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

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Title: Quantitative in vivo optical tomography of cancer progression & vasculature development in adult zebrafish
Authors: Kumar, S
Lockward, N
Ramel, M-C
Correia, T
Ellis, M
Alexandrov, Y
Andrews, N
Patel, R
Bugeon, L
Dallman, M
Brandner, S
Arridge, S
Katan, M
McGinty, J
Frankel, P
French, PMW
Item Type: Journal Article
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.
Issue Date: 1-Jun-2016
Date of Acceptance: 28-Apr-2016
URI: http://hdl.handle.net/10044/1/33325
DOI: https://dx.doi.org/10.18632/oncotarget.9756
ISSN: 1949-2553
Publisher: Impact Journals
Start Page: 43939
End Page: 43948
Journal / Book Title: Oncotarget
Volume: 7
Issue: 28
Copyright Statement: Licensed under a Creative Commons Attribution 3.0 License.
Sponsor/Funder: Medical Research Council (MRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: MR/K011561/1
Keywords: KRas
adult zebrafish
hepatocellular carcinoma
optical projection tomography
Publication Status: Published
Appears in Collections:Physics
Faculty of Natural Sciences