Realtime Nonlinear Optical-Resolution Photoacoustic Imaging using Novel Fiber-Laser Technology

我们将在微观尺度上开发无标记功能和化学键特异性成像的策略。在过去，光声对比主要限于血红蛋白和外源性造影剂。受激拉曼和振动泛频光学分辨光声显微镜（OR-PAM）将进行研究。这些非线性模式的基础上直接转移能量的分子振动，并可能提供新的机会，如脂质，神经元髓鞘，核酸等分子靶点的新物种的无标记成像，这应该提供的分子特异性的CARS显微镜与改进的成像深度，并可能提供临床医生和生物学家的组织病理学的诊断能力没有活检样本。通过使用调谐的泵浦和探测光束，使得它们的波数位移是拉曼峰，我们有效地将能量直接泵浦到特定化学键的振动模式中。在振动泛音成像的情况下，将以拉曼峰的泛音为目标。我们将使用一个可调谐的光纤激光源，在近红外振动泛音波长的脂质，DNA和其他分子目标（血红蛋白吸收非常小）照明组织。振动模式激发的效率在高峰强度下将是最有效的，这可以用ps激光器实现。利用NIR ps脉冲，我们的计算表明，由于血红蛋白（占主导地位的亚表面吸收发色团），拉曼脂质信号对比度应该> 10倍线性吸收信号。一些拟议的进展将只可能由于新的可调谐ps光纤激光器系统正在开发的Genia光子学，高度新颖的文献和市场。我们将开发用于转化和临床研究的实时C扫描临床前桌面系统和临床显微内窥镜系统。我们预计在口腔癌，皮肤科，胃肠应用，以及其他应用程序中的临床应用扩展目前由当前内镜系统服务。

We will develop strategies for label-free functional and chemical-bond-specific imaging at a microscale. In the past photoacoustic contrast has primarily been restricted to hemoglobin and exogenous contrast agents. Stimulated Raman and vibrational overtone optical-resolution photoacoustic microscopy (OR-PAM) will be investigated. These nonlinear modes are based on transferring energy directly to molecular vibrations and may provide new opportunities for label-free imaging of new species of molecular targets such as lipids, neuronal myelin sheaths, nucleic acids, etc. This should provide the molecular specificity of CARS-microscopy with improved imaging depth and may offer clinicians and biologists the diagnostic power of histopathology without biopsy samples. By using pump and probe beams tuned so that their wavenumber shift is a Raman peak, we effectively pump energy directly into vibrational modes of specific chemical bonds. In the case of vibrational overtone imaging, an overtone of a Raman peak will be targeted. We will use a tunable fiber-laser source, illuminating tissues at NIR vibrational overtone-wavelengths of lipids, DNA, and other molecular targets (where haemoglobin absorption is very minimal). Efficiency of vibrational mode excitation will be most efficient at high peak intensities, achievable with ps-lasers. With NIR ps-pulses, our calculations show that Raman lipid signal contrast should be >10x linear absorption signals due to haemoglobin, the dominant sub-surface absorbing chromophore. Some of the proposed advances will only be possible due to novel tunable ps-fiber-laser systems being developed by Genia Photonics, highly novel to the literature and the market. We will develop realtime C-scanning pre-clinical tabletop systems and clinical micro-endoscopy systems for translational and clinical research. We anticipate clinical applications in oral cancer, dermatology, gastro-intestinal applications, and other applications extending those currently served by current endo-microscopy systems.