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

描述（由申请人提供）：在过去十年中，基于超短（皮秒和飞秒持续时间）光脉冲的生物成像出现了重大科学进展，并且还报告了短脉冲诊断和治疗疾病的初步演示。实例包括多光子显微术、光学相干断层扫描术和相干反斯托克斯拉曼光谱（汽车）显微术。光学成像技术的一个相对弱点是其较差的深度穿透：可见光波长下的成像仅限于厚度小于约1毫米的样本和浅表组织。组织中更深的结构的图像可以用1000和1300 nm之间的红外波长获得。在这个波长范围内的超短光脉冲源是复杂和昂贵的，这阻碍了非线性成像技术的应用。将开发产生非线性显微镜理想的短脉冲的光纤激光器。该项目的目标是展示飞秒和皮秒光纤激光器，其性能与目前非线性显微镜中使用的固态激光器相匹配或超过，但具有光纤的主要优势：光源紧凑、稳定、用户友好、与内窥镜仪器兼容且价格低廉。这些激光器将与康奈尔大学、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。三次谐波发生显微镜将被应用于在大鼠皮层的小规模中风引起的细胞的形态学变化的体内表征，而多重汽车显微镜将被用来确定血液氧合在体内从个别血管。将研究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，交钥匙源的高能量超短脉冲的可用性将促进生物医学成像技术的发展与增强的能力，并将使非线性显微镜的扩散超出研究实验室，并进入诊所。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.