Fundamental studies and novel approaches enabling the generation and characterization of ultrasound and photoacoustic contrast to probe the structure and function of cells, biomaterials and biological systems

该提案的目标是开发利用超声波、声学和光声技术来表征细胞和组织的结构和功能状态的技术。到目前为止，这位研究人员的工作重点是使用光学和超声散射作为表征细胞和组织的一种手段，特别强调对细胞死亡的非侵入性检测。这些技术将根据最近的理论和实验结果产生的新知识加以改进。拟议工作的一部分将是对超声和光学技术的技术方面进行渐进但重大的改进。基于我们最近关于微泡如何对超声波做出反应的发现，以及令人兴奋的是，纳米气泡如何用于成像治疗目的，我们建议进行测量，以证实我们开发的理论模型。我们已经证明了气泡外壳在这些造影剂中的关键作用，并将操纵外壳属性并测量气泡对超声波的响应。将开发新的光声技术，这将允许更清晰的图像和更准确的功能组织参数测量。这些都是基于复杂的计算机模型，这些模型考虑了用户如何在目标区域扫描超声换能器。提出了一种新的光声探测方法，通过探测通过空气传播的光声波来探测气雾化物质的含量。为了探索细胞和气泡的机械特性，我们将使用从上一次发现拨款中开发的技术。我们将使用声学流式细胞仪测量单个粒子的散射，并使用模型计算相关性质。最后，我们将进一步开发一种基于细胞对微流控通道中振动的响应的新技术。我们发现，暴露在振动底物下的细胞会产生微流，使我们能够探测它们的机械性能。这些技术的发展将有助于对细胞和组织的功能状态进行非侵入性和持续的监测，具有潜在的医学应用前景。

The proposal's objective is to develop techniques to characterize the structure and functional state of cells and tissues using ultrasound, acoustic and photoacoustic techniques. The investigator's work to date has focused on using optical and ultrasound scattering as a means to characterize cells and tissues, with a particular emphasis on the non-invasive detection of cell death. These techniques will be refined based on new knowledge generated from recent theoretical and experimental findings. Part of the proposed work would represent incremental but significant improvements to technical aspects of the ultrasound and optical techniques. Based on our recent findings on how microbubbles respond to ultrasound and, excitingly, how nanobubbles can be used for imaging therapeutic purposes, we propose to make measurements that will confirm the theoretical models we have developed. We have demonstrated the critical role of the bubble shell in these contrast agents and will manipulate the shell properties and measure the bubble response to ultrasound. New photoacoustic techniques will be developed, which will allow for clearer images and more accurate measurements of functional tissue parameters. These are based on sophisticated computer models that consider how a user scans an ultrasound transducer over a target area. Novel photoacoustic approaches are proposed to probe the content of aerosolized material by detecting the photoacoustic waves that travel through the air. To probe the mechanical properties of cells and bubbles, we will use techniques developed from the previous Discovery Grant. We will use an acoustic flow cytometer to measure the scattering from single particles and use models to calculate the relevant properties. Finally, we will further develop a new technique based on the response of cells to vibrations in a microfluidic channel. We discovered that cells exposed to a vibrating substrate create microflows that allow us to probe their mechanical properties. The development of these techniques will aid in the non-invasive and continuous monitoring of the functional states of cells and tissues, with potential applications in medicine.