Monitoring the biological activity of abdominal aortic aneurysms Beyond Ultrasound

Abstract

Abdominal aortic aneurysms (AAAs) are an important cause of morbidity and, when ruptured, are associated with >80% mortality. Current management decisions are based on assessment of aneurysm diameter by abdominal ultrasound. However, AAA growth is non-linear and rupture can occur at small diameters or may never occur in those with large AAAs. There is a need to develop better imaging biomarkers that can identify the potential risk of rupture independent of the aneurysm diameter. Key pathobiological processes of AAA progression and rupture include neovascularisation, necrotic inflammation, microcalcification and proteolytic degradation of the extracellular matrix. These processes represent key targets for emerging imaging techniques and may confer an increased risk of expansion or rupture over and above the known patient-related risk factors. Magnetic resonance imaging, using ultrasmall superparamagnetic particles of iron oxide, can identify and track hotspots of macrophage activity. Positron emission tomography, using a variety of targeted tracers, can detect areas of inflammation, angiogenesis, hypoxia and microcalcification. By going beyond the simple monitoring of diameter expansion using ultrasound, these cellular and molecular imaging techniques may have the potential to allow improved prediction of expansion or rupture and to better guide elective surgical intervention.

Figure 1

Comparison of pathobiological characteristics of atherosclerosis and abdominal aortic aneurysm (AAA) disease. While AAA disease shares similar pathobiological processes involved in atherosclerotic disease, there are notable distinctions. In particular, the location of the disease processes is an important difference, with atherosclerosis affecting primarily the vessel intima, whereas AAA disease has a predilection for the media and adventitia. The resulting clinical manifestation is that AAA disease causes vessel dilatation and rupture, whereas atherosclerosis leads to vessel stenosis occlusion. However, the common ground between these two pathological conditions means that molecular imaging techniques thus far used in the study of atherosclerotic vessels (such as the coronary and carotid arteries) may prove useful in the study of AAA disease.

Figure 2

Biological targets and potential molecular imaging techniques in abdominal aortic aneurysm (AAA) disease. As well as patient factors (such as smoking, hypertension and advancing age) that contribute to the risk of AAA formation, biological processes have been identified that are implicit in aneurysm formation. The key processes are illustrated above, along with the corresponding molecular imaging techniques (written in green arrows) that have been used in experimental or clinical studies to date (primarily in the coronary arteries). The combination of patient-related risk factors and biological processes leads to increased wall stress and decreased wall strength (which can be investigated using computational modelling techniques), and all of these factors lead to aneurysm expansion and vulnerability to rupture.

Figure 3

Magnetic resonance imaging (MRI) using ultrasmall superparamagnetic particles of iron oxide (USPIO) in abdominal aortic aneurysm disease. This technique is currently being investigated in the MA³RS study (MRI in Abdominal Aortic Aneurysms to Predict Rupture or Surgery—ISRCTN76413758).

Figure 4

¹⁸F-NaF positron emission tomography–computed tomography (PET-CT) in abdominal aortic aneurysm disease. This technique is currently being investigated in the SoFIA³ study (Sodium Fluoride Imaging (¹⁸F-NaF PET-CT) in Abdominal Aortic Aneurysms—NCT02229006).