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Cardiovascular Research 2000 45(1):27-35; doi:10.1016/S0008-6363(99)00282-5
© 2000 by European Society of Cardiology
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Copyright © 2000, European Society of Cardiology

Noninvasive vascular ultrasound

An asset in vascular medicine

Robert S Renemana,* and Arnold P.G Hoeksb

aDepartment of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands
bDepartment of Biophysics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

* Corresponding author. Tel.: +31-43-388-1198; fax: +31-43-367-1028 Reneman{at}fys.unimaas.nl

KEYWORDS Arteries; Blood flow; Endothelial factors; Ultrasound


   1 General introduction
Top
 1 General introduction
2 Basic aspects of...
 3 Clinical applications
 4 Conclusions
 References
 
1.1 Introduction
There are always moments in life, inviting to look back on the past. Entering the next millennium is certainly such an occasion, because it happens generally only once in a life-time. Therefore, we very much liked the idea of the Editors to publish a special issue of Cardiovascular Research on the occasion of this event and to explore the impact of the articles in the journal most frequently cited over the years on further developments in the field. We gladly accepted their invitation to evaluate in this respect the article by Levenson et al. published in Cardiovascular Research in 1981 [1].

1.2 Content of the article
In this article the authors described an ultrasound system to assess diameter, blood flow velocity and volume flow in the brachial artery in man. The apparatus consisted of an adjustable range-gated pulsed Doppler system, emitter frequency 8 MHz, combined with a double transducer system to accurately determine the angle between ultrasound beam and vessel axis. The latter is a prerequisite for accurate determination of both the velocity in and the diameter of the artery and, hence, for proper calculation of volume flow. The length of the sample volume could be adjusted by varying the length of the reception duration. A small sample volume was used to measure velocity locally in the artery and to determine the diameter of the vessel accurately and a large one to estimate the average velocity over the cross-sectional area of the vessel. A static high-pass filter with a lower cut-off frequency of 250 Hz was used to reduce interference of high amplitude low frequency signals reflected by the arterial walls. The validity of the system was tested in an in vitro set-up and the results showed that the diameter as assessed with the system compared favorably with the diameter of the tubing in the range between 3 and 9 mm (r=0.99; P<0.001) and it was indicated that the velocities measured with the system were within 95% of those delivered by the hydraulic test device for flow velocities between 5 and 100 cm·s–1. In vivo measurements were performed on healthy volunteers and it was shown that increases in brachial artery diameter following the intravenous administration of nitroglycerine could be adequately followed with the ultrasound device.

1.3 The impact of the article
The main purpose of the study presented by Levenson et al. [1] was to develop a technique to measure reliably the diameter of and volume flow in human arteries. The brachial artery was chosen, because of its easy access for ultrasound and the possibility to keep the transducer in place after the correct position had been obtained. Therefore, the impact of the article can be rephrased in terms of the importance of diameter and volume flow measurements in the brachial artery in clinical studies. Although in terms of hemodynamics, interesting information was obtained by means of this ultrasound technique, for example, in patients with established hypertension [2], its impact had originally to be considered as limited. Proper evaluation of alterations in artery wall properties and structure in disease require the assessment of other parameters than volume flow and arterial diameter alone. Besides, several studies have shown that the brachial artery is not necessarily representative to study arterial changes in such diseases as hypertension and diabetes. In recent years, however, the determination of flow induced vasodilation in the brachial artery is used as a test to assess endothelial dysfunction in diseases such as hypertension [3] and atherosclerosis [4], and in chronic hemodialysis patients [5]. The ultrasound technique developed by Levenson et al. [1] seems to be very suited for this application.

This article is very important in terms of marking the beginning of a series of developments, ultimately enabling the noninvasive investigation of, for instance, the changes in arterial wall properties and intima–media thickness (IMT) in hypertension in man; studies to which the authors of the 1981 publication [1] have made major contributions themselves. More recently noninvasive techniques were developed to study in humans, wall shear rate/stress along the arterial tree and the relation between these fluid dynamic parameters and IMT in and near arterial bifurcations. These developments will contribute to the further progression of vascular medicine, an independent and probably the most important discipline in the clinic in the next millennium.

1.4 Comments to the article
The authors should have provided more details regarding the accuracy of the flow velocity assessment with their system. Even when a large sample volume was used, systematic overestimation of the blood flow velocity as measured with the ultrasound system may be anticipated, because the contribution of low velocities near the vessel wall to the average velocity over the cross-sectional area will be limited. Low blood flow velocity information is lost due to the cut-off frequency of 250 Hz and the relatively narrow ultrasound beam as a consequence of the relatively small diameter of the transducer (5 mm for an on average 4 mm diameter artery). For reliable assessment of the average velocity over the cross-sectional area of an artery the diameter of the transducer should be at least 1.5-times the vessel diameter [6].

1.5 Content of the present review
In this review we will discuss the most relevant developments in noninvasive ultrasound and summarize some of the recent findings in clinical vascular research.


   2 Basic aspects of vascular assessment
Top
 1 General introduction
 2 Basic aspects of...
3 Clinical applications
 4 Conclusions
 References
 
2.1 Parameters to characterize artery wall properties and which can be assessed noninvasively
Parameters commonly used to characterize the elastic behavior of arteries are distensibility and compliance, defined as the relative ({Delta}V/V) and absolute ({Delta}V) change in arterial volume (V) for a change in pressure, assuming a linear relationship between the time-dependent change in lumen cross-sectional area and pressure. The error arising from this assumption is small for the observed changes in pressure and lumen cross-sectional area during the cardiac cycle, especially in elastic arteries. Therefore, in clinical investigations the increase in volume and pressure in the systolic phase of the cardiac cycle is commonly used to describe arterial distensibility and compliance. Distensibility and compliance are generally expressed in terms of changes in lumen cross-sectional area, A, (({Delta}A/A)/{Delta}p and {Delta}A/{Delta}p, respectively), because it is practically impossible to accurately determine volume and volume changes noninvasively in vivo. The terms area compliance and area distensibility are often used for these relations. This simplification is allowed because in unimpeded arteries length is constant so that the change in volume during the cardiac cycle is caused by a change in luminal cross-sectional area alone [7]. The constant length can be explained by the fact that arteries are longitudinally tethered at their in vivo length [8,9] and by the experimental finding that, at in vivo length, isolated vessels neither lengthen nor shorten with pressure changes [10]. The expression for distensibility coefficient (DC) in terms of lumen cross-sectional area is

Formula

For practical purposes this relation can be rewritten as a function of diameter (d) rather than area. This is allowed if it is assumed that the artery lumen is circular in cross-section, a reasonable assumption in humans, and that the change in diameter ({Delta}d) is small relative to d. Then, this relation becomes

Formula

Similarly, compliance can be expressed in terms of lumen cross-sectional area, providing

Formula

This relation can also be rewritten in terms of diameter

Formula

One usually measures {Delta}d as the increase in arterial diameter during the systolic phase of the cardiac cycle. The end-diastolic diameter is generally used as reference diameter. This diameter (d) and {Delta}d can be measured accurately and reliably noninvasively by means of ultrasound (see below), but determination of {Delta}p at the site of measurement of d and {Delta}d or at a representative site elsewhere is still not without problems. It has been shown that for the assessment of DC and CC in the carotid arteries {Delta}p in the brachial artery is a good substitute [11]. Recent studies in our institute, however, showed that brachial artery {Delta}p or {Delta}p as assessed in a finger are not representative of {Delta}p in the femoral artery (unpublished results).

An alternative way to assess arterial stiffness is the use of pulse wave velocity (PWV); the stiffer the artery is, the higher this velocity will be [12–14]. In relation to distensibility, PWV can be written as

Formula
where {rho}=the density of blood.

A major advantage of this approach is that no arterial pressure recordings are necessary to determine DC and, hence, CC. PWV velocity as determined with conventional techniques, however, provides information about arterial stiffness averaged over a relatively long artery segment. This is a limitation because arterial distensibility may vary substantially locally. Recently, we developed a technique to measure PWV in short artery segments of about 1 cm, allowing the local assessment of DC and CC without the necessity of measuring arterial pressure [15].

Strain is the change in length relative to the mean length. For arteries (radial) strain provides a measure of the relative deformations to which arteries are exposed. It can be calculated as {Delta}d/d. This strain is not a material property, because it depends on pulse pressure and wall thickness. Wall material can be characterized by the Young's modulus, E, which is the ratio of stress and strain in the vessel wall [16,17]. Assuming pressure independence, E can be derived through the Moens–Korteweg equation of pulse wave velocity, Formula (where h=wall thickness). The Young's modulus can then be written as

Formula

2.2 Noninvasive assessment of d and {Delta}d
Beside the method described by Levenson et al. [1] a variety of techniques has been used to assess not only d but also {Delta}d (for review, see Ref. [18]). These techniques make use of amplitude tracking, instantaneous or average phase detection or echo tracking. In the most recent systems echo tracking is used and the displacement detection algorithm is based on radiofrequent (RF) correlation tracking rather than Doppler processing [19]. Processing in the RF domain has several advantages. First, the result obtained is not sensitive to the carrier frequency of the received signal. Second, it can be applied to spatial sample windows of arbitrary length. Third, it is still accurate when extremely short temporal estimation windows of a few milliseconds are employed. The reader is referred to Hoeks [19] for a more detailed discussion on the advantages and limitations.

The system currently in use in our institute and in many other laboratories consists of a two-dimensional B-mode imager attached to a vessel wall moving detector system (Pie Medical, Maastricht, The Netherlands) and is based on the principles previously described by Hoeks et al. [19,20]. On the B-mode image of the artery under investigation, an M-line perpendicular to the artery of interest is selected and the RF signals induced within a sample volume coinciding with the artery walls are processed. Originally the anterior and posterior wall boundaries were identified by placing cursors, representing the sample windows for data processing, on the RF signals displayed on the screen, but in the newly developed system the arterial walls can also be identified automatically allowing the real-time presentation of d and {Delta}d (Fig. 1) and, hence, {Delta}d/d [21,22]. With this system arterial wall displacements of a few micrometers can be resolved [20]. The intra- and interobserver variability for the assessment of {Delta}d/d is about 8% (coefficient of variation) for the carotid arteries and about 12% for the femoral arteries [23]. The arterial diameter can be determined with an intra- and interobserver variability of 2.8–4.5% for the carotid arteries and 2–3% for the femoral arteries [23].


Figure 1
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  		Fig. 1 Arterial diameter as a function of time (a), and the changes in arterial diameter per heart beat (distension) as a function of time (b) as recorded in a healthy subject; 800 heart beats are recorded. The pronounced increase in diameter and the decrease in distension at about 200 heart beats is due to swallowing movements of the volunteer.

 
2.3 IMT and its noninvasive assessment
Two-dimensional echosystems are also used to determine arterial wall thickness, a parameter necessary to calculate the Young's modulus. Besides, wall thickness has gained increasing attention because of its involvement in adaptive responses to physiological and pathophysiological processes [24] as, for example, in ageing and hypertension. Moreover, increase in wall thickness in the carotid arteries has been proposed as a marker of atherosclerosis elsewhere in the arterial system [25–27]. The noninvasive assessment of wall thickness by means of ultrasound is limited to IMT, because the adventitia can not be distinguished reliably from the surrounding structures. On a B-mode image only the intima is visible as a distinct layer and the media appears as a relatively dark narrow band, because of its low echogenicity. Since the echogenicity of the adventitia is relatively high, as compared with the other layers in the wall, in the anterior wall the large trailing echos from the adventitia tend to obscure the weaker signals from the closely spaced intima. Therefore, measurements of IMT are usually made on the posterior wall of arteries.

Since the first IMT measurements made by Pignoli et al. [28], using calipers, a variety of techniques has been developed, making use of automated digitization of the B-mode image [29,30], automated interpolation of the intima–media complex [31,32], automated spatial averaging procedures [33,34] or improved display and zoom techniques [35]. All these techniques provide a mean IMT over a length of 10–20 mm. When interested in the use of IMT as an indicator of a specific disorder, averaging over a certain segment may be appropriate. When studying the relation between IMT on the one hand and artery wall properties or wall shear rate/stress on the other, however, local assessment of IMT is indicated, because in an artery segment significant differences in IMT can be observed at short distances from each other [36]. Recently we developed an automated method to assess IMT locally, which is based on processing of the received RF signals [37], using the system for the assessment of d and {Delta}d (see above). After RF data acquisition the first M-line activated is displayed on a personal computer screen, allowing identification of a window of 3 mm covering the posterior lumen-wall and interwall transitions. Data from this window over time are then stored on hard disk for further off-line processing. In this processing the amplitude envelope of the RF-signals is taken and after phase alignment of the signals the time average of the envelope is determined to reduce speckle interference. An edge detection algorithm with preselected threshold is applied to the time-averaged envelope to assess IMT. With this technique IMT can be assessed in vivo with a precision of the order of 45 µm [37]. The results obtained with this method compare favorably with those obtained with other methods currently in use [38]. The method is independent of the B-mode imager used and allows the assessment of differences in IMT in short artery segments.

2.4 Wall shear rate and its noninvasive assessment
Blood flowing through a vascular segment exerts a tangentially directed shear stress on the luminal surface of endothelial cells. Wall shear stress is the product of wall shear rate, i.e. the radial derivative of the velocity near the wall, and local blood viscosity. Wall shear stress has been shown to be an important determinant of the release of vasoactive substances from the endothelial cells [39–41] and, hence, of vessel wall function. Several of the vasoactive molecules stimulate the expression of adhesion molecules and chemokines involved in intima–media thickening [4].

Since in large arteries the velocity profile, i.e. the velocity distribution over the cross-sectional area, is a flattened parabola, shear is low in the center of a vessel and high near the vessel wall. Reliable noninvasive assessment of wall shear rate requires accurate measurement of low blood flow velocities close to the vessel wall. This can only be achieved when the high amplitude low frequency signals reflected by the vessel wall are adequately suppressed without loosing the low blood flow velocity information. Originally static high-pass filters with a cut-off frequency in accordance with the highest anticipated temporal frequency induced by the slowly moving vessel wall were used to suppress these high amplitude reflections, but in this approach the scattering induced by the slowly moving red blood cells near the wall is suppressed as well. A better approach is to consider the time-dependent aspects of the reflections and to use a band stop filter which adapts its rejection range to the mean frequency of the reflections from the vessel wall. In this adaptive filtering technique these reflections are suppressed by shifting the temporal frequency distribution towards zero frequency, where the shift is given by the estimated mean frequency of the reflected signal. Subsequently, the reflections, then centered around zero frequency, are suppressed by a high pass filter with a low cut-off frequency. By means of adaptive filtering low velocities near the vessel wall can be determined reliably [42].

For the assessment of wall shear rate a conventional B-mode imager is combined with dedicated signal processing to measure the blood flow velocity distribution along a selected line of observation across the center of the vessel. After identification of the wall–lumen interfaces by placing cursors, representing sample volumes, on the reflections from the anterior and posterior walls as displayed on the screen, the time-dependent blood flow velocity distribution is obtained with the use of a modeled cross-correlation function applied to the RF data between the cursors. Calculation of the mean velocity for all RF segments provides a time-dependent velocity profile. The shear rate distribution is derived from the radial derivative of the velocity profile at each site and at each time instant. Because of the limited resolution due to the finite size of the sample volume, velocities cannot be determined at the wall. Therefore, the maximum value of the radial derivative of the velocity is considered as the estimate of instantaneous wall shear rate. In general the maximum shear rate is assessed about 300 µm from the blood–intima boundary. This implies that the measured shear rate has to be considered as a least estimate, because shear rate may be higher near the wall than at the site of assessment. From the shear distribution mean wall shear rate, the time-averaged shear rate over one cardiac cycle, and peak wall shear rate, the value at peak systole, can be determined. In the common carotid artery the intrasubject intrasession variability on different days varies between 13 and 15% for peak wall shear rate and between 10 and 12% for mean wall shear rate (coefficients of variation) and the intersubject intrasession variability on different days varies between 16 and 19% for peak wall shear rate and between 11 and 17% for mean wall shear rate [43]. In the femoral artery these values are somewhat higher [44]. Therefore, about 16 measurements have to be performed to obtain reliable values of mean and peak wall shear rate.

Because in large arteries the plasma layer is only 3–7 µm [45], which is substantially smaller than the spatial resolution of our wall shear rate system, the effect of this layer on blood viscosity can be neglected and local whole blood viscosity can be used for the determination of wall shear stress.

Recently the assessment of arterial diameter, the change in arterial diameter during the cardiac cycle, IMT and wall shear rate has been integrated in one system, facilitating studies on the relation between these parameters under normal and pathological circumstances [22].

Beside ultrasound techniques, magnetic resonance imaging (MRI) is used to assess wall shear rate in vivo [46,47]. The results obtained with MRI are promising, and for the carotid artery compare favorably with those obtained with ultrasound [47].


   3 Clinical applications
Top
 1 General introduction
 2 Basic aspects of...
 3 Clinical applications
4 Conclusions
 References
 
3.1 Introduction
Over the years the ultrasound techniques described have been widely used in clinical studies, especially in assessing artery wall properties and IMT in ageing and hypertension, and more recently to evaluate the influence of female hormones on these properties [48,49] or to assess flow mediated arterial dilation to determine endothelial dysfunction in disease [3–5]. In this part of the review we will summarize some of the findings in ageing and hypertension and of the recent observations on wall shear rate/stress along the arterial tree and their relation with IMT at different sites in one artery to illustrate the state of the art of noninvasive vascular ultrasound. Moreover, attention will be paid to the possible usefulness of the ultrasound technique described by Levenson et al. [1] to assess flow mediated arterial dilation.

3.2 Changes with increasing age
It has been known for quite some time from in vitro studies that arteries become stiffer with increasing age [50], even when the elastic properties are assessed at similar pressure [51]. The introduction of noninvasive ultrasound techniques, however, enabled the study of the changes in artery wall properties with ageing in more detail. It could be demonstrated that distensibility and compliance of the elastic common carotid artery decrease linearly with age from the third age decade onwards, the reduction of compliance being less steep than the reduction of distensibility [7]. The less pronounced decrease in compliance can be explained by the increase in arterial diameter observed with increasing age [7,16,52,53]. In this way the ability of the arteries to store volume energy is reduced less than expected on the basis of the loss of distensibility, limiting the increase in systolic arterial blood pressure at older age. The Young's modulus of the carotid artery [16] increases with age, indicating loss of elastic properties of the artery wall. The distensibility [54] of the common femoral artery is reduced at older age, but the compliance of the brachial artery [55] and the distensibility of the deep and superficial femoral arteries are not [54]. These findings indicate that the changes in artery wall properties with age are not homogeneous along the arterial tree and that differences between arteries have to be appreciated.

The loss of distensibility with increasing age is not necessarily homogeneous along arterial bifurcations either. In the carotid artery bifurcation, for example, the carotid artery bulb, where predominantly the baroreceptors are located, is more severely affected by age than the remainder of the bifurcation [52,56]. Also in the femoral artery bifurcation local differences in reduction of distensibility with increasing age have to be appreciated [54].

The increase in artery wall thickness with increasing age results mainly from adaptive intimal thickening, a physiological adaptation to mechanical stresses, secondary to variations in flow, wall tension or both [57]. Beside intimal thickening, which is caused by enhanced contents of reticulated nonfibrous connective tissue and smooth muscle cells [57], there is progressive fibrosis of the media [58]. The relative cell content of both intima and media decreases as extracellular material accumulates [58]. Whether these changes in artery wall composition can be held responsible for the loss of arterial distensibility and the increase in arterial diameter with increasing age is still a matter of debate. Recent studies in rats indicate that neither changes in collagen and elastin content and density, nor in the degree of collagen cross-linking can be held responsible for the changes in artery wall properties with increasing age [59]. It has been proposed that the increase in arterial stiffness with age is associated with a relative loss of glycosaminoglycans and proteoglycans [60], substances likely to have elastic properties [61].

3.3 Changes in hypertension
Over the years it has been shown that arteries are stiffer in patients with established hypertension than in normotensive control subjects [62,63], but also in studies on hypertension the introduction of noninvasive ultrasound techniques has provided more details regarding the changes in artery wall properties in this disorder. It could be demonstrated that the loss of distensibility and compliance is not a generalized phenomenon along the arterial tree. For example, in the elastic carotid artery at ambient mean arterial pressure, both distensibility and compliance are significantly lower in untreated mild and moderate essential hypertensive patients than in age-matched control subjects [64]. In the radial artery, however, no significant differences in distensibility and compliance could be detected between untreated hypertensive patients and age-matched controls [65]. As compared to normotensive subjects, in patients with established hypertension the diameter was found to be significantly increased in the carotid artery [64] and the brachial artery [2,66], but not in the radial artery [65].

Loss of compliance of the elastic arteries will lead to an increase in systolic arterial pressure, an independent risk factor for cardiovascular disease [67,68], and will expose increased load on the heart [69].

Wall thickness, artery mass and the wall thickness–lumen diameter ratio are significantly larger in patients with established hypertension than in age-matched control subjects, at least in the radial artery [70]. This observation is consistent with the hypothesis that arteries try to keep wall stress constant [24,57]. Whether this adaptational process takes place also in other human arteries is as yet unknown. In the radial artery the Young's modulus was found to be similar in established hypertensive patients and in age-matched control subjects, despite the increase in wall mass [17].

Although structural changes have been observed in arteries of hypertensive patients [71], it is still a matter of debate whether in hypertension the reduction of artery wall distensibility is mainly caused by the increase in arterial blood pressure or whether structural changes in the wall contribute to this process. The results of Laurent et al. [64] are in favor of a dominant role of increased arterial blood pressure, but observations in patients with borderline hypertension (see below) and recent findings in spontaneously hypertensive rats (SHR) [59] argue against a dominant role of elevated blood pressure. In 6-week-old SHR, compliance and distensibility are significantly reduced and media mass is significantly increased, as compared with normotensive Wistar Kyoto rats, while arterial blood pressure is not significantly different between these strains at this age. These findings indicate that in some forms of genetic hypertension alterations in artery wall properties are not dependent on elevated blood pressure.

Not only in established hypertension, but also in borderline hypertension (140/90<blood pressure<160/100 mmHg) elastic arteries are less distensible and less compliant than in age-matched control subjects [72–74]. Because in the carotid arteries these differences in distensibility and compliance are already apparent at a relatively young age, it has been proposed that these arteries age more quickly in patients with borderline hypertension than in normotensive subjects, especially since the decrease in arterial distensibility and compliance is substantial and the difference in arterial blood pressure between patients and normotensives is limited [74]. If this hypothesis is correct, in borderline hypertensives the decrease in distensibility of the carotid artery should be most pronounced in the carotid artery bulb, because in this part of the carotid artery bifurcation artery wall distensibility is most affected by age [52]. This is indeed the case, the proximal part of the bulb being significantly less distensible than the rest of the bulb [56]. Whether this local wall stiffening leads to disturbed baroreceptor sensitivity in these patients is as yet unknown. If reduced wall distensibility hampers proper functioning of the baroreceptors, which have to regulate pressure on information derived from a smaller range of distension than in the normal more distensible carotid artery bulb, it may quite well be that this process plays a role in the development of borderline hypertension. The observations that distensibility and compliance are substantially reduced in borderline hypertensives, as compared with normotensives, despite relatively small differences in arterial blood pressure and that the bulb is more affected than the remainder of the carotid artery bifurcation, although these parts are exposed to the same mean blood pressure, also indicate that the changes in artery wall properties in these patients cannot be explained by increased blood pressure alone.

3.4 Wall shear rate/stress in humans
Based on the theory of minimal energy expenditure, mean wall shear stress should be regulated via diameter adaptation and be more or less the same along the vascular tree [75–77]. In several studies it has indeed been shown that if volume flow is forced to change from its physiological state, and thus mean wall shear stress, the arterial diameter adapts and mean wall shear stress is restored towards its baseline value [78,79]. This also holds for changes in blood viscosity [80].

It is basically this adaptation mechanism that is made use of clinically, when assessing flow mediated arterial dilation to test the integrity of the endothelium [3–5]. Under normal circumstances increased volume flow results in arterial dilation through endothelium-mediated mechanisms. In patients with such diseases such as hypertension and atherosclerosis, however, increased volume flow is not followed by arterial dilation, or only to a limited extent, as a consequence of disturbed endothelial cell function. Although ultrasonic wall track systems are generally used to record the arterial dilation, the ultrasound device described by Levenson et al. [1] is likely to be a good alternative, especially because it enables the assessment of both diameter and volume flow.

In recent studies it was shown that mean wall shear stress in the human common carotid artery is close to the theoretical value of 1.5 Pa and that this value decreases significantly with increasing age, in both males and females, reaching values around 1.1–1.2 Pa at the age of 60 years [81]. These values are still within 25% of the optimal value predicted by the model of minimal energy expenditure. The decrease in mean wall shear stress with increasing age can be explained by the increase in arterial diameter to reduce the loss of compliance at older age; a good example of compromise between two parameters to be regulated. At rest, in the femoral artery bifurcation, however, mean wall shear stress was found to be substantially lower in both the common (0.35 Pa) and the superficial (0.49 Pa) femoral artery. The lower mean wall shear stress values in the femoral artery bifurcation can likely be explained by reflections from the periphery [44]. Unlike in the common carotid artery, in the femoral artery bifurcation mean wall shear stress does not change with increasing age [44]. The lower mean wall shear stress in the common than in the superficial femoral artery was found to be associated with a greater IMT, indicating that these differences do have structural consequences [44]. A similar observation was made in the common carotid artery [82]. Near the carotid artery bifurcation mean wall shear rate was lower, probably due to reflections from the external carotid artery, than about 3 cm more proximally in the common carotid artery, where the influence of reflections has greatly disappeared. Also in this artery IMT was greater at the site of lower wall shear rate. Studies on the interaction between wall shear rate/stress and artery wall properties are on their way.


   4 Conclusions
Top
 1 General introduction
 2 Basic aspects of...
 3 Clinical applications
 4 Conclusions
References
 
The publication of the article by Levenson et al. on the development of a noninvasive ultrasound technique to determine diameter, blood flow velocity and volume flow in the brachial artery [1], and more specifically the application of this technique in patients with established hypertension [2], marks the start of a series of developments aiming at obtaining insights into alterations in artery wall properties in vascular diseases and into the relation between wall shear rate/stress and artery wall structure and function in humans. The methods presently available make it possible to study vascular changes under physiological and pathophysiological circumstances with relatively great detail. Important lessons learned are that most of the alterations in, for example, ageing and hypertension, are not homogeneous along the arterial tree and even not in arterial bifurcations. The latter observation demonstrates that the availability of techniques to locally assess artery wall structure and function is required to follow vascular processes adequately. Several of the observations described do have clinical implications and it is very likely that in the near future the noninvasive ultrasound techniques described will not only be used in clinical and epidemiological vascular studies, but also in patient management. At the present state of the art, the most important limitation in the noninvasive assessment of artery wall properties is that arterial blood pressure, an indispensable parameter to calculate distensibility and compliance, cannot be reliably assessed noninvasively at the site of determination of arterial diameter and the change of this diameter during the cardiac cycle. It has been shown that brachial artery pressure is a good alternative for the pressure in the carotid artery, but this certainly does not hold for pressures at other locations. Therefore, the local assessment of artery wall distensibility without the necessity of measuring arterial blood pressure [15] can be considered an important asset. It is of interest to note that after nearly two decades the technique developed by Levenson et al. [1] may be used to assess endothelial dysfunction in humans, an application it was not invented for.


   Acknowledgements
 
The authors are indebted to Karin van Brussel and Jos Heemskerk for their help in preparing the manuscript.


   References
Top
 1 General introduction
 2 Basic aspects of...
 3 Clinical applications
 4 Conclusions
 References
 

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