The goal of the proposed research is to develop a novel optical imaging technology for in vivo functional imaging of biological tissue. Encoding light by high-frequency ultrasound in biological tissue yields high spatial resolution: 100 mu/m in the R21 phase and 20 m/um in the R33 phase with a maximum imaging depth of 2-4 mm. The current optical technologies for in vivo high-resolution imaging of biological tissue include primarily confocal microscopy and optical-coherence tomography. Confocal microscopy can achieve approximately 10-mu/mm resolution but can image up to only 0.5 mm into biological tissue. Optical-coherence tomography can achieve approximately 10-mu/m resolution but can image only approximately -1 mm into scattering biological tissue. Although both technologies are useful in their areas of strength, many superficial lesions of interest are deep beyond reach. Both of the technologies depend primarily on singly backscattered photons for spatial resolution. Because biological tissues, with the exception of ocular tissue, are highly scattering for light transport, singly backscattered light attenuates rapidly with imaging depth. Therefore, both of the technologies have fundamentally limited maximum imaging depths that restrict their applications. The proposed optical imaging system overcomes this limitation on maximum imaging depth. The proposed technology does not depend on singly backscattered light. A chirped ultrasonic wave is focused into biological tissue. Any light that is encoded by ultrasound, including both singly and multiply scattered photons, contributes to the imaging signal. The axial resolution is achieved with ultrasonic-frequency sweeping and Fourier transformation. The lateral resolution is acquired by focusing the ultrasonic wave. The imaging resolutions as well as the maximum imaging depth are scaleable with the ultrasonic frequency. Dual wavelengths will be employed in the R33 phase for the functional imaging of oxygenation saturation of hemoglobin. Focused optical delivery and optical spatial filtering are used to improve the signal-to-noise ratio. The proposed technology--a quantum leap from the state of the art--is complementary to confocal microscopy and optical-coherence tomography and has the potential for broad application in biomedicine.
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