Automated Screening System for Modifiers of Cardiac Output in Zebrafish

斑马鱼心输出量调节因素的自动筛选系统

• 批准号: 7156129
• 负责人: ANTHONY A Ferrante
• 金额: $ 21.09万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156129
• 关键词: bioengineering /biomedical engineering; bioimaging /biomedical imaging; blood circulation; blood flow measurement; brain circulation; cardiovascular imaging /visualization; embryo /fetus; heart function; heart rate; hemodynamics; high throughput technology; image processing; laser Doppler flowmetry; optical tomography; technology /technique development; ultrasound blood flow measurement; zebrafish

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.

描述（由申请人提供）：斑马鱼Danio rerio已被广泛接受为人类疾病的模型。已经进行小分子筛选以鉴定正常心血管过程的修饰剂和心血管疾病的修饰剂。正在开发的高通量系统旨在测量心率，但不解决心血管功能的其他关键参数，如血液速度和分布。我们建议开发一种高通量系统，同时：1）测量心率; 2）生成主要血管的血流图; 3）测量这些血管中的血流速度。基于显微镜的系统将利用多普勒光谱域光学相干断层扫描技术在几秒钟内生成斑马鱼胚胎和幼虫的三维结构图像，并测量血流。在第一阶段，我们将开发一个实验板系统，该系统将能够从动物的背侧和腹侧视图收集图像。将收集大脑和尾部血管系统的图像。在试验板系统中，将定位动物，并手动调整扫描角度。在第II阶段，将开发一个完整的自动筛选系统，包括：1）软件算法，用于快速定位动物进行成像，并沿着其轴向长度调整扫描角度; 2）自动图像收集; 3）自动图像处理。第二阶段的测试将包括一个试点化合物筛选，以确定修改心输出量。 这项研究将开发技术，使人类疾病的斑马鱼模型能够用于活性药物化合物的高通量筛选。特别是，这种筛选有望加速治疗心血管疾病的新药的发现。