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 (T1 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 (fs). 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. fs was also fitted, and its correlations with the CESTR and AREX were assessed to evaluate their capabilities to reflect fs. Results The CESTR-quantified APT shows “positive” contrast in tumors, which arises primarily from R1w at low powers and both R1w 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 R1w and NOE (−3.5), which have opposite contributions. CESTR-quantified APT has a stronger correlation with APT fs than AREX-quantified APT. CESTR-quantified NOE (−3.5) has a weaker correlation with NOE (−3.5) fs than AREX-quantified NOE (−3.5). Conclusion CESTR reflects a combined effect of T1 weighting and CEST/NOE. Both factors depend on fs, which contributes positively to the dependence of CESTR on fs in APT imaging and enhances its correlation with fs. In contrast, these factors have opposite contributions to its dependence on fs in NOE (−3.5) imaging, thereby weakening the correlation.