Noninvasive imaging of vascular permeability to predict the risk of rupture in abdominal aortic aneurysms using an albumin-binding probe

Lisa C Adams,Bernd Hamm,Carolin Reimann,Kristin Nowak,Rene M Botnar,Uwe Karst,Rebecca Buchholz,Julia Brangsch,Marcus R Makowski,Jan O Kaufmann

doi:10.1038/s41598-020-59842-2

Abstract

Abdominal aortic aneurysm (AAA) remains a fatal disease. Its development encompasses a complex interplay between hemodynamic stimuli on and changes in the arterial wall. Currently available biomarkers fail to predict the risk of AAA rupture independent of aneurysm size. Therefore, novel biomarkers for AAA characterization are needed. In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance imaging (MRI) with an albumin-binding probe to assess changes in vascular permeability at different stages of aneurysm growth. Two imaging studies were performed: a longitudinal study with follow-up and death as endpoint to predict rupture risk and a week-by-week study to characterize AAA development. AAAs, which eventually ruptured, demonstrated a significantly higher in vivo MR signal enhancement from the albumin-binding probe (p = 0.047) and a smaller nonenhancing thrombus area compared to intact AAAs (p = 0.001). The ratio of albumin-binding-probe enhancement of the aneurysm wall to size of nonenhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%). More advanced aneurysms with higher vascular permeability demonstrated an increased uptake of the albumin-binding-probe. These results indicate that MRI with an albumin-binding probe may enable noninvasive assessment of vascular permeability in murine AAAs and prediction of rupture risk.

Highlights

Abdominal aortic aneurysm (AAA) poses an increasing burden on healthcare systems and is among the challenges currently facing society, with prevalence ranging from 5% to 10% in Western populations[1]
To evaluate the potential of delayed-enhancement magnetic resonance imaging (MRI) using gadofosveset as a prognostic tool for aneurysm rupture, we performed a longitudinal study of ApoE−/− mice with gadofosveset imaging after 1 week of angiotensin II (AngII) infusion and with fatal aneurysm rupture as the endpoint
We observed that, while there was no significant difference in aneurysm size (p = 0.061), increased enhancement (CNR) of the aneurysm wall in combination with the absence of nonenhancing intraluminal thrombus was associated with an increased rupture risk

Summary

Introduction

Abdominal aortic aneurysm (AAA) poses an increasing burden on healthcare systems and is among the challenges currently facing society, with prevalence ranging from 5% to 10% in Western populations[1]. The main limitation of aneurysm diameter as the primary criterion for intervention is that it fails to account for smaller aneurysms with high rupture risk and for large unruptured AAAs10. This is further complicated by the scarcity of longitudinal data on ruptured AAAs, as most patients are followed up until meeting criteria for intervention, while prior AAA existence is often unknown in patients presenting with rupture. Noninvasive magnetic resonance imaging (MRI) with its high spatial resolution for evaluation of the aortic wall and aneurysm components is a promising tool in this context[12]. Based on a mouse model of AAA, this study investigates, firstly, if in vivo MRI with gadofosveset could allow assessment of vascular permeability at different stages of AAA and, secondly, if it might allow prediction of AAA rupture

Methods

Results

Conclusion