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In vivo photoacoustic multi-contrast imaging and detection of protein interactions using a small near-infrared photochromic protein

Li, Lei and Shemetov, Anton A. and Hu, Peng and Shcherbakova, Daria M. and Shi, Junhui and Yao, Junjie and Verkhusha, Vladislav V. and Wang, Lihong V. (2019) In vivo photoacoustic multi-contrast imaging and detection of protein interactions using a small near-infrared photochromic protein. In: Photons Plus Ultrasound: Imaging and Sensing 2019. Proceedings of SPIE. No.10878. Society of Photo-optical Instrumentation Engineers (SPIE) , Bellingham, WA, Art. No. 1087818. ISBN 9781510623989. https://resolver.caltech.edu/CaltechAUTHORS:20190408-105837786

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Abstract

Photoacoustic (PA) computed tomography (PACT) is a non-invasive imaging technique offering optical contrast, high resolution, and deep penetration in biological tissues. PACT, highly sensitive to optical absorption by molecules, is inherently suited for molecular imaging using optically absorbing probes. Genetically encoded probes with photochromic behavior dramatically increase detection sensitivity and specificity of PACT through photoswitching and differential imaging. Starting with a DrBphP bacterial phytochrome, we have engineered a near-infrared photochromic probe, DrBphP-PCM, which is superior to the full-length RpBphP1 phytochrome previously used in differential PACT. DrBphP-PCM has a smaller size, better folding, and higher photoswitching contrast. We have also developed an advanced PACT technique, which combines the reversibly-switchable photochromic probes with single-impulse panoramic PACT, termed RS-SIP-PACT. Using RS-SIP-PACT, we have characterized DrBphP-PCM both in vitro and in vivo as an advanced near-infrared photochromic probe for PACT. We introduce two phytochromes into the same mammalian cells, resulting in a distinctive decay characteristic in comparison with the cells expressing DrBphP-PCM only. By discriminating the different decay characteristics, we successfully separate multiple cell types in deep tissues. The simple structural organization of DrBphP-PCM allows engineering a bimolecular PA complementation reporter, a split version of DrBphP-PCM, termed DrSplit. DrSplit enables PA detection of protein-protein interactions in deepseated mouse tumors and livers, achieving 125-μm spatial resolution and 530-cell sensitivity in vivo. The combination of RS-SIP-PACT with DrBphP-PCM and DrSplit holds great potential for non-invasive multi-contrast deep-tissue functional imaging.


Item Type:Book Section
Related URLs:
URLURL TypeDescription
https://doi.org/10.1117/12.2509198DOIArticle
ORCID:
AuthorORCID
Hu, Peng0000-0002-2933-1239
Shi, Junhui0000-0002-5741-2781
Wang, Lihong V.0000-0001-9783-4383
Additional Information:© 2019 Society of Photo-Optical Instrumentation Engineers (SPIE).
Subject Keywords:Photoacoustic computed tomography, near infrared photoswitchable protein, multicontrast imaging, protein-protein interactions
Series Name:Proceedings of SPIE
Issue or Number:10878
Record Number:CaltechAUTHORS:20190408-105837786
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190408-105837786
Official Citation:Lei Li, Anton A. Shemetov, Peng Hu, Daria M. Shcherbakova, Junhui Shi, Junjie Yao, Vladislav V. Verkhusha, and Lihong V. Wang "In vivo photoacoustic multi-contrast imaging and detection of protein interactions using a small near-infrared photochromic protein", Proc. SPIE 10878, Photons Plus Ultrasound: Imaging and Sensing 2019, 1087818 (27 February 2019); doi: 10.1117/12.2509198; https://doi.org/10.1117/12.2509198
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94561
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Apr 2019 15:03
Last Modified:03 Oct 2019 21:05

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