MODEL-BASED DEVELOPMENT OF NEW DIAGNOSTIC MEASURES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 (A)目标 当前NBCR更新提案的主要推动力之一是增加对临床诊断和治疗的连续性应用。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的室壁运动测量方法，以提高心脏负荷测试的准确性(Herz 2005,2006)。与弗吉尼亚大学的心脏MRI和超声成像小组合作，CBG现在正在扩展这种基于模型的开发方法，以满足其他诊断目标，包括在负荷测试中改善对先前未识别的心肌梗死(UMI)的诊断，对收缩同步性的非侵入性评估(Ingria，2007)，以及在心脏再同步治疗(CRT)期间指导起搏器电极植入的梗塞组织解剖标测。这些努力得到了NBCR的建模能力的大力支持，但也提出了关于患者特定图像信息集成的新的建模挑战。由于研究转基因小鼠的科学价值，弗吉尼亚大学的心脏核磁共振小组安装了一台专用的小动物扫描仪，其控制台和编程接口与我们的临床核磁共振单位相同。这使我们能够利用正在进行的小动物研究，同时开发和改进临床适用的诊断方法，如用刺激回声进行置换编码(Density)(Density)(Kim 2004)。这一领域的工作将受益于改进的老鼠心脏模型。最后，更好地结合多尺度信息的能力将使整个临床和小动物成像工作受益，例如缺血、激素刺激、钙循环中断等细胞模型。 下面的三个具体目标总结了在每个领域提出的新的合作建议：现有的和新的细胞模型与现有的心脏有限元模型的集成，结合图像衍生的信息来为特定的患者量身定做这些有限元模型，以及改进小鼠心脏的建模，用于开发和验证转基因模型中的新诊断方法。在每个示例中，将使用一个特定的原型示例来说明预期的方法，但所开发的方法将适用于广泛的类似问题。 与NBCR拟议的协作工作的具体目标是： 1)提高将新的和现有的细胞模型与现有的心脏有限元模型(典型的区域缺血)相耦合的多尺度能力。 2)开发结合图像导出的患者特定功能信息的方法，以生成定制的心脏模型(典型示例密集位移数据)。 3)完成并验证一个全功能的小鼠心脏有限元模型，以补充其他物种的现有模型(小鼠脑梗塞后愈合的原型例子)。 这些目标将依赖于连续性方面拟议的新发展，特别是动态编写和编译细胞收缩和离子模型的能力[4A.2B目标1a]，以及适应患者MRI和CT数据的新模型以及解决和优化患者特定模型的能力[4A.2B目标3]。该合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。

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.