Experimental investigation of intravascular OCT for imaging of intracranial aneurysms

Purpose

Rupture risk assessment of an intracranial aneurysm (IA) is an important factor for indication of therapy. Until today, there is no suitable objective prediction method. Conventional imaging modalities cannot assess the IA’s vessel wall. We investigated the ability of intravascular optical coherence tomography (OCT) as a new tool for the characterization and evaluation of IAs.

Materials and methods

An experimental setup for acquisition of geometrical aneurysm parameters was developed. Object of basic investigation was a silicone phantom with six IAs from patient data. For structural information, three circle of Willis were dissected and imaged postmortem. All image data were postprocessed by medical imaging software.

Results

Geometrical image data of a phantom with six different IAs were acquired. The geometrical image data showed a signal loss, e.g., in aneurysms with a high bottleneck ratio. Imaging data of vessel specimens were evaluated with respect to structural information that is valuable for the characterization of IAs. Those included thin structures (intimal flaps), changes of the vessel wall morphology (intimal thickening, layers), adjacent vessels, small vessel outlets, arterial branches and histological information.

Conclusion

Intravascular OCT provides new possibilities for diagnosis and rupture assessment of IAs. However, currently used imaging system parameters have to be adapted and new catheter techniques have to be developed for a complete assessment of the morphology of IAs.

     

Semiautomatic neck curve reconstruction for intracranial aneurysm rupture risk assessment based on morphological parameters

Purpose

Morphological parameters of intracranial aneurysms (IAs) are well established for rupture risk assessment. However, a manual measurement is error-prone, not reproducible and cumbersome. For an automatic extraction of morphological parameters, a 3D neck curve reconstruction approach to delineate the aneurysm from the parent vessel is required.

Methods

We present a 3D semiautomatic aneurysm neck curve reconstruction for the automatic extraction of morphological parameters which was developed and evaluated with an experienced neuroradiologist. We calculate common parameters from the literature and include two novel angle-based parameters: the characteristic dome point angle and the angle difference of base points.

Results

We applied our method to 100 IAs acquired with rotational angiography in clinical routine. For validation, we compared our approach to manual segmentations yielding highly significant correlations. We analyzed 95 of these datasets regarding rupture state. Statistically significant differences were found in ruptured and unruptured groups for maximum diameter, maximum height, aspect ratio and the characteristic dome point angle. These parameters were also found to statistically significantly correlate with each other.

Conclusions

The new 3D neck curve reconstruction provides robust results for all datasets. The reproducibility depends on the vessel tree centerline and the user input for the initial dome point and parameters characterizing the aneurysm neck region. The characteristic dome point angle as a new metric regarding rupture risk assessment can be extracted. It requires less computational effort than the complete neck curve reconstruction.

     

Fusion of fibrous cap thickness and wall shear stress to assess plaque vulnerability in coronary arteries: a pilot study

Purpose

Identification of rupture-prone plaques in coronary arteries is a major clinical challenge. Fibrous cap thickness and wall shear stress are two relevant image-based risk factors, but these two parameters are generally computed and analyzed separately. Accordingly, combining these two parameters can potentially improve the identification of at-risk regions. Therefore, the purpose of this study is to investigate the feasibility of the fusion of wall shear stress and fibrous cap thickness of coronary arteries in patient data.

Methods

Fourteen patients were included in this pilot study. Imaging of the coronary arteries was performed with optical coherence tomography and with angiography. Fibrous cap thickness was automatically quantified from optical coherence tomography pullbacks using a contour segmentation approach based on fast marching. Wall shear stress was computed by applying computational fluid dynamics on the 3D volume reconstructed from two angiograms. The two parameters then were co-registered using anatomical landmarks such as side branches.

Results

The two image modalities were successfully co-registered, with a mean (±SD) error corresponding to \(8.6\,\pm \,6.7\,\%\) of the length of the analyzed region. For all the analyzed participants, the average thinnest portion of each fibrous cap was \(129\,\pm \,69\,\upmu \text {m}\), and the average WSS value at the location of the fibrous cap was \(1.46\,\pm \,1.16\,\text {Pa}\). A unique index was finally generated for each patient via the fusion of fibrous cap thickness and wall shear stress measurements, to translate all the measured parameters into a single risk map.

Conclusion

The introduced risk map integrates two complementary parameters and has potential to provide valuable information about plaque vulnerability.

     

Development and internal validation of an aneurysm rupture probability model based on patient characteristics and aneurysm location,morphology, and hemodynamics

Purpose

Unruptured cerebral aneurysms pose a dilemma for physicians who need to weigh the risk of a devastating subarachnoid hemorrhage against the risk of surgery or endovascular treatment and their complications when deciding on a treatment strategy. A prediction model could potentially support such treatment decisions. The aim of this study was to develop and internally validate a model for aneurysm rupture based on hemodynamic and geometric parameters, aneurysm location, and patient gender and age.

Methods

Cross-sectional data from 1061 patients were used for image-based computational fluid dynamics and shape characterization of 1631 aneurysms for training an aneurysm rupture probability model using logistic group Lasso regression. The model’s discrimination and calibration were internally validated based on the area under the curve (AUC) of the receiver operating characteristic and calibration plots.

Results

The final model retained 11 hemodynamic and 12 morphological variables, aneurysm location, as well as patient age and gender. An adverse hemodynamic environment characterized by a higher maximum oscillatory shear index, higher kinetic energy and smaller low shear area as well as a more complex aneurysm shape, male gender and younger age were associated with an increased rupture risk. The corresponding AUC of the model was 0.86 (95% CI [0.85, 0.86], after correction for optimism 0.84).

Conclusion

The model combining variables from various domains was able to discriminate between ruptured and unruptured aneurysms with an AUC of 86%. Internal validation indicated potential for the application of this model in clinical practice after evaluation with longitudinal data.

     

Wall shear stress measured by phase contrast cardiovascular magnetic resonance in children and adolescents with pulmonary arterial hypertension

Background

Pulmonary arterial hypertension (PAH) is a devastating disease with significant morbidity and mortality. At the macroscopic level, disease progression is observed as a complex interplay between mean pulmonary artery pressure, pulmonary vascular resistance, pulmonary vascular stiffness, arterial size, and flow. Wall shear stress (WSS) is known to mediate or be dependent on a number of these factors. Given that WSS is known to promote architectural vessel remodeling, it is imperative that the changes of this factor be quantified in the presence of PAH.

Methods

In this study, we analyzed phase contrast imaging of the right pulmonary artery derived from cardiovascular magnetic resonance to quantify the local, temporal and circumferentially averaged WSS of a PAH population and a pediatric control population. In addition, information about flow and relative area change were derived.

Results

Although the normotensive and PAH shear waveform exhibited a WSS profile which is uniform in magnitude and direction along the vessel circumference at systole, time-averaged WSS (2.2 ± 1.6 vs. 6.6 ± 3.4 dynes/cm², P = 0.018) and systolic WSS (8.2 ± 5.0 v. 20.0 ± 9.1 dynes/cm², P = 0.018) was significantly depressed in the PAH population as compared to the controls. BSA-indexed PA diameter was significantly larger in the PAH population (1.5 ± 0.4 vs. 0.7 ± 0.1 cm/m², P = 0.003).

Conclusions

In the presence of preserved flow rates through a large PAH pulmonary artery, WSS is significantly decreased. This may have implications for proximal pulmonary artery remodeling and cellular function in the progression of PAH.     

利用血流剪应力定量分析软件评价颈动脉粥样硬化

目的 应用血流剪应力定量分析软件,与传统Hagen-Poiseuille公式法进行比较,分析健康颈总动脉与内中膜增厚处颈总动脉壁面剪应力（WSS）,探讨血流剪应力定量分析软件评估颈动脉WSS值的价值。方法 运用剪应力定量分析软件分析50名健康体检者（健康组）和50例颈总动脉内中膜增厚（厚度为1.0~1.3 mm）患者（增厚组）颈总动脉多普勒血流图像,以Matlab为软件平台绘制血流剪应力二维空间分布图、三维空间分布图及剪应力融合图像,计算颈总动脉WSS分布均值（WSS值）,并与Hagen-Poiseuille公式计算结果进行比较。结果 健康组血流剪应力定量分析软件计算所得颈总动脉WSS值为（6.91±1.20）dyne/cm²,Hagen-Poiseuille公式法结果为（7.13±1.24）dyne/cm²（P>0.05）;增厚组两种方法计算得出的颈总动脉WSS值分别为（2.87±0.59）dyne/cm²、（3.12±0.65）dyne/cm²,差异无统计学意义（P>0.05）,均显著低于健康组（P<0.05）。结论 利用血流剪应力定量分析软件可以准确、快捷地评估动脉血流WSS。     

MR血管成像血流动力学预测椎-基底动脉交界处裂隙型开窗患者发生后循环脑梗死

目的 评估基于MR血管成像(MRA)血流动力学预测椎-基底动脉交界处裂隙型开窗患者发生后循环脑梗死的价值。方法 随机收集40例经头部MRA诊断的椎-基底动脉交界处裂隙型开窗患者，将其中20例伴后循环脑梗死归为脑梗死组，20例无脑梗死者纳入对照组。基于MRA建立椎-基底动脉模型，以开窗汇合处为A位，开窗左侧血管支为B位，开窗右侧血管支为C位，开窗起点处为D位，分别测量血流动力学参数，包括血流速度(V)、梯度振荡数(GON)、振荡剪应指数(OSI)、壁面压力(WP)、壁面切应力(WSS)及动脉瘤形成指数(AFI)。采用单因素及二元logistic逐步回归分析筛选椎-基底动脉交界处裂隙型开窗患者发生后循环脑梗死的血流动力学参数相关独立危险因素，并以之建立回归模型；绘制受试者工作特征(ROC)曲线，计算曲线下面积(AUC),评估单一独立危险因素及回归模型预测椎-基底动脉交界处裂隙型开窗患者发生后循环脑梗死的效能。结果 脑梗死组V(A)、V(B)及WSS(D)均高于对照组(P均<0.05),且三者均为椎-基底动脉交界处裂隙型开窗患者发生后循环脑梗死的独立危险因素。以V(A)、V(B)及WS...     

Evaluation of 3D blood flow patterns and wall shear stress in the normal and dilated thoracic aorta using flow-sensitive 4D CMR

Background

The purpose of this study was to investigate 3D flow patterns and vessel wall parameters in patients with dilated ascending aorta, age-matched subjects, and healthy volunteers.

Methods

Thoracic time-resolved 3D phase contrast CMR with 3-directional velocity encoding was applied to 33 patients with dilated ascending aorta (diameter ≥40 mm, age=60±16 years), 15 age-matched normal controls (diameter ≤37 mm, age=68±7.5 years) and 15 young healthy volunteers (diameter ≤30 mm, age=23±2 years). 3D blood flow was visualized and flow patterns were graded regarding presence of supra-physiologic-helix and vortex flow using a semi-quantitative 3-point grading scale. Blood flow velocities, regional wall shear stress (WSS), and oscillatory shear index (OSI) were quantified.

Results

Incidence and strength of supra-physiologic-helix and vortex flow in the ascending aorta (AAo) was significantly higher in patients with dilated AAo (16/33 and 31/33, grade 0.9±1.0 and 1.5±0.6) than in controls (2/15 and 7/15, grade 0.2 ± 0.6 and 0.6 ± 0.7, P<.05) or healthy volunteers (1/15 and 0/15, grade 0.1 ± 0.3 P<.05). Greater strength of the ascending aortic helix and vortex flow were associated with significant differences in AAo diameters (P<.05). Peak systolic WSS in the ascending aorta and aortic arch was significantly lower in patients with dilated AAo (P<.0157-.0488). AAo diameter positively correlated to time to peak systolic velocities (r=0.30-0.53, P<.04), OSI (r=0.33-0.49, P<0.02) and inversely correlated to peak systolic WSS (r=0.32-0.40, P<.03). Peak systolic WSS was significantly lower in AAo aneurysms at the right and outer curvature within the AAo and proximal arch (P<.01-.05).

Conclusions

Increase in AAo diameter is significantly correlated with the presence and strength of supra-physiologic-helix and vortex formation in the AAo, as well with decrease in systolic WSS and increase in OSI.     

AneuSearch: a software prototype for intracranial aneurysm searching and clinical decision support

Purpose

Clinical decisions for treating intracranial aneurysms (IA) require integrating information in various forms and from multiple sources. We aim to establish a framework namely AneuSearch to integrate relevant information in IA management and also allow for efficient IA searching based on carefully designed criteria.

Methods

The backbone of AneuSearch is an open-source three-tier DICOM image management system called DCM4Chee, which is a Java implementation for PACS. A supplementary database (AneuSearchDB) was developed to contain morphological features, hemodynamic and histological data. The relational tables in AneuSearchDB correspond to the most fundamental questions raised by neurosurgeons during IA treatment. The system was developed through collaborations between bioengineers and neurosurgeons.

Results

The prototype software has been deployed to computers in a Mianyang Central Hospital in China. Currently, the system contains the data of 105 IA patients, seven hemodynamic simulation results and nine histological section images. This system was queried as per given criteria and can also provide blood flow data after running an external computational fluid dynamics software.

Conclusions

The prototype software provides a novel tool to IA management. Future works include incorporating IA treatment criteria in IA rupture risk assessment.     

Blood Flow Visualization and Wall Shear Stress Measurement of Carotid Arteries Using Vascular Vector Flow Mapping

Carotid artery ultrasound is extensively used to assess early- and late-stage atherosclerosis via the intima–media thickness and increased blood flow velocity caused by stenosis, respectively. However, the effect of wall shear stress (WSS) has not been considered to date. This study aimed to visualize the blood flow of carotid arteries and measured WSS using vector flow mapping (VFM) developed specifically for vascular use. Patients with cerebrovascular diseases were prospectively enrolled and examined with carotid ultrasound using VFM Vascular. WSS was calculated in the common carotid artery and internal carotid artery. Blood flow in 82 common carotid arteries was visualized with VFM Vascular. The maximum and mean WSSs were negatively correlated with age and intima–media thickness. The WSS in 16 internal carotid artery plaques was significantly higher upstream of the plaque than downstream. Therefore, VFM Vascular is a promising method that provides a novel indicator of atherosclerosis.     

Role of ultrasonic shear rate estimation errors in assessing inflammatory response and vascular risk

Atherosclerotic lesions preferentially originate in arterial regions that experience low wall shear stress (WSS) and reversing flow patterns. Therefore, routinely monitoring arterial WSS may help to identify the potential sites of early atherosclerosis. A new noninvasive ultrasonic method implemented with coded excitation techniques was utilized to improve WSS estimation accuracy and precision by providing high spatial and temporal resolution. WSS measurement errors were quantified in a model system by scanning a linearly varying WSS field (0.3 to 1.9 Pa) within a flow chamber. A 13-bit optimal code (Opt) was found to be most effective in reducing bias and standard deviation in WSS estimates down to approximately 10% and approximately 8%. The measurement errors slowly increased with input WSS for all imaging pulses. The expression of endothelial cellular adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (E-selectin) was investigated over a similar shear range (0 to 1.6 Pa) to study the impact of relating shear-mediated cellular adhesion molecule (CAM) expression to inaccuracies in WSS measurements. We quantified this influence as the prediction error, which accounts for the ultrasonic measurement errors and the sensitivity of CAM expression within certain shear ranges. The highest prediction errors were observed at WSS <0.8 Pa, where CAM expression is most responsive to WSS. The results emphasize the importance of minimizing estimation errors, especially within low shear regions. Preliminary two-dimensional in vivo shear imaging is also presented to provide information about the spatial heterogeneity in arterial WSS distribution.     

Multiple intracranial aneurysms: a direct hemodynamic comparison between ruptured and unruptured vessel malformations

Purpose

Despite numerous studies addressing the rupture risk of intracranial aneurysms that have been published, the assessment thereof still remains challenging. Image-based simulations enable a precise prediction of patient-specific blood flow information. However, those approaches normally consider only small segments of the complete cerebral vasculature.

Methods

To test the validity of the consideration of single aneurysms in one computational setup, domains of the complete anterior and posterior circulations with multiple intracranial aneurysms (MIA) were simulated. Six patients with MIA were investigated, while 3D surfaces of eleven unruptured and six ruptured aneurysms were segmented. The segmentations were used for the determination of morphological parameters and also for image-based blood flow simulations used to characterize the hemodynamic properties of each aneurysm.

Results

In the geometric comparison, neck aspect ratios of unruptured and ruptured aneurysms did not differ significantly. In contrast, size ratios, aspect ratios, surface areas, volumes, and non-sphericity indices were significantly higher in the ruptured cases. The analysis of hemodynamic parameters demonstrated that in each patient, the ruptured aneurysm exhibited the lowest averaged wall shear stresses and highest oscillatory shears. Unstable flow was also detected in ruptured aneurysms based on increased oscillatory velocity.

Conclusion

In this small study involving patients with MIA, different morphologies and flow patterns were observed between ruptured and unruptured aneurysms. The analysis of the hemodynamics in such patients revealed a good agreement with studies that only considered single malformations. Additionally, complex flow patterns are detected in ruptured cases, which require deeper investigation.

     

Unruptured cerebral aneurysms in elderly patients: key challenges and management

Unruptured cerebral aneurysms are increasingly identified in elderly patients as the global life expectancy continues to rise and non-invasive vascular imaging becomes more prevalent. The optimal management of unruptured aneurysms in elderly patients remains controversial. Variability in life expectancy, comorbidities and rupture risk coupled with heterogenous endovascular and surgical treatments contribute to a paucity of clear guidelines, and current management is highly individualized. Elderly patients present unique considerations including frailty, cognitive dysfunction, vasculopathy, reduced life expectancy and overall worse prognosis in case of rupture which shape the risks and likelihood of success of endovascular and microsurgical treatment. In this review, we provide a comprehensive overview of unruptured cerebral aneurysms in the elderly, with a particular focus on the natural history, key challenges associated with advanced age, management and future innovations to further refine treatment.

Key Messages

1. The management of unruptured cerebral aneurysms in elderly patients remains controversial.
2. Key challenges including frailty, cognitive dysfunction, reduced life expectancy, vasculopathy and poor prognosis with aneurysm rupture add complexity to endovascular and surgical decision making not encountered with younger demographics.
3. A thorough understanding of available treatment options, likelihood of treatment success and associated risks weighed against the risk of aneurysm rupture informs patient discussion and management.

     

以CT图像为基础构建人狭窄颈动脉的血流动力学模型

目的探索以CT图像为基础构建动脉血流动力学模型的技术方法,对颈动脉狭窄局部进行计算血流动力学（computationalfluid dynamics,CFD）数值模拟。方法以CT图像为基础进行颈动脉三维几何建模,依据MRI测量的模型出入口血流速度确定数值模拟的边界条件。结果数值模拟结果包括狭窄颈动脉内的速度场和壁面剪应力（wall shear stress,WSS）分布,可见狭窄段血管WSS增高,且在狭窄邻近区域出现新的血液逆流区（对应低或振荡的WSS）。结论以CT图像为基础的CFD技术是在体评价人狭窄颈动脉内血流动力学状况与颈动脉斑块之间关系的有效方法。     

In vivo wall shear stress measurements using phase-contrast MRI

There is growing evidence to suggest that endothelial biology and atherosclerosis depend on arterial wall shear stress (WSS). We review the existing literature on in vivo measurements of WSS in healthy individuals using phase-contrast MRI, which is a promising, noninvasive technique for determinating various blood flow characteristics. WSS data exist for the following arteries: carotid, brachial, aorta and femoral. Measured values indicate that WSS is site specific, a finding which opposes the notion that physiological WSS values are maintained at a constant magnitude in all parts of the arterial system. Among the WSS values obtained at the same site by different investigators there is qualitative agreement; however, differences exist in absolute values mainly due to the dependence on the method used to obtain WSS values from velocity data.     

基于对比增强流场的2型糖尿病患者颈动脉窦区壁剪应力分布分析

目的 采用对比增强流场（CEFF）技术观察2型糖尿病（T2DM）患者颈动脉窦区壁面剪应力（WSS）的分布规律。方法 选取47例T2DM患者和25名健康志愿者（对照组）,并根据颈总动脉内中膜厚度（IMT）将T2DM患者分为IMT正常组（n=21）和IMT增厚组（n=26）,采用CEFF分析软件,计算颈动脉窦区WSS,绘制相应WSS空间分布图,记录颈内动脉起始段后壁WSS值并进行统计学分析。结果 3组颈动脉窦区均存在两个低WSS区和一个高WSS区：颈总动脉远端至颈内动脉起始段后壁存在大范围低WSS区,颈总动脉远端前壁存在小范围低WSS区,颈内动脉起始段前壁为高WSS区。IMT正常组[（3.39±0.60）dyne/cm²]和IMT增厚组[（2.58±0.46）dyne/cm²]患者颈内动脉后壁WSS值均较对照组[（3.74±0.53）dyne/cm²]显著减低（P均<0.05）;IMT增厚组较IMT正常组减低（P<0.05）。结论 CEFF图像技术可初步定量检测动脉WSS,有望早期、可视化评估颈动脉硬化。     

Image-based carotid flow reconstruction: a comparison between MRI and ultrasound

Atherosclerosis is a major cause of morbidity and mortality. Its apparent link with wall shear stress (WSS) has led to considerable interest in the in vivo estimation of WSS. Determining WSS by combining medical images with computational fluid dynamics (CFD) simulations can be performed both with magnetic resonance imaging (MRI) and three-dimensional ultrasound (3DUS). This study compares predicted 3D flow patterns based on black blood MRI and 3DUS. Velocity fields in the carotid arteries of nine subjects have been reconstructed, and the haemodynamic wall parameters WSS, oscillatory shear index (OSI), WSS gradients (WSSG) and angle gradients (WSSAG) were compared between the two imaging techniques. There was a good qualitative agreement between results derived from MRI and 3DUS (average correlation strength above 0.60). The root mean square error between haemodynamic wall parameters was comparable to the range of the expected variability of each imaging technique (WSS: 0.411 N m(-2); OSI: 0.048; temporal WSSG: 150 N s(-1) m(-2); spatial WSSG: 2.29 N m(-3); WSSAG: 87.6 rad m(-1)). In conclusion, MRI and 3DUS are capable of providing haemodynamic parameters when combined with CFD, and the predictions are in most cases qualitatively and quantitatively similar. The relatively high cost of MRI and continuing improvement in ultrasound favour US to MRI for future haemodynamic studies of superficial arteries.     

4D cardiovascular magnetic resonance velocity mapping of alterations of right heart flow patterns and main pulmonary artery hemodynamics in tetralogy of Fallot

Background

To assess changes in right heart flow and pulmonary artery hemodynamics in patients with repaired Tetralogy of Fallot (rTOF) we used whole heart, four dimensional (4D) velocity mapping (VM) cardiovascular magnetic resonance (CMR).

Methods

CMR studies were performed in 11 subjects with rTOF (5M/6F; 20.1 ± 12.4 years) and 10 normal volunteers (6M/4F; 34.2 ± 13.4 years) on clinical 1.5T and 3.0T MR scanners. 4D VM-CMR was performed using PC VIPR (Phase Contrast Vastly undersampled Isotropic Projection Reconstruction). Interactive streamline and particle trace visualizations of the superior and inferior vena cava (IVC and SVC, respectively), right atrium (RA), right ventricle (RV), and pulmonary artery (PA) were generated and reviewed by three experienced readers. Main PA net flow, retrograde flow, peak flow, time-to-peak flow, peak acceleration, resistance index and mean wall shear stress were quantified. Differences in flow patterns between the two groups were tested using Fisher''s exact test. Differences in quantitative parameters were analyzed with the Kruskal-Wallis rank sum test.

Results

4D VM-CMR was successfully performed in all volunteers and subjects with TOF. Right heart flow patterns in rTOF subjects were characterized by (a) greater SVC/IVC flow during diastole than systole, (b) increased vortical flow patterns in the RA and in the RV during diastole, and (c) increased helical or vortical flow features in the PA''s. Differences in main PA retrograde flow, resistance index, peak flow, time-to-peak flow, peak acceleration and mean wall shear stress were statistically significant.

Conclusions

Whole heart 4D VM-CMR with PC VIPR enables detection of both normal and abnormal right heart flow patterns, which may allow for comprehensive studies to evaluate interdependencies of post-surgically altered geometries and hemodynamics.     

Sealed rupture of abdominal aortic aneurysms: CT features in 6 patients and a review of the literature

Purpose  

To assess the CT features of sealed rupture of abdominal aortic aneurysm.     

High wall shear stress and high-risk plaque: an emerging concept

In recent years, there has been a significant effort to identify high-risk plaques in vivo prior to acute events. While number of imaging modalities have been developed to identify morphologic characteristics of high-risk plaques, prospective natural-history observational studies suggest that vulnerability is not solely dependent on plaque morphology and likely involves additional contributing mechanisms. High wall shear stress (WSS) has recently been proposed as one possible causative factor, promoting the development of high-risk plaques. High WSS has been shown to induce specific changes in endothelial cell behavior, exacerbating inflammation and stimulating progression of the atherosclerotic lipid core. In line with experimental and autopsy studies, several human studies have shown associations between high WSS and known morphological features of high-risk plaques. However, despite increasing evidence, there is still no longitudinal data linking high WSS to clinical events. As the interplay between atherosclerotic plaque, artery, and WSS is highly dynamic, large natural history studies of atherosclerosis that include WSS measurements are now warranted. This review will summarize the available clinical evidence on high WSS as a possible etiological mechanism underlying high-risk plaque development.