The general context of this dissertation is to evaluate patient-specific approaches to the risk of rupture of abdominal aortic aneurysm (AAA), using imaging techniques with ability to assess biological processes. Following a thorough description of available imaging techniques, our work is divided in two main research objectives, namely: (i) to provide greater clinical value to existing but unproven imaging concepts, and (ii) to suggest new concepts for improved AAA risk of rupture assessment.
The first research objective evaluated how far imaging biological activities using 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) and modeling wall stress using finite element simulations (FES) may help clinical decision-making in patients with AAA, and what would be their incremental value as compared to diameter-based patient management algorithms. On a patient basis, clinical outcomes were evaluated with regard to FDG PET and FES signaling. Further, the concept of AAA risk-equivalent diameter using FES was described and retrospectively validated using data from large multicenter trials. The second research objective included the assessment of the biological activities of the intraluminal thrombus (ILT) and the demonstration of its deleterious role in AAA using multimodality imaging. A special emphasis was put on the ability of magnetic resonance imaging (MRI) to monitor the biological activities of ILT without exogenous contrast, by evaluating its iron content.
Increased FDG uptake was a diameter-independent marker of AAA-related events over 2 years. Missing dichotomy prevented such a finding for increased wall stress, although its correlation with increased FDG uptake indicates a potentially comparable value in terms of risk management. Wall metabolism is influenced by patient-specific susceptibility factors, indicating hereditary or acquired alteration of the biological responses to wall stress. The concept of risk-equivalent diameters on FES links biomechanical estimates to basic conclusions drawn from large diameter-based clinical AAA trials. Our retrospective and diameter-adjusted validation analysis verified that biomechanical risk indicators are higher in ruptured than non-ruptured AAAs. Part of the FDG uptake is associated with biological activity along the luminal surface of the ILT, where we experimentally demonstrated phagocytosis of superparamagnetic iron oxide on MRI , both ex vivo and in vivo. This phagocytosis is correlated with the abundance of leukocytes and proteolytic activity. In addition, unenhanced MRI appearances resulting from the endogenous iron distribution within ILT also relate to these biological activities. Lastly, multimodality imaging was used to confirm the concept of the deleterious role of the ILT in AAA growth in a model of AAA by infusion of elastase in the rat.
MRI and FDG PET are capable of evidencing and quantifying in vivo some of the notoriously deleterious biological processes taking place in the aneurysmal sac, especially related to the entrapped phagocytes and red blood cells in ILT and the periadventitial inflammatory response. The central role played by ILT and its biological activities was demonstrated in vivo using several imaging techniques. The clinical value of imaging these biological activities is epitomized by a diameter-independent 2-year increased risk of event in AAA with increased wall metabolism.