Determination of multipool contributions to endogenous amide proton transfer effects in global ischemia with high spectral resolution in vivo chemical exchange saturation transfer MRI
Iris Yuwen Zhou
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Search for more papers by this authorDongshuang Lu
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Search for more papers by this authorYang Ji
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Search for more papers by this authorLimin Wu
Neuroscience Center and Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Search for more papers by this authorEnfeng Wang
Department of Radiology, Third Affiliated Hospital, Zhengzhou University, Henan, China
Search for more papers by this authorJerry S. Cheung
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Search for more papers by this authorXiao-An Zhang
Department of Radiology, Third Affiliated Hospital, Zhengzhou University, Henan, China
Search for more papers by this authorCorresponding Author
Phillip Zhe Sun
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia
Department of Radiology, Emory University School of Medicine, Atlanta, Georgia
Correspondence
Phillip Zhe Sun, Yerkes National Primate Research Center, Emory University, Department of Radiology, Emory University School of Medicine, 954 Gatewood Road NE, Atlanta, GA 30329.
Email: [email protected]
Search for more papers by this authorIris Yuwen Zhou
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Search for more papers by this authorDongshuang Lu
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Search for more papers by this authorYang Ji
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Search for more papers by this authorLimin Wu
Neuroscience Center and Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Search for more papers by this authorEnfeng Wang
Department of Radiology, Third Affiliated Hospital, Zhengzhou University, Henan, China
Search for more papers by this authorJerry S. Cheung
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Search for more papers by this authorXiao-An Zhang
Department of Radiology, Third Affiliated Hospital, Zhengzhou University, Henan, China
Search for more papers by this authorCorresponding Author
Phillip Zhe Sun
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts
Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia
Department of Radiology, Emory University School of Medicine, Atlanta, Georgia
Correspondence
Phillip Zhe Sun, Yerkes National Primate Research Center, Emory University, Department of Radiology, Emory University School of Medicine, 954 Gatewood Road NE, Atlanta, GA 30329.
Email: [email protected]
Search for more papers by this authorFunding information: National Institutes of Health (R21NS085574 [to P.Z.S.], R01NS083654 [to P.Z.S.], and P51OD011132 [to Yerkes National Primate Research Center])
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.
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