Cellular imaging of blood flow rheological disorders

描述（由申请人提供）： 这项研究计划的重点是发展超声成像方法，以检测和表征体内血流流变性疾病归因于红细胞（RBC）超聚集。已知由血液反向散射的超声信号的强度由RBC聚集调制。理论模型进一步建立了超声信号功率和聚集体体积之间的联系。在人类和动物血管中，RBC聚集体的聚集和解聚受到流动条件以及影响血浆蛋白质含量的病理的存在的动态调节。红细胞聚集在哺乳动物生理学中的流变学影响是众多的，并且涉及宏观和微循环。其中可以引用其对微血管中的淤泥血液的形成、增加血液粘度、血管血栓形成的发生和增加流动阻力的影响。血液执行其主要功能的能力，即运输氧气、二氧化碳、营养物质和代谢产物的能力可能受到异常高水平的RBC聚集的影响。据推测，超声可以提供一种工具，以非侵入性地测量红细胞聚集和血流障碍。具体目标是：1）在大鼠或小鼠模型中，通过超声手段测量由共聚物涂层诱导的RBC聚集的结构变化; 2）通过超声手段测量注射血管活性剂后的内皮血管活性反应，3）通过超声手段测量镰状细胞性贫血和b-地中海贫血小鼠模型中的外周血流阻力，4）通过超声手段测量，通过超声测量RBC聚集水平、超声测量内皮血管活性反应、超声测量外周血流阻力和/或超声测量RBC组织灌注障碍，随访镰状细胞性贫血和b-地中海贫血的遗传疗法的成功。

DESCRIPTION (provided by applicant): This research proposal is focusing on the development of ultrasound imaging methods to detect and characterize in vivo blood flow rheological disorders attributed to red blood cell (RBC) hyper-aggregation. It is known that the intensity of the ultrasound signal backscattered by blood is modulated by RBC aggregation. Theoretical models have further established the link between the ultrasound signal power and the volume of aggregates. In human and animal blood vessels, the aggregation and disaggregation of RBC aggregates are dynamically modulated by the flow condition, and the existence of pathologies affecting the protein content of the plasma. The rheological impacts of RBC aggregation in mammalian physiology are numerous and involve both the macro- and microcirculation. Among them may be cited its effect on the formation of sludge blood in microvessels, increased blood viscosity, occurrence of vascular thrombosis, and increased flow resistance. The ability of blood to perform its main function, i.e. to transport oxygen, carbon dioxide, nutrients and metabolic products can be affected by abnormally high levels of RBC aggregation. It is hypothesized that ultrasound can provide a tool to non-invasively measure RBC aggregation and blood flow disorders. The specific objectives are: 1) To measure, by ultrasonic means, the structural changes in RBC aggregation induced by copolymer coating, in either rat or mouse models; 2) To measure, by ultrasonic means, the endothelial vasoactive response following injection of vasoactive agents, 3) To measure, by ultrasonic means, the peripheral blood flow resistance in mouse models of sickle cell anemia and b-thalassemia, 4) To measure, by ultrasonic means, RBC perfusion disorders with an ultrasonic contrast agent, and 5) To follow-up the success of genetic therapies for sickle cell anemia and b-thalassemia by measuring either the RBC aggregation level with ultrasound, the endothelial vasoactive response with ultrasound, the peripheral blood flow resistance with ultrasound, and/or the RBC tissue perfusion disorders with an ultrasound contrast agent.