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.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
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Conroy, Richard
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Cornell University
Engineering (All Types)
Schools of Engineering
United States
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Lamb, Erin S; Wright, Logan G; Wise, Frank W (2014) Divided-pulse lasers. Opt Lett 39:2775-7
Liu, Hui; Liu, Zhanwei; Lamb, Erin S et al. (2014) Self-similar erbium-doped fiber laser with large normal dispersion. Opt Lett 39:1019-21
Cianchetti, Flor A; Kim, Dong Hwan; Dimiduk, Sally et al. (2013) Stimulus-evoked calcium transients in somatosensory cortex are temporarily inhibited by a nearby microhemorrhage. PLoS One 8:e65663
Lefrancois, Simon; Liu, Chi-Hung; Stock, Michelle L et al. (2013) High-energy similariton fiber laser using chirally coupled core fiber. Opt Lett 38:43-5
Wise, Frank (2013) Lasers for nonlinear microscopy. Cold Spring Harb Protoc 2013:
Zhao, L M; Bartnik, A C; Tai, Q Q et al. (2013) Generation of 8 nJ pulses from a dissipative-soliton fiber laser with a nonlinear optical loop mirror. Opt Lett 38:1942-4
Farrar, Matthew J; Bernstein, Ida M; Schlafer, Donald H et al. (2012) Chronic in vivo imaging in the mouse spinal cord using an implanted chamber. Nat Methods 9:297-302
Ding, Edwin; Lefrancois, Simon; Kutz, Jose Nathan et al. (2011) Scaling Fiber Lasers to Large Mode Area: An Investigation of Passive Mode-Locking Using a Multi-Mode Fiber. IEEE J Quantum Electron 47:597-606
Renninger, William H; Chong, Andy; Wise, Frank W (2011) Amplifier similaritons in a dispersion-mapped fiber laser [Invited]. Opt Express 19:22496-501
Lauer, Arne; Cianchetti, Flor A; Van Cott, Elizabeth M et al. (2011) Anticoagulation with the oral direct thrombin inhibitor dabigatran does not enlarge hematoma volume in experimental intracerebral hemorrhage. Circulation 124:1654-62

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