New Imaging Tools, Looking Deep into Tissue

Nonlinear microscopy is a powerful technique for investigating cellular processes that underlie normal and disease states in tissue. Existing microscope designs and excitation lasers limit the number of imaging channels and imaging depth. Increasing these will enable studies of more-complex cell interactions in a greater variety of anatomical structures. Recent work has identified the optimal conditions—light pulse energy, duration, wavelength, and repetition rate—for imaging deep in tissue using multiphoton fluorescence and harmonic-generation microscopies. Sources that supply the needed light pulses and are compatible with bioimaging laboratories, however, are not available.

Frank W. Wise, Applied and Engineering Physics, and Chris B. Schaffer, Meinig School of Biomedical Engineering, are developing fiber-based sources of ultrashort light pulses and a new microscope. Both will enhance deep-tissue imaging.

New understanding of nonlinear pulse propagation in fiber underlies the design of lasers that generate the short-duration, high-energy pulses needed for deep imaging. Furthermore, lasers made of this optical fiber hold promise to be extremely stable, compact, robust, and cost-effective. The new lasers will be evaluated quantitatively through a series of imaging experiments, on test samples and in vivo.

The researchers will also develop a hyperspectral multiphoton microscope that makes use of the new lasers. This will employ multiple excitation and detection wavelengths to vastly increase the amount of information acquired. When combined with dense fluorescent labeling strategies, this hyperspectral microscope has the potential to transform in vivo imaging from a tool used primarily for testing hypotheses into a technique for biological discovery. NIH Award Number: 2R01EB002019-16A1

Cornell Researchers

Funding Received

$1.6 Million spanning 4 years

Other Research Sponsored by National Institutes of Health