MODEL-BASED DEVELOPMENT OF NEW DIAGNOSTIC MEASURES

基于模型的新诊断措施开发

• 批准号: 7955292
• 负责人: JEFFREY W HOLMES
• 金额: $ 0.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955292
• 关键词: Address; Anatomy; Animals; Area; Basic Science; Biomechanics; Biomedical Computing; Calcium; Cardiac; Cell model; Clinical; Collaborations; Complement; Computer Retrieval of Information on Scientific Projects Database; Coupling; Data; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Elements; Funding; Goals; Grant; Healed; Heart; Hormonal; Image; Infarction; Institution; Ischemia; Lead; Magnetic Resonance Imaging; Maps; Measures; Methods; Modeling; Motion; Mus; Myocardial Infarction; Pacemakers; Patients; Research; Research Personnel; Resources; Source; Stress Tests; Tissues; Transgenic Mice; Transgenic Model; Ultrasonography; United States National Institutes of Health; Universities; Virginia; Work; base; clinical Diagnosis; healing; implantation; improved; mouse model; novel; novel diagnostics; programs; technology development

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. (A) OBJECTIVES One of the major thrusts of the current NBCR renewal proposal is increased application of Continuity to clinical diagnosis and treatment. The Cardiac Biomechanics Group (CBG) at the University of Virginia has recently used Continuity to develop novel measures of wall motion to improve the accuracy of cardiac stress testing (Herz 2005, 2006). In collaboration with the cardiac MRI and ultrasound imaging groups at the University of Virginia, the CBG is now expanding this model-based development approach to address other diagnostic goals, including improved diagnosis of prior unrecognized myocardial infarction (UMI) during stress testing, noninvasive assessment of synchrony of contraction (Ingrassia 2007), and anatomic mapping of infarct tissue to guide pacemaker lead implantation during cardiac resynchronization therapy (CRT). These efforts are strongly supported by the modeling capabilities of the NBCR but have also raised new modeling challenges regarding the integration of patient-specific image information. Due to the scientific value of studying transgenic mice, the cardiac MRI group at UVa has installed a dedicated small-animal scanner with a console and programming interface identical to our clinical MRI units. This allows us to use ongoing small-animal studies to simultaneously develop and refine clinically applicable diagnostic methods such as Displacement-Encoding with Stimulated Echoes (DENSE) (Kim 2004). Work in this area would benefit from improved models of the mouse heart. Finally, a whole range of clinical and small-animal imaging work would benefit from the ability to better incorporate multi-scale information such as cellular models of ischemia, hormonal stimulation, disrupted calcium cycling, etc. The three Specific Aims below summarize new proposed collaborations in each of these areas: integration of existing and new cellular models with existing cardiac finite-element models, incorporation of image-derived information to tailor those finite-element models to specific patients, and improved modeling of the mouse heart for use in developing and validating new diagnostic methods in transgenic models. In each example, a specific prototypic example will be used to illustrate the intended approach, but the methods developed will be applicable to a wide range of similar problems. The Specific Aims of the proposed collaborative work with the NBCR are: 1) Improve multi-scale capabilities for coupling new and existing cellular models to existing cardiac finite-element models (prototypic example  regional ischemia). 2) Develop methods for incorporating image-derived patient-specific functional information to generate customized cardiac models (prototypic example  DENSE displacement data). 3) Complete and validate a fully functional mouse cardiac finite-element model to complement existing models of other species (prototypic example  post-infarction healing in the mouse). These aims will rely on proposed new developments in Continuity, especially the ability to dynamically author and compile cellular contractile and ionic models [4A.2B Aim 1a], and the ability to fit new models to patient MRI and CT data and to solve and optimize patient-specific models [4A.2B Aim 3]. This Collaborative Project will help drive the basic science and translational applications of Core 2B research and technology development.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 （a）目标 当前NBCR更新建议的主要推力之一是增加连续性在临床诊断和治疗中的应用。弗吉尼亚大学的心脏生物力学小组（CBG）最近使用连续性来开发新颖的壁运动测量，以提高心脏应激测试的准确性（Herz 2005，2006）。 In collaboration with the cardiac MRI and ultrasound imaging groups at the University of Virginia, the CBG is now expanding this model-based development approach to address other diagnostic goals, including improved diagnosis of prior unrecognized myocardial infarction (UMI) during stress testing, noninvasive assessment of synchrony of contraction (Ingrassia 2007), and anatomic mapping of infarct tissue to guide pacemaker lead implantation during心脏重新同步疗法（CRT）。这些努力得到了NBCR的建模能力的强烈支持，但也提出了有关特定于患者图像信息的整合的新建模挑战。由于研究转基因小鼠的科学价值，UVA的心脏MRI组安装了专用的小动物扫描仪，其控制台和编程界面与我们的临床MRI单元相同。这使我们能够使用正在进行的小动物研究同时开发和完善临床适用的诊断方法，例如用刺激的回声进行置换编码（密集）（Kim 2004）。在这一领域的工作将受益于改善小鼠心脏的模型。最后，一系列临床和小动物成像工作将受益于更好地纳入多尺度信息的能力，例如缺血，激素刺激，钙循环中断等等的细胞模型。 下面的三个具体目的总结了这些领域的新提议的合作：现有和新的蜂窝模型与现有心脏有限元模型的集成，将图像衍生的信息合并以将这些有限元模型量身定制为特定患者，以及改进鼠标心脏的模型，用于在传播模型中开发和验证新的诊断方法。在每个示例中，都将使用一个特定的原型示例来说明预期的方法，但是开发的方法将适用于广泛的类似问题。 拟议与NBCR合作的特定目的是： 1）提高将新的和现有的细胞模型与现有心脏有限元模型耦合的多尺度功能（原型示例区域缺血）。 2）开发合并图像衍生的患者特异性功能信息以生成自定义心脏模型的方法（原型示例密集的位移数据）。 3）完成并验证一个功能齐全的小鼠心脏有限元模型，以补充其他物种的现有模型（小鼠中孔疗法后的原型示例）。 这些目标将依赖于连续性的拟议新发展，尤其是动态作者和编译细胞收缩和离子模型的能力[4A.2B AIM 1A]，以及将新模型拟合到患者MRI和CT数据并求解和优化患者特异性模型的能力[4A.2B AIM 3]。这个协作项目将有助于推动Core 2B研究和技术开发的基础科学和翻译应用。