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In vivo characterization of a new abdominal aortic aneurysm mouse model with conventional and molecular magnetic resonance imaging.

ABSTRACT: The goal of this study was to use noninvasive conventional and molecular magnetic resonance imaging (MRI) to detect and characterize abdominal aortic aneurysms (AAAs) in vivo.Collagen is an essential constituent of aneurysms. Noninvasive MRI of collagen may represent an opportunity to help detect and better characterize AAAs and initiate intervention.We used an AAA C57BL/6 mouse model in which a combination of angiotensin II infusion and transforming growth factor-? neutralization results in AAA formation with incidence of aortic rupture. High-resolution, multisequence MRI was performed to characterize the temporal progression of an AAA. To allow molecular MRI of collagen, paramagnetic/fluorescent micellar nanoparticles functionalized with a collagen-binding protein (CNA-35) were intravenously administered. In vivo imaging results were corroborated with immunohistochemistry and confocal fluorescence microscopy.High-resolution, multisequence MRI allowed the visualization of the primary fibrotic response in the aortic wall. As the aneurysm progressed, the formation of a secondary channel or dissection was detected. Further analysis revealed a dramatic increase of the aortic diameter. Injection of CNA-35 micelles resulted in a significantly higher magnetic resonance signal enhancement in the aneurysmal wall compared with nonspecific micelles. Histological studies revealed the presence of collagen in regions of magnetic resonance signal enhancement, and confocal microscopy proved the precise co-localization of CNA-35 micelles with type I collagen. In addition, in a proof-of-concept experiment, we reported the potential of CNA-35 micelles to discriminate between stable AAA lesions and aneurysms that were likely to rapidly progress or rupture.High-resolution, multisequence MRI allowed longitudinal monitoring of AAA progression while the presence of collagen was visualized by nanoparticle-enhanced MRI.

SUBMITTER: Klink A

PROVIDER: S-EPMC4095885 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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In vivo characterization of a new abdominal aortic aneurysm mouse model with conventional and molecular magnetic resonance imaging.

Klink Ahmed A Heynens Joeri J Herranz Beatriz B Lobatto Mark E ME Arias Teresa T Sanders Honorius M H F HM Strijkers Gustav J GJ Merkx Maarten M Nicolay Klaas K Fuster Valentin V Tedgui Alain A Mallat Ziad Z Mulder Willem J M WJ Fayad Zahi A ZA

Journal of the American College of Cardiology 20111201 24

<h4>Objectives</h4>The goal of this study was to use noninvasive conventional and molecular magnetic resonance imaging (MRI) to detect and characterize abdominal aortic aneurysms (AAAs) in vivo.<h4>Background</h4>Collagen is an essential constituent of aneurysms. Noninvasive MRI of collagen may represent an opportunity to help detect and better characterize AAAs and initiate intervention.<h4>Methods</h4>We used an AAA C57BL/6 mouse model in which a combination of angiotensin II infusion and tran ...[more]

PMID: 22133853

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Project description:ObjectivesUsing maximum diameter of an abdominal aortic aneurysm (AAA) alone for management can lead to delayed interventions or unnecessary urgent repairs. Abdominal aortic aneurysm stiffness plays an important role in its expansion and rupture. In vivo aortic magnetic resonance elastography (MRE) was developed to spatially measure AAA stiffness in previous pilot studies and has not been thoroughly validated and evaluated for its potential clinical value. This study aims to evaluate noninvasive in vivo aortic MRE-derived stiffness in an AAA porcine model and investigate the relationships between MRE-derived AAA stiffness and (1) histopathology, (2) uniaxial tensile test, and (3) burst testing for assessing MRE's potential in evaluating AAA rupture risk.Materials and methodsAbdominal aortic aneurysm was induced in 31 Yorkshire pigs (n = 226 stiffness measurements). Animals were randomly divided into 3 cohorts: 2-week, 4-week, and 4-week-burst. Aortic MRE was sequentially performed. Histopathologic analyses were performed to quantify elastin, collagen, and mineral densities. Uniaxial tensile test and burst testing were conducted to measure peak stress and burst pressure for assessing the ultimate wall strength.ResultsMagnetic resonance elastography-derived AAA stiffness was significantly higher than the normal aorta. Significant reduction in elastin and collagen densities as well as increased mineralization was observed in AAAs. Uniaxial tensile test and burst testing revealed reduced ultimate wall strength. Magnetic resonance elastography-derived aortic stiffness correlated to elastin density (ρ = -0.68; P < 0.0001; n = 60) and mineralization (ρ = 0.59; P < 0.0001; n = 60). Inverse correlations were observed between aortic stiffness and peak stress (ρ = -0.32; P = 0.0495; n = 38) as well as burst pressure (ρ = -0.55; P = 0.0116; n = 20).ConclusionsNoninvasive in vivo aortic MRE successfully detected aortic wall stiffening, confirming the extracellular matrix remodeling observed in the histopathologic analyses. These mural changes diminished wall strength. Inverse correlation between MRE-derived aortic stiffness and aortic wall strength suggests that MRE-derived stiffness can be a potential biomarker for clinically assessing AAA wall status and rupture potential.

Project description: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 indicated that local changes in wall stiffness can be detected with pulse wave imaging (PWI), which is a non-invasive technique for tracking the propagation of pulse waves along the aorta at high spatial and temporal resolutions. The aim of this study was to assess 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 d after implantation using a 30-MHz VisualSonics Vevo 770 with 15-?m lateral resolution. Pulse wave propagation was monitored at an effective frame rate of 8 kHz by using retrospective electrocardiogram gating and by performing 1-D cross-correlation on the radiofrequency 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, r(2) = 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 (r(2) = 0.66 ± 0.23). Moreover, the wave-induced wall displacements were at least 80% lower within the sacs compared with 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 (r(2) < 0.20) were observed throughout the cardiac cycle. These findings indicate 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-mode ultrasound.

Dataset Information

In vivo characterization of a new abdominal aortic aneurysm mouse model with conventional and molecular magnetic resonance imaging.

Publications

In vivo characterization of a new abdominal aortic aneurysm mouse model with conventional and molecular magnetic resonance imaging.

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