Integrated photoacoustic/ultrasound imaging : Applications and new techniques

Abstract

Photoacoustic imaging (PAI) is a unique combination of optical sensitivity to tissue chromophores like hemoglobin, and ultrasonic resolution. Research in this PhD thesis is made possible by the development of a probe that combines PAI with regular ultrasound imaging. This probe is handheld and integrates a diode laser source inside the housing, thus minimizing the footprint of the system and facilitating (pre-)clinical translation. Both photoacoustic (PA) and ultrasound (US) modalities generate pressure waves in the ultrasound regime that can be detected using the same type of ultrasound transducers. They image complementary information as well: PAI visualizes vasculature and provides functional information, whereas US imaging gives structural information and provides clinicians landmarks with which to interpret the PA data. The thesis starts with performance testing of the probe in terms of imaging depth and resolution. Imaging up to 15 mm in depth at a resolution below 0.5 mm was achieved. Subsequently, two applications are considered as pilot tests with the developed probe: detecting liver fibrosis in mice and rheumatoid arthritis in human finger joints. In both cases vascular remodeling takes place – in addition to collagen deposition in liver fibrosis – making these inflammatory diseases interesting starting points for PAI. In both applications, afflicted livers or fingers could easily (and significantly) be distinguished from healthy counterparts. However, more research will be required to determine the clinical use of PAI compared to existing techniques. Multi-wavelength PAI can furthermore provide information about the types of tissue chromophore present. Now only a single-wavelength diode laser is used for PAI, which then only depicts places with high optical absorption. In the second part of this thesis, photoacoustic flow imaging is considered: using PAI to determine the amount and velocity of flowing blood, to further help with assessing inflammation. The various flow imaging methods that PAI can employ are wide-ranging, and reviewed first. Then, one flow imaging technique is developed using the developed probe, and tested on micron-sized particles. The technique was further improved using a custom setup – double pulse laser and higher resolution probe – for flow imaging of whole blood.