Simultaneous ultrasound assessment of brachial artery shear stimulus and flow-mediated dilation during reactive hyperemia

In flow-mediated dilation (FMD) studies, brachial artery diameter changes due to reactive hyperaemia are typically measured through manual or automatic analysis of high resolution B-mode images while the stimulus of diameter change, i.e., the flow change, is qualitatively estimated by measuring the mean velocity in the vessel and assuming a parabolic velocity profile. This article describes an experimental approach to simultaneously measure the wall shear rate (WSR) and the diameter variations, through multigate spectral Doppler and B-mode image processing, respectively. By using an ultrasound advanced open platform (ULA-OP), experimental results from the brachial arteries of 15 presumed healthy volunteers have been obtained. The mean increments during reflow against baseline were 105% ± 22% for the peak WSR and 8% ± 3% for the FMD. The mean time interval between the WSR peak and the beginning of plateau of diameter waveform was 38 ± 8 s. The results confirm that in young healthy subjects the postischemic vasodilation of brachial artery is largely correlated to the WSR increase.     

Spatio-Temporal Flow and Wall Shear Stress Mapping Based on Incoherent Ensemble-Correlation of Ultrafast Contrast Enhanced Ultrasound Images

In this study, a technique for high-frame-rate ultrasound imaging velocimetry (UIV) is extended first to provide more robust quantitative flow velocity mapping using ensemble correlation of images without coherent compounding, and second to generate spatio-temporal wall shear stress (WSS) distribution. A simulation model, which couples the ultrasound simulator with analytical flow solution, was implemented to evaluate its accuracy. It is shown that the proposed approach can reduce errors in velocity estimation by up to 10-fold in comparison with the coherent correlation approach. Mean errors (ME) of 3.2% and 8.6% were estimated under a steady flow condition, while 3.0% and 10.6% were found under a pulsatile condition for the velocity and wall shear rate (WSR) measurement, respectively. Appropriate filter parameters were selected to constrain the velocity profiles before WSR estimations and the effects of incorrect wall tracking were quantified under a controlled environment. Although accurate wall tracking is found to be critical in WSR measurement (as a 200?µm deviation from the wall may yield up to a 60% error), this can be mitigated by HFR imaging (of up to 10?kHz) with contrast agents, which allow for improved differentiation of the wall-fluid boundaries. In vitro investigations on two carotid bifurcation phantoms, normal and diseased, were conducted, and their relative differences in terms of the flow patterns and WSR distribution were demonstrated. It is shown that high-frame-rate UIV technique can be a non-invasive tool to measure quantitatively the spatio-temporal velocity and WSS distribution.     

Clinical validation of common carotid artery wall distension assessment based on multigate Doppler processing

Mechanical properties of human large arteries result from the interaction between blood pressure, wall distensibility and shear stress. Both the arterial diameter changes through the cardiac cycle (distension) and blood flow velocities can be noninvasively investigated through Doppler ultrasound approaches. Recently, an integrated system processing in real-time all the echo signals produced along an M-line has been developed. This system has been so far demonstrated to be suitable for accurate hemodynamic studies through the detection of blood velocity profiles. This paper reports on the extension of its processing capabilities to the real-time measurement of arterial distension. Tissue motion estimation is based on a modified 2-D autocorrelation algorithm. A novel adaptive approach to track wall position over time using the sum of the high-pass filtered displacement waveform and the low-pass filtered wall position is described. By observing the blood velocity profile, a rapid and accurate positioning of the ultrasound probe and an inherent check on perpendicular observation are provided. First clinical results obtained by measuring the distension of common carotid arteries in a group of 41 volunteers are reported and measurements are validated against those provided by a dedicated wall-track reference system. Average measured distension and diameter were 499 +/- 188 microm and 6.90 +/- 0.66 mm and intraobserver intrasession reproducibility tests showed coefficients of variability of 8.5% and 5.9%, respectively. The agreement between the proposed system and the reference system, expressed as bias +/- 2 SD of the differences, was -34 +/- 141 microm for distension and 0.05 +/- 1.07 mm for diameter.     

Investigation of Ultrasound-Measured Flow Velocity,Flow Rate and Wall Shear Rate in Radial and Ulnar Arteries Using Simulation

Parameters of blood flow measured by ultrasound in radial and ulnar arteries, such as flow velocity, flow rate and wall shear rate, are widely used in clinical practice and clinical research. Investigation of these measurements is useful for evaluating accuracy and providing knowledge of error sources. A method for simulating the spectral Doppler ultrasound measurement process was developed with computational fluid dynamics providing flow-field data. Specific scanning factors were adjusted to investigate their influence on estimation of the maximum velocity waveform, and flow rate and wall shear rate were derived using the Womersley equation. The overestimation in maximum velocity increases greatly (peak systolic from about 10% to 30%, time-averaged from about 30% to 50%) when the beam–vessel angle is changed from 30° to 70°. The Womersley equation was able to estimate flow rate in both arteries with less than 3% error, but performed better in the radial artery (2.3% overestimation) than the ulnar artery (15.4% underestimation) in estimating wall shear rate. It is concluded that measurements of flow parameters in the radial and ulnar arteries with clinical ultrasound scanners are prone to clinically significant errors.     

In vitro and preliminary in vivo validation of echo particle image velocimetry in carotid vascular imaging

Noninvasive, easy-to-use and accurate measurements of wall shear stress (WSS) in human blood vessels have always been challenging in clinical applications. Echo particle image velocimetry (Echo PIV) has shown promise for clinical measurements of local hemodynamics and wall shear rate. Thus far, however, the method has only been validated under simple flow conditions. In this study, we validated Echo PIV under in vitro and in vivo conditions. For in vitro validation, we used an anatomically correct, compliant carotid bifurcation flow phantom with pulsatile flow conditions, using optical particle image velocimetry (optical PIV) as the reference standard. For in vivo validation, we compared Echo PIV-derived 2-D velocity fields obtained at the carotid bifurcation in five normal subjects against phase-contrast magnetic resonance imaging (PC-MRI)-derived velocity measurements obtained at the same locations. For both studies, time-dependent, 2-D, two-component velocity vectors; peak/centerline velocity, flow rate and wall shear rate (WSR) waveforms at the common carotid artery (CCA), carotid bifurcation and distal internal carotid artery (ICA) were examined. Linear regression, correlation analysis and Bland-Altman analysis were used to quantify the agreement of different waveforms measured by the two techniques. In vitro results showed that Echo PIV produced good images of time-dependent velocity vector maps over the cardiac cycle with excellent temporal (up to 0.7 ms) and spatial (∼0.5 mm) resolutions and quality, comparable with optical PIV results. Further, good agreement was found between Echo PIV and optical PIV results for velocity and WSR measurements. In vivo results also showed good agreement between Echo PIV velocities and phase contrast MRI velocities. We conclude that Echo PIV provides accurate velocity vector and WSR measurements in the carotid bifurcation and has significant potential as a clinical tool for cardiovascular hemodynamics evaluation. (E-mail: Robin.shandas@ucdenver.edu)     

A method to estimate wall shear rate with a clinical ultrasound scanner

A simple technique to estimate the wall shear rate in healthy arteries using a clinical ultrasound scanner has been developed. This method uses the theory of fully developed oscillatory flow together with a spectral Doppler trace and an estimate of mean arterial diameter. A method using color flow imaging was compared with the spectral Doppler method in vascular phantoms and found to have errors that were on average 35% greater. Differences from the theoretic value for the time averaged wall shear rate using the spectral Doppler method varied by artery: brachial −9 (1) %; carotid −7 (1) %; femoral −22 (4) %; and fetal aorta −17 (10) %. Test measurements obtained from one healthy volunteer demonstrated the feasibility of the technique in vivo. E-mail: (james.blake@ed.ac.uk)     

Toward noninvasive blood pressure assessment in arteries by using ultrasound

A new method has been developed to measure local pressure waveforms in large arteries by using ultrasound. The method is based on a simultaneous estimation of distension waveforms and velocity profiles from a single noninvasive perpendicular ultrasound B-mode measurement. Velocity vectors were measured by applying a cross-correlation based technique to ultrasound radio-frequency (RF) data. From the ratio between changes in flow and changes in cross-sectional area of the vessel, the local pulse wave velocity (PWV) was estimated. This PWV value was used to convert the distension waveforms into pressure waveforms. The method was validated in a phantom set-up. Physiologically relevant pulsating flows were considered, employing a fluid which mimics both the acoustic and rheologic properties of blood. A linear array probe attached to a commercially available ultrasound scanner was positioned parallel to the vessel wall. Since no steering was used, the beam was perpendicular to the flow. The noninvasively estimated pressure waveforms showed a good agreement with the reference pressure waveforms. Pressure values were predicted with a precision of 0.2 kPa (1.5 mm Hg). An accurate beat to beat pressure estimation could be obtained, indicating that a noninvasive pressure assessment in large arteries by means of ultrasound is feasible.(E-mail:n.bijnens@tue.nl)     

A viscoelastic model of arterial wall motion in pulsatile flow: implications for Doppler ultrasound clutter assessment

The existing computational model studies of pulsatile blood flow in arteries have assumed either rigid wall characteristics or elastic arterial wall behavior with wall movement limited to the radial direction. Recent in vivo studies have identified significant viscoelastic wall properties and longitudinal wall displacements over the cardiac cycle. Determining the nature of these movements is important for predicting the effects of ultrasound clutter in Doppler ultrasound measurements. It is also important for developing an improved understanding of the physiology of vessel wall motion. We present an analytically-based computational model based on the Womersley equations for pulsatile blood flow within elastic and viscoelastic arteries. By comparison with published in vivo data of the human common carotid artery as well as uncertainty and sensitivity analyses, it is found that the predicted waveforms are in reasonable quantitative agreement. Either a pressure, pressure gradient or volumetric flow rate waveform over a single cardiac cycle is used as an input. Outputs include the pressure, pressure gradient, radial and longitudinal fluid velocities and arterial wall displacements, volumetric flow rate and average longitudinal velocity. It is concluded that longitudinal wall displacements comparable to the radial displacements can be present and should be considered when studying the effects of tissue movement on Doppler ultrasound clutter.     

Quantification of Ultrasound Correlation‐Based Flow Velocity Mapping and Edge Velocity Gradient Measurement

This study investigated the use of ultrasound speckle decorrelation‐ and correlation‐based lateral speckle‐tracking methods for transverse and longitudinal blood velocity profile measurement, respectively. By studying the blood velocity gradient at the vessel wall, vascular wall shear stress, which is important in vascular physiology as well as the pathophysiologic mechanisms of vascular diseases, can be obtained. Decorrelation‐based blood velocity profile measurement transverse to the flow direction is a novel approach, which provides advantages for vascular wall shear stress measurement over longitudinal blood velocity measurement methods. Blood flow velocity profiles are obtained from measurements of frame‐to‐frame decorrelation. In this research, both decorrelation and lateral speckle‐tracking flow estimation methods were compared with Poiseuille theory over physiologic flows ranging from 50 to 1000 mm/s. The decorrelation flow velocity measurement method demonstrated more accurate prediction of the flow velocity gradient at the wall edge than the correlation‐based lateral speckle‐tracking method. The novelty of this study is that speckle decorrelation‐based flow velocity measurements determine the blood velocity across a vessel. In addition, speckle decor‐relation‐based flow velocity measurements have higher axial spatial resolution than Doppler ultrasound measurements to enable more accurate measurement of blood velocity near a vessel wall and determine the physiologically important wall shear.     

Measurement of Wall Shear Stress Exerted by Flowing Blood in the Human Carotid Artery: Ultrasound Doppler Velocimetry and Echo Particle Image Velocimetry

Vascular endothelial cells lining the arteries are sensitive to wall shear stress (WSS) exerted by flowing blood. An important component of the pathophysiology of vascular diseases, WSS is commonly estimated by centerline ultrasound Doppler velocimetry (UDV). However, the accuracy of this method is uncertain. We have previously validated the use of a novel, ultrasound-based, particle image velocimetry technique (echo PIV) to compute 2-D velocity vector fields, which can easily be converted into WSS data. We compared WSS data derived from UDV and echo PIV in the common carotid artery of 27 healthy participants. Compared with echo PIV, time-averaged WSS was lower using UDV (28 ± 35%). Echo PIV revealed that this was due to considerable spatiotemporal variation in the flow velocity profile, contrary to the assumption that flow is steady and the velocity profile is parabolic throughout the cardiac cycle. The largest WSS underestimation by UDV was found during peak systole (118 ± 16%) and the smallest during mid-diastole (4.3± 46%). The UDV method underestimated WSS for the accelerating and decelerating systolic measurements (68 ± 30% and 24 ± 51%), whereas WSS was overestimated for end-diastolic measurements (?44 ± 55%). Our data indicate that UDV estimates of WSS provided limited and largely inaccurate information about WSS and that the complex spatiotemporal flow patterns do not fit well with traditional assumptions about blood flow in arteries. Echo PIV-derived WSS provides detailed information about this important but poorly understood stimulus that influences vascular endothelial pathophysiology.     

Noninvasive assessment of wall-shear rate and vascular elasticity using combined ARFI/SWEI/spectral Doppler imaging system

The progression of atherosclerotic disease is a complex process believed to be a function of the localized mechanical properties and hemodynamic loading associated with the arterial wall. It is hypothesized that measurements of cardiovascular stiffness and wall-shear rate (WSR) may provide important information regarding vascular remodeling, endothelial function and the growth of soft lipid-filled plaques that could help a clinician better predict the occurrence of clinical events such as stroke. Two novel ARFI based imaging techniques, combined on-axis/off-axis ARFI/Spectral Doppler Imaging (SAD-SWEI) and Gated 2D ARFI/Spectral Doppler Imaging (SAD-Gated), were developed to form co-registered depictions of B-mode echogenicity, ARFI displacements, ARF-excited transverse wave velocity estimates and estimates ofwall-shear rate throughout the cardiac cycle. Implemented on a commercial ultrasound scanner, the developed techniques were evaluated in tissue-mimicking and steady-state flow phantoms and compared with conventional techniques, other published study results and theoretical values. Initial in vivo feasibility of the method is demonstrated with results obtained from scanning the carotid arteries of five healthy volunteers. Cyclic variations over the cardiac cycle were observed in on-axis displacements, off-axis transverse-wave velocities and wall-shear rates.     

Simulation and validation of arterial ultrasound imaging and blood flow

We reviewed the simulation and validation of arterial ultrasound imaging and blood flow assessment. The physical process of ultrasound imaging and measurement is complex, especially in disease. Simulation of physiological flow in a phantom with tissue equivalence of soft tissue, vessel wall and blood is now achievable. Outstanding issues are concerned with production of anatomical models, simulation of arterial disease, refinement of blood mimics to account for non-Newtonian behavior and validation of velocity measurements against an independent technique such as particle image velocimetry. String and belt phantoms offer simplicity of design, especially for evaluation of velocity estimators, and have a role as portable test objects. Electronic injection and vibrating test objects produce nonphysiologic Doppler signals, and their role is limited. Computational models of the ultrasound imaging and measurement process offer considerable flexibility in their ability to alter multiple parameters of both the propagation medium and ultrasound instrument. For these models, outstanding issues are concerned with the inclusion of different tissue types, multilayer arteries, inhomogeneous tissues and diseased tissues. (E-mail: P.Hoskins@ed.ac.uk)     

Imaging of wall motion coupled with blood flow velocity in the heart and vessels in vivo: a feasibility study

The mechanical property and geometry changes as a result of cardiovascular disease affect both the wall motion and blood flow in the heart and vessels, whereas the latter two are also coupled and therefore continuously influence one another. Simultaneous and registered imaging of both cardiovascular wall motion and blood velocity may thus contribute to more complete computational models of cardiovascular mechanical and fluid dynamics as well as provide additional diagnostic information. The objective of this paper was to determine the feasibility of imaging cardiovascular wall motion coupled with blood flow in vivo. Normal (n = 6) and infarcted (n = 5) murine left ventricles, and normal (n = 5) and aneurysmal (n = 4) murine abdominal aortas, were imaged in longitudinal views with a 30-MHz ultrasound probe. Using electrocardiogram (ECG) gating, 2-D radio-frequency (RF) data were acquired at a frame rate of 8 kHz. The axial wall velocity and blood velocity were estimated using a speckle-tracking technique. Spatially and temporally registered imaging of both cardiovascular wall motion and blood flow was shown to be feasible. Reduced wall motion was detected in the infarcted region, whereas vortex flow patterns were imaged in diastolic phases of both normal and infarcted left ventricles. The myocardial wall motion and blood flow were found to be more synchronous in the normal heart, where the blood moves toward the anteroseptal wall after the mitral valve opens (i.e., rapid filling phase), and the anteroseptal wall simultaneously undergoes outward motion. In the infarcted heart, however, in the rapid filling phase, the basal anteroseptal wall starts moving about 20 ms before the mitral valve opens and the blood enters the left ventricle. In the normal aorta, the wall motion and blood velocity were uniform and synchronous. In the aneurysmal aorta, reduced and spatially varied wall motion and vortex flow patterns in the aneurysmal sac were found. The wall motion and blood velocity were thus less synchronous in the aneurysmal aorta. Cardiovascular wall motion and blood flow were both imaged in mice in vivo. This dual information may provide important insights for the diagnosis of cardiovascular disease as well as essential parameters for its biomechanical modeling.     

In vitro examination of the coronary artery wall after balloon angioplasty using intracoronary ultrasound

After autopsy 12 human coronary arteries were investigated by intracoronary ultrasound in order to measure the vessel wall dimensions and to detect damage on the vessel wall architecture after balloon angioplasty. Histology revealed artherosclerosis in 11/12 arteries. A total of 41 representative coronary segments were selected for further off-line ultrasound and histological analysis. Intracoronary ultrasound and histological measurements of the vessel wall thickness after balloon dilatation demonstrated a good correlation between the maximum thickness of the intima (histology 0.62 mm vs. intracoronary ultrasound 0.65 mm, r = 0.87) and the intima-media complex (0.80 mm vs. 0.83 mm, r = 0.87), in contrast to a weak one between the minimum thickness (r = 0.46 and r = 0.37). A total of 21 cases of damage occurred during angioplasty; intracoronary ultrasound detected 17. Further analysis showed that it imaged 10 of 11 cases of damage involving more than 30° of the vessel circumference and 7 of 10 cases of damage involving less than 30° of the vessel circumference. After balloon angioplasty of diseased coronary arteries, intracoronary ultrasound is therefore reliable in measuring the maximum wall thickness and in imaging damage involving more than 30° of the vessel wall circumference.     

Validation of a newly developed B-mode image-processing technique versus wall-tracking ultrasound for the study of wall mechanics in small-calibre arteries

Purpose: To validate a newly developed image‐processing technique for the assessment of arterial wall compliance and distensibility from non‐invasive B‐mode ultrasound compared with the invasive wall‐tracking technique. Materials and methods: Arterial wall compliance and distensibility coefficient were measured invasively by wall‐tracking with an ultrasonic transducer implanted on the vessel wall, and non‐invasively by automatic processing of B‐mode ultrasound images, with a dedicated workstation and software (IO^ 3·1, IO^DP, Paris). Measurements were performed in the normal aorta of five animals, and upstream, at the stent level, and downstream from the stent in eight other animals (immediately after stenting in six, and 3 months later in four), for a total of 35 paired measurements. Results: There was no significant difference between the two techniques for compliance but there was a significant difference in diameter (P<0·005) and distensibility (P<0·05) as external ultrasound measured the inner diameter, while wall‐tracking measured the outer diameter. Agreement between the two methods as assessed by the Bland–Altman approach was acceptable for aortic diameter, compliance and distensibility. Conclusion: Automatic processing of B‐mode ultrasound images is a reliable non‐invasive technique to assess the compliance of small‐calibre arteries.     

Assessment of tissue Doppler imaging measurements of arterial wall motion using a tissue mimicking test rig

The aim of this in vitro study is to assess the accuracy of the tissue Doppler imaging arterial wall motion (TDI AWM) technique in measuring dilation over a range of distances and velocities. A test rig, consisting of two parallel blocks of tissue mimicking material (TMM), has been developed to generate known wall motion. One block remains stationary while the other moves in a cyclical motion. A calibrated laser range finder was used to measure the TMM motion. The TDI AWM measurements were found to underestimate the dilation by 21% +/- 4.7% when using the recommended scanner parameters. The size of the error was found to increase with a decrease in ultrasound output power. Results suggested that errors in the TDI AWM dilation measurements relate to underestimates in the velocity measured by the TDI technique. The error demonstrated in this study indicates a limitation in the value of TDI AWM result obtained in vivo. (E-mail: abigail.thrush@bartsandthelondon.nhs.uk).     

An integrated system for the non-invasive assessment of vessel wall and hemodynamic properties of large arteries by means of ultrasound.

OBJECTIVES: To integrate methods for non-invasive assessment of vessel wall properties (diastolic diameter, distension waveform and intima-media thickness) and hemodynamic properties (blood flow velocity and shear rate distribution) of large arteries by means of dedicated ultrasound signal processing. METHODS: we have developed an arterial laboratory (ART-lab) system. ART-lab consists of software running on a standard personal computer, equipped with a data acquisition card for the acquisition of radio frequency (RF) ultrasound signals obtained with a conventional echo scanner. It operates either (1) off-line or (2) in real-time. Real-time operation is restricted to the assessment of vessel wall properties because of limitations in computational power. RESULTS: This paper provides an overview of ART-lab ultrasound radio frequency data acquisition and dedicated RF-signal processing methods. The capabilities of the system are illustrated with some typical applications. CONCLUSIONS: ART-lab in real-time mode is a useful tool for monitoring arterial vessel wall dynamics, while off-line it can be employed to investigate the elastic vessel wall properties in combination with hemodynamics, such as blood flow velocity and shear rate distribution.     

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 determining 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.     

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.     

Design and characterisation of a wall motion phantom

Arterial wall motion is an essential feature of a healthy cardiovascular system and it is known that wall motion is affected by age and disease. In recent years, methods have been developed for measurement of wall motion with the intention of providing diagnostically useful information. An issue with all of these techniques is the accuracy and variability of both wall motion and derived quantities such as elasticity, which requires the development of suitable test tools. In this paper, a vessel wall phantom is described for use in ultrasound studies of wall motion. The vessel was made from polyvinyl alcohol (PVA) subjected to a freeze-thaw process to form a cryogel (PVA-C). The elastic modulus, acoustic velocity and attenuation coefficient varied from 57 kPa, 1543 m s(-1) and 0.18 dB cm(-1) MHz(-1) for one freeze-thaw cycle to 330 kPa, 1583 m s(-1) and 0.42 dB cm(-1) MHz(-1) for 10 freeze-thaw cycles. Wall motion was effected by the use of pulsatile flow produced from a gear pump. The use of a downstream flow resistor removed gross distortions in the wall motion waveform, possibly by removal of reflected pressure waves. However, a low amplitude 20 Hz oscillation remained, which is unphysiologic and thought to be caused by the vibration of the distended PVA-C vessel.