Multiscale Photoacoustic Tomography of a Genetically Encoded Near‐Infrared FRET Biosensor
Open Access
- 17 September 2021
- journal article
- research article
- Published by Wiley in Advanced Science
- Vol. 8 (21), 2102474
- https://doi.org/10.1002/advs.202102474
Abstract
Photoacoustic tomography (PAT) with genetically encoded near-infrared probes enables visualization of specific cell populations in vivo at high resolution deeply in biological tissues. However, because of a lack of proper probes, PAT of cellular dynamics remains unexplored. Here, the authors report a near-infrared Forster resonance energy transfer (FRET) biosensor based on a miRFP670-iRFP720 pair of the near-infrared fluorescent proteins, which enables dynamic functional imaging of active biological processes in deep tissues. By photoacoustically detecting the changes in the optical absorption of the miRFP670 FRET-donor, they monitored cell apoptosis in deep tissue at high spatiotemporal resolution using PAT. Specifically, they detected apoptosis in single cells at a resolution of ≈3 µm in a mouse ear tumor, and in deep brain tumors (>3 mm beneath the scalp) of living mice at a spatial resolution of ≈150 µm with a 20 Hz frame rate. These results open the way for high-resolution photoacoustic imaging of dynamic biological processes in deep tissues using NIR biosensors and PAT.Funding Information
- National Institutes of Health (GM122567 (to V.V.V.), EY030705 (to D.M.S.), CA186567, NS102213, NS099717 (all to L.V.W))
- Academy of Finland (322226 (to V.V.V.))
- Russian Science Foundation (21‐64‐00025 (to V.V.V.))
This publication has 49 references indexed in Scilit:
- Near-infrared fluorescent proteins for multicolor in vivo imagingNature Methods, 2013
- In vivo three-photon microscopy of subcortical structures within an intact mouse brainNature Photonics, 2013
- Förster resonance energy transfer photoacoustic microscopyJournal of Biomedical Optics, 2012
- Deep‐Tissue Photoacoustic Tomography of a Genetically Encoded Near‐Infrared Fluorescent ProbeAngewandte Chemie, 2011
- Bright and stable near-infrared fluorescent protein for in vivo imagingNature Biotechnology, 2011
- Going deeper than microscopy: the optical imaging frontier in biologyNature Methods, 2010
- Carbon nanotubes as photoacoustic molecular imaging agents in living miceNature Nanotechnology, 2008
- Imaging cellular signals in the heart in vivo : Cardiac expression of the high-signal Ca 2+ indicator GCaMP2Proceedings of the National Academy of Sciences of the United States of America, 2006
- Looking and listening to light: the evolution of whole-body photonic imagingNature Biotechnology, 2005
- FRET imagingNature Biotechnology, 2003