背景:动物或临床模型中急性深静脉血栓形成(DVT)或血栓后综合征(PTS)的影像学评估仅限于对血栓位置和范围的解剖学评估。我们假设铁磁共振成像,用于评估其他炎症性疾病中的巨噬细胞含量,可用于评估DVT后随时间的血栓炎症特征。
方法:19只野生型CD-1小鼠接受手术IVC结扎以诱导DVT。小鼠接受生理盐水或5mg/kg的因子XI抑制剂14E11,在程序之前。结扎后第6-7天进行Fe-MRI以评估血栓体积,灌注,和巨噬细胞含量通过T2加权图像。在手术后第3-15天对小鼠实施安乐死。切除血栓和邻近的静脉壁,称重,福尔马林固定,和石蜡包埋的免疫组织学分析。标本用特异性抗体染色以评估巨噬细胞含量,胶原蛋白沉积,新生血管形成,和再通。使用Mann-WhitneyU或Student'st检验确定显著性。
结果:对照小鼠IVC结扎后,从第3天到第15天,血栓重量减少了59%.血栓体积在第5天达到峰值,然后在第13天下降85%。FXI抑制导致血栓(p=.008)和静脉壁(p=.01)的巨噬细胞含量降低,血栓体积减少(p=0.03),与对照小鼠相比,血栓质量降低(p=0.01)。CCR2+染色证实了这些发现,显示在血栓(p=0.002)和静脉壁(p=0.002)中存在显著减少的巨噬细胞。
结论:Fe-MRIT2弛豫时间可用于表征和量化血栓后灌注的变化,巨噬细胞含量,在静脉血栓形成的手术小鼠模型中,血栓体积随时间的变化。这种方法可以更好地量化体内炎症,从而解决血栓和静脉内的单核细胞和巨噬细胞含量,并且可以作为研究和临床评估血栓形成后环境的有用工具。
BACKGROUND: Imaging evaluation of acute deep vein thrombosis (DVT) or post-thrombotic syndrome (PTS) in animal or clinical models is limited to anatomical assessment of the location and extent of thrombi. We hypothesize that Fe-MRI, used to evaluate macrophage content in other inflammatory diseases, can be useful to evaluate the thromboinflammatory features after DVT over time.
METHODS: Nineteen wild-type CD-1 mice underwent surgical IVC ligation to induce DVT. Mice received either saline or 5 mg/kg of 14E11, a Factor XI inhibitor, before the procedure. Fe-MRI was performed on days 6-7 after ligation to evaluate thrombus volume, perfusion, and macrophage content via T2-weighted images. Mice were euthanized at days 3-15 after surgery. The thrombi and adjacent vein walls were excised, weighed, formalin-fixed, and paraffin-embedded for immunohistological analysis. Specimens were stained with specific antibodies to evaluate macrophage content, collagen deposition, neovascularization, and recanalization. Significance was determined using the Mann-Whitney U or Student\'s t-test.
RESULTS: After IVC-ligation in control mice, thrombus weights decreased by 59 % from day 3 to 15. Thrombus volumes peaked on day 5 before decreasing by 85 % by day 13. FXI inhibition led to reduced macrophage content in both thrombi (p = .008) and vein walls (p = .01), decreased thrombus volume (p = .03), and decreased thrombus mass (p = .01) compared to control mice. CCR2+ staining corroborated these findings, showing significantly reduced macrophage presence in the thrombi (p = .002) and vein wall (p = .002).
CONCLUSIONS: Fe-MRI T2 relaxation times can be used to characterize and quantify post-thrombotic changes of perfusion, macrophage content, and thrombus volume over time in a surgical mouse model of venous thrombosis. This approach could lead to better quantification of in vivo inflammation correlating monocyte and macrophage content within resolving thrombi and veins and may serve as a useful tool for research and clinically in the evaluation of the post-thrombotic environment.