Porcine carotid arterial material property alterations with induced atheroma: an in vivo study

https://doi.org/10.1016/j.medengphy.2004.09.014Get rights and content

Abstract

Objective:

A novel methodology has been developed to evaluate regional alterations in arterial wall material properties with induced atheroma in an animal model.

Methods:

Atheromatous lesions (fatty, fibro-fatty, and fibrous) were induced in the carotid arteries of a Yucatan miniswine model by endothelial cell denudation and high cholesterol diet. The images at base line and 8 weeks after denudation were obtained using intravascular ultrasound (IVUS) imaging along with hemodynamic data. Finite element analysis (FEA) along with optimization was employed to assess regional alterations in elastic modulus in the presence of atheroma confirmed by histology.

Results:

In animals with 8 weeks of induced atherosclerosis, the elastic modulus increased—(elastic modulus—all values × 104 Pa, mean ± S.D.) normal elements (9.34 ± 0.36) compared to abnormal elements (9.52 ± 0.36) (p < 0.05 versus normal elements). Wall thickness increased with atheroma formation. These data demonstrate stiffening vascular wall elastic modulus with lesion progression. This is different from the behavior of femoral arteries, where the elastic modulus decreases with early stages of atheroma development followed by an increase as lesions progress.

Conclusions:

This methodology permits determination of areas with early atheroma development, follow atheroma progression, and potentially evaluate interventions aimed at decreasing atheroma load and normalizing vascular material properties.

Introduction

The mechanical properties of the arterial wall are thought to play an important role in vascular physiology. Classical studies of Bergel [1], [2], [3] and Canfield and Dobrin [4] have investigated the passive elastic behavior of large arteries. Other studies have shown the effect of arterial material properties on vascular reactivity responsive to neural, humoral and hemodynamic stimuli [5]; mass transport within the arterial wall[5], [6], [7]; blood flow in arterial conduits [6], [8]; evolution of atherosclerotic disease [5], [9], [10]; stress distribution within the arterial wall [9], [11], [12], [13], [14]; and arterial response to therapeutic intervention [15], [16].

Atherosclerosis is a diffuse and highly variable disease process which is distinguished by the subintimal accumulation of varying amounts of extracellular lipid, fibrous tissue, smooth muscle, and calcium. Atherosclerosis changes arterial wall morphology [8], [17] and alters its mechanical properties [16], [18]. This pathologically altered morphology of diseased arterial tissue results in a complex structure that is geometrically irregular, structurally inhomogeneous, anisotropic, incompressible, nonlinearly viscoelastic, subject to large strain deformations, and defies straightforward rheological characterization [19], [20].

The diffuse and variable nature of atherosclerosis is manifested in the conflicting results reported by different investigators on the constitutive relationships of arterial tissue [21]. Previous attempts to describe the mechanical behavior of arterial wall tissue have used various methods (strain gauge, linear differential transformer, sonomicrometer, angiography, ultrasound imaging) to measure arterial tissue deformation in response to an applied transmural pressure load [8], [21], [22], [23]. In vitro approaches typically focus on the behavior of tissue strips, rings, or segments cut from the post mortem arterial wall while in vivo attempts look at intact, in situ vascular segments, ideally undisturbed by surgical intervention. A common drawback of conventional methods applied to intact vascular segments is an inference of the mechanical behavior of an entire segment by using only discrete measurements in a localized area of the artery (e.g. external diameter at a specific axial location). These methods have severe limitations especially when applied to atherosclerotic vessels, in which composition and structure vary as a function of both longitudinal and circumferential position within the artery [19]. A method to assess regional variability in material properties is essential to determine the extent and location of atherosclerotic lesions in vivo.

Numerical analyses such as finite element analysis (FEA) are more amenable to analyzing the complex morphology of the mechanical behavior exhibited by vascular tissues [16], [24], [25]. FEA is performed on a spatially discretized model of arterial structure and has the ability to incorporate more realistic assumptions regarding arterial tissue behavior, account for 3-dimensional (3D) variations in material composition and geometry, and thus provide accurate region-dependent solutions [25].

Intravascular ultrasound (IVUS) is a minimally-invasive high resolution imaging technique (typical 2-point structural resolution of ∼0.1 mm) enabling cross-sectional images of vascular wall structure. As IVUS portrays accurately the morphology of normal and atheromatous tissue components within the arterial wall [15], [16], [26], [27], [28], it provides comprehensive information characterizing the geometry and composition of single, transverse sections. Using a constant pullback technique and subsequent segmentation of arterial wall boundaries, morphologically realistic three-dimensional reconstruction of arterial segments can be obtained.

We have previously shown, in ex vivo human atherosclerotic arterial segments, that three-dimensional reconstruction of intravascular ultrasound image data with finite element analysis can identify regional vascular material properties when compared with histology [29]. These in vitro data demonstrated that the elastic moduli of non-diseased tissue regions was greater than early fatty atherosclerotic regions for transmural pressure loads ranging from 10.7 to 21.3 kPa (80–160 mmHg) representing normal and hypertensive magnitudes.

In the present work, we have utilized a Yucatan miniswine animal model for atherosclerotic lesion development. We have used IVUS imaging and 3D reconstruction of vascular segments with and without atheroma formation and performed finite element and optimization analysis to identify regional alterations in arterial wall material property and correlated the same with histology. Our discussion focuses on the benefits of these methodologies to evaluate atheroma growth and formation in vivo and compares our findings in the carotid with alterations in other arterial beds.

Section snippets

Animal model and data acquisition

A Yucatan miniswine atheroma model with similar atherosclerotic characteristics to humans (n = 10; weight 20–25 kg) was used [30]. All procedures were approved by the Northwestern University Animal Care and Use Committee. All animal and handling procedures conform to the “Guide for the Care and Use of Laboratory Animals” (National Institutes of Health. Guide for the Care and Use of Laboratory Animals. Publication #85-23, 1996).

Following full anesthesia, one carotid artery was exposed with a neck

Results

Fig. 4 illustrates wall thickness and elastic modulus distributions and corresponding histologic data for a carotid artery at baseline and following 8 weeks of induced atheroma development. On the top row, the results of the analysis in arterial segments at baseline (left carotid at t = 0 weeks before endothelial denudation) show uniform distribution of wall thickness and the predicted elastic modulus distribution. In the middle panel, similar data are shown in the arterial segment without

Discussion

Employing 3D-IVUS reconstruction and finite element and optimization analysis, these data demonstrate that wall thickness and elastic material properties increase in the carotid artery with induced atheroma in the animal model. Our discussion will focus on the benefits of this methodology for evaluating atheroma growth and formation, the implications of our results, and factors influencing the results. It is known that atherosclerotic lesions develop diffusely in arteries and result in a

Summary

The methodology presented allows tracking of atheroma growth and development in vivo and alterations in material properties from one point in time to another, as well as from region to region that would correspond to different types of atheroma formation. These data demonstrate that, in the carotid artery with atheroma formation, the elastic modulus increases with atheroma growth and component deposition. These data provide insights into factors that would influence structural changes with

Acknowledgements

Sponsored in Part by HL 62504 (National Institutes of Health) and the Feinberg Cardiovascular Research Institute.

References (39)

  • D.H. Bergel

    The dynamic elastic properties of the arterial wall

    J Physiol Lond

    (1961)
  • D.H. Bergel
  • T.R. Canfield et al.
  • D.L. Fry et al.
  • R.M. Nerem et al.
  • K. Rosenfield et al.

    3-Dimensional Reconstruction of human coronary and peripheral arteries from images recorded during 2-dimensional intravascular ultrasound examination

    Circulation

    (1991)
  • D.J. Farrar et al.

    Aortic pulse wave velocity, elasticity, and composition in a nonhuman primate model of atherosclerosis

    Circ Res

    (1978)
  • S. Middleman
  • S. Glagov et al.

    Hemodynamics and atherosclerosis insights and perspectives gained from studies of human arteries

    Arch Pathol Lab Med

    (1988)
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