Functional Optical Coherence Tomography for Monitoring Drug Resistance in Cancer

分子信号转导是癌症治疗的关键靶点，分子治疗学已经取得了一些成果。 成功地治疗了多种癌症。然而，我们对药效学效应的不完全了解 活体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 光热光学相干层析成像(OCT)技术，它延长了高强度激光的穿透深度 分辨率超过显微镜极限的分子成像。目前的提议将进一步发展 光热OCT用于细胞受体的活体成像，并将这项新技术与 血流动力学成像能力为多普勒OCT和光谱显微镜提供了全面的 分子癌症治疗对人细胞生长为肿瘤的药效学效应图 老鼠窗的房间。第一个目标将使用组合光谱/OCT显微镜来定量 随着肿瘤的生长，代谢率和血流动力学的变化。第二个目标是发展光热。 OCT用于细胞受体的活体成像，并将量化受体抑制的药效学 老鼠窗口室。最终目标是将OCT和显微镜相结合，以量化 小鼠窗内受体表达与联合治疗的血流动力学/代谢反应 室内瘤。这些研究将建立我们新的血流动力学、代谢和分子成像 临床前应用的高分辨率、三维药物筛选方法等技术。这 多学科环境将为专业成长和科学发展提供绝佳机会 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.