Fiber-Assisted Photoacoustic Imaging for Biomedical Applications

Abstract

The present thesis is about the development and characterization of fiber-assisted photoacoustic imaging (PAI) systems to be used in biomedical applications, such as identification of atherosclerotic plaques, superficial blood vessels imaging, and nanoparticle (NP)-mediated cancer therapy. PAI is a novel noninvasive and nonionizing imaging tool to generate in vivo optical absorbing contrasts with high ultrasonic resolution and superior optical sensitivity. Specifically, it is proposed as an alternative technique to guide and monitor NP-mediated cancer therapy and to overcome the limitations of conventional imaging systems, such as ionizing radiation, insensitiveness, and optical diffusion limit. My doctoral research focuses on developments and biomedical applications of fiber-assisted PAI. The first part of my dissertation presents the development of a fiber-based intravascular ultrasonic-photoacoustic (IVUP) imaging system, which is capable of visualizing macrophages inside the blood vessel walls. Macrophages are excellent imaging targets for detecting atherosclerotic plaques since they are involved in all the developmental stages of atherosclerosis. In this section, I demonstrate the feasibility of mapping macrophages labeled with the Food and Drug Administration (FDA)-approved indocyanine green (ICG) as a contrast agent to provide morphological and compositional information on the targeted samples. Both tissue-mimicking vessel phantoms and atherosclerotic plaques-mimicking porcine arterial tissues are used to demonstrate the feasibility of mapping macrophages labeled with ICG by endoscopically applying the proposed hybrid IVUP imaging technique. A delay pulse triggering technique is able to sequentially acquire photoacoustic and ultrasound signals from a single scan without using any external devices. Due to high imaging contrast and sensitivity, the IVUP imaging vividly reveals structural information and detects the spatial distribution of the ICG-labeled macrophages inside the samples. The ICG-assisted IVUP imaging can be a feasible imaging modality for endoscopic detection of the atherosclerotic plaques. The second part of my dissertation focuses on the development of a stimulated Raman scattering (SRS)-assisted optical-resolution photoacoustic microscopy (OR-PAM) system. In this section, FDA-approved Prussian blue (PB) is synthesized in the form of NPs with the peak absorption at 712 nm for photoacoustically imaging tumor-bearing mouse models. To monitor PB NPs from the background tissue in vivo, a new 700-nm-region SRS source (pulse energy up to 200 nJ and repetition rate up to 50 kHz) was also developed and implemented OR-PAM. The SRS-assisted OR-PAM system was able to monitor PB NPs in the tumor model with micrometer resolution. Due to strong light absorption at 712 nm, the developed SRS light yielded a two-fold higher contrast from PB NPs, in comparison with a 532-nm pumping source. The proposed laser source involved cost-effective and simple system implementation along with high compatibility with the fiber-assisted OR-PAM system. The OR-PAM system in conjunction with the tunable-color SRS light source can be a feasible tool to assist NP-mediated cancer therapy.