Static and dynamic light and ultrasound measurements for the elucidation of biological and biomaterial structure and function

该提案的目标是开发光学和超声波技术，以利用光学、超声波和光声技术来表征细胞和组织的功能状态。到目前为止，我的工作主要集中在使用静态光学和超声波散射。在拟议的工作中，这些静态技术将根据最近理论和实验发现产生的新知识进行改进。拟议新工作的主要创新之处将是a)扩展开发的包括光声组织表征的技术，以及b)扩展静态超声和光学散射测量，以包括动态散射测量(散射强度随时间的波动)，以推断细胞和组织的状态。尽管最近光声成像领域得到了很多关注，但关于光声信号的起源以及当血管(光声信号的主要发生器)尚未分辨时如何表征信号的基本问题仍未得到回答。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光声信号。基于对单个血管产生的光声信号进行建模的新技术将被用于开发光声组织表征的方法。同时，还将根据(光学/超声)散射强度随时间的波动来开发技术。我们最近发现，死亡的细胞表现出显著更短的光学相干层析散斑去相关时间(散射强度随时间的更快波动)，并且散斑去相关时间可以用来评估细胞/组织内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，以便仅评估组织和细胞的运动。开发的光学和超声波技术将有助于对细胞和组织的功能状态进行非侵入性监测。

The objective of the proposal is to develop optical and ultrasound techniques to characterise the functional state of cells and tissues using optical, ultrasound and photoacoustic techniques. My work to date has been focused on using static optical and ultrasound scattering. In the proposed work these static techniques will be refined based on new knowledge generated from recent theoretical and experimental findings. The main novelty of the new work proposed will be a) to extend the techniques developed to include photoacoustic tissue characterization and b) to extended the static ultrasound and optical scattering measurements to include dynamic scattering measurements (fluctuations of scattering intensity as a function of time) to infer the states of cells and tissues. Whereas the field of photoacoustic imaging has recently gained a lot of attention, fundamental questions as to the origin of the photoacoustic signal and how to characterize the signal when blood vessels (the main generator of photoacoustic signals) are unresolved remain unanswered. As for most clinically relevant ultrasound frequencies blood vessels of interest cannot be resolved, a new technique is required to analyze the photoacoustic signals. New techniques based on modeling the photoacoustic signals generated by individual blood vessels will be used to develop methods for photoacoustic tissue characterization. In parallel, techniques will be also developed based on the fluctuations of (optical / ultrasound) scattering intensity as a function of time. We recently discovered that dying cells exhibit significantly shorter optical coherence tomography speckle decorrelation times (faster fluctuations of scattering intensity as a function of time), and that the speckle decorrelation time can be used to assess intracellular motion of the main scattering sources within cells / tissues. While the most common application relates to blood flow measurements, in these new techniques signals from blood are supressed so as to assess motion in tissues and cells alone. The optical and ultrasound techniques developed will aid in the non-invasive monitoring of the functional states of cells and tissues.