Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe.

Abstract

Photoacoustic tomography (PAT) of genetically encoded probes allows for imaging of targeted biological processes deep in tissues with high spatial resolution; however, high background signals from blood can limit the achievable detection sensitivity. Here we describe a reversibly switchable nonfluorescent bacterial phytochrome for use in multiscale photoacoustic imaging, BphP1, with the most red-shifted absorption among genetically encoded probes. BphP1 binds a heme-derived biliverdin chromophore and is reversibly photoconvertible between red and near-infrared light-absorption states. We combined single-wavelength PAT with efficient BphP1 photoswitching, which enabled differential imaging with substantially decreased background signals, enhanced detection sensitivity, increased penetration depth and improved spatial resolution. We monitored tumor growth and metastasis with ∼ 100-μm resolution at depths approaching 10 mm using photoacoustic computed tomography, and we imaged individual cancer cells with a suboptical-diffraction resolution of ∼ 140 nm using photoacoustic microscopy. This technology is promising for biomedical studies at several scales.

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Journal article

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Citation

Published Version (Please cite this version)

10.1038/nmeth.3656

Publication Info

Yao, Junjie, Andrii A Kaberniuk, Lei Li, Daria M Shcherbakova, Ruiying Zhang, Lidai Wang, Guo Li, Vladislav V Verkhusha, et al. (2016). Multiscale photoacoustic tomography using reversibly switchable bacterial phytochrome as a near-infrared photochromic probe. Nat Methods, 13(1). pp. 67–73. 10.1038/nmeth.3656 Retrieved from https://hdl.handle.net/10161/12772.

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Scholars@Duke

Yao

Junjie Yao

Associate Professor of Biomedical Engineering

Our mission at PI-Lab is to develop state-of-the-art photoacoustic tomography (PAT) technologies and translate PAT advances into diagnostic and therapeutic applications, especially in functional brain imaging and early cancer theranostics. PAT is the most sensitive modality for imaging rich optical absorption contrast over a wide range of spatial scales at high speed, and is one of the fastest growing biomedical imaging technologies. Using numerous endogenous and exogenous contrasts, PAT can provide high-resolution images at scales covering organelles, cells, tissues, organs, small-animal organisms, up to humans, and can reveal tissue’s anatomical, functional, metabolic, and even histologic properties, with molecular and neuronal specificity.

At PI-Lab, we develop PAT technologies with novel and advanced imaging performance, in terms of spatial resolutions, imaging speed, penetration depth, detection sensitivity, and functionality. We are interested with all aspects of PAT technology innovations, including efficient light illumination, high-sensitivity ultrasonic detection, super-resolution PAT, high-speed imaging acquisition, novel PA genetic contrast, and precise image reconstruction. On top of the technological advancements, we are devoted to serve the broad life science and medical communities with matching PAT systems for various research and clinical needs. With its unique contrast mechanism, high scalability, and inherent functional and molecular imaging capabilities, PAT is well suited for a variety of pre-clinical applications, especially for studying tumor angiogenesis, cancer hypoxia, and brain disorders; it is also a promising tool for clinical applications in procedures such as cancer screening, melanoma staging, and endoscopic examination.


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