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 high resolution hemodynamic imaging capabilities of Doppler OCT and hyperspectral imaging 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 hyperspectral / OCT microscope to quantify changes in blood oxygenation, and three dimensional blood flow and microvessel morphology with tumor growth and with antiangiogenic treatment.
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 photothermal OCT and hyperspectral / Doppler OCT to quantify longitudinal changes in both receptor expression and hemodyanmic response to combined receptor inhibition and antiangiogenic therapies in mouse window chamber tumors. These studies will establish our novel hemodynamic (Doppler OCT and hyperspectral imaging) and molecular (photothermal OCT) imaging techniques as high resolution, three-dimensional drug screening methods for preclinical applications. This work will be conducted under the co-mentorship of Drs. Mark Dewhirst and Joseph Izatt, who are experts in the fields of tumor therapy and optical imaging, respectfully, at Duke University. This multi-disciplinary environment will provide an excellent opportunity for professional growth and scientific advancement.
This work will develop imaging methods to study the hemodynamic 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. The optical imaging approach developed in this proposal is attractive because it provides a unique set of multi-functional information that is difficult to obtain with other techniques;it is cheap and readily applied across a broad range of disciplines. In the future, similar technologies could be translated to clinical use to provide individualized care to patients with a variety of diseases including cancer, Alzheimer's, and neural diseases, thus decreasing morbidity and mortality.
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| Skala, Melissa C; Fontanella, Andrew; Lan, Lan et al. (2010) Longitudinal optical imaging of tumor metabolism and hemodynamics. J Biomed Opt 15:011112 |
| Skala, Melissa; Ramanujam, Nirmala (2010) Multiphoton redox ratio imaging for metabolic monitoring in vivo. Methods Mol Biol 594:155-62 |
