Biomedical Engineering, Boston University, Boston, MA, USA.
Department of Biology and Bioinformatics Program, Boston University, Boston, MA, USA.
Sci Rep. 2022 Apr 7;12(1):5864. doi: 10.1038/s41598-022-09671-2.
Spatial Frequency Domain Imaging (SFDI) can provide longitudinal, label-free, and widefield hemodynamic and scattering measurements of murine tumors in vivo. Our previous work has shown that the reduced scattering coefficient (μ') at 800 nm, as well as the wavelength dependence of scattering, both have prognostic value in tracking apoptosis and proliferation during treatment with anti-cancer therapies. However, there is limited work in validating these optical biomarkers in clinically relevant tumor models that manifest specific treatment resistance mechanisms that mimic the clinical setting. It was recently demonstrated that metronomic dosing of cyclophosphamide induces a strong anti-tumor immune response and tumor volume reduction in the E0771 murine breast cancer model. This immune activation mechanism can be blocked with an IFNAR-1 antibody, leading to treatment resistance. Here we present a longitudinal study utilizing SFDI to monitor this paired responsive-resistant model for up to 30 days of drug treatment. Mice receiving the immune modulatory metronomic cyclophosphamide schedule had a significant increase in tumor optical scattering compared to mice receiving cyclophosphamide in combination with the IFNAR-1 antibody (9% increase vs 10% decrease on day 5 of treatment, p < 0.001). The magnitude of these differences increased throughout the duration of treatment. Additionally, scattering changes on day 4 of treatment could discriminate responsive versus resistant tumors with an accuracy of 78%, while tumor volume had an accuracy of only 52%. These results validate optical scattering as a promising prognostic biomarker that can discriminate between treatment responsive and resistant tumor models.
空间域光频成像（SFDI）可提供体内鼠肿瘤的纵向、无标记和宽视场血流动力学和散射测量。我们之前的工作表明，800nm 处的散射系数（μ'）以及散射的波长依赖性，在跟踪癌症治疗过程中的细胞凋亡和增殖方面都具有预后价值。然而，在验证这些光学生物标志物方面，临床相关肿瘤模型的验证工作有限，这些模型表现出特定的治疗抵抗机制，模拟了临床环境。最近的研究表明，环磷酰胺的节拍式给药在 E0771 鼠乳腺癌模型中诱导强烈的抗肿瘤免疫反应和肿瘤体积缩小。这种免疫激活机制可以被 IFNAR-1 抗体阻断，导致治疗耐药。在这里，我们进行了一项纵向研究，利用 SFDI 监测这种配对的反应性-耐药模型，最长可达 30 天的药物治疗。与接受 IFNAR-1 抗体联合环磷酰胺治疗的小鼠相比，接受免疫调节节拍式环磷酰胺方案的小鼠肿瘤的光学散射显著增加（治疗第 5 天增加 9%，减少 10%，p<0.001）。这些差异的幅度在整个治疗过程中增加。此外，治疗第 4 天的散射变化可以以 78%的准确率区分反应性和耐药性肿瘤，而肿瘤体积的准确率仅为 52%。这些结果验证了散射作为一种有前途的预后生物标志物，可以区分治疗反应性和耐药性肿瘤模型。
