PhD Thesis Defense

Imaging of small animals has played an indispensable role in preclinical research by providing high dimensional physiological, pathological, and phenotypic insights with clinical relevance. Yet pure optical imaging suffers from either shallow penetration (up to ~1–2 mm) or a poor depth-to-resolution ratio (~3), and non-optical techniques for whole-body imaging of small animals lack either spatiotemporal resolution or functional contrast. A standalone single-impulse photoacoustic computed tomography system has been built, which successfully mitigates these limitations by integrating high spatiotemporal resolution, deep penetration, anatomical, dynamical and functional contrasts, and full-view fidelity. Based on hemoglobin absorption contrast, whole-body dynamics and large scale brain functions of rodents have been imaged in real time. The absorption contrast between cytochrome and lipid has enabled PACT to resolve MRI-like whole brain structures. Taking advantage of the distinct absorption signature of melanin, unlabeled circulating melanoma cells have been tracked in real time in vivo.

Assisted by near-infrared dyes, the perfusion processes have been visualized in rodents. By localizing the single-dyed droplets, the spatial resolution of PACT has been improved by six-fold in vivo. The migration of metallic-based microrobots toward the targeted regions in intestines has been monitored in real time. Genetically encoded photochromic proteins benefit PACT in detection sensitivity and specificity. The unique photoswitching characteristics of different photochromic proteins allow quantitative multi-contrast imaging at depths. A split version of the photochromic protein has permitted PA detection of protein-protein interactions in deep-seated tumors. The photochromic behaviors have also been used to guide photons to form an optical focus inside live tissue. In addition, a high-throughput, low-cost PA imaging technique—photoacoustic topography through an ergodic relay—has been developed to capture a widefield image with a single laser shot using only a single element detector. As a rapidly evolving imaging technique, PACT promises pre-clinical applications and clinical translation.