Collaborative Research in Biophotonics: Towards high-resolution, label-free molecular imaging in deep tissue via stimulated Raman excitation and ultrasound detection

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1066776/1066562Zhang/YakovlevThe grand challenge of optical tissue imaging is the ability to penetrate deeply into tissue while preserving molecular specificity and high spatial resolution. The proposed project tackles this grand challenge by developing a novel imaging modality based on stimulated Raman excitation and detection of the nonlinearly induced photoacoustic waves. Referred to as stimulated Raman photoacoustic microscopy, the proposed modality combines chemical specificity through the molecularly selective stimulated Raman excitation with the deep penetration and high-resolution photoacoustic imaging. Compared with existing spontaneous and nonlinear Raman microscopic imaging, the maximum imaging depth is expected to be extended by at least one order of magnitude. Compared with existing photoacoustic imaging, the much needed molecular specificity is achieved without resorting to extrinsic molecular labeling.This project will extend the existing knowledge on how advanced spectroscopic tools can be successfully used for biomedical imaging. It lays the foundation to develop a stand-alone molecular imaging microscope, capable of providing high-resolution deep tissue imaging without external labels. In the proposed research, the mechanism of the photoacoustic generation under the stimulated Raman excitation will be investigated. The investigations focus on how the elastic scattering in tissue will affect the proposed imaging modality. Monte Carlo simulations will model the effect of dual wavelength, short-pulse light propagation in scattering medium. These results will direct the design of the optimal optical illumination geometry in the future prototyping of the proposed microscope. Quantitative experimental studies will be carried out following the guidance of the theoretical estimation and Monte Carlo simulation. The sensitivity of the photoacoustic detection will be improved by matching the signal bandwidth and employing novel ultrasonic detectors. In non-scattering media, the sensitivity of stimulated Raman photoacoustic detection will be experimentally quantified in the presence of background linear optical absorption, whose effect will be mitigated by wavelength and/or time-delay modulation.