Evaluation of contributors to amide proton transfer-weighted imaging and nuclear Overhauser enhancement-weighted imaging contrast in tumors at a high magnetic field

Purpose: The purpose is to evaluate the relative contribution from confounding factors (T-1 weighting and magnetization transfer) to the CEST ratio (CESTR)-quantified amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) (-3.5) in tumors as well as whether the CESTR can reflect the distribution of the solute concentration (f(s)).Methods: We first provided a signal model that shows the separate dependence of CESTR on these confounding factors and the clean CEST/NOE effects quantified by an apparent exchange-dependent relaxation (AREX) method. We then measured the change in these effects in the 9-L tumor model in rats, through which we calculated the relative contribution of each confounding factor. f(s) was also fitted, and its correlations with the CESTR and AREX were assessed to evaluate their capabilities to reflect f(s).Results: The CESTR-quantified APT shows "positive" contrast in tumors, which arises primarily from R-1w at low powers and both R-1w and magnetization transfer at high powers. CESTR-quantified NOE (-3.5) shows no or weak contrast in tumors, which is due to the cancelation of R-1w and NOE (-3.5), which have opposite contributions. CESTR-quantified APT has a stronger correlation with APT f(s) than AREX-quantified APT. CESTR-quantified NOE (-3.5) has a weaker correlation with NOE (-3.5) f(s) than AREX-quantified NOE (-3.5).Conclusion: CESTR reflects a combined effect of T-1 weighting and CEST/NOE. Both factors depend on f(s), which contributes positively to the dependence of CESTR on f(s) in APT imaging and enhances its correlation with f(s). In contrast, these factors have opposite contributions to its dependence on f(s) in NOE (-3.5) imaging, thereby weakening the correlation.