Our research aims to develop and validate quantitative pH imaging technique, and evaluate its diagnostic utility in pathologies such as acute ischemia. Recently, it has been shown that chemical exchange saturation transfer (CEST) MRI can monitor microenvironment pH, and amide proton transfer (APT) MRI, a variant of CEST imaging, has been shown promising in imaging acute ischemic tissue damage. However, APT imaging provides only pH-weighted information, and its contrast varies with experimental conditions, and under the influence of edema, protein content and tissue relaxation time change. While on the other hand, it is of tremendous interest to develop an absolute tissue pH imaging that provide quantitative information about tissue energy metabolism. In validated, an absolute pH MRI technique may complement conventional spectroscopy-based techniques (e.g., lactate and ^V) to improve its spatiotemporal resolution. In addition, a validated non-invasive pH MRI technique may serve as a surrogate marker for altered tissue metabolic status, and hence, may eventually augment commonly used perfusion and diffusion MRI for more acute characterization of pathological tissue status. In fact, a non-invasive pH MRI technique can aid the diagnosis of a host of metabolic disorders beyond acute stroke. In the proposed research, we will 1) develop, quantitate and calibrate CEST MRI for absolute pH. 2) validate in vivo pH MRI using both global and focal ischemia aninrial stroke model. 3) test the diagnostic value of pH MRI by evaluating a new experimental therapeutic drug, acid sensing ion channel (ASIC) blockade.

Public Health Relevance

Non invasive pH imaging is generally an unmet need, and we propose to quantitate endogenous amide proton transfer MRI for mapping absolute tissue pH. Once verified, we will evaluate its diagnostic use in pathologies such as acute stroke.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Scientist Development Award - Research & Training (K01)
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Special Emphasis Panel (ZEB1-OSR-E (M1))
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Erim, Zeynep
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Massachusetts General Hospital
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Sun, Phillip Zhe; Xiao, Gang; Zhou, Iris Yuwen et al. (2016) A method for accurate pH mapping with chemical exchange saturation transfer (CEST) MRI. Contrast Media Mol Imaging 11:195-202
Jiang, Weiping; Zhou, Iris Yuwen; Wen, Lingyi et al. (2016) A theoretical analysis of chemical exchange saturation transfer echo planar imaging (CEST-EPI) steady state solution and the CEST sensitivity efficiency-based optimization approach. Contrast Media Mol Imaging 11:415-423
Wu, Renhua; Xiao, Gang; Zhou, Iris Yuwen et al. (2015) Quantitative chemical exchange saturation transfer (qCEST) MRI - omega plot analysis of RF-spillover-corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate. NMR Biomed 28:376-83
Wu, Renhua; Longo, Dario Livio; Aime, Silvio et al. (2015) Quantitative description of radiofrequency (RF) power-based ratiometric chemical exchange saturation transfer (CEST) pH imaging. NMR Biomed 28:555-65
Kim, Jinsuh; Wu, Yin; Guo, Yingkun et al. (2015) A review of optimization and quantification techniques for chemical exchange saturation transfer MRI toward sensitive in vivo imaging. Contrast Media Mol Imaging 10:163-78
Xiao, Gang; Sun, Phillip Zhe; Wu, Renhua (2015) Fast simulation and optimization of pulse-train chemical exchange saturation transfer (CEST) imaging. Phys Med Biol 60:4719-30
Sun, Phillip Zhe; Wang, Yu; Mandeville, Emiri et al. (2014) Validation of fast diffusion kurtosis MRI for imaging acute ischemia in a rodent model of stroke. NMR Biomed 27:1413-8
Sun, Phillip Zhe; Longo, Dario Livio; Hu, Wei et al. (2014) Quantification of iopamidol multi-site chemical exchange properties for ratiometric chemical exchange saturation transfer (CEST) imaging of pH. Phys Med Biol 59:4493-504
Longo, Dario L; Sun, Phillip Zhe; Consolino, Lorena et al. (2014) A general MRI-CEST ratiometric approach for pH imaging: demonstration of in vivo pH mapping with iobitridol. J Am Chem Soc 136:14333-6
Sun, Phillip Zhe; Wang, Yu; Dai, ZhuoZhi et al. (2014) Quantitative chemical exchange saturation transfer (qCEST) MRI--RF spillover effect-corrected omega plot for simultaneous determination of labile proton fraction ratio and exchange rate. Contrast Media Mol Imaging 9:268-75

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