Output details

Automated System and method for screening zebrafish

A developmental atlas for zebrafish that enables the automatic extraction of high-content signatures (or endpoints) from images. This methodology facilitates new applications in toxicity screening as demonstrated in collaboration with Phylonix Inc. on a 14 endpoint teratogenicity assay. M. Baker highlighted the developed method in her review of key tools for zebrafish in Screening: the age of fishes (Nature Methods, 2011). This innovation provided the foundation for the SBIR grant High-Content Analysis Tools for Developmental Toxicity Screens in Zebrafish funded by the National Institute of Health (ES017590). The development was commercialized as a module of General Electric’s Investigator platform.

Most internal organs of the zebrafish, including the cardiovascular system, gut, liver, and kidney develop in the first 24 to 48 hour. Zebrafish embryos are transparent, which facilitates observation and analysis. Generic imaging software can be used to measure quantities such as liver size, tail length, tail curvature, and the presence or absence of axons. This invention introduces a developmental stage dependent anatomical model that uses a subdivision mesh to model the central 2D optical section of the fish. The model for the 120 hour zebrafish includes 12 organ specific regions. Any required measurement can be defined on the subdivision mesh.

The model itself, definition of the anatomical measurements, and the associated application requirements have been developed in collaboration with expert biologists at Phylonix Inc. In order to support high-throughput toxicity studies the model fitting algorithm needs to robust to image variation, poor initialization, and large anatomical variations. Additional algorithms were developed to support the imaging of multiple fish in a well plate format. The ZETAX™ teratogenicity assay was used to validate the accuracy of the model based measurements. The system allows definition of a model for a specific strain and measure the anatomical variation with respect to this model.

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