Clinical transitions in photoacoustic imaging

Abstract

Optical imaging has long been a gold standard for medical imaging. However, due to the high optical scattering in tissues, it has not been possible to image deeper than a few wavelengths with a useful resolution. Photoacoustic imaging - the use of short-pulsed lasers to induce an ultrasound signal - can provide optical contrast at ultrasonic resolution. This thesis focuses on the refinement of photoacoustic imaging for practical use by clinicians in clinical and preclinical studies. The first focus of this work is in system development. Beginning with a single-element based system suitable for some preclinical studies, we have worked towards a more practical ultrasound array based system. This system provides several different ultrasound modes to augment the photoacoustic data available including ultrasound flash imaging, synthetic aperture imaging, and ultrasound Doppler imaging. With this array system we demonstrate two fundamentally different clinically-applicable photoacoustic techniques using both optical and acoustic resolution. Similar methods may be used with both of these using multiple interrogation wavelengths providing label-free functional imaging. Other system development work has focused on transducer design and fabrication to provide better imaging capabilities. The second focus of this thesis is image reconstruction. We explore alternative imaging techniques using different source/array geometries and illumination patterns, demonstrate the applicability of ultrasound beamformers to photoacoustic imaging, and even work with different ultrasound imaging techniques including s-sequence excitation and minimum variance beamforming. The final focus is on clinical applications. We show photoacoustic imaging of gene expression through a tyrosinase reporter gene developed by my colleagues with exciting applications in studying metabolic pathways and cancer development. Using a longer wavelength, we also demonstrate the imaging of small metallic seeds used in brachytherapy which may aid in localizing them during radiotherapy of prostate cancer. Finally, we demonstrate multi-modal human imaging of the thyroid in vivo. Through exploration of system development, image reconstruction, and applications, this thesis aims to prove the clinical practicality of photoacoustic imaging.