Determination of multipool contributions to endogenous amide proton transfer effects in global ischemia with high spectral resolution in vivo chemical exchange saturation transfer <scp>MRI</scp>

Abstract

Purpose Chemical exchange saturation transfer (CEST) MRI has been used for quantitative assessment of dilute metabolites and/or pH in disorders such as acute stroke and tumor. However, routine asymmetry analysis (MTR asym ) may be confounded by concomitant effects such as semisolid macromolecular magnetization transfer (MT) and nuclear Overhauser enhancement. Resolving multiple contributions is essential for elucidating the origins of in vivo CEST contrast. Methods Here we used a newly proposed image downsampling expedited adaptive least‐squares fitting on densely sampled Z‐spectrum to quantify multipool contribution from water, nuclear Overhauser enhancement, MT, guanidinium, amine, and amide protons in adult male Wistar rats before and after global ischemia. Results Our results revealed the major contributors to in vivo T 1 ‐normalized MTR asym (3.5 ppm) contrast between white and gray matter (WM/GM) in normal brain (−1.96%/second) are pH‐insensitive macromolecular MT (−0.89%/second) and nuclear Overhauser enhancement (−1.04%/second). Additionally, global ischemia resulted in significant changes of MTR asym , being −2.05%/second and −1.56%/second in WM and GM, which are dominated by changes in amide (−1.05%/second, −1.14%/second) and MT (−0.88%/second, −0.62%/second). Notably, the pH‐sensitive amine and amide effects account for nearly 60% and 80% of the MTR asym changes seen in WM and GM, respectively, after global ischemia, indicating that MTR asym is predominantly pH‐sensitive. Conclusion Combined amide and amine effects dominated the MTR asym changes after global ischemia, indicating that MTR asym is predominantly pH‐sensitive and suitable for detecting tissue acidosis following acute stroke.