title: Current approaches and future role of high content imaging in safety sciences and drug discovery.
abstract: High content imaging combines automated microscopy with image analysis approaches to simultaneously quantify multiple phenotypic and/or functional parameters in biological systems. The technology has become an important tool in the fields of safety sciences and drug discovery, because it can be used for mode-of-action identification, determination of hazard potency and the discovery of toxicity targets and biomarkers. In contrast to conventional biochemical endpoints, high content imaging provides insight into the spatial distribution and dynamics of responses in biological systems. This allows the identification of signaling pathways underlying cell defense, adaptation, toxicity and death. Therefore, high content imaging is considered a promising technology to address the challenges for the "Toxicity testing in the 21st century" approach. Currently, high content imaging technologies are frequently applied in academia for mechanistic toxicity studies and in pharmaceutical industry for the ranking and selection of lead drug compounds or to identify/confirm mechanisms underlying effects observed in vivo. A recent workshop gathered scientists working on high content imaging in academia, pharmaceutical industry and regulatory bodies with the objective to compile the state-of-the-art of the technology in the different institutions. Together they defined technical and methodological gaps, proposed quality control measures and performance standards, highlighted cell sources and new readouts and discussed future requirements for regulatory implementation. This review summarizes the discussion, proposed solutions and recommendations of the specialists contributing to the workshop.
authors.affiliation: Innovitox consultation & services, Barcelona, Spain.
authors.forename: Erwin
authors.initials: E
authors.lastname: van Vliet
authors.forename: Mardas
authors.initials: M
authors.lastname: Daneshian
authors.forename: Mario
authors.initials: M
authors.lastname: Beilmann
authors.forename: Anthony
authors.initials: A
authors.lastname: Davies
authors.forename: Eugenio
authors.initials: E
authors.lastname: Fava
authors.forename: Roland
authors.initials: R
authors.lastname: Fleck
authors.forename: Yvon
authors.initials: Y
authors.lastname: Julé
authors.forename: Manfred
authors.initials: M
authors.lastname: Kansy
authors.forename: Stefan
authors.initials: S
authors.lastname: Kustermann
authors.forename: Peter
authors.initials: P
authors.lastname: Macko
authors.forename: William R
authors.initials: WR
authors.lastname: Mundy
authors.forename: Adrian
authors.initials: A
authors.lastname: Roth
authors.forename: Imran
authors.initials: I
authors.lastname: Shah
authors.forename: Marianne
authors.initials: M
authors.lastname: Uteng
authors.forename: Bob
authors.initials: B
authors.lastname: van de Water
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D015386:Hazardous Substances; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008954:Models, Biological; D004364:Pharmaceutical Preparations; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D015386:Hazardous Substances; D004364:Pharmaceutical Preparations