Altered probe pressure and body position increase diagnostic accuracy for men and women in detecting hepatic steatosis using quantitative ultrasound.

OBJECTIVES: To evaluate the diagnostic performance of ultrasound guided attenuation parameter (UGAP) for evaluating liver fat content with different probe forces and body positions, in relation to sex, and compared with proton density fat fraction (PDFF). METHODS: We prospectively enrolled a metabolic dysfunction-associated steatotic liver disease (MASLD) cohort that underwent UGAP and PDFF in the autumn of 2022. Mean UGAP values were obtained in supine and 30° left decubitus body position with normal 4 N and increased 30 N probe force. The diagnostic performance was evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: Among 60 individuals (mean age 52.9 years, SD 12.9; 30 men), we found the best diagnostic performance with increased probe force in 30° left decubitus position (AUC 0.90; 95% CI 0.82-0.98) with a cut-off of 0.58 dB/cm/MHz. For men, the best performance was in supine (AUC 0.91; 95% CI 0.81-1.00) with a cut-off of 0.60 dB/cm/MHz, and for women, 30° left decubitus position (AUC 0.93; 95% CI 0.83-1.00), with a cut-off 0.56 dB/cm/MHz, and increased 30 N probe force for both genders. No difference was in the mean UGAP value when altering body position. UGAP showed good to excellent intra-reproducibility (Intra-class correlation 0.872; 95% CI 0.794-0.921). CONCLUSION: UGAP provides excellent diagnostic performance to detect liver fat content in metabolic dysfunction-associated steatotic liver diseases, with good to excellent intra-reproducibility. Regardless of sex, the highest diagnostic accuracy is achieved with increased probe force with men in supine and women in 30° left decubitus position, yielding different cut-offs. CLINICAL RELEVANCE STATEMENT: The ultrasound method ultrasound-guided attenuation parameter shows excellent diagnostic accuracy and performs with good to excellent reproducibility. There is a possibility to alter body position and increase probe pressure, and different performances for men and women should be considered for the highest accuracy. KEY POINTS: • There is a possibility to alter body position when performing the ultrasound method ultrasound-guided attenuation parameter. • Increase probe pressure for the highest accuracy. • Different performances for men and women should be considered.

Spatially repeatable components from ultrafast ultrasound are associated with motor unit activity in human isometric contractions.

Objective.Ultrafast ultrasound (UUS) imaging has been used to detect intramuscular mechanical dynamics associated with single motor units (MUs). Detecting MUs from ultrasound sequences requires decomposing a velocity field into components, each consisting of an image and a signal. These components can be associated with putative MU activity or spurious movements (noise). The differentiation between putative MUs and noise has been accomplished by comparing the signals with MU firings obtained from needle electromyography (EMG). Here, we examined whether the repeatability of the images over brief time intervals can serve as a criterion for distinguishing putative MUs from noise in low-force isometric contractions.Approach.UUS images and high-density surface EMG (HDsEMG) were recorded simultaneously from 99 MUs in the biceps brachii of five healthy subjects. The MUs identified through HDsEMG decomposition were used as a reference to assess the outcomes of the ultrasound-based components. For each contraction, velocity sequences from the same eight-second ultrasound recording were separated into consecutive two-second epochs and decomposed. To evaluate the repeatability of components' images across epochs, we calculated the Jaccard similarity coefficient (JSC). JSC compares the similarity between two images providing values between 0 and 1. Finally, the association between the components and the MUs from HDsEMG was assessed.Main results.All the MU-matched components had JSC > 0.38, indicating they were repeatable and accounted for about one-third of the HDsEMG-detected MUs (1.8 ± 1.6 matches over 4.9 ± 1.8 MUs). The repeatable components (JSC > 0.38) represented 14% of the total components (6.5 ± 3.3 components). These findings align with our hypothesis that intra-sequence repeatability can differentiate putative MUs from noise and can be used for data reduction.Significance.This study provides the foundation for developing stand-alone methods to identify MU in UUS sequences and towards real-time imaging of MUs. These methods are relevant for studying muscle neuromechanics and designing novel neural interfaces.

Multi-view carotid ultrasound is stronger associated with cardiovascular risk factors than presence of plaque or single carotid intima media thickness measurements in subclinical atherosclerosis.

We aimed to explore the prevalence of atherosclerosis by using multi-view ultrasound examination of the carotid arteries and its association with clinical risk factors in a middle-aged population at low to intermediate risk of cardiovascular disease (CVD). Carotid vascular ultrasound was performed in 3532 participants in the VIPVIZA trial. Mean and maximal carotid intima media thickness (cIMT) at prespecified angles and plaque presence were examined on the left and right side. Associations between CVD risk factors and ultrasound variables were quantified by partial least squares (PLS) regression. A combined ultrasound variable was computed using weights of the first PLS component. Associations between CVD risk factors and the combined multi-view ultrasound variable, single cIMT and plaque measurements, respectively, were determined using linear regression modelling. The participants' mean age was 55.7 years and 52.9% were women. Plaque prevalence was 51.1% in men and 39.0% in women. cIMT was higher in men than in women and in the left compared with the right carotid artery. The strongest association of CVD risk factors was observed with the combined multi-view ultrasound variable (R2 = 24%), compared with single cIMT variables (R2 = 14-18%) and plaque presence (R2 = 15%). The pattern was similar in both sexes. The association with CVD risk factors and the combined ultrasound variable was stronger in 40-year olds (R2 = 22%) compared with 50- or 60-year olds (R = 12%). CVD risk factors are stronger associated with a combined ultrasound variable than plaque presence or single cIMT measures suggesting that carotid multi-view ultrasonography better captures the focality of early atherosclerosis.Clinical Trial Registration: ClinicalTrials.gov, number NCT01849575. May 8, 2013.

Reduced progression of carotid intima media thickness by personalised pictorial presentation of subclinical atherosclerosis in VIPVIZA-A randomised controlled trial.

OBJECTIVES: Reduced progression of atherosclerosis can decrease the risk of cardiovascular disease (CVD). This study aimed at evaluating the effect of a pictorial intervention showing atherosclerotic severity on the progression of carotid atherosclerosis. METHODS: A prospective randomised open-label blinded end-point trial with participants aged 40-60 years enroled from a routine CVD prevention programme. The intervention group (n: 1575) and their treating physicians received an image based presentation of subclinical atherosclerotic severity measured by carotid ultrasound. The control group (n: 1579) did not receive any information about ultrasound results. Carotid ultrasound at baseline and at 3-year follow-up contained plaque detection and measurements of carotid intima media thickness (cIMT). The left, right and bilateral-mean-cIMT, plaque prevalence and total plaque area (TPA) at 3-year follow-up were compared between groups. Significance level was set to p = 0.01 to adjust for multiple comparisons. RESULTS: The intervention group revealed reduced cIMT progression in the left-mean-cIMT of -0.011 mm (p = 0.001) compared with the control group. The intervention effect on cIMT progression was most prominent in individuals with increased cIMT and plaque prevalence at baseline (-0.021 mm, p = 0.005). There were no differences in progression between groups for the right-and bilateral-mean-cIMT (-0.005 mm, p = 0.223 and -0.005 mm, p = 0.036, respectively), nor any differences between groups for plaque prevalence or TPA (odds ratio 0.88, p = 0.09 and 0.89, p = 0.21, respectively). CONCLUSION: Pictorial presentation of subclinical atherosclerotic severity sent to both the individual and their treating physician resulted in significantly reduced left cIMT progression. Pictorial presentation has the potential to increase adherence in CVD prevention.

Early adulthood exercise capacity, but not muscle strength, associates with subclinical atherosclerosis 40 years later in Swedish men.

AIMS: Poor exercise capacity and muscle strength in early adulthood are risk factors for cardiovascular disease (CVD). However, it is unclear how these factors relate to subclinical atherosclerosis due to a lack of longitudinal studies. This study investigated whether early adulthood exercise capacity and muscle strength associated with later adulthood subclinical atherosclerosis. METHODS AND RESULTS: This study included Swedish men (n = 797) who were eligible for military conscription (at ∼18-years of age) and who participated in the baseline assessment of the visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention trial between 2013 and 2016 (at 60 years of age). At conscription, isometric muscle strength (dynamometer) and maximum exercise capacity (maximal load cycle ergometer test) were measured. During later adulthood (at 60 years old), the presence of carotid plaques and intima media thickness were measured by using high-resolution ultrasound. At follow-up, plaques were present in 62% (n = 493) of men. Exercise capacity in early adulthood associated with 19% lower odds of plaques [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.68-0.96], independent of muscle strength. This association was not mediated by any single CVD risk factor. However, the total indirect effect of later, but not early, adulthood CVD risk factors was significant, while the direct effect was non-significant (OR 0.85, 95% CI 0.71-1.02). Associations between muscle strength and subclinical atherosclerosis were non-significant. CONCLUSION: Higher exercise capacity during early adulthood, but not muscle strength, may protect against carotid plaque development during adulthood mediated by the combination rather than a single later adulthood CVD risk factors.

Swedish men who had high fitness at ∼18 years of age (early adulthood) had a lower prevalence of atherosclerotic plaques 40 years later (later adulthood), independent of muscle strength. The underlying mechanism of this protective association of higher fitness on the presence of plaques may be through the combination of later adulthood body mass index, systolic blood pressure, glucose tolerance status, non-HDL cholesterol, and triglycerides instead of through any single risk factor.Muscle strength during early adulthood was not associated with atherosclerosis during later adulthood.

Carotid wall echogenicity at baseline associates with accelerated vascular aging in a middle-aged population.

Ultrasonic echolucent carotid intima-media (IM) complex and accelerated progression of carotid intima mediathickness (cIMT) have both separately been shown to predict future cardiovascular events. The aim of this studywas to evaluate if the echogenicity of the IM-complex is associated with the 3-year progression of cIMT. B-modeultrasound images captured at baseline and 3-year follow-up in the 'Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention' (VIPVIZA) trial were included (n: 3154). The bilateral mean cIMT and IM-echogenicity by greyscale median (GSM) were measured in the common carotid artery. Associations between IM-GSM at baseline and the 3-year cIMT progression were investigated using linear regression models for the whole population and stratified by sex, age and VIPVIZA study group (intervention versus control). In addition, adjusted analyses for confounding factors were performed. Unadjusted analysis showed that decreased IM-GSM at baseline was associated with increased progression of cIMT (p < 0.001). Stratified by age, the association was significant among 40 (p < 0.001) and 60 years old (p < 0.001). The association was statistically significant in both sexes and on comparison of VIPVIZA study subgroups. Adjustments for confounding factors did not alter the estimated relationship between IM-GSM and cIMT progression. Echolucent carotid intima media at baseline associates with increased 3-year cIMT progression among an asymptomatic, middle-aged population. Echogenicity of the intima media may identify individuals at risk for accelerated vascular aging.

Interframe Echo Intensity Variation of Subregions and Whole Plaque in Two-Dimensional Carotid Ultrasonography: Simulations and In Vivo Observations.

OBJECTIVES: The risk of cardiovascular disease is associated with the echo intensity of carotid plaques in ultrasound images and their cardiac cycle-induced intensity variations. In this study, we aimed to 1) explore the underlying origin of echo intensity variations by using simulations and 2) evaluate the association between the two-dimensional (2D) spatial distribution of these echo intensity variations and plaque vulnerability. METHODS: First, we analyzed how out-of-plane motion and compression of simulated scattering spheres of different sizes affect the ultrasound echo intensity. Next, we propose a method to analyze the features of the 2D spatial distribution of interframe plaque echo intensity in carotid ultrasound image sequences and explore their associations with plaque vulnerability in experimental data. RESULTS: The simulations showed that the magnitude of echo intensity changes was similar for both the out-of-plane motion and compression, but for scattering objects smaller than 1 mm radius, the out-of-plane motion dominated. In experimental data, maps of the 2D spatial distribution of the echo intensity variations had a low correlation with standard B-mode echo intensity distribution, indicating complementary information on plaque tissue composition. In addition, we found the existence of ∼1 mm diameter subregions with pronounced echo intensity variations associated with plaque vulnerability. CONCLUSIONS: The results indicate that out-of-plane motion contributes to intra-plaque regions of high echo intensity variation. The 2D echo intensity variation maps may provide complementary information for assessing plaque composition and vulnerability. Further studies are needed to verify this method's role in identifying vulnerable plaques and predicting cardiovascular disease risk.

Optimization and comparison of two methods for spike train estimation in an unfused tetanic contraction of low threshold motor units.

BACKGROUND: Recent findings have shown that imaging voluntarily activated motor units (MUs) by decomposing ultrasound-based displacement images provides estimates of unfused tetanic signals evoked by spinal motoneurons' neural discharges (spikes). Two methods have been suggested to estimate its spike trains: band-pass filter (BPM) and Haar wavelet transform (HWM). However, the methods' optimal parameters and which method performs the best are unknown. This study will answer these questions. METHOD: HWM and BPM were optimized using simulations. Their performance was evaluated based on simulations and 21 experimental datasets, considering their rate of agreement, spike offset, and spike offset variability to the simulated or experimental spikes. RESULTS: A range of parameter sets that resulted in the highest possible agreement with simulated spikes was provided. Both methods highly agreed with simulated and experimental spikes, but HWM was a better spike estimation method than BPM because it had a higher agreement, less bias, and less variation (p < 0.001). CONCLUSIONS: The optimized HWM will be an important contributor to further developing the identification and analysis of MUs using imaging, providing indirect access to the neural drive of the spinal cord to the muscle by the unfused tetanic signals.

Estimation of contractile parameters of successive twitches in unfused tetanic contractions of single motor units - A proof-of-concept study using ultrafast ultrasound imaging in vivo.

During a voluntary contraction, motor units (MUs) fire a train of action potentials, causing summation of the twitch forces, resulting in fused or unfused tetanus. Twitches have been important in studying whole-muscle contractile properties and differentiation between MU types. However, there are still knowledge gaps concerning the voluntary force generation mechanisms. Current methods rely on the spike-triggered averaging technique, which cannot track changes in successive twitches' properties in response to individual neural firings. This study proposes a method that estimates successive twitches contractile parameters of single MUs during low force voluntary isometric contractions in human biceps brachii. We used a previously developed ultrafast ultrasound imaging method to estimate unfused tetanic activity signals of single MUs. A twitch decomposition model was used to decompose unfused tetanic activity signals into individual twitches. This study found that the contractile parameters varied within and across MUs. There was an association between the inter-spike interval and the contraction time (r = 0.49,p < 0.001) and the half-relaxation time (r = 0.58,p < 0.001), respectively. The method shows the proof-of-concept to study MU contractile properties of individual twitches in vivo, which can provide further insights into the force generation mechanisms of voluntary contractions and response to individual neural discharges.

Modelling intra-muscular contraction dynamics using in silico to in vivo domain translation.

BACKGROUND: Advances in sports medicine, rehabilitation applications and diagnostics of neuromuscular disorders are based on the analysis of skeletal muscle contractions. Recently, medical imaging techniques have transformed the study of muscle contractions, by allowing identification of individual motor units' activity, within the whole studied muscle. However, appropriate image-based simulation models, which would assist the continued development of these new imaging methods are missing. This is mainly due to a lack of models that describe the complex interaction between tissues within a muscle and its surroundings, e.g., muscle fibres, fascia, vasculature, bone, skin, and subcutaneous fat. Herein, we propose a new approach to overcome this limitation. METHODS: In this work, we propose to use deep learning to model the authentic intra-muscular skeletal muscle contraction pattern using domain-to-domain translation between in silico (simulated) and in vivo (experimental) image sequences of skeletal muscle contraction dynamics. For this purpose, the 3D cycle generative adversarial network (cycleGAN) models were evaluated on several hyperparameter settings and modifications. The results show that there were large differences between the spatial features of in silico and in vivo data, and that a model could be trained to generate authentic spatio-temporal features similar to those obtained from in vivo experimental data. In addition, we used difference maps between input and output of the trained model generator to study the translated characteristics of in vivo data. RESULTS: This work provides a model to generate authentic intra-muscular skeletal muscle contraction dynamics that could be used to gain further and much needed physiological and pathological insights and assess and overcome limitations within the newly developed research field of neuromuscular imaging.

R2U++: a multiscale recurrent residual U-Net with dense skip connections for medical image segmentation.

U-Net is a widely adopted neural network in the domain of medical image segmentation. Despite its quick embracement by the medical imaging community, its performance suffers on complicated datasets. The problem can be ascribed to its simple feature extracting blocks: encoder/decoder, and the semantic gap between encoder and decoder. Variants of U-Net (such as R2U-Net) have been proposed to address the problem of simple feature extracting blocks by making the network deeper, but it does not deal with the semantic gap problem. On the other hand, another variant UNET++ deals with the semantic gap problem by introducing dense skip connections but has simple feature extraction blocks. To overcome these issues, we propose a new U-Net based medical image segmentation architecture R2U++. In the proposed architecture, the adapted changes from vanilla U-Net are: (1) the plain convolutional backbone is replaced by a deeper recurrent residual convolution block. The increased field of view with these blocks aids in extracting crucial features for segmentation which is proven by improvement in the overall performance of the network. (2) The semantic gap between encoder and decoder is reduced by dense skip pathways. These pathways accumulate features coming from multiple scales and apply concatenation accordingly. The modified architecture has embedded multi-depth models, and an ensemble of outputs taken from varying depths improves the performance on foreground objects appearing at various scales in the images. The performance of R2U++ is evaluated on four distinct medical imaging modalities: electron microscopy, X-rays, fundus, and computed tomography. The average gain achieved in IoU score is 1.5 ± 0.37% and in dice score is 0.9 ± 0.33% over UNET++, whereas, 4.21 ± 2.72 in IoU and 3.47 ± 1.89 in dice score over R2U-Net across different medical imaging segmentation datasets.

Comparison of decomposition algorithms for identification of single motor units in ultrafast ultrasound image sequences of low force voluntary skeletal muscle contractions.

OBJECTIVE: In this study, the aim was to compare the performance of four spatiotemporal decomposition algorithms (stICA, stJADE, stSOBI, and sPCA) and parameters for identifying single motor units in human skeletal muscle under voluntary isometric contractions in ultrafast ultrasound image sequences as an extension of a previous study. The performance was quantified using two measures: (1) the similarity of components' temporal characteristics against gold standard needle electromyography recordings and (2) the agreement of detected sets of components between the different algorithms. RESULTS: We found that out of these four algorithms, no algorithm significantly improved the motor unit identification success compared to stICA using spatial information, which was the best together with stSOBI using either spatial or temporal information. Moreover, there was a strong agreement of detected sets of components between the different algorithms. However, stJADE (using temporal information) provided with complementary successful detections. These results suggest that the choice of decomposition algorithm is not critical, but there may be a methodological improvement potential to detect more motor units.

Long-term exposure to particulate air pollution and presence and progression of carotid artery plaques - A northern Sweden VIPVIZA cohort study.

AIMS: To estimate the association between long-term exposure to particulate air pollution and sub-clinical atherosclerosis based on the existence of plaque and the carotid intima-media thickness (cIMT). METHODS: Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) is a randomised controlled trial integrated within the Västerbotten Intervention Programme, an ongoing population-based cardiovascular disease (CVD) prevention programme in northern Sweden. Individuals aged 40, 50, or 60 years with one or more conventional CVD risk factors in Umeå municipality were eligible to participate. The 1425 participants underwent an ultrasound assessment of cIMT and plaque formation during the period 2013-2016 and at 3-year follow-up. Source-specific annual mean concentrations of particulate matter with aerodynamic diameter ≤10 µm (PM10) and ≤2.5 µm (PM2.5), and black carbon (BC) at the individual's residential address were modelled for the calendar years 1990, 2001 and 2011. Poisson regression was used to estimate prevalence ratios for presence of carotid artery plaques, and linear regression for cIMT. RESULTS: The plaque prevalence was 43% at baseline and 47% at follow-up. An interquartile range (IQR) increase in PM10 (range in year 2011: 7.1-13.5 µg/m3) was associated with a prevalence ratio at baseline ultrasound of 1.11 (95% CI 0.99-1.25), 1.08 (95% CI 0.99-1.17), and 1.00 (95% CI 0.93-1.08) for lag 23, 12 and 2 years, and at follow-up 1.04 (95% CI 0.95-1.14), 1.08 (95% CI 1.00-1.16), and 1.01 (95% CI 0.95-1.08). Similar prevalence ratios per IQR were found for PM2.5 and BC, but with somewhat lower precision for the later. Particle concentrations were however not associated with the progression of plaque. No cross-sectional or longitudinal associations of change were found for cIMT. CONCLUSIONS: This study of individuals with low/moderate risk for CVD give some additional support for an effect of long-term air pollution in early subclinical atherosclerosis.

The beneficial effect over 3 years by pictorial information to patients and their physician about subclinical atherosclerosis and cardiovascular risk: Results from the VIPVIZA randomized clinical trial.

OBJECTIVE: Non-adherence to guidelines and preventive measures is a major challenge, particularly so to obtain long-term adherence to lifestyle changes and recommended medication. The objective was to investigate if pictorial information regarding subclinical carotid atherosclerosis provided to individuals and physicians gave sustained effects on cardiovascular risk beyond the previously reported effect after 1 year and up to 3 years. METHODS: A Prospective Randomized Open Blinded End-point (PROBE) trial. Within a CVD prevention program in Västerbotten County, Sweden, 3532 healthy individuals aged 40, 50 or 60 years were enrolled and 1:1 randomized to intervention (n = 1749; pictorial information with additional prevention materials to participants and physicians) or control group (n = 1783; no pictorial information to participants and physicians). Preventive measures were managed within primary care. Participants were investigated at baseline during 2013-2016 and at follow-up after 1 and 3 years. RESULTS: A beneficial effect on cardiovascular risk was observed at 3-year follow-up; Framingham Risk Score (FRS) was 13.38 for the intervention group and 14.08 for the control group (p = 0.047) and SCORE was 1.69 vs. 1.82 (p = 0.022). The effect observed at 1-year was sustained over 3 years after adjustment for sex and education and more pronounced among participants with a severe atherosclerotic picture at baseline. CONCLUSIONS: This study provides evidence of sustained beneficial effects on the adherence to prevention guidelines over 3 years of pictorial information about subclinical carotid atherosclerosis, resulting in lower cardiovascular risk regardless of sex and educational level. Direct visualization of the underlying still subclinical atherosclerotic disease, rather than just indirect information about risk factors and statistical risk of future myocardial infarction, stroke and death, is one way to tackle the problem of non-adherence to prevention of cardiovascular diseases.

Identification of single motor units in skeletal muscle under low force isometric voluntary contractions using ultrafast ultrasound.

The central nervous system (CNS) controls skeletal muscles by the recruitment of motor units (MUs). Understanding MU function is critical in the diagnosis of neuromuscular diseases, exercise physiology and sports, and rehabilitation medicine. Recording and analyzing the MUs' electrical depolarization is the basis for state-of-the-art methods. Ultrafast ultrasound is a method that has the potential to study MUs because of the electrical depolarizations and consequent mechanical twitches. In this study, we evaluate if single MUs and their mechanical twitches can be identified using ultrafast ultrasound imaging of voluntary contractions. We compared decomposed spatio-temporal components of ultrasound image sequences against the gold standard needle electromyography. We found that 31% of the MUs could be successfully located and their firing pattern extracted. This method allows new non-invasive opportunities to study mechanical properties of MUs and the CNS control in neuromuscular physiology.

Ultrasound risk marker variability in symptomatic carotid plaque: impact on risk reclassification and association with temporal variation pattern.

PURPOSE: Ultrasound examinations of atherosclerotic carotid plaques can be used to calculate risk markers associated with plaque vulnerability. Recent studies demonstrate significant inter-frame variability in risk markers. Here, we investigate risk marker variability in symptomatic plaques and its impact on reclassification of plaque vulnerability, as well as its association with the shape of the temporal variation over the cardiac cycle. METHODS: 56 patients with symptomatic carotid stenosis were included in this study. 88 plaques were identified and the plaque risk markers size (area), echogenicity (gray scale median, GSM) and heterogeneity (coarseness) were measured in all frames of ultrasound B-mode image sequences. Inter-frame variability was quantified using the coefficient of variation (CV). RESULTS: Inter-frame variabilities of the risk markers were area CV 5-8%; GSM CV 4-7%; coarseness CV 8-15% and was in general significantly lower in large as compared to smaller plaques. The variability in GSM risk marker caused a reclassification of vulnerability in 30 to 38% of the plaques. Temporal variations in GSM with a heart rate periodic or drift/trending pattern were found in smaller plaques (< 26 mm2), whereas random pattern was found in larger plaques. In addition, hypoechoic plaques (GSM < 25) were associated with cyclic variation pattern, independent of their size. CONCLUSIONS: Risk marker variability causes substantial reclassification of plaque vulnerability in symptomatic patients. Inter-frame variation and its temporal pattern should be considered in the design of future studies related to risk markers.

Inter-sonographer reproducibility of carotid ultrasound plaque detection using Mannheim consensus in subclinical atherosclerosis.

AIMS: To determine the inter-sonographer reproducibility of carotid ultrasound plaque detection using Mannheim consensus in a subclinical population and evaluate associations related to the reproducibility. METHODS AND RESULTS: Bilateral ultrasound screening for carotid plaques defined by Mannheim consensus was performed on 106 subclinical participants. Two different sonographers scanned the same participant, and reproducibility of plaque detection was measured by Cohens kappa. Associations with reproducibility were evaluated by comparing wall, and plaque characteristics between subjects with plaques identified in one and both scans. In general, the inter-sonographer reproducibility of plaque detection was substantial with a kappa value of 0·70 (95% CI 0·60-0·80). Plaques detected in only one scan had significantly lower plaque area and plaque thickness (6·82 mm2 and 1·45 mm) as compared to plaques detected in both scans (11·65 mm2 and 1·96 mm, P<0·001). CONCLUSION: Minor carotid plaques contribute to decreased reproducibility as compared to large plaques when screening for subclinical atherosclerosis using Mannheim consensus. Using an alternative plaque definition based on plaque thickness >1.5 mm and plaque area >10 mm2 could increase the reproducibility of plaque detection in subclinical atherosclerosis.

Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA): a pragmatic, open-label, randomised controlled trial.

BACKGROUND: Primary prevention of cardiovascular disease often fails because of poor adherence among practitioners and individuals to prevention guidelines. We aimed to investigate whether ultrasound-based pictorial information about subclinical carotid atherosclerosis, targeting both primary care physicians and individuals, improves prevention. METHODS: Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) is a pragmatic, open-label, randomised controlled trial that was integrated within the Västerbotten Intervention Programme, an ongoing population-based cardiovascular disease prevention programme in northern Sweden. Individuals aged 40, 50, or 60 years with one or more conventional risk factors were eligible to participate. Participants underwent clinical examination, blood sampling, and ultrasound assessment of carotid intima media wall thickness and plaque formation. Participants were randomly assigned 1:1 with a computer-generated randomisation list to an intervention group (pictorial representation of carotid ultrasound plus a nurse phone call to confirm understanding) or a control group (not informed). The primary outcomes, Framingham risk score (FRS) and European systematic coronary risk evaluation (SCORE), were assessed after 1 year among participants who were followed up. This study is registered with ClinicalTrials.gov, number NCT01849575. FINDINGS: 3532 individuals were enrolled between April 29, 2013, and June 7, 2016, of which 1783 were randomly assigned to the control group and 1749 were assigned to the intervention group. 3175 participants completed the 1-year follow-up. At the 1-year follow-up, FRS and SCORE differed significantly between groups (FRS 1·07 [95% CI 0·11 to 2·03, p=0·0017] and SCORE 0·16 [0·02 to 0·30, p=0·0010]). FRS decreased from baseline to the 1-year follow-up in the intervention group and increased in the control group (-0·58 [95% CI -0·86 to -0·30] vs 0·35 [0·08 to 0·63]). SCORE increased in both groups (0·13 [95% CI 0·09 to 0·18] vs 0·27 [0·23 to 0·30]). INTERPRETATION: This study provides evidence of the contributory role of pictorial presentation of silent atherosclerosis for prevention of cardiovascular disease. It supports further development of methods to reduce the major problem of low adherence to medication and lifestyle modification. FUNDING: Västerbotten County Council, the Swedish Research Council, the Heart and Lung Foundation, the Swedish Society of Medicine, and Carl Bennet Ltd, Sweden.

Risk Marker Variability in Subclinical Carotid Plaques Based on Ultrasound is Influenced by Cardiac Phase, Echogenicity and Size.

Identification of risk markers based on quantitative ultrasound texture analysis of carotid plaques has the ability to define vulnerable components that correlate with increased cardiovascular risk. However, data describing factors with the potential to influence the measurement variability of risk markers are limited. The aim of this study was to evaluate the influence of electrocardiogram-guided image selection, plaque echogenicity and area on carotid plaque risk markers and their variability in asymptomatic carotid plaques. Plaque risk markers were measured in 57 plaques during three consecutive heartbeats at two cardiac cycle time instants corresponding to the electrocardiogram R-wave (end diastole) and end of T-wave (end systole), resulting in six measurements for each plaque. Risk marker variability was quantified by computing the coefficient of variation (CV) across the three heartbeats. The CV was significantly higher for small plaques (area <15 mm2, 10%) than for large plaques (area >15 mm2, 6%) (p < 0.001) in measurements of area, and the CV for measurements of gray-scale median were higher for echolucent plaques (<40, 15%) than for echogenic plaques (>40, 9%) (p < 0.001). No significant differences were found between systole and diastole for the mean of any risk marker or the corresponding CV value. However, in a sub-analysis, the echolucent plaques were found to have a higher CV during systole compared with diastole. The variability also caused plaque type reclassification in 16% to 25% of the plaques depending on cutoff value. The results of this study indicate that echolucent and small plaques each contribute to increased risk marker variability. Based on these results, we recommend that measurements in diastole are preferred to reduce variation, although we found that it may not be possible to characterize small plaques accurately using contemporary applied risk markers.