(638c) Multi-Contrast Photoacoustic Tomography

Whole-body imaging has played an indispensable role in both preclinical and clinical 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 lack either spatiotemporal resolution or functional contrasts. A stand-alone single-impulse photoacoustic computed tomography (PACT) system has been built, which successfully mitigates these limitations by integrating high spatiotemporal resolution, deep penetration, and full-view fidelity, as well as anatomical, dynamical, and functional contrasts. Based on hemoglobin absorption contrast, the whole-body dynamics and large scale brain functions of rodents have been imaged in real time. The absorption difference 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 the brain and internal organs. 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 visualized in real time. The integration of the newly developed microrobotic system and PACT realizes deep imaging and precise control of the micromotors in vivo and promises practical biomedical applications, such as drug delivery. 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, providing a powerful tool for fundamental tumor study. The photochromic behaviors have also been used to guide photons to form an optical focus inside live tissue, enabling deep tissue photodynamic therapy and deep brain optogenetics.

In addition, a high-throughput, low-cost PA imaging technique—photoacoustic topography through an ergodic relay (PATER)—has been developed to capture a widefield image with a single laser shot using only a single element detector, which is expected to be suitable for portable and wearable applications. As a rapidly evolving imaging technique, PACT promises preclinical applications, clinical translation, as well as consumer electronics.