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

我们将开发在微尺度上无标签功能和化学键特异性成像的策略。过去光声造影主要局限于血红蛋白和外源性造影剂。受激拉曼和振动泛音光学分辨率光声显微镜（OR-PAM）将进行研究。这些非线性模式基于将能量直接转移到分子振动上，可能为脂质、神经髓鞘、核酸等新型分子靶点的无标记成像提供新的机会。这将提高car - s显微镜的分子特异性和成像深度，并可能为临床医生和生物学家提供无需活检样本的组织病理学诊断能力。通过调整泵浦和探针光束，使其波数位移为拉曼峰，我们有效地将能量直接泵入特定化学键的振动模式。在振动泛音成像的情况下，拉曼峰的泛音将被瞄准。我们将使用可调谐光纤激光源，以近红外振动泛音波长照亮脂质、DNA和其他分子靶标（其中血红蛋白吸收非常小）的组织。振动模式激发的效率将是最有效的在高峰强度，实现与ps激光器。使用近红外ps脉冲，我们的计算表明，由于血红蛋白（主要的亚表面吸收发色团）的作用，拉曼脂质信号的对比度应该是线性吸收信号的10倍。由于Genia Photonics公司开发的新型可调谐ps-光纤激光系统，在文献和市场上都是高度新颖的，因此一些提出的进展将成为可能。我们将开发实时c扫描临床前桌面系统和临床显微内窥镜系统，用于转化和临床研究。我们期望在口腔癌、皮肤病学、胃肠道应用和其他应用方面的临床应用扩展了当前的内窥镜系统。

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.