Molecular imaging of pathophysiologic processes in aortic disease

Background:

Diseases of the aorta are relatively common and potentially fatal. Although aortic disease can be detected at an early stage, there are limited possibilities to hinder disease progression, as the pathophysiologic processes involved are poorly understood. In previous research supported by HLF, we have studied the possibility to visualize the pathological processes in the aortic wall with molecular imaging using a combination of positron emission tomography (PET) and magnetic resonance imaging (MRI), and link this to disease progress.

Aims:

To assess the possibility to predict aortic disease progression based on molecular imaging findings at the early stages of the disease. Additionally, to evaluate the possibility to monitor the effect of medical intervention on aortic wall pathology. Work plan: The project involves two main themes:

1) Established PET-MRI markers of aortic disease: We have previously been able to identify PET-MRI markers of aortic wall inflammation in large aneurysms, as well as in acute aortic dissection. In a longitudinal cohort study, we aim to assess presence of inflammation in the aortic wall in early stages of the disease in a cohort of patients, and follow these individuals over time to evaluate disease progression and identify markers for rapid versus slow progress.

Additonally we aim to evaluate the effect of medical intervention with established cardiovascular drugs on changes in aortic wall inflammation.

2) Evaluation of a new PET-tracer for aortic wall degradation: We have been involved in development of a new PET tracer for elastase activity. We aim to evaluate this tracer as a marker of the aortic wall degradation process in aortic aneurysm formation. If successful, the tracer will be further studied in the longitudinal cohort studies and intervention studies depicted above.

The project involves the Departments of Vascular Surgery, Radiology, Pharmaceutical Radiochemistry and Medical and Cell Biology at Uppsala University. Clinical significance:

The concept of molecular imaging for evaluation of vessel wall disease activity is increasingly established in the cardiovascular field. In aortic disease, where the pathophysiologic processes involved in disease progress are not fully understood, molecular imaging offers a unique possibility for evaluation of disease activity. Successful imaging of aortic wall pathology would enable a possibility to further develop medical intervention for aortic disease.