High shear stress relates to intraplaque haemorrhage in asymptomatic carotid plaques.

BACKGROUND AND AIMS: Carotid artery plaques with vulnerable plaque components are related to a higher risk of cerebrovascular accidents. It is unknown which factors drive vulnerable plaque development. Shear stress, the frictional force of blood at the vessel wall, is known to influence plaque formation. We evaluated the association between shear stress and plaque components (intraplaque haemorrhage (IPH), lipid rich necrotic core (LRNC) and/or calcifications) in relatively small carotid artery plaques in asymptomatic persons. METHODS: Participants (n = 74) from the population-based Rotterdam Study, all with carotid atherosclerosis assessed on ultrasound, underwent carotid MRI. Multiple MRI sequences were used to evaluate the presence of IPH, LRNC and/or calcifications in plaques in the carotid arteries. Images were automatically segmented for lumen and outer wall to obtain a 3D reconstruction of the carotid bifurcation. These reconstructions were used to calculate minimum, mean and maximum shear stresses by applying computational fluid dynamics with subject-specific inflow conditions. Associations between shear stress measures and plaque composition were studied using generalized estimating equations analysis, adjusting for age, sex and carotid wall thickness. RESULTS: The study group consisted of 93 atherosclerotic carotid arteries of 74 participants. In plaques with higher maximum shear stresses, IPH was more often present (OR per unit increase in maximum shear stress (log transformed) = 12.14; p = 0.001). Higher maximum shear stress was also significantly associated with the presence of calcifications (OR = 4.28; p = 0.015). CONCLUSIONS: Higher maximum shear stress is associated with intraplaque haemorrhage and calcifications.

Future water resources for food production in five South Asian river basins and potential for adaptation--a modeling study.

The Indian subcontinent faces a population increase from 1.6 billion in 2000 towards 2 billion around 2050. Therefore, expansion of agricultural area combined with increases in productivity will be necessary to produce the food needed in the future. However, with pressure on water resources already being high, and potential effects of climate change still uncertain, the question rises whether there will be enough water resources available to sustain this production. The objective of this study is to make a spatially explicit quantitative analysis of water requirements and availability for current and future food production in five South Asian basins (Indus, Ganges, Brahmaputra, Godavari and Krishna), in the absence or presence of two different adaptation strategies: an overall improvement in irrigation efficiency, and an increase of reservoir storage capacity. The analysis is performed by using the coupled hydrology and crop production model LPJmL. It is found that the Godavari and Krishna basins will benefit most from an increased storage capacity, whereas in the Ganges and the Indus water scarcity mainly takes place in areas where this additional storage would not provide additional utility. Increasing the irrigation efficiency will be beneficial in all basins, but most in the Indus and Ganges, as it decreases the pressure on groundwater resources and decreases the fraction of food production that would become at risk because of water shortage. A combination of both options seems to be the best strategy in all basins. The large-scale model used in this study is suitable to identify hotspot areas and support the first step in the policy process, but the final design and implementation of adaptation options requires supporting studies at finer scales.

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.

Initial stress in biomechanical models of atherosclerotic plaques.

Rupture of atherosclerotic plaques is the underlying cause for the majority of acute strokes and myocardial infarctions. Rupture of the plaque occurs when the stress in the plaque exceeds the strength of the material locally. Biomechanical stress analyses are commonly based on pressurized geometries, in most cases measured by in-vivo MRI. The geometry is therefore not stress-free. The aim of this study is to identify the effect of neglecting the initial stress state on the plaque stress distribution. Fifty 2D histological sections (7 patients, 9 diseased coronary artery segments), perfusion fixed at 100 mmHg, were segmented and finite element models were created. The Backward Incremental method was applied to determine the initial stress state and the zero-pressure state. Peak plaque and cap stresses were compared with and without initial stress. The effect of initial stress on the peak stress was related to the minimum cap thickness, maximum necrotic core thickness, and necrotic core angle. When accounting for initial stress, the general relations between geometrical features and peak cap stress remain intact. However, on a patient-specific basis, accounting for initial stress has a different effect on the absolute cap stress for each plaque. Incorporating initial stress may therefore improve the accuracy of future stress based rupture risk analyses for atherosclerotic plaques.

The influence of wall stress on AAA growth and biomarkers.

OBJECTIVES: This study investigated the relation between abdominal aortic aneurysm (AAA) wall stress, AAA growth rate and biomarker concentrations. With increasing wall stress, more damage may be caused to the AAA wall, possibly leading to progression of the aneurysm and reflection in up- or downregulation of specific circulating biomarkers. Levels of matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1, C-reactive protein and alpha 1-antitrypsin were therefore evaluated. METHODS: Thirty-seven patients (maximum AAA diameter 41-55mm) with two, three or four consecutive computed tomography angiography (CTA) scans were prospectively included. Diameter growth rate in mm/year was determined between each pair of two sequential CTA scans. AAA wall stress was computed by finite element analysis, based on the first of the two sequential CTA scans only (n=69 pairs). Biomarker information was determined in 46 measurements in 18 patients. The relation between AAA diameter and wall stress was determined and the AAA's were divided into three equally sized groups (relative low, medium and high stress). Growth rate and biomarker concentrations were compared between these groups. Additionally, correlation coefficients were computed between absolute wall stress, AAA growth and biomarker concentrations. RESULTS: A relative low AAA wall stress was associated with a lower aneurysm growth rate. Growth rate was also positively related to MMP-9 plasma concentration (r=0.32). The average MMP-9 and CRP concentrations increased with increasing degrees of relative wall stress, although the absolute and relative wall stress did not correlate with any of the biomarkers. CONCLUSION: Although lower relative wall stress was associated to a lower AAA growth rate, no relation was found between biomarker concentrations and wall stress. Future research may focus on more and extensive biomarker measurements in relation to AAA wall stress.

Importance of initial stress for abdominal aortic aneurysm wall motion: dynamic MRI validated finite element analysis.

Currently the transverse diameter is the primary decision criterion to assess rupture risk in patients with an abdominal aortic aneurysm (AAA). To obtain a measure for more patient-specific risk assessment, aneurysm wall stress, calculated using finite element analysis (FEA), has been evaluated in literature. In many cases, initial stress, present in the AAA wall during image acquisition, is not taken into account. In the current study the effect of initial stress incorporation (ISI) is determined by directly comparing wall displacements extracted from FEA and dynamic MRI. Ten patients with an aneurysm diameter >5.5 cm were scanned with cardiac triggered MRI. Semi-automatic segmentation of the AAA was performed on the diastolic phase. The segmented in-slice contours were propagated through the remaining cardiac phases using an active contour model as to track wall displacements on MRI. Consequently, FEA with and without ISI (no-ISI) was performed using the diastolic geometry with simultaneously measured intra-aneurysm pressure values as boundary condition. Contours extracted from FEA were compared with MRI contours at corresponding cardiac phases by distance and relative area differences. The wall displacements from FEA with ISI show significant better correspondence with wall motion from MRI data in comparison with the no-ISI FEA (deviation in wall displacement 1.7% vs. 12.4%; p<0.001). Based on these results it can be concluded that incorporation of initial stress significantly improves wall displacement accuracy of FEA and therefore it should be incorporated in future analyses.

Initial stress and nonlinear material behavior in patient-specific AAA wall stress analysis.

Rupture risk estimation of abdominal aortic aneurysms (AAA) is currently based on the maximum diameter of the AAA. A more critical approach is based on AAA wall stress analysis. For that, in most cases, the AAA geometry is obtained from CT-data and treated as a stress free geometry. However, during CT imaging, the AAA is subjected to a time-averaged blood pressure and is therefore not stress free. The aim of this study is to evaluate the effect of neglecting these initial stresses (IS) on the patient-specific AAA wall stress as computed by finite element analysis. Additionally, the contribution of the nonlinear material behavior of the AAA wall is evaluated. Thirty patients with maximum AAA diameters below the current surgery criterion were scanned with contrast-enhanced CT and the AAA's were segmented from the image data. The mean arterial blood pressure (MAP) was measured immediately after the CT-scan and used to compute the IS corresponding with the CT geometry and MAP. Comparisons were made between wall stress obtained with and without IS and with linear and nonlinear material properties. On average, AAA wall stresses as computed with IS were higher than without IS. This was also the case for the stresses computed with the nonlinear material model compared to the linear material model. However, omitting initial stress and material nonlinearity in AAA wall stress computations leads to different effects in the resulting wall stress for each AAA. Therefore, provided that other assumptions made are not predominant, IS cannot be discarded and a nonlinear material model should be used in future patient-specific AAA wall stress analyses.

Patient-specific AAA wall stress analysis: 99-percentile versus peak stress.

OBJECTIVE: Biomechanically, rupture of an Abdominal Aortic Aneurysm (AAA) occurs when the stress acting on the wall due to the blood pressure, exceeds the strength of the wall. Peak wall stress estimations, based on CT reconstruction, may be prone to observer variation. This study focuses on the robustness and reproducibility of AAA wall stress assessment and the relation with geometrical features of the AAA. METHODS: The AAAs of twenty patients were reconstructed by three operators. Both the peak and 99-percentile stress were used for intra- and inter-operator variability using the intraclass correlation coefficient (ICC). A regression analysis was performed to relate the stress parameters with the maximum diameter. Outliers were analyzed by their geometrical characteristics. RESULTS: The intra-operator ICC was 0.73-0.79 for the peak stress and 0.94 for the 99-percentile stress. The inter-operator ICC was 0.71 for the peak stress and 0.95 for the 99-percentile stress. A significant linear relation with the diameter was found only for the 99-percentile stress. CONCLUSIONS: The 99-percentile stress is more reproducible than peak wall stress. A significant relation between wall stress and diameter was found. Other geometrical features had no statistical relation with high stress.

Towards patient-specific risk assessment of abdominal aortic aneurysm.

Diagnosis of vascular disease and selection and planning of therapy are to a large extent based on the geometry of the diseased vessel. Treatment of a particular vascular disease is usually considered if the geometrical parameter that characterizes the severity of the disease, e.g. % vessel narrowing, exceeds a threshold. The thresholds that are used in clinical practice are based on epidemiological knowledge, which has been obtained by clinical studies including large numbers of patients. They may apply "on average", but they can be sub-optimal for individual patients. To realize more patient-specific treatment decision criteria, more detailed knowledge may be required about the vascular hemodynamics, i.e. the blood flow and pressure in the diseased vessel and the biomechanical reaction of the vessel wall to this flow and pressure. Over the last decade, a substantial number of publications have appeared on hemodynamic modeling. Some studies have provided first evidence that this modeling may indeed be used to support therapeutic decisions. The goal of the research reported in this paper is to go one step further, namely to investigate the feasibility of a patient-specific hemodynamic modeling methodology that is not only effective (improves therapeutic decisions), but that is also efficient (easy to use, fast, as much as possible automatic) and robust (insensitive to variation in the quality of the input data, same outcome for different users). A review is presented of our research performed during the last 5 years and the results that were achieved. This research focused on the risk assessment for one particular disease, namely abdominal aortic aneurysm, a life-threatening dilatation of the abdominal aorta.