Noninvasive multitarget-imaging of vascular inflammation and its progression in atherosclerosis using MRI

动脉粥样硬化及其后遗症对发病率和死亡率有重大影响。发炎的动脉粥样硬化斑块的破裂是一个至关重要的事件，因为它可以导致急性血管闭合。因此，不仅检测具有即将闭合的早期斑块破裂具有临床意义，而且及时检测血管炎症和动脉粥样硬化斑块进展也具有临床意义。本项目的目的是通过非侵入性MRI对反映小鼠血管炎症的不同表位进行成像。使用多标记物/多靶点方法和专用MRI方案，在高脂饮食的ApoE-/--小鼠中斑块进展期间的不同时间点定量LOX-1、VCAM和GPVI的表达。此外，他汀类药物的影响，作为复律剂将通过这种技术进行研究。 所描述的方法将允许在斑块/疾病进展期间对动脉粥样硬化斑块中的炎症活性进行无创体内评价，以及监测药物治疗。该技术不仅对于使用人类相容性造影剂的潜在未来转移到人类中是有意义的，而且对于在动物模型中的动脉粥样硬化炎症活性的非侵入性评估也是有意义的，所述动物模型强调基因敲除或特定治疗对疾病进展的影响

Atherosclerosis and its sequelae have a major impact on morbidity and mortality. The rupture of an inflamed atherosclerotic plaque is a crucial event, since it can result in acute vessel closure. Not only detection of early plaque rupture with imminent closure is therefore of clinical interest, but also timely detection of vascular inflammation and atherosclerotic plaque progression. The aim of this project is to image different epitopes reflecting vascular inflammation by noninvasive MRI in mice. Using a multimarker/multitarget approach and a dedicated MRI protocol, expression of LOX-1, VCAM and GPVI will be quantified at different timepoints during plaque progression in ApoE-/--mice on high fat diet. Furthermore, the influence of statins as antiinflammatory agent will be studied by this technique. The described approach will allow a nonvasive in vivo evaluation of inflammatory activity in atherosclerotic plaques during plaque/disease progression, as well as monitoring of antiinflammatory drug therapy. This technique is not only of interest for a potential future transfer into humans using human compatible contrast agents, but also for the noninvasive evaluation of atherosclerotic inflammatory activity in animal models adressing the influence of knockouts or specific therapies on disease progression