SPECT/CT Imaging of Systemic AA-Amyloidosis in Mice

超出所提供的空间。高分辨率成像正在成为生物医学研究的宝贵工具，就像它对临床医生一样。在临床上，影像学提供了一种精确的、非侵入性的诊断手段，并直接影响治疗方法和预后。不幸的是，研究人员所要求的高分辨率成像工具的发展落后于临床；因此，体内病理动力学的表征和新型有效治疗方法的后续发展受到阻碍。在淀粉样蛋白相关疾病领域尤其如此，包括阿尔茨海默病、i型糖尿病和原发性（AL）淀粉样变性。如果没有能力在单个动物体内进行纵向研究，就不可能充分认识和理解这些疾病的复杂性，以及它们可能被阻止的方法。为此，开发能够检测和定量体内淀粉样蛋白沉积的高分辨率微成像技术是必要和必要的。我们打算通过设计和应用一种强大的新型双模成像技术来解决这些重要问题，microSPECT结合microCT，由最先进的3d图像重建和分析软件支持。这项新技术将用于识别活体动物的放射性标记淀粉样蛋白沉积，并在内脏地形的高分辨率CT图像中呈现淀粉样蛋白分布。有了这项技术，定量体内器官特异性淀粉样蛋白负荷的目标是可以实现的。因此，目标是：(i)完成高分辨率、小动物专用的双spect /CT成像系统的设计和实现。(二)。开发淀粉样蛋白定量系统，其中显微spect图像数据可以直接与淀粉样蛋白负荷相关。（iii）利用这些技术在两种小鼠模型中研究系统性AA-淀粉样变性的进展及其对新型免疫疗法的反应。这项研究不仅将导致小动物成像和淀粉样蛋白特异性放射性示踪剂领域的技术进步，而且将提供丰富的体内淀粉样变自然进展的信息，并为人类疾病动物模型的治疗药物筛选建立一个范例。此外，淀粉样蛋白特异性成像技术的转化将产生切实的临床效益。PERFORMANCESITE ( ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. High resolution imaging is becoming an invaluable tool in biomedicalresearch much as it has to the clinician. In the clinic, imaging offers a precise, non-invasive means of diagnosis and directly influences both the therapeutic approach and prognosis. Unfortunately, the developmentof high-resolution imaging tools demandedby researchers has lagged behind that of the clinic; thus, characterization of the kinetics of in vivo pathology and the subsequent development of novel, effective therapeutics has been hampered. This is particularly true in the field of amyloid- related diseases which include Alzheimer's disease, type I1 diabetes and primary (AL) amyloidosis. It is impossible to fully appreciate and understand the complexityof these diseases, and the means by which they may be halted, without the ability to perform longitudinal studies in individual animals in vivo. To that end, the developmenthigh- resolution micro-imaging technologies capable of detecting and quantifying amyloid deposits in vivo is warranted and imperative. We intend to address these important issues through the design and application of a powerful new dual-modality imagingtechnology, microSPECT, combined with microCT, supported by state-of-the-art3-D image reconstruction and analysis software. This new technology will be employed to identify radiolabeled amyloid ldeposits in live animals and present the amyloiddistribution within the context of a high-resolution CT image of the 1visceral terrain. With this technology, the goal of quantifying organ-specific amyloid burden in vivo is attainable. IThe goals are thus to: (i) Complete the design and implementation of a high-resolution, small-animal speciJic dual lSPECT/CT imaging system. (ii). Develop a system of amyloid quantijkation in which microSPECT image data can be directly correlated to amyloid burden. (iii) Use these technologies to study the progression of systemic AA- amyloidosis in two murine models and the regression thereof in response to novel immunotherapies. This study will not only result in technological advancements in the field of small-animal imaging and amyloid-specific radio- tracers but will also provide a wealth of information on the natural progression of amyloidosis in vivo and establish a paradigm for the screening of therapeutic drugs in animal models of human disease. Furthermore, the translation of amyloid-specificimagingtechnologies will yield tangible clinicalbenefit. PERFORMANCESITE( ========================================Section End===========================================