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，光学相干断层扫描，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它们的深度穿透性差：可见光波长的成像仅限于小于大约一毫米厚的样本和表面组织。在1000到1300纳米的红外波长范围内，可以获得组织中更深层的结构图像。该波长范围内的超短光脉冲源复杂且昂贵，这阻碍了非线性成像技术的应用。产生短脉冲的光纤激光器是非线性显微镜的理想选择。该项目的目标是展示飞秒和皮秒光纤激光器，它们的性能可以媲美或超过目前在非线性显微镜中使用的固态激光器，但具有光纤激光器的主要优点：光源紧凑、稳定、用户友好、与内窥镜仪器兼容，而且价格低廉。该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。三次谐波显微镜将用于在体内表征大鼠皮层小范围中风引起的细胞形态学变化，而多重CARS显微镜将用于测定单个血管的体内血氧。将研究通过自适应的激励脉冲整形来增强图像信号和减少损伤。

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.