Author: Deng-Yuan Chang, Matthew L. Scarpelli 👨🔬
Affiliation: Purdue University 🌍
Purpose: Tumor-associated macrophages (TAMs) can be assessed by Ferumoxytol-MRI in breast cancer because they are negatively correlated with the prognosis of patient outcome. However, some studies have been shown that ferumoxytol was not only engulfed in the macrophages but the tumor hypoxia region, which affects the accuracy of quantitation of TAMs for tumor radiation responses by non-invasive ferumoxytol MRI. This study utilizes ferumoxytol-MRI to display hypoxia regions, then evaluating the correlation between the therapeutic outcomes.
Methods: Sixteen mice with subcutaneously implanted primary orthotopic tumor and secondary tumor, at 14-day post-implantation, were separated into two groups: ferumoxytol only (FMX) and ferumoxytol combined with radiation (Comb). T2*-weighted (MGE) and T1-weighted (FLASH) images were acquired pre-injection and 24h post-injection before the radiotherapy (Day 15 & 16) and after the radiotherapy (Day 23 & 24) for assessing the distribution of ferumoxytol in the tumor. The FLASH images were used to set the threshold for detecting the tumor hypoxia regions.
Results: The %T2* change of hypoxia region was positively correlated with mammary tumor responses, suggesting the higher the intensity of the FLASH imaging, the lower the mammary tumor responses could be (r = 0.9497, p = 0.0503), and it was not observed in the flank tumor (r = 0.2002, p =0.6345). Tumor responses were also positively correlated with mean %T2* change of hypoxia region (r = 0.9240, p = 0.0760). Additionally, the %T2* change of hypoxia region was negatively correlated with M2 macrophages (r = -0.7118, p=0.1126).
Conclusion: In conclusion, it showed that the hypoxia region can be evaluated by FLASH images, and the %T2* change in this region were positively correlated with tumor responses, and almost negatively correlated with M2 macrophages. Future work is to use quantitative susceptibility mapping (QSM) for better sensitively visualizing the distribution of the macrophages and tumor vessels.