Tissue-dynamics Imaging for Therapeutic Efficacy in Ovarian Cancer

描述(申请人提供)：该项目将使用一种名为组织动力学成像(TDI)的非传统成像技术来测量卵巢肿瘤对化疗和生物治疗的敏感性。组织动力学成像是第一个使用细胞内运动作为癌症组织内部生命体征监测器的成像技术。TDI使用低相干照明的数字全息术来构建组织内高达一毫米的3D全息图。动态成像在功能成像方法中检测不同的细胞运动作为内源性图像对比。三维实体肿瘤模型，如肿瘤移植物和多细胞肿瘤球体，是研究复杂的三维肿瘤微环境、肿瘤异质性和多细胞耐药性的理想体外模型。组织动力学成像提供了所需的深度能力、对细胞运动的敏感性以及不同动态细胞功能的特征，以提供对细胞功能和增殖的定量测量。在这项拟议的工作中，将使用组织动力学成像来生成癌症生物学中应用于肿瘤移植物的第一个药物反应表型曲线。其目标是设计一种可重复性和灵敏的治疗预测标记物。目前测量化疗耐药性的方法很麻烦，而且不能预测生物学和临床反应。通过在癌症生物学和相干光学物理领域之间架起桥梁，我们提出，通过利用卵巢肿瘤或转移性植入物的体外细胞内动力学特性，这项新技术可以适用于克服对卵巢癌女性具有高度临床相关性的问题。一个商业合作伙伴，动画动力有限责任公司，将接受技术转让，并建立第一个基于诊所的TDI系统。

DESCRIPTION (provided by applicant): This project will employ a non-traditional imaging technology called tissue-dynamics imaging (TDI) to measure the sensitivity of ovarian tumors to chemotherapy and biological treatments. Tissue-dynamics imaging is the first imaging technology to use intracellular motion as an internal vital-signs monitor of cancer tissue. TDI uses digital holography with low-coherence illumination to construct 3D holograms up to a millimeter inside tissue. Dynamic imaging detects diverse cellular motions as endogenous image contrast in a functional imaging approach. Three-dimensional solid tumor models, such as tumor exgrafts and multicellular tumor spheroids, are ideal in vitro models to study complex three-dimensional tumor microenvironments, tumor heterogeneity, and multicellular drug resistance. Tissue dynamics imaging provides the required depth capability, the sensitivity to cellular motions, and the signatures of different dynamical cellular functions to provide quantitative measurements of cellular functioning and proliferation. In the proposed work, tissue dynamics imaging will be used to generate the first drug-response phenotypic profiles in cancer biology applied to tumor exgrafts. The goal is to design a reproducible and sensitive predictive marker to therapy. Current approaches that measure chemo-resistance are cumbersome and not predictive of biological and clinical response. By bridging between the fields of cancer biology and coherent optical physics, we propose that by exploiting the intracellular dynamical properties of ovarian tumors or metastatic implants ex-vivo, this new technology can be adapted to overcome a problem of high clinical relevance for women with ovarian cancer. A commercial partner, Animated Dynamics LLC, will receive technology transfer and construct the first clinic-based TDI system.