Cellular imaging of blood flow rheological disorders

血流流变疾病的细胞成像

基本信息

批准号：
7278174
负责人：
GUY CLOUTIER
金额：
$ 9.23万
依托单位：
UNIVERSITY OF MONTREAL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-22 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7278174
关键词：
Abnormal Hemoglobins Acetylcholine Acute Address Affect Alleles Anemia Animal Model Animals Bioenergetics Biological Biophysics Blood Blood Circulation Blood Pressure Blood Vessels Blood Viscosity Blood flow Calorimetry Carbon Dioxide Cell Adhesion Cell Aggregation Cell Communication Cell membrane Cells Cerebral Ischemia Chemistry Chronic Clinical Collection Condition Contrast Media Development Disease Disodium Salt Nitroprusside Effectiveness Endothelial Cells Endothelium Endothelium-Dependent Relaxing Factors Environmental sludge Erythrocytes Genes Globin Goals Hand Hemoglobin Heterozygote Human Image Imaging technology Impairment In Vitro Individual Inherited Injection of therapeutic agent Invasive Knock-out Lesion Ligands Link Longevity Lower Extremity Measurement Measures Mechanics Medicine Metabolic Methods Microcirculation Microscopic Modeling Molecular Abnormality Mus Mutation Nature Neutrons Nitric Oxide Nutrient Organ Paper Pathology Patients Perfusion Pharmacologic Substance Physiology Plasma Pluronics Production Property Proteins Publishing Quality of life Rattus Reporting Research Research Proposals Resistance Roentgen Rays Shapes Sickle Cell Sickle Cell Anemia Signal Transduction Structure Syndrome System Techniques Thalassemia Theoretical model Thermodynamics Thrombosis Tissues Ulcer Ultrasonics Ultrasonography Vasodilator Agents cellular imaging copolymer follow-up gene therapy in vivo laser tweezer light scattering mouse model novel oxygen transport peripheral blood physical property polymerization polypeptide programs protein structure research study response sensor sickling success tool vasoactive agent

项目摘要

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）：该研究计划的重点是开发超声成像方法来检测和表征红细胞（RBC）过度聚集引起的体内血流流变障碍。已知血液反向散射的超声信号的强度由红细胞聚集调节。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，红细胞聚集体的聚集和解聚受到流动条件和影响血浆蛋白质含量的病理的存在的动态调节。红细胞聚集对哺乳动物生理学的流变学影响很多，涉及宏观循环和微循环。其中可以提到的是它对微血管中淤血的形成、血液粘度增加、血管血栓形成和流动阻力增加的影响。血液执行其主要功能（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，超声波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。具体目标是： 1) 在大鼠或小鼠模型中，通过超声波方法测量共聚物涂层诱导的红细胞聚集的结构变化； 2) 通过超声方法测量注射血管活性药物后的内皮血管活性反应， 3) 通过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) 测量， 5) 通过测量红细胞聚集水平来跟踪镰状细胞性贫血和 B 地中海贫血基因治疗的成功超声检查、超声检查的内皮血管活性反应、超声检查的外周血流阻力和/或超声造影剂的红细胞组织灌注障碍。