Atlas-Based Structural Models of the Mouse Myocardium

描述（由申请人提供）：基于心肌结构模型的生物力学和电生理学计算研究提供了对正常和患病心脏功能的宝贵见解，超出了经验性实验。然而，到目前为止，心脏的计算模型很少，大多数现有的模型在方法上受到传统组织学技术的劳动密集型和破坏性的阻碍。更重要的是，由于以前的模型是从有限数量的标本中构建的，因此它们在多大程度上代表了“典型”心脏，即使是相同物种，性别，年龄和收缩状态，也是不清楚的。这些挑战对于小鼠心脏的结构模型来说是加剧的，因为它的物理尺寸很小，尽管该物种通常是研究人类疾病的病理生理学和治疗的首选。目前的提案旨在通过开发和结合先进的高分辨率MRI采集方法和基于图像的人群“图谱”分析技术来满足这些关键需求。总体假设是，可以从有限数量的弥散MRI数据集构建代表不同性别、品系、年龄和心动周期的正常小鼠心肌的结构模型。具体目标包括（1a）开发减少的k空间采样数据的多维约束重建并优化扩散编码方案以加速扩散成像扫描时间，（1b）增强扩散MRI用于表征心肌结构的效用，（2a）构建并验证正常小鼠心肌的静态结构图谱，（2b）应用遗传映射研究小鼠心脏结构图谱的性别和基因型依赖性，（2c）结合联合收割机和遗传映射研究正常小鼠心脏的成熟适应性调节，（3）通过对静态结构模型进行超弹性Warping分析，生成了经过验证的正常跳动小鼠心肌的动态结构模型。公共卫生相关性：本提案的总体目标是构建正常小鼠心脏的结构图谱，这些图谱代表了不同性别、品系、年龄和心脏收缩状态的物种。本研究的结果将为正常和病变心脏的解剖学、电生理学和生物力学的计算研究提供必要的基础。

DESCRIPTION (provided by applicant): Computational studies, both biomechanical and electrophysiological, based on structural models of the myocardium have provided valuable insight into the functions of both normal and diseased hearts beyond empirical experimentation. However, to date, few computational models of the heart are available, and most existing models are methodologically hampered by the labor-intensive and destructive nature of conventional histological techniques. More importantly, since previous models were constructed from limited numbers of specimens, the degree to which they represent the "typical" heart, even of the same species, gender, age and contractile state, is unclear. These challenges are exacerbated for structural models of the mouse heart because of its small physical size, despite that the species is often preferred for investigating the pathophysiology and treatment of human diseases. The current proposal seeks to address these critical needs by developing and combining advanced high-resolution MRI acquisition methods and imaged-based population "atlas" analysis techniques. The overall hypothesis is that structural models representative of the normal mouse myocardium across gender, strain, age, and cardiac cycle can be constructed from a finite number of diffusion MRI datasets. Specific aims include (1a) develop multi-dimensional constrained reconstruction of reduced k- space sampling data and optimize diffusion-encoding schemes to accelerate diffusion imaging scan time, (1b) enhance the utility of diffusion MRI for characterizing myocardial structures, (2a) construct and validate static structural atlases of the normal mouse myocardium, (2b) apply diffeomorphic mapping to investigate the gender and genotype-dependence of mouse heart structural atlases, (2c) combine group regression analysis and diffeomorphic mapping to investigate the maturational adaptive modulation of the normal mouse heart, and (3) generate validated dynamic structural models of the beating normal mouse myocardium by applying Hyperelastic Warping analysis to static structural models. PUBLIC HEALTH RELEVANCE: The overall aim of this proposal is to construct structural atlases of the normal mouse heart that are representative of the species regardless of gender, strain, age, and cardiac contractile state. Results of this research will provide essential foundations for computational studies of the anatomy, electrophysiology and biomechanics of both normal and diseased hearts.