Cellular imaging of blood flow rheological disorders

血流流变疾病的细胞成像

• 批准号: 6950818
• 负责人: GUY CLOUTIER
• 金额: $ 9.71万
• 依托单位: UNIVERSITY OF MONTREAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-22 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6950818
• 关键词: acetylcholine; angiocardioultrasonography; bioimaging /biomedical imaging; biomaterial interface interaction; blood flow measurement; cardiovascular disorder diagnosis; cardiovascular imaging /visualization; cell aggregation; contrast media; copolymer; diagnosis design /evaluation; disease /disorder model; erythrocytes; laboratory mouse; laboratory rat; molecular /cellular imaging; nitroferricyanide; sickle cell anemia; thalassemia; vasomotion

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.

描述（由申请人提供）： 该研究建议的重点是开发超声成像方法，以检测和表征归因于红细胞（RBC）超聚集的体内血流流变障碍。众所周知，由RBC聚集调节了由血液反向散射的超声信号的强度。理论模型进一步建立了超声信号功率与骨料量之间的联系。在人类和动物血管中，RBC聚集体的聚集和分解是通过流动条件动态调节的，并且存在影响血浆蛋白质含量的病理。 RBC聚集在哺乳动物生理学中的流变学影响很多，并且涉及宏观和微循环。其中可能会引用其对微血管中污泥血的形成，血液粘度的增加，血管血栓形成的发生以及增加的流动阻力的影响。血液执行其主要功能的能力，即运输氧气，二氧化碳，营养和代谢产物的能力可能会受到异常高水平的RBC聚集的影响。假设超声可以为非侵入性测量RBC聚集和血流障碍提供工具。特定目标是：1）通过超声均值测量大鼠或小鼠模型中共聚物涂层引起的RBC聚集的结构变化； 2）用超声均值测量注射血管活性剂后的内皮血管活性反应，3）通过超声均值测量镰状细胞贫血和b-丘脑贫血的小鼠模型中的外周血流阻力，4），以测量，测量，测量，测量，测量，测量，测量，测量，测量，测量通过超声均值，具有超声造影剂的RBC灌注障碍和5）通过测量超声测量RBC聚集水平，以超声测量镰状细胞贫血和b- thalassymia的遗传疗法的成功，即内皮血管活性响应，并具有超声波反应，超声检查的外周血流动阻力和/或带有超声对比剂的RBC组织灌注障碍。