Targeted CEU Imaging of Atherosclerosis and Angiogenesis

描述(由申请人提供)： 分子和细胞过程成像的非侵入性方法可以在许多方面对医学产生积极影响。这种方法可以用来描述疾病的病理生理学特征，在非常早期的阶段诊断疾病，并评估新的治疗策略。 这项建议的总体目标是探索在临床相关疾病模型中使用对比增强超声(CEU)对动脉粥样硬化和血管生成的分子和细胞介质进行成像的新方法。为了对动脉粥样硬化进行成像，针对内皮细胞黏附分子VCAM-1和P-选择素的微泡造影剂已经被开发出来，以成像导致动脉粥样硬化和斑块不稳定性的血管炎症过程。使用这些试剂的靶向CEU成像将在不同年龄的野生型和Apo-E缺陷小鼠中进行，无论是否喂饲胆固醇，这提供了一种与人类相似的进行性炎性动脉粥样硬化模型。这些数据将决定靶向CEU是否可以用于评估动脉粥样硬化性炎症表型，并检测非常早期的病变发展。为了在空间和时间上评估血管生成，针对新生血管内皮细胞表达的整合素α-vβ-3和参与血管生成的激活单核细胞的微泡CEU将应用于严重周围血管疾病的大鼠后肢缺血模型。在这个模型中，还将确定评估使用成纤维细胞生长因子-2进行促血管生成治疗的能力。 这些研究的成功完成将为一种新的非侵入性诊断技术提供基础，该技术能够成像动脉粥样硬化和血管生成的分子介质。这项技术可能会对诊断和评估治疗反应产生重大影响。CEU可以快速进行，并依赖于相对便宜和广泛可用的成像技术，使其非常适合临床应用和实验室的高通量筛查。 (摘要结束)

DESCRIPTION (provided by applicant): Non-invasive methods for imaging molecular and cellular processes could positively impact medicine in many ways. Such a method could be used to characterize disease pathophysiology, to diagnose disease at a very early stage, and to assess new therapeutic strategies. The overall aim of this proposal is to investigate novel methods for imaging molecular and cellular mediators of atherosclerosis and angiogenesis with contrast-enhanced ultrasound (CEU) in clinically-relevant models of disease. For imaging atherosclerosis, microbubble contrast agents targeted against the endothelial cell adhesion molecules VCAM-1 and P-selectin have been developed in order to image the vascular inflammatory processes that contribute to atherogenesis and plaque instability. Targeted CEU imaging with these agents will be performed in wild-type and Apo-E-deficient mice of different ages, with and without cholesterol feeding, which provides a model of progressive, inflammatory atherosclerosis similar to that found in humans. These data will determine whether targeted CEU can be used to assess atherosclerotic inflammatory phenotype, and to detect very early lesion development. For spatially and temporally assessing angiogenesis, CEU with microbubbles targeted to the integrin alpha-v beta-3 expressed by the neovascular endothelium, and to activated monocytes that participate in angiogenesis, will be applied in a rat ischemic hindlimb model of severe peripheral vascular disease. The ability to assess pro-angiogenic therapy with FGF-2 will also be determined in this model. Successful completion of these studies will provide the basis for a new non-invasive diagnostic technique capable of imaging the molecular mediators of atherosclerosis and angiogenesis. This technique may have a major impact for diagnosis and assessing response to therapy. CEU can be performed rapidly and relies on relatively inexpensive and widely available imaging technology, making it well-suited for clinical applications and for high-throughput screening in the laboratory. (End of Abstract)