Monitoring and Staging Abdominal Aortic Aneurysm Disease With Pulse Wave Imaging

Abstract

The Abdominal Aortic Aneurysm (AAA) is a silent and often deadly vascular disease caused by the localized weakening of the arterial wall. Previous work has shown that local changes in wall stiffness can be detected with Pulse Wave Imaging (PWI), which is a noninvasive technique for tracking the propagation of pulse waves along the aorta at high spatial and temporal resolutions. This study aims at assessing the capability of PWI to monitor and stage AAA progression in a murine model of the disease. ApoE/TIMP-1 knockout mice (N = 18) were given angiotensin II for 30 days via subcutaneously implanted osmotic pumps. The suprarenal sections of the abdominal aortas were imaged every 2-3 days after implantation using a 30 MHz Visualsonics Vevo 770 with 115 μm lateral resolution. Pulse wave propagation was monitored at an effective frame rate of 8 kHz by using retrospective electrocardiogram (ECG) gating and by performing 1-D cross-correlation on the radio-frequency (RF) signals to obtain the displacements induced by the waves. In normal aortas, the pulse waves propagated at constant velocities (2.8±0. 9 m/s, r2 = 0.89±0.11), indicating that the composition of these vessels was relatively homogeneous. In the mice that developed AAAs (N = 10), the wave speeds in the aneurysm sac were 45% lower (1.6±0.6 m/s) and were more variable (r2 = 0.66±0.23). Moreover, the wave-induced wall displacements were at least 80% lower within the sacs compared to the surrounding vessel. Finally, in mice that developed fissures (N = 5) or ruptures (N = 3) at the sites of their AAA, higher displacements directed out of the lumen and with no discernible wave pattern (r2 < 0.20) were observed throughout the cardiac cycle. These findings show that PWI can be used to distinguish normal murine aortas from aneurysmal, fissured, and ruptured ones. Hence, PWI could potentially be used to monitor and stage human aneurysms by providing information complementary to standard B-modes.

Assessing the Stability of Aortic Aneurysms with Pulse Wave Imaging

“…In agreement with previous work (19)(20)(21), the differences between aneurysm sacs and normal tissue are easily detected with PWI. From a qualitative perspective, the pulse waves propagate less uniformly in aneurysms and have lower displacement amplitudes, while from a quantitative perspective, PWV and the standard deviation of local PWV change significantly in aneurysms.…”

“…Previous work with the animal model used in this study has shown that changes in the overall diameter and stiffness of an aneurysm play an important role in staging the progression of aortic aneurysm disease (19). It is possible that in our study, we did not have sufficient statistical power to detect a difference in PWV or aneurysm diameter between the stable AAA and unstable AAA groups.…”

“…This sample size was chosen to obtain a statistical power of 0.9, based on an anticipated effect size of 1.4 (Cohen d) observed in previous work conducted by the authors (19) with the same animal model. One mouse was retained solely as a control for histologic examination, while the other 26 mice were infused with angiotensin II (A9525; Sigma-Aldrich, St Louis, Mo) for 30 days via subcutaneously implanted osmotic pumps (Alzet Model 2004; Durect, Cupertino, Calif).…”

“…Pulse wave imaging (PWI) is a noninvasive ultrasonography (US)-based technique for visualizing and tracking the propagation of pulse waves along the arterial wall at high spatial and temporal resolutions (19,20). The purpose of this study was to assess whether the stability of murine aortic aneurysms is associated with the homogeneity of pulse wave propagation within the saccular wall.…”

“…During histologic examination, the abdominal section of each aorta (from the diaphragm to just before the events. This is based on the aforementioned previous study by Nandlall et al (19) by using the same animal model and doses of angiotensin II, in which 10 mice developed aneurysms and three mice experienced rupture events. In this study, the distribution of mice and dosages was chosen with the aim of obtaining a rate of aneurysm rupture of approximately 50% by the end of the observation period.…”