D. Buchanan

Progression of Carotid Plaque Volume Predicts Cardiovascular Events

Background and Purpose— Carotid ultrasound evaluation of intima-media thickness (IMT) and plaque burden has been used for risk stratification and for evaluation of antiatherosclerotic therapies. Increasing evidence indicates that measuring plaque burden is superior to measuring IMT for both purposes. We compared progression/regression of IMT, total plaque area (TPA), and total plaque volume (TPV) as predictors of cardiovascular outcomes. Methods— IMT, TPA, and TPV were measured at baseline in 349 patients attending vascular prevention clinics; they had TPA of 40 to 600 mm2 at baseline to qualify for enrollment. Participants were followed up for ⩽5 years (median, 3.17 years) to ascertain vascular death, myocardial infarction, stroke, and transient ischemic attacks. Follow-up measurements 1 year later were available in 323 cases for IMT and TPA, and in 306 for TPV. Results— Progression of TPV predicted stroke, death or TIA (Kaplan-Meier logrank P=0.001), stroke/death/MI (P=0.008) and Stroke/Death/TIA/Myocardial infarction (any Cardiovascular event) (P=0.001). Progression of TPA weakly predicted Stroke/Death/TIA (P=0.097) but not stroke/death/MI (P=0.59) or any CV event (P=0.143); likewise change in IMT did not predict Stroke/Death/MI (P=0.13) or any CV event (P=0.455 ). In Cox regression, TPV progression remained a significant predictor of events after adjustment for coronary risk factors (P=0.001) but change in TPA did not. IMT change predicted events in an inverse manner; regression of IMT predicted events (P=0.004). Conclusions— For assessment of response to antiatherosclerotic therapy, measurement of TPV is superior to both IMT and TPA.

Three‐dimensional ultrasound of carotid atherosclerosis: Semiautomated segmentation using a level set‐based method

PURPOSE Three-dimensional ultrasound (3D US) of the carotid artery provides measurements of arterial wall and plaque [vessel wall volume (VWV)] that are complementary to the one-dimensional measurement of the carotid artery intima-media thickness. 3D US VWV requires an observer to delineate the media-adventitia boundary (MAB) and lumen-intima boundary (LIB) of the carotid artery. The main purpose of this work was to develop and evaluate a semiautomated segmentation algorithm for delineating the MAB and LIB of the carotid artery from 3D US images. METHODS To segment the MAB and LIB, the authors used a level set method and combined several low-level image cues with high-level domain knowledge and limited user interaction. First, the operator initialized the algorithm by choosing anchor points on the boundaries, identified in the images. The MAB was segmented using local region- and edge-based energies and an energy that encourages the boundary to pass through anchor points from the preprocessed images. For the LIB segmentation, the authors used local and global region-based energies, the anchor point-based energy, as well as a constraint promoting a boundary separation between the MAB and LIB. The data set consisted of 231 2D images (11 2D images per each of 21 subjects) extracted from 3D US images. The image slices were segmented five times each by a single observer using the algorithm and the manual method. Volume-based, region-based, and boundary distance-based metrics were used to evaluate accuracy. Moreover, repeated measures analysis was used to evaluate precision. RESULTS The algorithm yielded an absolute VWV difference of 5.0% +/- 4.3% with a segmentation bias of -0.9% +/- 6.6%. For the MAB and LIB segmentations, the method gave absolute volume differences of 2.5% +/- 1.8% and 5.6% +/- 3.0%, Dice coefficients of 95.4% +/- 1.6% and 93.1% +/- 3.1%, mean absolute distances of 0.2 +/- 0.1 and 0.2 +/- 0.1 mm, and maximum absolute distances of 0.6 +/- 0.3 and 0.7 +/- 0.6 mm, respectively. The coefficients of variation of the algorithm (5.1%) and manual methods (3.9%) were not significantly different, but the average time saved using the algorithm (2.8 min versus 8.3 min) was substantial. CONCLUSIONS The authors generated and tested a semiautomated carotid artery VWV measurement tool to provide measurements with reduced operator time and interaction, with high Dice coefficients, and with necessary required precision.

Semi-automated segmentation of carotid artery total plaque volume from three dimensional ultrasound carotid imaging

Carotid artery total plaque volume (TPV) is a three-dimensional (3D) ultrasound (US) imaging measurement of carotid atherosclerosis, providing a direct non-invasive and regional estimation of atherosclerotic plaque volume - the direct determinant of carotid stenosis and ischemic stroke. While 3DUS measurements of TPV provide the potential to monitor plaque in individual patients and in populations enrolled in clinical trials, until now, such measurements have been performed manually which is laborious, time-consuming and prone to intra-observer and inter-observer variability. To address this critical translational limitation, here we describe the development and application of a semi-automated 3DUS plaque volume measurement. This semi-automated TPV measurement incorporates three user-selected boundaries in two views of the 3DUS volume to generate a geometric approximation of TPV for each plaque measured. We compared semi-automated repeated measurements to manual segmentation of 22 individual plaques ranging in volume from 2mm3 to 151mm3. Mean plaque volume was 43±40mm3 for semi-automated and 48±46mm3 for manual measurements and these were not significantly different (p=0.60). Mean coefficient of variation (CV) was 12.0±5.1% for the semi-automated measurements.

The relationship of carotid three-dimensional ultrasound vessel wall volume with age and sex: comparison to carotid intima-media thickness.

The relationship of three-dimensional ultrasound (3DUS)-derived carotid vessel wall volume (VWV) was evaluated with respect to age and sex. B-mode and 3DUS images were acquired for 316 subjects from diverse groups including obese primary prevention, diabetic nephropathy, renal transplant and rheumatoid arthritis populations. The relationship for intima-media thickness (IMT) and VWV with age and sex were determined using Pearson-product-moment correlations. Mean IMT (r = 0.18, p = 0.001) and VWV (r = 0.24, p < 0.01) correlated modestly with age. There were modest correlations in males (IMT, r = 0.19, p = 0.003; VWV, r = 0.34, p < 0.001) and in females for IMT and age (r = 0.30, p = 0.007) but not between 3DUS VWV and age in females (r = 0.10, p = 0.4). Significant associations between plaque and VWV (r = 0.36, p = 0.001) but not IMT suggest different correlations in females that may be attributed to plaque.

Coupled level set approach to segment carotid arteries from 3D ultrasound images

In this paper, we described and validated a semi-automated algorithm based on the level set method to segment the media-adventitia boundary (MAB) and lumen-intima boundary (LIB) of the carotid arteries from 3D ultrasound (3DUS) images to support the computation of carotid vessel wall volume (VWV). We incorporated local region-based and edge-based energies for the MAB segmentation, and both local and global region-based energies for the LIB segmentation. The two level set functions are coupled using a boundary separation-based energy to encourage an anatomically-motivated boundary separation between the MAB and LIB. An additional energy term attracts the boundary to pass through anchor points placed by an operator. The algorithm was evaluated with 231 2D transverse images extracted from 21 3DUS images. The algorithm gave a VWV error of 5.2%±3.9%, yielded Dice coefficients of 95.6% ± 1.5%, 92.8% ± 3.2% for the MAB and LIB, respectively, and gave sub-millimeter boundary distance errors. The coefficients of variation of VWV from the semi-automated (5.0%) and manual (3.9%) methods were not significantly different.

One, two and three-dimensional ultrasound measurements of carotid atherosclerosis before and after cardiac rehabilitation: preliminary results of a randomized controlled trial

BackgroundIt is still not known how patients who are post-transient ischemic attack (TIA) or post-stroke might benefit from prospectively planned comprehensive cardiac rehabilitation (CCR). In this pilot evaluation of a larger ongoing randomized-controlled-trial, we evaluated ultrasound (US) measurements of carotid atherosclerosis in subjects following TIA or mild non-disabling stroke and their relationship with risk factors before and after 6-months of CCR.MethodsCarotid ultrasound (US) measurements of one-dimensional intima-media-thickness (IMT), two-dimensional total-plaque-area (TPA), three-dimensional total-plaque-volume (TPV) and vessel-wall-volume (VWV) were acquired before and after 6-months CCR for 39 subjects who had previously experienced a TIA and provided written informed consent to participate in this randomized controlled trial. We maintained blinding for this ongoing study by representing treatment and control groups as A or B, although we did not identify which of A or B was treatment or control. Carotid IMT, TPA, TPV and VWV were measured before and after CCR as were changes in body mass index (BMI), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP).ResultsThere were no significant differences in US measurements or risk factors between groups A and B. There was no significant change in carotid ultrasound measurements for group A (IMT, p = .728; TPA, p = .629; TPV, p = .674; VWV, p = .507) or B (IMT, p = .054; TPA, p = .567; TPV, p = .773; VWV, p = .431) at the end of CCR. There were significant but weak-to-moderate correlations between IMT and VWV (r = 0.25, p = .01), IMT and TPV (r = 0.21, p = .01), TPV and TPA (r = 0.60, p < .0001) and VWV and TPV (r = 0.22, p = .02). Subjects with improved TC/HDL ratios showed improved carotid VWV although, this was not statistically significant.ConclusionIn this preliminary evaluation, there were no significant differences in carotid US measurements in the control or CCR group; a larger sample size and/or longer duration is required to detect significant changes in US or other risk factor measurements.

Three-dimensional semi-automated segmentation of carotid atherosclerosis from three-dimensional ultrasound images

Three-dimensional ultrasound (3DUS) provides non-invasive and precise measurements of carotid atherosclerosis that directly reflects arterial wall abnormalities that are thought to be related to stroke risk. Here we describe a threedimensional segmentation method based on the sparse field level set method to automate the segmentation of the mediaadventitia (MAB) and lumen-intima (LIB) boundaries of the common carotid artery from 3DUS images. To initiate the process, an expert chooses four anchor points on each boundary on a subset of transverse slices that are orthogonal to the axis of the artery. An initial surface is generated using the anchor points as initial guess for the segmentation. The MAB is segmented first using five energies: length minimization energy, local region-based energy, edge-based energy, anchor point-based energy, and local smoothness energy. Five energies are also used for the LIB segmentation: length minimization energy, local region-based energy, global region-based energy, anchor point-based energy, and boundary separation-based energy. The algorithm was evaluated with respect to manual segmentations on a slice-by-slice basis using 15 3DUS images. To generate results in this paper, inter-slice distance of 2 mm is used for the initialization. For the MAB and LIB segmentations, our method yielded Dice coefficients of more than 92% and sub-millimeter values for mean and maximum absolute distance errors. Our method also yielded a vessel wall volume error of 7.1% ± 3.4%. The realization of a semi-automated algorithm will aid in the translation of 3DUS measurements to clinical research for the rapid, non-invasive, and economical monitoring of atherosclerotic disease.

Three-dimensional Ultrasound Imaging of Carotid Atherosclerosis

Three-dimensional ultrasound (3DUS) imaging measurements of carotid atherosclerosis are increasingly being investigated for monitoring the progression and regression of plaque burden in longitudinal studies. In this paper, we review the recent advancements of 3DUS imaging in terms of novel carotid atherosclerosis measurements, image processing techniques, and clinical trials. Lumen stenos is is the current imaging clinical standard for monitoring atherosclerosis. In addition, during the last two decades intima-media thickness is also used as a surrogate measurement of carotid atherosclerosis to assess disease severity in clinical trials. However, 3DUS measurements such as total plaque volume, vessel wall volume, and vessel wall thickness maps may be more sensitive metrics of the disease as they reflect the volumetric changes of the lesion along the length of the artery. Recently, numerous semi-automated techniques have been developed to segment the lumen and outer wall boundaries and plaque. There are also attempts to compute plaque composition from 3DUS images. Finally, we will review the clinical trials that involve 3DUS imaging.

Effect of wine on carotid atherosclerosis in type 2 diabetes: a 2-year randomized controlled trial

Background/ObjectivesThe progression of carotid-plaque volume in patients with type 2 diabetes is common. Previous observational studies showed an association between moderate alcohol and reduced risk of coronary disease. We examined whether consuming moderate wine affects the progression of carotid atherosclerosis.Subjects/MethodsIn the CASCADE (CArdiovaSCulAr Diabetes and Ethanol), a 2-year randomized controlled trial, we randomized abstainers with type 2 diabetes were to drink 150 ml of either red wine, white wine, or water, provided for 2 years. In addition, groups were guided to maintain a Mediterranean diet. We followed 2-year changes in carotid total plaque volume (carotid-TPV) and carotid vessel wall volume (carotid-VWV), using three-dimensional ultrasound.ResultsCarotid images were available from 174 of the 224 CASCADE participants (67% men; age = 59 yr; HbA1C = 6.8%). Forty-five percent had detectable plaque at baseline. After 2 years, no significant progression in carotid-TPV was observed (water, −1.4 (17.0) mm3, CI (−2.7, 5.5), white-wine, −1.2 (16.9) mm3, CI (−3.8, 6.2), red wine, −1.3 (17.6) mm3, CI (−3.4, 6.0; p = 0.9 between groups)). In post hoc analysis, we divided the 78 participants with detectable baseline carotid plaque into tertiles. Those with the higher baseline plaque burden, whom were assigned to drink wine, reduced their plaque volume significantly after 2 years, as compared to baseline.Two-year reductions in Apo(B)/Apo(A) ratio(s) were independently associated with regression in carotid-TPV (β = 0.4; p < 0.001). Two-year decreases in systolic blood pressure were independently associated with regression in carotid-VWV (β = 0.2; p = 0.005).ConclusionsNo progression in carotid-TPV was observed. In subgroup analyses, those with the greatest plaque burden assigned to drink wine may have had a small regression of plaque burden

MO‐D‐220‐07: Semi‐Automated Segmentation Method to Quantify Carotid Atherosclerosis from 3D Ultrasound Images

Purpose: 3D ultrasound (3DUS) vessel wall volume (VWV) is a 3D measurement of vessel wall thickness plus plaque within the carotid artery for monitoring carotid plaque progression and regression. In this paper, we describe a segmentation algorithm to delineate the media‐adventitia (MAB) and lumen‐intima (LIB) boundaries of the carotid arteries to quantify VWV measurements. Methods: An operator places four anchor points on each boundary of every transverse carotid image slice to initialize the algorithm. The MAB and LIB boundaries are segmented using two level set segmentations that are coupled. The two segmentations evolve independently based on their objective functions, when they are separated by more than a minimum allowable separation distance. When two curves are closer than the minimal allowable distance, they repel each other to maintain the separation. The algorithm was evaluated with respect to manual segmentations using volume‐, region‐, and boundary distance‐based metrics. Our data set consisted of manual and algorithm repeatedly (5) segmented boundaries of 231 transverse 2D slices extracted from 21 3DUS carotid images. Results: The algorithm provided a mean VWV error of 5.2%±3.9%. For the MAB and LIB respectively, our method yielded Dice coefficients of 95.6%±1.5% and 92.8%±3.2%, and mean absolute distances of 0.2±0.1 mm and 0.3±0.1 mm. The algorithm yielded a minimum detectable difference (MDD) of 63.1 mm3, which is smaller than the previously reported annual VWV change of 120 mm3/year. The average time saved using the algorithm was 4.6 min (8.3 min − 3.7 min). Conclusions: The algorithm provided small volume‐based errors, high Dice coefficients, and sub‐millimeter boundary distance‐based errors. The MDD suggests that a follow‐up period of seven months or more would be appropriate using our method for monitoring carotid atherosclerosis. The realization of a semi‐automated method would assist the translation of carotid 3DUS for clinical research and clinical care.