IMAGE BASED PHENOTYPING

基于图像的表型分析

• 批准号: 7723098
• 负责人: ROSS T WHITAKER
• 金额: $ 4.62万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723098
• 关键词: Animal Experimentation; Biomedical Computing; Collaborations; Complex; Computer Retrieval of Information on Scientific Projects Database; Data Set; Defect; Development; Developmental Biology; Disruption; Funding; Genes; Goals; Grant; Growth; Hand; Human Genetics; Image; Imagery; Institutes; Institution; Invasive; Investments; Laboratories; Length; Manuals; Measurement; Measures; Methods; Metric; Microscope; Minor; Modeling; Molecular Abnormality; Mus; Mutation; Noise; Phenotype; Preparation; Process; Protocols documentation; Publications; Research; Research Personnel; Research Project Grants; Resources; Shapes; Skeletal system; Skeleton; Source; Specimen; Standards of Weights and Measures; Statistical Computing; Structure; Surface; Techniques; Time; United States National Institutes of Health; Universities; Utah; Variant; base; bone; density; human disease; humerus; image processing; imaging Segmentation; insight; morphometry; research study; shape analysis; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The laboratory of Dr. Mario Capecchi at the University of Utah's Eccles Institute of Human Genetics is investigating the phenotypic expression of specific, induced genetic abnormalities in mice, a model that has been shown to provide insight into the ontogeny of congenital human disease. ¿Conventional analysis of mouse skeletal structure requires sacrificing the research animal and a labor-intensive, time-consuming process of skeleton preparation and physical inspection under a dissecting microscope. ¿Many tens or even hundreds of specimens are often required for a meaningful statistical analysis, which represents an enormous investment of time and money. ¿The goal of the Center for Integrative Biomedical Computing collaboration with the Capecchi lab is to develop a faster, non-invasive protocol for skeletal analysis that uses semi-automated image processing of three-dimensional micro-CT rather than hand measurements of prepared skeletal specimens.¿We are developing a set of image segmentation, measurement and visualization tools for quantitative morphometry that allow us to experiment with new metrics such as the analysis of bone shape that would not be possible with prepared skeletal specimens. ¿Furthermore, we expect that our tools will allow for more precise and repeatable measurements for length, density and volume, and therefore give insight into genetic alterations that have previously been described as pleiotropic (partially penetrant) or that have been misinterpreted as minor effects. In the short term, the Center for Integrative Biomedical Computing is targeting two specific research projects for publication. The first project is to validate our non-invasive CT-based protocol for skeletal analysis against the results obtained using prepared specimens and manual bone measurements by researchers in the Capecchi lab (Boulet and Capecchi, 2002; Davies and Capecchi, 1994). ¿In this study, we will use scalar measurements of bone length and bone taken with our image processing and visualization tools. ¿As in the Boulet-Capecchi study (Boulet and Capecchi, 2002), the length of the various bones of the paw will be compared to the length of the humerus. Our hypothesis is that we can reproduce the physical measurements to a greater accuracy (smaller standard deviation) and perhaps even measure additional variation that was lost in the measurement noise inherent to the physical study. Our second research project will apply our methods for computing statistical shape models to the segmented mouse bones. ¿The mouse bones are a very challenging data set because their surfaces are composed of many complex and irregular features. ¿We have developed a new technique for computing shape correspondence points, an essential step in the shape analysis pipeline, that we believe are more suited for these surfaces than conventional methods which parameterize surfaces as spheres. REFERENCES "Duplication of the Hoxd11 Gene Causes Alterations in the Axial and Appendicular Skeleton of the Mouse", ¿Anne Boulet and Mario Capecchi. ¿Developmental Biology, 249, 96-102, 2002 "Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of hoxd-11", ¿Allan Peter Davies and Mario Capecchi. ¿Development, 120, 2187-2198, 1994.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 犹他州大学埃克尔斯人类遗传学研究所的马里奥·卡佩奇博士的实验室正在研究 表型表达的特定，诱导遗传异常的小鼠，一个模型，已被证明提供洞察力 人类先天性疾病的个体发生传统的小鼠骨骼结构分析需要牺牲 研究动物和一个劳动密集、耗时的骨骼准备和身体检查过程 在解剖显微镜下对于一个有意义的统计，通常需要数十甚至数百个标本。 分析，这意味着时间和金钱的巨大投资。该中心的目标为综合 生物医学计算与Capecchi实验室的合作是为了开发一种更快，非侵入性的骨骼 使用三维显微CT的半自动图像处理而不是手动测量的分析。 准备好的骨骼标本。我们正在开发一套图像分割，测量和可视化工具， 定量形态测量学，使我们能够实验新的指标，如骨形状的分析， 不可能用准备好的骨骼标本。此外，我们希望我们的工具将允许更精确， 可重复测量的长度，密度和体积，因此可以深入了解遗传改变， 以前被描述为多效性（部分渗透）或被误解为轻微影响。 在短期内，综合生物医学计算中心的目标是两个具体的研究项目， 出版物第一个项目是验证我们的非侵入性CT为基础的协议骨骼分析的结果 通过Capecchi实验室的研究人员使用准备好的标本和手动骨测量获得（Boulet和 Capecchi，2002年; Davies和Capecchi，1994年）。在这项研究中，我们将使用骨长度和骨的标量测量， 使用我们的图像处理和可视化工具。正如Boulet和Capecchi的研究（Boulet和Capecchi，2002年）一样， 将爪子的各种骨头的长度与肱骨的长度进行比较。我们的假设是 可以以更高的精度（更小的标准偏差）再现物理测量，甚至可以测量 在物理研究固有的测量噪声中丢失的附加变化。 我们的第二个研究项目将应用我们的方法计算统计形状模型分割鼠标 骨头鼠标骨骼是一个非常具有挑战性的数据集，因为它们的表面由许多复杂的， 不规则的特征我们开发了一种计算形状对应点的新技术，这是 我们认为，形状分析管道比传统方法更适合这些表面， 参数化曲面为球体。 引用 “Hoxd 11基因的复制导致小鼠中轴和外骨骼的改变”，安妮·布利特 和马里奥·卡佩奇发育生物学，249，96-102，2002 “Axial homeosis and apapapular skeleton defects in mice with a targeted disruption of hoxd-11”，<$Allan Peter Davies 和马里奥·卡佩奇Development，120，2187-2198，1994.