Developments in Photoacoustic-Ultrasound Tomography

Abstract

For cancer research, a powerful imaging modality for both preclinical (where the focus is on imaging small animals) and clinical (where the focus is on imaging human subjects) applications should be inexpensive, portable, noninvasive, safe, and capable of measuring a myriad of information. Furthermore, scalability between small and large subjects will allow this modality to be easily utilized for both preclinical and clinical applications. An emerging multimodality system that _ts these criteria is photoacoustic-ultrasound tomography. Ultrasound tomography where ultrasound waves are transmitted through a target and then received can provide not only morphological image, but due to its geometry, it can also provide quantitative information such as acoustic speed-of-sound and attenuation within a target. Photoacoustic tomography where short light pulses are used to produce ultrasound signal - can provide other quantitative information based on optical parameters, such as optical absorption, and is capable of molecular imaging. Both modalities are easily scalable, non-invasive, portable, and use nonionizing radiation. Combining these two modalities may provide a powerful medical imaging system for both preclinical and clinical applications. This thesis focuses on the development of this type of system. The first focus of this thesis is to improve the scalability of photoacoustic tomography by implementing a novel illumination technique, where a small-area illumination is scanned across a large-area target. This is in replacement of the conventional method of illumination the whole large-area target at once. By scanning a small-area illumination beam, the signal-to-noise ratio (SNR) of any photoacoustic tomography system can be maximized, regardless of the illumination power used. The second focus is on improving SNR for ultrasound tomography without reducing its high-resolution capabilities. Ultrasound tomography techniques are inherently low-SNR, and the techniques to mitigate this problem tend to rely on sacrificing resolution, or necessitating an enormous amount of data to be collected. Our technique avoids both adverse effects, providing images with high SNR and high resolution for any amount of data collected. The final focus of this thesis is to develop novel reconstruction techniques to measure and visualize ultrasound scattering anisotropy. Scattering anisotropy where the scattered signal intensity is dependent on angular direction is caused by many different scatterer parameters, such as the geometry of the scatterer, and its material composition. The first novel reconstruction technique involves measuring the direction of fibre-like scattering objects. These objects will produce high scattering intensities orthogonal to their direction, and low scattering intensities parallel to their direction. By measuring signal intensities from many angles around the target (of which ultrasound tomography is uniquely capable), the direction of the fibre-like structures can be estimated and visualized. Applications of this visualization may be for fibre-orientation imaging, or to measure extracellular matrix reorganization caused by malignant tumours in breast cancer. The second novel reconstruction technique exploits the fact that the level of anisotropy for spherical scatterers depends on their compressibility and density. Compressibility will produce isotropic, monopole scattering whereas density will produce anisotropic, dipole scattering. The novel reconstruction technique utilizes this difference and can produce compressibility and density-weighted images, able to differentiate highly compressible targets from highly dense targets. These types of images may be impactful for breast cancer diagnosis with respect to imaging breast microcalcifications small calcium deposits in breast tissue that are used to detect early signs of breast cancer. Ultimately, by improving the scalability and effectiveness for photoacoustic and ultrasound tomography, and by introducing new quantitative parameters that can be imaged by ultrasound tomography, this thesis hopes to improve the strength and capacity of photoacoustic-ultrasound tomography systems for medical imaging for cancer research.