Journal
MAGNETIC RESONANCE IN MEDICINE
Volume 67, Issue 3, Pages 760-768Publisher
WILEY-BLACKWELL
DOI: 10.1002/mrm.23038
Keywords
contrast agents; contrast; biophysics; technical research; molecular imaging; technique development
Funding
- National Cancer Institute [CA133455, CA017094]
- Arizona Cancer Center [CA023074]
- NCI [CA 017094, CA 133455-01]
- US Army Medical Research and Material Command [W81XWH-09-1-0053]
- CWRU MSTP [T32 GM007250]
- US Department of Defense
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Paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents have been developed that can measure pH in solution studies, but these agents have not previously been detected in vivo. To use the PARACEST agent Yb-DO3A-oAA to measure the extracellular pH (pHe) in tumor tissue, a chemical exchange saturation transfer fast imaging with steady state precession MRI protocol was developed, the saturation period was optimized for sensitive chemical exchange saturation transfer (CEST) detection, and median filtering was used to remove artifacts in CEST spectra. These improvements were used to correlate pH with a ratio of two CEST effects of Yb-DO3A-oAA at a 7 T magnetic field strength (R2 = 0.99, standard deviation of precision = 0.011 pH units). The PARACEST agent could not be detected in tumor tissue following i.v. injection due to the low sensitivity of in vivo CEST MRI. Yb-DO3A-oAA was detected in tumor tissue and leg muscle after directly injecting the PARACEST agent into these tissues. The measured CEST effects were used to measure a tumor pH of 6.82 +/- 0.21 and a leg muscle pH of 7.26 +/- 0.14, and parametric pH maps were also generated from these tissue regions. These results demonstrated that tumor pHe can be measured with a PARACEST agent and a rapid CEST-MRI protocol. Magn Reson Med, 2012. (c) 2011 Wiley Periodicals, Inc.
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