Novel Strategy of the Determination of Mechanical Properties of Human Carotid Atherosclerotic Plaques

Author(s):  
Renate W. Boekhoven ◽  
Richard G. P. Lopata ◽  
Marcel C. M. Rutten ◽  
Marc R. H. M. van Sambeek ◽  
Frans N. van de Vosse

Carotid endarterectomy is the procedure of choice in patients with a recent symptomatic stenosis of 70–99%. Currently, the selection of candidates eligible for carotid endarterectomy is based on stenosis size only. However, the treatment is only beneficial for patients with unstable plaques, which comprises only 16% of the patient population [1]. Hence, identifying plaque stability at an early stage would permit timely intervention, while substantially reducing overtreatment of stable plaques. The objective of this study is to distinguish between stable and unstable carotid atherosclerotic plaques by determining the plaque geometry, the plaque composition and the mechanical properties of plaque components in three dimensions (3D). Mechanical properties from healthy vessels were assessed earlier by van den Broek et al. [2] using ultrasound (US) imaging. They obtained a dynamic dataset in 2D + t. When blood pressure and vessel wall movement are known, mechanical properties can be extracted from these data using a constitutive model. However, atherosclerotic plaques are mostly asymmetric, and present calcifications will cause unfavorable acoustic shadowing when using US. In this study, the focus is on the assessment of plaque geometry, from in vitro echo-CT data, overcoming the aforementioned problems. In an experimental set-up (Fig. 1) both healthy and endarterectomy specimens were mounted, and exposed to physiological intraluminal pressures. Echo-CT was used to image the arterial segments in 3D+t. Automated geometry assessment of the arterial segments will be demonstrated and validated using microCT (μCT).

Author(s):  
Renate W. Boekhoven ◽  
Marcel C. M. Rutten ◽  
Marc R. H. M. van Sambeek ◽  
Frans N. van de Vosse

Ruptured atherosclerotic plaques in the carotid artery are the main cause of stroke (70–80%). To prevent it, carotid endarterectomy is the procedure of choice in patients with a recent symptomatic 70–99% stenosis. Today, the selection of candidates is based on stenosis size only. However, endarterectomy is beneficial for only 1 out of 6 patients [1], the patients with unstable plaques (Fig. 1). Knowledge of mechanical properties of different components in the atherosclerotic arteries is important, because it will allow the identification of plaque stability at an early stage.


Author(s):  
Renate W. Boekhoven ◽  
Marcel C. M. Rutten ◽  
Marc R. H. M. van Sambeek ◽  
Frans N. van de Vosse ◽  
Richard G. P. Lopata

Treatment of rupture-prone carotid atherosclerotic plaques, by means of endarterectomy, is only beneficial for patients with unstable plaques, which comprise only 16% of the patient population [1]. It is therefore of great interest to assess morphology, geometry and mechanical deformation of the plaque and its components, to prevent unnecessary treatment. However, due to the complex geometry of stenotic arteries, 3D information at both high temporal and spatial resolution is required. Besides, assessment of plaque morphology in vivo can still not be routinely performed. Therefore, one has to rely on in vitro methods to obtain morphology and mechanical properties, and thus rupture risk.


Author(s):  
Wei Huan ◽  
Liu Yandong ◽  
Wang Chao ◽  
Zou Sili ◽  
Bai Jun ◽  
...  

Objective: programmed cell removal in atherosclerotic plaques plays a crucial role in retarding lesion progression. Macrophage apoptosis has a critical role in PrCR, especially in early-stage lesions. YKL-40 has been shown to be elevated as lesions develop and is closely related to macrophages. This study aimed to determine the effect of YKL-40 on regulating macrophage apoptosis and early-stage atherosclerosis progression.Research design and Methods: The correlations among the expression level of YKL-40, the area of early-stage plaque, and the macrophage apoptosis rate in plaques have been shown in human carotid atherosclerotic plaques through pathological and molecular biological detection. These results were successively confirmed in vivo (Ldlr−/- mice treated by YKL-40 recombinant protein/neutralizing antibody) and in vitro (macrophages that Ykl40 up-/down-expressed) experiments. The downstream targets were predicted by iTRAQ analysis.Results: In early-stage human carotid plaques and murine plaques, the YKL-40 expression level had a significant positive correlation with the area of the lesion and a significant negative correlation with the macrophage apoptosis rate. In vivo, the plaque area of aortic roots was significantly larger in the recomb-YKL-40 group than that in IgG group (p = 0.0247) and was significantly smaller in the anti-YKL-40 group than in the IgG group (p = 0.0067); the macrophage apoptosis rate of the plaque in aortic roots was significantly lower in the recomb-YKL-40 group than that in IgG group (p = 0.0018) and was higher in anti-YKL-40 group than that in VC group. In vitro, the activation level of caspase-9 was significantly lower in RAW264.7 with Ykl40 overexpressed than that in controls (p = 0.0054), while the expression level of Aven was significantly higher than that in controls (p = 0.0031). The apoptosis rate of RAW264.7 treated by recomb-YKL40 was significantly higher in the Aven down-regulated group than that in the control group (p < 0.001). The apoptosis inhibitor Aven was confirmed as the target molecule of YKL-40. Mechanistically, YKL-40 could inhibit macrophage apoptosis by upregulating Aven to suppress the activation of caspase-9.Conclusion: YKL-40 inhibits macrophage apoptosis by upregulating the apoptosis inhibitor Aven to suppress the activation of caspase-9, which may impede normal PrCR and promote substantial accumulation in early-stage plaques, thereby leading to the progression of atherosclerosis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rui Li ◽  
Yang Bu ◽  
Chendong Yang ◽  
Jizeng Wang

Hepatic steatosis is associated with various liver diseases. The main pathological feature of steatosis is the excessive lipid accumulation. Ultrasound has been extensively used for the diagnosis of hepatic steatosis. However, most ultrasound-based non-invasive methods are still not accurate enough for cases with light lipid infiltration. One important reason is that the extent to which lipid infiltration may affect mechanical properties of hepatocytes remains unknown. In this work, we used atomic force microscope and in vitro dose-dependent lipid deposition model to detect the quantitative changes of mechanical properties under different degrees of steatosis in a single-cell level. The results show that hepatic cells with lipid deposition can be treated as linear viscoelastic materials with the power law creep compliance and relaxation modulus. Further analysis showed that even slight accumulation of lipid can lead to measurable decrease of stiffness and increased fluidity in liver cells. The accurate detection of viscoelastic properties of hepatocytes and the analysis methods may provide novel insights into hepatic steatosis grading, especially in the very early stage with reversible liver lesion. The application of viscoelasticity index for grading fat deposition might be a new detection indicator in future clinical diagnosis.


Author(s):  
Sanaz S Hashemi ◽  
Masoud Asgari ◽  
Akbar Rasoulian

Accurate modelling of biological tissues has been a significant need for analysis of the human body. In this article, a comprehensive in vitro experimental study has been done on the fresh bovine skeletal muscle before the onset of rigour mortis in order to provide an experimental description of passive skeletal muscle properties in three dimensions. Different situations including various deformation modes, different loading rates and loading directions are tested to consider all features of skeletal muscle behaviour. Based on the nonlinear continuum mechanics, a three-dimensional visco-hyperelastic model is introduced which considers all aspects of skeletal muscle’s features such as nonlinear hyperelastic, time-dependent behaviour, anisotropy and quasi-incompressibility. Visco-hyperelastic material constants are obtained for passive behaviour of the muscle based on genetic algorithm optimization method via comparing the theoretical and experimental results. Experiments show that the rate of loading affects the configuration of experimental curves considerably. It could be also concluded that compression–tension asymmetry, as well as anisotropic behaviour, of the muscle is due to fibres orientation. Obtained experimental results help to achieve a better understanding of mechanical properties and nonlinear behaviour of the skeletal muscles.


2007 ◽  
Vol 107 (6) ◽  
pp. 1198-1204 ◽  
Author(s):  
Alexander C. Mamourian ◽  
Namrata Mahadevan ◽  
Nischala Reddy ◽  
Steven P. Marra ◽  
John Weaver

Object The aim of this study was to explore the possibility that a hybrid aneurysm clip with polymeric jaws bonded to a metal spring could provide mechanical properties comparable to those of an all-metal clip as well as diminished artifacts on computed tomography (CT) scanning. Methods Three clips were created, and Clips 1 and 2 were tested for mechanical properties. Clip 1 consisted of an Elgiloy spring (a cobalt-chromium-nickel alloy) bonded to carbon fiber limbs; Clip 2 consisted of an Elgiloy spring with polymethylmethacrylate (PMMA) jaws; and Clip 3 consisted of PMMA limbs identical to those in Clip 2 but bonded to a titanium spring. Custom testing equipment was set up to measure the aneurysm clip clamping forces and slippage. Clips 2 and 3 were visualized in vivo using a 64-slice CT unit, and the slices were reformatted into 3D images. Results According to the testing apparatus, Clip 2 had a similar closing force but less slippage than three similar commercial aneurysm clips. The artifact from the cobalt alloy spring on CT scanning largely offset the advantage of the nonmetal PMMA limbs, which created no artifact. The hybrid titanium/PMMA clip (Clip 3) created very little artifact on CT and allowed visualization of the phantom through the limbs. Conclusions It is feasible to build a potentially biocompatible hybrid cerebral aneurysm clip with mechanical properties that closely resemble those of conventional metallic clips. Further testing should be directed toward establishing the reliability and biocompatibility of such a clip and optimizing the contour and surface treatments of the polymer limbs.


1998 ◽  
Vol 80 (09) ◽  
pp. 437-442 ◽  
Author(s):  
I. Hioki ◽  
K. Onoda ◽  
T. Shimono ◽  
H. Shimpo ◽  
K. Tanaka ◽  
...  

SummaryAlterations in platelet aggregability may play a role in the pathogenesis of qualitative platelet defects associated with cardiopulmonary bypass (CPB). We circulated fresh heparinized whole blood through tubing sets coated with heparin (C group, n = 10) and through non-coated sets (N group, n = 10) as a simulated CPB circuit. Shear stress (108 dyne/cm2)-induced platelet aggregation (hSIPA), plasma von Willebrand factor (vWF) activity and platelet glycoprotein (GP) Ib expression were measured, before, during, and after this in vitro set up of circulation. In the two groups, the extent of hSIPA significantly decreased during circulation and was partially restored after circulation. Decreases in the extent of hSIPA were significantly less with use of heparin-coated circuits. There was an equivalent reduction in plasma vWF activity, in the two groups. Expression of platelet surface GP Ib decreased significantly during circulation and recovered after circulation. Reduction of surface GP Ib expression during circulation was significantly less in the C group than that in the N group. Decrease in surface GP Ib expression correlated (r = 0.88 in either group) with the magnitude of hSIPA, in the two groups. The progressive removal of surface GP Ib was mainly attributed to redistribution of GP Ib from the membrane skeleton into the cytoskeleton. Our observations suggest that use of heparin-coated circuits partly blocks the reduction of hSIPA, as a result of a lesser degree of redistribution of GP Ib.


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