Harm A. Nieuwstadt

The influence of axial image resolution on atherosclerotic plaque stress computations

Biomechanical models are used extensively to study risk factors, such as peak stresses, for vulnerable atherosclerotic plaque rupture. Typically, 3D patient-specific arterial models are reconstructed by interpolating between cross sectional contour data which have a certain axial sampling, or image, resolution. The influence of the axial sampling resolution on computed stresses, as well as the comparison of 3D with 2D simulations, is quantified in this study. A set of histological data of four atherosclerotic human coronary arteries was used which were reconstructed in 3D with a high sampling (HS) and low sampling (LS) axial resolution, and 4 slices were treated separately for 2D simulations. Stresses were calculated using finite element analysis (FEA). High stresses were found in thin cap regions and regions of thin vessel walls, low stresses were found inside the necrotic cores and media and adventitia layers. Axial sampling resolution was found to have a minor effect on general stress distributions, peak plaque/cap stress locations and the relationship between peak cap stress and minimum cap thickness. Axial sampling resolution did have a profound influence on the error in computed magnitude of peak plaque/cap stresses (±15.5% for HS vs. LS geometries and ±24.0% for HS vs. 2D geometries for cap stresses). The findings of this study show that axial under sampling does not influence the qualitative stress distribution significantly but that high axially sampled 3D models are needed when accurate computation of peak stress magnitudes is required.

A computer-simulation study on the effects of MRI voxel dimensions on carotid plaque lipid-core and fibrous cap segmentation and stress modeling

Background The benefits of a decreased slice thickness and/or in-plane voxel size in carotid MRI for atherosclerotic plaque component quantification accuracy and biomechanical peak cap stress analysis have not yet been investigated in detail because of practical limitations. Methods In order to provide a methodology that allows such an investigation in detail, numerical simulations of a T1-weighted, contrast-enhanced, 2D MRI sequence were employed. Both the slice thickness (2 mm, 1 mm, and 0.5 mm) and the in plane acquired voxel size (0.62x0.62 mm2 and 0.31x0.31 mm2) were varied. This virtual MRI approach was applied to 8 histology-based 3D patient carotid atherosclerotic plaque models. Results A decreased slice thickness did not result in major improvements in lumen, vessel wall, and lipid-rich necrotic core size measurements. At 0.62x0.62 mm2 in-plane, only a 0.5 mm slice thickness resulted in improved minimum fibrous cap thickness measurements (a 2–3 fold reduction in measurement error) and only marginally improved peak cap stress computations. Acquiring voxels of 0.31x0.31 mm2 in-plane, however, led to either similar or significantly larger improvements in plaque component quantification and computed peak cap stress. Conclusions This study provides evidence that for currently-used 2D carotid MRI protocols, a decreased slice thickness might not be more beneficial for plaque measurement accuracy than a decreased in-plane voxel size. The MRI simulations performed indicate that not a reduced slice thickness (i.e. more isotropic imaging), but the acquisition of anisotropic voxels with a relatively smaller in-plane voxel size could improve carotid plaque quantification and computed peak cap stress accuracy.

Numerical simulations of carotid MRI quantify the accuracy in measuring atherosclerotic plaque components in vivo

Atherosclerotic carotid plaques can be quantified in vivo by MRI. However, the accuracy in segmentation and quantification of components such as the thin fibrous cap (FC) and lipid‐rich necrotic core (LRNC) remains unknown due to the lack of a submillimeter scale ground truth.

Carotid Plaque Morphological Classification Compared With Biomechanical Cap Stress Implications for a Magnetic Resonance Imaging–Based Assessment

Background and Purpose— Two approaches to target plaque vulnerability—a histopathologic classification scheme and a biomechanical analysis—were compared and the implications for noninvasive risk stratification of carotid plaques using magnetic resonance imaging were assessed. Methods— Seventy-five histological plaque cross sections were obtained from carotid endarterectomy specimens from 34 patients (>70% stenosis) and subjected to both a Virmani histopathologic classification (thin fibrous cap atheroma with <0.2-mm cap thickness, presumed vulnerable) and a peak cap stress computation (<140 kPa: presumed stable; >300 kPa: presumed vulnerable). To demonstrate the implications for noninvasive plaque assessment, numeric simulations of a typical carotid magnetic resonance imaging protocol were performed (0.62×0.62 mm2 in-plane acquired voxel size) and used to obtain the magnetic resonance imaging–based peak cap stress. Results— Peak cap stress was generally associated with histological classification. However, only 16 of 25 plaque cross sections could be labeled as high-risk (peak cap stress>300 kPa and classified as a thin fibrous cap atheroma). Twenty-eight of 50 plaque cross sections could be labeled as low-risk (a peak cap stress<140 kPa and not a thin fibrous cap atheroma), leading to a &kgr;=0.39. 31 plaques (41%) had a disagreement between both classifications. Because of the limited magnetic resonance imaging voxel size with regard to cap thickness, a noninvasive identification of only a group of low-risk, thick-cap plaques was reliable. Conclusions— Instead of trying to target only vulnerable plaques, a more reliable noninvasive identification of a select group of stable plaques with a thick cap and low stress might be a more fruitful approach to start reducing surgical interventions on carotid plaques.

The effects of plaque morphology and material properties on peak cap stress in human coronary arteries

Heart attacks are often caused by rupture of caps of atherosclerotic plaques in coronary arteries. Cap rupture occurs when cap stress exceeds cap strength. We investigated the effects of plaque morphology and material properties on cap stress. Histological data from 77 coronary lesions were obtained and segmented. In these patient-specific cross sections, peak cap stresses were computed by using finite element analyses. The finite element analyses were 2D, assumed isotropic material behavior, and ignored residual stresses. To represent the wide spread in material properties, we applied soft and stiff material models for the intima. Measures of geometric plaque features for all lesions were determined and their relations to peak cap stress were examined using regression analyses. Patient-specific geometrical plaque features greatly influence peak cap stresses. Especially, local irregularities in lumen and necrotic core shape as well as a thin intima layer near the shoulder of the plaque induce local stress maxima. For stiff models, cap stress increased with decreasing cap thickness and increasing lumen radius (R = 0.79). For soft models, this relationship changed: increasing lumen radius and increasing lumen curvature were associated with increased cap stress (R = 0.66). The results of this study imply that not only accurate assessment of plaque geometry, but also of intima properties is essential for cap stress analyses in atherosclerotic plaques in human coronary arteries.

The influence of inaccuracies in carotid MRI segmentation on atherosclerotic plaque stress computations

Biomechanical finite element analysis (FEA) based on in vivo carotid magnetic resonance imaging (MRI) can be used to assess carotid plaque vulnerability noninvasively by computing peak cap stress. However, the accuracy of MRI plaque segmentation and the influence this has on FEA has remained unreported due to the lack of a reliable submillimeter ground truth. In this study, we quantify this influence using novel numerical simulations of carotid MRI. Histological sections from carotid plaques from 12 patients were used to create 33 ground truth plaque models. These models were subjected to numerical computer simulations of a currently used clinically applied 3.0 T T1-weighted black-blood carotid MRI protocol (in-plane acquisition voxel size of 0.62 × 0.62 mm2) to generate simulated in vivo MR images from a known underlying ground truth. The simulated images were manually segmented by three MRI readers. FEA models based on the MRI segmentations were compared with the FEA models based on the ground truth. MRI-based FEA model peak cap stress was consistently underestimated, but still correlated (R) moderately with the ground truth stress: R = 0.71, R = 0.47, and R = 0.76 for the three MRI readers respectively (p < 0.01). Peak plaque stretch was underestimated as well. The peak cap stress in thick-cap, low stress plaques was substantially more accurately and precisely predicted (error of -12 ± 44 kPa) than the peak cap stress in plaques with caps thinner than the acquisition voxel size (error of -177 ± 168 kPa). For reliable MRI-based FEA to compute the peak cap stress of carotid plaques with thin caps, the current clinically used in-plane acquisition voxel size (∼0.6 mm) is inadequate. FEA plaque stress computations would be considerably more reliable if they would be used to identify thick-cap carotid plaques with low stresses instead.

Atherosclerotic plaque fibrous cap assessment under an oblique scan plane orientation in carotid MRI.

Carotid magnetic resonance imaging (MRI) is used to noninvasively assess atherosclerotic plaque fibrous cap (FC) status, which is closely related to ischemic stroke. Acquiring anisotropic voxels improves in-plane visualization, however, an oblique scan plane orientation could then obscure a FC (i.e., contrast below the noise level) and thus impair a reliable status assessment. To quantify this, we performed single-slice numerical simulations of a clinical 3.0T, 2D T1-weighted, black-blood, contrast-enhanced pulse sequence with various voxel dimensions: in-plane voxel size of 0.62 mm × 0.62 mm and 0.31 mm × 0.31 mm, slice thickness of 1, 2, and 3 mm. Idealized plaque models (FC thickness of 0.5, 1, and 1.5 mm) were imaged at various scan plane angles (0°-40° in steps of 10°), and the FC contrast was quantified. We found that when imaging thin FCs with anisotropic voxels, the FC contrast decreased when the scan plane orientation angle increased. However, a reduced in-plane voxel size at the cost of an increased slice thickness often led to enhanced FC contrast even in the presence of scan plane orientation angles of up to 40°. It can be concluded that while isotropic-voxel imaging eliminates the issue of scan plane obliqueness, it comes at the cost of reduced FC contrast, thus likely decreasing the reliability of FC status assessment in carotid MRI. If scan plane orientation obliquity at the slice of interest is moderate (<40°) or otherwise diminished through careful scan planning, voxel anisotropy could increase FC contrast and, in effect, increase the reliability of FC status assessment.

Can We use in vivo MRI and FEA to determine peak cap stress in carotid plaques? MRI simulations provide answers

Vulnerable plaques are characterized by a large lipid-rich necrotic core (LRNC) separated by a thin fibrous cap (FC) from the lumen. Plaque rupture occurs when the peak stress in the FC exceeds its strength. Carotid in vivo magnetic resonance imaging (MRI) data can be segmented to obtain the plaque geometry noninvasively. An increasing number of studies use MR imaging for biomechanical finite element analysis (FEA) to compute peak cap stresses [1, 2]. Previous studies have shown that the thickness of the FC is an important determinant of peak cap stress: the thinner the FC, the higher the stress, the higher the plaque rupture risk [3].Copyright

3D Stress Computations in Atherosclerotic Arteries: The Influence of Axial Image Resolution

Sudden rupture of vulnerable atherosclerotic plaques is a major contributing cause of acute myocardial infarctions and ischemic strokes [1]. A vulnerable plaque is defined as a plaque with a large necrotic core and a thin fibrous cap. In order to characterize, and further comprehend, plaque vulnerability from a mechanical point of view, the rupture process can be seen as a mechanical process which occurs when the tensile stress in the fibrous cap exceeds its material strength. Biomechanical stress modeling of plaques using the Finite Element Method (FEM) has been used as a tool to provide insight in the stress distribution in plaques and shows potential to facilitate identification of vulnerable plaques using novel biomechanics-based risk-stratification criteria [1, 2, 3]. Accurate stress prediction using computational modeling depends on a number of factors including material models, computational methods, initial conditions and accurate reconstruction of the plaque geometry from ex vivo or in vivo imaging. The latter received limited attention and lacks a critical evaluation. In case of 3D modeling, the arterial geometry is typically reconstructed by stacking MRI or histology slices in the axial direction and interpolating the geometry without consensus on minimal requirements of inter slice distance (axial sampling distance) [4]. Due to time constraints during the imaging procedure, especially MRI suffers from a limited axial resolution (typically an inter slice distance of 1–3 mm), which might compromise accurate geometry reconstruction which could in turn influence resulting stress computations.Copyright

Plaque Deformation in Atherosclerotic Porcine Arteries

Atherosclerosis is the main cause of cardiovascular disease and is characterized by plaque formation, with lipid accumulation in the arterial wall, covered by a fibrous cap. Rupture of such a cap is the main underlying cause of sudden coronary deaths and strokes. Cap rupture occurs when the mechanical stress in the cap exceeds local cap strength. Accurate determination of cap stresses might therefore play an important role in the prediction of cap rupture. An important determinant of plaque deformation and cap stress is the mechanical behaviour of the diseased plaque components, of which little is known. The aim of this study is to determine material properties of atherosclerotic plaques using a mixed experimental-numerical approach. Plaque deformation as measured ex-vivo with magnetic resonance imaging (MRI) will be matched with computed deformations based on the measured plaque geometry.Copyright