Quantification of iopamidol multi-site chemical exchange properties for ratiometric chemical exchange saturation transfer (CEST) imaging of pH
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Institute of Physics and Engineering in Medicine Phys. Med. Biol. 59 (2014) 4493–4504
Physics in Medicine & Biology doi:10.1088/0031-9155/59/16/4493
Quantification of iopamidol multi-site chemical exchange properties for ratiometric chemical exchange saturation transfer (CEST) imaging of pH Phillip Zhe Sun1,5, Dario Livio Longo2, Wei Hu3, Gang Xiao3,4 and Renhua Wu3,5 1
Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA 2 Institute for Biostructures and Bioimages (CNR) c/o Molecular Biotechnology Center and Molecular Imaging Center, University of Torino, Torino, Italy 3 Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China 4 Department of Math and Applied Mathematics, Hanshan Normal University, Chaozhou, People’s Republic of China E-mail: [email protected]
and [email protected]
Received 27 February 2014, revised 24 May 2014 Accepted for publication 23 June 2014 Published 23 July 2014 Abstract
pH-sensitive chemical exchange saturation transfer (CEST) MRI holds great promise for in vivo applications. However, the CEST effect depends on not only exchange rate and hence pH, but also on the contrast agent concentration, which must be determined independently for pH quantification. Ratiometric CEST MRI normalizes the concentration effect by comparing CEST measurements of multiple labile protons to simplify pH determination. Iopamidol, a commonly used x-ray contrast agent, has been explored as a ratiometric CEST agent for imaging pH. However, iopamidol CEST properties have not been solved, determination of which is important for optimization and quantification of iopamidol pH imaging. Our study numerically solved iopamidol multi-site pH-dependent chemical exchange properties. We found that iopamidol CEST MRI is suitable for measuring pH between 6 and 7.5 despite that T1 and T2 measurements varied substantially with pH and concentration. The pH MRI precision decreased with pH and concentration. The standard deviation of pH determined from MRI was 0.2 and 0.4 pH unit for 40 and 20 mM iopamidol solution of pH 6, and it improved to be less than 5
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0031-9155/14/594493+12$33.00 © 2014 Institute of Physics and Engineering in Medicine Printed in the UK & the USA 4493
P Z Sun et al
Phys. Med. Biol. 59 (2014) 1
0.1 unit for pH above 7. Moreover, we determined base-catalyzed chemical exchange for 2-hydrooxypropanamido (ksw = 1.2*10pH−4.1) and amide (ksw = 1.2*10pH−4.6) protons that are statistically different from each other (P