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.     

Effects of adrenaline on longitudinal arterial wall movements and resulting intramural shear strain: a first report

Using ultrasound we recently demonstrated that in central elastic arteries as well as in large muscular arteries in humans there is a distinct longitudinal displacement of the arterial wall during the cardiac cycle. Further, for the first time, we also demonstrated that the inner parts of the vessel wall, the intima‐media complex, in these vessels exhibit a larger longitudinal displacement than the outer part of the vessel wall, the adventitial region, introducing the presence of substantial shear strain, and thus shear stress within the vessel wall. The role of these unexplored phenomena is unknown. Here, in a first study on the longitudinal movements of the porcine common carotid artery, we show that administration of adrenaline (epinephrine) might have pronounced effects on the longitudinal displacement of the intima‐media complex. In this experiment the longitudinal displacement of the intima‐media complex increased >200% at the highest blood pressure levels as compared to baseline. Further, shear strain within the wall increased >250%; the longitudinal displacement of the adventitial region being smaller than that of the intima‐media complex. Thus, our results indicate that adrenaline can markedly influence the longitudinal displacement of the arterial wall and the resulting shear strain, and thus shear stress, within the arterial wall. This opens up a new field within cardiovascular research, revealing a previously unknown mechanism in the circulatory system. Further studies on larger materials are needed to confirm our findings and to elucidate the underlying mechanisms and the physiological, pathophysiological and clinical implications of this phenomenon.     

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.     

Doppler ultrasound in aortic stenosis: in vitro studies of pressure gradient determination

Torricelli's equation expresses a simple relationship between fluid velocity and pressure gradient in orifice flow and is currently used in conjunction with noninvasive Doppler ultrasound to determine gradients in mitral stenosis, and aortic stenosis, as well as other cardiovascular orifices. In theory, however, the Torricelli equation overestimates the gradient in aortic stenosis and the Borda equation should be more applicable. A brief tutorial derivation of the Borda and Torricelli equations is presented. The applicability of Torricelli's equation in aortic stenosis was studied experimentally with a rigid wall, pulsatile flow analogue. Doppler ultrasound and manometric data were collected simultaneously. Percent stenosis, peak flow rate and fluid viscosity were varied. The results demonstrated that the Torricelli equation consistently overestimated the pressure gradient. At 61% area stenosis, the overestimation exceeded 100%. In vivo studies are required to determine the relevance of the observations to clinical situations.     

A new non-invasive ultrasonic method for simultaneous measurements of longitudinal and radial arterial wall movements: first in vivo trial

During recent years, the radial movement of the arterial wall has been extensively studied, and measurements of the radial movement are now an important tool in cardiovascular research for characterizing the mechanical properties of the arterial wall. In contrast, the longitudinal movement of vessels has gained little or no attention as it has been presumed that this movement is negligible. With modern high-resolution ultrasound, it can, however, be seen that the intima-media complex of the arterial wall moves not only in the radial direction, but also in the longitudinal direction during pulse-wave propagation. This paper describes a new non-invasive ultrasonic method that is able to measure simultaneously two dimensionally arterial vessel wall movements. The method is demonstrated in a limited in vivo trial. Results from the in vivo trial show that, apart from the well-known radial movement, there is a distinct longitudinal movement in the human common carotid artery with, in this case, the intima-media complex moving substantially as compared with the region of the tunica adventitia. Two-dimensional evaluation of the vessel-wall movements, taking not only the radial movement, but also the longitudinal movement into account, may provide novel information of importance in the evaluation of vessel-wall function.     

High Spatial and Temporal Resolution Observations of Pulsatile Changes in Blood Echogenicity in the Common Carotid Artery of Rats

Previous studies have found that ultrasound backscatter from blood in vascular flow systems varies under pulsatile flow, with the maximum values occurring during the systolic period. This phenomenon is of particular interest in hemorheology because it is contrary to the well-known fact that red blood cell (RBC) aggregation, which determines the intensity of ultrasound backscatter from blood, decreases at a high systolic shear rate. In the present study, a rat model was used to provide basic information on the characteristics of blood echogenicity in arterial blood flow to investigate the phenomenon of RBC aggregation under pulsatile flow. Blood echogenicity in the common carotid arteries of rats was measured using a high-frequency ultrasound imaging system with a 40-MHz probe. The electrocardiography-based kilohertz visualization reconstruction technique was employed to obtain high-temporal-resolution and high-spatial-resolution time-course B-mode cross-sectional and longitudinal images of the vessel. The experimental results indicate that blood echogenicity in rat carotid arteries varies during a cardiac cycle. Blood echogenicity tends to decrease during early systole and reaches its peak during late systole, followed by a slow decline thereafter. The time delay of the echogenicity peak from peak systole in the present results is the main difference from previous in vitro and in vivo observations of backscattering peaks during early systole, which may be caused by the very rapid heart rates and low RBC aggregation tendency of rats compared with humans and other mammalian species. The present study may provide useful information elucidating the characteristics of RBC aggregation in arterial blood flow.     

Reduced common carotid artery longitudinal wall motion and intramural shear strain in individuals with elevated cardiovascular disease risk using speckle tracking

Longitudinal motion of the intima–media and adventitia layers of the common carotid artery (CCA) wall were assessed with ultrasound speckle tracking in seven individuals with spinal cord injury (SCI), who are considered at increased risk of cardiovascular disease, and in seven able-bodied participants. CCA longitudinal wall displacement and intramural shear strain were compared to traditional markers of arterial health, including CCA stiffness and intima–media thickness (IMT). For each cardiac cycle, longitudinal CCA wall motion was characterized by bidirectional movement patterns containing motion retrograde to blood flow during systole, followed by antegrade motion during diastole. Relative displacement of the intima–media versus the adventitia was used to calculate longitudinal intramural shear strain and provided insight to local arterial wall properties. The retrograde intramural shear strain was smaller in individuals with SCI by 60·2% (P<0·05) compared to able-bodied participants, showing smaller peak displacements in both the intima–media (P<0·05) and adventitia (P<0·05). In the antegrade direction, there were no group differences in either longitudinal displacements or shear strain. The group differences observed in the retrograde wall motion phase were greater than those observed for CCA stiffness or IMT and were found to be independent of both indices, indicating indices of the retrograde phase intramural shear strain may be a novel and sensitive marker of vascular health. Our findings demonstrate that assessment of longitudinal arterial wall shear strain may provide valuable insight into vascular structure and function and may hold potential for the early detection of cardiovascular disease.     

Feasibility of Dual Doppler Velocity Measurements to Estimate Volume Pulsations of an Arterial Segment

If volume flow was measured at each end of an arterial segment with no branches, any instantaneous differences would indicate that volume was increasing or decreasing transiently within the segment. This concept could provide an alternative method to assess the mechanical properties or distensibility of an artery noninvasively using ultrasound. The goal of this study was to determine the feasibility of using Doppler measurements of pulsatile velocity (opposed to flow) at two sites to estimate the volume pulsations of the intervening arterial segment. To test the concept over a wide range of dimensions, we made simultaneous measurements of velocity in a short 5 mm segment of a mouse common carotid artery and in a longer 20 cm segment of a human brachial-radial artery using a two-channel 20 MHz pulsed Doppler and calculated the waveforms and magnitudes of the volume pulsations during the cardiac cycle. We also estimated pulse wave velocity from the velocity upstroke arrival times and measured artery wall motion using tissue Doppler methods for comparison of magnitudes and waveforms. Volume pulsations estimated from Doppler velocity measurements were 16% for the mouse carotid artery and 4% for the human brachial artery. These values are consistent with the measured pulse wave velocities of 4.2 m/s and 10 m/s, respectively, and with the mouse carotid diameter pulsation. In addition, the segmental volume waveforms resemble diameter and pressure waveforms as expected. We conclude that with proper application and further validation, dual Doppler velocity measurements can be used to estimate the magnitude and waveform of volume pulsations of an arterial segment and to provide an alternative noninvasive index of arterial mechanical properties. (E-mail: cjhartley@ieee.org)     

Turbulence measurements with pulsed doppler ultrasound employing a frequency tracking method

A phase lock loop method of tracking Doppler ultrasound frequencies is applied to the measurement of turbulent velocities. A pulsed Doppler ultrasound system capable of detecting two velocity components was employed to resolve axial and radial velocity components at the centerline of turbulent pipe flows and distal to stenoses in pulsatile flow. Measurements with the ultrasound system are compared with laser Doppler and hot film anemometer data. The results demonstrate that the phase lock loop method of tracking accurately follows turbulent velocity fluctuations for turbulence intensities up to approx. 20%, after which signal dropout becomes a significant factor. An important application of the method is that of detecting flow disturbances created by mild to moderate degrees of stenosis in arterial disease.     

Pulsed Doppler ultrasound detection of flow disturbances in arteriosclerosis.

Pulsed Doppler ultrasound blood flow detection has been used in a noninvasive manner to detect arterial abnormalities associated with arteriosclerosis. Sound spectrograms of ultrasound signals obtained from in vitro and animal studies in which flow was disturbed by obstacles placed in the flow stream showed a different distribution of energy over frequency than signals obtained from studies with no flow disturbances. Similar findings were seen clinically. A technique has been developed which can detect disturbed flow patterns resulting from partial occlusion in important superficial arteries (e.g. femoral and carotid) up to 15 cm distal to localized arterial wall abnormalities. Thirty-five arterial examinations of normal and arteriographically abnormal arteries in 12 patients revealed a sensitivity of 83 percent and a specificity of 61 percent. This study suggests that pulsed Doppler ultrasound may be useful as a screening technique for detection of arteriosclerotic lesions in major superficial arteries.     

Transcutaneous detection of relative changes in artery diameter

The extent of the excursions of the arterial walls during the cardiac cycle depends on both the compliance of the vessel wall and the local pressure fluctuations. Simultaneous assessment of the relative change in artery diameter in combination with the velocity distribution along the vessel cross section can reveal the cause of loss of distensibility. As will be demonstrated, a multigate pulsed Doppler system with a high spatial resolution can perform simultaneously both functions. The relative change in diameter during the cardiac cycle is obtained by taking the ratio of the distension and the diameter of the artery as observed along the ultrasound beam. It can be shown that this ratio will be angle independent. Statistical and experimental evaluations demonstrate that the system allows the assessment of the relative change in diameter of major peripheral arteries as a continuous function of time with an accuracy of about 0.5%.     

Vascular intramural strain imaging using arterial pressure equalization

Peripheral vascular strain imaging has limited strain dynamic range because arterial wall deformations only exhibit small strains under physiologic pressures. A noninvasive freehand ultrasound (US) scanning procedure was performed to apply external force, comparable to the force generated in measuring a subject's blood pressure, to achieve higher strains by equalizing the internal arterial baseline pressure. When the applied pressure matched the internal baseline diastolic pressure, intramural strain and strain rate increased by a factor of 10 over a cardiac cycle. Radial arterial strain was assessed within the vessel wall over the entire deformation procedure using a phase-sensitive 2-D speckle-tracking algorithm. The feasibility of this technique to assess vascular nonlinear elastic properties is demonstrated in an ex vivo experiment and further supported by in vivo measurements. With some uncertainty associated with the elastic properties of surrounding tissue, an elastic modulus reconstruction procedure was developed to estimate the nonlinear elastic properties of the vascular wall.     

Doppler ultrasound diastolic flow analysis for the early identification of peripheral arterial disease.

OBJECTIVE: The viscoelastic mechanical compliance properties of the human arterial system were examined in 100 subjects with A-mode Doppler ultrasound diastolic flow analysis. This technique of diastolic flow analysis is utilized to identify early atherogenic peripheral arterial disease. The sensitivity of the commonly utilized standard traditional ultrasound pressure-grade pneumatic cuff examination will be increased when accompanied by the diastolic flow analysis technique. SETTING: Diastolic flow analysis will aid in the early identification of lower extremity vascular claudication when lumbar spinal canal stenosis and elevated cardiovascular risk factors are present. This examination may be performed in the office setting with standard A-mode Doppler ultrasound equipment along with the usual pneumatic cuff procedure. The standard ultrasound cuff examinations are based on pressure gradients to identify lower extremity arterial disease. The low level of sensitivity of this test requires arterial obstruction of at least 50% to be present before positive identification is possible. Pathological alterations of the arterial wall occur during the early stages of atherosclerotic disease, are reflected by reduced wall distensibility and may be quantified by Doppler ultrasound. SUBJECTS: Studied were a total of 100 subjects, 50 with arterial disease risk factors and 50 normal controls. All subjects were screened for aortic coarctation, myocardial infarction, tachyarrhythmia, aortic value stenosis and mitral prolapse. The risk group subjects were all smokers and had a mixed distribution of hypertension, hypercholesterolemia and hyperglycemia. The commonly utilized standard traditional ultrasound pneumatic cuff examination was negative in all subjects. Anthropometric measurements and percent body fat were also obtained. Arterial diastolic antegrade flow analysis was performed with Doppler ultrasound on each subject. RESULTS: This study demonstrated that the elevated vascular risk factor group had a mean arterial distensibility measurement of 4.4 +/- 5.0%, and the control group displayed a mean measurement of 20.0 +/- 6.0%. The 50 elevated risk factor subjects showed approximately 5 times greater arterial stiffness and were identified with significance at an F test level of (p less than .001). CONCLUSION: This arterial compliance evaluation procedure is shown to be a reliable sensitive indicator of early atherosclerotic disease prior to the development of obstructive arterial lesions.     

Signal losses with real-time three-dimensional power Doppler imaging

Power Doppler imaging (PDI) has been shown to be influenced by the wall filter when assessing arterial stenoses. Real-time 3-D Doppler imaging may likely become a widespread practice in the near future, but how the wall filter could affect PDI during the cardiac cycle has not been investigated. The objective of the study was to demonstrate that the wall filter may produce unexpected major signal losses in real-time 3-D PDI. To test our hypothesis, we first validated binary images obtained from analytical simulations with in vitro PDI acquisitions performed in a tube under pulsatile flow conditions. We then simulated PDI images in the presence of a severe stenosis, considering physiological conditions by finite element modeling. Power Doppler imaging simulations revealed important signal losses within the lumen area at different instants of the flow cycle, and there was a very good concordance between measured and predicted PDI binary images in the tube. Our results show that the wall filter may induce severe PDI signal losses that could negatively influence the assessment of vascular stenosis. Clinicians should therefore be aware of this cause of signal loss to properly interpret power Doppler angiographic images.     

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.     

Nitric oxide modulation of ophthalmic artery blood flow velocity waveform morphology in healthy volunteers

Quantitative analysis of the arterial pressure pulse waveform recorded by applanation tonometry of the radial artery can track NO (nitric oxide)-mediated modulation of arterial smooth muscle tone. The changes in pressure pulse waveform morphology result from pulse wave reflection arising predominantly from smaller arteries and arterioles. Employing Doppler ultrasound to record the spectral flow velocity waveform in the ophthalmic artery, we studied the effects of NO modulation on waveforms recorded in the proximity of the terminal ocular microcirculatory bed. In healthy young men (n=10; age 18-26 years), recordings were made at baseline, following 300 mug of sublingual GTN (glyceryl trinitrate) and during the intravenous infusion of 0.25 and 0.5 mg/kg of L-NAME (N(G)-nitro-L-arginine methyl ester). Peaks (P1, P2 and P3) and nodes (N1, N2 and N3) on the arterial flow velocity waveform were identified during the cardiac cycle and employed to quantify wave shape change in response to the haemodynamic actions of the pharmacological interventions. The administration of GTN resulted in a significant (P<0.05) increase in heart rate without significant alteration in blood pressure. At the doses employed, L-NAME did not significantly alter systemic haemodynamics. With the exception of peak Doppler systolic velocity, all other peaks and nodes decreased significantly in response to GTN (P<0.05 for all points compared with baseline). In response to the administration of L-NAME, all peaks and nodes decreased significantly (P<0.05 for all points compared with baseline). The resistive index, a ratio calculated from the peak and trough flow velocities employed to assess change in flow resistance, increased significantly in response to GTN (0.77 at baseline compared with 0.85; P<0.05). Quantification of changes in the flow velocity spectral waveform during the cardiac cycle sensitively identified NO modulation of smooth muscle tone prior to alteration in systemic haemodynamics. Focusing on the resistive index, which identifies isolated points on the waveform describing the excursions of flow, may provide misleading information in relation to the haemodynamic effects of drug interventions.     

Pressure pulse velocity is related to the longitudinal elastic properties of the artery

It is known that arteries in their natural position are always subject to a longitudinal stress. However, the effect of this strong longitudinal tension has seldom been addressed. In this paper, we point out that the traditional pulse wave velocity formulae considering only the circumferential elasticity fail to include all the important energies. We present a vigorous derivation of a pressure wave equation, the pressure wave equation with total energy, which considers all the important energies of the whole arterial system by treating the arterial wall and the blood as one system. Our model proposes that the energy transport in the main arterial system is primarily via the transverse vibration motion of the elastic wall. The final equation indicates that the longitudinal stress is essential and the high frequency phase velocity is related to the longitudinal tension along the arterial wall and its Young's shearing modulus. By applying this equation, we suggest that longitudinal elastic property is an important factor in hemodynamics and in the treatment of cardiovascular diseases.     

A reproducibility study of a TDI-based method to calculate indices of arterial stiffness

The aim of the study was to investigate the reproducibility of estimation of Young's modulus E and pressure strain elastic modulus Ep, derived from a tissue Doppler imaging (TDI) wall motion technique. Healthy subjects had their arteries insonated at the same sitting by two different observers and at two different sittings by the same observer. From 32 subjects in the reproducibility study, within-scan coefficient of variation (CV) was 4.5%. Intraobserver between-scan CV for E was 12.7% and for Ep 11.0%. Interobserver CVs were 8.3% and 9.3%, respectively. TDI is a reproducible, valid and highly sensitive direct assessment of arterial wall parameters. It is at least as reproducible as other ultrasound based methods for assessing arterial stiffness and also provides increased information about the arterial distension waveform.     

彩色多普勒超声诊断下肢动脉闭塞性疾病

目的探讨彩色及频谱多普勒技术在诊断下肢动脉闭塞性疾病的价值。方法对52例87条临床拟诊断下肢动脉闭塞性疾病的血管进行彩色多普勒超声检查，并与CT血管成像对照。结果彩色多普勒血流显像可以直观地显示动脉管壁情况、管腔回声及血流充盈情况，频谱多普勒可以显示血流动力学改变。诊断的准确率分别为动脉硬化和（或）闭塞症100％、动脉栓塞92％、血栓闭塞性脉管炎84％。结论彩色多普勒超声诊断下肢动脉闭塞性疾病是一种敏感、准确、方便的诊断方法。     

High-Definition Imaging of Carotid Artery Wall Dynamics

The carotid artery (CA) is central to cardiovascular research, because of the clinical relevance of CA plaques as culprits of stroke and the accessibility of the CA for cardiovascular screening. The viscoelastic state of this artery, essential for clinical evaluation, can be assessed by observing arterial deformation in response to the pressure changes throughout the cardiac cycle. Ultrasound imaging has proven to be an excellent tool to monitor these dynamic deformation processes. We describe how a new technique called high-frame-rate ultrasound imaging captures the tissue deformation dynamics throughout the cardiac cycle in unprecedented detail. Local tissue motion exhibits distinct features of sub-micrometer displacements on a sub-millisecond time scale. We present a high-definition motion analysis technique based on plane wave ultrasound imaging able to capture these features. We validated this method by screening a group of healthy volunteers and compared the results with those for two patients known to have atherosclerosis to illustrate the potential utility of this technique.