Development and application of photoacoustic/ultrasound microscopy systems

Abstract

Development of biomedical microscopy largely promotes the research of life science and medicine. Emerging as a hybrid imaging technique, Photoacoustic (PA) microscopy (PAM) transfers the absorbed light energy by intrinsic chromophores into heat, and induces ultrasonic signal. PAM combines the merits of optical high contrast and ultrasonic low scattering, which has been a new important modality of biomedical optics microscopy, as well as shows significance for clinical research. Using transducer to detect the ultrasound, PAM has the potential to do ultrasound (US) imaging. Integrated the PA/US dual-modality microscopy can provide complementary information of pure optics imaging and US imaging. Focusing on high resolution PA/US dual-modality imaging technique, this thesis has done a lot of work including theoretical analysis, simulation, system setup, phantom and small animal experiments. The major work and innovation include: 1. Developing a novel high resolution PA/US dual-modality microscopy, and realizing noninvasively in vivo small animal whole eye dual-modality imaging at the first time. The system developed in this thesis is capable to image microcirculatory system of living tissue, as well as provide US structure information. 2. Proposing a new design to use parabolic mirror in PA/US dual-modality microscopy, achieving the confocal effect of collimated light and parallel US. With parabolic mirror, the focusing length of laser and US is decreased largely, which improves the system resolution by the simple design. Combined with water-immersible microelectromechanical systems (MEMS) scanning mirror, this system can achieve a fast scanning speed. 3. Investigating the effect of transducer deflection angle on functional PAM accuracy, in off-axial PAM systems. With multiple wavelengths, PAM has the advantage to provide functional information, such as oxygen saturation (SO2). This thesis demonstrates that the oblique detection will lead to the inaccuracy of SO2 measurement severely, providing valuable guidance for the design of functional PAM. 4. Besides, this thesis introduces other two parts of work. One is continuing the PAM study. We explore the feasibility of a new PA contrast agent- DNA-templated silver nanocluster, and compare its PA signal with other organic dyes. In another work, we investigate the 2D kinetics by fluorescence correlation spectroscopy (FCS), demonstrating FCS is a potential method to study molecular mechanism of immunology pathway. This thesis mainly contains five parts: Introduction part gives a brief idea about PAM background; The second and third chapter introduce the development and application of PA/US dual-modality microscopies; The forth chapter investigates the effect of oblique detection angle on functional PAM quantitative measurement; The fifth chapter introduces the study on new PA imaging contrast agent and molecular 2D kinetics by FCS; The last chapter gives the conclusion of whole thesis.