High-Resolution 3D Ultrasound Imaging & Quantification of Murine Cardiac Function

高分辨率 3D 超声成像

• 批准号: 7662633
• 负责人: John A Hossack
• 金额: $ 33.21万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-05 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7662633
• 关键词: Action Potentials; Adherence; Algorithms; Anatomy; Antibodies; Apical; Appearance; Blood Platelets; C57BL/6 Mouse; CD31 Antigens; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cell Adhesion Molecules; Cicatrix; Complex; Contrast Media; Coronary; Data; Data Analyses; Data Set; Development; Doctor of Philosophy; Electrocardiogram; Event; Evolution; Fibrosis; Figs - dietary; Frequencies; Functional disorder; Future; Gap Junctions; Generic Drugs; Goals; Grant; Health; Heart; Heart Diseases; Heart Hypertrophy; Human; Image; Imagery; Imaging Techniques; Infarction; Inflammation; Knock-out; Knockout Mice; Knowledge; Laboratories; Lateral; Left Ventricular Remodeling; Left ventricular structure; Ligands; Link; Location; Manuals; Maps; Measurable; Mediating; Medical; Medical Device; Methods; Microbubbles; Modality; Modeling; Molecular Target; Motion; Mus; Muscle Cells; Myocardial; Myocardial Infarction; Myocardium; Nature; Necrosis; Noise; Patients; Performance; Pharmacotherapy; Physiological; Process; Prolate; Radio; Recovery; Reperfusion Therapy; Research; Research Personnel; Resolution; Risk; Sampling; Scanning; Selectins; Shapes; Slice; Solutions; Structure; Surface; Techniques; Technology; Testing; Thick; Time; Tissues; Training; Translating; Ultrasonography; United States National Institutes of Health; Variant; Wild Type Mouse; Work; active method; base; design; heart imaging; human NOS2A protein; image processing; imaging modality; improved; innovation; instrument; instrumentation; interest; mathematical model; molecular imaging; molecular marker; mouse model; prevent; programs; public health relevance; research study; response; spatiotemporal; success; two-dimensional; vector

DESCRIPTION (provided by applicant): Modern cardiovascular research relies on the mouse species for providing a model for human cardiovascular disease. A significant portion of basic cardiovascular research relates to the anatomic and physiological response of the heart to myocardial infarction (MI). There is a pressing need for improvements in noninvasive imaging methods for quantifying myocardial function with fine spatial and temporal resolution so as to differentiate wall function at the intramyocardial level and to characterize the precise location and nature of the "border zone" adjacent to the post MI necrotic tissue. The long term goals of the proposed work are to develop the instrumentation and techniques for investigating noninvasively the time evolution of the complex interactions between a coronary ischemic event and resulting measurable phenomena. The work encompasses 4D (3D + time) assessment of wall function (i.e. strain, contractile function) using a blend of new image processing techniques and mathematical model fitting. Additionally, we plan to map the presence of specific cell adhesion molecules (i.e., PECAM and selectin) that are presented on the endothelial surface following an ischemic event. Finally, we will test the hypothesis that inter-regional dyssynchrony post-MI (as detected by high-resolution ultrasound) will be reduced in inducible Nitric Oxide Synthase (iNOS) knock out (KO) mice. The Specific Aims are to: A.1 Develop instrumentation enabling fine spatial (<100 um) and temporal (8000 frame/s) resolution 3D tracking for assessing strain using orthogonal sets of acquired 2D data and 3D mathematical models of the murine heart, A.2 Develop an automated tissue analysis technique: "active trajectory field models" to recover 4D (3D + time) myocardial motion from echocardiographic imagery via a 4D myocardial deformation model, A.3 Develop methods for 3D mapping of the molecular markers of inflammation resulting from MI - specifically: Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM) and P/E Selectin, and A.4 Test the hypothesis that the cardiac dyssynchrony that develops late after MI in the remote LV will be markedly reduced in iNOS knock-out mice vs. wild-type mice. Broadly speaking, the proposed work involves developing improved techniques for mouse heart imaging that will facilitate more precise mouse-based heart disease research. The knowledge gained using experiments on mice may ultimately result in the improved management of human cardiovascular disease patients. PUBLIC HEALTH RELEVANCE: Cardiovascular research relies heavily on the mouse species for providing a model for human cardiovascular disease. A significant proportion of basic cardiovascular research relates to tracking the anatomic and physiological response of the heart muscle post myocardial infarction (MI). There is a pressing need for improvements in noninvasive imaging methods for quantifying myocardial function with fine spatial and temporal resolution so as to differentiate wall function at the intramyocardial level and to characterize the precise location and nature of the "border", or "at-risk", zone in vicinity of post MI necrotic tissue. The proposed work involves developing improved imaging techniques for mouse hearts that will facilitate more precise mouse-based heart disease research. The knowledge gained using experiments on mice may ultimately result in improved management of human cardiovascular disease patients. This knowledge may help direct the development of new drug therapies or medical devices related to heart health management.

描述（由申请人提供）：现代心血管研究依赖于小鼠物种为人类心血管疾病提供模型。心血管基础研究的一个重要部分涉及心脏对心肌梗死（MI）的解剖和生理反应。迫切需要改进无创成像方法，以精细的空间和时间分辨率量化心肌功能，以区分心肌内水平的壁功能，并表征心肌梗死后坏死组织附近“边界区”的精确位置和性质。这项工作的长期目标是开发仪器和技术，用于无创地研究冠状动脉缺血事件和由此产生的可测量现象之间复杂相互作用的时间演变。这项工作包括使用新的图像处理技术和数学模型拟合的混合对墙体功能（即应变，收缩功能）进行4D （3D +时间）评估。此外，我们计划绘制在缺血事件后出现在内皮表面的特定细胞粘附分子（即PECAM和选择素）的存在。最后，我们将验证一个假设，即在诱导型一氧化氮合酶（iNOS）敲除（KO）小鼠中，心肌梗死后区域间不同步（通过高分辨率超声检测）会减少。具体目标是：A.1开发能够实现精细空间（<100微米）和时间（8000帧/秒）分辨率3D跟踪的仪器，用于使用获得的2D数据和小鼠心脏的3D数学模型的正交集来评估应变；A.2开发自动化组织分析技术；通过4D心肌变形模型从超声心动图图像中恢复4D （3D +时间）心肌运动的“主动轨迹场模型”，a .3开发心肌梗死引起炎症的分子标记物的3D制图方法，特别是血小板/内皮细胞粘附分子-1 （PECAM）和P/E选择素，a .4验证iNOS敲除小鼠与野生型小鼠相比，远端左室心肌梗死后晚期发生的心脏不同步运动明显减少的假设。总的来说，拟议的工作包括开发改进的小鼠心脏成像技术，这将促进更精确的基于小鼠的心脏病研究。通过小鼠实验获得的知识可能最终导致改善人类心血管疾病患者的管理。公共卫生相关性：心血管研究在很大程度上依赖于为人类心血管疾病提供模型的小鼠物种。很大一部分心血管基础研究涉及心肌梗死后的解剖和生理反应的跟踪。迫切需要改进无创成像方法，以精细的空间和时间分辨率量化心肌功能，以区分心肌内水平的壁功能，并表征心肌梗死后坏死组织附近“边界”或“危险”区域的精确位置和性质。拟议的工作包括开发改进的小鼠心脏成像技术，这将促进更精确的基于小鼠的心脏病研究。通过小鼠实验获得的知识可能最终导致改善人类心血管疾病患者的管理。这些知识可能有助于指导与心脏健康管理相关的新药物疗法或医疗设备的开发。