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A parametric study of inflammatory effects on plaque mechanical stress
International Journal of Cardiology 205 (2016) 157–159
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
A parametric study of inflammatory effects on plaque mechanical stress Xuan Pei a, Seemantini Nadkarni b, Zhi-Yong Li a,c,⁎ a b c
School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane (QUT), QLD 4001, Australia
a r t i c l e
i n f o
Article history: Received 24 November 2015 Accepted 12 December 2015 Available online 15 December 2015 Keywords: Inflammation Atherosclerosis Vulnerable plaque Parametric finite element analysis
Acute myocardial infarction (AMI), caused by the rupture of vulnerable coronary plaque is the leading cause of death and disability worldwide. Inflammation as a risk factor is commonly found in atherosclerosis and strong evidence reported in the literature suggests that plaques with high macrophage accumulation are often unstable and susceptible to rupture [4,5]. Although a series of non-invasive imaging techniques has been developed to identify inflammation in the fibrous cap and inflammation has been proved to be a prominent imaging target due to its useful application in each stage of plaque evolution [2,3], the studies are inadequate in addressing whether inflammation directly impacts the mechanical stability of the plaque by altering the maximum tensile stress in the fibrous cap. In this work, we investigated the influence of focal inflammation on the mechanical stress in plaque by varying three key parameters of the inflammation region — its Young's modulus, size and location. We create a set of idealized models for an arterial cross-section of the plaque, including a circular lumen, a fibrous cap and a blunt crescentshaped lipid pool. The diameters of the lumen and vessel are chosen to be 20 and 60 mm, respectively, and the thickness of the vessel wall is 2 mm. The thicknesses of the fibrous cap and lipid pool are 10 and 15 mm, respectively. In the models, we partitioned an inflammation region into a circle to investigate the impact of inflammation region on the mechanical stability of plaque. Three controlling parameters are adopted to represent the properties of inflammation region, including its Young's modulus EIR, size and location. We set the Young's moduli of the arterial wall, EAW = 0.15 MPa; fibrous cap, EFC = 0.5 MPa; and lipid
pool, ELP = 0.005 MPa, and vary the value of EIR between 0.005 MPa and 0.5 MPa [1]. The size and location of the inflammation region are varied by increasing the radius of the circle and characterized through the orientation between the line directed to the center of inflammation region and the x-axis, respectively. The baseline we chose for the inflammation region was EIR = 0.25 MPa, rIR = 2.5 mm and θ LP = 0°. Each part is considered as an almost-incompressible material with a Poisson's ratio of νAW = νFC = νLP = 0.48. The finite element analysis (FEA) is performed in using the ABAQUS software (Version 6.10). A two-dimensional fournode quadrilateral element is used to mesh the whole structure and an internal pressure of 16 kPa (120 mmHg) is simulated on the lumen wall to represent the mean physiological systolic blood pressure in the artery. We found that at the initial stage of focal fibrous cap degradation due to inflammation, the reduction in the Young's modulus of inflammation region has a very limited effect on the stress level in plaque. However, when further the cap degradation occurs such that the modulus reduces by over 60% (from 0.5 to 0.2 MPa); there is significant enhancement of the maximum tensile stress in plaque (Fig. 1). As a result, the rapid increase in the stress in this phase can significantly increase the risk of plaque rupture. This trend illustrates that the influence of the reduction in the Young's modulus on the stress is segmented and related to the extent of collagen fiber degradation. The maximum plaque tensile stress is similarly affected by the size of the focal inflammation. When the radius exceeds a threshold value of 3.5 mm, a significant increase in the plaque stress is expected (Fig. 2(a)). In contrast, the location of inflammation region has negligible effect on the maximum tensile stress in plaque. It is also important to note that over 70% of acute coronary events are caused by the intimal disruption of an inflamed plaque (Fig. 2(b)). Overall, in this work we use the finite element method to simulate the risk of fibrous material weakening by considering three controlling parameters of the inflammation region in plaque. We conclude that even a small focal region of fibrous cap degradation due to inflammation may directly impact plaque structural stress. Meanwhile, the position of the inflammation seems to have very limited effect on the stress, suggesting that the presence rather than the location of inflammation is an important risk factor in predicting plaque stability. Taken together, these results offer an improved understanding of development of critical stresses in plaques that cause rupture. Conflict of interest
⁎ Corresponding author at: School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China. E-mail address: [email protected] (Z.-Y. Li).
http://dx.doi.org/10.1016/j.ijcard.2015.12.019 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
The authors report no relationships that could be construed as a conflict of interest.
158
Correspondence
Fig. 1. Color maps of whole tensile stress distribution and the dependence of the maximum tensile stress on the Young's modulus of inflammation region.
Acknowledgment This research is supported by the 973 Program (No. 2013CB733800), the NSFC (No. 11272091, 11422222, 31470043) and ARC (FT140101152). References [1] S. Le Floc'H, et al., Vulnerable atherosclerotic plaque elasticity reconstruction based on a segmentation-driven optimization procedure using strain measurements: theoretical framework, IEEE Trans. Med. Imaging 28 (7) (2009) 1126–1137.
[2] J. Hur, et al., Use of contrast enhancement and high-resolution 3D black-blood MRI to identify inflammation in atherosclerosis, J. Am. Coll. Cardiol. Img. 3 (11) (2010) 1127–1135. [3] M.K. Jezovnik, et al., Identification of inflamed atherosclerotic lesions in vivo using PET-CT, Inflammation 37 (2) (2014) 426–434. [4] W.S. Kerwin, Noninvasive imaging of plaque inflammation: role of contrastenhanced MRI, J. Am. Coll. Cardiol. Img. 3 (11) (2010) 1136–1138. [5] T. Saam, et al., Association of inflammation of the left anterior descending coronary artery with cardiovascular risk factors, plaque burden and pericardial fat volume: a PET/CT study, Eur. J. Nucl. Med. Mol. Imaging 37 (6) (2010) 1203–1212.
Correspondence
159
Fig. 2. Color maps of whole tensile stress distribution and the dependence of the maximum tensile stress on (a) the radius of inflammation region and (b) the location of inflammation region.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
A parametric study of inflammatory effects on plaque mechanical stress Xuan Pei a, Seemantini Nadkarni b, Zhi-Yong Li a,c,⁎ a b c
School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane (QUT), QLD 4001, Australia
a r t i c l e
i n f o
Article history: Received 24 November 2015 Accepted 12 December 2015 Available online 15 December 2015 Keywords: Inflammation Atherosclerosis Vulnerable plaque Parametric finite element analysis
Acute myocardial infarction (AMI), caused by the rupture of vulnerable coronary plaque is the leading cause of death and disability worldwide. Inflammation as a risk factor is commonly found in atherosclerosis and strong evidence reported in the literature suggests that plaques with high macrophage accumulation are often unstable and susceptible to rupture [4,5]. Although a series of non-invasive imaging techniques has been developed to identify inflammation in the fibrous cap and inflammation has been proved to be a prominent imaging target due to its useful application in each stage of plaque evolution [2,3], the studies are inadequate in addressing whether inflammation directly impacts the mechanical stability of the plaque by altering the maximum tensile stress in the fibrous cap. In this work, we investigated the influence of focal inflammation on the mechanical stress in plaque by varying three key parameters of the inflammation region — its Young's modulus, size and location. We create a set of idealized models for an arterial cross-section of the plaque, including a circular lumen, a fibrous cap and a blunt crescentshaped lipid pool. The diameters of the lumen and vessel are chosen to be 20 and 60 mm, respectively, and the thickness of the vessel wall is 2 mm. The thicknesses of the fibrous cap and lipid pool are 10 and 15 mm, respectively. In the models, we partitioned an inflammation region into a circle to investigate the impact of inflammation region on the mechanical stability of plaque. Three controlling parameters are adopted to represent the properties of inflammation region, including its Young's modulus EIR, size and location. We set the Young's moduli of the arterial wall, EAW = 0.15 MPa; fibrous cap, EFC = 0.5 MPa; and lipid
pool, ELP = 0.005 MPa, and vary the value of EIR between 0.005 MPa and 0.5 MPa [1]. The size and location of the inflammation region are varied by increasing the radius of the circle and characterized through the orientation between the line directed to the center of inflammation region and the x-axis, respectively. The baseline we chose for the inflammation region was EIR = 0.25 MPa, rIR = 2.5 mm and θ LP = 0°. Each part is considered as an almost-incompressible material with a Poisson's ratio of νAW = νFC = νLP = 0.48. The finite element analysis (FEA) is performed in using the ABAQUS software (Version 6.10). A two-dimensional fournode quadrilateral element is used to mesh the whole structure and an internal pressure of 16 kPa (120 mmHg) is simulated on the lumen wall to represent the mean physiological systolic blood pressure in the artery. We found that at the initial stage of focal fibrous cap degradation due to inflammation, the reduction in the Young's modulus of inflammation region has a very limited effect on the stress level in plaque. However, when further the cap degradation occurs such that the modulus reduces by over 60% (from 0.5 to 0.2 MPa); there is significant enhancement of the maximum tensile stress in plaque (Fig. 1). As a result, the rapid increase in the stress in this phase can significantly increase the risk of plaque rupture. This trend illustrates that the influence of the reduction in the Young's modulus on the stress is segmented and related to the extent of collagen fiber degradation. The maximum plaque tensile stress is similarly affected by the size of the focal inflammation. When the radius exceeds a threshold value of 3.5 mm, a significant increase in the plaque stress is expected (Fig. 2(a)). In contrast, the location of inflammation region has negligible effect on the maximum tensile stress in plaque. It is also important to note that over 70% of acute coronary events are caused by the intimal disruption of an inflamed plaque (Fig. 2(b)). Overall, in this work we use the finite element method to simulate the risk of fibrous material weakening by considering three controlling parameters of the inflammation region in plaque. We conclude that even a small focal region of fibrous cap degradation due to inflammation may directly impact plaque structural stress. Meanwhile, the position of the inflammation seems to have very limited effect on the stress, suggesting that the presence rather than the location of inflammation is an important risk factor in predicting plaque stability. Taken together, these results offer an improved understanding of development of critical stresses in plaques that cause rupture. Conflict of interest
⁎ Corresponding author at: School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China. E-mail address: [email protected] (Z.-Y. Li).
http://dx.doi.org/10.1016/j.ijcard.2015.12.019 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
The authors report no relationships that could be construed as a conflict of interest.
158
Correspondence
Fig. 1. Color maps of whole tensile stress distribution and the dependence of the maximum tensile stress on the Young's modulus of inflammation region.
Acknowledgment This research is supported by the 973 Program (No. 2013CB733800), the NSFC (No. 11272091, 11422222, 31470043) and ARC (FT140101152). References [1] S. Le Floc'H, et al., Vulnerable atherosclerotic plaque elasticity reconstruction based on a segmentation-driven optimization procedure using strain measurements: theoretical framework, IEEE Trans. Med. Imaging 28 (7) (2009) 1126–1137.
[2] J. Hur, et al., Use of contrast enhancement and high-resolution 3D black-blood MRI to identify inflammation in atherosclerosis, J. Am. Coll. Cardiol. Img. 3 (11) (2010) 1127–1135. [3] M.K. Jezovnik, et al., Identification of inflamed atherosclerotic lesions in vivo using PET-CT, Inflammation 37 (2) (2014) 426–434. [4] W.S. Kerwin, Noninvasive imaging of plaque inflammation: role of contrastenhanced MRI, J. Am. Coll. Cardiol. Img. 3 (11) (2010) 1136–1138. [5] T. Saam, et al., Association of inflammation of the left anterior descending coronary artery with cardiovascular risk factors, plaque burden and pericardial fat volume: a PET/CT study, Eur. J. Nucl. Med. Mol. Imaging 37 (6) (2010) 1203–1212.
Correspondence
159
Fig. 2. Color maps of whole tensile stress distribution and the dependence of the maximum tensile stress on (a) the radius of inflammation region and (b) the location of inflammation region.