(3al) Multiconstrast Photoacoustic Tomography of Wholebody and Whole Brain

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 contrast.

We have recently developed a stand-alone single-impulse photoacoustic computed tomography (PACT) system, 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 wholebody 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 the brain and internal organs. By localizing the single-dyed droplets, the spatial resolution of PACT has been improved by six-fold in vivo to 25 µm. 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.

Research Interests

My research interest is to develop next-generation medical imaging devices to better understand the brain and more clearly perceive human diseases, especially cancer. The central problem I want to tackle is to visualize whole brain functions and tumor metastasis in detail using light. To address this, I have been working on developing the novel optical imaging technology, specifically, photoacoustic computed tomography (PACT). Combining PACT with multiple contrast agents, including genetically encode proteins, organic dyes, and metallic nano/microrobots, brain functions, tumor growth and metastasis, and drug delivery processes have been revealed at high resolution in deep tissue. I am highly interested in expanding this research to engineer new imaging technology to visualize neural responses in the deep brain, monitor tumor responses during therapy, and provide real-time navigation for drug delivery in deep tissue.

Teaching interests

I obtained my Ph.D. degree from the Department of Electrical Engineering at California Institute of Technology in 2019. I am currently a postdoctoral scholar in the Andrew and Peggy Cherng Department of Medical Engineering at Caltech. During my graduate study and research, I received comprehensive training in electronics, optics, mechanics, mathematics, and signal processing.

I have assumed several teaching and mentorship roles throughout my graduate study. I have been invited to lecture the Principles and Applications of Photoacoustic Tomography for the course Molecular Imaging and served as a teaching assistant for three graduate-level courses, including Detection and Estimation Theory, Biomedical Optics: Principles, and Biomedical Optics: Imaging. As a lecturer or teaching assistant, I got chances to interact with students to learn how they are thinking about the topics and knowledge that are frequently used in my daily research. By communicating with them, I have learned how to figuratively explain the abstract equations and concepts and help them connect the textbook contents to real experimental practice. In addition, I have mentored three undergraduate students and five graduate students. While at times, it was challenging to motivate or encourage a strong work ethic in some students, I learned how to be a forthcoming and supportive mentor, how to understand their personal goals, and invest in their success in science. I have designed specific projects for my mentees to fit their research interests and take advantage of their expertise. For example, some image reconstruction related projects were delegated to the students who have a strong mathematical background with vast interests in theoretical development, while some students were assigned tasks such as hardware construction and PCB design according to their hardcore electrical engineering training. Till now, my undergraduate mentees have been admitted to renowned universities, such as Stanford, ETH, etc., for graduate studies. And my graduate mentees have published four peer-reviewed articles. The teaching and mentorship experiences have taught me how to establish mutually respectful, transparent, and supportive scientific relationships with my students. More importantly, these experiences have built my confidence and interest in teaching, and I look forward to the opportunity to not only teach existing courses but also to develop new ones.

References

1. [Y. Li, Li], Liren Zhu, K. Maslov, J. Shi, P. Hu, E. Bo, J. Yao, J. Liang, L. Wang, L. V. Wang (2020). "Snapshot Photoacoustic Topography through an Ergodic Relay for High-Throughput Imaging of Optical Absorption," Nature Photonics. https://doi.org/10.1038/s41566-019-0576-2
2. [J. Yang, Li], A. A. Shemetov, S. Lee, Y. Zhao, Y. Liu, Y. Shen, J. Li, Y. Oka, V. V. Verkhusha, L. V. Wang (2019). “Focusing light inside live tissue using reversibly switchable bacterial phytochrome as a genetically encoded photochromic guide star,” Science Advances 5 (12), eaay1211
3. [Z. Wu, Li], Y. Yang, P. Hu, Y. Li, S. Yang, L. V. Wang, W. Gao (2019). “A microrobotic system guided by photoacoustic computed tomography for targeted navigation in intestines in vivo,” Science Robotics 4 (32): eaax0613
4. Shi, J., T. T. Wong, Y, He, Li, R. Zhang, C. Yung, J. Hwang, K. Maslov, L. V. Wang (2019). “High-resolution, high-contrast mid-infrared imaging of fresh biological samples with ultraviolet-localized photoacoustic microscopy,” Nature Photonics 13(9), 609-615
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