Introduction CEST MRI permits quantitation of macromolecules such as amide proteins that are of interest in cancer metabolism. However, optimal CEST acquisition and analysis methods remain undetermined. In this study, we investigated CEST MRI as an imaging biomarker for early treatment response in 51 TNBC patients receiving NAST and compared the performance with two different CEST saturation power levels and two analysis methods.

Methods A total of 51 stage I-III TNBC patients enrolled in the prospective ARTEMIS trial (NCT02276443) had CEST imaging performed on a 3T MRI scanner at baseline before NAST (BL, N = 51), after 2 cycles (C2, N = 37), and 4 cycles (C4, N = 44) of NAST. 33 of the 51 patients had imaging at all 3 time points. 29 of the 33 patients had pathological findings, with N = 16 with pathological complete response (pCR) and N = 13 with non-pCR. Two sets of CEST images using 0.9 and 2.0 µT saturation power levels were acquired and analyzed using the magnetization transfer ratio asymmetry (MTRasym) and the Lorentzian line fitting (Mag3.5) methods, for a total of 4 acquisition/analysis combinations. The group averaged CEST signals, MTRasym at 0.9 and 2.0 µT and Mag3.5 at 0.9 and 2.0 µT, at BL, C2 and C4 were determined and evaluated using unpaired (51 patients) and paired (33 patients) Kruskal-Wallis tests. The Mag3.5 at 0.9 µT and the MTRasym at 2.0 µT were further compared between pCR and non-pCR. The group averaged CEST signals at BL, C2, and C4 were evaluated using the Friedman test for the pCR and the non-PCR groups. Separately, the change in the CEST signal from BL to C2 and C4 was determined for each patient and evaluated using the Mann-Whitney test for both groups. P < 0.05 was considered statistically significant.

Results The MTRasym at BL was higher at 2.0 µT than at 0.9 µT. In contrast, the Mag3.5 at BL was higher at 0.9 µT than at 2.0 µT. The MTRasym at 2.0 µT and the Mag3.5 at 0.9 µT decreased during treatment while the MTRasym at 0.9 µT and the Mag3.5 at 2.0 µT were similar. Both the unpaired and the paired Mag3.5 at 0.9 µT showed a significant decrease at C2 and C4 vs. BL (p < 0.01). The unpaired and paired MTRasym at 2.0 µT showed a decrease, although the change was not significant except for the unpaired data at C4. The decrease in the group averaged Mag3.5 at 0.9 µT was significant at C2 vs. BL for the pCR group (p = 0.04), while it was not significant for the pCR group at C4 vs. BL and for the non-pCR group at either C2 or C4 vs. BL. The group averaged MTRasym at 2.0 µT changes were not significant for either the pCR or the non-pCR groups. None of the CEST signal changes on a per patient basis at C2-BL, C4-BL and C4-C2 were significantly different between the pCR and the non-pCR groups. Further, none of the group averaged CEST signals at BL, C2 and C4 were significantly different between the pCR and the non-pCR groups.

Conclusion Our study demonstrates that the CEST quantitation in TNBC patients undergoing NAST depends on acquisition and analysis. For a maximum change in the CEST effect, Lorentzian line fitting is better paired with acquisition at a low saturation power (0.9 µT) and MTRasym is better paired with acquisition at a high saturation power (2.0 µT). Further, a significant CEST signal decrease was observed in TNBC patients with pCR after NAST when a 0.9 µT saturation power and the Lorentzian line fitting were used. In comparison, the decrease was not significant in non-pCR patients using the same saturation power and analysis method. The results suggest that the CEST signal acquired at 0.9 µT saturation power and analyzed using Lorentzian line fitting may be able to differentiate between pCR and non-pCR among TNBC patients undergoing NAST. Additional studies with a larger patient population are ongoing to further validate our findings and their potential for determining pCR.

Citation Format: Shu Zhang, Gaiane M Rauch, Beatriz E Adrada, Medine Boge, Rania MM Mohamed, Abeer H Abdelhafez, Jong Bum Son, Jia Sun, Nabil A Elshafeey, Jason B White, Deanna L Lane, Jessica WT Leung, Marion E Scoggins, David A Spak, Elsa Arribas, Elizabeth Ravenberg, Lumarie Santiago, Tanya W Moseley, Gary J Whitman, Huong Le-Petross, Benjamin C Musall, Mitsuharu Miyoshi, Xinzeng Wang, Brandy Willis, Stacy Hash, Aikaterini Kotrotsou, Peng Wei, Ken-Pin Hwang, Alastair Thompson, Stacy L Moulder, Rosalind P Candelaria, Wei Yang, Jingfei Ma, Mark D Pagel. Assessment of early response to neoadjuvant systemic therapy (NAST) of triple-negative breast cancer (TNBC) using chemical exchange saturation transfer (CEST) MRI: A pilot study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-08.