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技术，以表征细胞和组织的结构和功能状态使用超声，声学和光声技术。迄今为止，研究者的工作主要集中在使用光学和超声散射作为表征细胞和组织的手段，特别强调细胞死亡的非侵入性检测。这些技术将根据从最近的理论和实验发现中产生的新知识进行改进。拟议工作的一部分将代表对超声波和光学技术的技术方面的渐进但重大的改进。基于我们最近关于微泡对超声波的反应，以及令人兴奋的是，纳米泡如何用于成像治疗目的的发现，我们建议进行测量，以证实我们开发的理论模型。我们已经证明了泡沫壳在这些造影剂中的关键作用，并将操纵壳的性质和测量泡沫对超声波的响应。新的光声技术将被开发，这将允许更清晰的图像和更准确的测量功能组织参数。这些都是基于复杂的计算机模型，考虑用户如何扫描目标区域的超声波换能器。提出了一种新的光声方法，通过检测在空气中传播的光声波来探测雾化物质的含量。为了探测细胞和气泡的力学特性，我们将使用以前的发现基金开发的技术。我们将使用声学流式细胞仪来测量单个粒子的散射，并使用模型来计算相关特性。最后，我们将进一步开发一种基于微流体通道中细胞对振动响应的新技术。我们发现，细胞暴露在振动的基底下会产生微流，这使我们能够探测它们的机械特性。这些技术的发展将有助于对细胞和组织的功能状态进行无创和连续监测，在医学上具有潜在的应用前景。

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.