PUBLICATION

Quantitative in vivo optical tomography of cancer progression & vasculature development in adult zebrafish

Authors
Kumar, S., Lockwood, N., Ramel, M.C., Correia, T., Ellis, M., Alexandrov, Y., Andrews, N., Patel, R., Bugeon, L., Dallman, M.J., Brandner, S., Arridge, S., Katan, M., McGinty, J., Frankel, P., French, P.M.
ID
ZDB-PUB-160604-1
Date
2016
Source
Oncotarget   7(28): 43939-43948 (Journal)
Registered Authors
Andrews, Natalie, Bugeon, Laurence, Dallman, Maggie, Ramel, Marie-Christine
Keywords
KRas, adult zebrafish, cancer, hepatocellular carcinoma, optical projection tomography
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal*
  • Disease Progression
  • Imaging, Three-Dimensional/methods*
  • Liver Neoplasms/pathology*
  • Neovascularization, Pathologic/pathology*
  • Tomography, Optical/methods*
  • Zebrafish
PubMed
27259259 Full text @ Oncotarget
Abstract
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.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping