The impact of geometry, intramural friction, and pressure on the antegrade longitudinal motion of the arterial wall: A phantom and finite element study.

Longitudinal motion of the carotid arterial wall, as measured with ultrasound, has shown promise as an indicator of vascular health. The underlying mechanisms are however not fully understood. We have found, in in vivo studies, that blood pressure has a strong relation to the antegrade longitudinal displacement in early systole. Further, we have identified that a tapered geometry and the intramural friction in-between two parts of a vessel wall influence the longitudinal displacement. We therefore studied the interaction between pressure, vessel geometry and intramural friction, tapered and straight ultrasound phantoms in a paralleled hydraulic bench study and corresponding numerical models. Profound antegrade longitudinal motion was induced in the innermost part of both tapered phantoms and the numerical models, but to a lesser extent when intramural friction was increased in the simulations. Strong correlations (R = 0.82-0.96; p < 1e-3; k = 9.3-14 µm/mmHg) between longitudinal displacement and pulse pressure were found in six of seven regions of interest in tapered phantoms. The motion of the straight phantom and the corresponding numerical model was smaller, on average zero or close to zero. This study demonstrates that tapering of the lumen, low intramural friction, and pressure might be important conducive features to the antegrade longitudinal motion of the arterial wall in vivo.

Response of the carotid artery longitudinal motion to submaximal physical activity in healthy humans-Marked changes already at low workload.

The longitudinal motion of the arterial wall, that is, the displacement of the arterial wall along the artery, parallel to blood flow, is still largely unexplored. The magnitude and nature of putative changes in longitudinal motion of the arterial wall in response to physical activity in humans remain unknown. The aim of this study was therefore to study the longitudinal motion of the carotid artery wall during physical activity in healthy humans. Using in-house developed non-invasive ultrasonic methods, the longitudinal motion of the intima-media complex and the diameter changes of the right common carotid artery (CCA) in 40 healthy volunteers (20 volunteers aged 22-35 years; 20 volunteers aged 55-68 years) were assessed at rest and during submaximal supine bicycle exercise. In a subset of the subjects (n = 18) also intramural shear strain were analyzed. The longitudinal motion of the intima-media complex underwent marked changes in response to physical activity, already at low workload; with most evident a marked increase of the first antegrade displacement (p < 0.001) in early systole. Likewise, the corresponding shear strain also increased significantly (p = 0.004). The increase in longitudinal motion showed significant correlation to increase in blood pressure, but not to blood flow velocity or wall shear stress. In conclusion, physical activity markedly influences the longitudinal motion of the carotid artery wall in healthy humans already at low load. A possible "cushioning" function as well as possible implications for the function of the vasa vasorum, endothelium, and smooth muscle cells and extracellular matrix of the media, are discussed.

Comparison of the multi-phasic longitudinal displacement of the left and right common carotid artery in healthy humans.

BACKGROUND: During the cardiac cycle, there is a multi-phasic bidirectional longitudinal movement (LMov) of the intima-media complex of large arteries, i.e. along the arteries. On the left side the common carotid artery (CCA) arises directly from the aortic arc, whereas on the right side the CCA originate from the innominate artery. AIM: The aim of this study was to compare LMov of the left and right CCA of healthy subjects to investigate whether the difference in anatomy is of importance for LMov. MATERIAL AND METHODS: The CCA's of 93 healthy subjects were investigated using in-house developed ultrasound methods. RESULTS: Although the basic pattern were the same in the majority of subjects, several phases of LMov were significantly larger on the left side (the first retrograde phase, p = 0.0006; the second antegrade, "returning" phase, p < 0.00001; and the rapid retrograde phase of movement at the end of the cardiac cycle, p < 0.000001). In contrast, no significant side-difference in the amplitude of the first antegrade movement was seen. The maximal (peak-to-peak) LMov was significantly larger on the left side (p = 0.002). DISCUSSION AND CONCLUSION: The side-differences found in LMov may be related to the difference in anatomy, including possible difference in distance to the heart and especially the presence of an extra bifurcation on the right side. Our data provide an important base for the further study of the relation between LMov and cardiovascular risk factors and atherosclerosis.

Longitudinal Movement of the Common Carotid Artery Wall: New Information on Cardiovascular Aging.

Putative changes in the multiphasic pattern of longitudinal movement of the common carotid artery wall in the normal aging process are unknown. The aim of this study was to explore the phases, and resulting patterns, of the longitudinal movement of the intima-media complex of the human common carotid artery with respect to age and gender. One hundred thirty-five healthy non-smoking patients of different ages were investigated using in-house-developed ultrasound methods. The patterns of longitudinal movement seen in middle-aged and older patients were markedly different from those commonly seen in young patients, including the appearance of two additional phases of motion and, thus, new complex patterns. The displacement and maximum velocity of one of the phases, occurring at the time of aortic valve closure, increased quadratically with age in both men and women.

Design and Fabrication of a Conceptual Arterial Ultrasound Phantom Capable of Exhibiting Longitudinal Wall Movement.

The longitudinal movement of the arterial wall of large human arteries has shown promise to be an independent indicator of vascular health. Despite growing interest in this movement, its nature, causes, and implications are not fully understood, and existing phantoms have failed to show a pure longitudinal movement that is not secondary to the distension. An often overlooked aspect of the arterial wall is the interaction between the different layers. The longitudinal movement of the innermost layers, the intima and media, can be several hundred micrometers in the direction of flow during early systole. This is markedly larger than that of the adventitia, indicating that sliding occurs between the two layers. This feature was incorporated into a phantom by casting it in two parts. The molds were developed in-house using mainly a 3-D printer, a versatile and easy production method. Additionally, the phantom contains a tapered region. Using the phantom, we were able to demonstrate a pure longitudinal movement; when it was subjected to a pulsatile pressure, the wall displaced 220 [Formula: see text] (SD 40) radially and 560 [Formula: see text] (SD 74) longitudinally distal to the tapering. The motion followed the pressure variations. This paper serves as a guide for phantom production, explaining each step of the process.

A combination of parabolic and grid slope interpolation for 2D tissue displacement estimations.

Parabolic sub-sample interpolation for 2D block-matching motion estimation is computationally efficient. However, it is well known that the parabolic interpolation gives a biased motion estimate for displacements greater than |y.2| samples (y = 0, 1, …). Grid slope sub-sample interpolation is less biased, but it shows large variability for displacements close to y.0. We therefore propose to combine these sub-sample methods into one method (GS15PI) using a threshold to determine when to use which method. The proposed method was evaluated on simulated, phantom, and in vivo ultrasound cine loops and was compared to three sub-sample interpolation methods. On average, GS15PI reduced the absolute sub-sample estimation errors in the simulated and phantom cine loops by 14, 8, and 24% compared to sub-sample interpolation of the image, parabolic sub-sample interpolation, and grid slope sub-sample interpolation, respectively. The limited in vivo evaluation of estimations of the longitudinal movement of the common carotid artery using parabolic and grid slope sub-sample interpolation and GS15PI resulted in coefficient of variation (CV) values of 6.9, 7.5, and 6.8%, respectively. The proposed method is computationally efficient and has low bias and variance. The method is another step toward a fast and reliable method for clinical investigations of longitudinal movement of the arterial wall.

Increased cardiovascular risk without generalized arterial dilating diathesis in persons who do not have abdominal aortic aneurysm but who are first-degree relatives of abdominal aortic aneurysm patients.

There is a strong genetic predisposition towards abdominal aortic aneurysm (AAA), but it is unknown whether persons without AAA but with first-degree relatives who are AAA patients have a generalized dilating diathesis, defect arterial wall mechanics, or increased cardiovascular risk. The aim of the study was to investigate arterial diameters and wall mechanics at multiple arterial sites in these subjects and compare them with controls without a family history of AAA. This study included 118 first-degree relatives of patients with AAA and 66 controls (age: 40-80 years). The abdominal aorta, common carotid artery, common femoral artery, and popliteal artery were investigated by echo-tracking ultrasound. The relatives had no arterial dilatation, but they did tend to have smaller diameters than controls. Relatives had a higher heart rate, diastolic blood pressure, and mean arterial pressure than controls. The distensibility coefficient and the compliance coefficient were decreased in all arteries in male relatives, adjusted for age and smoking; these coefficients were normalized after adjustment for mean arterial pressure and heart rate. Female relatives had a lower compliance coefficient in the abdominal aorta, adjusted for age and smoking. After adjustment for mean arterial pressure and heart rate, the difference disappeared. No general arterial dilatation in relatives without AAA was found, supporting the hypothesis that the dilating diathesis is linked to the aneurysmal manifestation in the abdominal aorta. Although the threat of aneurysmal dilatation and rupture seems to be lacking in these subjects, heart rate, blood pressure, and arterial wall stiffness were all increased, which may indicate a higher risk of developing cardiovascular morbidity and mortality.

Profound increase in longitudinal displacements of the porcine carotid artery wall can take place independently of wall shear stress: a continuation report.

The mechanisms underlying longitudinal displacements of the arterial wall, that is, displacements of the wall layers along the artery, and the resulting intramural shear strain remain largely unknown. We have already found that these displacements undergo profound changes in response to catecholamines. Wall shear stress, closely related to wall shear rate, represents the viscous drag exerted on the vessel wall by flowing blood. The aim of the work described here was to study possible relations between the wall shear rate and the longitudinal displacements. We investigated the carotid arteries of five anesthetized pigs in different hemodynamic situations using in-house developed non-invasive ultrasound techniques. The study protocol included administration of epinephrine, norepinephrine and ß-blockade (metoprolol). No significant correlation between longitudinal displacement of the intima-media complex and wall shear rate was found. This result suggests that one or multiple pulsatile forces other than wall shear stress are also working along arteries, strongly influencing arterial wall behavior.

Improved tracking performance of Lagrangian block-matching methodologies using block expansion in the time domain: in silico, phantom and in vivo evaluations.

The aim of this study was to evaluate tracking performance when an extra reference block is added to a basic block-matching method, where the two reference blocks originate from two consecutive ultrasound frames. The use of an extra reference block was evaluated for two putative benefits: (i) an increase in tracking performance while maintaining the size of the reference blocks, evaluated using in silico and phantom cine loops; (ii) a reduction in the size of the reference blocks while maintaining the tracking performance, evaluated using in vivo cine loops of the common carotid artery where the longitudinal movement of the wall was estimated. The results indicated that tracking accuracy improved (mean = 48%, p < 0.005 [in silico]; mean = 43%, p < 0.01 [phantom]), and there was a reduction in size of the reference blocks while maintaining tracking performance (mean = 19%, p < 0.01 [in vivo]). This novel method will facilitate further exploration of the longitudinal movement of the arterial wall.

Low wall stress in the popliteal artery: Other mechanisms responsible for the predilection of aneurysmal dilatation?

The popliteal artery (PA) is, after aorta, the most common site for aneurysm formation. Why the PA is more susceptible than other peripheral muscular arteries is unknown. We hypothesized that the wall composition, which in turn affects wall properties, as well as the circumferential wall stress (WS) imposed on the arterial wall, might differ compared to other muscular arteries. The aim was to study the WS of the PA in healthy subjects with the adjacent, muscular, common femoral artery (CFA) as a comparison. Ninety-four healthy subjects were included in this study (45 males, aged 10-78 years and 49 females, aged 10-83 years). The diameter and intima-media thickness (IMT) in the PA and CFA were investigated with ultrasound. Together with blood pressure the WS was defined according to the law of Laplace adjusted for IMT. The diameter increased with age in both PA and CFA (p<0.001), with males having a larger diameter than females (p<0.001). IMT increased with age in both PA and CFA (p<0.001), with higher IMT values in males only in PA (p<0.001). The calculated WS was unchanged with age in both arteries, but lower in PA than in CFA in both sexes (p<0.001). In conclusion, this study shows that the PA and CFA WS is maintained during aging, probably due to a compensatory remodelling response with an increase in arterial wall thickness. However, the stress imposed on the PA wall is quite low, indicating that mechanisms other than WS contribute to the process of pathological arterial dilatation in the PA.

Accuracy and reproducibility of a novel dynamic volume flow measurement method.

In clinical practice, blood volume flow (BVF) is typically calculated assuming a perfect parabolic and axisymmetric velocity distribution. This simple approach cannot account for the complex flow configurations that are produced by vessel curvatures, pulsatility and diameter changes and, therefore, results in a poor estimation. Application of the Womersley model allows compensation for the flow distortion caused by pulsatility and, with some adjustment, the effects of slight curvatures, but several problems remain unanswered. Two- and three-dimensional approaches can acquire the actual velocity field over the whole vessel section, but are typically affected by a limited temporal resolution. The multigate technique allows acquisition of the actual velocity profile over a line intersecting the vessel lumen and, when coupled with a suitable wall-tracking method, can offer the ideal trade-off among attainable accuracy, temporal resolution and required calculation power. In this article, we describe a BVF measurement method based on the multigate spectral Doppler and a B-mode edge detector algorithm for wall-position tracking. The method has been extensively tested on the research platform ULA-OP, with more than 1700 phantom measurements at flow rates between 60 and 750 mL/min, steering angles between 10 ° and 22 ° and constant, sinusoidal or pulsed flow trends. In the averaged BVF measurement, we found an underestimation of about -5% and a coefficient of variability (CV) less than 6%. In instantaneous measurements (e.g., systolic peak) the CV was in the range 2%-8.5%. These results were confirmed by a preliminary test on the common carotid artery of 10 volunteers (CV = 2%-11%).

Different patterns of longitudinal displacement of the common carotid artery wall in healthy humans are stable over a four-month period.

Using an in-house developed ultrasonic method, we have shown that there is distinct longitudinal multiphasic displacement of the human common carotid artery (CCA) wall during the cardiac cycle. Different subjects showed markedly different patterns of displacement. At present, it is not known if the pattern of displacement in an individual is stable over time. Therefore, in this study, we measured the longitudinal displacement of the right CCA in 10 healthy humans at two different occasions 4 months apart. The basic pattern of longitudinal displacement for an individual was highly stable, including intraclass correlation coefficient (ICC) of 0.88 for the ratio between the first antegrade and the retrograde displacement, and ICC of 0.76 for the magnitude of the first antegrade displacement. The stable basic pattern of displacement showed marked differences among subjects, also of the same age and gender. Further studies are needed to elucidate the underlying mechanisms, the physiologic, pathophysiologic and clinical implications of this phenomenon.

Longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines.

The effects of catecholamines on longitudinal displacements and intramural shear strain of the arterial wall are unexplored. Therefore, the common carotid artery of five anaesthetized pigs was investigated using an in-house developed noninvasive ultrasonic technique. The study protocol included intravenous infusion of low-dose epinephrine (ß-adrenoceptor activation), as well as intravenous boluses of norepinephrine (α-adrenoceptor activation). Further, the effects of ß-blockade (metoprolol) were studied. There were significant positive correlations between pulse pressure and longitudinal displacement of the intima-media complex (r = 0.72; P < 0.001), as well as between pulse pressure and intramural shear strain (r = 0.48; P < 0.001). Following administration of norepinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain profoundly increased (median 190%, range 102-296%, and median 141%, range 101-182%, respectively, compared with baseline), also when given during ß-blockade (median 228%, range 133-266%, and median 158%, range 152-235%, respectively). During infusion of low-dose epinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain decreased (median 88%, range 69-122%, and median 69%, range 47-117%, respectively, compared with baseline). In conclusion, the present study shows, for the first time, that the longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines. Increase in longitudinal displacements seems to be strongly related to α-adrenoceptor activation. Thus metoprolol is insufficient to counteract a profound increase in longitudinal displacement and intramural shear strain following a surge of norepinephrine.

A method for arterial diameter change measurements using ultrasonic B-mode data.

Arterial diameter change is related to distending blood pressure and is used in estimation of arterial stiffness parameters. A common technique to track the arterial walls is by integration of wall velocities estimated by different methods using cross correlation or tissue Doppler. However, because of the high pulse repetition frequency and the need for separate pulsing sequences, the B-mode image quality is affected. We have previously developed a fast algorithm for direct measurement of lumen diameter using B-mode images. In this study we have improved the technique to be more robust and also implemented measurements of diameter change, maximum differential wall velocity and relative diameter change of the common carotid artery noninvasively in vivo. The influence of the lateral width of the region of interest (ROI; 1 pixel, 0.1 mm, 0.5 mm, 1 mm, 2.5 mm and 5 mm) was evaluated. Using the optimal lateral width (2.5 mm), the systematic and random differences between two consecutive measurements were 21 microm and 105 microm, respectively, for lumen diameter measurement; -7 microm and 39 microm, respectively, for lumen diameter change measurements; -0.2 mm/s and 0.9 mm/s, respectively, for maximum relative wall velocity; and -0.2 % and 0.8 %, respectively, for measurements of the relative diameter change. The coefficient of variation (CV) was 1.9%, 5.2%, 7.9% and 6.0%, respectively. The study indicates that the reproducibility is sufficient for in vivo studies when the width of the ROI is 1.0 mm or wider.

Evaluation of an algorithm for arterial lumen diameter measurements by means of ultrasound.

We have developed an algorithm for arterial luminal diameter measurement by means of ultrasound and evaluated the algorithm on agar vessel phantoms and in vivo. The algorithm utilises relative threshold detection on the inner slopes of the arterial walls before the resolution is improved by solving the equation of a straight line between the samples around the threshold value. Further, correction distances added to compensate for the underestimation when using the inner slopes were found to be 304 µm for the near wall and 415 µm for the far wall. The measured mean diameters of ten consecutive images of 3-, 6- and 9-mm phantoms were 3,006 µm (SD 4), 5,918 µm (SD 1) and 8,936 µm (SD 2), respectively. The mean differences between the images were 0.19, 0.04 and 0.37 µm, respectively. In vivo, the intra- and inter-observer variabilities were -64 µm (2SD 358) and -57 µm (2SD 366), respectively.

Intra-observer variability of longitudinal displacement and intramural shear strain measurements of the arterial wall using ultrasound noninvasively in vivo.

Using a recently developed high-resolution noninvasive ultrasonic method, we recently demonstrated that the intima-media complex of the common carotid artery show a bidirectional multiphasic longitudinal displacement of the same magnitude as the diameter change during the cardiac cycle. The longitudinal movement of the adventitial region was smaller, thus, we identified shear strain and, thus, shear stress, within the arterial wall. The aim of this study was to evaluate the intra-observer variability of measurement of the longitudinal displacement of the intima-media complex and the intramural shear strain of the common carotid artery in vivo using the new ultrasonic method. The evaluation was carried out by comparing two consecutive measurements on the common carotid artery of 20 healthy human subjects. According to the method of Bland Altman, we show that the systematic and random differences for the different phases of movement are acceptable in comparison to the measured displacement and no significant differences between the two measurements could be detected (p > 0.05 for all measured parameters). The coefficient of variation (CV) for measurement of the different phases of movement was

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.

Decreased heart rate variability may predict the progression of carotid atherosclerosis in type 2 diabetes.

Heart rate variability (HRV), a measure of autonomic function, can predict survival outcomes. Cardiovascular disease is a known complication of diabetes, and we aimed to determine if autonomic dysfunction was associated with carotid artery atherosclerotic plaques in type 2 diabetic patients. We assessed frequency domain HRV from power spectral analysis of 24 h Holter ECG recordings, expiration/inspiration (E/I) ratio during deep breathing, acceleration index (AI) of R-R interval in response to head-up tilt, and the degree of carotid artery atherosclerosis in 61 type-2 diabetic patients (39 males, 45-69 years). Studies were carried out 5-6 years after diagnosis (baseline) and repeated 8 years after diagnosis (follow-up). At baseline, patients diagnosed with autonomic neuropathy, with abnormal E/I ratio and abnormal AI measurements, had decreased low frequency (LF) HRV. Baseline E/I ratio correlated with day (r = 0.34; P < 0.001) and night-time (r = 0.44; P < 0.001) LF power. Night-time HRV did not differ in patient with and without autonomic neuropathy. Reduced common carotid artery diameter and atherosclerotic intima-media thickness (IMT) both correlated with HRV at baseline. At follow-up, all HRV variables decreased significantly. Furthermore, patients with lower LF power at baseline, had a larger increase in the thickness of the carotid bulb intima-media at follow-up. Our results show that LF HRV power is associated with the extent and progression of carotid atherosclerosis in type 2 diabetes. A low LF HRV may predict the progression of atherosclerosis in these patients.

Longitudinal movements and resulting shear strain of the arterial wall.

There has been little interest in the longitudinal movement of the arterial wall. It has been assumed that this movement is negligible compared with the diameter change. Using a new high-resolution noninvasive ultrasonic method, we measured longitudinal movements and diameter change of the common carotid artery of 10 healthy humans. During the cardiac cycle, a distinct bidirectional longitudinal movement of the intima-media complex could be observed in all the subjects. An antegrade longitudinal movement, i.e., in the direction of blood flow, in early systole [0.39 mm (SD 0.26)] was followed by a retrograde longitudinal movement, i.e., in the direction opposite blood flow [-0.52 mm (SD 0.27)], later in systole and a second antegrade longitudinal movement [0.41 mm (SD 0.33)] in diastole. The corresponding diameter change was 0.65 mm (SD 0.19). The adventitial region showed the same basic pattern of longitudinal movement; however, the magnitude of the movements was smaller than that of the intima-media complex, thereby introducing shear strain and, thus, shear stress within the wall [maximum shear strain between the intima-media complex and the adventitial region was 0.36 rad (SD 0.26). These phenomena have not previously been described. Measurements were also performed on the abdominal aorta (n = 3) and brachial (n = 3) and popliteal (n = 3) arteries. Our new information seems to be of fundamental importance for further study and evaluation of vascular biology and hemodynamics and, thus, for study of atherosclerosis and vascular diseases.

Evaluation of an ultrasonic echo-tracking method for measurements of arterial wall movements in two dimensions.

The longitudinal movement of blood vessel walls has so far gained little or no attention, as it has been presumed that these movements are of a negligible magnitude. However, modern high-resolution ultrasound scanners can demonstrate that the inner layers of the arterial wall exhibit considerable movements in the longitudinal direction. This paper evaluates a new, noninvasive, echo-tracking technique, which simultaneously can track both the radial and the longitudinal movements of the arterial wall with high resolution in vivo. Initially, the method is evaluated in vitro using a specially designed ultrasound phantom, which is attached to and moved by an X-Y system, the movement of which was compared with two high-resolution triangulation lasers. The results show an inaccuracy of 2.5% full scale deflection (fsd), reproducibility of 12 microm and a resolution of 5 microm, which should be more than sufficient for in vivo studies. The ability of the method is also demonstrated in a limited in vivo study in which a preselected part of the inner vessel wall of the right common carotid artery of a healthy volunteer is tracked in two dimensions over many cardiac cycles. The results show well reproducible x-y movement loops in which the recorded radial and longitudinal movements both are of the magnitude millimetre.