Development and Application of Short-Pulse Fiber Lasers for Biomedical Imaging

描述(申请人提供)：在过去的十年中，基于使用超短(皮秒和飞秒)光脉冲的生物成像方面取得了重大的科学进展，还报道了短脉冲诊断和治疗疾病的初步演示。例如多光子显微镜、光学相干层析成像和相干反斯托克斯拉曼光谱(CARS)显微镜。光学成像技术的一个相对弱点是深度穿透性差：在可见光波长下的成像仅限于厚度小于约一毫米的样品和浅层组织。红外波长在1000到1300纳米之间，可以获得组织中更深层次的结构的图像。在这个波长范围内的超短光脉冲的来源复杂且昂贵，这阻碍了非线性成像技术的应用。产生适合于非线性显微镜的短脉冲的光纤激光器将被开发出来。该项目的目标是展示飞秒和皮秒光纤激光器，其性能达到或超过目前用于非线性显微镜的固态激光器的性能，但具有光纤的主要优势：光源将紧凑、稳定、用户友好、与内窥镜仪器兼容且价格低廉。激光将与康奈尔大学、哈佛大学和密歇根州立大学的生物医学成像专家合作开发和使用。三次谐波显微镜将用于体内表征小范围中风引起的大鼠大脑皮质细胞的形态变化，而多重CARS显微镜将用于确定体内单个血管的血液氧合。本课程将研究如何通过激励脉冲的自适应整形来增强图像信号和减少损伤。 公共卫生相关性：可靠、廉价、交钥匙的高能超短脉冲来源的可获得性将促进具有增强能力的生物医学成像技术的发展，并将使非线性显微镜的扩散超越研究实验室，进入临床。这将有助于疾病的诊断和治疗。

DESCRIPTION (provided by applicant): In the last decade, major scientific advances in bioimaging based on the use of ultrashort (picosecond- and femtosecond-duration) light 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, and coherent anti-Stokes Raman spectroscopy (CARS) microscopy. A relative weakness of optical imaging techniques is their poor depth-penetration: imaging at visible wavelengths is limited to samples less than approximately one millimeter thick, and superficial tissue. Images of structures much deeper in tissue could be obtained with infrared wavelengths between 1000 and 1300 nm. Sources of ultrashort light pulses in this wavelength range are complicated and expensive, and this hinders the applications of nonlinear-imaging techniques. Fiber lasers that generate short pulses ideal for nonlinear microscopies will be developed. The goal of this project is to demonstrate femtosecond and picosecond fiber lasers that match or exceed the performance of the solid-state lasers currently employed in nonlinear microscopies, but with the major advantages of fiber: the sources will be compact, stable, user-friendly, compatible with endoscopic instruments, and inexpensive. The lasers will be developed and used in collaboration with experts in biomedical imaging at Cornell, Harvard, and Michigan State universities. Third-harmonic generation microscopy will be applied to in vivo characterization of morphological changes in cells caused by small-scale strokes in the rat cortex, while multiplex CARS microscopy will be employed to determine blood oxygenation in vivo from individual blood vessels. Enhancement of image signals and reduction of damage through adaptive shaping of excitation pulses will be investigated. PUBLIC HEALTH RELEVANCE: The availability of reliable, inexpensive, turn-key sources of high-energy ultrashort pulses will facilitate the development of biomedical imaging techniques with enhanced capabilities, and will enable the proliferation of nonlinear microscopies beyond research laboratories and into clinics. This will aid in the diagnosis and treatment of disease.