CAREER: Imaging multi-scale viscoelastic properties of cancer-associated remodeling

#1351474P.I.：Amy L.OldenburgPI建议构建一种新的集成系统，该系统将光学相干断层扫描(OCT)与在线数字全息术相结合，光学相干断层扫描(OCT)是一种可视化厚组织中细胞横截面的方法，在线数字全息术可以快速成像组织表面附近的平面内运动。OCT组件将监测扩散的金纳米棒的光散射波动，金纳米棒充当纳米拓扑环境的探测器。全息组件将捕获诱导的表面弹性波，这些弹性波将被重建为高分辨率组织弹性图。这些成像系统的集成使得能够在多个长度尺度上共同配准驱动和扩散运动，以便将亚细胞结构与主体粘弹性属性相关联。该集成系统将用于研究早期乳腺癌组织培养模型，在该模型中，正常和癌前乳腺上皮细胞(MECs)与间质成纤维细胞共培养。微尺度细胞外基质硬度的测量与微血管内皮细胞和基质细胞内及周围的纳米流变学测量相结合，将为导致乳腺癌的生物物理过程提供新的见解。

#1351474P.I.: Amy L. OldenburgThe PI proposes to construct a novel integrated system that incorporates optical coherence tomography (OCT), a method for visualizing cross-sections of cells in thick tissues, with in-line digital holography to rapidly image in-plane motions near the tissue surface. The OCT component will monitor light scattering fluctuations from diffusing gold nanorods which act as probes of the nanotopological environment. The holography component will capture induced surface elastic waves, which will be reconstructed into high resolution tissue elastograms. Integration of these imaging systems enables coregistration of driven and diffusive motions at multiple length scales in order to relate subcellular architecture with bulk viscoelastic properties. The proposed integrated system will be employed to study an early-stage breast cancer tissue culture model in which normal and pre-malignant mammary epithelial cells (MECs) are co-cultured with stromal fibroblasts. Measuring the microscale extracellular matrix stiffness in conjunction with nanorheological measurements in and around MECs and stromal cells will provide new insight into the biophysical processes that lead to breast cancer.