Department of Chemistry, Imperial College London, London SW7 2AZ, United Kingdom.
Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9225-30. doi: 10.1073/pnas.1301479110. Epub 2013 May 20.
Encapsulated microbubbles are well established as highly effective contrast agents for ultrasound imaging. There remain, however, some significant challenges to fully realize the potential of microbubbles in advanced applications such as perfusion mapping, targeted drug delivery, and gene therapy. A key requirement is accurate characterization of the viscoelastic surface properties of the microbubbles, but methods for independent, nondestructive quantification and mapping of these properties are currently lacking. We present here a strategy for performing these measurements that uses a small fluorophore termed a "molecular rotor" embedded in the microbubble surface, whose fluorescence lifetime is directly related to the viscosity of its surroundings. We apply fluorescence lifetime imaging to show that shell viscosities vary widely across the population of the microbubbles and are influenced by the shell composition and the manufacturing process. We also demonstrate that heterogeneous viscosity distributions exist within individual microbubble shells even with a single surfactant component.
微泡被广泛认为是超声成像的高效对比剂。然而，在灌注成像、靶向药物输送和基因治疗等高级应用中，要充分发挥微泡的潜力，仍然存在一些重大挑战。一个关键要求是准确描述微泡的粘弹性表面特性，但目前缺乏独立、无损的定量和映射这些特性的方法。我们在这里提出了一种使用嵌入在微泡表面的一种小分子荧光染料（称为“分子转子”）进行这些测量的策略，其荧光寿命与周围环境的粘度直接相关。我们应用荧光寿命成像来表明，壳层粘度在微泡群体中差异很大，并且受到壳层组成和制造工艺的影响。我们还证明，即使使用单一的表面活性剂成分，单个微泡壳层内也存在不均匀的粘度分布。
