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Abstract

Grant Number: 5R43HL086809-02
Project Title: Automated Screening System for Modifiers of Cardiac Output in Zebrafish
PI Information:NameEmailTitle
FERRANTE, ANTHONY A. ferrante@psicorp.com PRINCIPAL RESEARCH SCIENTIST

Abstract: DESCRIPTION (provided by applicant): The zebrafish, Danio rerio, has become widely accepted as a model for human disease. Small molecule screens have been performed to identify both modifiers of normal cardiovascular processes and modifiers of cardiovascular disease. High-throughput systems under development aim to measure heart rate but do not address other critical parameters of cardiovascular function such as blood velocity and distribution. We propose to develop a high-throughput system that would simultaneously: 1) measure heart rate; 2) generate a flow map of the major blood vessels; and 3) measure blood velocity in those vessels. The microscope-based system will utilize spectral domain optical coherence tomography with Doppler to generate, within a matter of seconds, a three dimensional structural image of zebrafish embryos and larvae and measure blood flow. In Phase I we will develop a breadboard system that will enable collection of images from both the dorsal and ventral views of the animals. Images of the vasculature both of the brain and of the tail will be collected. In the breadboard system the animals will be located and the scan angle will be adjusted manually. In Phase II a complete, automated screening system will be developed that includes: 1) software algorithms to rapidly locate the animals for imaging and adjust the scan angle along their axial length; 2) automated image collection; and 3) automated image processing. Phase II testing will include a pilot compound screen to identify modifiers of cardiac output. This research will develop technologies that will enable the use of zebrafish models of human disease in high-throughput screens for active pharmaceutical compounds. In particular, such screens are expected to accelerate discovery of new pharmaceuticals to treat cardiovascular diseases.

Thesaurus Terms:
blood flow measurement, cardiovascular imaging /visualization, heart function, hemodynamics, high throughput technology, laser Doppler flowmetry, optical tomography, technology /technique development, ultrasound blood flow measurement
blood circulation, brain circulation, heart rate, image processing
bioengineering /biomedical engineering, bioimaging /biomedical imaging, embryo /fetus, zebrafish

Institution: PHYSICAL SCIENCES, INC
20 NEW ENGLAND BUSINESS CENTER
ANDOVER, MA 018101022
Fiscal Year: 2007
Department:
Project Start: 15-SEP-2006
Project End: 28-FEB-2008
ICD: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
IRG: ZRG1


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