Early Detection of Aortic Degeneration in a Mouse Model of Sporadic Aortic Aneurysm and Dissection Using Nanoparticle Contrast-Enhanced Computed Tomography.
Early Detection of Aortic Degeneration in a Mouse Model of Sporadic Aortic Aneurysm and Dissection Using Nanoparticle Contrast-Enhanced Computed Tomography.
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DOI：
10.1161/atvbaha.120.315210
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
LeMaire SA
中科院分区：
文献类型：
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作者：
Ghaghada KB;Ren P;Devkota L;Starosolski Z;Zhang C;Vela D;Stupin IV;Tanifum EA;Annapragada AV;Shen YH;LeMaire SA
早期发现主动脉变性对于改善主动脉瘤和夹层（AAD）患者的结局至关重要。我们研究了纳米粒子对比增强计算机断层扫描（n-CECT）用于主动脉损伤的早期检测。在散发性AAD的小鼠模型中，用高脂饮食和血管紧张素II输注激发C57 BL/6 J小鼠（n=20）。未激发的对照小鼠接受标准实验室饮食和盐水输注（n=19）。进行CT血管造影（CTA）以评价主动脉扩大，并进行延迟n-CECT（CTD）成像以检测指示主动脉壁变性的壁信号增强。显示CTD结果但CTA显示正常的主动脉节段被称为临床前主动脉疾病。根据切除的腹主动脉瘤的大体检查确定AAD的发展。通过组织学和免疫荧光（IF）分析检查主动脉变性和炎症。伊文思蓝（EB）染料泄漏到主动脉壁中用于验证血管通透性的变化。在激发小鼠中，在41%的主动脉节段中发现主动脉疾病的大体发现。33%的主动脉节段的CTA结果为轻度疾病（扩张）和晚期疾病（存在假腔的AAD）。CTD显示63%的主动脉节段壁信号增强。其中48%在CTA上表现正常。CTD发现的主动脉节段在组织学和IF分析中显示主动脉壁变性和炎症。IF分析和EB染料摄取表明，由于内皮损伤导致的纳米颗粒造影剂被动泄漏是CTD检测主动脉疾病的潜在机制。在小鼠中，CTD成像显示出在CTA中血管扩张变得明显之前检测主动脉壁变性和炎症的高灵敏度。
Early detection of aortic degeneration is critical for improving outcomes in patients with aortic aneurysm and dissection (AAD). We investigated nanoparticle contrast-enhanced computed tomography (n-CECT) for the early detection of aortic injury. In a mouse model of sporadic AAD, C57BL/6J mice were challenged with a high-fat diet and angiotensin II infusion (n=20). Unchallenged control mice received a standard laboratory diet and saline infusion (n=19). CT angiography (CTA) was performed to evaluate aortic enlargement, and delayed n-CECT (CTD) imaging was performed to detect wall signal enhancement indicative of aortic wall degeneration. Aortic segments that exhibited CTD findings but appeared normal on CTA were termed preclinical aortic disease. AAD development was determined upon the gross examination of excised aortas. Aortic degeneration and inflammation were examined by performing histologic and immunofluorescence (IF) analyses. Leakage of Evans Blue (EB) dye into aortic wall was used to validate changes in vascular permeability. In challenged mice, gross findings of aortic disease were found in 41% of aortic segments. CTA findings of mild disease (dilatation) and advanced disease (AAD with the presence of false lumen) were seen in 33% of aortic segments. CTD findings of wall signal enhancement were seen in 63% of aortic segments. Of those, 48% appeared normal on CTA. Aortic segments with CTD findings showed aortic wall degeneration and inflammation on histologic and IF analyses. IF analysis and EB dye uptake suggested passive leakage of nanoparticle contrast agent due to endothelial injury as a potential mechanism underlying the detection of aortic disease on CTD. In mice, CTD imaging exhibits high sensitivity for detecting aortic wall degeneration and inflammation before vessel enlargement becomes evident in CTA.