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Local arterial stiffness can be assessed with high accuracy and precision by measuring arterial distension on the basis of phase tracking of radiofrequency ultrasound signals acquired at a high frame rate. However, in clinical practice, B-mode ultrasound registrations are made at a low frame rate (20-50 Hz). We compared the accuracy and intra-subject precision of edge tracking and phase tracking distension in symptomatic carotid artery patients. B-mode ultrasound recordings (40 mm, 37 fps) and radiofrequency recordings (31 lines covering 29 mm, 300 fps) were acquired from the left common carotid artery of 30 patients (aged 45-88 y) with recent cerebrovascular events. To extract the distension, semi-automatic echo edge and phase tracking algorithms were applied to B-mode and radiofrequency recordings, respectively. Both methods exhibited a similar intra-subject precision for distension (standard deviation = 44 μm and 47 μm, p = 0.66) and mean distension (difference: -6 ± 69 μm, p = 0.67). Intra-subject distension inhomogeneity tends to be larger for edge tracking (difference: 15 ± 35 μm, p = 0.04). Standard B-mode scanners are suitable for measuring local artery characteristics in symptomatic carotid artery patients with good precision and accuracy., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Transcutaneous ultrasound measurements of common carotid artery (CCA) diameter and intima-media thickness (IMT) give insight on arterial dynamics and anatomy, both correlating well with atherosclerosis and risk of cardiovascular disease. We propose a novel automatic algorithm to estimate CCA diameter and IMT in ultrasound (US) images, based on separate analysis of anterior and posterior CCA walls and able to distinguish internal (intima-intima) and external (adventitia-adventitia) diameter. The method combines off-line signal- and image-processing techniques to accommodate echo images acquired at a frame rate of 30 Hz and composed directly from RF data, circumventing digital video-grabbing. Segmentation consists of automatic CCA recognition, followed by adventitial delineation performed with a sustain-attack filter with exponentially decaying reference functions. Intimal delineation is then based on the multiscale anisotropic barycenter (MAB), which is an extension of a known delineation method involving the "first order absolute central moment" of the echo amplitude. An automatic measure of the quality of the US beam incidence for each wall is superimosed on the CCA contour overlays for visual feedback. Validation is carried out on 36 US CCA acquisitions from 12 healthy volunteers, as well as on synthetic US images. Results indicate good accuracy on synthetic US images (within 1.3% for diameter and 3% for IMT). The in vivo intra-recording beat-to-beat variations are on average lower than 50 microm for external diameter and IMT, and lower than 100 microm for internal diameter. A comparison with a commercial device (ART.LAB system) shows that the proposed algorithm performs better in terms of inter-recording precision. The beam incidence control significantly improves the repeatability of IMT estimates, and motivates sonographers actively to maintain a proper scan plane throughout the acquisition to minimize the incidence of confounding factors. The method is clinically viable, providing robust estimates of CCA internal and external diameter and IMT waveforms for both CCA walls, even at a low B-mode update rate of 30 Hz., (Copyright 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Molecular imaging may provide new insights into the early detection and development of atherosclerosis before first symptoms occur. One of the techniques in use employs noninvasive ultrasound. In the past decade, experimental and clinical validation studies showed that for the microcirculation targeted ultrasound contrast agents, such as echogenic liposomes, microbubbles and perfluorocarbon emulsions, do improve visualization of specific structures. For large arteries, however, successful application is less obvious. In this review, we will address the challenges for molecular imaging of large arteries. We will discuss the problems encountered in the use of targeted ultrasound contrast agents presently available, mainly based on data obtained in flow chambers and animal studies because clinical studies are lacking. We conclude that molecular imaging of activated endothelium in large- and middle-sized arteries by site-specific accumulation of contrast material is still difficult to achieve due to wall shear stress conditions in these vessels., (World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

In addition to intima-media thickness (IMT), IMT inhomogeneity may carry information about atherosclerosis progression. In 147 vascular diseased patients (mean 66 y, 48% male), we determined the carotid bulb stenosis degree based on local Doppler blood flow velocities. Common carotid artery (CCA) morphologic characteristics, i.e. IMT, IMT-inhomogeneity (intraregistration variation) and IMT uni- and bilateral intrasubject variation (DeltaIMT), were measured using multiple M-mode. Associations of morphologic characteristics, stenosis degree and Framingham score were evaluated with Pearson correlation (r) and multiple regression analysis. The IMT distributions for subjects without and with stenosis were not similar. The stenosis degree score correlated significantly to unilateral (r=0.68) and bilateral DeltaIMT (r=0.62), IMT (r=0.41) and IMT-inhomogeneity (r=0.45). The averaged IMT and IMT-inhomogeneity increased slightly for singular stenosis and abruptly for multiple stenoses. Mean uni- and bilateral DeltaIMT per stenosis degree increased linearly with this degree, reaching a correlation close to 1 (r=0.98 and r=0.97). Interestingly, the majority of the subjects with a moderate to severe bulb stenosis exhibited a carotid IMT lower than the considered critical threshold of 0.9 mm. In conclusion, although CCA is not prone to plaques, its morphologic characteristics are positively correlated with stenosis degree score and other risk scores. DeltaIMT can be more reliable derived from inter-registration rather than from intra-registration variation. In the CCA, DeltaIMT substantiates vascular alteration better than IMT.

Noninvasive diameter assessment in the common carotid artery (CCA) by means of ultrasound is a useful technique for estimation of arterial mechanical and dynamic properties, clinical screening and treatment monitoring. Before presentation on screen, ultrasound images are subjected to nonlinear processing, e.g., logarithmic compression and noise-level thresholding, to improve visualization. In addition, signal saturation may occur, either in the received radiofrequency (RF) signals or in their envelopes. The objective of this study is to evaluate the effect of signal nonlinearities on CCA diameter measurements by means of noninvasive B-mode ultrasound, comparing the performance of two different edge detectors. In 14 healthy subjects, three repeated ultrasonic acquisitions (6 s) without saturation were performed. The acquired RF signals were subjected off-line to envelope detection, logarithmic compression and various degrees of saturation applied to the signals before or after envelope detection. For the purpose of CCA diameter estimation, artery walls were automatically outlined frame by frame. As automatic edge detectors, we considered the sustain attack filter (SAF), based on exponentially decaying reference functions, and a derivative approach (DER), relying on the positions of first derivative maxima. Both methods are applied within a region-of-interest located on the CCA. No regularization of the detected wall positions by means of pre- or postprocessing is presently applied to directly relate the outcome of the edge detectors to the applied nonlinear processing. Diameter values assessed with SAF are unaffected by logarithmic compression because of the possibility to integrate the compression characteristic of the ultrasound system into the method. The estimated diameters values obtained with DER instead show differences in the order of 10% because of compression. Saturation affects DER more than SAF; DER exhibits larger intrarecording and intrasubject variations in the estimated diameter values. Therefore, SAF gives more precise and robust CCA diameter estimates than DER, and is more suited for integration in algorithms meant for vascular ultrasound image segmentation. This study demonstrates the relevant effects of nonlinearities such as saturation and logarithmic compression on the quality of noninvasive US CCA diameter measurements.

Pulse wave velocity (PWV) provides information about the mechanical properties of the vessel: the stiffer the artery is, the higher the PWV will be. PWV measured over a short arterial segment facilitates direct characterization of local wall properties corrected for prevailing pressure without the necessity of measuring pulse pressure locally. Current methods for local PWV assessment have a poor precision, but it can be improved by applying linear regression to a characteristic time-point in distension waveforms as recorded simultaneously by multiple M-line ultrasounds. We investigated the precision of this method in a phantom scaled according to realistic in vivo conditions. Special attention was paid to the identification of the foot of the wave, using the maximum of the second derivative, the intersecting tangent and the 20% threshold method. Before foot detection, the distension waveforms were subjected to preprocessing with various filters. The precision of the maximum of the second derivative had a coefficient of variation (CV) of 0.45% and 10.45% for an eighth and second order low pass filter, respectively. The intersecting tangent and the threshold method were less sensitive to filtering; the CVs were 0.66% and 0.68% for the high order filter and 2.36% and 1.43% for the low order filter, respectively. We conclude that foot detection by a threshold of 20% or by the tangent method are more suitable to identify the foot of the wave to measure local PWV. Both methods are less sensitive to (phase) noise than the maximum of the second derivative method and exhibit good precision with a CV of less than 1%.

The blood pressure waveform carries information about the cardiac contraction and the impedance characteristics of the vascular bed. Here, we demonstrate that the start of isovolumic ventricular contraction is persistently reflected as an inflection point in the pressure wave as recorded in the aortic root (TP(IC)) as well as in the carotid artery distension waveform (TD(IC)) as it travels down the arterial tree. In a group of six patients with normal pressure gradients across the aortic valve after valve replacement, the TP(IC) had a small delay with respect to the onset of isovolumic ventricular contraction (<10 ms). In a group (n = 21) of young presumably healthy volunteers, the inflection point occurred persistently in the carotid distension waveform, as recorded by means of ultrasound, before the systolic foot (intersubject delay between inflection point and systolic foot: mean +/- SD = 40.0 +/- 9.4 ms, intrasubject SD 4.6 ms). Retrograde coronary blood flow during isovolumic ventricular contraction may be the origin of the persistent end-diastolic pressure and distension perturbation. This study shows that the duration of the isovolumic contraction can be reliably extracted from the carotid artery distension waveform.

Arterial remodeling in response to flow changes is controlled by the endothelium, sensing wall shear stress (SS) changes. The present study focuses on the remodeling capacities of the brachial (BA) and radial artery (RA) of 16 renal failure patients after arteriovenous fistula creation. Pre- and postoperatively at predetermined time-points, diameter, wall thickness and peak and mean SS were assessed. After arteriovenous fistula creation, acute increases in BA SS (p = 0.018) and lumen diameter (p = 0.028) were observed. The diameter further increased in the next year (p = 0.023), whereas BA SS remained unchanged. RA SS and diameter increased acutely (p = 0.005) and remained unaltered after 1 y. RA wall thickness tended to decrease acutely (p = 0.059) and increased steadily during 1 y (p = 0.008). BA and RA diameter acutely increased after an acute SS rise and remained augmented after 1 y. Also, the RA vessel wall thickness enlarged, indicating structural remodeling. After 1 y, however, these changes did not result in SS restoration.

Skin biopsies in patients with pseudoxanthoma elasticum (PXE) show elastic fiber fragmentation and calcium and proteoglycans accumulation. Assuming such changes to be present in the artery wall as well, we studied the influence of such alterations on function and structure of the human common carotid artery (CCA). Indeed, elastin fragmentation and increased calcium and proteoglycans content were present in the arteries of the two PXE patients examined. Internal diameter, distension and intima-media thickness (IMT) in the CCA of PXE patients (n = 19) and controls (n = 39) were determined by ultrasound (US). Pulse pressure was assessed in the brachial artery. The distensibility and compliance coefficients as well as the Young's modulus were calculated. Diameter and pulse pressure were not significantly different in PXE patients and controls. The distensibility and compliance coefficients were significantly greater in older PXE patients than in older controls. The distensibility coefficient decreased with age in both PXE patients and in controls. Unlike in controls, the compliance coefficient did not decrease and the Young's modulus barely increased with age in PXE patients. IMT was significantly greater at both younger and older ages and the Young's modulus was significantly smaller at older ages in PXE patients than in controls. The carotid artery is thicker and more elastic in PXE patients than in control subjects; differences are most pronounced at older ages. These alterations might be explained by the elastin fragmentation and proteoglycans accumulation as observed in these patients.

Simultaneous assessment of diameter and pressure waveforms allows the calculation of the incremental compliance, distensibility, pulse wave velocity and elastic modulus as function of the distending pressure. However, the waveforms must be obtained at the same position and acquired and processed with the same filter characteristics to circumvent possible temporal and spatial changes in amplitude and phase. In this paper, arterial diameter waveforms are assessed by means of ultrasound (US) and converted to pressure using an empirically derived exponential relationship between pressure and arterial cross-section. The derived pressure waveform is calibrated to brachial end diastolic and mean arterial pressure by iteratively changing the wall rigidity coefficient (i.e., the exponential power). Because pressure is derived directly from arterial cross-section, no phase delay is introduced due to spatial separation or different filter characteristics. The method was evaluated for the left common carotid artery of 51 healthy subjects ranging in age from 22 to 75 years old. In healthy subjects, the carotid pulse pressure is 29% lower than the brachial pulse pressure. Continuous assessment of arterial properties confirms that pulse-wave velocity and incremental elastic modulus increase, whereas distensibility and compliance decrease, as function of increasing distending blood pressure.

The objective of the present study was to obtain brachial artery (BA) baseline shear stress (SS) values in healthy volunteers and to relate this to gender and age. Peak and mean wall shear rate (SR) were noninvasively measured in 30 healthy subjects using an SR estimation system. Arterial diameter and wall characteristics were obtained with a wall tracking system. SS was estimated from SR and calculated whole blood viscosity. Intrasubject variability and the effects of age and gender were assessed. Intrasubject variability of BA peak and mean SR were 16.2% and 28.6%. Baseline peak ( approximately 3.0 +/- 0.7 Pa) and mean SS ( approximately 0.5 +/- 0.2 Pa) were not gender-dependent, nor were they influenced by age. No vessel wall parameter related to BA SS. No differences in BA SS were observed between the genders and no influence of age was apparent. Our results indicate that the BA adequately responds to chronic changes in blood flow.