Molecular signaling is a critical therapeutic target in cancer, and molecular therapeutics have achieved some success in treating a variety of cancers. However, our incomplete knowledge of pharmacodynamic effects in vivo limits the success of these molecular therapies. We have recently developed a new molecular imaging technique, photothermal optical coherence tomography (OCT), that extends the penetration depth of high resolution molecular Imaging beyond the microscopy limit. The current proposal will further develop photothermal OCT for in vivo imaging of cell receptors, and will combine this new technique with the hemodynamic imaging capabilities of Doppler OCT and spectral microscopy to provide a comprehensive picture of the pharmacodynamic effects of molecular cancer therapies in human cells grown into tumors in the mouse window chamber.
The first aim will use a combined spectral / OCT microscope lo quantify changes in metabolic rate and hemodynamics with tumor growth.
The second aim will develop photothermal OCT for in vivo imaging of cell receptors, and will quantify the pharmocodynamics of receptor inhibition in the mouse window chamber.
The final aim will combine OCT and microscopy to quantify longitudinal changes in receptor expression and hemodyanmic / metabolic response to combination therapies in mouse window chamber tumors. These studies will establish our novel hemodynamic, metabolic and molecular imaging techniques as high resolution, three-dimensional drug screening methods for preclinical applications. This multi-disciplinary environment will provide an excellent opportunity for professional growth and scientific advancement.

Public Health Relevance

This work will develop imaging methods to study the hemodynamic, metabolic and molecular response to drugs in preclinical models, allowing for the formulation of rational dosing and scheduling strategies that maximize the effect of these drugs. In the future, similar technologies could be translated to clinical use to provide individualized care to cancer patients.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Nordstrom, Robert J
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Vanderbilt University Medical Center
Biomedical Engineering
Schools of Engineering
United States
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Heaster, Tiffany M; Walsh, Alex J; Zhao, Yue et al. (2018) Autofluorescence imaging identifies tumor cell-cycle status on a single-cell level. J Biophotonics 11:
Lapierre-Landry, Maryse; Gordon, Andrew Y; Penn, John S et al. (2017) In vivo photothermal optical coherence tomography of endogenous and exogenous contrast agents in the eye. Sci Rep 7:9228
Lapierre-Landry, Maryse; Tucker-Schwartz, Jason M; Skala, Melissa C (2016) Depth-resolved analytical model and correction algorithm for photothermal optical coherence tomography. Biomed Opt Express 7:2607-22
Cannon, Taylor M; Shah, Amy T; Walsh, Alex J et al. (2015) High-throughput measurements of the optical redox ratio using a commercial microplate reader. J Biomed Opt 20:010503
Walsh, Alex J; Skala, Melissa C (2015) Optical metabolic imaging quantifies heterogeneous cell populations. Biomed Opt Express 6:559-73
Tucker-Schwartz, Jason M; Lapierre-Landry, Maryse; Patil, Chetan A et al. (2015) Photothermal optical lock-in optical coherence tomography for in vivo imaging. Biomed Opt Express 6:2268-82
Tucker-Schwartz, Jason M; Beavers, Kelsey R; Sit, Wesley W et al. (2014) In vivo imaging of nanoparticle delivery and tumor microvasculature with multimodal optical coherence tomography. Biomed Opt Express 5:1731-43
McCormack, Devin R; Walsh, Alex J; Sit, Wesley et al. (2014) In vivo hyperspectral imaging of microvessel response to trastuzumab treatment in breast cancer xenografts. Biomed Opt Express 5:2247-61
Walsh, Alex J; Cook, Rebecca S; Sanders, Melinda E et al. (2014) Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer. Cancer Res 74:5184-94
Zachman, Angela L; Wang, Xintong; Tucker-Schwartz, Jason M et al. (2014) Uncoupling angiogenesis and inflammation in peripheral artery disease with therapeutic peptide-loaded microgels. Biomaterials 35:9635-48

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