Shared Instrumentation: Vevo 770 Ultrasound System

描述（由申请人提供）：当前提案的目标是获得资金，用于购买专为非侵入性小动物研究设计的高分辨率超声显微成像系统。Visualsonics Vevo 770的空间分辨率低至30微米，这是所有其他商用系统的显著优势。该工具最初将支持10个项目，每个项目由一位既定的研究人员指导，并由NIH赠款。这些项目的重点是心血管疾病的体内模型。这些项目的需求各不相同，包括ECHO心动描记术、血管壁结构成像、脉冲多普勒血流测量和用于定量肾内血流和跟踪血管炎症生物标志物的微泡。除了基本的成像单元、计算机和软件之外，还需要一些配件。这些包括1）针对拟议研究中使用的各种应用的各种扫描头：大鼠/小鼠腹部（RMV-703）、小鼠腹部和小小鼠心脏（RMV-706）、成年小鼠心脏（RMV-707 B）和大鼠心脏（RM-710 B），2）具有捕获和分析软件的脉搏波多普勒，3）3D采集和可视化电机和控制软件，以及4）用于维持体温、扫描头定位、ECG和呼吸监测的体内轨道系统。由于每个项目的不同需求，需要不同的扫描头。同样，一些项目需要利用脉冲多普勒功能和/或3D可视化。最后，所有项目都需要使用体内导轨系统，以减少成像期间的运动伪影并保持动物的健康。这种仪器使我们能够在没有手术干预和长时间的情况下定量血流和血管结构。这代表了我们在对各种动物模型进行表型分析和探索与心血管疾病发病机制相关的新机制方面的重大进展。考虑到大鼠在心血管研究中的历史使用和基因操纵小鼠的日益使用，在大鼠和小鼠中使用这种方法的能力特别重要。各种项目的目标包括但不限于确定：1）盐依赖性高血压模型中控制钠排泄的髓质血流变化; 2）代谢疾病中肥胖和胰岛素抵抗对后肢和内分泌器官灌注的影响; 3）心力衰竭时下丘脑室旁核中兴奋性和抑制性突触传递的平衡如何受到影响; 4）血管紧张素II、P2 X1和A1受体产生的肾血流量的长期变化; 5）NOS 1是否有助于调节血管重塑和控制钠排泄; 6）血小板分泌是否是急性损伤后和动脉粥样硬化期间血栓形成和炎症过程的关键介导物; 7）生物钟基因是否调节狭窄动脉中的血管重塑。 公共卫生相关性：当前提案的目标是获得资金用于购买高分辨率超声显微成像系统Visualsonics Vevo 770，该系统专门用于可视化活体大鼠和小鼠的解剖结构，血管动力学和心脏功能，而无需任何手术干预。在啮齿动物中进行类似于在人类中进行的非侵入性程序的能力将为我们的研究计划提供一个独特的进步，该研究计划高度关注心血管转化研究领域。

DESCRIPTION (provided by applicant): The goal of the current proposal is to obtain funds for the purchase of a high-resolution ultrasound micro- imaging system designed specifically for non-invasive small animal research. The Visualsonics Vevo 770 offers spatial resolution down to 30 microns, a significant advantage over all other commercially available systems designed for human use. The instrument will initially support ten projects, each directed by an established investigator and funded by NIH grants. These projects focus on in vivo models of cardiovascular disease. The needs of these projects are varied and include ECHO cardiography, vascular wall structural imaging, pulse Doppler flow measurements, and microbubbles for quantification of intrarenal blood flow and tracking biomarkers of vascular inflammation. In addition to the basic imaging unit, computer, and software, there are several accessories that are required. These include 1) a variety of scan heads that are specific for the various applications used in the proposed studies: rat/mouse abdominal (RMV-703), mouse abdominal & small mouse cardiac (RMV-706), adult mouse cardiac (RMV-707B), and rat cardiac (RM-710B), 2) pulse wave Doppler with capture and analysis software, 3) 3D acquisition and visualization motor and control software, and 4) in vivo rail system for maintaining body temperature, scan head positioning, ECG and respiration monitoring. The different scan heads are required because of the different needs of each project. Similarly, several projects need to take advantage of the pulse Doppler capabilities and/or the 3D visualization. Finally, all projects will need to use the in vivo rail system for reducing movement artifacts and maintaining health of the animals during imaging. This instrumentation gives us the ability to quantitate blood flow and vascular structure without surgical intervention and over prolonged periods of time. This represents a major advance in our capabilities to phenotype various animal models and explore novel mechanisms related to the pathogenesis of cardiovascular disease. The ability to use this methodology in both rats and mice is particularly important given the historical use of rats in cardiovascular research and the growing use of genetically manipulated mice. The goals of the various projects include but are not limited to determining: 1) changes in medullary blood flow that control of sodium excretion in salt-dependent models of hypertension; 2) the impact of obesity and insulin resistance on hindlimb and endocrine organ perfusion in metabolic disease; 3) how the balance of excitatory and inhibitory synaptic transmission in the hypothalamic paraventricular nucleus is influenced in heart failure; 4) long-term changes in renal blood flow produced by angiotensin II, P2X1, and A1 receptors; 5) whether NOS1 contributes to regulation of vascular remodeling and control of sodium excretion; 6) whether platelet secretion is a key mediator of thrombotic and inflammatory processes after acute injury and during atherosclerosis; 7) if the biological clock gene regulates vascular remodeling in stenotic arteries. PUBLIC HEALTH RELEVANCE: The goal of the current proposal is to obtain funds for the purchase of a high-resolution ultrasound micro imaging system, Visualsonics Vevo 770, designed specifically for visualizing anatomical structures, vascular dynamics, and cardiac function within living rats and mice without any surgical intervention. The ability to conduct non-invasive procedures in rodents similar to what is done in humans will provide a distinct advance in our research program that is highly focused in the area of cardiovascular translational research.