Abstract

Abdominal aortic aneurysms (AAAs) are currently one of the leading causes of death in developed countries. Inflammation is crucial in the disease progression, having a substantial impact on various determinants in AAAs development. Magnetic particle imaging (MPI) is an innovative imaging modality, enabling the highly sensitive detection of magnetic nanoparticles (MNPs), suitable as surrogate marker for molecular targeting of vascular inflammation. For this study, Apolipoprotein E-deficient-mice underwent surgical implantation of osmotic minipumps with constant Angiotensin II infusion. After 3 and 4 weeks respectively, in-vivo-magnetic resonance imaging (MRI), ex-vivo-MPI and ex-vivo-magnetic particle spectroscopy (MPS) were performed. The results were validated by histological analysis, immunohistology and laser ablation-inductively coupled plasma-mass spectrometry. MR-angiography enabled the visualization of aneurysmal development and dilatation in the experimental group. A close correlation (R = 0.87) with histological area assessment was measured. Ex-vivo-MPS revealed abundant iron deposits in AAA samples and ex-vivo histopathology measurements were in good agreement (R = 0.76). Ex-vivo-MPI and MPS results correlated greatly (R = 0.99). CD68-immunohistology stain and Perls’-Prussian-Blue-stain confirmed the colocalization of macrophages and MNPs. This study demonstrates the feasibility of ex-vivo-MPI for detecting inflammation in AAA. The quantitative ability for mapping MNPs establishes MPI as a promising tool for monitoring inflammatory progression in AAA in an experimental setting.

Highlights

  • Abdominal aortic aneurysms (AAAs) are currently one of the leading causes of death in developed countries

  • There are several different approaches for detecting inflammation in AAA. 18F-fluorodeoxyglucose (FDG) is a radiopharmaceutical tracer for positron emission tomography (PET) and PET computed tomography (CT), targeting high-glucose-using cells including macrophages in aneurysm inflammatory sites, yet it relies on ionizing ­radiation[14]

  • In the experimental group (n = 23), the continuous infusion of angiotensin II (Ang II) via osmotic minipumps led to the formation of suprarenal aortic aneurysms (Figs. 1, 2)

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Summary

Introduction

Abdominal aortic aneurysms (AAAs) are currently one of the leading causes of death in developed countries. CD68-immunohistology stain and Perls’-Prussian-Blue-stain confirmed the colocalization of macrophages and MNPs. This study demonstrates the feasibility of ex-vivo-MPI for detecting inflammation in AAA. Chronic inflammation is characterized by the infiltration of inflammatory cell types, mainly macrophages and monocytes in the thrombus and throughout all layers of the aortic ­wall[3]. These cells release several proteolytic enzymes such as matrix metalloproteinases, cytokines and oxidation-derived free radicals, leading to vascular smooth muscle cell apoptosis and degradation of the aortic tunica m­ edia[3]. MNPs are internalized into macrophages/monocytes and represent a promising target for molecular imaging of inflammation and predicting aneurysm g­ rowth[8,9,10]. A reference scan before MNP injection is required to perform quantification

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