Study on the relationship between plaque composition and shear stress in human coronary arteries in vivo

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Journal o f Biomechanics 2006, Vol. 39 (Suppl 1)

5009 Tu, 09:15-09:30 (P17) Study on the relationship between plaque composition and shear stress in human coronary arteries in vivo J. Wentzel 1, EJ.H. Gijsen 1, J.C.H. Schuurbiers 1, H.M. Garcia-Garcia 2, A.EW. van der Steen 1, P.W. Serruys 2. 1Biomedical Engineering, Erasmus

MC, Rotterdam, the Netherlands, 21nterventional Cardiology, Erasmus MC, Rotterdam, the Netherlands Background: Atherosclerotic plaques are known to develop at low shear stress (LSS) regions. However, when plaques encroach into the lumen high shear stress (HSS) starts to act at the plaque. HSS is known to stimulate tissue regression and might therefore influence the plaque composition and stability. We aimed at studying the mutual relationship between SS and plaque composition in human coronary arteries in vivo. Methods: In 10 patients, 3D reconstruction of lumen and wall was performed of a non-treated coronary artery with a combined ANGiographic and ivUS technique (ANGUS). Combined with patient-specific flow and viscosity data, the 3D-lumen data served as input to compute the SS distribution. Another IVUS pullback in the same artery was performed to obtain plaque composition by virtual histology (VH). VH provides, based on the IVUS derived RF-signals and a classification system, the spatial distribution of major plaque components (lipid, fibro-lipid, fibrous and calcium). To map plaque composition on the SS distribution, the two IVUS data sets were carefully matched using corresponding landmarks. Regions with plaques, having wall thickness >20% of local lumen diameter, were selected for further analysis. Plaque composition at the LSS sites, being <25% percentile of SS distribution, was compared with the other HSS regions. Results: Data of 4 patients showed high correlation between lumen areas of VH and ANGUS (r2 =0.88±0.11). Average LSS was 1.73±0.61 Pa and HSS 8.06±6.90Pa. Lipid concentration was highest at HSS (20.2% vs. 14.8%), while the fibrous content was lowest (46.5% vs 50.4%). Data analysis of the other patients is ongoing. Conclusion: For the first time, we showed the feasibility to study plaque composition in its mutual relationship with SS in patients in vivo. Our results show a co-localization of HSS, higher lipid content and lower fibrous tissue content, indicating that HSS is involved in higher plaque vulnerability. 6683 Tu, 09:30-09:45 (P17) Hemodynamic wall shear stress and expression of VCAM-1 and ICAM-1 in the mouse aorta S. Jin 1, D.E. Ferrara 2, J. Oshinski 1,3, R.W. Taylor 1,2, D.P. Giddens 1. 1Wallace

H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emery University School of Medicine, Atlanta, USA, 2Department of Medicine and 3Department of Radiology, Emery University School of Medicine, Atlanta, USA There is interest in understanding relationships between hemodynamic factors and the localization of atherosclerotic plaques. Although mice are frequently employed as animal models, mouse hemodynamics have not been extensively characterized. We are investigating flow fields and wall shear stresses (WSS) in the aortas of mice using computational fluid dynamics (CFD) and are relating these to expression of various biological markers associated with atherogenesis. Our objectives are to explore similarities and differences between humans and mice in order to understand better the mouse model. One group of C57BI/6 mice was used to develop the CFD model. After euthanasia, the proximal aortic tree was retrogradely perfused using microfil ® without opening the thorax. The whole dissected thoraces were then scanned by micro-CT at a spatial resolution of 0.021 0.021 0.021 mm. CFD geometric models were reconstructed from these images, and the velocity conditions were obtained from ultrasound measurements. We limited our study to the ascending aorta and aortic arch, where the vessel diameter is approximately 1 mm, allowing use of the Navier-Stokes equations. Mice in a second group were dissected and imaged by an immunohistochemical (IHC) en face method employing quantum dots. We found that: (i) WSS values in the mouse aorta are an order of magnitude greater than in the human aorta; and (ii) expression of VCAM-1 and ICAM-1 in the mouse was greater in regions where the WSS was relatively low and oscillated in direction. Thus, although the magnitudes of WSS are very different between mouse and human aortas, the distribution of these two adhesion molecules in the mouse aorta was found to be similar to plaque distribution in the aorta of humans.

Oral Presentations

14.3.2. Hemedynamics and Vascular Biology II 6386 Tu, 11:00-11:15 (P19) A novel computerized biomechanical perfusion system for ex vivo expression studies o f artificial endothelial cell monolayer vessels N. Bergh, E. Ulfhammer, M. Andersson, S. Jern. Clinical Experimental

Research Laboratoury, Heart and lung Institute, Sahlgrenska University Hespital/(Dstra, G6teberg, Sweden The majority of cases of myocardial infarction and ischemic stroke are caused by sudden activation of intravascular clotting mechanisms that, when unopposed, rapidly can progress into formation of an occluding arterial thrombosis. To protect against this, the vascular endothelium of healthy individuals has the capacity to activate an acute thromboprotective response if intravascular clotting should occur. This thromboprotective capacity is suppressed in patient with essential and renal hypertension, in atherosclerosis and other proatherothrombotic conditions. Several of these conditions are associated with disturbed hemodynamic flow patterns as well as a low-grade inflammation with increased circulating levels of proinflammatory cytokines. We have developed a novel computerized biomechanical system where artificial vessel can be stimulated under well defined biomechanical stress. Cultured human umbilical vein endothelial cells is shear stress stimulated (2, 13 or 25dyn/cm 2) or compressive stress stimulated (80 or 120 mmHg with a static or pulsatile flow). In addition to the biomechanical stress the endothelial cells is exposed to various cytokines (TNFalfa or IL-6). Effects on the gene expression of t-PA, PAl-l, TM, u-PA and VCAM-1 are evaluated using real-time RT-PCR. The mRNA expression of t-PA and VCAM-1 is suppressed by both low and high shear stress, with a more pronounced reduction by high shear (-50%). The mRNA expression of PAl-l, TM and u-PA is 3-fold induced by high shear stress. To the compressive stress the genes of interest was not found to be regulated. By using this experimental model for biomechanical and inflammatory stress stimulation of cultered vascular endothelial cells, we will gain more knowledge of how the endothelial cells fibrinolytic capacity is regulated. This project is funded by the Swedish Research Council, Swedixh Heart-Lung Foundation. 6640 Tu, 11:15-11:30 (P19) Development of atherosclerotic phantom with a lipid inclusion V. Pazos 1,2, R. Mongrain 1,2, R. Galaz 1, R. Leask 1, J.-C. Tardif2. 1McGill

University, Montreal, Quebec, Canada, 21nstitut de Cardiologie de Montreal, Quebec, Canada Atherosclerosis plaques may rupture without warning and cause subsequent acute syndrome such as myocardial infarction and cerebral stroke. Accurate methods are needed to identify vulnerable plaque and quantify conditions under which rupture may occur. Obtaining such information in-vivo would be important for predicting possible rupture and aid in the development of optimal medical and surgical treatments. Vulnerable plaques are typically associated with a large lipid-rich core, superficial plaque inflammation and a thin fibrous cap. To evaluate the feasibility of characterizing hyperelastic properties using intravascular ultrasound imaging, we made an in-vitro model having the morphology, derived from clinical observation of a stenotic coronary artery with a lipid inclusion. The lumen shape that presents a 50% stenotic asymmetric Gaussian profile and a nominal normal diameter of 3 mm was modeled using CAD software then fabricated by rapid prototyping. The artery wall was made out of agar hydrogel. Hydrogels have been widely used for tissue-equivalent ultrasound phantoms because of their acoustic impedance which is in the same range as human tissues. They also present hyperelastic behaviour, relatively similar to vascular tissue. Cellulose powder was added to the solution for scattering and animal fat (lard) was injected inside the stenotic part. The artery phantom was subjected to incremental hydrostatic pressures and intravascular ultrasound images were acquired. Based on echogenicity contrast, contours were segmented to provide the geometry of the phantom and compute the deformations between the incremental acquisitions. The resulting model mimicks the geometry and echogenicity contrasts of an atherosclerotic artery and behaves non-linearly under intraluminal pressure differentials similar to actual artery tissues. 6311 Tu, 11:30-11:45 (P19) Nitric oxide is significantly reduced in porcine arteries during reverse flow X. Lu, G.S. Kassab. Department of Biomedical Engineering, University of

California, Irvine, CA, USA Oscillatory and negative flows occur normally in the cardiovascular system, which predispose those regions to atherosclerosis. Nitric oxide (NO) production