Speckle-Tracking-Based Evaluation of Vascular Strain at Different Sites of the Arterial Tree in Healthy Adults

Abstract

Purpose: Vascular ultrasound (US) allows the analysis of vascular strain by speckle-tracking. This study sought to assess the extent to which vas cular strain varies between different segments of the arterial tree. Furthermore, this study aimed to investigate the reproducibility of vascular strain determination as well as of the components that contribute to the variance of vascular strain measurements in different vascular beds.

Materials and Methods: Speckle-tracking was used to determine the vascular strain of the abdominal aorta (AA), the common carotid artery (CCA), the common femoral (CFA) and the popliteal artery (PA) of healthy adults. Intra- and interday reproducibility and the components of variance of vascular strain of the respective arteries were determined.

Results: A total of 589 US clips obtained in 10 healthy adults (7 males, 28.3 ± 3.2 years) were analyzable. Vascular strain was 7.2 ± 3.0 % in the AA, 5.7 ± 2.1 % in the CCA, 2.1 ± 1.1 % in the CFA and 1.9 ± 1.1 % in the PA. The intraday coefficients of variation of vascular strain were 6.2 % (AA), 3.9 % (CCA), 3.3 % (CFA) and 6.1 % (PA), and the interday coefficients of variation were 5.9 % (AA), 8.4 % (CCA), 10 % (CFA) and 4.6 % (PA). The variance of vascular strain mainly depended on the investigated vessel and subject. Individual DUS clips, the day of examination and the (right/left) body side (in paired arteries) had no impact on the variance of vascular strain.

Conclusion: Vascular strain substantially varies between different sites of the arterial tree. Speckle-tracking by DUS allows the reliable determination of vascular strain at different arterial sites.

Zusammenfassung

Ziel: Vaskulärer Strain (Gefäßwandspannung) kann mit Gefäßultraschall (US) und Speckle-Tracking bestimmt werden. Ziel dieser Studie ist es zu untersuchen, in welchem Ausmaß sich vaskulärer Strain zwischen einzelnen Gefäßabschnitten unterscheidet. Zudem sollen die Reproduzierbarkeit und die Varianzkomponenten vaskulärer Strain-Messungen in den verschiedenen Gefäßabschnitten bestimmt werden.

Material und Methoden: Mittels Speckle-Tracking wurde der vaskuläre Strain der Aorta abdominalis (AA), der Arteria carotis communis (ACC), der Arteria femoralis communis (AFC) sowie der Arteria poplitea (AP) bei gesunden Individuen bestimmt. Die Reproduzierbarkeit und die Varianzkomponenten der vaskulären Strain-Untersuchungen wurden je Proband durch 3 Untersuchungen pro Tag über 3 verschiedene Tagen ermittelt.

Ergebnisse: Insgesamt wurden 589 US-Clips von 10 gesunden Erwachsenen analysiert (7 Männer, 28,3 ± 3,2 Jahre). Der vaskuläre Strain betrug 7,2 ± 3,0 % in der AA, 5,7 ± 2,1 % in der ACC, 2,1 ± 1,1 % in der AFC und 1,9 ± 1,1 % in der AP. Der Variationskoeffizienten von vaskulärem Strain innerhalb eines Tages betrug 6,2 % (AA), 3,9 % (ACC), 3,3 % (AFC) und 6,1 % (AP), an unterschiedlichen Tagen betrug der Variationskoeffizienten 5,9 % (AA), 8,4 % (ACC), 10 % (AFC) und 4,6 % (AP). Die Varianz des vaskulären Strain hing vor allem vom untersuchten Gefäßabschnitt und dem jeweiligen Probanden ab. Der Untersuchungstag, der jeweilige US-Clip und die Körperseite (rechts/links bei paarig angelegten Gefäßen) hatte keinen Einfluss auf die Varianz.

Schlussfolgerung: Vaskulärer Strain variiert zwischen unterschiedlichen Gefäßabschnitten. Mit Speckle-Tracking kann vaskulärer Strain an unterschiedlichen Abschnitten des Gefäßsystems verlässlich bestimmt werden.

Key words

ultrasound Doppler - ultrasound - arteries - aorta - strain - speckle-tracking - duplex ultrasound - vascular elasticity

Introduction

Cardiovascular diseases are the leading cause of death in Western societies and may be promoted by an increase in arterial stiffness. Stiffening of large arteries subsequently affects vascular hemodynamics leading to a rise in arterial pulse pressure. A high pulse pressure again accelerates arterial stiffening and might itself result in an increase in vascular strain [1]. Apart from these primarily nonatherosclerotic changes, arterial stiffening may be paralleled by a reduction in oscillatory shear stress [1]. Low shear stress affects endothelial function and might thereby contribute to the development of atherosclerosis [2]. Atherosclerosis-associated mechanisms, such as endothelial dysfunction and inflammation, potentially overlap with pathophysiological changes that are provoked by arterial stiffening [3].

To assess arterial stiffness, previous studies determined the distensibility of the carotid artery through the heart cycle by echo tracking using the ultrasonographic M-mode [4] [5] [6] [7]. Although these distensibility measurements have been related to the occurrence of cerebrovascular events, the M-mode based determination of arterial distensibility is considerably limited by the acquisition of measurements from only one single axis of a cross-sectional view of the artery [4] [5]. Hence, this method may miss segmental differences of vascular elasticity and it allows no conclusion to be drawn with respect to circumferential vascular strain.

Recent studies have shown that circumferential strain of the common carotid artery and the abdominal aorta can be determined by two-dimensional (2 D) imaging using vascular ultrasound (US) and speckle-tracking [8] [9] [10] [11]. Accumulating evidence suggests that ultrasonographic 2 D strain determination by speckle-tracking can be used as a sensitive, noninvasive imaging technique for the detection of local differences in arterial elasticity [9] [11]. Additionally, it has been proposed that ultrasonographic measurement of vascular strain by speckle-tracking allows determination of the vulnerability of atherosclerotic plaques [12]. Despite these promising data, it still remains to be clarified to what extent vascular strain varies between elastic arteries, such as the common carotid artery (CCA) and the abdominal aorta (AA), and muscular arteries, such as the common femoral artery (CFA) and popliteal artery (PA). Furthermore, it is not known whether the variability of measurements as well as possible confounders to the variance of vascular strain measurements differ between various vascular beds.

Hence, this study sought to assess the distribution of circumferential vascular strain among different parts of the vascular tree. Moreover, we aimed to investigate the differences in the reproducibility and in the components of variance of ultrasonographic determination of circumferential vascular strain in various vascular beds.

Methods

Study participants

The study was performed in accordance with the regulations of the institutional ethical committee. Healthy non-smoking volunteers were recruited to participate in the study. A medical history was obtained prior to inclusion. Previously known arterial hypertension, diabetes mellitus, dyslipidemia, heart failure, clinically manifest cardiovascular disease, other chronic disorders, a body mass index (BMI) > 25 kgm^-2, cardiac arrhythmias as well as a heart rate < 60 or > 100 bpm were predefined exclusion criteria. Furthermore, study participants had to be free of any medication.

Vascular ultrasound (US)

Vascular US investigations were performed in the morning (between 7:30 and 9:00 AM) – after a fasting period of at least 8 hours – in the same quiet and darkened room. For acclimatization, study participants had to rest in this room in a supine position for 15 minutes before the US examinations were initiated. A constant room temperature of 23.3 ± 0.6 °C was achieved by a central air-conditioning system. The following arterial segments were investigated: the AA 2 cm distal to the branching of the right renal artery, the right and left CCA 2 cm proximal to the carotid bifurcation, the right and left CFA 2 cm proximal to the femoral bifurcation and the right and left PA 2 cm proximal to the branching of the gastrocnemic artery. The AA, the CCA and the CFA were examined in a supine position, while the PA was examined in a prone position of the study participant.

All vascular US examinations were done by the use of the same Acuson machine [Acuson Sequoia 512 (Siemens, Erlangen, Germany)]. A 4 MHz curvilinear array transducer was applied for the examination of the AA and a 9 MHz linear-array transducer probe was used for scanning the CCA, the CFA and the PA. First, each arterial segment was carefully scanned to exclude plaques, stenoses, aneurysms or other vascular abnormalities. Then, clips of cross-sectional views – perpendicular to the direction of the blood flow – of the target segment of the respective artery were recorded. During clip acquisition electrocardiographic (ECG) gating was used. Each predefined arterial segment was assessed three times per examination; thereby, clips of each arterial segment were recorded through a period of three cardiac cycles. During clip acquisition study participants were requested not to breathe and to lie still. In total, 630 US clips (10 subjects * 3 days * 3 clips * 7 anatomic locations, thereof 3 pairs of bilateral arteries) were recorded. All clips were digitally stored in DICOM format for offline analysis of vascular strain.

Vascular strain

Vascular strain mirrors the deformation of the vessel wall through the cardiac cycle. It is expressed as the percentage change of the distance of two adjacent image points over time. For determination of vascular strain, US clips were stored on an external computer workstation and analyzed using the Syngo US Workplace software (Siemens Healthcare) by utilization of a speckle-tracking algorithm. First, the vessel-wall-blood-interface was manually marked starting at the near wall segment. Thereafter, this manually marked line was automatically divided into equidistant points by the Syngo software. Subsequently, these marking points were tracked over time using the Syngo vector velocity algorithm for speckle-tracking. According to this speckle-tracking process, the circumferential strain of six cross-sectional arterial wall segments was automatically calculated using global motion coherence and analysis of consistency of periodicity.

Circumferential vascular strain was depicted in color-coded strain-time graphs ([Fig. 1]). Referring to these strain-time graphs, peak positive strain and peak negative strain were determined. Segmental strain values were averaged over the whole vessel circumference and the resulting circumferential strain was averaged over three cardiac cycles. The total vascular strain, which was defined as the difference between the peak positive and peak negative strain, was used for further analysis. In the case of unreliable ECG signals, unanticipated movements during clip acquisition or inadequate image quality clips were excluded from the final analysis. To assess the intraday and interday coefficients of variation of vascular strain measurements and to determine the components of variance of vascular strain measurements, study participants were repeatedly examined three times per day and on three consecutive days. Vascular US as well as the offline analyses of vascular strain were performed by one trained investigator (SCR) under supervision of a senior investigator (OS).

Fig. 1 Cross-sectional duplex ultrasound image of the common carotid artery and the corresponding strain curves (each curve refers to one segment of the vessel circumference) through 3 cardiac cycles.

Statistical analysis

Calculations were performed using SPSS Statistics 21.0 (IBM) and SAS 9.3 (SAS institute). First, we assessed differences in vascular strain between individual arteries (AA, CCA, CFA, PA) by a repeated measures ANOVA. Hereby, the Bonferroni correction was applied to adjust confidence intervals. Secondly, we determined the intraday and interday reproducibility of vascular strain for each artery (AA, CCA, CFA, PA). Therefore, the respective coefficients of variation were calculated for each vessel location.

Thirdly, the components that contribute to the variance of vascular strain were analyzed considering the following parameters: subject, day of investigation, vessel, the body side (left or right), US clip with fixed vessel location and site in the same subject. Finally, the percentage proportions of the variance components (subjects, day of investigation, the body side (left or right), variation between US clips) were calculated for each vessel separately.

Correlations are expressed as Pearson’s correlations coefficient with two-tailed significance.

Results

Demographics

10 healthy volunteers (7 males, mean age 28.3 ± 3.2 years) were included in the present study. Before inclusion a detailed medical history was taken. Only non-smokers were included and none of the included study participants suffered from arterial hypertension, hyperlipidemia, diabetes mellitus or obesity. The mean heart rate was 64.0 ± 8.3 bpm, the mean systolic blood pressure was 113 ± 8 mmHg and the mean diastolic blood pressure was 68 ± 9 mmHg.

In total, 630 US clips were recorded. Of these 630 clips, 41 clips (6.5 %) had to be excluded because of unreliable ECG signals, unanticipated movements during clip acquisition or inadequate image quality. Thus, 589 clips (93.5 %) were included in the final analysis.

Vascular strain

Vascular strain differed between the AA, the CCA, the CFA and the PA (p < 0.0001, [Fig. 2]). The highest values of vascular strain were found in the AA (7.2 ± 3 %). Comparing the AA with other arteries, the vascular strain was lower in the CCA (5.7 ± 2.1 %) and in the CFA (2.1 ± 1.1 %). The lowest values of vascular strain were found in the PA (1.9 ± 1.1 %).

Fig. 2 Circumferential vascular strain as assessed by ultrasonographic speckle-tracking of the abdominal aorta, common carotid artery, common femoral and popliteal artery in healthy adults (10 subjects, 589 measurements). Boxplots indicate medians and interquartile ranges, whiskers display 1.5 interquartile ranges from the upper and lower quartile.

In the AA and CCA, the arterial diameters (AA: 12.8 ± 1 mm; CCA: 5.7 ± 0.5 mm) were not related to vascular strain (AA: r = –0.21, p = 0.06; CCA: r = –0.01, p = 0.85). There was a moderately inverse relation of the arterial diameters of the CFA and the PA (CFA: 7.6 ± 0.8 mm; PA: 5.2 ± 0.8 mm) with the vascular strain of the respective vessels (CFA: r = –0.20, p < 0.01; PA: r = –0.18, p = 0.02).

Reproducibility and components of variance

The intraday coefficients of variation of vascular strain were lower in the CCA and in the CFA than in the AA and in the PA. The interday coefficients of variation were lower in the AA and in the PA than in the CCA and in the CFA ([Table 1]).

Table 1 Intra- and interday reproducibility of circumferential vascular strain analyses of the abdominal aorta, common carotid artery, the common femoral artery and the popliteal artery in healthy adults (10 subjects, 589 measurements).

vessel	intraday coefficient of variation (%)	interday coefficient of variation (%)
abdominal aorta	6.2	5.9
common carotid artery	3.9	8.4
common femoral artery	3.3	10.0
popliteal artery	6.1	4.6

Regarding the variance of vascular strain measurements, we determined the distribution of predefined variance components. Within the spectrum of the considered variance components (the investigated subject, the day of investigation, the investigated artery and the investigated body side (left/right) and the individual clips with fixed vessel location), the individual artery itself had the highest impact on the variance of vascular strain. The investigated subject had a moderate impact on the variance of vascular strain, while the day of investigation, the investigated body side (left/right) and the individual clips with fixed vessel location hardly had any impact on the variance of vascular strain ([Fig. 3]). In addition, we analyzed the components that contribute to the variance of vascular strain stratified by the investigated artery. The distribution of variance components did not vary between the investigated arteries ([Table 2]).

Fig. 3 Percentage proportions of predefined components (the investigated subject, the day of measurement, the investigated vessel, the investigated body side (left/right), the clip (within one day)) that contribute to the variance of circumferential vascular strain in ten healthy volunteers.

Table 2 Components of variance of circumferential vascular strain in healthy adults (10 subjects, 589 measurements) separately analyzed for the abdominal aorta, the carotid artery, the common femoral artery and the popliteal artery.

components of variance	abdominal aorta [%]	carotid artery [%]	common femoral artery [%]	popliteal artery [%]
subject	55.3	53.1	30.5	10.3
day	0.5	3.3	2.2	0
body side (left/right)	0	0	0	0.1
clip	0.5	0.3	0	0
not explicable	43.7	43.2	67.3	89.7

Variance components are given as percentage proportions of the total variance for each artery. The variable “not explicable” indicates the proportion of the total variance not attributable to the investigated parameters.

Discussion

Distributional pattern of vascular strain

The present study demonstrates that vascular strain considerably varies between different arteries: vascular strain was higher in the AA and the CCA than in the CFA and the PA. High circumferential vascular strain reflects a high degree of circumferential arterial wall movement through the cardiac cycle. Hence, the differences of circumferential vascular strain between the AA and CCA on the one hand and the CFA and PA on the other hand might be attributed to the different wall properties of elastic and muscular arteries. Therefore, circumferential vascular strain – as a measure of circumferential elasticity – might also be related to the Windkessel function of the respective artery [13]. The Windkessel effect is defined as the distension of the respective vessel during systole and subsequent recoil during diastole to enable continuous blood flow to the periphery [14].

According to these hemodynamic properties, one might speculate that the extent of vascular strain depends on the diameter of the respective artery. In the present study, however, no substantial association was found between the arterial diameters and vascular strain. Thereby, it has to be noted that the major aim of this study was not to assess the relationship between vascular strain and diameters. Larger studies are needed to further elucidate the relationship between vascular strain and arterial diameters.

Reproducibility of vascular strain

An acceptable reproducibility of vascular strain in all anatomic locations – as assessed by US – is a main finding of the present study. For further specification we analyzed the components that contribute to the variance of vascular strain. Therefore, we considered the parameters anatomic site, body side (left/ride), interindividual differences (subject), interday variations as well as intraday variations (clip). Interestingly, we found that the anatomic site of strain measurement has the greatest impact on the variance between measurements indicating considerable differences of vascular strain in various segments of the vascular tree. Moreover, the low impact of the day of investigation, the body side and the respective US clip on the variance of vascular strain confirms the satisfactorily low inter- and intraday coefficients of variation of vascular strain measurements.

Methodological issues

To appropriately interpret these findings, it appears important to differentiate the ultrasonographic determination of circumferential vascular strain using speckle-tracking from other ultrasonographic methods that have been applied to assess arterial elasticity.

Previously, the carotid distensibility as measured by echo tracking using M-mode has been associated with vascular stiffness [4] [5]. It has to be noted that this method is limited by the acquisition of measurements from a single axis and might thereby miss segmental differences of vascular elasticity. Furthermore, this method assumes true circularity of the arterial cross section, which might often not reflect the anatomic reality.

In this context, it should be emphasized that the speckle-tracking-based determination of circumferential vascular strain accounts for the wall elasticity of the entire arterial circumference.

Nevertheless, data on the strain of peripheral arteries are scarce and there is no standardized method for the determination of vascular strain. Most studies focused on vascular strain of the common carotid arteries by gathering strain values at the time of the R-wave during ECG gating [9] [15].

When aiming to assess and compare vascular strain at different locations of the vascular tree, one has to be aware of different pulse wave transit times to the respective arterial sites [16].

According to the respective pulse wave transit time, the determination of vascular strain at the time of R-wave peak would not correctly correspond with the peak systolic vascular strain. Especially in lower limb arteries with longer distances between the left ventricular outflow tract of the heart and the measurement site, the R-wave gated determination of vascular strain would result in considerably lower strain values because of the period of latency between the systole linked R-wave and the approaching pulse wave at peripheral measurement sites.

Furthermore, the period of latency between the systole linked R-wave and the approaching pulse wave considerably differs between various sites of the vascular tree [17]. Therefore, we decided to refrain from the R-wave-gated determination of vascular strain values. Based on these considerations on the determination of vascular strain at different anatomic sites, we consequently studied the total vascular strain, defined as the absolute difference between the maximum vascular strain and the minimum vascular strain that can be measured through the heart cycle. The determination of total vascular strain is independent of the respective pulse wave transit time and, most importantly, allows the direct comparison of vascular strain at various anatomic sites, irrespective of different periods of latency between the ventricular systole and the time of measurement. Therefore, the R-wave-independent determination of total vascular strain has to be differentiated from the R-wave-gated measurement of vascular strain [8]. These methodological variations between studies on vascular strain underline the need for standardized protocols for vascular strain determination.

Perspectives of vascular strain

In the present study cross-sectional views of the respective vessel were used to determine the total vascular strain. Cross-sectional views were used to allow the evaluation of vascular strain around the entire vessel circumference. Furthermore, we aimed at studying the circumferential strain of the respective artery, which requires cross-sectional imaging by US.

Apart from circumferential strain, the Syngo US Workplace software (Siemens Healthcare) additionally provides the possibility to assess longitudinal strain as well as radial strain. For longitudinal strain analysis, longitudinal sections of the respective artery have to be viewed by US. Since longitudinal shifting of vessel wall speckles in the respective US clips are considerably low, it appears questionable whether longitudinal vascular strain can be reliably determined by US. Similarly to longitudinal strain, the assessment of radial strain might be limited by US imaging resolution. For radial strain measurements the border between the media and the adventitia as well as the intimal vessel surface need to be visualized around the whole vascular circumference. Especially in less superficial arterial segments, a precise discrimination between these two boundaries might not be achievable by moving clips recorded by US. Focusing on circumferential vascular strain, adequate visualization of the intima-blood-interface only is sufficient. Taking these considerations together, circumferential strain appears to be most suitable for vascular strain analysis.

Limitations

The strengths and limitations of this study warrant mention: much emphasis has to be put on the acquisition of clips with a clear vessel border and without lateral signal extinction, which comes from the deflexion of ultrasound waves at the border of anatomic structures with different densities. The software used for analysis could mistake these artifacts as low motion. Therefore, it is necessary to manually exclude clips in post-processing whenever artifacts obscure the vessel wall. Moreover, we are aware of the limited number of study participants. Hence, we aimed at measuring the vascular strain at several vascular sites of the same study participants with an appropriate number of repetitions. Thereby, we were able to demonstrate an acceptable reproducibility of vascular strain measurements at different parts of the vascular tree. According to the limited number of healthy study participants with consistently normotensive blood pressure values, no conclusions can be drawn with respect to an association between vascular strain and blood pressure. To address the relationship between normotensive blood pressure values and vascular strain, larger sample sizes are needed. Additionally, further studies in large populations are required to reliably determine the impact of age and gender on the distribution of vascular strain.

As a major strength, the present study demonstrates the feasibility of vascular strain measurements in histologically different types of arteries. The findings of this investigation allow a direct comparison of the reproducibility and the components of variance of vascular strain between various vascular beds. This information is essential for the implementation of vascular strain measurements in a larger scale of clinical studies.

In summary, the present study demonstrates that vascular strain substantially differs between various parts of the vascular tree. Circumferential vascular strain can be reliably determined by ultrasonographic speckle-tracking with acceptable reproducibility. Whether this method allows the detection of early vascular damage as a consequence of cardiovascular risk factor exposure or inflammatory processes remains to be investigated in further studies.

Funding/Conflict of Interest

This study was financially supported by the Jubilee Fond of the Austrian National Bank (OeNB-Fonds [grant number 14 536]).

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