Cardiovascular disease is the leading cause of death and disability in the world. Non-invasive imaging has become vital for the detection and monitoring of disease progression, aiding in the development of therapeutics and devices. Our research is at the interface of engineering and medicine as we work to develop and use multiple imaging modalities to better understand cardiac and vascular disease. With continued efforts, we hope to eventually make a positive impact on the clinical care of patients.
Our laboratory has a VisualSonics Vevo 2100 small animal ultrasound system. Previous efforts have focused on in vivo abdominal aortic motion using M-mode ultrasound. We have found in a cross-species study that vessel wall dynamics are similar in animals and humans regardless of aortic size, with more anterior than posterior wall motion. The results suggest increased dynamic strain in the anterior wall and may correspond to increased elastin fatigue in this region (Goergen, et al., JEVT, 2007). A second study used similar ultrasound methods to quantify the differences in aortic motion in mice with genetic deletions mimicking Williams-Beuren syndrome. Altered elastin gene expression, blood pressure, vessel structure, and abdominal aortic wall dynamics in vivo all suggest vascular abnormalities in these animals that resemble the human disease (Goergen, et al., JVR, 2010).
An abdominal aortic aneurysm (AAA) is a pathological expansion of the aorta. We studied two established experimental models of this disease in an article published in the Animal Models of Human Pathology issue of BioMed Research International (Phillips, et al. BMRI 2015). The elastase perfusion model leads to fusiform AAAs with focally degraded elastin, while angiotensin II infusion in apolipoprotein-E-deficient animals causes spontaneous dissecting AAAs with a saccular shape. We presented our findings of the changes in morphological, biomechanical, and hemodynamic characteristics occurring in each model over 28 days using in vivo ultrasound. Volumetric growth, reduced vessel strain, and altered blood flow dynamics were quantified in both models. Furthermore, we used nonlinear optical microscopy to observe the changes in elastin and collagen in AAA tissues as compared to healthy aorta ex vivo.
We are also developing techniques to image murine abdominal aortic motion using magnetic resonance (Goergen, et al., JMRI, 2010). In this work, we found that abdominal aortic motion and curvature were significantly larger and more leftward above the renal vessels than below in mice. These methods were then used to measure abdominal aortic aneurysm progression in two different murine models (Goergen, et al., ATVB, 2011). The results suggested the direction of angiotensin II (AngII)-induced aneurysm expansion correlated with the direction of motion, medial elastin dissection, and adventitial remodeling (Figure 1). Conversely, anterior infrarenal aortic motion correlated with medial elastin degradation in elastase-induced aneurysms. Results from both models suggest a relationship between aneurysm pathological features and aortic geometry and motion.
We have focused on the development of optical imaging techniques for the study of cardiac disease. Previous work has shown that lifetime-based time domain fluorescence imaging can distinguish liver and heart signals using a protease-activatable fluorochrome (Goergen, et al., JBO, 2012). The results suggest that fluorescence lifetime contrast can improve the accuracy of in vivo fluorescence imaging of the myocardium (Figure 2). Other work of ours has used optical coherence tomography (OCT) to detect changes in the left ventricle due to ischemic injury in mice ex vivo (Goergen, et al., OL, 2012). Our efforts have shown that optical clearing and volumetric imaging techniques have significant advantages over histology where complex fiber architecture needs to be preserved.
Our future research will continue to focus on multi-modality physiologic and molecular imaging of the cardiovascular system. With funding from Purdue University, federal research grants, and industry collaborators, we hope to further our understanding of heart and vascular disease, leading to improvements in patient care and quality of life.