Cellular imaging of blood flow rheological disorders

描述(由申请人提供)： 这项研究计划致力于开发超声成像方法来检测和表征由红细胞(RBC)超聚集引起的体内血液流变性疾病。众所周知，血液后向散射的超声信号的强度受红细胞聚集的调制。理论模型进一步建立了超声信号功率与聚集体体积之间的联系。在人和动物的血管中，RBC聚集体的聚集和解聚受到血流条件和影响血浆蛋白质含量的病理因素的动态调节。红细胞聚集对哺乳动物生理的流变学影响是多方面的，涉及到大循环和微循环。其中可列举其在微血管中形成淤泥血、增加血液粘度、发生血管血栓形成和增加流动阻力的作用。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，可能会受到异常高水平的红细胞聚集的影响。据推测，超声可以提供一种非侵入性测量红细胞聚集和血流紊乱的工具。其具体目的是：1)用超声方法测定大鼠和小鼠共聚物包衣后红细胞聚集性的结构变化；2)用超声方法测量注射血管活性物质后的内皮血管活性反应，3)用超声方法测量镰状细胞性贫血和b-地中海贫血小鼠模型的外周血流阻力，4)用超声造影剂测量红细胞灌流障碍，以及5)通过用超声波测量红细胞聚集水平、用超声测量内皮血管活性反应、用超声波测量外周血流阻力和/或用超声造影剂测量红细胞组织灌流障碍来追踪基因治疗镰状细胞性贫血和b-地中海贫血的成功。

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.