| Microcirculation is referred to as blood circulation within microvasculature, and the mass exchange between blood and tissue is the fundamental function of microcirculation. Since many serious diseases are involved with the abnormal change of microcirculation, it is of great clinical significance to study microcirculation by in vivo imaging techniques with high temporalspatial resolution. Because the spatial structure of the microcirculation network is complicated, and the diameters of the microvasculature vary from several micrometers to200micrometer, imaging techniques with single scale are not able to map microcirculation well. Photoacoustic microscopy (PAM) encodes the optical absorption to ultrasound, and can provide multiscale imaging for biolgy tissue with the same contrast source. Furthermore, due to that the ultrasound scattering is much lower than optical scattering in tissue, PAM can obtain higher image depth than other optical imaging tools. Therefore, PAM has advantages on imaging of the complicated microcirculation network in deep tissue in vivo with multiple scales in three dimensions (3-D). This study aimed to develop and utilize the multiscale PAM system for the research on microcirculation. More detail is desacribed as follows:(1) In order to image the microcirculation in deep biology tissue, the previously built acoustic-resolution functional photoacoustic microscopy (fPAM) system in our lab was used. The system lateral resolution was measured to be45μm, and the system imaging depth was measured to be3mm in tissue. Microvasculatures in dorsal skin and cerebral cortex in rat and the palm of volunteers were studied by fPAM, it was demonstrated that this system of fPAM has the ability to image the strcuture of microcirculation in deep biology tissue.(2) As the resolution of the acoustic-resolution fPAM described above is not sufficient to image capillaries of microcircution, meanwhile, in order to improve the imaging depth of high resolution PAM systems, a new photoacoustic probe was designed and a high resolution optical-resolution PAM (OR-PAM) system based on a reflective objective was developed. The reflective objective was used to obtain near optical diffraction-limited focus. Meanwhile, the ultrasound transducer was located into the hollow optical cone of the objective to realize direct ultrasonic detection, and the ultrasonic detection efficiency is improved without the loss of ultrasound transmission energy due to reflection on multiple interfaces. A polyvinylidene difluoride (PVDF) ultrasonic transducer with high sensitivity was utilized to collect the excited ultrasound, which guaranteed that the system could image a single capillaries and red blood cells with sufficient sensitivity. The lateral resolution of this new system at focus was measured to be1.2μm, and the system could image the targets with relatively high penetration depth of0.9mm in biological tissue. These make the system can resolve a single capillaries and discrete red blood cells in vivo. The system was demonstrated to have the capacity to study microcirculation in capillary level by imaging the microvasculature in mouse ear.(3) In order to realize the multiple-information image of the cortex, the multiple-parameter imaging of the rat cortex microcirculation in early cerebral hypoperfusion was performed by combining the fPAM with laser speckle imaging (LSI). The transient changes in cerebral blood flow (CBF), oxygen saturation (SO2) and total hemoglobin concentration (HbT) in single micro blood vessels of ipsilateral cortex were observed during transient cerebral hypoperfusion by ligating the unilateral common carotid artery (CCA) in rats. CBF, SO2, and HbT respectively decreased to37±3%,72±7%, and93±2%of baseline in6seconds immediately after occlusion, and then recovered with different degree. In summary, these parameters showed the decrease with different degree and the following recovery over time after ligation, the recovery of SO2lagged behind those of CBF and HbT, which had the similar response. |
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