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

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. 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. AAA development is a multifactorial, mainly degenerative process encompassing a complex interplay between hemodynamic stimuli on and changes in the arterial wall, including endothelial dysfunction 2-7. Rupture of AAA is a life-threatening complication and surgical emergency with high mortality 1. While larger (≥55 mm), symptomatic, or fast-growing (>10 mm/year) AAAs are recommended to undergo endovascular or operative repair as the only available treatment options, patients with smaller AAAs, who are considered to have a lower risk of rupture, are often monitored with non-invasive imaging 8. By contrast, the management of medium-sized AAAs remains controversial 9. Apart from diameter and growth rate, there is currently no recognized biomarker for evaluating AAA characteristics and rupture risk 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 also for large

Simultaneous molecular MRI of extracellular matrix collagen and inflammatory activity to predict abdominal aortic aneurysm rupture

“…For AAA, similar findings could apply. Our findings from a previous study on AAA using an albumin-binding probe already suggested an increased vascular permeability in murine AAA 25 . Another benefit in molecular imaging studies could be obtained by using quantitative MRI protocols, which would not only allow to visualize, but also to quantify the molecular probes used.…”

Effect of Doxycycline on Survival in Abdominal Aortic Aneurysms in a Mouse Model

“…As an albumin-binding extracellular contrast agent, gadofosveset showed a strong signal in the disrupted areas of the aneurysm wall in all animals, which could be quantified by CNR. e protective effect in the doxycycline group was shown, as expected, by a significantly reduced CNR in the gadofosveset-enhanced MR angiography compared to the untreated control group from the previous study [21]. is could be interpreted as a sign of reduced endothelial damage in this group and thus reduced leakage of albumin and consecutively gadofosveset into the aneurysm wall.…”

“…Noninvasive imaging techniques such as magnetic resonance imaging have already been successfully used to evaluate structural components of AAA and potential rupture risks in a mouse model [20][21][22].…”

Elastin-specific MRI of extracellular matrix-remodelling following hepatic radiofrequency-ablation in a VX2 liver tumor model

“…LA-ICP-MS was performed for quantitative elemental imaging of Gd, Fe, Zn, and P as described previously 43 , 44 . To determine the gadolinium distribution within the periablational rim following the injection of the elastin-specific gadolinium-based agent, x-ray spectra were acquired in the gadolinium distribution and the gadolinium distribution was mapped.…”