Molecular UBM and MRI of Vascular Development

血管发育的分子 UBM 和 MRI

• 批准号: 8769741
• 负责人: Daniel H Turnbull
• 金额: $ 16.85万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8769741
• 关键词: Address; Adult; Anatomy; Animal Model; Animals; Area; Atherosclerosis; Avidin; Binding; Biological; Biotin; Biotinylation; Birth; Blood Vessels; Blood flow; Brain; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cell physiology; Cell surface; Cells; Contrast Media; Defect; Development; Diabetes Mellitus; Disease; Disease Progression; Embryo; Embryonic Development; Event; Future; Gene Expression; Gene Targeting; Genes; Genetic; Genetically Engineered Mouse; Health; Heart; Histology; Human Development; Image; Imagery; Injection of therapeutic agent; Investigation; Knockout Mice; Label; Laboratories; Life; Link; Liver; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Membrane Proteins; Microbubbles; Modeling; Molecular; Morphology; Motion; Mus; Mutation; Nature; Nucleic Acid Regulatory Sequences; Optical Methods; Optics; Organ; Pathogenesis; Pattern; Penetration; Physiological; Play; Proteins; Protocols documentation; Regulatory Element; Reporter; Reporting; Research; Resolution; Respiration; Role; Rotation; Specimen; Staging; Surface; System; Testing; Three-dimensional analysis; Time; Tissues; Transgenes; Transgenic Mice; Transgenic Organisms; Translations; Ultrasonographic Biomicroscopy; Ultrasonography; Uterus; Vascular Endothelial Cell; Vascular System; Virus; body system; cardiovascular imaging; design; fetal; flexibility; heart imaging; heart motion; hemodynamics; human disease; imaging modality; improved; in utero; in vivo; insight; interest; molecular imaging; mouse genome; mouse model; neovascularization; novel; optical imaging; reconstruction; tool; transgene expression

DESCRIPTION (provided by applicant): Over the past decade, investigations using genetically-engineered mice have led to new insights into the genetic control of embryonic vascular development, which has also had a major impact on our understanding of neovascularization in many human diseases including cancer, atherosclerosis and diabetes. Micro-imaging methods such as ultrasound biomicroscopy (UBM) and magnetic resonance micro-imaging (micro-MRI) can play an important role in this research, enabling direct in utero visualization of the developing mouse embryo. To date, there has been relatively little progress in the area of molecular imaging with ultrasound and MRI, especially in the area of vascular development. UBM is a real time imaging method enabling noninvasive in vivo analysis of mouse embryonic cardiovascular anatomy and hemodynamics, and can also be applied for image-guided intravascular injection of contrast agents. Micro-MRI provides better 3D resolution and more flexibility than UBM in manipulating cellular/tissue contrast, including more available contrast agents and approaches for cell-targeted imaging, but requires longer acquisition times, and has only recently been demonstrated for effective in utero imaging of mouse embryos. Several reports have recently demonstrated that biotinylation of cell surfaces can be achieved, allowing cell-targeted imaging with avidin-conjugated contrast agents, which are now available for both ultrasound and MRI. This is an attractive option for imaging vascular endothelial cells (VECs), since contrast agents can be delivered to the cells of interest via intravascular injection, even at embryonic stages of development. Moreover, the binding between avidin and biotin is the strongest found in nature, which should make it possible to label vascular cells even in the face of high wall shear rates associated with arterial blood flow. The specific aims of this project are: 1) To optimize the micro-MRI protocols required for in utero analysis of cardiovascular development; 2) To produce transgenic mice designed for targeted imaging of VECs with UBM and micro-MRI; and 3) To establish VEC-targeted micro-MRI approaches for improved analyses of embryonic vasculature. The approaches developed in this project will provide powerful new tools for direct analysis of vascular development in living mouse embryos. Significantly, these new molecular imaging methods will provide, for the first time, the ability to detect vascular gene expression in utero in normal and genetically-engineered mice.

描述（由申请人提供）：在过去的十年中，使用遗传学工程小鼠进行的调查导致了对胚胎血管发育的遗传控制的新见解，这也对我们对许多人类疾病的新生血管化的理解产生了重大影响，包括癌症，动脉粥样硬化和糖尿病。微成像方法，例如超声生物显微镜（UBM）和磁共振微成像（微-MRI）可以在这项研究中起重要作用，从而直接可以直接地可视化发育​​中的小鼠胚胎。迄今为止，超声和MRI的分子成像区域的进展相对较少，尤其是在血管发育领域。 UBM是一种实时成像方法，可实现小鼠胚胎心血管解剖结构和血液动力学的体内分析，也可以用于图像引导的对比剂的血管内注射。在操纵细胞/组织对比度中，Micro-MRI比UBM提供了更好的3D分辨率和更高的灵活性，包括更多可用的对比剂和用于细胞靶向成像的方法，但需要更长的获取时间，并且直到最近才在小鼠胚胎的子宫内成像有效证明。最近有几份报告表明，可以实现细胞表面的生物素化，从而可以使用抗生蛋白蛋白偶联的对比剂进行细胞靶向成像，该对比剂现在可用于超声和MRI。这是成像血管内皮细胞（VEC）的有吸引力的选择，因为即使在发育的胚胎阶段，对比度也可以通过血管内注射传递到感兴趣的细胞。此外，抗原素和生物素之间的结合是自然界中最强的，即使面对与动脉血流相关的高壁剪切速率，这也可以标记血管细胞。该项目的具体目的是：1）优化心血管发育分析所需的微MRI方案； 2）生产用于使用UBM和Micro-MRI的VEC靶向成像的转基因小鼠； 3）建立了靶向vec的微MRI方法，以改善胚胎脉管系统的分析。该项目中开发的方法将为直接分析活小鼠胚胎的血管发育提供强大的新工具。值得注意的是，这些新的分子成像方法将首次提供在正常和遗传工程小鼠中检测子宫内血管表达的能力。