CT-based Phenotype for Airway Remodeling in COPD based on Airway Wall Density

基于气道壁密度的 COPD 气道重塑 CT 表型

基本信息

批准号：
8685303
负责人：
Raul San Jose Estepar
金额：
$ 15.32万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-16 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8685303
关键词：
Address Affect Area Atlases Candidate Disease Gene Cartilage Cause of Death Characteristics Chest Chronic Obstructive Airway Disease Clinical Clinical Data Clinical Research Clinical Trials Code Committee Members Communities Computer software Computers Correlative Study Data Development Development Plans Disease Disease susceptibility Environment Epidemiologic Studies Fibrosis Forced expiratory volume function Fostering Generations Genetic Genetic Determinism Heterogeneity High Resolution Computed Tomography Histocompatibility Testing Histology Histopathology Hospitals Human Image Image Analysis Individual Inflammation Inflammatory Investigation Lead Location Lung Lung diseases Measurement Measures Medical Imaging Mentorship Methodology Methods Metric Microscopy Modality Modeling Morphology Obstruction Paraffin Embedding Pathologist Phase Phenotype Physiological Physiology Play Process Property Public Health Public Health Schools Pulmonary Function Test/Forced Expiratory Volume 1 Relative (related person)Research Respiratory physiology Roentgen Rays Role Sampling Scanning Scientist Severities Simulate Slice Software Tools Specimen Staining method Stains Structure of parenchyma of lung Surrogate Endpoint Techniques Technology Testing Thick Tissue Sample Tissues Tomography, Computed, Scanners Training Trees United States Universities Validation Variant Woman X-Ray Computed Tomography airway remodeling attenuation base career career development clinical care clinically relevant cohort computerized density digital imaging functional disability genetic association genetic epidemiology genome wide association study image reconstruction in vivo interest lung imaging medical schools multimodality novel open source particle research clinical testing respiratory smooth muscle small airways disease software development validation studies

项目摘要

DESCRIPTION (provided by applicant): Airway remodeling plays a fundamental role in the function of the airways in Chronic Obstructive Pulmonary Diseases (COPD). This remodeling is driven by an inflammatory and fibrotic process that changes both the airway morphology and composition. This proposal tests the hypothesis that Computed Tomography (CT) may be used to evaluate the histopathological changes in the airway walls associated with airway remodeling and that that those changes can be used to define a new phenotype to establish genome-wide associations in candidate genes. The mural inflammation and fibrosis characteristic of this process may change airway size and tissue density to such a degree that it is detectable on CT scans. The broad objective of this proposal is to validate and apply a new phenotype for COPD, airway power, based on X-ray attenuation of the airway wall that correlates with the histopathology components of the disease. This new phenotype has the property that can be accurately computed in CT with respect to an idealized model of an airway. Specifically, we will validate this new phenotype using computerized and artificial phantoms. Then, we propose an ex-vivo validation study that assesses central airway tissue blocks by means of multiple modalities; specifically, histology microscopy digital images, microfocal X-ray-computed tomography (microCT) and standard clinical CT. Tissue samples will be scanned with microCT technology to provide a radiological baseline that can be used to compare morphology measurements and X-ray attenuation values with histopathology components assessed by a pathologist. The same tissue samples will be scanned in standard High Resolution CT (HRCT) scanners used in standard clinical care of COPD and correlations will be established with the measurements obtained at the microCT level and the histology level. In addition, this new phenotype, as well as wall thickness phenotypes, will be used to establish genome-wide associations in candidate genes using 3000 subject CT scans from COPDGene. This research is the core of a five year career development plan for Dr. San Josi Estipar under the mentorship of three outstanding researches and the advice of four committee members with expertise in the following areas: lung physiology, genetic epidemiology and image analysis. The proposed career plan combines didactic and practical training in these areas within the unique academic and research environment of Harvard Medical School, Harvard School of Public Health and Brigham and Women's Hospital. The career plan will foster Dr. San Josi Estipar into an established independent quantitative research scientist with the expertise to develop image-based quantitative approaches to enable clinical and genetic studies in COPD and related lung diseases.

描述（由申请人提供）：气道重塑在气道功能中在慢性阻塞性肺部疾病（COPD）中起着基本作用。这种重塑是由炎症和纤维化过程驱动的，该过程改变了气道形态和组成。该提案检验了计算机断层扫描（CT）可用于评估与气道重塑相关的气道壁的组织病理学变化的假设，并且可以使用这些变化来定义一种新的表型来建立候选基因基因组范围的关联。该过程的壁画炎症和纤维化特征可能会改变气道的大小和组织密度，以至于可以在CT扫描中检测到它。该提案的广泛目的是基于与该疾病的组织病理学成分相关的气道壁的X射线衰减，验证和应用新的表型为COPD，气道功率。这种新的表型具有可以在CT中准确计算的相对于气道的理想化模型来准确计算的属性。具体而言，我们将使用计算机化和人工幻影验证这种新的表型。然后，我们提出了一项前体验证研究，该研究通过多种方式评估了中央气道组织块。具体而言，组织学显微镜数字图像，微焦X射线计算机断层扫描（Microct）和标准临床CT。组织样品将使用MicroCT技术扫描，以提供放射线基线，可用于将形态测量和X射线衰减值与病理学家评估的组织病理学成分进行比较。将在COPD标准临床护理中使用的标准高分辨率CT（HRCT）扫描仪中扫描相同的组织样品，并通过在MicroCT水平和组织学水平上获得的测量值建立相关性。此外，这种新的表型以及壁厚表型将用于使用COCDGENE的3000名受试者CT扫描在候选基因中建立全基因组关联。这项研究是在三项杰出研究的指导下为圣乔西·埃斯蒂帕尔（San Josi Estipar）博士进行五年职业发展计划的核心，以及在以下领域具有专业知识的四名委员会成员的建议：肺部生理学，遗传流行病学和图像分析。拟议的职业计划结合了哈佛医学院，哈佛公共卫生和杨百翰和妇女医院的独特学术和研究环境中的这些领域的教学和实践培训。职业计划将促进圣何塞·埃斯蒂帕尔（San Josi Estipar）博士，成为一位知名的独立定量研究科学家，其专业知识旨在开发基于图像的定量方法，以实现COPD和相关肺部疾病的临床和遗传研究。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A theoretical framework to three-dimensional ultrasound reconstruction from irregularly sampled data.

DOI：
10.1016/s0301-5629(02)00762-7
发表时间：
2003-02
期刊：
Ultrasound in medicine & biology
影响因子：
2.9
作者：
Raúl San José Estépar;M. Martín-Fernández;P. P. Caballero-Martínez-P.;C. Alberola-López;J. Ruiz-Alzola
通讯作者：
Raúl San José Estépar;M. Martín-Fernández;P. P. Caballero-Martínez-P.;C. Alberola-López;J. Ruiz-Alzola

RANKING AND CLASSIFICATION OF MONOTONIC EMPHYSEMA PATTERNS WITH A MULTI-CLASS HIERARCHICAL APPROACH.

使用多类分层方法对单调肺气肿模式进行排序和分类。