Turner Gregory H, Olzinski Alan R, Bernard Roberta E, Aravindhan Karpagam, Boyle Ryan J, Newman Matt J, Gardner Scott D, Willette Robert N, Gough Peter J, Jucker Beat M
Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
J Magn Reson Imaging. 2009 Aug;30(2):455-60. doi: 10.1002/jmri.21843.
To evaluate the use of an ultrasmall superparamagnetic iron oxide (USPIO) contrast agent as a marker for the detection of macrophage in a preclinical abdominal aortic aneurysm animal (AAA) model.
Osmotic pumps were implanted subcutaneously in apoE(-/-) mice for continuous infusion of Angiotensin II (Ang-II). Weekly bright-blood gradient echo scans were performed on the suprarenal abdominal aorta to evaluate aneurysm development. Once an AAA was detected, animals were administered 1000 mumol/kg of the USPIO contrast agent ferumoxtran-10 (Combidex) followed by in vivo scanning 24 h post-USPIO administration. After in vivo imaging, aortas were harvested for ex vivo imaging, histology, iron quantification, and gene expression analysis.
Reduced signal intensity was evident in the post-USPIO transverse images of the abdominal aorta. The areas of reduced signal were primarily along the aneurysm shoulder and outer perianeurysm areas and corresponded to regions of macrophage infiltration and colocalized USPIO determination by means of histological staining. The absolute iron content measured significantly correlated to the area of signal reduction in the ex vivo images (r = 0.9; P < 0.01). In the AAA tissue, the macrophage-driven cytokine gene expression was up-regulated along with a matrix metalloproteinase known to mediate extracellular matrix breakdown in this disease model.
These results demonstrate the feasibility of using an USPIO contrast agent as a surrogate for detecting the acute inflammatory process involved in the development of abdominal aneurysms.
评估超小型超顺磁性氧化铁（USPIO）造影剂作为临床前腹主动脉瘤动物（AAA）模型中巨噬细胞检测标志物的应用。
将渗透泵皮下植入载脂蛋白E基因敲除（apoE(-/-)）小鼠体内，用于持续输注血管紧张素II（Ang-II）。每周对肾上腹主动脉进行一次亮血梯度回波扫描，以评估动脉瘤的发展情况。一旦检测到AAA，给动物注射1000 μmol/kg的USPIO造影剂ferumoxtran-10（Combidex），然后在注射USPIO后24小时进行体内扫描。体内成像后，采集主动脉进行体外成像、组织学检查、铁定量分析和基因表达分析。
在USPIO注射后的腹主动脉横向图像中，信号强度明显降低。信号降低的区域主要沿着动脉瘤肩部和动脉瘤外周区域，并且通过组织学染色与巨噬细胞浸润区域以及USPIO共定位区域相对应。体外图像中测量的绝对铁含量与信号降低区域显著相关（r = 0.9；P < 0.01）。在AAA组织中，巨噬细胞驱动的细胞因子基因表达上调，同时一种已知在该疾病模型中介导细胞外基质分解的基质金属蛋白酶也上调。
这些结果证明了使用USPIO造影剂作为检测腹主动脉瘤发展过程中急性炎症过程替代物的可行性。
