Isolation of amide proton transfer effect and relayed nuclear Overhauser enhancement effect at ‐3.5ppm using CEST with double saturation powers

Abstract

Purpose: Quantifications of amide proton transfer (APT) and nuclear Overhauser enhancement (rNOE(−3.5)) mediated saturation transfer with high specificity are challenging because their signals measured in a Z-spectrum are overlapped with confounding signals from direct water saturation (DS), semi-solid magnetization transfer (MT), and CEST of fast-exchange pools. In this study, based on two canonical CEST acquisitions with double saturation powers (DSP), a new data-postprocessing method is proposed to specifically quantify the effects of APT and rNOE. Methods: For CEST imaging with relatively low saturation powers (ω 2 1 ), both the fast-exchange CEST effect and the semi-solid MT effect roughly depend on ω 2 1 , whereas the slow-exchange APT/rNOE(−3.5) effect do not, which is exploited to isolate a part of the APT and rNOE effects from the confounding signals in this study. After a mathematical derivation for the establishment of the proposed method, numerical simulations based on Bloch equations are then performed to demonstrate its specificity to detections of the APT and rNOE effects.Finally, an in vivo validation of the proposed method is conducted using an animal tumor model at a 4.7 T MRI scanner. Results:The simulations show that DSP-CEST can quantify the effects of APT and rNOE and substantially eliminate the confounding signals. The in vivo experiments demonstrate that the proposed DSP-CEST method is feasible for the imaging of tumors. Conclusion:The data-postprocessing method proposed in this study can quantify the APT and rNOE effects with considerably increased specificities and a reduced cost of imaging time.

Evaluation of the molecular origin of amide proton transfer–weighted imaging

“…This divergence at high $$$ {\omega}_1 $$$ facilitates their differentiation. Therefore, unlike our previous paper that used low $$$ {\omega}_1, $$$ 34 wherein the baseline signals beyond ±5 ppm in S L and S A were close, the baseline signals beyond ±5 ppm in S L and S A in Figures 1 and 3 in this paper are different due to the varying MT effect contributions. Furthermore, in our simulations, we opted for a Lorentzian MT line shape instead of the super‐Lorentzian MT line shape that better fits biological tissues, 44 to avoid encountering singularities.…”

“…It should be noted that while the dependence of the MT effect on $$$ {\omega}_1 $$$ is approximately similar to that of the amine/guanidinium CEST effects at relatively low $$$ {\omega}_1 $$$, notable disparities emerge at high $$$ {\omega}_1 $$$, as illustrated by the derived equation for the MT signal in the Appendix Eq. () of our previous publication 34 . This divergence at high $$$ {\omega}_1 $$$ facilitates their differentiation.…”

“…Furthermore, in our simulations, we opted for a Lorentzian MT line shape instead of the super‐Lorentzian MT line shape that better fits biological tissues, 44 to avoid encountering singularities. According to the derived equation for the MT signal in our previous paper, 34 the dependence of the MT effect on $$$ {\omega}_1 $$$ should not be heavily reliant on the MT line shape. As demonstrated in Figure S27, which replicates Figures S1I,J and S2I,J but incorporates a super‐Lorentzian MT line shape, It is evident that the auxiliary process can still significantly reduce the MT contribution akin to simulations using the Lorentzian MT line shape.…”

“…Recently, we developed a new CEST quantification method called double saturation power (DSP) CEST, which involves generating an auxiliary Z‐spectrum that has varied contributions from different exchangeable pools compared with the conventional Z‐spectrum 34 . In this study, we extended the auxiliary Z‐spectrum to much higher powers, based on which we created two auxiliary asymmetric analysis spectra that can approximately separate the contributions of amine/guanidinium CEST from those of APT/rNOE/MT effects.…”

Specific and rapid guanidinium CEST imaging using double saturation power and QUASS analysis in a rodent model of global ischemia

“…Recently, a new CEST quantification method called double saturation power (DSP)‐CEST has been developed to highlight the slow exchange CEST effects while reducing the contribution from intermediate to fast exchange CEST effect as well as MT effect 29 . It has been successfully used to isolate APT from confounding factors.…”