Radiomics versus Conventional Assessment to Identify Symptomatic Participants at Carotid Computed Tomography Angiography.

INTRODUCTION: Carotid computed tomography angiography (CTA) is routinely used for evaluating the atherosclerotic process. Radiomics allows the extraction of imaging markers of lesion heterogeneity and spatial complexity. These quantitative features can be used as the input for machine learning (ML). Therefore, in this study, we aimed to evaluate the diagnostic performance of radiomics-based ML assessment of carotid CTA data to identify symptomatic patients with carotid artery atherosclerosis. METHODS: In this retrospective study, participants with carotid artery atherosclerosis who underwent carotid CTA and brain magnetic resonance imaging from May 2010 to December 2017 were studied. The participants were grouped into symptomatic and asymptomatic groups according to their recent symptoms (determination of ipsilateral ischemic stroke). Eight conventional plaque features and 2,107 radiomics parameters were extracted from carotid CTA images. A radiomics-based ML model was fitted on the training set, and the radiomics-based ML model and conventional assessment were compared using the area under the curve (AUC) to identify symptomatic participants. RESULTS: After excluding participants with other stroke sources, 120 patients with 148 carotid arteries were analyzed. Of these 148 carotid arteries, 34 (22.97%) were classified into the symptomatic group. Plaque ulceration (odds ratio [OR] = 0.257; 95% confidence interval [CI], 0.094-0.698) and plaque enhancement (OR = 0.305; 95% CI, 0.094-0.988) were associated with the symptomatic status. Twenty radiomics parameters were chosen to be inputs in the radiomics-based ML model. In the identification of symptomatic participants, the discriminatory value of the radiomics-based ML model was significantly higher than that of the conventional assessment (AUC = 0.858 vs. AUC = 0.706, p = 0.021). CONCLUSION: Radiomics-based ML analysis improves the discriminatory power of carotid CTA in the identification of recent ischemic symptoms in patients with carotid artery atherosclerosis.

Evaluation of coronary stenosis versus plaque burden for atherosclerotic cardiovascular disease risk assessment and management.

PURPOSE OF REVIEW: To provide a summary of recent literature on the relative impact of luminal stenosis versus atherosclerotic plaque burden in atherosclerotic cardiovascular disease (ASCVD) risk stratification and management. RECENT FINDINGS: Recent results from both randomized controlled clinical trials as well as observational cohort studies have demonstrated that ASCVD risk is mediated mainly by the extent of atherosclerotic disease burden rather than by the presence of coronary stenosis or inducible ischemia. Although patients with obstructive CAD are generally at higher risk for ASCVD events than patients with nonobstructive CAD, this is driven by a higher plaque burden in those with obstructive CAD. Accordingly, the ASCVD risk for a given plaque burden is similar in patients with and without obstructive CAD. Accompanying these observations are randomized controlled trial data, which show that optimization of medical therapy instead of early revascularization is most important for improving prognosis in patients with stable obstructive CAD. SUMMARY: Emerging evidence shows that atherosclerotic plaque burden, and not stenosis per se, is the main driver of ASCVD risk in patients with CAD. This information challenges the current paradigm of selecting patients for intensive secondary prevention measures based primarily on the presence of obstructive CAD.

Nuclear magnetic resonance-based metabolomic analysis in the assessment of preclinical atherosclerosis in type 1 diabetes and preeclampsia.

AIMS: Evaluate the role of plasma metabolomics in atherosclerosis according to the presence of type 1 diabetes (T1D) or previous preeclampsia. METHODS: We recruited 105 women without cardiovascular disease and last pregnancy ≥5 years previously, divided according to the presence of T1D or previous preeclampsia. Preclinical atherosclerosis was defined as the presence of carotid plaque (intima-media thickness ≥1.5 mm) assessed by ultrasonography. Metabolomics were evaluated by nuclear magnetic resonance (NMR). Bivariate and multivariate-adjusted differences in NMR-metabolomics were evaluated. RESULTS: The participants were 44.9 ± 8.1 years-old; 20% harbored plaques. There were significant differences in lipidic-, energetic- and nitrogen-related metabolites according to the presence of T1D/preeclampsia (p < 0.05). In multivariate-adjusted models (by age, statins, blood pressure and T1D/preeclampsia), only lipidomic-related metabolites were associated with atherosclerosis in the whole sample. However, stronger associations were observed in women with previous preeclampsia (vs. without; per 0.5 mmol/L increments); phosphatidylcholine, OR 4.08 (1.32-27.22); free cholesterol, 5.18 (1.22-21.97); saturated fatty acids, OR 2.99 (1.37-6.48); w-7, OR 2.29 (1.15-4.56); and w-9 fatty acids, OR 1.49 (1.00-2.23). CONCLUSIONS: NMR-metabolomics showed a differential pattern according to the presence of T1D/preeclampsia in relation to preclinical atherosclerosis. Since most of these metabolites mirror lifestyle factors, they could help tailor dietetic advice in high-risk women.

Quantitative and Qualitative Coronary Plaque Assessment Using Computed Tomography Coronary Angiography: A Comparison With Intravascular Ultrasound.

BACKGROUND: To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment. METHODS: Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS. RESULTS: There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06±0.07, p=0.44; Bland-Altman 95% limits of agreement -2.19-2.08 mm3, bias of -0.06mm3) and per vessel (3.1mm3 ± -2.85mm3, p=0.92). In contrast, there was significant difference between automated-software and IVUS per slice (2.3±0.09mm3, p<0.001; 95% LoA -6.78 to 2.25mm3, bias of -2.2mm3) and per vessel (33.04±10.3 mm3, p<0.01). The sensitivity, specificity, positive and negative predictive value of CTCA to detect plaques that had features of echo-attenuation on IVUS was 93.3%, 99.6%, 93.3% and 99.6% respectively. The association of ≥2 high-risk plaque features on CTCA with echo attenuation (EA) plaque features on IVUS was excellent (86.7%, 99.6%, 92.9% and 99.2%). In comparison, the association of high-risk plaque features on CTCA and plaques with echo-lucency on IVUS was only modest. CONCLUSION: Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS.

Comparing the feasibility and accuracy of three-dimensional ultrasound to two-dimensional ultrasound and computed tomography angiography in the assessment of carotid atherosclerosis.

AIMS: Two-dimensional ultrasound (2D-US) is the mainstay imaging technique used to evaluate carotid atherosclerosis. An automated single sweep three-dimensional ultrasound (3D-US) technique became available. We evaluated the feasibility and accuracy of 3D-US in the assessment of carotid plaques compared to those of 2D-US. Carotid computed tomography angiography (CTA) was used as a reference. METHODS AND RESULTS: Among 126 stroke patients who underwent carotid 2D-US, 73 underwent 3D-US and carotid CTA. 3D-US was pursued when there were carotid plaques or when area stenosis was ≥ 20% by 2D-US. Both 2D- and 3D-US images of the carotid arteries were acquired using a dedicated ultrasound system that was equipped with the single sweep volumetric transducer. In total, 266 arteries from 73 patients were selected for comparison of the detection rate of carotid plaques between 2D- and 3D-US. Among the 73 patients, carotid CTA detected 139 plaques. 3D-US demonstrated a higher detection rate of carotid plaques than did 2D-US (108 plaques (77.9%) vs. 70 plaques (50.4%)) when using carotid CTA as a reference standard. Carotid plaque volume (PV) of 133 vessels from 73 patients were quantitatively evaluated using both 3D-US and carotid CTA. Plaque volume of carotid artery was comparable between 3D-US and CTA (148.5 ± 133.0 mm3 vs. 154.1 ± 134.6 mm3 , P = .998, R: 0.9825, P-value for r < .001). CONCLUSION: 3D-US using a single sweep technique was a feasible and accurate method of detecting arterial plaques and assessing plaque volume.

Comprehensive coronary plaque assessment in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Previous studies have assessed the relationship between OSA and coronary artery disease (CAD) using coronary artery calcium score (CAC) measurements. However, limited data are available regarding the association of OSA with non-calcified plaque burden. We therefore aimed to assess the relationship between CAD severity as assessed by coronary computed tomography angiography (CTA) and OSA. Forty-one adult subjects (59 ± 9 years, 15 men) underwent a 256-slice coronary CTA, which was followed by a diagnostic attended cardiorespiratory polygraphy (n = 13) or polysomnography (n = 28). Segment involvement score (SIS), segment stenosis score (SSS) and CAC were used to quantify total CAD burden. Correlation analysis was used to assess potential associations between CAD and OSA. Twenty-two patients were diagnosed with OSA. SIS and SSS were elevated in OSA (2.90 ± 2.78 versus 1.79 ± 2.39 and 4.91 ± 5.94 versus 1.79 ± 4.54, OSA versus controls, SIS and SSS respectively, both p < 0.01) and correlated with OSA severity as measured by the apnea-hypopnea index (AHI, r = 0.41 and 0.43, p < 0.01) and oxygen desaturation index (ODI, r = 0.45 and 0.46, p < 0.01). However, no significant correlation was observed between CAC and OSA. Compared to CAC, SIS and SSS provide additional information on coronary plaque burden in OSA, which shows a significant association with OSA.

Ultrasound assessment of carotid arteries: Current concepts, methodologies, diagnostic criteria, and technological advancements.

Following cardiac disease and cancer, stroke continues to be the third leading cause of death and disability due to chronic disease in the developed world. Appropriate screening tools are integral to early detection and prevention of major cardiovascular events. In a carotid artery, the presence of increased intima-media thickness, plaque, or stenosis is associated with increased risk of a transient ischemic attack or a stroke. Carotid artery ultrasound remains a long-standing and reliable tool in the current armamentarium of diagnostic modalities used to assess vascular morbidity at an early stage. The procedure has, over the last two decades, undergone considerable upgrades in technology, approach, and utility. This review examines in detail the current state and usage of this integrally important means of extracranial cerebrovascular assessment.

Feasibility of Coronary 18F-Sodium Fluoride Positron-Emission Tomography Assessment With the Utilization of Previously Acquired Computed Tomography Angiography.

BACKGROUND: We assessed the feasibility of utilizing previously acquired computed tomography angiography (CTA) with subsequent positron-emission tomography (PET)-only scan for the quantitative evaluation of 18F-NaF PET coronary uptake. METHODS AND RESULTS: Forty-five patients (age 67.1±6.9 years; 76% males) underwent CTA (CTA1) and combined 18F-NaF PET/CTA (CTA2) imaging within 14 [10, 21] days. We fused CTA1 from visit 1 with 18F-NaF PET (PET) from visit 2 and compared visual pattern of activity, maximal standard uptake (SUVmax) values, and target to background ratio (TBR) measurements on (PET/CTA1) fused versus hybrid (PET/CTA2). On PET/CTA2, 226 coronary plaques were identified. Fifty-eight coronary segments from 28 (62%) patients had high 18F-NaF uptake (TBR >1.25), whereas 168 segments had lesions with 18F-NaF TBR ≤1.25. Uptake in all lesions was categorized identically on coregistered PET/CTA1. There was no significant difference in 18F-NaF uptake values between PET/CTA1 and PET/CTA2 (SUVmax, 1.16±0.40 versus 1.15±0.39; P=0.53; TBR, 1.10±0.45 versus 1.09±0.46; P=0.55). The intraclass correlation coefficient for SUVmax and TBR was 0.987 (95% CI, 0.983-0.991) and 0.986 (95% CI, 0.981-0.992). There was no fixed or proportional bias between PET/CTA1 and PET/CTA2 for SUVmax and TBR. Cardiac motion correction of PET scans improved reproducibility with tighter 95% limits of agreement (±0.14 for SUVmax and ±0.15 for TBR versus ±0.20 and ±0.20 on diastolic imaging; P<0.001). CONCLUSIONS: Coronary CTA/PET protocol with CTA first followed by PET-only allows for reliable and reproducible quantification of 18F-NaF coronary uptake. This approach may facilitate selection of high-risk patients for PET-only imaging based on results from prior CTA, providing a practical workflow for clinical application.

Neutrophil-Lymphocyte ratio in cardiovascular disease risk assessment / Relação Neutrófilo-Linfócito na avaliação de risco de doença cardiovascular

The development of cardiovascular diseases with atherosclerotic origin is associated with a severe inflammatory process. Neutrophils and lymphocytes are cells sensitive to this type of disorder and their ratio, known as the NLR (neutrophil/lymphocyte ratio), has shown to be useful in clinical practice. The aim of this study was to assess the role of NLR in cardiovascular disease risk assessment. We carried out a literature review in the PubMed databases searching for articles published between 2001 to 2017 and found that NLR is in fact a useful marker for cardiovascular disease. Using NLR in patients at cardiovascular risk would be useful to delineate the prognosis of patients with this disease pattern

Intravascular Ultrasound and Angioscopy Assessment of Coronary Plaque Components in Chronic Totally Occluded Lesions.

BACKGROUND: The in vivo lesion morphologies and plaque components of coronary chronic total occlusion (CTO) lesions remain unclear.Methods and Results:We investigated 57 consecutive CTO lesions in 57 patients with stable angina pectoris undergoing elective percutaneous coronary intervention with intravascular ultrasound (IVUS) and coronary angioscopy (CAS) examination. All CTO lesions were classified according to the proximal angiographic lumen pattern; tapered-type (T-CTO) and abrupt-type (A-CTO). The differences in the intracoronary images of these lesion types were evaluated according to the location within the CTO segment. A total of 35 lesions (61.4%) were T-CTO. T-CTO lesions had higher frequencies of red thrombi (proximal 71.4%; middle 74.3%; distal 31.4%; P<0.001) and bright-yellow plaques (yellow-grade 2-3) (48.6%; 74.3%; 2.9%; P<0.001) at the proximal or middle than at the distal subsegment; A-CTO lesions showed no significant differences among the 3 sub-segments. At the middle subsegment, T-CTO lesions showed higher frequencies of positive remodeling (51.4% vs. 18.2%, P=0.01) and bright-yellow plaques (74.3% vs. 13.6%, P<0.001) compared with A-CTO lesions. Multivariate analysis identified bright-yellow plaque as an independent predictor (odds ratio, 7.25; 95% confidence interval, 1.25-42.04; P=0.03) of the occurrence of periprocedural myocardial necrosis. CONCLUSIONS: The combination of IVUS and CAS analysis may be useful for identifying lesion morphology and plaque components, which may help clarify the pathogenetic mechanism of CTO lesions.

Assessment of multidirectional movements of the common carotid artery in atherothrombotic stroke using dimensional speckle tracking carotid ultrasonography: A prospective, controlled cohort study.

AIM: We aimed to explore the relevance of multidirectional movements of the common carotid artery in atherothrombotic stroke. METHODS AND RESULTS: We prospectively enrolled 69 patients with atherothrombotic stroke (stroke group) and 69 age-matched and sex-matched controls (control group) who underwent carotid ultrasonography. Based on the speckle tracking technique, circumferential and radial movements of the common carotid artery were analyzed from transverse and longitudinal B-mode images of the common carotid artery. Peak longitudinal and radial displacements, strain, and strain rate were measured. Mean age of the overall population was 64 ± 11 years, and 57% (78 patients) were men. In the transverse image, circumferential strain was significantly lower in the stroke group than in the control group (5.6 ± 1.6 vs 4.2 ± 1.7, P < .001). In multivariate logistic regression analysis, circumferential strain was independently associated with stroke (odds ratio: 0.60, P = .001). Compared with conventional risk factors, as well as carotid intima-media thickness and carotid plaque, the addition of a strain parameter appeared to improve discrimination of a stroke event (area under the receiver operating characteristic curve: 0.65 and 0.75 vs 0.84, respectively; P < .05 for both). CONCLUSIONS: Circumferential strain of the common carotid artery might serve as a novel surrogate marker of atherothrombotic stroke. Multidirectional strain imaging of the common carotid artery may provide more information than conventional carotid ultrasonography and identify clinical risk factors for risk stratification of an acute stroke event.

Subclinical cardiovascular disease assessment and its relationship with cardiovascular risk SCORE in a healthy adult population: A cross-sectional community-based study.

INTRODUCTION: The aim of this study is to evaluate the relationship and the accuracy of SCORE (Systematic Coronary Risk Evaluation Project) risk correlated to multiple methods for determining subclinical cardiovascular disease (CVD) in a healthy population. MATERIAL AND METHODS: This cross-sectional study included 120 completely asymptomatic subjects, with an age range 35-75 years, and randomly selected from the general population. The individuals were evaluated clinically and biochemical, and the SCORE risk was computed. Subclinical atherosclerosis was assessed by various methods: carotid ultrasound for intima-media thickness (cIMT) and plaque detection; aortic pulse wave velocity (aPWV); echocardiography - left ventricular mass index (LVMI) and aortic atheromatosis (AA); ankle-brachial index (ABI). RESULTS: SCORE mean value was 2.95±2.71, with 76% of subjects having SCORE <5. Sixty-four percent of all subjects have had increased subclinical CVD changes, and SCORE risk score was correlated positively with all markers, except for ABI. In the multivariate analysis, increased cIMT and aPWV were significantly associated with high value of SCORE risk (OR 4.14, 95% CI: 1.42-12.15, p=0.009; respectively OR 1.41, 95% CI: 1.01-1.96, p=0.039). A positive linear relationship was observed between 3 territories of subclinical CVD (cIMT, LVMI, aPWV) and SCORE risk (p<0.0001). There was evidence of subclinical CVD in 60% of subjects with a SCORE value <5. CONCLUSIONS: As most subjects with a SCORE value <5 have subclinical CVD abnormalities, a more tailored subclinical CVD primary prevention program should be encouraged.

Three-Dimensional and Conventional Carotid Ultrasound for Assessment of Carotid Plaque in a Stroke Patient: A Simple Way to Validate Findings.

Single-sweep automated 3-D ultrasound is a new imaging modality for the assessment of carotid plaque. Its most important application is the measurement of the plaque volume. To our knowledge, to date there is not a widely accepted "gold standard" to validate 3-D plaque volume measurement. We compared the findings of 2-dimensional and 3-D carotid ultrasound imaging with those of postsurgical plaque specimen using a simple method.

Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation: IVUS Assessment of Cardiac Allograft Vasculopathy.

BACKGROUND: Although cardiac allograft vasculopathy (CAV) is typically characterized by diffuse coronary intimal thickening with pathological vessel remodeling, plaque instability may also play an important role in CAV. Previous studies of native coronary atherosclerosis have demonstrated associations between attenuated-signal plaque (ASP), plaque instability, and adverse clinical events. OBJECTIVES: This study's aim was to characterize the association between ASP and long-term mortality post-heart transplantation. METHODS: In 105 heart transplant recipients, serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in the first 50 mm of the left anterior descending artery. The ASP score was calculated by grading the measured angle of attenuation from grades 0 to 4 (specifically, 0°, 1° to 90°, 91° to 180°, 181° to 270°, and >270°) at 1-mm intervals. The primary endpoint was all-cause death or retransplantation. RESULTS: At 1-year post-transplant, 10.5% of patients demonstrated ASP progression (newly developed or increased ASP). Patients with ASP progression had a higher incidence of acute cellular rejection during the first year (63.6% vs. 22.3%; p = 0.006) and tendency for greater intimal growth (percent intimal volume: 9.2 ± 9.3% vs. 4.4 ± 5.3%; p = 0.07) than those without. Over a median follow-up of 4.6 years, there was a significantly lower event-free survival rate in patients with ASP progression at 1-year post-transplant compared with those without. In contrast, maximum intimal thickness did not predict long-term mortality. CONCLUSIONS: ASP progression appears to reflect chronic inflammation related to acute cellular rejection and is an independent predictor of long-term mortality after heart transplantation. Serial assessments of plaque instability may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

[Simultaneous magnetic resonance angiographic and tomographic assessment of atherosclerotic plaques of carotid arteries with paramagnetic contrasting by cyclomang].

The authors studied a possibility of simultaneously performing magnetic resonance (MR) angiography of carotid arteries and contrast-enhanced MR tomography of atherosclerotic plaques of carotid arteries. We examined a total of 16 patients presenting with disseminated atherosclerosis and 8 patients of the control group. Quadrature coils for examination of the head were used in order to sequentially perform MR tomography of the brain, MR angiography of carotid arteries and MR tomography of atherosclerotic plaques of carotid arteries with contrasting by 0.5M cyclomang. Angiography was carried out by means of the technique of 3D GR FFE of rapid gradient echo (TR/TE/FA/ST=10 ms/2.7 ms/20°/1.5 mm). MR tomography of the carotid arteries bifurcation was performed in the T1-weighted spin-echo mode: TR=500-900 ms, TE=10 ms, slice sickness 1-3 mm into the matrix 256x256 voxels, with the voxel size measuring 0.2x0.2x2 mm. The average time of passing of the paramagnetic through the blood vessels of the cerebral hemispheres in the control group amounted to 4.23±0.14 s for the left hemisphere and to 4.27±0.15 s for the right one. The mean time of bolus passing in patients with predominantly unilateral stenosis of the internal carotid artery amounted to 4.89±0.23 on the affected side, equalling 4.56±0.19 s on the unaffected side (p>0.05). In bilateral lesions these indices for the left and right hemispheres amounted to 4.98±0.21 s and 5.01±0.16 s (p>0.05), respectively. Contrast-enhanced MR angiography with cyclomang made it possible in all cases to visualize the localization and character of stenosis. The index of stenosis degree calculated for MR-angiogram highly significantly correlated with the indices of the ultrasonographic examination performed according to the ECST technique both for cases of unilateral (r=0.87, p<0.05) and cases of bilateral stenotic lesion (r=0.85, p<0.05). Inhomogeneous soft plaques with high content of lipids had high values of the enhancement index on contrasting--1.26±0.07, whereas hard fibrous avascular plaques--1.09±0.04 (p<0.05). The total time of the examination amounted to 41±5 min while performing time-fly MR-angiography and to 29±5 min without it. A conclusion was made that simultaneous MR angiography and contrast-enhanced (with Mn-paramagnetic) MR tomography of carotid arteries is possible and appropriate within the framework of a single study using quadratic coil for the head.

Plaque Assessment in the Management of Patients with Asymptomatic Carotid Stenosis.

The continued occurrence of stroke despite advances in medical therapy for asymptomatic carotid stenosis (ACS) strongly indicates that individual response to medical therapy may vary widely. This article reviews the literature that identifies MR imaging and ultrasound plaque features which are seen in patients at increased risk of future cardiovascular events. Imaging can identify plaque phenotype that is the most amendable to intensive medical therapy. There is also good evidence that plaque imaging can measure the individual response to medical therapy and the lack of response identifies a high-risk group of ACS patients.

Carotid artery plaque assessment using quantitative expansive remodeling evaluation and MRI plaque signal intensity.

OBJECTIVE: Plaque characteristics and morphology are important indicators of plaque vulnerability. MRI-detected intraplaque hemorrhage has a great effect on plaque vulnerability. Expansive remodeling, which has been considered compensatory enlargement of the arterial wall in the progression of atherosclerosis, is one of the criteria of vulnerable plaque in the coronary circulation. The purpose of this study was risk stratification of carotid artery plaque through the evaluation of quantitative expansive remodeling and MRI plaque signal intensity. METHODS: Both preoperative carotid artery T1-weighted axial and long-axis MR images of 70 patients who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS) were studied. The expansive remodeling ratio (ERR) was calculated from the ratio of the linear diameter of the artery at the thickest segment of the plaque to the diameter of the artery on the long-axis image. Relative plaque signal intensity (rSI) was also calculated from the axial image, and the patients were grouped as follows: Group A = rSI ≥ 1.40 and ERR ≥ 1.66; Group B = rSI< 1.40 and ERR ≥ 1.66; Group C = rSI ≥ 1.40 and ERR < 1.66; and Group D = rSI < 1.40 and ERR < 1.66. Ischemic events within 6 months were retrospectively evaluated in each group. RESULTS: Of the 70 patients, 17 (74%) in Group A, 6 (43%) in Group B, 7 (44%) in Group C, and 6 (35%) in Group D had ischemic events. Ischemic events were significantly more common in Group A than in Group D (p = 0.01). CONCLUSIONS: In the present series of patients with carotid artery stenosis scheduled for CEA or CAS, patients with plaque with a high degree of expansion of the vessel and T1 high signal intensity were at higher risk of ischemic events. The combined assessment of plaque characterization with MRI and morphological evaluation using ERR might be useful in risk stratification for carotid lesions, which should be validated by a prospective, randomized study of asymptomatic patients.

The Additive Value of Femoral Ultrasound for Subclinical Atherosclerosis Assessment in a Single Center Cohort of 962 Adults, Including High Risk Patients with Rheumatoid Arthritis, Human Immunodeficiency Virus Infection and Type 2 Diabetes Mellitus.

BACKGROUND: Presence of femoral atheromatic plaques, an emerging cardiovascular disease (CVD) biomarker additional to carotid plaques, is poorly investigated in conditions associating with accelerated atherosclerosis such as Rheumatoid Arthritis (RA), Human Immunodeficiency Virus (HIV) infection and Type 2 Diabetes Mellitus (T2DM). OBJECTIVE/METHODS: To assess the frequency of femoral/carotid subclinical atheromatosis phenotypes in RA, HIV and T2DM and search for each disease-specific probability of either femoral and/or carotid subclinical atheromatosis, we examined by ultrasound a single-center cohort of CVD-free individuals comprised of consecutive non-diabetic patients with RA (n=226) and HIV (n=133), T2DM patients (n=109) and non-diabetic individuals with suspected/known hypertension (n=494) who served as reference group. RESULTS: Subclinical atheromatosis--defined as local plaque presence in at least on arterial bed--was diagnosed in 50% of the overall population. Among them, femoral plaques only were found in 25% of either RA or HIV patients, as well as in 16% of T2DM patients and 35% of reference subjects. After adjusting for all classical CVD risk factors, RA and HIV patients had comparable probability to reference group of having femoral plaques, but higher probability (1.75; 1.17-2.63 (odds ratio; 95% confidence intervals), 2.04; 1.14-3.64, respectively) of having carotid plaques, whereas T2DM patients had higher probability to have femoral and carotid plaques, albeit, due to their pronounced dyslipidemic profile. CONCLUSION: RA and HIV accelerate predominantly carotid than femoral. A "two windows" carotid/femoral, rather than carotid alone ultrasound, screening improves substantially subclinical atheromatosis detection in patients at high CVD risk.

Quantitative assessment of binding affinities for nanoparticles targeted to vulnerable plaque.

Recent successes in targeted immune and cell-based therapies have driven new directions for pharmaceutical research. With the rise of these new therapies there is an unfilled need for companion diagnostics to assess patients' potential for therapeutic response. Targeted nanomaterials have been widely investigated to fill this niche; however, in contrast to small molecule or peptide-based targeted agents, binding affinities are not reported for nanomaterials, and to date there has been no standard, quantitative measure for the interaction of targeted nanoparticle agents with their targets. Without a standard measure, accurate comparisons between systems and optimization of targeting behavior are challenging. Here, we demonstrate a method for quantitative assessment of the binding affinity for targeted nanoparticles to cell surface receptors in living systems and apply it to optimize the development of a novel targeted nanoprobe for imaging vulnerable atherosclerotic plaques. In this work, we developed sulfated dextran-coated iron oxide nanoparticles with specific targeting to macrophages, a cell type whose density strongly correlates with plaque vulnerability. Detailed quantitative, in vitro characterizations of (111)In(3+) radiolabeled probes show high-affinity binding to the macrophage scavenger receptor A (SR-A). Cell uptake studies illustrate that higher surface sulfation levels result in much higher uptake efficiency by macrophages. We use a modified Scatchard analysis to quantitatively describe nanoparticle binding to targeted receptors. This characterization represents a potential new standard metric for targeted nanomaterials.