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

• Type of Material: Article
• Authors: Iris Yuwen Zhou, Massachusetts General Hospital; Dongshuang Lu, Massachusetts General Hospital; Yang Ji, Massachusetts General Hospital; Limin Wu, Harvard Med Sch; Enfeng Wang, Zhengzhou University; Jerry S. Cheung, Massachusetts General Hospital; Xiao-An Zhang, Zhengzhou University; Phillip Zhe Sun, Emory University
• Language: English
• Date: 2019-01-01
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 International Society for Magnetic Resonance in Medicine
• Final Published Version (URL): http://dx.doi.org/10.1002/mrm.27385
• Title of Journal or Parent Work: MAGNETIC RESONANCE IN MEDICINE
• Volume: 81
• Issue: 1
• Start Page: 645
• End Page: 652
• Grant/Funding Information: This study was supported by grants from National Institutes of Health R21NS085574 (to Sun), R01NS083654 (to Sun) and P51OD011132 (to Yerkes National Primate Research Center).
• Keywords: Radiology, Nuclear Medicine & Medical Imaging; global ischemia; magnetization transfer; image downsampling expedited adaptive least-squares fitting; Science & Technology; nuclear overhauser enhancement; FOCAL CEREBRAL-ISCHEMIA; RELAXATION; MAGNETIZATION-TRANSFER; Life Sciences & Biomedicine; ACUTE STROKE; WATER SATURATION; INTRACELLULAR PH; PH-WEIGHTED MRI; amide proton transfer; HUMAN BRAIN; TRANSFER CEST MRI; chemical exchange saturation transfer; QUANTITATIVE DESCRIPTION
• Research Categories: Health Sciences, Radiology; Biology, Neuroscience; Biology, Cell

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 (MTRasym) 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 T1-normalized MTRasym (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 MTRasym, 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 MTRasym changes seen in WM and GM, respectively, after global ischemia, indicating that MTRasym is predominantly pH-sensitive. Conclusion: Combined amide and amine effects dominated the MTRasym changes after global ischemia, indicating that MTRasym is predominantly pH-sensitive and suitable for detecting tissue acidosis following acute stroke.