In Vivo PIV: A Platform Technology For Phenotyping Flow In Animal Model Systems

体内 PIV：动物模型系统中表型分析流程的平台技术

• 批准号: 7638415
• 负责人: JAY Robert HOVE
• 金额: $ 36.5万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-06 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7638415
• 关键词: 3-Dimensional; Accounting; Affect; Algorithms; Animal Model; Animals; Area; Arts; Atherosclerosis; Biological; Biological Models; Biomedical Research; Blood; Cardiomyopathies; Cardiovascular system; Cells; Cerebrospinal Fluid; Characteristics; Collection; Complex; Data; Defect; Development; Disease; Embryo; Embryonic Development; Engineering; Environment; Foundations; Funding; Genetic; Goals; Hydrocephalus; Image; Image Analysis; Imagery; Imaging Device; Imaging technology; Kidney; Lasers; Life; Liquid substance; Measurement; Mechanical Stress; Mechanics; Methodology; Methods; Microscope; Microscopic; Microscopy; Modality; Motion; Operative Surgical Procedures; Optics; Organism; Pathogenesis; Phenotype; Physiology; Play; Polycystic Kidney Diseases; Research; Research Personnel; Resolution; Role; Scientific Advances and Accomplishments; Scientist; Speed; Syringomyelia; System; Techniques; Technology; Time; Tracer; Urine; Velocimetries; Work; Zebrafish; base; body system; digital; fluid flow; image processing; in vivo; innovation; interest; multidisciplinary; mutant; nervous system disorder; novel; particle; research study; submicron; technological innovation; tool

DESCRIPTION (provided by applicant): Flow-induced forces resulting from intravital biofluids (e.g., blood, urine, cerebrospinal fluid) are widely acknowledged to be critical for proper embryonic development. Defects in embryonic biofluid flow are associated with renal, cardiovascular and nervous system disorders . Genetic, surgical, and pharmacological animal models exist or are being developed for both normal development and disease states. However, existing methods for intravital flow imaging are inadequate as all current modalities lack the spatial and/or temporal resolution necessary to describe the wide range of complex developmental flows that exist in biological organisms. We propose to create a cutting-edge, cross-platform technology for 4-D imaging (3-D + time) of biofluid flows within the living embryonic zebrafish, a widely-used animal model for developmental studies. The foundation of this critically-needed technology will be a laser-based multidimensional microscopic imaging system to visualize and track the motions of submicron fluorescent tracer particles suspended within the anatomical flows of interest. We will utilize a unique defocusing digital particle image velocimetry (DDPIV) technique to obtain the required spatial and temporal sensitivity. In addition, by developing new image analysis algorithms we will, for the first time, be able to account for the large velocity gradients and moving boundaries that are so prevalent in living systems and which have been so problematic for existing in vivo imaging technologies. The creation of a novel in vivo micro-DDPIV technology will greatly impact our ability to understand how biofluid flow affects development in both healthy and flow-compromised animals. This is an area of great need as we are currently capable of creating large numbers of flow-related mutants in zebrafish, but are far less able to reliably quantify the resulting dynamic flow changes in order to understand their effects on developmental pathogenesis. This work will significantly aid a wide-range of biomedical research efforts, as flow-dependent phenomena are key factors in a great many diseases including polycystic kidney disease, atherosclerosis, syringomyelia, cardiomyopathy, and hydrocephalus-related disorders.

描述（由申请人提供）：被广泛认为是由胚胎发育适当至关重要的流动性生物流体（例如，血液，尿液，脑脊液）引起的流量引起的力。胚胎生物流体流中的缺陷与肾脏，心血管和神经系统疾病有关。存在或正在为正常发育状态和疾病状态开发遗传，外科和药理动物模型。但是，现有的静脉流成像方法是不足的，因为所有当前的方式都缺乏描述生物生物体中存在的广泛复杂发育流所需的空间和/或时间分辨率。我们建议创建一种尖端的，跨平台的技术，用于生物流动的4-D成像（3-D +时间），这是一种广泛使用的发育研究动物模型。这项急需的技术的基础将是基于激光的多维显微成像系统，可视化和跟踪悬浮在感兴趣的解剖学流中的亚微米荧光示踪剂颗粒的运动。我们将利用独特的散落数字粒子图像速度法（DDPIV）技术来获得所需的空间和时间灵敏度。此外，通过开发新的图像分析算法，我们将首次能够说明在生命系统中如此普遍的较大速度梯度和移动边界，并且对于现有的体内成像技术而言是如此的问题。创建一种新型的体内微二醇技术将极大地影响我们了解生物流动流如何影响健康和流动性动物的发展的能力。这是一个非常需要的领域，因为我们目前能够在斑马鱼中创建大量与流动相关的突变体，但无法可靠地量化所得的动态流动变化，以了解其对发育发病机理的影响。这项工作将大大有助于广泛的生物医学研究工作，因为流动依赖的现象是许多疾病的关键因素，包括多囊性肾脏疾病，动脉粥样硬化，脊​​椎毒，疗法，心肌病和脑积水相关疾病。