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

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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.