Reversibly switchable photoacoustic tomography using a genetically encoded near-infrared phytochrome

Junjie Yao, Andrii Kaberniuk, Lei Li, Daria M. Shcherbakova, Ruiying Zhang, Lidai Wang, Guo Li, Vladislav V. Verkhusha, Lihong V. Wanga

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


Optical imaging of genetically encoded probes has revolutionized biomedical studies by providing valuable information about targeted biological processes. Here, we report a novel imaging technique, termed reversibly switchable photoacoustic tomography (RS-PAT), which exhibits large penetration depth, high detection sensitivity, and super-resolution. RS-PAT combines advanced photoacoustic imaging techniques with, for the first time, a nonfluorescent photoswitchable bacterial phytochrome. This bacterial phytochrome is the most near-infrared shifted genetically encoded probe reported so far. Moreover, this bacterial phytochrome is reversibly photoconvertible between its far-red and near-infrared light absorption states. Taking maximum advantage of the powerful imaging capability of PAT and the unique photochemical properties of the phytochrome, RS-PAT has broken through both the optical diffusion limit for deep-tissue imaging and the optical diffraction limit for super-resolution photoacoustic microscopy. Specifically, with RS-PAT we have achieved an unprecedented detection sensitivity of ∼2 μM, or as few as ∼20 tumor cells, at a centimeter depth. Such high sensitivity is fully demonstrated in our study by monitoring tumor growth and metastasis at whole-body level with ∼100 μm resolution. Moreover, our microscopic implementation of RS-PAT is capable of imaging mammalian cells with a sub-diffraction lateral resolution of ∼140 nm and axial resolution of ∼400 nm, which are respectively ∼2-fold and ∼75-fold finer than those of our conventional photoacoustic microscopy. Overall, RS-PAT is a new and promising imaging technology for studying biological processes at different length scales.

Original languageEnglish (US)
Title of host publicationPhotons Plus Ultrasound
Subtitle of host publicationImaging and Sensing 2016
EditorsAlexander A. Oraevsky, Lihong V. Wang
ISBN (Electronic)9781628419429
StatePublished - 2016
EventPhotons Plus Ultrasound: Imaging and Sensing 2016 - San Francisco, United States
Duration: Feb 14 2016Feb 17 2016

Publication series

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


OtherPhotons Plus Ultrasound: Imaging and Sensing 2016
Country/TerritoryUnited States
CitySan Francisco


  • Bacterial phytochrome
  • Deep tissue imaging
  • Genetic imaging
  • Near-infrared protein
  • Photoacoustic microscopy
  • Photoacoustic tomography
  • Reversibly switchable protein
  • Super-resolution imaging

ASJC Scopus subject areas

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


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