Date of Award
Doctor of Philosophy (PhD)
Photoacoustic (PA) tomography (PAT) is a novel imaging modality that combines the fine lateral resolution from optical imaging and the deep penetration from ultrasonic imaging, and provides rich optical-absorption–based images. PAT has been widely used in extracting structural and functional information from both ex vivo tissue samples to in vivo animals and humans with different length scales by imaging various endogenous and exogenous contrasts at the ultraviolet to infrared spectrum. For example, hemoglobin in red blood cells is of particular interest in PAT since it is one of the dominant absorbers in tissue at the visible wavelength.The main focus of this dissertation is to develop high-speed PA microscopy (PAM) technologies. Novel optical scanning, ultrasonic detection, and laser source techniques are introduced in this dissertation to advance the performance of PAM systems. These upgrades open up new avenues for PAM to be applicable to address important biomedical challenges and enable fundamental physiological studies.First, we investigated the feasibility of applying high-speed PAM to the detection and imaging of circulating tumor cells (CTCs) in melanoma models, which can provide valuable information about a tumor’s metastasis potentials. We probed the melanoma CTCs at the near-infrared wavelength of 1064 nm, where the melanosomes absorb more strongly than hemoglobin. Our high-speed PA flow cytography system successfully imaged melanoma CTCs in travelling trunk vessels. We also developed a concurrent laser therapy device, hardware-triggered by the CTC signal, to photothermally lyse the CTC on the spot in an effort to inhibit metastasis.Next, we addressed the detection sensitivity issue in the previous study. We employed the stimulated Raman scattering (SRS) effect to construct a high-repetition-rate Raman laser at 658 nm, where the contrast between a melanoma CTC and the blood background is near the highest. Our upgraded PA flow cytography successfully captured sequential images of CTCs in mouse melanoma xenograft model, with a significantly improved contrast-to-noise ratio compared to our previous results. This technology is readily translatable to the clinics to extract the information of a tumor’s metastasis risks.We extended the Raman laser technology to the field of brain functional studies. We developed a MEMS (micro-electromechanical systems) scanner for fast optical scanning, and incorporated it to a dual-wavelength functional PAM (fPAM) for high-speed imaging of cerebral hemodynamics in mouse. This fPAM system successfully imaged transient changes in blood oxygenation at cerebral micro-vessels in response to brief somatic stimulations. This fPAM technology is a powerful tool for neurological studies.Finally, we explored some approaches of reducing the size the PAM imaging head in an effort to translate our work to the field of wearable biometric monitors. To miniaturize the ultrasonic detection device, we fabricated a thin-film optically transparent piezoelectric detector for detecting PA waves. This technology could enable longitudinal studies on free-moving animals through a wearable version of PAM.
Quing Zhu Lihong Wang
Jin-Moo Lee, Jung-Tsung Shen, Hong Chen, Mark A. Anastasio,