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: 7286677
• 负责人: ANTHONY A Ferrante
• 金额: $ 8.91万
• 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/7286677
• 关键词: Achievement; Address; Affect; Algorithms; Anesthetics; Animal Model; Animals; Aorta; Arteries; Automation; Biological Assay; Blood; Blood Vessels; Blood capillaries; Blood flow; Brain; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Collection; Compatible; Computer software; Detection; Development; Disease; Dorsal; Embryo; Environment; Erythrocytes; Fertilization; Functional Imaging; Goals; Heart Diseases; Heart Rate; Human; Image; Imaging technology; Invasive; Laboratories; Larva; Laser Scanning Confocal Microscopy; Length; Life; Light; Lighting; Maps; Measures; Methods; Microscope; Modeling; Monitor; Optical Coherence Tomography; Optics; Performance; Pharmacologic Substance; Phase; Phase I Clinical Trials; Physiology; Process; Pulsatile Flow; Range; Research; Resolution; Retina; Scanning; Screening procedure; Source; Speed; Standards of Weights and Measures; Stress; Structure of posterior cardinal vein; System; Tail; Techniques; Technology; Testing; TimeLine; Vascular Diseases; Veins; Work; Zebrafish; aortic arch; base; capillary; concept; day; design; drug discovery; fluorescence imaging; high throughput screening; human disease; image processing; instrumentation; interest; multi-photon; novel; prevent; response; small molecule; technology development; tomography

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。已经进行了小分子筛选，以识别正常心血管过程的修饰符和心血管疾病的修饰符。开发中的高通量系统旨在衡量心率，但不能解决心血管功能的其他关键参数，例如血液速度和分布。我们建议开发同时的高通量系统：1）衡量心率； 2）生成主要血管的流图； 3）测量这些血管中的血液速度。基于显微镜的系统将利用光谱域光学相干断层扫描与多普勒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，我们将开发一个面包板系统，该系统将从动物的背侧和腹侧视图中收集图像。脉管系统的图像将被收集。在面包板系统中，动物将被定位，扫描角将手动调整。在II期中，将开发完整的自动筛选系统，其中包括：1）软件算法快速定位动物以进行成像并沿其轴向长度调节扫描角度； 2）自动图像收集； 3）自动图像处理。 II期测试将包括一个试点复合屏幕，以识别心输出量的修饰符。 这项研究将开发技术，该技术将使人类疾病的斑马鱼模型在高通量筛选中用于活性药物化合物。特别是，这种筛查有望加速发现新药以治疗心血管疾病。