Novel proton exchange rate MRI presents unique contrast in brains of ischemic stroke patients

Background: To map and quantify the proton exchange rate (k_ex) of brain tissues using improved omega plots in ischemic stroke patients and to investigate whether k_ex can serve as a potential endogenous surrogate imaging biomarker for detecting the metabolic state and the pathologic changes due to ischemic stroke. New Method: Three sets of Z-spectra were acquired from seventeen ischemic stroke patients using a spin echo-echo planar imaging sequence with pre-saturation chemical exchange saturation transfer (CEST) pulse at B₁ of 1.5, 2.5, and 3.5 μT, respectively. Pixel-wise k_ex was calculated from improved omega plot of water direct saturation (DS)-removed Z-spectral signals. Results: The derived k_ex maps can differentiate infarcts from contralateral normal brain tissues with significantly increased signal (893 ± 52 s^-1 vs. 739 ± 34 s^-1, P < 0.001). Comparison with Existing Method(s): The k_ex maps were found to be different from conventional contrasts from diffusion-weighted imaging (DWI), CEST, and semi-solid magnetization transfer (MT) MRI. In brief, k_ex MRI showed larger lesion areas than DWI with different degrees and different lesion contrast compared to CEST and MT. Conclusions: In this preliminary translational research, the k_ex MRI based on DS-removed omega plots has been demonstrated for in vivo imaging of clinical ischemic stroke patients. As a noninvasive and unique MRI contrast, k_ex MRI at 3 T may serve as a potential surrogate imaging biomarker for the metabolic changes of stroke and help for monitoring the evolution and the treatment of stroke.