Development of Optical-resolution Photoacoustic Microscopy with Compensation of Absorption Saturation

Project: Research

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High-resolution imaging of oxygen transport in living tissue provides valuable information for many biomedical applications, such as mapping neuron activities in the brain via neurovascular coupling, studying tumor progress via quantitative imaging of oxygen metabolic rate. Most oxygen in the human body binds to hemoglobin and transports through the blood circulation. As an emerging biomedical imaging modality, optical-resolution photoacoustic microscopy (OR-PAM) can image oxygen saturation (sO2) of blood with sub-cellular spatial resolution, high imaging speed, and high signal-to- noise ratio. Conventional OR-PAM usually assumes a linear relationship between the measured photoacoustic (PA) amplitude and the absorption coefficient. Based on the linear assumption, OR-PAM determines the sO2 value from PA signals measured at two or more optical wavelengths. Limited by high pulse repetition rate laser technique, most conventional OR-PAM systems use wavelengths in the Q-band. The absorption coefficient of blood in the Q-band is too high and may lead to an absorption saturation problem. With absorption saturation, the measured sO2 value may have a significant systematic error.To avoid the systematic error in sO2 imaging, we propose to develop a new functional OR-PAM imaging technique that can compensate the absorption saturation in sO2 imaging, as well as maintain other performances, such as high imaging speed and high signal-to-noise ratio. We will model the absorption saturation into a nonlinear relationship between the PA amplitude and the absorption coefficient. Via measuring PA signals at three or more wavelengths, we can solve the nonlinear equations and determine the sO2 values without systematic errors. We will develop a new OR-PAM system to test the proposed sO2 imaging method. A multi-wavelength pulsed laser will be built for the OR-PAM system. The new laser will have three or more wavelengths for sO2 imaging, a high pulse repetition rate, and sufficient pulse energy for each wavelength. The accuracy of the new sO2 imaging method will be validated in phantom experiments. In vivo imaging of sO2 will be demonstrated in the mouse brain to show the neurovascular coupling. Combining the sO2 with hemoglobin concentration and blood flow, we may further quantify the metabolic rate of oxygen in a tumor model. The new technical advance in OR-PAM may potentially enable many biomedical applications related to oxygen metabolism.


Project number9042617
Grant typeGRF
Effective start/end date1/01/19 → …