Interpreting amide proton transfer-weighted imaging contrast between normal and tumor brain tissues using the asymmetry analysis method at 4.7 T.

Purpose: To provide a comprehensive analysis of the contributors to the amide proton transfer-weighted (APTw) imaging signal using an asymmetry analysis method, as well as its contrast between tumors and the contralateral normal tissues at 4.7 T.

Methods: First, a signal model was developed to demonstrate the dependence of APTw signal on various contributors, including water T₁, reference signal containing direct water saturation (DS) and magnetization transfer (MT), as well as APT, amine CEST, and nuclear Overhauser enhancement (NOE) effects. Second, these effects were measured in rat brains bearing 9 L tumors, with saturation field strengths (B₁) of 2 and 3 μT, at 4.7 T to assess their relative contributions. Specifically, the reference signal was determined using an extrapolated MT reference approach. The amine CEST effect was isolated using an auxiliary asymmetry analysis method, while the APT and NOE effects were quantified through a multiple-pool Lorentzian fit of CEST Z-spectra acquired at 15.2 T.

Results: Our findings reveal that at 2 μT, the APT effect is comparable to the NOE/asymmetric MT effects in tumors. Whereas at 3 μT, the APT effect becomes greater than the NOE/asymmetric MT effects in tumors. At these two B₁ levels, the contribution from the amine CEST effect cannot be ignored. APTw contrast between tumors and normal tissues primarily arises from decreased NOE/asymmetric MT effects, with an additional spillover-dilution effect from the reduced MT effect in tumors.

Conclusion: This study provides insights into the contributors to APTw signal and its contrast between tumors and normal tissues, thereby enhancing our understanding of APTw imaging.