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Mapping intracellular pH in tumors using amide and guanidyl CEST‐MRI at 9.4 T
Author(s) -
Boyd Philip S.,
Breitling Johannes,
Korzowski Andreas,
Zaiss Moritz,
Franke Vanessa L.,
MuellerDecker Karin,
Glinka Andrey,
Ladd Mark E.,
Bachert Peter,
Goerke Steffen
Publication year - 2022
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.29133
Subject(s) - chemistry , magnetization transfer , in vivo , nuclear magnetic resonance , amide , magnetic resonance imaging , biochemistry , medicine , physics , microbiology and biotechnology , radiology , biology
Purpose In principle, non‐invasive mapping of the intracellular pH (pH i ) in vivo is possible using endogenous chemical exchange saturation transfer (CEST)‐MRI of the amide and guanidyl signals. However, the application for cancer imaging is still impeded, as current state‐of‐the‐art approaches do not allow for simultaneous compensation of concomitant effects that vary within tumors. In this study, we present a novel method for absolute pH i mapping using endogenous CEST‐MRI, which simultaneously compensates for concentration changes, superimposing CEST signals, magnetization transfer contrast, and spillover dilution. Theory and Methods Compensation of the concomitant effects was achieved by a ratiometric approach (i.e. the ratio of one CEST signal at different B 1 ) in combination with the relaxation‐compensated inverse magnetization transfer ratio MTR Rex and a separate first‐order polynomial‐Lorentzian fit of the amide and guanidyl signals at 9.4 T. Calibration of pH values was accomplished using in vivo‐like model suspensions from porcine brain lysates. Applicability of the presented method in vivo was demonstrated in n = 19 tumor‐bearing mice. Results In porcine brain lysates, measurement of pH was feasible over a broad range of physiologically relevant pH values of 6.2 to 8.0, while being independent of changes in concentration. A median pH i of approximately 7.2 was found in the lesions of 19 tumor‐bearing mice. Conclusion The presented method enables non‐invasive mapping of absolute pH i values in tumors using CEST‐MRI, which was so far prevented by concomitant effects. Consequently, pre‐clinical studies on pH i changes in tumors are possible allowing the assessment of pH i in vivo as a biomarker for cancer diagnosis or treatment monitoring.