Quantitative in vivo optical tomography of cancer progression & vasculature development in adult zebrafish
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Sunil Kumar1,*, Nicola Lockwood2,3,*, Marie-Christine Ramel2,4, Teresa Correia5, Matthew Ellis6, Yuriy Alexandrov1, Natalie Andrews4,7, Rachel Patel2, Laurence Bugeon4, Margaret J. Dallman4, Sebastian Brandner6,8, Simon Arridge5, Matilda Katan9, James McGinty1,*, Paul Frankel2,*, Paul M.W. French1,*
1Department of Physics, Imperial College London, London SW7 2AZ, UK
2Division of Medicine, University College London, London WC1E 6JF, UK
3CoMPLEX, University College London, London WC1E 6BT, UK
4Department of Life Sciences, Imperial College London, London SW7 2AZ, UK
5Department of Computer Science, University College London, London WC1E 6BT, UK
6Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK
7Institute of Chemical Biology, Department of Chemistry, Imperial College, London SW7 2AZ, UK
8Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London WC1N 3BG, UK
9Division of Structural and Molecular Biology, University College London, London WC1E 6BT, UK
*Denotes equal contribution
Paul Frankel, email: [email protected]
Paul M.W. French, email: [email protected]
Keywords: cancer, adult zebrafish, optical projection tomography, hepatocellular carcinoma, KRas
Received: March 03, 2016 Accepted: April 28, 2016 Published: June 01, 2016
We describe a novel approach to study tumour progression and vasculature development in vivo via global 3-D fluorescence imaging of live non-pigmented adult zebrafish utilising angularly multiplexed optical projection tomography with compressive sensing (CS-OPT). This “mesoscopic” imaging method bridges a gap between established ~μm resolution 3-D fluorescence microscopy techniques and ~mm-resolved whole body planar imaging and diffuse tomography. Implementing angular multiplexing with CS-OPT, we demonstrate the in vivo global imaging of an inducible fluorescently labelled genetic model of liver cancer in adult non-pigmented zebrafish that also present fluorescently labelled vasculature. In this disease model, addition of a chemical inducer (doxycycline) drives expression of eGFP tagged oncogenic K-RASV12 in the liver of immune competent animals. We show that our novel in vivo global imaging methodology enables non-invasive quantitative imaging of the development of tumour and vasculature throughout the progression of the disease, which we have validated against established methods of pathology including immunohistochemistry. We have also demonstrated its potential for longitudinal imaging through a study of vascular development in the same zebrafish from early embryo to adulthood. We believe that this instrument, together with its associated analysis and data management tools, constitute a new platform for in vivo cancer studies and drug discovery in zebrafish disease models.
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