Murine ultrasound imaging for circumferential strain analyses in the angiotensin II abdominal aortic aneurysm model

Abstract

Objective The underlying causes of abdominal aortic aneurysms (AAAs) remain obscure, although research tools such as the angiotensin II (Ang II) apolipoprotein E-deficient (apoE−/−) mouse model have aided investigations. Longitudinal imaging and determination of biomechanical forces in this small-scale model have been difficult. We hypothesized that high-frequency ultrasound biomicroscopy combined with speckle-tracking analytical strategies can be used to define the role of circumferential mechanical strain in AAA formation in the Ang II/apoE−/− mouse model of AAAs. We simultaneously examined dietary perturbations that might impact the biomechanical properties of the aortic wall, hypothesizing that the generalized inflammatory phenotype associated with diet-induced obesity would be associated with accelerated loss of circumferential strain and aneurysmal aortic degeneration. Methods Receiving either a 60 kcal% fat Western diet or standard 10 kcal% fat normal chow, Ang II-treated apoE−/− mice (n = 34) underwent sequential aortic duplex ultrasound scan imaging (Vevo 2100 System; VisualSonics, Toronto, Ontario, Canada) of their entire aorta. Circumferential strains were calculated using speckle-tracking algorithms and a custom MatLab analysis. Results Decreased strains in all aortic locations after just 3 days of Ang II treatment were observed, and this effect progressed during the 4-week observation period. Anatomic segments along the aorta impacted wall strain (baseline highest in ascending aorta; P < .05), whereas diet did not. At 2 and 4 weeks, there was the largest progressive decrease in strain in the paravisceral/supraceliac aorta (P < .05), which was the segment most likely to be involved in aneurysm formation in this model. Conclusions In the Ang II/apoE−/− aneurysm model, the aorta significantly stiffens (with decreased strain) shortly after Ang II infusion, and this progressively continues through the next 4 weeks. High-fat feeding did not have an impact on wall strain. Delineation of biomechanical factors and AAA morphology via duplex scan and speckle-tracking algorithms in mouse models should accelerate insights into human AAAs.

Multi-Modality Imaging Enables Detailed Hemodynamic Simulations in Dissecting Aneurysms in Mice

“…Thus, the increased resolution of the combined US-OCT approach allowed us to demarcate better the false lumen boundaries, even allowing detection of a small (0.08 mm 3 ) volume for M2 that was not visible on 3D US images but was evident with histology. This demarcation is in contrast to previous studies that have used US alone and have not been able to delineate the composition of the aortic wall or the inner and outer aortic diameters [7]. …”

“…Whereas the aforementioned studies focused on imaging-based models for computing normal hemodynamics, both US [7, 18] and MRI [19–22] have also been used to assess lesion growth or wall strain in the AngII infusion model of dissecting aneurysms. Favreau et al [7] used high-frequency US alone, which did not allow them to “accurately differentiate between the intraluminal and extraluminal aortic wall.” To the best of our knowledge, only Ford et al [23] have built mouse-specific US imaging-based models of hemodynamics within such lesions.…”

“…Favreau et al [7] used high-frequency US alone, which did not allow them to “accurately differentiate between the intraluminal and extraluminal aortic wall.” To the best of our knowledge, only Ford et al [23] have built mouse-specific US imaging-based models of hemodynamics within such lesions. Their study was carried out using a single-element transducer with an equivalent 40 μm axial and 90 μm lateral spatial resolution (RMV704 transducer, Vevo770).…”

Acute reductions in mechanical wall strain precede the formation of intimal hyperplasia in a murine model of arterial occlusive disease

“…35 We have previously presented a method to measure cyclic wall strains on the murine aortic wall to assess the changes in wall strain during aneurysm formation. 25 In this study, we translated our previously reported methods to assess strain in a murine model of IH.…”

“…23 In the current study, we hypothesized that there is a direct positive relationship between reduced cyclic arterial wall strain and the formation of intimal hyperplasia. To test this hypothesis, we combined a validated murine model of intimal hyperplasia 24 with a recently developed method for measuring arterial wall strains in vivo 25 to unravel the relationship between wall strain and neointima formation.…”