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

高分辨率 3D 超声成像

• 批准号: 7888306
• 负责人: John A Hossack
• 金额: $ 35.82万
• 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/7888306
• 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来提供人类心血管疾病的模型。基础心血管研究的很大一部分涉及心脏对心肌梗塞 (MI) 的解剖和生理反应。迫切需要改进非侵入性成像方法，以精细的空间和时间分辨率量化心肌功能，以便区分心肌内水平的壁功能，并表征与 MI 后坏死组织相邻的“边界区”的精确位置和性质。拟议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与由此产生的可测量现象之间复杂相互作用的时间演变。这项工作包括结合使用新的图像处理技术和数学模型拟合来对壁功能（即应变、收缩功能）进行 4D（3D + 时间）评估。此外，我们计划绘制缺血事件后内皮表面出现的特定细胞粘附分子（即 PECAM 和选择素）的存在情况。最后，我们将检验这样的假设：在诱导型一氧化氮合酶 (iNOS) 敲除 (KO) 小鼠中，MI 后区域间不同步（通过高分辨率超声检测）将会减少。具体目标是： A.1 开发能够进行精细空间（<100 um）和时间（8000 帧/秒）分辨率 3D 跟踪的仪器，用于使用采集的 2D 数据和小鼠心脏 3D 数学模型的正交集来评估应变， A.2 开发自动组织分析技术：“主动轨迹场模型”，通过超声心动图图像恢复 4D（3D + 时间）心肌运动。 4D 心肌变形模型，A.3 开发 MI 引起的炎症分子标记物的 3D 绘图方法，特别是：血小板/内皮细胞粘附分子-1 (PECAM) 和 P/E 选择素，A.4 检验以下假设：与 iNOS 敲除小鼠相比，远端左心室 MI 后晚期发生的心脏不同步将显着减少。 野生型小鼠。从广义上讲，拟议的工作涉及开发改进的小鼠心脏成像技术，这将有助于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最终可能会改善人类心血管疾病患者的治疗。公共卫生相关性：心血管研究在很大程度上依赖于小鼠物种来提供人类心血管疾病的模型。基础心血管研究的很大一部分涉及追踪心肌梗死 (MI) 后心肌的解剖和生理反应。迫切需要改进非侵入性成像方法，以精细的空间和时间分辨率量化心肌功能，以便区分心肌内水平的壁功能，并表征 MI 后坏死组织附近的“边界”或“危险”区域的精确位置和性质。拟议的工作涉及开发改进的小鼠心脏成像技术，这将有助于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最终可能会改善对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。