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 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 ).

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 was also fitted, and its correlations with the CESTR and AREX were assessed to evaluate their capabilities to reflect f .

Results: The CESTR-quantified APT shows "positive" contrast in tumors, which arises primarily from R at low powers and both R 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 and NOE (-3.5), which have opposite contributions. CESTR-quantified APT has a stronger correlation with APT f than AREX-quantified APT. CESTR-quantified NOE (-3.5) has a weaker correlation with NOE (-3.5) f than AREX-quantified NOE (-3.5).

Conclusion: CESTR reflects a combined effect of T weighting and CEST/NOE. Both factors depend on f , which contributes positively to the dependence of CESTR on f in APT imaging and enhances its correlation with f . In contrast, these factors have opposite contributions to its dependence on f in NOE (-3.5) imaging, thereby weakening the correlation.