IN VIVO MICROCT SYSTEM

描述（由申请人提供）：我们拟购买一种高分辨率微型计算机断层扫描（microCT）系统，用于小动物（小鼠、大鼠）的体内成像。VivaCT 40系统（Sévio Medical）的最大空间分辨率为10 μ m，适用于小鼠骨小梁显微结构、皮质厚度和血管钙化成像。MicroCT已成为小鼠骨骼研究中骨形态（尤其是骨小梁）定量离体评估的标准。通过体内microCT，我们将microCT的优势扩展到纵向评估。我们已经确定了一个由12名研究人员组成的主要和次要用户组，代表六个部门（解剖学和神经生物学，生物学，医学，分子生物学和药理学，整形外科，病理学）。该工具将立即使五个研究所（NIAMS，NCI，NICHD，NIDDK，NHLBI）的14个NIH赠款资助的项目受益。主要用途包括：在1500只来自重组和高级杂交近交系的小鼠中评估骨骼表型，所述重组和高级杂交近交系用于绘制调节糖尿病、肥胖和骨特性的基因图谱;评估骨质疏松小鼠中和损伤性疲劳负荷后对机械负荷的骨骼响应;评估成骨细胞特异性缺失差距连接蛋白连接蛋白43的小鼠中对负荷和卸载的骨骼响应;监测高脂饮食小鼠主动脉中血管钙化的进展，并操纵调节促成骨BMP 2-Msx 2-Wnt信号级联的基因。该仪器将促进统计学上强大的纵向（重复测量）研究设计，以监测目前不可能执行的骨骼变化，除非使用低分辨率方法，如DXA。此外，通过减少每个时间点对多组的需求，体内扫描将在多个项目中更有效地利用现有的人类和动物资源。最后，获得体内microCT仪器赠款将有助于在华盛顿大学建立一个肌肉骨骼研究中心的长期目标。相关性：对体内microCT扫描仪的支持将有利于正在进行的研究，这些研究旨在了解调节糖尿病和骨质疏松症等疾病的基因，以及了解糖尿病背景下血管钙化的进展。这也将有利于旨在了解骨骼如何响应机械力的研究，这反过来将有助于发现提高骨质疏松症骨密度和强度的策略。

DESCRIPTION (provided by applicant): We propose to purchase a high-resolution micro-computed tomography (microCT) system for in vivo imaging of small animals (mouse, rat). The VivaCT 40 system (Scanco Medical) has a maximal spatial resolution of 10 ¿m, making it appropriate for imaging trabecular bone microstructure, cortical thickness and vascular calcification in mice. MicroCT has become the standard for quantitative ex vivo assessment of bone morphology (especially of trabecular bone) in skeletal studies in mice. With in vivo microCT we will extend the benefits of microCT to longitudinal assessment. We have identified a major and minor user group of 12 investigators that represent six departments (Anatomy & Neurobiology, Biology, Medicine, Molecular Biology & Pharmacology, Orthopaedic Surgery, Pathology). The instrument will immediately benefit projects that are funded by 14 NIH grants from five Institutes (NIAMS, NCI, NICHD, NIDDK, NHLBI). Major uses include: assessing skeletal phenotypes in 1500 mice from recombinant and advanced intercross inbred strains used to map genes that regulate diabetes, obesity and bone properties; assessing skeletal responses to mechanical loading in osteoporotic mice and after damaging fatigue loading; assessing skeletal responses to loading and unloading in mice with osteoblast-specific deletion of the gap junction protein connexin43; monitoring the progression of vascular calcification in the aorta of mice on high fat diets and with manipulation of genes regulating the pro-osteogenic BMP2-Msx2-Wnt signaling cascade. The instrument will facilitate statistically powerful, longitudinal (repeated measures) study designs to monitor skeletal changes that are currently impossible to perform, except with low resolution methods such as DXA. In addition, by reducing the need for multiple groups for each timepoint, in vivo scanning will create more efficient utilization of existing human and animal resources across multiple projects. Finally, acquisition of the in vivo microCT instrumentation grant will contribute to the long-term goal of developing a Center for Musculoskeletal Research at Washington University. Relevance: Support of an in vivo microCT scanner will benefit ongoing research studies aimed at understanding the genes that regulate diseases such as diabetes and osteoporosis, as well as understanding how vascular calcification progresses in the context of diabetes. It will also benefit studies aimed at understanding how the skeleton responds to mechanical forces, which will in turn will contribute to discovery of strategies to enhance bone density and strength in osteoporosis.