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On the origins of chemical exchange saturation transfer (CEST) contrast in tumors at 9.4 T.

ABSTRACT: Chemical exchange saturation transfer (CEST) provides an indirect means to detect exchangeable protons within tissues through their effects on the water signal. Previous studies have suggested that amide proton transfer (APT) imaging, a specific form of CEST, detects endogenous amide protons with a resonance frequency offset 3.5 ppm downfield from water, and thus may be sensitive to variations in mobile proteins/peptides in tumors. However, as CEST measurements are influenced by various confounding effects, such as spillover saturation, magnetization transfer (MT) and MT asymmetry, the mechanism or degree of increased APT signal in tumors is not certain. In addition to APT, nuclear Overhauser enhancement (NOE) effects upfield from water may also provide distinct information on tissue composition. In the current study, APT, NOE and several other MR parameters were measured and compared comprehensively in order to elucidate the origins of APT and NOE contrasts in tumors at 9.4 T. In addition to conventional CEST methods, a new intrinsic inverse metric was applied to correct for relaxation and other effects. After corrections for spillover, MT and T1 effects, corrected APT in tumors was found not to be significantly different from that in normal tissues, but corrected NOE effects in tumors showed significant decreases compared with those in normal tissues. Biochemical measurements verified that there was no significant enhancement of protein contents in the tumors studied, consistent with the corrected APT measurements and previous literature, whereas quantitative MT data showed decreases in the fractions of immobile macromolecules in tumors. Our results may assist in the better understanding of the contrast depicted by CEST imaging in tumors, and in the development of improved APT and NOE measurements for cancer imaging.

SUBMITTER: Xu J

PROVIDER: S-EPMC3972041 | biostudies-other | 2014 Apr

REPOSITORIES: biostudies-other

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Project description:Accurate quantification of chemical exchange saturation transfer (CEST) effects, including dipole-dipole mediated relayed nuclear Overhauser enhancement (rNOE) saturation transfer, is important for applications and studies of molecular concentration and transfer rate (and thereby pH or temperature). Although several quantification methods, such as Lorentzian difference (LD) analysis, multiple-pool Lorentzian fits, and the three-point method, have been extensively used in several preclinical and clinical applications, the accuracy of these methods has not been evaluated. Here we simulated multiple-pool Z spectra containing the pools that contribute to the main CEST and rNOE saturation transfer signals in the brain, numerically fit them using the different methods, and then compared their derived CEST metrics with the known solute concentrations and exchange rates. Our results show that the LD analysis overestimates contributions from amide proton transfer (APT) and intermediate exchanging amine protons; the three-point method significantly underestimates both APT and rNOE saturation transfer at -3.5 ppm (NOE(-3.5)). The multiple-pool Lorentzian fit is more accurate than the other two methods, but only at lower irradiation powers (?1 ?T at 9.4 T) within the range of our simulations. At higher irradiation powers, this method is also inaccurate because of the presence of a fast exchanging CEST signal that has a non-Lorentzian lineshape. Quantitative parameters derived from in vivo images of rodent brain tumor obtained using an irradiation power of 1 ?T were also compared. Our results demonstrate that all three quantification methods show similar contrasts between tumor and contralateral normal tissue for both APT and the NOE(-3.5). However, the quantified values of the three methods are significantly different. Our work provides insight into the fitting accuracy obtainable in a complex tissue model and provides guidelines for evaluating other newly developed quantification methods.

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On the origins of chemical exchange saturation transfer (CEST) contrast in tumors at 9.4 T.

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