Ferumoxtran-10-enhanced MRI of the hypercholesterolemic rabbit aorta: relationship between signal loss and macrophage
Fabien Hyafil1, Jean-Pierre Laissy, Mikael Mazighi
1INSERM U698, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France.
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).
Conclusions:
Ferumoxtran-10-enhanced MRI allows quantitative assessment of macrophage infiltration induced by balloon angioplasty in the aorta of hypercholesterolemic rabbits.
Insights
Ferumoxtran-10 enhanced MRI can quantify macrophage infiltration in rabbit aortas after injury. This method accurately measures macrophage accumulation, aiding in the study of atherosclerosis.
Area of Science:
- Cardiovascular Research
- Medical Imaging
- Immunology
Background:
- Macrophage infiltration is key in atherosclerosis development.
- Accurate quantification of macrophages is crucial for studying vascular disease.
- Ferumoxtran-10 is an MRI contrast agent that targets macrophages.
Purpose of the Study:
- To evaluate ferumoxtran-10 enhanced MRI for quantifying macrophage infiltration in the aortic wall.
- To assess the correlation between MRI findings and histological macrophage counts.
Main Methods:
- Hypercholesterolemic rabbits underwent MRI before and after ferumoxtran-10 injection.
- Magnetic susceptibility artifacts (MSAs) were detected and quantified.
- Aortas were analyzed using histology and immunohistochemistry.
Main Results:
- Ferumoxtran-10 accumulated in neointimal macrophages of injured aortas.
- MSAs were detected in injured aortas 5 days post-injection.
- The MRI-derived parameter for MSAs correlated significantly with macrophage infiltration (r=0.82; P<0.05).
Conclusions:
- Ferumoxtran-10 enhanced MRI provides a quantitative assessment of macrophage infiltration.
- This technique is valuable for studying macrophage-driven processes in the aorta.
