Femtosecond Lasers for Bioimaging Deep in Tissue

描述（由申请人提供）：在过去十年中，基于使用超短（皮秒和飞秒持续时间）光脉冲的生物成像取得了重大科学进展，并且也报道了短脉冲诊断和治疗疾病的初步演示。例子包括多光子显微镜、光学相干断层成像和飞秒角膜手术。光学成像技术的一个相对弱点是深度穿透性差：成像仅限于薄（<1毫米）的样本和表面组织。可以用波长超过1微米的波长获得组织中更深层的结构图像；1-1.3微米的范围似乎提供了数量级的优势。在这个波长范围内可调谐的飞秒脉冲源将被开发出来。光源的设计将满足非线性显微镜和光学相干层析成像的需要。该光源的核心将是飞秒光纤激光器，它比现有的固态激光器具有更大的稳定性和更低的成本等实际优势。开发的激光器将用于两项独立的合作研究。在康奈尔大学，第三次谐波生成显微镜将被应用于大鼠皮层中由光学诱导的小规模中风引起的细胞形态学变化的体内表征。这些图像将使我们能够绘制出血管病变对未标记神经细胞的影响。在加州大学欧文分校，二次谐波光学相干断层扫描将被用于监测仓鼠颊袋模型的癌症进展。新的和增强的组织可视化能力的发展将有助于疾病的诊断和治疗。特别是，三次谐波显微镜将提供有关组织的详细形态学信息，这些信息可直接或通过内窥镜检查获得，而无需外源标记。二次谐波光学相干断层扫描具有早期发现口腔癌的潜力。

DESCRIPTION (provided by applicant): In the last decade, major scientific advances in bioimaging based on the use of ultrashort (picosecond- and femtosecond-duration) optical pulses have occurred, and initial demonstrations of short-pulse diagnosis and treatment of disease have also been reported. Examples include multiphoton microscopy, optical coherence tomography imaging, and femtosecond corneal surgery. A relative weakness of optical imaging techniques is their poor depth-penetration: imaging is limited to thin (<1 mm) samples and superficial tissue. Images of structures much deeper in tissue could be obtained with wavelengths beyond 1 micron; the 1-1.3 micron range appears to offer order-of-magnitude advantages. Femtosecond-pulse sources that are tunable across this wavelength range will be developed. The sources will be designed for the needs of nonlinear microscopies and optical coherence tomography. The heart of the sources will be femtosecond fiber lasers, which offer practical advantages over existing solid-state lasers including greater stability and lower cost. The developed lasers will be used in two separate collaborative studies. At Cornell University, third harmonic generation microscopy will be applied to in vivo characterization of morphological changes in cells caused by optically-induced small-scale strokes in the rat cortex. The images will allow us to map the effects of the vascular lesion on unlabeled neural cells. At the University of California at Irvine, second-harmonic optical coherence tomography will be employed to monitor the progression of cancer in the hamster cheek pouch model. The development of new and enhanced capabilities for visualizing tissue will aid in the diagnosis and treatment of disease. In particular, third-harmonic microscopy will provide detailed morphological information about tissue that is accessible directly or by endoscopy, without exogenous labels. Second-harmonic optical coherence tomography has potential for early detection of oral cancers.