Atherosclerotic Plaque Characteristics Research Articles

Machine Learning From Quantitative Coronary Computed Tomography Angiography Predicts Ischemia And Impaired Myocardial Blood Flow

Introduction: Atherosclerotic plaque characteristics may influence the hemodynamic consequences of coronary lesions. This study sought to assess the performance of a machine learning (ML) score integrating coronary computed tomography angiography (CCTA)-based quantitative plaque features for the prediction of ischemia by invasive fractional flow reserve (FFR) and impaired myocardial blood flow (MBF) by [15O]H2O positron emission tomography (PET).

Differential Effects Of Apixaban Versus Rivaroxaban On Atherosclerosis Plaque Progression In Patients With Atrial Fibrillation

Introduction: Direct anticoagulants (DOAC) have been associated with less calcification and coronary plaque progression in previous trials, since they don’t interfere with vitamin K metabolism. To date, whether different DOACs are associated with differential effects on coronary plaque burden and progression, is not known. We evaluated the 12-month effects of apixaban vs rivaroxaban on atherosclerotic plaque characteristics and vascular morphology in patients with atrial fibrillation, as assessed by quantitative coronary computed tomographic angiography (CCTA).

Artificial Intelligence Guided Evaluation Of Atherosclerosis And Vessel Morphology In Non-ST Elevation Myocardial Infarction From Cardiac Computed Tomography (AI NSTEMI-CCTA)

Introduction: Cardiac computed tomography angiography (CCTA) is evolving in low to intermediate risk Non-ST Elevation Myocardial Infarction (NSTEMI), however quantitative assessment of atherosclerosis and vessel morphology from CCTA has been rarely performed. This study evaluates atherosclerotic plaque characteristics (APC) via a novel artificial intelligence (AI) guided approach in NSTEMI patients with CCTA.

Acute Coronary Syndromes In Patients With Zero Coronary Calcium: ICONIC Trial Analysis

Introduction: High-risk atherosclerosis may be demonstrated in the absence of coronary artery calcium (CAC) and may lead to acute coronary syndromes (ACS). The purpose of this study was to evaluate quantitative atherosclerotic plaque characteristics (APCs) and cardiovascular events derived from cardiac computed tomography angiography (CCTA) prior to the development of ACS.

Coronary Atherosclerotic Plaque Characteristics By Ultra-high-resolution Cardiac Ct Compared To Conventional Image Reconstructions In Patients With Severe Coronary Artery Disease

Introduction: Evaluation of the coronary atherosclerosis by conventional CT angiography (CTA) in calcified or stented lesions is hindered by the partial volume effect of dense calcium or metal. Ultra-high-resolution CT (UHRCT) with twice the spatial resolution may allow superior plaque characterization and quantification.

Functional assessment of coronary plaques using CT based hemodynamic simulations: Current status, technical principles and clinical value

AbstractIn recent years, coronary computed tomography angiography (CCTA) has emerged as an accurate and safe non-invasive imaging modality in terms of detecting and excluding coronary artery disease (CAD). In the latest European Society of Cardiology Guidelines CCTA received Class I recommendation for the evaluation of patients with stable chest pain with low to intermediate clinical likelihood of CAD. Despite its high negative predictive value, the diagnostic performance of CCTA is limited by the relatively low specificity, especially in patients with heavily calcified lesions. The discrepancy between the degree of stenosis and ischemia is well established based on both invasive and non-invasive tests. The rapid evolution of computational flow dynamics has allowed the simulation of CCTA derived fractional flow reserve (FFR-CT), which improves specificity by combining anatomic and functional information regarding coronary atherosclerosis. FFR-CT has been extensively validated against invasively measured FFR as the reference standard. Due to recent technological advancements FFR-CT values can also be calculated locally, without offsite processing. Wall shear stress (WSS) and axial plaque stress (APS) are additional key hemodynamic elements of atherosclerotic plaque characteristics, which can also be measured using CCTA images. Current evidence suggests that WSS and APS are important hemodynamic features of adverse coronary plaques. CCTA based hemodynamic calculations could therefore improve prognostication and the management of patients with stable CAD.

Frequency-Domain Optical Coherence Tomography for Intracranial Atherosclerotic Stenosis: Feasibility, Safety, and Preliminary Experience.

Background: Despite advances in non-invasive imaging, the characterization of atherosclerotic plaque remains superior with frequency-domain optical coherence tomography (FD-OCT) in the clinical coronary and experimental cerebrovascular literature. An assessment of the feasibility and safety of FD-OCT for intracranial atherosclerotic stenosis (ICAS) is desirable.Methods: We analyzed a cohort of all consecutive FD-OCT evaluations for ICAS performed at our institution from April 2017 to August 2018 (16 months) in patients who suffered from transient ischemic attack (TIA) or non-disabling stroke despite optimal medical management within 90 days of admission attributable to angiographically verified 70–99% stenosis of an intracranial artery.Results: Thirty-three patients harboring 36 lesions with an average age of (57.6 ± 7.1) years (male sex 27 cases) comprising nine cases of lesions located within the anterior circulation and 24 cases within the posterior circulation were identified. Of the 33 patients with 36 lesions, the FD-OCT imaging catheter detected 35/36 (97%) lesions except in one case in which the FD-OCT catheter failed to navigate excessively tortuous vessels, and FD-OCT images in 27 patients (81.8%) were finally obtained successful, where the target lesion was fully visible, and image quality under at least one pullback was graded 2 or 3. There were no symptomatic complications. Blood flow was the most common artifact encountered (51.9%).Conclusion: FD-OCT is safe and feasible for the assessment of ICAS in the anterior and posterior circulation. The use of diagnostic interferometry will have to be weighed against its cost, and these preliminary findings should be verified by prospective large-scale studies.

Comparative study on hemodynamic environments around patient-specific carotid atherosclerotic plaques with different symmetrical features

Atherosclerotic plaque near the carotid sinus is a key risk factor for ischemic stroke. Although disturbed hemodynamic environments around atherosclerotic plaque had been investigated in many studies, the effect of their symmetrical features, especially longitudinal asymmetrical characteristics, had not been comparatively studied. In this study, three-dimensional carotid bifurcation models were established based on CT images of three patients with 50% stenosis and with different symmetrical features of carotid atherosclerotic plaques including concentric plaque, eccentric plaque, or eccentric longitudinal asymmetrical plaque. A healthy subject was chosen as the control. Wall shear stress (WSS) and oscillating shear index in the regions of upstream, downstream, downstream shoulders and regions around the point of maximum stenosis were analyzed. The results indicated that the maximum WSS around the eccentric longitudinal asymmetrical plaque were 8.6 times larger than that of the eccentric plaque and 1.9 times larger than that of the concentric plaque. And the distributions of WSS and OSI around the eccentric longitudinal asymmetric plaque were more disordered than those of the others. Our results highlighted the risk of the eccentric longitudinal asymmetrical plaque on plaque development and rupture and might provide a new index for evaluating the development of atherosclerosis.

Lipoprotein(a) levels and atherosclerotic plaque characteristics in the carotid artery: The Plaque at RISK (PARISK) study

Background and aimsLipoprotein(a) is an independent risk factor for cardiovascular disease and recurrent ischemic stroke. Lipoprotein(a) levels are known to be associated with carotid artery stenosis, but the relation of lipoprotein(a) levels to carotid atherosclerotic plaque composition and morphology is less known. We hypothesize that higher lipoprotein(a) levels and lipoprotein(a)-related SNPs are associated with a more vulnerable carotid plaque and that this effect is sex-specific. MethodsIn 182 patients of the Plaque At RISK study we determined lipoprotein(a) concentrations, apo(a) KIV-2 repeats and LPA SNPs. Imaging characteristics of carotid atherosclerosis were determined by MDCTA (n = 161) and/or MRI (n = 171). Regressions analyses were used to investigate sex-stratified associations between lipoprotein(a) levels, apo(a) KIV-2 repeats, and LPA SNPs and imaging characteristics. ResultsLipoprotein(a) was associated with presence of lipid-rich necrotic core (LRNC) (aOR = 1.07, 95% CI: 1.00; 1.15), thin-or-ruptured fibrous cap (TRFC) (aOR = 1.07, 95% CI: 1.01; 1.14), and degree of stenosis (β = 0.44, 95% CI: 0.00; 0.88). In women, lipoprotein(a) was associated with presence of intraplaque hemorrhage (IPH) (aOR = 1.25, 95% CI: 1.06; 1.61). In men, lipoprotein(a) was associated with degree of stenosis (β = 0.58, 95% CI: 0.04; 1.12). Rs10455872 was significantly associated with increased calcification volume (β = 1.07, 95% CI: 0.25; 1.89) and absence of plaque ulceration (aOR = 0.25, 95% CI: 0.04; 0.93). T3888P was associated with absence of LRNC (aOR = 0.36, 95% CI: 0.16; 0.78) and smaller maximum vessel wall area (β = -10.24, 95%CI: -19.03; -1.44). ConclusionsIn patients with symptomatic carotid artery stenosis, increased lipoprotein(a) levels were associated with degree of stenosis, and IPH, LRNC, and TRFC, known as vulnerable plaque characteristics, in the carotid artery. T3888P was associated with lower LRNC prevalence and smaller maximum vessel wall area. Further research in larger study populations is needed to confirm these results.

Sex-Specific Plaque Signature: Uniqueness of Atherosclerosis in Women.

Cardiovascular disease is a leading cause of morbidity and mortality in both men and women, although there are notable differences in presentation between men and women. Atherosclerosis remains the predominant driver of coronary heart disease in both sexes; however, sex differences in atherosclerosis should be investigated further to understand clinical manifestations between men and women. There are sex differences in the prevalence, progression, and prognostic impact of atherosclerosis. Furthermore, developing evidence demonstrates unique differences in atherosclerotic plaque characteristics between men and women on both noninvasive and invasive imaging modalities. Coronary microvascular dysfunction may be present even if no obstructive lesions are found. Most importantly, non-obstructive coronary artery disease is associated with a heightened risk of future adverse cardiovascular events and should not be ignored. The distinct plaque signature in women should be recognized, and optimal preventive strategies should be performed for both sexes.

Finasteride Reduces Total Cholesterol in LDLR-Deficient Mice

Abstract Objectives Androgen imbalance is associated with cardiovascular disease risk but the exact impact on lipid and glucose profile is unknown. Finasteride (FIN) prevents the conversion of testosterone to its active metabolite dihydrotestosterone (DHT) by inhibiting the type II 5alpha-reductase. Our objective is to examine the impact of FIN on cardiovascular disease risk. We hypothesize that FIN delays the progression of atherosclerosis by ameliorating hyperglycemia and dyslipidemia. Methods We used the low-density lipoprotein receptor (LDLR)-deficient (Ldlr−/−) mouse model as a widely regarded model of atherosclerotic plaque development in rodents. Four-week-old male mice (n = 9–15/group) were fed a Western-diet containing 41% fat +0.3% cholesterol with increasing doses of FIN (10 mg/kg, 100 mg/kg, and 1000 mg/kg diet) for 12 weeks. Littermates fed Western-diet without FIN were used as a control group. A week before tissue harvest, mice were subjected to a glucose tolerance test (GTT). At the end of the experiment, mice were sacrificed, and their tissue and body weights were analyzed. A total cholesterol assay was performed at 0, 4, 8, and 12 weeks. Results We examined prostate size, whose growth is DHT dependent, as an indicator of the effect of finasteride in our experimental model. We observed a dose-dependent effect of FIN on prostate size for all the doses (P < .0001), indicating FIN had a physiological impact on these mice. No changes in food intake or circulating transaminase levels were observed, discarding any evidence of food intolerability or hepatic toxicity. FIN did not alter GTT among experimental groups or any other biometric parameter. However, we observed a significant reduction in body weight gain in the high dose group (P = .0027) in comparison to the other experimental groups. Total cholesterol levels at the time of the sacrifice were significantly reduced in the high dose group (P < .0001) in comparison to the other experimental groups. Future experiments will include atherosclerotic plaque characterization of both size and composition. Conclusions Our findings suggest that a high dose of FIN is associated with a reduction of total plasma cholesterol and body weight in Ldlr−/− mice. Funding Sources USDA multistate hatch project (W4002)

Abstract P154: Leisure-Time Physical Activity, Sedentary Behavior, And Carotid Atherosclerosis Morphology: The ARIC Carotid-MRI Study

Introduction: Studies suggest that greater physical activity (PA) may be associated with favorable carotid artery characteristics, while greater time spent in sedentary behavior (SB) may be a potential risk factor for atherosclerosis development and progression. We evaluated the association between leisure-time PA and SB in midlife and their temporal patterns with carotid atherosclerotic morphology measured by MRI. Methods: ARIC Carotid-MRI participants (n=1582, mean age: 53 years, 43% male, 18% Black) with self-reported assessments of PA and SB at visits 1 (1987-1989) and 3 (1993-1995), who participated in the Carotid MRI substudy in 2004-2006 were included. Self-reported leisure-time PA was categorized based on the American Heart Association’s Life Simple 7 categorization of ideal, intermediate, or poor PA. SB was ascertained based on participant report of how often they watched television during leisure-time, and categorized as low [“never”/ “seldom”], medium [“sometimes”], or high [“often”/“very often”]. To measure persistent PA and SB, we examined participants who reported the same level of PA (n=849) or SB (n=954) at both visits 1 and 3. Carotid MRI using a 1.5T scanner quantified internal carotid artery wall thickness, lipid core, and calcification measures. Weighted analyses accounted for the sampling design allowing for generalizability to the visit 1 ARIC population. Multivariable linear and logistic regression were used for continuous and categorical outcomes, respectively. All models were adjusted for demographic, behavioral, and lifestyle factors. Results: Though no clear trends were observed for PA, higher levels of SB were associated with a greater odds of lipid core presence and lower odds of calcification (Table). Similar trends were observed for the persistence analyses, though none were statistically significant. Conclusions: PA and SB may influence atherosclerotic plaque characteristics. SB and lack of PA may have different measurable effects on plaque morphology.

A deep learning-based model for characterization of atherosclerotic plaque in coronary arteries using optical coherence tomography images.

Coronary artery events are mainly associated with atherosclerosis in adult population, which is recognized as accumulation of plaques in arterial wall tissues. Optical Coherence Tomography (OCT) is a light-based imaging system used in cardiology to analyze intracoronary tissue layers and pathological formations including plaque accumulation. This state-of-the-art catheter-based imaging system provides intracoronary cross-sectional images with high resolution of 10-15µm. But interpretation of the acquired images is operator dependent, which is not only very time-consuming but also highly error prone from one observer to another. An automatic and accurate coronary plaque tagging using OCT image post-processing can contribute to wide adoption of the OCT system and reducing the diagnostic error rate. In this study, we propose a combination of spatial pyramid pooling module with dilated convolutions for semantic segmentation to extract atherosclerotic tissues regardless of their types and training a sparse auto-encoder to reconstruct the input features and enlarge the training data as well as plaque type characterization in OCT images. The results demonstrate high precision of the proposed model with reduced computational complexity, which can be appropriate for real-time analysis of OCT images. At each step of the work, measured accuracy, sensitivity, specificity of more than 93% demonstrate high performance of the model. The main focus of this study is atherosclerotic tissue characterization using OCT imaging. This contributes to wide adoption of the OCT imaging system by providing clinicians with a fully automatic interpretation of various atherosclerotic tissues. Future studies will be focused on analyzing atherosclerotic vulnerable plaques, those coronary plaques which are prone to rupture.

Visual Scale as a Non-Invasive Method for Evaluation of Risk and Severity of Coronary Atherosclerosis.

Aim To evaluate quantitative and qualitative characteristics of atherosclerotic plaques (ASP) in carotid arteries (CA) and femoral arteries (FA) and to use these data for developing a visual scale (VS) for noninvasive diagnosis and determination of severity of coronary atherosclerosis.Material and methods This study included 216 patients (115 men and 101 women) aged 24 to 87 years (mean age, 61.5±10.73 years). All patients underwent coronary angiography (CAG) for detecting and determining severity of CA atherosclerosis and duplex scanning (DS) for detecting atherosclerosis of CA and FA.Results Analysis of ultrasound parameters of ASP in CA and FA showed that the maximal ASP height, moderate stenosis and maximal stenosis of the arterial bed had higher predictive values than other ultrasound parameters. These parameters were used for forming diagnostic complexes, on the basis of which two individual VSs for CA and FA were developed. Based on the high prognostic value of both scales, they were combined into one that was named VSCOMB. A ROC analysis determined cut-off points of the VSCOMB for diagnosis of CA atherosclerosis of various severity. VSCOMB scores >4 indicated pronounced CA atherosclerosis with sensitivity of 86.1 % and specificity of 87.5 % whereas VSCOMB scores ≤4 excluded it. Thus, VSCOMB score 0-1 indicated the absence of CA atherosclerosis; score 2-4 indicated the presence of subclinical CA atherosclerosis; and score >4 indicated severe CA atherosclerosis.Conclusion A VSCOMB was developed that includes a set of ultrasound parameters for CA and FA and is useful for noninvasive diagnosis of CA atherosclerosis of various severity. Simple and convenient use of VSCOMB allows it to be used at the screening stage to detect subclinical CA atherosclerosis and to prevent its progression.

Shear-Wave Elastography Enables Identification of Unstable Carotid Plaque

Shear-wave elastography (SWE) is a novel ultrasound technique for quantifying tissue elasticity. The aim of this study was to identify differences in atherosclerotic plaque elasticity measured using SWE among individuals with symptomatic, asymptomatic progressive and asymptomatic stable carotid plaques. Consecutive patients from the Atherosclerotic Plaque Characteristics Associated with a Progression Rate of the Plaque and a Risk of Stroke in Patients with the Carotid Bifurcation Plaque Study were screened for this research. Neurosonography examination of carotid arteries was performed to identify plaque stenosis of ≥50% using B-mode ultrasound and SWE imaging to measure the mean, maximal and minimal elasticity. The set consisted of 97 participants—74 with asymptomatic stable stenosis, 12 with asymptomatic progressive stenosis and 11 with symptomatic stenosis. The mean elasticity in the asymptomatic stable plaque group was significantly higher than in the asymptomatic progressive (52.2 vs. 30.4 kPa; p < 0.001) and symptomatic (52.2 vs. 36.4 kPa; p = 0.033) plaque groups. No significant differences were found between asymptomatic progressive and symptomatic (p > 0.1) plaque groups. Asymptomatic stable, asymptomatic progressive and symptomatic plaques did not differ in echogenicity, calcifications, homogeneity, occurrence of ulcerated surface, or intra-plaque hemorrhage (p > 0.05 in all cases). SWE was a helpful modality for differentiating between stable and unstable atherosclerotic plaques in carotid arteries.

Prevalence and Characterization of Subclinical Coronary Atherosclerotic Plaque with CT among Individuals with HIV: Results from the Canadian HIV and Aging Cohort Study

Background People living with HIV (PLWH) have a higher risk of myocardial infarction. Coronary atherosclerotic plaque CT characterization helps to predict cardiovascular risk. Purpose To measure CT characteristics of coronary plaque in PLWH without known cardiovascular disease and healthy volunteers without HIV. Materials and Methods In this prospective study, noncontrast CT (all participants, n = 265) was used for coronary artery calcium (CAC) scoring in asymptomatic PLWH and healthy volunteers without HIV, without known cardiovascular disease, from 2012 to 2019. At coronary CT angiography (n = 233), prevalence, frequency, and volume of calcified, mixed, and noncalcified plaque were measured. Poisson regressions were used with adjustment for cardiovascular risk factors. Results There were 181 PLWH (mean age, 56 years ± 7; 167 men) and 84 healthy volunteers (mean age, 57 years ± 8; 65 men) evaluated by using noncontrast CT. CT angiography was performed in 155 PLWH and 78 healthy volunteers. Median 10-year Framingham risk score was not different between PLWH and healthy volunteers (10% vs 9%, respectively; P = .45), as were CAC score (odds ratio [OR], 1.06; 95% CI: 0.58, 1.94; P = .85) and overall plaque prevalence (prevalence ratio, 1.07; 95% CI: 0.86, 1.32; P = .55) after adjustment for cardiovascular risk. Noncalcified plaque prevalence (prevalence ratio, 2.5; 95% CI: 1.07, 5.67; P = .03) and volume (OR, 2.8; 95% CI: 1.05, 7.40; P = .04) were higher in PLWH. Calcified plaque frequency was reduced in PLWH (OR, 0.6; 95% CI: 0.40, 0.91; P = .02). Treatment with protease inhibitors was associated with higher volume of overall (OR, 1.8; 95% CI: 1.09, 2.85; P = .02) and mixed plaque (OR, 1.6; 95% CI: 1.04, 2.45; P = .03). Conclusion Noncalcified coronary plaque burden at coronary CT angiography was two- to threefold higher in asymptomatic people living with HIV without known cardiovascular disease compared with healthy volunteers without HIV. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lai in this issue.

Circulatory markers of immunity and carotid atherosclerotic plaque

Background and aimsWe aimed to determine the association of circulatory markers of innate and adaptive immunity with carotid atherosclerotic plaque characteristics. MethodsIn 1602 participants from the population-based Rotterdam Study with subclinicalcarotid atherosclerosis, blood sampling was performed to determine granulocyte, platelet, monocyte (innate immunity) and lymphocyte (adaptive immunity) counts, from which the granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], monocyte-to-lymphocyte ratio [MLR] and systemic immune-inflammation index [SII] were calculated. All participants underwent carotid MRI for evaluation of plaque characteristics. Plaque size (stenosis >30%, maximum plaque thickness) and plaque composition (presence of intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], and calcification) were assessed. Using linear and logistic regression models, the association of innate and adaptive immunity markers with plaque size and plaque components, adjusting for relevant confounders, was assessed. ResultsHigher levels of granulocytes were significantly associated with larger plaque thickness (mean difference [Ln (mm)] per Ln increase granulocyte count [95% CI]: 0.06 [0.02; 0.10]). Conversely, more lymphocytes related with smaller maximum plaque thickness (mean difference [Ln (mm)] per Ln increase lymphocyte count: 0.09 [-0.14;-0.04]) and a lower prevalence of IPH (odds ratio per Ln increase lymphocyte count: 0.60 [0.37; 0.97]). Moreover, all ratio measures were associated with larger plaque thickness, of which the MLR also associated with more frequent LRNC (odds ratio per Ln increase MLR: 1.26 [1.02; 1.56]). ConclusionsThe innate immunity links to larger plaques, whilst the adaptive immunity seems to relate to smaller plaques and a lower frequency of IPH. These results suggest that an imbalance in innate and adaptive immunity may play a role in the vulnerability of carotid atherosclerotic plaques.

Peripheral Vascular Resistance in Cerebral Arteries in Patients With Carotid Atherosclerosis - Substudy Results of the Atherosclerotic Plaque Characteristics Associated With a Progression Rate of the Plaque and a Risk of Stroke in Patients With the Carotid Bifurcation Plaque Study (ANTIQUE).

Transcranial color-coded duplex sonography (TCCS) enables to measure blood flow characteristics in cerebral vessels, including vascular resistance and pulsatility. The study aims to identify factors influencing pulsatility (PI) and resistance (RI) indices measured using TCCS in patients with carotid atherosclerosis. Self-sufficient patients with atherosclerotic plaque causing 20-70% carotid stenosis were consecutively enrolled to the study. All patients underwent duplex sonography of cervical arteries and TCCS with measurement of PI and RI in the middle cerebral artery, neurological, and physical examinations. Following data were recorded: age, gender, height, weight, body mass index, systolic and diastolic blood pressure, occurrence of current and previous diseases, surgery, medication, smoking, and daily dose of alcohol. Univariant and multivariant logistic regression analysis were used for identification of the factors influencing RI and PI. Totally 1863 subjects were enrolled to the study: 139 healthy controls (54 males, age 55.52 ± 7.05 years) in derivation cohort and 1724 patients (777 males, age 68.73 ± 9.39 years) in validation cohort. The cut off value for RI was 0.63 and for PI 1.21. Independent factors for increased RI/PI were age (odds ratio [OR]=1.108/1.105 per 1 year), occurrence of diabetes mellitus (OR=1.767/2.170), arterial hypertension (OR=1.700 for RI only), width of the carotid plaque (OR=1.260 per 10% stenosis for RI only), and male gender (OR=1.530 for PI only; P ˂.01 in all cases). The independent predictors of increased cerebral arterial resistance and/or pulsatility in patients with carotid atherosclerosis were age, arterial hypertension, diabetes mellitus, carotid plaque width, and male gender.

Targeting Nanostrategies for Imaging of Atherosclerosis

Despite the progress in cardiovascular research, atherosclerosis still represents the main cause of death worldwide. Clinically, the diagnosis of Atherosclerotic Cardiovascular Disease (ASCVD) relies on imaging methodologies including X-ray angiography and computed tomography (CT), which however still fails in the identification of patients at high risk of plaque rupture, the main cause of severe clinical events as stroke and heart attack. Magnetic resonance imaging, which is characterized by very high spatial resolution, could provide a better characterization of atherosclerotic plaque (AP) anatomy and composition, aiding in the identification of “vulnerable” plaques. In this context, hydrogel matrices, which have been demonstrated able to boost relaxometric properties of Gd-based contrast agents (CAs) by the effect of Hydrodenticity, represent a valuable tool towards the precision imaging of ASCVD improving the performance of this class of CAs while reducing systemic toxicity. In particular, hydrogel nanoparticles encapsulating Gd-DTPA can further contribute to providing CA-specific accumulation in the AP by nanoparticle surface decoration triggering an active targeting of the AP with the overall effect of allowing an earlier and more accurate diagnosis. In this work, we tested crosslinked Hyaluronic Acid Nanoparticles (cHANPs) in the complex environment of human atherosclerotic plaque. In addition, the surface of cHANPs was decorated with the antibody anti-CD36 (Ab36-cHANPs) for the active targeting of AP-associated macrophages. Results demonstrate that the Hydrodenticity of cHANPs and Ab36-cHANPs is preserved in this complex system and, preliminarily, that interaction of these probes with the AP is present.

Association of Type 2 Diabetes Mellitus and Glycemic Control With Intracranial Plaque Characteristics in Patients With Acute Ischemic Stroke.

Type 2 diabetes mellitus (T2DM) has shown to be associated with carotid plaque vulnerability. However, the impact of T2DM on intracranial artery atherosclerosis is not well-understood. To evaluate the association of diabetes and glycemic control with intracranial atherosclerotic plaque characteristics identified by three-dimensional contrast enhanced MR vessel wall imaging in patients after acute ischemic stroke. Prospective. Two hundred and eighty-eight symptomatic patients with acute ischemic stroke due to intracranial atherosclerotic plaque. T1 WI volume isotropic turbo spin-echo acquisition sequence at 3.0 T. Clinical profiles, blood biomarkers, the number of intracranial plaques, plaque enhanced score, and the features (location, luminal stenotic rate, intraplaque hemorrhage, length, burden, enhancement grade, and ratio) of culprit plaque (defined as the most stenotic lesion ipsilateral to the ischemic event) and nonculprit plaque were analyzed by three radiologists. Analysis of variance (ANOVA), Shapiro-Wilk normality test, Levene's test, ANOVA with Bonferroni post-hoc test, Kruskal Wallis H test with subsequent pairwise comparisons, chi-square with Bonferroni post-hoc test, generalized linear regression, Pearson correlation test, Kendall's W and intra-class correlation coefficient. Two hundred and twenty-five participants (age 60 ± 10 years, 58.7% male) with 958 intracranial plaques were included. More intracranial plaques were found in the T2DM group than the non-T2DM group (4.80 ± 2.22 vs. 3.60 ± 1.78, P < 0.05). Patients with poorly-controlled T2DM exhibited higher culprit plaque enhancement ratio than patients with well-controlled T2DM and non-T2DM (2.32 ± 0.61 vs. 1.60 ± 0.62 and 1.39 ± 0.39; respectively, P < 0.05). After adjusting for other clinical variables, T2DM was independently associated with increased intracranial plaque number (β=0.269, P < 0.05), and HbA1c level was independently associated with culprit plaque enhancement ratio (β=0.641, P < 0.05) in multivariate analysis. T2DM is associated with an increased intracranial plaque number. Higher HbA1c is associated with stronger plaque enhancement. 3D contrast enhanced MR vessel wall imaging may help better understand the association of T2DM and glycemic control with intracranial plaque. 1 TECHNICAL EFFICACY STAGE: 3.