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.
Tissue-Dynamics Imaging for Therapeutic Efficacy in Ovarian Cancer Project Narrative: Tissue-dynamics imaging is a radically new platform technology that uses intracellular motion as an internal vital-signs monitor. It bridges between advances in the physics of light scattering in tissue and cancer biology to solve the important clinical problem of patient stratification and therapy selection. At the completion of this project intracellular motio will be established as a novel drug response biomarker that could transform personalized cancer care.
|Sun, Hao; Merrill, Daniel; An, Ran et al. (2017) Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture. J Biomed Opt 22:16007|
|Merrill, Daniel; An, Ran; Sun, Hao et al. (2016) Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts. Sci Rep 6:18821|
|Condello, S; Morgan, C A; Nagdas, S et al. (2015) ?-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids. Oncogene 34:2297-308|
|An, Ran; Wang, Chunmin; Turek, John et al. (2015) Biodynamic imaging of live porcine oocytes, zygotes and blastocysts for viability assessment in assisted reproductive technologies. Biomed Opt Express 6:963-76|
|Custead, M R; An, R; Turek, J J et al. (2015) Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin's lymphomas: a preliminary study. Converg Sci Phys Oncol 1:|
|Merrill, Daniel; An, Ran; Turek, John et al. (2015) Digital holography of intracellular dynamics to probe tissue physiology. Appl Opt 54:A89-97|
|An, Ran; Merrill, Dan; Avramova, Larisa et al. (2014) Phenotypic profiling of Raf inhibitors and mitochondrial toxicity in 3D tissue using biodynamic imaging. J Biomol Screen 19:526-37|