Opt Lett. 2019 Aug 1;44(15):3773-3776. doi: 10.1364/OL.44.003773.
Hypoxia, a low tissue oxygenation condition caused by insufficient oxygen supply, leads to potentially irreversible tissue damage, such as brain infarction during stroke. Intravascular oxygenation has long been used by photoacoustic imaging, among other imaging modalities, to study hypoxia. However, intravascular oxygenation describes only the oxygen supply via microcirculation, which does not directly reflect the amount of free oxygen available for metabolism in the interstitial fluid. Therefore, to fully understand hypoxia, it is highly desirable to monitor blood oxygenation as well as tissue oxygenation during the same biological process. In this work, by combining high-resolution photoacoustic microscopy (PAM) and a novel bioreducible N-oxide-based hypoxia-sensitive probe HyP-650, we have demonstrated simultaneous imaging of intravascular oxygenation and tissue hypoxia. We have established detailed chemical, optical, and photoacoustic properties of HyP-650 for hypoxic activation in vitro and in living cells. We have also performed PAM on hindlimb ischemia models and tumor-bearing mice to study the correlation between intravascular oxygenation and tissue oxygenation at various hypoxic levels. We expect that Hyp-650 enhanced photoacoustic imaging will find a variety of applications in brain and cancer research.
缺氧是由于供氧不足导致的组织氧合水平降低，可能导致不可逆转的组织损伤，如中风时的脑梗死。血管内氧合一直被光声成像等成像方式用于研究缺氧。然而，血管内氧合仅描述了通过微循环的供氧情况，并不能直接反映间质液中可用的代谢自由氧的量。因此，要全面了解缺氧，在同一生物过程中监测血氧和组织氧合非常重要。在这项工作中，我们通过结合高分辨率光声显微镜 (PAM) 和一种新型的基于生物还原 N-氧化物的缺氧敏感探针 HyP-650，成功实现了血管内氧合和组织缺氧的同步成像。我们已经建立了 HyP-650 在体外和活细胞中缺氧激活的详细化学、光学和光声特性。我们还在肢体缺血模型和荷瘤小鼠中进行了 PAM，以研究不同缺氧水平下血管内氧合和组织氧合之间的相关性。我们期望 HyP-650 增强的光声成像将在脑和癌症研究中找到多种应用。
