Ferumoxtran-10-enhanced MRI of the hypercholesterolemic rabbit aorta -: Relationship between signal loss and macrophage infiltration

Ferumoxtran-10-enhanced MRI of the hypercholesterolemic rabbit aorta -: Relationship between signal loss and macrophage infiltration
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DOI:
10.1161/01.atv.0000194098.82677.57
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发表时间:
2006-01-01
影响因子:
8.7
通讯作者:
Feldman, LJ
Feldman, LJ
中科院分区:
医学1区
文献类型:
--
作者:
Hyafil, F;Laissy, JP;Feldman, LJ

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目的:Ferumoxtran-10是一种MRI造影剂,在巨噬细胞中蓄积并诱导磁化率伪影(MSA)。我们评估的能力ferumoxtran-10增强MRI定量局灶性巨噬细胞浸润在主动脉壁hypercholesterolemic rabbits.Methods和Results:6周后双球囊损伤的肾下主动脉,12 hypercholesterolemic rabbits进行MRI的主动脉前(第一次MRI)和后(第二次MRI)静脉注射ferumoxtran-10(n = 10)或生理盐水(n = 2)。5天后进行第三次MRI,以检测主动脉壁中ferumoxtran-10诱导的MSA。随后对主动脉进行组织学、免疫组织化学和明胶酶谱研究。损伤的血管内膜富含巨噬细胞,基质金属蛋白酶2和9活性高。损伤血管的铁染色显示Ferumoxtran-10在新生内膜巨噬细胞中大量积聚。注射ferumoxtran-10后5天,通过体内MRI仅在损伤的腹主动脉中检测到MSA,并使用归因于这些MSA在主动脉腔内延伸的管腔面积减少百分比间接定量。结论:Ferumoxtran-10增强MRI可定量评价高胆固醇血症兔主动脉球囊成形术诱导的巨噬细胞浸润。
Objective: Ferumoxtran-10 is an MRI contrast agent, which accumulates in macrophages and induces magnetic susceptibility artifacts (MSAs). We evaluated the ability of ferumoxtran-10-enhanced MRI to quantify focal macrophage infiltration in the aortic wall of hypercholesterolemic rabbits.Methods and Results: Six weeks after a double-balloon injury of the infrarenal aorta, 12 hypercholesterolemic rabbits underwent MRI of the aorta before (first MRI) and after (second MRI) intravenous injection of ferumoxtran-10 (n = 10) or saline (n = 2). A third MRI was performed 5 days later to detect ferumoxtran-10-induced MSA in the aortic wall. Aortas were subsequently processed for histology, immunohistochemistry, and gelatin zymography studies. Injured aortas displayed a macrophage-rich neointima with high-matrix metalloproteinase 2 and 9 activities. Iron stain of injured aortas showed massive accumulation of ferumoxtran-10 in neointimal macrophages. Five days after the injection of ferumoxtran-10, MSAs were detected only in the injured aortas by in vivo MRI and were quantified indirectly using the percentage reduction of luminal area attributable to the extension of these MSAs in the aortic lumen. This parameter correlated with macrophage infiltration on corresponding aortic cross-sections (r = 0.82; P < 0.05).Conclusion: Ferumoxtran-10-enhanced MRI allows quantitative assessment of macrophage infiltration induced by balloon angioplasty in the aorta of hypercholesterolemic rabbits.