A Framework for Local Mechanical Characterization of Atherosclerotic Plaques: Combination of Ultrasound Displacement Imaging and Inverse Finite Element Analysis.

Biomechanical models have the potential to predict plaque rupture. For reliable models, correct material properties of plaque components are a prerequisite. This study presents a new technique, where high resolution ultrasound displacement imaging and inverse finite element (FE) modeling is combined, to estimate material properties of plaque components. Iliac arteries with plaques were excised from 6 atherosclerotic pigs and subjected to an inflation test with pressures ranging from 10 to 120 mmHg. The arteries were imaged with high frequency 40 MHz ultrasound. Deformation maps of the plaques were reconstructed by cross correlation of the ultrasound radiofrequency data. Subsequently, the arteries were perfusion fixed for histology and structural components were identified. The histological data were registered to the ultrasound data to construct FE model of the plaques. Material properties of the arterial wall and the intima of the atherosclerotic plaques were estimated using a grid search method. The computed displacement fields showed good agreement with the measured displacement fields, implying that the FE models were able to capture local inhomogeneities within the plaque. On average, nonlinear stiffening of both the wall and the intima was observed, and the wall of the atheroslcerotic porcine iliac arteries was markedly stiffer than the intima (877 ± 459 vs. 100 ± 68 kPa at 100 mmHg). The large spread in the data further illustrates the wide variation of the material properties. We demonstrated the feasibility of a mixed experimental-numerical framework to determine the material properties of arterial wall and intima of atherosclerotic plaques from intact arteries, and concluded that, due to the observed variation, plaque specific properties are required for accurate stress simulations.

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.

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 mm(2) 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 κ=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.

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.

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.

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

PURPOSE: 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. METHODS: A novel approach was taken by numerically simulating in vivo carotid MRI providing a ground truth comparison. Upon evaluation of a simulated clinical protocol, MR readers segmented simulated images of cross-sectional plaque geometries derived from histological data of 12 patients. RESULTS: MR readers showed high correlation (R) and intraclass correlation (ICC) in measuring the luminal area (R = 0.996, ICC = 0.99), vessel wall area (R = 0.96, ICC = 0.94) and LRNC area (R = 0.95, ICC = 0.94). LRNC area was underestimated (mean error, -24%). Minimum FC thickness showed a mediocre correlation and intraclass correlation (R = 0.71, ICC = 0.69). CONCLUSION: Current clinical MRI can quantify carotid plaques but shows limitations for thin FC thickness quantification. These limitations could influence the reliability of carotid MRI for assessing plaque rupture risk associated with FC thickness. Overall, MRI simulations provide a feasible methodology for assessing segmentation and quantification accuracy, as well as for improving scan protocol design.

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.

Microfluidic particle sorting utilizing inertial lift force.

A simple passive microfluidic device that continuously separates microparticles is presented. Its development is motivated by the need for specific size micro perfluorocarbon (PFC) droplets to be used for a novel gas embolotherapy method. The device consists of a rectangular channel in which inertial lift forces are utilized to separate particles in lateral distance. At the entrance of the channel, particles are introduced at the center by focusing the flow from a center channel with flow from two side channels. Downstream, large particles will occupy a lateral equilibrium position in shorter axial distance than small particles. At the exit of the channel, flow containing large particles is separated from flow containing small particles. It is shown that 10.2-µm diameter microspheres can be separated from 3.0-µm diameter microspheres with a separation efficiency of 69-78% and a throughput in the order of 2 ·104 particles per minute. Computational Fluid Dynamics (CFD) calculations were done to calculate flow fields and verify theoretical particle trajectories. Theory underlying this research shows that higher separation efficiencies for very specific diameter cut-off are possible. This microfluidic channel design has a simple structure and can operate without external forces which makes it feasible for lab-on-a-chip (LOC) applications.