Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published January 2016 | Accepted Version + Supplemental Material
Journal Article Open

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


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.

Additional Information

© 2016 Macmillan Publishers Limited. Received 07 May 2015; Accepted 16 October 2015; Published online 09 November 2015. We thank E. Giraud (Institute for Research and Development, Marseille, France) for the RpBphP1 gene, A. Krumholz and J. Shi for technical support, J. Ballard for reading of the manuscript, and Alafi Neuroimaging Laboratory for bright-field microscopy. This work was sponsored by the US National Institutes of Health (NIH) (grants DP1 EB016986 (NIH Director's Pioneer Award), R01 CA186567 (NIH Director's Transformative Research Award), U01 NS090579 (BRAIN Initiative), R01 EB016963 and S10 RR026922 to L.V.W.; grants GM073913, GM108579 and CA164468 to V.V.V.), the EU 7th Framework Programme (grant ERC-2013-ADG-340233 to V.V.V.) and the Neuroscience Blueprint Center (Core grant NS057105 to Alafi Neuroimaging Laboratory). Author Contributions: J.Y., V.V.V. and L.V.W. conceived and designed the study. J.Y., L.L. and L.W. constructed the imaging system. A.A.K. and D.M.S constructed the plasmids, purified and characterized the proteins in vitro, and established the stable bacterial and mammalian cell clones. J.Y., L.L., G.L. and R.Z. performed photoacoustic experiments and analyzed the data. V.V.V. and L.V.W. supervised the study. All authors wrote the manuscript. Competing Financial Interests: L.V.W. has a financial interest in Endra, Inc., and Microphotoacoustics, Inc., although these companies did not support this work.

Attached Files

Accepted Version - nihms731893.pdf

Supplemental Material - nmeth.3656-S1.pdf

Supplemental Material - nmeth.3656-sv1.mov

Supplemental Material - nmeth.3656-sv2.mov

Supplemental Material - nmeth.3656-sv3.mov

Supplemental Material - nmeth_3656-SF1.jpg

Supplemental Material - nmeth_3656-SF10.jpg

Supplemental Material - nmeth_3656-SF11.jpg

Supplemental Material - nmeth_3656-SF2.jpg

Supplemental Material - nmeth_3656-SF3.jpg

Supplemental Material - nmeth_3656-SF4.jpg

Supplemental Material - nmeth_3656-SF5.jpg

Supplemental Material - nmeth_3656-SF6.jpg

Supplemental Material - nmeth_3656-SF7.jpg

Supplemental Material - nmeth_3656-SF8.jpg

Supplemental Material - nmeth_3656-SF9.jpg


Files (17.6 MB)
Name Size Download all
56.6 kB Preview Download
85.7 kB Preview Download
7.5 MB Preview Download
5.9 MB Download
980.6 kB Download
232.3 kB Download
125.3 kB Preview Download
119.8 kB Preview Download
170.9 kB Preview Download
190.1 kB Preview Download
112.3 kB Preview Download
197.4 kB Preview Download
102.8 kB Preview Download
1.6 MB Preview Download
136.4 kB Preview Download
88.0 kB Preview Download

Additional details

August 20, 2023
October 19, 2023