Endogenous / exogenous Chemical Exchange Saturation Transfer (CEST) Applications in Oncology
Professor Xavier Golay, UCL Institute of Neurology
Date & Time:
Friday, 1 July 2016, 12:00
What are the clinical oncological applications of Chemical Exchange Saturation Transfer? What are its boundary conditions and its limits? The purpose of this presentation will be to show the power of CEST in many different oncological applications, from pH mapping to glucose uptake and metabolism. In vivo CEST-based imaging is a variant of magnetization transfer (MT) imaging (1), in which the selective saturation of the magnetization of amide protons is detected indirectly through chemical exchange with bulk water protons. Selective irradiation is possible because there are composite proton resonance between 1ppm and 4ppm downfield from the water resonance. Most of these exchangeable proton pools are small (mM concentration range), but continuous saturation leads to a measurable decrease by a few percent of the large water signal due to a sensitivity enhancement mechanism. The main applications of most CEST methods have been for the assessment of pH changes, as the exchange rate of most of the above-mentioned moieties is based-catalyzed (2). As such, some of the most important uses of this method have been in stroke (5, 6) using endogenous CEST contrast (i.e. looking at changes in the signal from amide protons due to an acidification of the tissue) and the imaging of pH in tumours using exogenous contrast agents such as iopamidol (7). In addition, measurement of protein contents have also been proposed, in particular in cancer 8, 9). This particular set of applications is really getting increasingly close to the clinics, and the second main part of this application will be presenting some of the challenges associated with its translation. Finally, one of the most exciting potential new applications of CEST are based on the exchange from hydroxyl groups, in particular using glucose (10, 11), leading to potential assessment of glucose uptake and metabolism in various cancers. In conclusion, CEST and its variants are very versatile and possibly very useful techniques, but, as often at the early stages of development of novel MRI techniques, currently suffer from a lack of harmonization in both sequences and processing techniques. In addition, there are remaining issues and ongoing debates on the source of some of the endogenous CEST applications, and much more work is needed before quantification of the exchangeable pool is possible. References: 1. Wolff SD, Balaban RS. Magnetization transfer imaging: practical aspects and clinical applications. Radiology. 1994;192(3):593-9. 2. van Zijl PC, Yadav NN. Chemical exchange saturation transfer (CEST): what is in a name and what isn't? Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2011;65(4):927-48. 3. Jones CK, Schlosser MJ, van Zijl PC, Pomper MG, Golay X, Zhou J. Amide proton transfer imaging of human brain tumors at 3T. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2006;56(3):585-92. 4. Zaiss M, Bachert P. Chemical exchange saturation transfer (CEST) and MR Z-spectroscopy in vivo: a review of theoretical approaches and methods. Physics in medicine and biology. 2013;58(22):R221-69. 5. Tee YK, Harston GW, Blockley N, Okell TW, Levman J, Sheerin F, et al. Comparing different analysis methods for quantifying the MRI amide proton transfer (APT) effect in hyperacute stroke patients. NMR in biomedicine. 2014;27(9):1019-29. 6. Zhou J, Payen JF, Wilson DA, Traystman RJ, van Zijl PC. Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nature medicine. 2003;9(8):1085-90. 7. Longo 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. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2013;70(3):859-64. 8. Zhou J, Lal B, Wilson DA, Laterra J, van Zijl PC. Amide proton transfer (APT) contrast for imaging of brain tumors. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2003;50(6):1120-6. 9. Zhou J, Tryggestad E, Wen Z, Lal B, Zhou T, Grossman R, et al. Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nature medicine. 2011;17(1):130-4. 10. Chan KW, McMahon MT, Kato Y, Liu G, Bulte JW, Bhujwalla ZM, et al. Natural D-glucose as a biodegradable MRI contrast agent for detecting cancer. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2012;68(6):1764-73. 11. Walker-Samuel S, Ramasawmy R, Torrealdea F, Rega M, Rajkumar V, Johnson SP, et al. In vivo imaging of glucose uptake and metabolism in tumors. Nature medicine. 2013;19(8):1067-72.