基于PET/CT成像技术探讨炎症和力学因素在腹主动脉瘤进展中的作用

The pathogenesis of Abdominal Aortic Aneurysms (AAAs) has not been clearly elucidated, and the current imaging modalities, such as ultrasonography, CT and MRI, though can accurately evaluate the morphological characteristics of AAAs, may not be able to provide information about risk of progression or rupture of AAAs. Current studies now suggest that AAAs are the results of a multifactorial process culminating in chronic inflammation and biomechanical stress. As a multi-imaging modality, Position Emission Tomography/ Computed tomography (PET/CT) can not only evaluate the bio-metabolic state by calculating Standardized Uptake Value (SUV), but obtain high-quality images with excellent resolution for morphological studies. Based on our previous researches on vulnerable plaques detected by PET/CT, we successfully established a rabbit aneurysmal model by intraluminal elastase infusion and conducted the preliminary experiment. Here, we are ready to continue our study on AAAs using the rabbit aneurysmal model, and precipitate the aneurysm formation by sustained hypertension, which is achieved by subcutaneously implanting a mini-pump with angiotensin II. Ultrasonography will be used for monitoring the development of the aneurysms since its high sensitivities and specificities approach 100%. PET will be used for assessment of bio-metabolic state of the focal aneurysm, while CT can provide standardized morphological properties of the aortic wall, and calculating the wall stress and shear stress. By comparing among sham group, AAA group and AAA with hypertension group in mechanical parameters, pathophysiological, histological, immunochemical analysis and RT-PCR results, combined with clinical case study with PET/CT follow-up, we aim at demonstrating the PET/CT characteristics of predicting AAAs progression and rupture, elucidating the comprehensive influences of inflammation, morphology, and wall stress on AAAs formation and progression, and establshing a risk stratification method for clinical assessment.

腹主动脉瘤（AAAs）的病因和进展机制尚不完全明确，也无有效手段预测其进展的风险。炎症和力学因素在AAAs发生和进展中可能起重要作用。在完成PET/CT检测动脉易损斑块研究的基础上，我们建立了胰蛋白酶灌注法诱导腹主动脉瘤的兔模型,并完成了PET/CT活体影像检测预实验。本课题将以兔腹主动脉瘤模型为研究对象，通过慢性血压升高来促进动脉瘤进展，以PET/CT复合成像技术为手段，PET评价动脉壁的代谢水平，检测其炎症状态；CT评价动脉壁和血管腔的形态和结构，并计算管壁应力和剪切力。通过对假手术组、动脉瘤组和高血压动脉瘤组动态观察和比较，并与病理、免疫组化和RT-PCR资料相关性分析，结合临床病例的PET/CT影像和炎症因子检测和随访，揭示动脉瘤进展与稳定状态的PET/CT影像特征，阐明炎症、形态结构和管壁剪切力在AAAs发生和发展中的作用，建立AAAs的危险积分方法，为临床风险预测提供理论基础。

在应用胰蛋白酶灌注法制作兔腹主动脉瘤模型的基础上,用Angll升高血压，促进动脉瘤进展，观察假手术组、动脉瘤组和高血压动脉瘤组的变化，分析腹主动脉瘤管壁组织病理、免疫组化变化特点；并对临床腹主动脉瘤患者进行PET/CT影像、炎症因子检测随访。本研究课题实际制作了75只实验动物的模型，选取了40例腹主动脉瘤患者，共完成了29例患者为期三年的追踪随访。结果如下：.1 我们改进了兔腹主动脉瘤模型的制作方法。研究发现，给予灌注浓度为100U/ml的弹力蛋白酶、灌注保持7-10分钟，是一种可靠的制作兔腹主动脉瘤模型方法。.2 动物研究发现，单用胰蛋白酶方法制作成功的腹主动脉瘤模型随时间的推移度主动脉瘤瘤体直径会逐渐虽小甚至恢复正常，而胰蛋白酶联合Angll制作的腹主动脉瘤则能较长时间的维持瘤体大小形态。.3 动物实验研究显示，术后7天动脉瘤管壁SUVmax与管壁巨噬细胞染色面积百分比、最大直径增长率呈正相关[r=0.459, p=0.042; r=0.468, p=0.037]。术后21天动脉瘤管壁SUVmax与管壁巨噬细胞染色面积百分比及最大直径增长率呈负相关[r=-0.531, p=0.016; r=-0.459, p=0.042]。.4临床研究显示，基线时以及随访2年后PET/CT的SUVmax吸收值与瘤体直径大小均呈正相关。