Ecotox

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Presentation of in vivo imaging applied to ecotoxicology

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Ecotox

  1. 1. In vivo imaging:  a powerful alternative in  ecotoxicology Rovaltain April 8th, 2010 a.briat@animascope.eu
  2. 2. ECOTOXICOLOGY ◦ Risk assessment: ‐biological impact of exogenous compounds ‐exposure probability. ◦ REACH: registration, evaluation, authorization and  restrictions of chemicals. ◦ In vivo studies are required to evaluate the risks. A. Briat Ethical impact (large number of animals)  Economical impact (time consuming, high cost) Rovaltain, April 8th 2010.
  3. 3. IMPACT ON THE 3R Reduce, Refine, Replace Quantitative, Precise, Predictive Reduces experimental Artifacts Longitudinal Studies ‐ Reduce Animal Usage  Reduction and Refinement of animal works are A. Briat Cost and Time‐effective Need to develop of alternative solutions = IN VIVO IMAGING 3 Rovaltain, April 8th 2010.
  4. 4. Non‐Invasive In Vivo Imaging Functional  Morphological  Imaging Imaging SPECT US (Echography) PET CT (X‐rays) (f)MRI MRI A. Briat Optical SPECT/CT Rovaltain, April 8th 2010.
  5. 5. Imaging applied to ecotoxicology (1) Air hypersensibilisation pollution Tissular Imaging Aqua  Oncogene toxicity Carcinogene Molecular imaging A. Briat Geo toxicity Teratogene 5 Rovaltain, April 8th 2010.
  6. 6. Imaging applied to ecotoxicology (2) Tissular effect Molecular effect Inflammation Imaging of  Embryo development A. Briat gene expression Cell metabolism 6 Rovaltain, April 8th 2010.
  7. 7. Imagerie de l’inflammation Par IRM Imaging of inflammation using MRI acute inflammation Chronic 1) Inflammatory nephropathy (Bessaad et al. 2010) inflammation T1 T2 T2* A. Briat 2) Atherosclerosis (Lutz et al. Radiology, 2004) 3) Polyarthritis (Hauger et al. JFR; 2006) Rovaltain, April 8th 2010.
  8. 8. Imaging of inflammation using optical imaging In vivo Near‐InfraRed Fluorescent (NIRF) imaging of  inflammatory joints in the lipopolysaccharide (LPS) induction  model (NIR2‐folate).  (a) White‐light images (b)  NIRF  images  after  NIR2‐folate  injection.  (c) Merged A. Briat (d) H&E‐staining (e)  NIRF  images  of  a  longitudinal  section  of the LPS‐treated ankles.  Chen, Arthritis Res Ther (2005) 8 Rovaltain, April 8th 2010.
  9. 9. Imaging of cell metabolism using  Positron Emission Tomography (PET) Visualisation of Lymph nodes formation with 18F-FDG PET A. Briat following 140 days TCDD treatment Vogel et al., Am J Pathology, 2007 9 Rovaltain, April 8th 2010.
  10. 10. Imaging of bone development  using X‐ray Computed Tomography (CT) 30 Influence of diet on Kinetics of medullary bone formation and desorption BV/TV ( %) 20 ** A. Briat 10 ** :p≤ 0 **:p≤0.01, **:0.001 vs d1, T A B #: p ≤0.05 vs matched BSP+/+ Rovaltain, April 8th 2010.
  11. 11. Imaging of embryo development using  UltraSonography (US) Echography Combined with Doppler analysis: provides the evaluation of functional parameters, particularly in the cardiovascular and muscular fields: -Embryo size A. Briat -Cardiac malformation Rovaltain, April 8th 2010.
  12. 12. Transgenic Animal Models in  Ecotoxicology Quantitative and real‐time molecular imaging based  on in vivo reporter gene expression: RE promoter Reporter gene Poly A Principle: biosensor genes implicated in tissue damage,  oxydative stress, apoptosis and other cellular pathways. A. Briat ‐Optical imaging (Luciferase, GFP) ‐Nuclear imaging (hNIS, HSV‐tk) 12 Rovaltain, April 8th 2010.
  13. 13. Imaging of ionizing radiations  impact on gene expression A. Briat 13 Rovaltain, April 8th 2010.
  14. 14. Imaging of chemicals exposure impact on gene expression A. Briat 14 Rovaltain, April 8th 2010.
  15. 15. Imaging embryotoxic and teratological effects of  chemicals in the transgenic zebrafish  Expression of  Dual  Specificity  Phosphatase  6  (dusp6,  also  known  as  Mkp3)  is  controlled  by  FGF  signaling  throughout  development.  The  Dusp6  promoter  drives the expression of GFP in transgenic embryos. chemical FGF signaling induction A. Briat Dusp6 activation GFP expression 15 Rovaltain, April 8th 2010.
  16. 16. Ecotoxicology and Imaging ‐ Positive impact on 3R, ‐ Quantitative  and  qualitative  answers  to  ecotoxicological questions, ‐ Dedicated animal facility, ‐ Integration of the imaging approach, ‐ Research  programs:  developement  of  new  animal models and new methodologies. A. Briat REACH the unreachable!  16 Rovaltain, April 8th 2010.
  17. 17. ANIMASCOPE One stop shop for preclinical in vivo imaging Customizable services and full studies are available depending on customer needs. Every project is  tailored to optimize outcomes and readouts PROTOCOL DESIGN Definition of biological parameters to be measured Choice of imaging modalities, tracers, biomarkers, contrast agents, animal models Design of image processing workflow STUDY MANAGEMENT Model Pre‐conditioning Image acquisition Recording and traceability IMAGE PROCESSING A. Briat Image handling and pre‐processing Data analysis REPORTING Technical reporting Biomedical reporting  Rovaltain, April 8th 2010.
  18. 18. ANIMASCOPE Multi‐Modality Imaging FLEXIBLE and VERSATILE Optimise and Customise Each Protocol Multi‐modality imaging allows to collect,  combine and compare multiple readouts  within the same anatomical structure and  experimental frame Animascope utilizes a wide set of non‐ A. Briat invasive technologies, all the main imaging  Imaging facility, Archamps techniques X‐Ray CT, MRI, PET/SPECT, US, OPTIC 18 Rovaltain, April 8th 2010.
  19. 19. CONTACTS ANIMASCOPE ZA Eurekalp, 38660 St.‐Vincent‐de‐Mercuze (Grenoble) FRANCE Tel: +33 (0)4 76979487 Fax: +33 (0)9 55753911 www.animascope.eu info@animascope.eu New imaging facility Current Animascope office located near Geneva (74) in Eurekalp (38) A. Briat Rovaltain, April 8th 2010.
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  21. 21. Zebra fish embryos as models for embryotoxic and  teratological effects of chemicals Whole  embryo  microarray  studies  yielded  robust  toxicogenomic  profiles  and  allowed  to  detect  highly  tissue  restricted  gene  responses. These  response  genes  will  be  the  basis  for  the  future  development  of  genetic  sensors  of  tissue  specific  A. Briat effects of toxicants. Toxicogenomic expression profiles induced by different toxins 21 Rovaltain, April 8th 2010.
  22. 22. Imaging of toxicity in the  Zebra fish using in vivo fluorescence imaging . A. Briat J. Vet. Sci. (2008) 22 Rovaltain, April 8th 2010.

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