Research On The Improvement Of Sensitivity Of Photoacoustic Microscopy

The microcirculation network, which locates between the venules and arterioles, is the critical structure to fulfill the material exchange. The abnormity of structure and hemodynamic parameters of the microcirculation network affects the metabolism, even causes dysfunction. The abnormity of structure and physiological parameters often occurs at the same time in pathological condition. As a result, the multi-parameter monitoring of microcirculation is important to early detection as well as the mechanism research of diseases. Several imaging techniques have been introduced to map the microcirculation network, however, lots of problems still need to be solved. For example, some imaging systems can only collect structural or hemodynamic information, some modalities are with poor resolution or imaging depth. Optical resolution photoacoustic microscopy utilizes tightly focused laser light to achieve high resolution imaging. Combined with high absorption contrast, photoacoustic microscopy is suitable for3D microcirculation imaging in vivo. In order to improve the sensitivity, several methods were proposed considering system implementation and sample preparation.In order to improve the detection sensitivity, an optical-resolution photoacoustic imaging system was implemented. A long working distance objective was utilized to focus the laser light to achieve high resolution. A high frequency ultrasonic transducer detected the stimulated photoacoustic wave. A home made opto-acoustic coupler was used to reflect the incident laser and meanwhile detect the transmitted photoacoustic wave. This kind of design avoided the photoacoustic wave conversion during reflection, thus improved the detection sensitivity. Both theoretical analysis and experimental test proved the improved sensitivity, thus guaranteed the experiments in vivo met the laser safety standards.In order to assess the imaging performance of microcirculation in vivo. The imaging capabilities were analyzed theoretically and assessed with phantom. Photoacoustic imaging of structure and oxygen saturation was conducted in vivo to further prove the imaging capability. The lateral and axial resolution were estimated to be4.4μm and14.4um, based on the imaging of carbon nanoparticles. The imaging depth was estimated to be 1mm with photoacoustic phantom. The temporal resolution was limited by the laser repetition rate, which was1KHz by now. The vasculature of mouse ear and brain cortex was mapped with high resolution in vivo, with the single capillaries clearly mapped. With three wavelength (576nm/580nm/584nm), the oxygen saturation was mapped. Furtherly, the monitoring of hemodynamic parameters and diameter of microvessels proved the capability to monitor rapid physiological response with photoacoustic microscopy.In order to improve the sensitivity and imaging depth in skin, the optical clearing techniques were tested for photoacoustic microscopy. The monitoring by photoacoustic microscopy and ultrasonography proved that optical clearing agents enhanced the photoacoustic signal, however, the reduced transmittance of photoacoustic wave restricted the enhancement. The results also reminded that optical clearing agents that can enhance both optical and acoustic transmittance should be further tested.