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

Lei Li, Anton Shemetov, Peng Hu, Daria Shcherbakova, Junhui Shi, Junjie Yao, Vladislav Verkhusha, Lihong V. Wang

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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.

Original languageEnglish (US)
Title of host publicationPhotons Plus Ultrasound
Subtitle of host publicationImaging and Sensing 2019
EditorsAlexander A. Oraevsky, Lihong V. Wang
PublisherSPIE
ISBN (Electronic)9781510623989
DOIs
StatePublished - Jan 1 2019
EventPhotons Plus Ultrasound: Imaging and Sensing 2019 - San Francisco, United States
Duration: Feb 3 2019Feb 6 2019

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume10878
ISSN (Print)1605-7422

Conference

ConferencePhotons Plus Ultrasound: Imaging and Sensing 2019
CountryUnited States
CitySan Francisco
Period2/3/192/6/19

Fingerprint

Photoacoustic effect
Tomography
Pulse code modulation
tomography
Infrared radiation
proteins
Proteins
Imaging techniques
phytochrome
Phytochrome
interactions
probes
Tissue
Cells
Molecular imaging
Molecular Imaging
decay
cells
liver
imaging techniques

Keywords

  • Multicontrast imaging
  • Near infrared photoswitchable protein
  • Photoacoustic computed tomography
  • Proteinprotein interactions

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Atomic and Molecular Physics, and Optics
  • Biomaterials
  • Radiology Nuclear Medicine and imaging

Cite this

Li, L., Shemetov, A., Hu, P., Shcherbakova, D., Shi, J., Yao, J., ... Wang, L. V. (2019). In vivo photoacoustic multi-contrast imaging and detection of protein interactions using a small near-infrared photochromic protein. In A. A. Oraevsky, & L. V. Wang (Eds.), Photons Plus Ultrasound: Imaging and Sensing 2019 [1087818] (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 10878). SPIE. https://doi.org/10.1117/12.2509198

In vivo photoacoustic multi-contrast imaging and detection of protein interactions using a small near-infrared photochromic protein. / Li, Lei; Shemetov, Anton; Hu, Peng; Shcherbakova, Daria; Shi, Junhui; Yao, Junjie; Verkhusha, Vladislav; Wang, Lihong V.

Photons Plus Ultrasound: Imaging and Sensing 2019. ed. / Alexander A. Oraevsky; Lihong V. Wang. SPIE, 2019. 1087818 (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 10878).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Li, L, Shemetov, A, Hu, P, Shcherbakova, D, Shi, J, Yao, J, Verkhusha, V & Wang, LV 2019, In vivo photoacoustic multi-contrast imaging and detection of protein interactions using a small near-infrared photochromic protein. in AA Oraevsky & LV Wang (eds), Photons Plus Ultrasound: Imaging and Sensing 2019., 1087818, Progress in Biomedical Optics and Imaging - Proceedings of SPIE, vol. 10878, SPIE, Photons Plus Ultrasound: Imaging and Sensing 2019, San Francisco, United States, 2/3/19. https://doi.org/10.1117/12.2509198
Li L, Shemetov A, Hu P, Shcherbakova D, Shi J, Yao J et al. In vivo photoacoustic multi-contrast imaging and detection of protein interactions using a small near-infrared photochromic protein. In Oraevsky AA, Wang LV, editors, Photons Plus Ultrasound: Imaging and Sensing 2019. SPIE. 2019. 1087818. (Progress in Biomedical Optics and Imaging - Proceedings of SPIE). https://doi.org/10.1117/12.2509198
Li, Lei ; Shemetov, Anton ; Hu, Peng ; Shcherbakova, Daria ; Shi, Junhui ; Yao, Junjie ; Verkhusha, Vladislav ; Wang, Lihong V. / In vivo photoacoustic multi-contrast imaging and detection of protein interactions using a small near-infrared photochromic protein. Photons Plus Ultrasound: Imaging and Sensing 2019. editor / Alexander A. Oraevsky ; Lihong V. Wang. SPIE, 2019. (Progress in Biomedical Optics and Imaging - Proceedings of SPIE).
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