A method for accurate pH mapping with chemical exchange saturation transfer (CEST) MRI
Corresponding Author
Phillip Zhe Sun
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Correspondence to: P. Z. Sun, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, MGH and Harvard Medical School, Rm 2301, 149 13th Street, Charlestown, MA 02129, USA. E-mail: [email protected]
R. Wu, Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China. E-mail: [email protected]
Search for more papers by this authorGang Xiao
Department of Math and Applied Mathematics, Hanshan Normal University, Chaozhou, China
Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou, China
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, Boston, MA, USA
Search for more papers by this authorYingkun Guo
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Search for more papers by this authorCorresponding Author
Renhua Wu
Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou, China
Correspondence to: P. Z. Sun, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, MGH and Harvard Medical School, Rm 2301, 149 13th Street, Charlestown, MA 02129, USA. E-mail: [email protected]
R. Wu, Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China. E-mail: [email protected]
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, Boston, MA, USA
Correspondence to: P. Z. Sun, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, MGH and Harvard Medical School, Rm 2301, 149 13th Street, Charlestown, MA 02129, USA. E-mail: [email protected]
R. Wu, Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China. E-mail: [email protected]
Search for more papers by this authorGang Xiao
Department of Math and Applied Mathematics, Hanshan Normal University, Chaozhou, China
Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou, China
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, Boston, MA, USA
Search for more papers by this authorYingkun Guo
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Search for more papers by this authorCorresponding Author
Renhua Wu
Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou, China
Correspondence to: P. Z. Sun, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, MGH and Harvard Medical School, Rm 2301, 149 13th Street, Charlestown, MA 02129, USA. E-mail: [email protected]
R. Wu, Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China. E-mail: [email protected]
Search for more papers by this authorAbstract
Chemical exchange saturation transfer (CEST) MRI holds enormous promise for imaging pH. Whereas the routine CEST-weighted MRI contrast is complex and susceptible to confounding factors such as labile proton ratio, chemical shift, bulk water relaxation and RF saturation, ratiometric CEST imaging simplifies pH determination. However, the conventional ratiometric CEST (RCEST) MRI approach is limited to CEST agents with multiple exchangeable groups. To address this limitation, RF power-based ratiometric CEST (PRCEST) imaging has been proposed that ratios CEST effects obtained under different RF power levels. Nevertheless, due to concomitant RF saturation (spillover) effect, the recently proposed PRCEST imaging is somewhat dependent on parameters including bulk water relaxation time and chemical shift. Herein we hypothesized that RF power-based ratiometric analysis of RF spillover effect-corrected inverse CEST asymmetry (PRICEST) provides enhanced pH measurement. The postulation was verified numerically, and validated experimentally using an in vitro phantom. Briefly, our study showed that the difference between MRI-determined pH (pHMRI) and electrode-measured pH being 0.12 ± 0.13 and 0.04 ± 0.03 for PRCEST and PRICEST imaging, respectively, and the newly proposed PRICEST imaging provides significantly more accurate pH determination than PRCEST imaging (P < 0.01, Wilcoxon signed-rank test). Notably, the exchange rate shows dominantly base-catalysed relationship with pH, independent of creatine concentration (P > 0.10, Analysis of Covariance). In addition, the derived labile proton ratio linearly scales with creatine concentration (P < 0.01, Pearson Regression). To summarize, PRICEST MRI provides concentration-independent pH imaging, augmenting prior quantitative CEST methods for accurate pH mapping. Copyright © 2015 John Wiley & Sons, Ltd.
References
- 1Ward KM, Aletras AH, Balaban RS. A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). J Magn Reson 2000; 143: 79–87.
- 2Aime S, Barge A, Delli Castelli D, Fedeli F, Mortillaro A, Nielsen FU, Terreno E. Paramagnetic Lanthanide(III) complexes as pH-sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications. Magn Reson Med 2002; 47: 639–648.
- 3Zhang S, Malloy CR, Sherry AD. MRI thermometry based on PARACEST agents. J Am Chem Soc 2005; 127(50): 17572–17573.
- 4Sun PZ, Sorensen AG. Imaging pH using the chemical exchange saturation transfer (CEST) MRI: correction of concomitant RF irradiation effects to quantify CEST MRI for chemical exchange rate and pH. Magn Reson Med 2008; 60(2): 390–397.
- 5Olatunde AO, Dorazio SJ, Spernyak JA, Morrow JR. The NiCEST approach: Nickel(II) ParaCEST MRI contrast agents. J Am Chem Soc 2012; 134(45): 18503–18505.
- 6Sun PZ, Wang E, Cheung JS. 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 2012; 60(1): 1–6.
- 7Dula AN, Asche EM, Landman BA, Welch EB, Pawate S, Sriram S, Gore JC, Smith SA. Development of chemical exchange saturation transfer at 7 T. Magn Reson Med 2012; 66(3): 831–838.
- 8Vinogradov E, Sherry AD, Lenkinski RE. CEST: From basic principles to applications, challenges and opportunities. J Magn Reson 2013; 229: 155–172.
- 9Castelli DD, Terreno E, Longo D, Aime S. Nanoparticle-based chemical exchange saturation transfer (CEST) agents. NMR Biomed 2013; 26(7): 839–849.
- 10Sun PZ, van Zijl PCM, Zhou J. Optimization of the irradiation power in chemical exchange dependent saturation transfer experiments. J Magn Reson 2005; 175(2): 193–200.
- 11Wu R, Liu C, Liu P, Sun PZ. Improved measurement of labile proton concentration-weighted chemical exchange rate (kws) with experimental factor-compensated and T1-normalized quantitative chemical exchange saturation transfer (CEST) MRI. Contrast Media Mol Imaging 2012; 7(4): 384–389.
- 12Sun PZ. Simplified quantification of labile proton concentration-weighted chemical exchange rate (kws) with RF saturation time dependent ratiometric analysis (QUESTRA): Normalization of relaxation and RF irradiation spillover effects for improved quantitative chemical exchange saturation transfer (CEST) MRI. Magn Reson Med 2012; 67(4): 936–942.
- 13Zaiss M, Bachert P. Exchange-dependent relaxation in the rotating frame for slow and intermediate exchange – modeling off-resonant spin-lock and chemical exchange saturation transfer. NMR Biomed 2013; 26(5): 507–518.
- 14Sun PZ. Simultaneous determination of labile proton concentration and exchange rate utilizing optimal RF power: radio frequency power (RFP) dependence of chemical exchange saturation transfer (CEST) MRI. J Magn Reson 2010; 202(2): 155–161.
- 15Zu Z, Janve VA, Li K, Does MD, Gore JC, Gochberg DF. Multi-angle ratiometric approach to measure chemical exchange in amide proton transfer imaging. Magn Reson Med 2012; 68(3): 711–719.
- 16Sun PZ, Wang Y, Xiao G, Wu R. 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 2013; 8(3): 246–251.
- 17Ward KM, Balaban RS. Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST). Magn Reson Med 2000; 44(5): 799–802.
- 18Ali MM, Liu G, Shah T, Flask CA, Pagel MD. Using two chemical exchange saturation transfer magnetic resonance imaging contrast agents for molecular imaging studies. Acc Chem Res 2009; 42(7): 915–924.
- 19Liu G, Li Y, Sheth VR, Pagel MD. Imaging in vivo extracellular pH with a single paramagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent. Mol Imaging 2012; 11(1): 47–57.
- 20Longo DL, Busato A, Lanzardo S, Antico F, Aime S. Imaging the pH evolution of an acute kidney injury model by means of iopamidol, a MRI-CEST pH-responsive contrast agent. Magn Reson Med 2012; 70(3): 859–864.
- 21Longo DL, Dastrù W, Digilio G, Keupp J, Langereis S, Lanzardo S, Prestigio S, Steinbach O, Terreno E, Uggeri F, Aime S. Iopamidol as a responsive MRI-chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T. Magn Reson Med 2011; 65(1): 202–211.
- 22McVicar N, Li AX, Goncalves DF, Bellyou M, Meakin SO, Prado MAM, Bartha R. Quantitative tissue pH measurement during cerebral ischemia using amine and amide concentration-independent detection (AACID) with MRI. J Cereb Blood Flow Metab 2014; 34(4): 690–698.
- 23Longo DL, Sun PZ, Consolino L, Michelotti FC, Uggeri F, Aime S. A general MRI-CEST ratiometric approach for pH imaging: demonstration of in vivo pH mapping with Iobitridol. J Am Chem Soc 2014; 136(41): 14333–14336.
- 24Wu R, Longo DL, Aime S, Sun PZ. Quantitative description of radiofrequency (RF) power-based ratiometric chemical exchange saturation transfer (CEST) pH imaging. NMR Biomed 2015; 28(5): 555–565.
- 25Woessner DE, Zhang S, Merritt ME, Sherry AD. Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI. Magn Reson Med 2005; 53(4): 790–799.
- 26McMahon M, Gilad A, Zhou J, Sun PZ, Bulte J, van Zijl PC. Quantifying exchange rates in chemical exchange saturation transfer agents using the saturation time and saturation power dependencies of the magnetization transfer effect on the magnetic resonance imaging signal (QUEST and QUESP): Ph calibration for poly-L-lysine and a starburst dendrimer. Magn Reson Med 2006; 55(4): 836–847.
- 27Sun PZ, Zhou J, Huang J, van Zijl P. Simplified quantitative description of amide proton transfer (APT) imaging during acute ischemia. Magn Reson Med 2007; 57(2): 405–410.
- 28Li AX, Hudson RHE, Barrett JW, Johns CK, Pasternak SH, Bartha R. Four-pool modeling of proton exchange processes in biological systems in the presence of MRI-paramagnetic chemical exchange saturation transfer (PARACEST) agents. Magn Reson Med 2008; 60(5): 1197–1206.
- 29Murase K, Tanki N. Numerical solutions to the time-dependent Bloch equations revisited. Magn Reson Imaging 2011; 29(1): 126–131.
- 30Sun PZ. Simplified and scalable numerical solution for describing multi-pool chemical exchange saturation transfer (CEST) MRI contrast. J Magn Reson 2010; 205(2): 235–241.
- 31Zaiss M, Xu J, Goerke S, Khan IS, Singer RJ, Gore JC, Gochberg DF, Bachert P. Inverse Z-spectrum analysis for spillover-, MT-, and T1-corrected steady-state pulsed CEST-MRI – application to pH-weighted MRI of acute stroke. NMR Biomed 2014; 27(3): 240–252.
- 32Sun PZ, Wang Y, Dai Z, Xiao G, Wu R. 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 2014; 9(4): 268–275.
- 33Jin T, Autio J, Obata T, Kim S-G. Spin-locking versus chemical exchange saturation transfer MRI for investigating chemical exchange process between water and labile metabolite protons. Magn Reson Med 2011; 65(5): 1448–1460.
- 34Jin T, Kim S-G. Advantages of chemical exchange-sensitive spin-lock (CESL) over chemical exchange saturation transfer (CEST) for hydroxyl– and amine–water proton exchange studies. NMR Biomed 2014; 27(11): 1313–1324.
- 35Zhou J, Wilson DA, Sun PZ, Klaus JA, van Zijl PCM. Quantitative description of proton exchange processes between water and endogenous and exogenous agents for WEX, CEST, and APT experiments. Magn Reson Med 2004; 51(5): 945–952.
- 36Wu R, Xiao G, Zhou IY, Ran C, Sun PZ. 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 2015; 28(3): 376–383.
- 37Goerke S, Zaiss M, Bachert P. Characterization of creatine guanidinium proton exchange by water-exchange (WEX) spectroscopy for absolute-pH CEST imaging in vitro. NMR Biomed 2014; 27(5): 507–518.
- 38Aime S, Calabi L, Biondi L, Miranda MD, Ghelli S, Paleari L, Rebaudengo C, Terreno E. Iopamidol: Exploring the potential use of a well-established x-ray contrast agent for MRI. Magn Reson Med 2005; 53(4): 830–834.
- 39Dixon TW, Ren J, Lubag A, Ratnakar J, Vinogradov E, Hancu I, Lenkinski RE, Sherry AD. A concentration-independent method to measure exchange rates in PARACEST agents. Magn Reson Med 2010; 63(3): 625–632.
- 40Zaiss M, Schmitt B, Bachert P. Quantitative separation of CEST effect from magnetization transfer and spillover effects by Lorentzian-line-fit analysis of z-spectra. J Magn Reson 2011; 211(2): 149–155.
- 41Shah T, Lu L, Dell KM, Pagel MD, Griswold MA, Flask CA. CEST-FISP: A novel technique for rapid chemical exchange saturation transfer MRI at 7 T. Magn Reson Med 2011; 65(2): 432–437.
- 42Jones CK, Polders D, Hua J, Zhu H, Hoogduin HJ, Zhou J, Luijten P, van Zijl PCM. In vivo three-dimensional whole-brain pulsed steady-state chemical exchange saturation transfer at 7 T. Magn Reson Med 2012; 67(6): 1579–1589.
- 43Zhou J, Tryggestad E, Wen Z, Lal B, Zhou T, Grossman R, Wang S, Yan K, Fu D-X, Ford E, Tyler B, Blakeley J, Laterra J, van Zijl PCM. Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nat Med 2011; 17(1): 130–134.
- 44Xu J, Zaiss M, Zu Z, Li H, Xie J, Gochberg DF, Bachert P, Gore JC. On the origins of chemical exchange saturation transfer (CEST) contrast in tumors at 9.4 T. NMR Biomed 2014; 27(4): 406–416.
- 45Sun PZ, Farrar CT, Sorensen AG. Correction for artifacts induced by B0 and B1 field inhomogeneities in pH-sensitive chemical exchange saturation transfer (CEST) imaging. Magn Reson Med 2007; 58(6): 1207–1215.