Fundamental studies in the temporal changes of light and sound scattering and absorption to generate new forms of biological and biomaterial contrast

该提案的目标是开发利用光学、超声波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。在拟议的工作中，将根据最近的理论和实验发现产生的新知识来改进这些技术。拟议工作的一部分将是对这些超声和光学技术的渐进但重要的改进。基于我们最近关于细胞吸收光产生的声音的令人兴奋的发现，主要的新颖性将是将技术扩展到包括光声组织表征。为了产生新的对比度(产生具有新信息的图像)，我们将开发包括动态散射测量(散射强度随时间波动)的超声和光学散射测量。对于光声学来说，关于光声信号的来源以及当血管未被分辨时如何表征信号的基本问题仍然没有答案。对于大多数临床相关的超声频率，不能分辨感兴趣的血管。需要一种新的技术来分析包含血管及其完整性信息的光声信号。依靠对光声波频率成分的分析，将发展新的光声技术。还将以类似于经典动态光散射技术的方式，基于(光学/超声/光声)信号强度作为时间函数的波动来开发技术。我们最近发现，死亡的细胞表现出显著更短的光学相干断层扫描散斑去相关时间(以及超声散斑去相关时间)，这可以用来评估细胞/组织中主要散射源的细胞内运动。虽然最常见的应用与血流测量有关，但在这些新技术中，来自血液的信号被抑制，以仅评估组织和细胞的运动。将使用先进的数学技术来提取相关参数，以表征这一运动。我们将研究是否可以将同样的技术应用于光声信号(不是由散射产生的，而是由光吸收组织结构产生的)。这些技术的发展将有助于对细胞和组织功能状态的非侵入性和连续监测，在医学上具有潜在的应用前景。

The objective of the proposal is to develop techniques to characterise the structure and functional state of cells and tissues using optical, ultrasound 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. In the proposed work 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 important, improvements to these ultrasound and optical techniques. Based on our recent exciting findings related to the sound produced by cells absorbing light, the main novelty will be extending the techniques to include photoacoustic tissue characterization. To generate new contrast (producing images with new information), we will develop ultrasound and optical scattering measurements that include dynamic scattering measurements (fluctuations of scattering intensity as a function of time). For photoacoustics, fundamental questions as to the origin of the photoacoustic signal and how to characterize the signal when blood vessels are unresolved remain unanswered. For most clinically relevant ultrasound frequencies blood vessels of interest cannot be resolved. A new technique is required to analyze the photoacoustic signals that contain information about blood vessels and their integrity. New photoacoustic techniques will be developed which rely of the analysis of the frequency content of the photoacoustic waves. Techniques will be also developed based on the fluctuations of (optical / ultrasound/photoacoustic) signal intensity as a function of time, in a manner similar to classical dynamic light scattering techniques. We recently discovered that dying cells exhibit significantly shorter optical coherence tomography speckle decorrelation times (as well as ultrasound speckle decorrelation times), and that this can be used to assess intracellular motion of the dominant scattering sources in the cells / tissues. While the most common application relates to blood flow measurements, in these new techniques signals from blood are supressed to assess motion in tissues and cells alone. Advanced mathematical techniques will be used to extract relevant parameters for the characterization of this motion. We will investigate as to whether the same techniques can be applied to photoacoustic signals (not produced by scattering, but by optically absorbing tissue structures). The development of these of techniques will aid in the non-invasive and continuous monitoring of the functional states of cells and tissues, with potential applications in medicine.