Research On Synthetic-aperture Focusing Technique For Photoacoustic Microscopy

Vasculature and microcirculation transport the necessities for normal metabolism to all parts of living tissues and organs, and collect the metabolic waste as well. The abnormal anatomy of the vasculature often affects the homeostasis of the organisms and ultimately leads to tissue inviability. Therefore, in vivo vasculature imaging with high spatial resolution is extremely important for disease diagnosis, clinical treatment, and the physiological mechanisms study. Photoacoustic microscopy (PAM) which is developed rapidly in recent years, combines the excellent optical contrast and the high ultrasonic spatial resolution. It has been proven to be an emerging tool for imaging tumor angiogenesis, subcutaneous microvasculature, oxygenation monitoring in blood vessels, and so on. However, the lateral resolution deteriorates significantly out of the focus, due to the limitation of the focal zone in the highly focused transducer of the system. Here, a two-dimensional synthetic-aperture focusing technique (2D SAFT) and an adaptive SAFT was researched to improve the lateral resolution out of focus in PAM conducted in our laboratory, and then we exploited the system to image the changes in cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen saturation (SO2) during and after3-hour acute focal ischemic rats with laser speckle imaging (LSI). The main contents are listed as follows:(1) Virtual-point-detector-based2D SAFT with CF was investigated to improve the resolution and make the lateral resolution isotropy simultaneously. In the depth range of0.6mm near the focal spot, the best resolution processed with1D-SAFT is40μm better than that processed with2D-SAFT. However, maximum difference of lateral resolution between z-x and z-y plane is about15μm processed with2D-SAFT, while it is145μm processed with1D-SAFT. Furthermore, the2D-SAFT increased the signal-to-noise ratio (SNR) by up to8dB higher than ID SAFT at the imaging depth of700μm below the focal spot.(2) Based on2D SAFT, we propose an adaptive synthetic-aperture focusing technique (ASAFT) in conjunction with the coherence weighting factor to improve the lateral resolution out of focus in photoacoustic microscopy (PAM) for microvasculature imaging. At first, the orientations of the vessel branches are obtained using PAM based on two-dimensional (2D) synthetic-aperture focusing technique (SAFT). And then the SAFT is performed along the direction that is perpendicular to the corresponding blood vessel with virtual-point-detector concept. The improved performance of the method is validated both in the phantom study and in vivo imaging. The results indicate that the proposed method can provide images of blood vessels with better precision at different depths and along various directions compared with one-dimensional and2D SAFT.(3) The maps of changes in CBF, CBV, SO2were yielded with LSI and PAM during and after3-hour acute focal ischemic rats. These hemodynamic measures were further synthesized to deduce the changes in oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2). The results indicated that all the hemodynamics except CBV had rapid declines within40-minute occlusion of middle cerebral artery (MCAO). CBV in arteries and veins firstly increased to the maximum value of112.42±36.69%and130.58±31.01%by15minutes MCAO, then all the hemodynamics had a persistent reduction with small fluctuations during the ischemic period. The study suggested that combining LSI and PAM could provide an attractive approach for the determination of the mechanism of stroke and detection in small animal studies.