Morphology of atherosclerotic coronary arteries

Abstract

Atherosclerosis, the narrowing of vessel diameter and build-up of plaques in coronary arteries, leads to an increase in the shear stresses present, which can be used as a physics-based trigger for targeted drug delivery. In order to develop appropriate nanometer-size containers, one has to know the morphology of the critical stenoses with isotropic micrometer resolution. Micro computed tomography in absorption and phase contrast mode provides the necessary spatial resolution and contrast. The present communication describes the pros and cons of the advanced laboratory and synchrotron radiation-based approaches in the visualization of diseased human and murine arteries. Using registered datasets, it also demonstrates that multi-modal imaging, including established histology, is even more powerful. The tomography data were evaluated with respect to cross-section, vessel radius and maximal constriction. The average cross-section of the diseased human artery (2.31 mm 2 ) was almost an order of magnitude larger than the murine one (0.27 mm 2 ), whereas the minimal radius differs only by a factor of two (0.51 mm versus 0.24 mm). The maximal constriction, however, was much larger for the human specimen (85% versus 49%). We could also show that a plastic model used for recent experiments in targeted drug delivery represents a very similar morphology, which is, for example, characterized by a maximal constriction of 82%. The tomography data build a sound basis for flow simulations, which allows for conclusions on shear stress distributions in stenosed blood vessels.

Influence of Initial Residual Stress on Growth and Pattern Creation for a Layered Aorta

“…By combining both effects, we can see circumferential and axial wrinkles arise and add constructively to form a further 2D pattern with m = 2, n = 1, see Figure 6(A) for examples. Figure 6(B) shows a comparison of the cross-section areas of the inner volume between an atherosclerotic and a healthy aorta 38 , which is qualitatively consistent with the conclusion drawn from Figure 6(A) when the initial residual stress gets bigger. So our results may provide another possible explanation of physical pathology for atherosclerosis.…”

“…By combining both effects, we can see circumferential and axial wrinkles arise and add constructively to form a further 2D pattern with m = 2, n = 1, see Figure 6(A) for examples. Figure 6(B) shows a comparison of the cross-section areas of the inner volume between an atherosclerotic and a healthy aorta [38], which is qualitatively consistent with Figure 6: A. Typical wrinkle creations induced by growth of the inner layer (J in g > 0) starting from certain initial residual stresses (as tracked by α).…”

“…When the numbers of circumferential (m) and axial (n) wrinkles are both non-zero, a 2D-pattern emerges, as in the first two examples here. B. Crosssectional area of the inner volume of an atherosclerotic human coronary artery (left) and healthy (right) artery model derived from laboratory µCT measurements (from Holme et al [38]). the conclusion drawn from Figure 6(A) when the initial residual stress gets bigger.…”

Histology-validated x-ray tomography for imaging human coronary arteries

“…Recently, a shear-stress sensitive nano-container formulation was discovered [5]. Figure 1 shows a schematic representation of the liposome and the related chemical structure.…”

“…Moreover, histology belongs to the destructive analysis methods. In order to overcome these difficulties, non-destructive three dimensional (3D) X-ray imaging, such as micro computed tomography (µCT), is promising alternative for the characterization of atherosclerotic coronary arteries [5,6,[8][9][10]. One of the problems of X-ray tomography in absorption mode is the simultaneous visualization of soft and highly absorbing tissues: If the photon energy is optimized for the visualization of highly absorbing tissues, the soft tissues are almost transparent to the X-rays and provide poor contrast.…”