High-resolution MR flow imaging for the characterization of arterial haemodynamics as an indicator of cellular pathomechanisms in early atherogenesis

动脉粥样硬化发病机制的非侵入性评估是开发新的治疗和诊断程序以改善心血管疾病的治疗和预防的重要工具。特别是，高分辨率磁共振成像是研究心血管系统的形态和功能参数的主要技术。由于血管功能的改变可能代表结构重塑的先兆，它们特别适合作为早期诊断标记物。然而，由于小鼠模型中的磁共振成像对空间和时间分辨率提出了很高的要求，因此需要高效的成像技术。近年来，我们和其他人在血管壁的功能磁共振成像、血管力学和局部炎症的可视化方面取得了重要进展。为了能够对整个主动脉区域的局部血管壁参数进行高分辨率检测，必须加速和优化现有的成像方法。拟议的项目的目标是开发基于高分辨率MR测量技术的新技术，用于在动脉粥样硬化的早期阶段评估和表征血管壁。一个特别的重点将是研究局部力学参数的变化，如脉搏波速度、壁面剪应力和血管阻抗。体外动脉模型提供了生理和病理条件的受控环境，因此特别适合于开发和验证新的检查方法。不同的流动动力学将通过高分辨率的MRT来实现和表征，它们对血管生理的影响将被深入到分子生物学水平。此外，动脉模型的扩展是为了提供生物因素对血管血流动力学的反应的信息。在进一步的过程中，功能成像将与分子和高分辨率的形态磁共振成像相结合，以研究对动脉粥样硬化发展的不同影响。早期诊断标记物随后将用于在动脉粥样硬化小鼠模型的纵向研究中评估动脉粥样硬化形成的生理过程。对动脉粥样硬化早期致病机制的了解有望成为制定治疗和预防措施的基础。

The non-invasive assessment of the pathomechanisms of atherosclerosis is an important tool for the development of new therapeutic and diagnostic procedures to improve the treatment and prevention of cardiovascular diseases. In particular, high-resolution MR imaging is a predominant technique for the investigation of morphological and functional parameters of the cardiovascular system. Since changes in the vascular function may represent precursors of structural remodeling, they are particularly suitable as an early diagnostic marker. As MR imaging in the mouse model, however, imposes high requirements on the spatial and temporal resolution, highly efficient imaging techniques are necessary. In recent years important advances could be achieved in functional MR imaging of the vessel wall, vascular mechanics and the visualization of local inflammation, by us and others. To enable high-resolution detection of local vessel wall parameters over the entire area of the aorta, existing imaging methods have to be accelerated and optimized.The goal of the proposed project is the development of new techniques for the assessment and characterization of the vessel wall in early stages of atherosclerosis, based on high resolution MR measurement techniques. A particular focus will be the study of local changes of mechanical parameters such as pulse wave velocity, wall shear stress and vascular impedance. In vitro arterial models provide a controlled environment of physiological and pathological conditions and thus are particularly suitable for the development and validation of new examination methods. Different flow dynamics are to be realized and characterized by means of highly resolved MRT, and their effects on the vessel physiology are to be examined down to a molecular biology level. Moreover, the extension of the arterial model to an atherosclerosis model is intended to provide information on the reaction of biological factors on the vessel hemodynamics.In the further course, functional imaging will be combined with the molecular and high-resolution morphological MR imaging in order to examine different influences on the development of atherosclerosis. Early diagnostic markers will subsequently be used to assess physiological processes of atherogenesis in longitudinal studies in atherosclerosis mouse models. Knowledge of the pathogenic mechanisms in the early stages of atherosclerosis is expected to serve as a basis for the development of therapeutic and prophylactic measures.