Carotid Ultrasound Boundary Study (CUBS): Technical considerations on an open multi-center analysis of computerized measurement systems for intima-media thickness measurement on common carotid artery longitudinal B-mode ultrasound scans.

After publishing an in-depth study that analyzed the ability of computerized methods to assist or replace human experts in obtaining carotid intima-media thickness (CIMT) measurements leading to correct therapeutic decisions, here the same consortium joined to present technical outlooks on computerized CIMT measurement systems and provide considerations for the community regarding the development and comparison of these methods, including considerations to encourage the standardization of computerized CIMT measurements and results presentation. A multi-center database of 500 images was collected, upon which three manual segmentations and seven computerized methods were employed to measure the CIMT, including traditional methods based on dynamic programming, deformable models, the first order absolute moment, anisotropic Gaussian derivative filters and deep learning-based image processing approaches based on U-Net convolutional neural networks. An inter- and intra-analyst variability analysis was conducted and segmentation results were analyzed by dividing the database based on carotid morphology, image signal-to-noise ratio, and research center. The computerized methods obtained CIMT absolute bias results that were comparable with studies in literature and they generally were similar and often better than the observed inter- and intra-analyst variability. Several computerized methods showed promising segmentation results, including one deep learning method (CIMT absolute bias = 106 ± 89 µm vs. 160 ± 140 µm intra-analyst variability) and three other traditional image processing methods (CIMT absolute bias = 139 ± 119 µm, 143 ± 118 µm and 139 ± 136 µm). The entire database used has been made publicly available for the community to facilitate future studies and to encourage an open comparison and technical analysis (https://doi.org/10.17632/m7ndn58sv6.1).

Carotid Ultrasound Boundary Study (CUBS): An Open Multicenter Analysis of Computerized Intima-Media Thickness Measurement Systems and Their Clinical Impact.

Common carotid intima-media thickness (CIMT) is a commonly used marker for atherosclerosis and is often computed in carotid ultrasound images. An analysis of different computerized techniques for CIMT measurement and their clinical impacts on the same patient data set is lacking. Here we compared and assessed five computerized CIMT algorithms against three expert analysts' manual measurements on a data set of 1088 patients from two centers. Inter- and intra-observer variability was assessed, and the computerized CIMT values were compared with those manually obtained. The CIMT measurements were used to assess the correlation with clinical parameters, cardiovascular event prediction through a generalized linear model and the Kaplan-Meier hazard ratio. CIMT measurements obtained with a skilled analyst's segmentation and the computerized segmentation were comparable in statistical analyses, suggesting they can be used interchangeably for CIMT quantification and clinical outcome investigation. To facilitate future studies, the entire data set used is made publicly available for the community at http://dx.doi.org/10.17632/fpv535fss7.1.

Carotid Wall Longitudinal Motion in Ultrasound Imaging: An Expert Consensus Review.

Motion extracted from the carotid artery wall provides unique information for vascular health evaluation. Carotid artery longitudinal wall motion corresponds to the multiphasic arterial wall excursion in the direction parallel to blood flow during the cardiac cycle. While this motion phenomenon has been well characterized, there is a general lack of awareness regarding its implications for vascular health assessment or even basic vascular physiology. In the last decade, novel estimation strategies and clinical investigations have greatly advanced our understanding of the bi-axial behavior of the carotid artery, necessitating an up-to-date review to summarize and classify the published literature in collaboration with technical and clinical experts in the field. Within this review, the state-of-the-art methodologies for carotid wall motion estimation are described, and the observed relationships between longitudinal motion-derived indices and vascular health are reported. The vast number of studies describing the longitudinal motion pattern in plaque-free arteries, with its putative application to cardiovascular disease prediction, point to the need for characterizing the added value and applicability of longitudinal motion beyond established biomarkers. To this aim, the main purpose of this review was to provide a strong base of theoretical knowledge, together with a curated set of practical guidelines and recommendations for longitudinal motion estimation in patients, to foster future discoveries in the field, toward the integration of longitudinal motion in basic science as well as clinical practice.

Skin Surface Detection in 3D Optoacoustic Mesoscopy Based on Dynamic Programming.

Optoacoustic (photoacoustic) mesoscopy offers unique capabilities in skin imaging and resolves skin features associated with detection, diagnosis, and management of disease. A critical first step in the quantitative analysis of clinical optoacoustic images is to identify the skin surface in a rapid, reliable, and automated manner. Nevertheless, most common edge- and surface-detection algorithms cannot reliably detect the skin surface on 3D raster-scan optoacoustic mesoscopy (RSOM) images, due to discontinuities and diffuse interfaces in the image. We present herein a novel dynamic programming approach that extracts the skin boundary as a 2D surface in one single step, as opposed to consecutive extraction of several independent 1D contours. A domain-specific energy function is introduced, taking into account the properties of volumetric optoacoustic mesoscopy images. The accuracy of the proposed method is validated on scans of the volar forearm of 19 volunteers with different skin complexions, for which the skin surface has been traced manually to provide a reference. In addition, the robustness and the limitations of the method are demonstrated on data where the skin boundaries are low-contrast or ill-defined. The automatic skin surface detection method can improve the speed and accuracy in the analysis of quantitative features seen on the RSOM images and accelerate the clinical translation of the technique. Our method can likely be extended to identify other types of surfaces in the RSOM and other imaging modalities.

Dynamic Block Matching to assess the longitudinal component of the dense motion field of the carotid artery wall in B-mode ultrasound sequences - Association with coronary artery disease.

PURPOSE: The motion of the common carotid artery tissue layers along the vessel axis during the cardiac cycle, observed in ultrasound imaging, is associated with the presence of established cardiovascular risk factors. However, the vast majority of the (semi-)automatic methods devised to measure this so-called "longitudinal kinetics" phenomenon are based on the tracking of a single point, thus failing to capture the overall - and potentially inhomogeneous - motion of the entire arterial wall. The aim of this work is to introduce a motion tracking a framework to simultaneously extract the temporal trajectory of a large collection of points (several hundred) horizontally aligned and spanning the entire exploitable width of the image, thus providing a dense motion field. METHOD: The only action required from the user is to indicate the left and right borders of the region to be processed. A previously validated contour segmentation method is used to position one point in the arterial wall in each column of the image. Between two consecutive frames, the radial motion of each point is predetermined by the position of the segmentation contours. The longitudinal motion, which is the main focus of the present work, is determined in two steps. First, a series of independent block matching operations are carried out for all the tracked points. Here, the displacement of each point is not determined yet, instead the similarity map is stored. Then, an original dynamic-programming approach is exploited to regularize the collection of similarity maps and estimate the globally optimal motion over the entire vessel wall. Sixty-two atherosclerotic participants at high cardiovascular risk were involved in this study. Method training and validation was performed with 20 and 42 participants, respectively. The amplitude-independent index σX was introduced to quantitate the motion inhomogeneity across the length of the artery. RESULTS: A dense displacement field, describing the longitudinal motion of the carotid far wall over time, was extracted from all participants. For each cine-loop, the method was evaluated against manual reference tracings performed on three local points, and showed a good accuracy, with an average absolute error (± STD) of 150 (±163) µm. It also demonstrated an overall greater robustness compared to a previously validated method based on single-point motion tracking. For all the 62 participants, the analyzed region had, in average, a width of 24.2 mm, involving the simultaneous tracking of 357 points along 151 temporal frames, and requiring a total computational time of 68 s. Analyzing the inhomogeneity of the carotid artery motion showed a strong correlation between σX and the presence of coronary artery disease (ß-coefficient = 0.586, P = 0.003). CONCLUSIONS: To the best of our knowledge, this is the first time that a method is specifically proposed to assess the dense motion field corresponding to the longitudinal kinetics of the carotid far wall. This approach has potential to evaluate the homogeneity (or lack thereof) of the wall dynamics. The proposed method has promising performances to improve the analysis of arterial longitudinal motion and the understanding of the underlying patho-physiological parameters.

Contour segmentation of the intima, media, and adventitia layers in intracoronary OCT images: application to fully automatic detection of healthy wall regions.

PURPOSE: Quantitative and automatic analysis of intracoronary optical coherence tomography images is useful and time-saving to assess cardiovascular risk in the clinical arena. METHODS: First, the interfaces of the intima, media, and adventitia layers are segmented, by means of an original front propagation scheme, running in a 4D multi-parametric space, to simultaneously extract three non-crossing contours in the initial cross-sectional image. Second, information resulting from the tentative contours is exploited by a machine learning approach to identify healthy and diseased regions of the arterial wall. The framework is fully automatic. RESULTS: The method was applied to 40 patients from two different medical centers. The framework was trained on 140 images and validated on 260 other images. For the contour segmentation method, the average segmentation errors were [Formula: see text] for the intima-media interface, [Formula: see text] for the media-adventitia interface, and [Formula: see text] for the adventitia-periadventitia interface. The classification method demonstrated a good accuracy, with a median Dice coefficient equal to 0.93 and an interquartile range of (0.78-0.98). CONCLUSION: The proposed framework demonstrated promising offline performances and could potentially be translated into a reliable tool for various clinical applications, such as quantification of tissue layer thickness and global summarization of healthy regions in entire pullbacks.

A Fully-Automatic Method to Segment the Carotid Artery Layers in Ultrasound Imaging: Application to Quantify the Compression-Decompression Pattern of the Intima-Media Complex During the Cardiac Cycle.

The aim of this study was to introduce and evaluate a contour segmentation method to extract the interfaces of the intima-media complex in carotid B-mode ultrasound images. The method was applied to assess the temporal variation of intima-media thickness during the cardiac cycle. The main methodological contribution of the proposed approach is the introduction of an augmented dimension to process 2-D images in a 3-D space. The third dimension, which is added to the two spatial dimensions of the image, corresponds to the tentative local thickness of the intima-media complex. The method is based on a dynamic programming scheme that runs in a 3-D space generated with a shape-adapted filter bank. The optimal solution corresponds to a single medial axis representation that fully describes the two anatomical interfaces of the arterial wall. The method is fully automatic and does not require any input from the user. The method was trained on 60 subjects and validated on 184 other subjects from six different cohorts and four different medical centers. The arterial wall was successfully segmented in all analyzed images (average pixel size = 57 ± 20 mm), with average segmentation errors of 47 ± 70 mm for the lumen-intima interface, 55 ± 68 mm for the media-adventitia interface and 66 ± 90 mm for the intima-media thickness. The amplitude of the temporal variations in IMT during the cardiac cycle was significantly higher in the diseased population than in healthy volunteers (106 ± 48 vs. 86 ± 34 mm, p = 0.001). The introduced framework is a promising approach to investigate an emerging functional parameter of the arterial wall by assessing the cyclic compression-decompression pattern of the tissues.

OCT-measured plaque free wall angle is indicative for plaque burden: overcoming the main limitation of OCT?

The aim of this study was to investigate the relationship between the plaque free wall (PFW) measured by optical coherence tomography (OCT) and the plaque burden (PB) measured by intravascular ultrasound (IVUS). We hypothesize that measurement of the PFW could help to estimate the PB, thereby overcoming the limited ability of OCT to visualize the external elastic membrane in the presence of plaque. This could enable selection of the optimal stent-landing zone by OCT, which is traditionally defined by IVUS as a region with a PB < 40 %. PB (IVUS) and PFW angle (OCT and IVUS) were measured in 18 matched IVUS and OCT pullbacks acquired in the same coronary artery. We determined the relationship between OCT measured PFW (PFWOCT) and IVUS PB (PBIVUS) by non-linear regression analysis. An ROC-curve analysis was used to determine the optimal cut-off value of PFW angle for the detection of PB < 40 %. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. There is a significant correlation between PFWOCT and PBIVUS (r(2) = 0.59). The optimal cut-off value of the PFWOCT for the prediction of a PBIVUS < 40 % is ≥220° with a PPV of 78 % and an NPV of 84 %. This study shows that PFWOCT can be considered as a surrogate marker for PBIVUS, which is currently a common criterion to select an optimal stent-landing zone.

Fusion of fibrous cap thickness and wall shear stress to assess plaque vulnerability in coronary arteries: a pilot study.

PURPOSE: Identification of rupture-prone plaques in coronary arteries is a major clinical challenge. Fibrous cap thickness and wall shear stress are two relevant image-based risk factors, but these two parameters are generally computed and analyzed separately. Accordingly, combining these two parameters can potentially improve the identification of at-risk regions. Therefore, the purpose of this study is to investigate the feasibility of the fusion of wall shear stress and fibrous cap thickness of coronary arteries in patient data. METHODS: Fourteen patients were included in this pilot study. Imaging of the coronary arteries was performed with optical coherence tomography and with angiography. Fibrous cap thickness was automatically quantified from optical coherence tomography pullbacks using a contour segmentation approach based on fast marching. Wall shear stress was computed by applying computational fluid dynamics on the 3D volume reconstructed from two angiograms. The two parameters then were co-registered using anatomical landmarks such as side branches. RESULTS: The two image modalities were successfully co-registered, with a mean (±SD) error corresponding to [Formula: see text] of the length of the analyzed region. For all the analyzed participants, the average thinnest portion of each fibrous cap was [Formula: see text], and the average WSS value at the location of the fibrous cap was [Formula: see text]. A unique index was finally generated for each patient via the fusion of fibrous cap thickness and wall shear stress measurements, to translate all the measured parameters into a single risk map. CONCLUSION: The introduced risk map integrates two complementary parameters and has potential to provide valuable information about plaque vulnerability.

Quantification of fibrous cap thickness in intracoronary optical coherence tomography with a contour segmentation method based on dynamic programming.

OBJECTIVES: Fibrous cap thickness is the most critical component of plaque stability. Therefore, in vivo quantification of cap thickness could yield valuable information for estimating the risk of plaque rupture. In the context of preoperative planning and perioperative decision making, intracoronary optical coherence tomography imaging can provide a very detailed characterization of the arterial wall structure. However, visual interpretation of the images is laborious, subject to variability, and therefore not always sufficiently reliable for immediate decision of treatment. METHODS: A novel semiautomatic segmentation method to quantify coronary fibrous cap thickness in optical coherence tomography is introduced. To cope with the most challenging issue when estimating cap thickness (namely the diffuse appearance of the anatomical abluminal interface to be detected), the proposed method is based on a robust dynamic programming framework using a geometrical a priori. To determine the optimal parameter settings, a training phase was conducted on 10 patients. RESULTS: Validated on a dataset of 179 images from 21 patients, the present framework could successfully extract the fibrous cap contours. When assessing minimal cap thickness, segmentation results from the proposed method were in good agreement with the reference tracings performed by a medical expert (mean absolute error and standard deviation of 22 ± 18 µm) and were similar to inter-observer reproducibility (21 ± 19 µm, R = .74), while being significantly faster and fully reproducible. CONCLUSION: The proposed framework demonstrated promising performances and could potentially be used for online identification of high-risk plaques.

Real-time ultrasound-tagging to track the 2D motion of the common carotid artery wall in vivo.

PURPOSE: Tracking the motion of biological tissues represents an important issue in the field of medical ultrasound imaging. However, the longitudinal component of the motion (i.e., perpendicular to the beam axis) remains more challenging to extract due to the rather coarse resolution cell of ultrasound scanners along this direction. The aim of this study is to introduce a real-time beamforming strategy dedicated to acquire tagged images featuring a distinct pattern in the objective to ease the tracking. METHODS: Under the conditions of the Fraunhofer approximation, a specific apodization function was applied to the received raw channel data, in real-time during image acquisition, in order to introduce a periodic oscillations pattern along the longitudinal direction of the radio frequency signal. Analytic signals were then extracted from the tagged images, and subpixel motion tracking of the intima-media complex was subsequently performed offline, by means of a previously introduced bidimensional analytic phase-based estimator. RESULTS: The authors' framework was applied in vivo on the common carotid artery from 20 young healthy volunteers and 6 elderly patients with high atherosclerosis risk. Cine-loops of tagged images were acquired during three cardiac cycles. Evaluated against reference trajectories manually generated by three experienced analysts, the mean absolute tracking error was 98 ± 84 µm and 55 ± 44 µm in the longitudinal and axial directions, respectively. These errors corresponded to 28% ± 23% and 13% ± 9% of the longitudinal and axial amplitude of the assessed motion, respectively. CONCLUSIONS: The proposed framework enables tagged ultrasound images of in vivo tissues to be acquired in real-time. Such unconventional beamforming strategy contributes to improve tracking accuracy and could potentially benefit to the interpretation and diagnosis of biomedical images.

Progressive attenuation of the longitudinal kinetics in the common carotid artery: preliminary in vivo assessment.

Longitudinal kinetics (LOKI) of the arterial wall consists of the shearing motion of the intima-media complex over the adventitia layer in the direction parallel to the blood flow during the cardiac cycle. The aim of this study was to investigate the local variability of LOKI amplitude along the length of the vessel. By use of a previously validated motion-estimation framework, 35 in vivo longitudinal B-mode ultrasound cine loops of healthy common carotid arteries were analyzed. Results indicated that LOKI amplitude is progressively attenuated along the length of the artery, as it is larger in regions located on the proximal side of the image (i.e., toward the heart) and smaller in regions located on the distal side of the image (i.e., toward the head), with an average attenuation coefficient of -2.5 ± 2.0%/mm. Reported for the first time in this study, this phenomenon is likely to be of great importance in improving understanding of atherosclerosis mechanisms, and has the potential to be a novel index of arterial stiffness.

Simultaneous extraction of carotid artery intima-media interfaces in ultrasound images: assessment of wall thickness temporal variation during the cardiac cycle.

OBJECTIVES: The aim of this work is to present and evaluate a novel segmentation method for localizing the contours of the intima-media complex in the carotid artery wall through longitudinal ultrasound B-mode imaging. The method is used to investigate the association between atherosclerosis risk factors and the cyclic variation of the intima-media thickness during the heart beat. METHODS: The framework introduced is based on two main features. The first is a simultaneous extraction of both the lumen-intima and the media-adventitia interfaces, using the combination of an original shape-adapted filter bank and a specific dynamic programming scheme. The second is an innovative spatial transformation that eases the extraction of skewed and curved contours, and exploits the result from the previous image as a priori information, when processing the current image. The intima-media thickness is automatically derived from the estimated contours for each time step during the cardiac cycle. Our method was evaluated in vivo on 57 healthy volunteers and 25 patients at high cardiovascular risk. Reference contours were generated for each subject by averaging the tracings performed by three experienced observers. RESULTS: Segmentation errors were 29 ± 27 µm for the lumen-intima interface, 42 ± 38 µm for the media-adventitia interface, and 22 ± 16 µm for the intima-media thickness. This uncertainty was similar to inter- and intra-observer variability. Furthermore, the amplitude of the temporal variation in thickness of the intima-media layers during the cardiac cycle was significantly higher in at-risk patients compared to healthy volunteers (79 ± 36 vs. 64 ± 26 µm, p = 0.032). Conclusion: The method proposed may provide a relevant diagnostic aid for atherosclerosis screening in clinical studies.

Evaluation of a Kalman-based block matching method to assess the bi-dimensional motion of the carotid artery wall in B-mode ultrasound sequences.

We aim at investigating arterial diseases at early stage, by assessing the longitudinal (i.e. in the same direction as the blood flow) motion of the intima-media complex. This recently evidenced phenomenon has been shown to provide relevant and complementary information about vascular health. Our method assesses the longitudinal and radial motion from clinical in vivo B-mode ultrasound sequences. To estimate the trajectory of a selected point during the cardiac cycle, we introduce a block matching method that involves a temporal update of the reference block using a pixel-wise Kalman filter. The filter uses the initial gray-level of the pixel as control signal to avoid divergence due to cumulating errors. The block and search-window sizes are adapted to the tissue of interest. The method was evaluated on image sequences of the common carotid artery, acquired in 57 healthy volunteers and in 25 patients at high cardiovascular risk. Reference trajectories were generated for each sequence by averaging the tracings performed by three observers. Six different computerized techniques were also compared to our method. With a pixel size of 30 µm, the average absolute motion estimation errors were 84 ± 107 µm and 20 ± 19 µm for the longitudinal and radial directions, respectively. This accuracy was of the same order of magnitude as the inter- and intra-observers variability, and smaller than for the other methods. The estimated longitudinal motion amplitude was significantly reduced in at-risk patients compared with healthy volunteers (408 ± 281 µm vs. 643 ± 274 µm, p<0.0001). Our method can constitute a reliable and time-saving technique to investigate the arterial stiffness in clinical studies, in the objective to detect early-stage atherosclerosis.

Longitudinal displacement of the carotid wall and cardiovascular risk factors: associations with aging, adiposity, blood pressure and periodontal disease independent of cross-sectional distensibility and intima-media thickness.

The recently discovered longitudinal displacement of the common carotid arterial wall (i.e., the motion along the same plane as the blood flow), may be associated with incident cardiovascular events and represents a novel and relevant clinical information. At present, there have only been a few studies that have been conducted to investigate this longitudinal movement. We propose here a method to assess noninvasively the wall bi-dimensional (two-dimensional [2-D], cross-sectional and longitudinal) motion and present an original approach that combines a robust speckle tracking scheme to guidance by minimal path contours segmentation. Our method is well suited to large clinical population studies as it does not necessitate strong imaging prerequisites. The aim of this study is to describe the association between the longitudinal displacement of the carotid arterial wall and cardiovascular risk factors, among which periodontal disease. Some 126 Indigenous Australians with periodontal disease, an emerging risk factor, and 27 healthy age- and sex-matched non-indigenous control subjects had high-resolution ultrasound scans of the common carotid artery. Carotid intima-media thickness and arterial wall 2-D motion were then assessed using our method in ultrasound B-mode sequences. Carotid longitudinal displacement was markedly lower in the periodontal disease group than the control group (geometric mean (IQR): 0.15 mm (0.13) vs. 0.42 mm (0.30), respectively; p < 0.0001), independent of cardiovascular risk factors, cross-sectional distensibility and carotid intima-media thickness (p < 0.0001). A multivariable model indicated that the strongest correlates of carotid longitudinal displacement in adults with periodontal disease were age (ß-coefficient = -.235, p = .03), waist (ß-coefficient = -.357, p = 0.001), and pulse pressure (ß-coefficient = .175, p = 0.07), independent of other cardiovascular risk factors, cross-sectional distensibility and pulse wave velocity. Carotid longitudinal displacement, estimated with our approach, is impaired in the periodontal disease group, independent of established cardiovascular risk factors and other noninvasive measures of arterial stiffness, and may represent an important marker of cardiovascular risk.

Measurement of two-dimensional movement parameters of the carotid artery wall for early detection of arteriosclerosis: a preliminary clinical study.

The aim of this study was to clinically investigate the association between the risk factors of early-stage atherosclerosis and the two-dimensional (2-D) movement of the artery wall. To meet this objective, a speckle tracking approach for the estimation of the 2-D trajectory of the vessel wall was proposed and applied to B-mode ultrasound (US) sequences of the left common carotid artery (CCA). A deformable skeleton model was also introduced in the block matching scheme. Finally, the 2-D movements of both proximal and distal walls were investigated in three different local regions, with 1.5 × 0.3 mm(2) kernel blocks. A clinical study was conducted in which two different populations (26 young healthy volunteers and 26 older diabetic patients) were studied. The results show that the mean amplitude value of the diameter change ΔD, of the longitudinal displacement of the proximal wall ΔX(p) and of the longitudinal displacement of the distal wall ΔX(d) were 0.65 ± 0.17 vs. 0.41 ± 0.12 mm (p < 0.001), 0.48 ± 0.21 vs. 0.26 ± 0.18 mm (p < 0.001) and 0.48 ± 0.20 vs. 0.35 ± 0.23 mm (p = 0.006) for the young healthy volunteers and the older diabetic patients, respectively. The results of the three dynamic parameters ΔD, ΔX(p) and ΔX(d) were systematically and significantly lower for the diabetic subjects, respectively 37%, 46% and 27%. The method introduced in this feasibility study might constitute a pertinent approach to assess the presence of early-stage arteriosclerosis by the noninvasive estimation of the 2-D motion of the intima-media complex in the CCA.