Photoacoustic imaging allows absorption-based high-resolution spectroscopic in vivo imaging at a depth beyond that of optical microscopy. Until recently, photoacoustic imaging has largely been restricted to visualizing the vasculature through endogenous haemoglobin contrast, with most non-vascularized tissues remaining invisible unless exogenous contrast agents are administered. Genetically encodable photoacoustic contrast is attractive as it allows selective labelling of cells, permitting studies of, for example, specific genetic expression, cell growth or more complex biological behaviours in vivo. In this study we report a novel photoacoustic imaging scanner and a tyrosinase-based reporter system that causes human cell lines to synthesize the absorbing pigment eumelanin, thus providing strong photoacoustic contrast. Detailed three-dimensional images of xenografts formed of tyrosinase-expressing cells implanted in mice are obtained in vivo to depths approaching 10 mm with a spatial resolution below 100 μm. This scheme is a powerful tool for studying cellular and genetic processes in deep mammalian tissues.
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This work was funded by the UK Biotechnology Research Council (BBSRC) grant no. BB/I014357/1. Additional funding was provided by the gene-therapy division of the UK NIHR University College London Hospital Biomedical Research Centre. This work was also supported by King's College London and University College London Comprehensive Cancer Imaging Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council (EPSRC), in association with the Medical Research Council and Department of Health, UK, and European Union project FAMOS (FP7 ICT, contract no. 317744). P.B. is funded by an EPSRC Leadership Fellowship and J.L. is funded by an ERC starting grant (281356). The authors thank J. Paterson (UCL Advanced Diagnostics) for assistance with immunohistochemistry, K. Venner for assistance with transmission electron microscopy (TEM) and C. Futter for assistance in interpreting the electron micrographs. H. Dortay (TU Berlin) is thanked for helpful comments on the manuscript and P. Varga (AO Research Institute Davos, Switzerland) for assistance with the use of Amira.
The authors declare no competing financial interests.
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Jathoul, A., Laufer, J., Ogunlade, O. et al. Deep in vivo photoacoustic imaging of mammalian tissues using a tyrosinase-based genetic reporter. Nature Photon 9, 239–246 (2015). https://doi.org/10.1038/nphoton.2015.22
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