Functional Optical Coherence Tomography for Monitoring Drug Resistance in Cancer

分子信号传导是癌症中的关键治疗靶标，并且分子治疗已经取得了一些进展。 成功治疗多种癌症。然而，我们对药效学作用的不完全了解， 限制了这些分子疗法的成功。我们最近开发了一种新的分子成像技术 技术，光热光学相干断层扫描（OCT），它扩展了穿透深度的高 分辨率超过显微镜极限的分子成像。目前的建议将进一步发展 光热OCT用于细胞受体的体内成像，并将联合收割机这种新技术与 多普勒OCT和光谱显微镜的血流动力学成像能力， 分子癌症疗法在生长成肿瘤的人类细胞中的药效学效应图， 老鼠的窗户第一个目标将使用组合的光谱/ OCT显微镜来量化 代谢率和血流动力学随肿瘤生长的变化。第二个目标是开发光热 OCT用于细胞受体的体内成像，并将量化在细胞中受体抑制的药效学。 小鼠窗口室。最终的目标是将联合收割机和显微镜相结合，以量化纵向变化， 小鼠窗口中受体表达和对联合治疗的血流动力学/代谢反应 腔室肿瘤这些研究将建立我们新的血流动力学、代谢和分子成像 高分辨率的三维药物筛选技术，用于临床前应用。这 多学科的环境将提供专业成长和科学的绝佳机会 进步。

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.