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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB002019-15
Application #
8301793
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Conroy, Richard
Project Start
1995-08-01
Project End
2013-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
15
Fiscal Year
2012
Total Cost
$314,147
Indirect Cost
$109,185
Name
Cornell University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Chong, Andy; Wright, Logan G; Wise, Frank W (2015) Ultrafast fiber lasers based on self-similar pulse evolution: a review of current progress. Rep Prog Phys 78:113901
Farrar, Matthew J; Rubin, Jonathan D; Diago, Darcy M et al. (2015) Characterization of blood flow in the mouse dorsal spinal venous system before and after dorsal spinal vein occlusion. J Cereb Blood Flow Metab 35:667-75
Lamb, Erin S; Wise, Frank W (2015) Multimodal fiber source for nonlinear microscopy based on a dissipative soliton laser. Biomed Opt Express 6:3248-55
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Lamb, Erin S; Lefrancois, Simon; Ji, Minbiao et al. (2013) Fiber optical parametric oscillator for coherent anti-Stokes Raman scattering microscopy. Opt Lett 38:4154-7
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