Significance: Tumor heterogeneity poses a challenge for the chemotherapeutic treatment of cancer. Tissue dynamics spectroscopy captures dynamic contrast and can capture the response of living tissue to applied therapeutics, but the current analysis averages over the complicated spatial response of living biopsy samples. Aim: To develop tissue dynamics spectroscopic imaging (TDSI) to map the heterogeneous spatial response of tumor tissue to anticancer drugs. Approach: TDSI is applied to tumor spheroids grown from cell lines and to ex vivo living esophageal biopsy samples. Doppler fluctuation spectroscopy is performed on a voxel basis to extract spatial maps of biodynamic biomarkers. Functional images and bivariate spatial maps are produced using a bivariate color merge to represent the spatial distribution of pairs of signed drug-response biodynamic biomarkers. Results: We have mapped the spatial variability of drug responses within biopsies and have tracked sample-to-sample variability. Sample heterogeneity observed in the biodynamic maps is associated with histological heterogeneity observed using inverted selective-plane illumination microscopy. Conclusion: We have demonstrated the utility of TDSI as a functional imaging method to measure tumor heterogeneity and its potential for use in drug-response profiling.

中文翻译：

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组织动力学光谱成像：异质癌组织的功能成像。

意义：肿瘤异质性对癌症的化疗提出了挑战。组织动力学光谱捕获动态对比度，并可以捕获活体组织对应用治疗的响应，但当前的分析对活体活检样本的复杂空间响应进行平均。目的：开发组织动力学光谱成像（TDSI）来绘制肿瘤组织对抗癌药物的异质空间反应。方法：TDSI 适用于从细胞系生长的肿瘤球体和离体活体食管活检样本。多普勒波动光谱在体素的基础上进行，以提取生物动力学生物标志物的空间图。使用双变量颜色合并生成功能图像和双变量空间图，以表示签名药物反应生物动力生物标志物对的空间分布。结果：我们绘制了活检中药物反应的空间变异性，并跟踪了样本间的变异性。在生物动力学图中观察到的样品异质性与使用倒置选择性平面照明显微镜观察到的组织学异质性相关。结论：我们已经证明了 TDSI 作为一种功能成像方法来测量肿瘤异质性的实用性及其在药物反应分析中的潜力。