Quantitative in vivo optical tomography of cancer progression & vasculature development in adult zebrafish.
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.
Department of Physics, Imperial College London, London SW7 2AZ, UK.
Sunil
S
Kumar
Division of Medicine, University College London, London WC1E 6JF, UK.|CoMPLEX, University College London, London WC1E 6BT, UK.
Nicola
N
Lockwood
Division of Medicine, University College London, London WC1E 6JF, UK.|Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
Marie-Christine
MC
Ramel
Department of Computer Science, University College London, London WC1E 6BT, UK.
Teresa
T
Correia
Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1 3BG, UK.
Matthew
M
Ellis
Department of Physics, Imperial College London, London SW7 2AZ, UK.
Yuriy
Y
Alexandrov
Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.|Institute of Chemical Biology, Department of Chemistry, Imperial College, London SW7 2AZ, UK.
Natalie
N
Andrews
Division of Medicine, University College London, London WC1E 6JF, UK.
Rachel
R
Patel
Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
Laurence
L
Bugeon
Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
Margaret J
MJ
Dallman
Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1 3BG, UK.|Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London WC1N 3BG, UK.
Sebastian
S
Brandner
Department of Computer Science, University College London, London WC1E 6BT, UK.
Simon
S
Arridge
Division of Structural and Molecular Biology, University College London, London WC1E 6BT, UK.
Matilda
M
Katan
Department of Physics, Imperial College London, London SW7 2AZ, UK.
James
J
McGinty
Division of Medicine, University College London, London WC1E 6JF, UK.
Paul
P
Frankel
Department of Physics, Imperial College London, London SW7 2AZ, UK.
Paul M W
PM
French
D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D018450:Disease Progression; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008113:Liver Neoplasms / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D041622:Tomography, Optical / Q000379:methods*; D015027:Zebrafish
KRas; adult zebrafish; cancer; hepatocellular carcinoma; optical projection tomography