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.