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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01EB009771-04
Application #
8326090
Study Section
Special Emphasis Panel (ZEB1-OSR-E (M1))
Program Officer
Erim, Zeynep
Project Start
2009-09-30
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$175,230
Indirect Cost
$12,980
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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
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; Wang, Yu; Lu, Jie (2014) Sensitivity-enhanced chemical exchange saturation transfer (CEST) MRI with least squares optimization of Carr Purcell Meiboom Gill multi-echo echo planar imaging. Contrast Media Mol Imaging 9:177-81
Sun, Phillip Zhe; Wang, Yu; Xiao, Gang et al. (2013) Simultaneous experimental determination of labile proton fraction ratio and exchange rate with irradiation radio frequency power-dependent quantitative CEST MRI analysis. Contrast Media Mol Imaging 8:246-51
Sun, Phillip Zhe; Lu, Jie; Wu, Yin et al. (2013) Evaluation of the dependence of CEST-EPI measurement on repetition time, RF irradiation duty cycle and imaging flip angle for enhanced pH sensitivity. Phys Med Biol 58:N229-40
Sun, Phillip Zhe (2012) Simplified quantification of labile proton concentration-weighted chemical exchange rate (k(ws) ) with RF saturation time dependent ratiometric analysis (QUESTRA): normalization of relaxation and RF irradiation spillover effects for improved quantitative Magn Reson Med 67:936-42
Sun, Phillip Zhe; Wang, Enfeng; Cheung, Jerry S (2012) Imaging acute ischemic tissue acidosis with pH-sensitive endogenous amide proton transfer (APT) MRI--correction of tissue relaxation and concomitant RF irradiation effects toward mapping quantitative cerebral tissue pH. Neuroimage 60:1-6
Sun, Phillip Zhe; Cheung, Jerry S; Wang, Enfeng et al. (2011) Association between pH-weighted endogenous amide proton chemical exchange saturation transfer MRI and tissue lactic acidosis during acute ischemic stroke. J Cereb Blood Flow Metab 31:1743-50

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