MT), aliphatic nuclear Overhauser effect (NOE), and direct saturation of water (DSW), were fitted with 4 and 5 Lorentzian functions, respectively. The CEST metrics were compared between ischemic lesions and contralateral normal white matter (CNWM), and the correlation between the CEST metrics and the apparent diffusion coefficient (ADC) was assessed. The differences in the Z-spectrum metrics under varied B1 values were also investigated.Ischemic lesions showed increased APTfitted, CEST@2ppm, APT&CEST@2ppm, NOE, and DSW as well as decreased MT. APT&CEST@2ppm, MT, and DSW showed a significant correlation with ADC [APT&CEST@2ppm at the 3 B1 values: R=0.584/0.467/0.551; MT at the 3 B1 values: R=-0.717/-0.695/-0.762 (4-parameter fitting), R=-0.734/-0.711/-0.785 (5-parameter fitting); DSW of 4-/5-parameter fitting: R=0.794/0.811 (2.5 µT), R=0.800/0.790 (3.5 µT)]. However, the asymmetric analysis of amide proton transfer (APTasym) could not differentiate the lesions from CNWM and showed no correlation with ADC. Furthermore, the Z-spectrum contrasts varied with B1.The Z-spectrum-fitted multiparametric CEST-MRI can comprehensively detect metabolic alterations in ischemic brain tissues.© 2023. Huazhong University of Science and Technology.