IEEE Trans Med Imaging. 2022 Oct;41(10):2704-2714. doi: 10.1109/TMI.2022.3168859. Epub 2022 Sep 30.
Non-invasive small-animal imaging technologies, such as optical imaging, magnetic resonance imaging and x -ray computed tomography, have enabled researchers to study normal biological phenomena or disease progression in their native conditions. However, existing small-animal imaging technologies often lack either the penetration capability for interrogating deep tissues (e.g., optical microscopy), or the functional and molecular sensitivity for tracking specific activities (e.g., magnetic resonance imaging). To achieve functional and molecular imaging in deep tissues, we have developed an integrated photoacoustic, ultrasound and acoustic angiographic tomography (PAUSAT) system by seamlessly combining light and ultrasound. PAUSAT can perform three imaging modes simultaneously with complementary contrast: high-frequency B-mode ultrasound imaging of tissue morphology, microbubble-enabled acoustic angiography of tissue vasculature, and multi-spectral photoacoustic imaging of molecular probes. PAUSAT can provide three-dimensional (3D) multi-contrast images that are co-registered, with high spatial resolutions at large depths. Using PAUSAT, we performed proof-of-concept in vivo experiments on various small animal models: monitoring longitudinal development of placenta and embryo during mouse pregnancy, tracking biodistribution and metabolism of near-infrared organic dye on the whole-body scale, and detecting breast tumor expressing genetically-encoded photoswitchable phytochromes. These results have collectively demonstrated that PAUSAT has broad applicability in biomedical research, providing comprehensive structural, functional, and molecular imaging of small animal models.
非侵入式小动物成像技术，如光学成像、磁共振成像和 X 射线计算机断层扫描，使研究人员能够在其自然状态下研究正常的生物学现象或疾病进展。然而，现有的小动物成像技术往往缺乏用于探测深层组织的穿透能力（例如，光学显微镜），或者用于跟踪特定活动的功能和分子灵敏度（例如，磁共振成像）。为了在深层组织中实现功能和分子成像，我们通过无缝结合光和超声，开发了一种集成的光声、超声和声血管造影断层扫描（PAUSAT）系统。PAUSAT 可以同时以互补对比进行三种成像模式：组织形态的高频 B 型超声成像、组织脉管系统的微泡声血管造影以及分子探针的多光谱光声成像。PAUSAT 可以提供三维（3D）多对比度图像，这些图像是配准的，在大深度处具有高空间分辨率。使用 PAUSAT，我们在各种小动物模型上进行了概念验证的体内实验：监测小鼠妊娠期间胎盘和胚胎的纵向发育，在全身范围内跟踪近红外有机染料的生物分布和代谢，以及检测表达遗传编码光致变色体的乳腺肿瘤。这些结果共同证明了 PAUSAT 在生物医学研究中有广泛的适用性，为小动物模型提供了全面的结构、功能和分子成像。
