Role of Imaging Modalities in the Quantitative Assessment of Atherosclerotic Plaques in the Thoracic Aorta.

AIM: Comparative analysis of the height of atherosclerotic plaques (AP) in the descending thoracic aorta (TA) according to two-dimensional (2D) and three-dimensional (3D) transesophageal echocardiography (TEE), and contrast-enhanced multislice computed tomography (MSCT). MATERIAL AND METHODS: The TA was examined using 2D, 3D TEE and contrast-enhanced MSCT in 34 patients (20 men and 14 women aged 68 [62; 71] years). AP heights were compared using the Bland-Altman method and the Spearman correlation analysis. This was a blinded comparative study which assessed the AP morphometry using each of the radiation modalities without knowing the results of the method being compared. RESULTS: 100 APs were examined in the descending TA. The mean height of all analyzed APs in the descending TA was 2.2 mm [2; 2.7] for 2D TEE, 3.1 mm [2.7; 3.55] for 3D TEE, and 3.05 mm [2.55; 3.55] for MSCT. The AP heights measured with 2D TEE was statistically significantly smaller than the heights of similar APs measured either with 3D TEE or MSCT. The mean difference (bias) was 0.88±0.34 mm between 2D and 3D TEE, and 0.83±0.41 mm between 2D TEE and MSCT. The correlation coefficients for the AP heights were r=0.87 (p<0.001) between 2D and 3D TEE and r=0.86 (p<0.001) between 2D TEE and MSCT. There were no differences in the height of similar APs between 3D TEE and MSCT. CONCLUSION: The three-dimensional reconstruction of AP in the TA by TEE is more accurate for quantitative assessment of AP than a two-dimensional study.

Evaluation of measured and calculated small dense low-density lipoprotein in capillary blood and association with the metabolic syndrome.

BACKGROUND AND AIMS: Small-dense-low-density-lipoprotein cholesterol (sdLDL-C) is proatherogenic and not commonly measured. The aims were to evaluate capillary blood and its stability for sdLDL-C measurement and measure sdLDL-C in patients with metabolic syndrome (MS). METHODS: 182 patients were studied (49 with MS). sdLDL-C was measured by electrophoresis (LipoPrint®), direct measurement (Roche Diagnostics) and Sampson equation. Intima-media thickness (IMT) and presence of atheroma was evaluated. sdLDL-C was compared in paired venous and capillary blood according to CLSI-EP09c (n = 40). sdLDL-C stability was studied after 24 h at room temperature (RT). RESULTS: sdLDL-C in capillary blood and venous blood showed agreement with the direct measurement (bias: 4.17 mg/dL, LOA 95 %:-5.66; 13.99) and estimation (bias:8.12 mg/dL, LOA 95 %:-8.59; 24.82). sdLDL-C is stable in capillary blood for 24 h at RT. The electrophoretic method yielded lower (p < 0.05) sdLDL-C than the equation or direct measurement. Patients with MS had (p < 0.05) higher sdLDL-C (%) than patients without MS. Patients with atheroma plaques had higher sdLDL-C (p < 0.05). Estimated sdLDL-C correlated with IMT (r = 0.259, p < 0.001). CONCLUSIONS: Capillary blood is an alternative to venous blood for sdLDL-C measurement and is stable for 24 h after collection. Estimated and directly measured sdLDL-C associate with the MS being accessible tools for cardiovascular risk assessment.

Prognostic impact of carotid plaque imaging using total plaque area added to SCORE2 in middle-aged subjects: the ARteris Cardiovascular Outcome (ARCO) cohort study.

AIMS: Many cardiovascular events occur in seemingly healthy individuals.We set out to assess the predictive value of atherosclerosis imaging in combination with cardiovascular risk calculators in subjects aged 40-65 years. METHODS: We compared PROCAM (PROspective CArdiovascular Münster study), SCORE (Systematic COronary Risk Evaluation) and SCORE2 with carotid ultrasound (total plaque area, TPA) in subjects without cardiovascular disease. In this prospective cohort study, follow-up was obtained by phone or mail from patients; or from clinical records, if needed. RESULTS: In 2842 subjects (mean age 50±8 years; 38% women), cardiovascular events occurred in 154 (5.4%) of them over an mean follow-up period of 5.9 (range 1-12) years, specifically: 41 cases of AMI (myocardial infarction), 16 strokes, 21 CABG (coronary artery bypass grafting), 41 PTCA (percutaneous transluminal coronary angioplasty) and 35 CAD (coronary artery disease). Mean PROCAM risk was 5±6%, mean SCORE risk was 1.3±1.6% and mean SCORE2 risk was 5±3%. Both for the primary outcome (major adverse cardiovascular events, MACEs, i.e. AMI + strokes) and the secondary outcome (atherosclerotic cardiovascular disease, ASCVD, i.e. MACEs + CABG + CAD + PTCA), hazards increased significantly for TPA tertiles and SCORE2 post-test risk between 6.7 to 12.8 after adjustment for risk factors (age, smoke, sex, systolic blood pressure, lipids, medication) and after adjustment for results from PROCAM, SCORE and SCORE2. Model performance was statistically improved regarding model fit in all models using TPA. Net reclassification improvement for SCORE2 with TPA post-test risk increased significantly by 24% for MACEs (p = 0.01) and 39% for ASCVD (p <0.0001). CONCLUSIONS: Integration of TPA post-test risk into SCORE2 adds prognostic information, supporting the use of carotid ultrasound when assessing ASCVD risk in subjects aged 40-65 years.

[How do I investigate... the vulnerability of a carotid artery plaque in 2024]. / Comment j'explore la vulnérablilité d'une plaque carotidienne en 2024.

Carotid artery atherosclerosis is one of the leading causes of stroke. Even though the association between the risk of stroke and the level of morphological stenosis of a carotid plaque has been known for a long time, growing evidence has since proven necessary to assess the composition of the plaque itself to identify vulnerability predictors. These vulnerable plaques, even more if non-stenosing, may be responsible for a significant - but hard to quantify - proportion of strokes so far classified cryptogenic. As a matter of fact, plaque composition may escape detection and characterisation with classical imaging. Several biomarkers associated with its vulnerability to destabilization and with the risk of stroke such as intraplaque hemorrhage and inflammation are now routinely assessable. After a few pathophysiological reminders and a critical reading of the historical literature concerning carotid artery atherosclerosis management, we will review in this article the imaging techniques that can be used in the routine work-up of a carotid atherosclerotic plaque, with a focus on vessel wall magnetic resonance imaging and contrast enhanced ultrasonography.

L'athérosclérose carotidienne est une des causes les plus fréquentes d'accident ischémique cérébral (AIC). Si la dangerosité d'une plaque d'athérome est historiquement vue uniquement à travers le prisme de la sténose qu'elle engendre, l'évolution des connaissances nous pousse à considérer sa composition à la recherche de facteurs de vulnérabilité. Ces plaques à risque, a fortiori «non sténosantes¼, sont responsables d'une proportion difficilement quantifiable, mais probablement non négligeable d'AIC jusqu'ici considérés cryptogéniques. En effet, ces critères échappent pour beaucoup aux méthodes d'imagerie traditionnelle. Plusieurs propriétés associées à la vulnérabilité de la plaque et au risque d'AIC, principalement l'hémorragie intra-plaque et l'inflammation, sont désormais accessibles en pratique courante. Après quelques rappels physiopathologiques et une lecture critique de la littérature historique de la prise en charge de l'athérome carotidien, nous passerons en revue les différentes techniques d'imagerie utilisables en routine dans la mise au point de la plaque d'athérosclérose, avec un focus pratique sur l'imagerie pariétale vasculaire par résonance magnétique et, dans une moindre mesure, par échographie de contraste.

The relationship between complement C1q and coronary plaque vulnerability based on optical coherence tomography analysis.

To determine the association between complement C1q and vulnerable plaque morphology among coronary artery disease (CAD) patients. We conducted a retrospective observational study of 221 CAD patients admitted to The Second Affiliated Hospital of Xi'an Jiaotong University. Intravascular optical coherence tomography was utilized to describe the culprit plaques' morphology. Using logistic regression analysis to explore the correlation between C1q and vulnerable plaques, and receiver operator characteristic (ROC) analysis assess the predictive accuracy. As reported, the complement C1q level was lower in ACS patients than CCS patients (18.25 ± 3.88 vs. 19.18 ± 4.25, P = 0.045). The low complement-C1q-level group was more prone to develop vulnerable plaques. In lipid-rich plaques, the complement C1q level was positively correlated with the thickness of fibrous cap (r = 0.480, P = 0.041). Univariate and multivariate logistic regression analyses suggested that complement C1q could be an independent contributor to plaques' vulnerability. For plaque rupture, erosion, thrombus, and cholesterol crystals, the areas under the ROC curve of complement C1q level were 0.873, 0.816, 0.785, and 0.837, respectively (P < 0.05 for all). In CAD patients, the complement C1q could be a valuable indicator of plaque vulnerability.

Matrix metallopeptidase 9 contributes to the beginning of plaque and is a potential biomarker for the early identification of atherosclerosis in asymptomatic patients with diabetes.

Aims: To determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) in vitro, early beginning of atherosclerosis in vivo in diabetic mice, and drug naïve patients with diabetes. Methods: Active human MMP9 (act-hMMP9) was added to HCASMCs and the expressions of MCP-1, ICAM-1, and VCAM-1 were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to diabetic KK.Cg-Ay/J (KK) mice. Carotid artery inflammation and atherosclerosis measurements were made at 2 and 10 weeks after treatment. An observational study of newly diagnosed drug naïve patients with type 2 diabetes mellitus (T2DM n=234) and healthy matched controls (n=41) was performed and patients had ultrasound of carotid arteries and some had coronary computed tomography angiogram for the assessment of atherosclerosis. Serum MMP9 was measured and its correlation with carotid artery or coronary artery plaques was determined. Results: In vitro, act-hMMP9 increased gene and protein expressions of MCP-1, ICAM-1, VCAM-1, and enhanced macrophage adhesion. Exogenous act-hMMP9 increased inflammation and initiated atherosclerosis in KK mice at 2 and 10 weeks: increased vessel wall thickness, lipid accumulation, and Galectin-3+ macrophage infiltration into the carotid arteries. In newly diagnosed T2DM patients, serum MMP9 correlated with carotid artery plaque size with a possible threshold cutoff point. In addition, serum MMP9 correlated with number of mixed plaques and grade of lumen stenosis in coronary arteries of patients with drug naïve T2DM. Conclusion: MMP9 may contribute to the initiation of atherosclerosis and may be a potential biomarker for the early identification of atherosclerosis in patients with diabetes. Clinical trial registration: https://clinicaltrials.gov, identifier NCT04424706.

Long-term outcomes of patients with embolic stroke of undetermined source according to subtype.

The prognosis of patients with embolic stroke of undetermined source (ESUS) may vary according to the underlying cause. Therefore, we aimed to divide ESUS into subtypes and assess the long-term outcomes. Consecutive patients with acute ischemic stroke who underwent a comprehensive workup, including transesophageal echocardiography and prolonged electrocardiography monitoring, were enrolled. We classified ESUS into minor cardioembolic (CE) ESUS, arteriogenic ESUS, two or more causes ESUS, and no cause ESUS. Arteriogenic ESUS was sub-classified into complex aortic plaque (CAP) ESUS and non-stenotic (< 50%) relevant artery plaque (NAP) ESUS. A total of 775 patients were enrolled. During 1286 ± 748 days follow-up, 116 major adverse cardiovascular events (MACE) occurred (4.2 events/100 patient-years). Among the ESUS subtypes, CAP ESUS was associated with the highest MACE frequency (9.7/100 patient-years, p = 0.021). Cox regression analyses showed that CAP ESUS was associated with MACE (hazard ratio 2.466, 95% confidence interval 1.305-4.660) and any stroke recurrence (hazard ratio 2.470, 95% confidence interval, 1.108-5.508). The prognosis of ESUS varies according to the subtype, with CAP ESUS having the worst prognosis. Categorizing ESUS into subtypes could improve patient care and refine clinical trials.

[A multiscale carotid plaque detection method based on two-stage analysis].

OBJECTIVE: To develop a method for accurate identification of multiscale carotid plaques in ultrasound images. METHODS: We proposed a two-stage carotid plaque detection method based on deep convolutional neural network (SM-YOLO).A series of algorithms such as median filtering, histogram equalization, and Gamma transformation were used to preprocess the dataset to improve image quality. In the first stage of the model construction, a candidate plaque set was built based on the YOLOX_l target detection network, using multiscale image training and multiscale image prediction strategies to accommodate carotid artery plaques of different shapes and sizes. In the second stage, the Histogram of Oriented Gradient (HOG) features and Local Binary Pattern (LBP) features were extracted and fused, and a Support Vector Machine (SVM) classifier was used to screen the candidate plaque set to obtain the final detection results. This model was compared quantitatively and visually with several target detection models (YOLOX_l, SSD, EfficientDet, YOLOV5_l, Faster R-CNN). RESULTS: SM-YOLO achieved a recall of 89.44%, an accuracy of 90.96%, a F1-Score of 90.19%, and an AP of 92.70% on the test set, outperforming other models in all performance indicators and visual effects. The constructed model had a much shorter detection time than the Faster R-CNN model (only one third of that of the latter), thus meeting the requirements of real-time detection. CONCLUSION: The proposed carotid artery plaque detection method has good performance for accurate identification of carotid plaques in ultrasound images.

Association between monocyte/high-density lipoprotein cholesterol ratio and carotid plaque in postmenopausal women: A cross-sectional study.

To investigate the relationship between carotid plaque and monocyte to high-density lipoprotein cholesterol ratio (MHR) in postmenopausal women. A cross-sectional study was conducted and 214 postmenopausal women who underwent physical examination at the Health Management Center of Heping Hospital affiliated to Changzhi Medical College between August 2018 and August 2022 were enrolled. The subjects were grouped according to the results of carotid ultrasound. The general information, blood pressure, biochemical markers, and routine blood indicators were compared between the 2 groups. Binary logistic regression was performed to analyze the correlation between MHR and carotid plaque in postmenopausal women, and receiver operating characteristics (ROC) curve was used to analyze the predictive value of MHR for carotid plaque in this population. The carotid plaque group showed a lower high-density lipoprotein cholesterol (HDL-C) (1.21 [1.08-1.425] vs 1.29 [1.15-1.445] mmol/L, Z = -2.115, P = .034) and a higher MHR [0.33 ±â€…0.1 vs 0.26 ±â€…0.1, t = -5.756, P < .001] when compared to the no carotid plaque group. After adjusting for potential confounders such height, weight, and HDL-C, binary logistic regression analysis revealed that MHR continued to be an independent risk factor for the formation of carotid plaque in postmenopausal women (odds ratio [OR] = 1.795, 95% confidence interval [CI] 1.198-2.689, P = .005). ROC curve analysis indicated that MHR had a 95% CI of 0.656 to 0.793 in predicting carotid plaque formation, an optimal cut-point of 0.265, and a sensitivity and specificity of 82.2% and 58.9%, respectively. MHR is a distinct risk factor for carotid plaque formation in postmenopausal women.

2024 Consensus Statement on Coronary Stenosis and Plaque Evaluation in CT Angiography From the Asian Society of Cardiovascular Imaging-Practical Tutorial (ASCI-PT).

The Asian Society of Cardiovascular Imaging-Practical Tutorial (ASCI-PT) is an instructional initiative of the ASCI School designed to enhance educational standards. In 2021, the ASCI-PT was convened with the goal of formulating a consensus statement on the assessment of coronary stenosis and coronary plaque using coronary CT angiography (CCTA). Nineteen experts from four countries conducted thorough reviews of current guidelines and deliberated on eight key issues to refine the process and improve the clarity of reporting CCTA findings. The experts engaged in both online and on-site sessions to establish a unified agreement. This document presents a summary of the ASCI-PT 2021 deliberations and offers a comprehensive consensus statement on the evaluation of coronary stenosis and coronary plaque in CCTA.

What Is the Added Value of Carotid CEUS in the Characterization of Atherosclerotic Plaque?

Background and Objectives: Unstable atherosclerotic plaque in the arteries is one of the main risk factors for cerebral ischemia. Duplex ultrasound is a frequently used diagnostic method, but it has some limitations for microvascularization and neovascularization evaluation. The aim of this review was to evaluate the role of the new multiparametric US method-contrast-enhanced ultrasound (CEUS)-in atherosclerotic plaque instability verification. Materials and Methods: Original studies, reviews, and meta-analyses were included in this article. A total of 53 studies were retrieved; 29 were included in this study. Results: Carotid artery CEUS as a part of the multiparametric ultrasound method shows promising results and provides additional characteristics of soft- and high-risk atherosclerotic plaques; it can be advised in clinical practice for patients with carotid artery soft- and high-risk plaques. However, there are some limitations, such as extensive calcinosis with important acoustic shadows in carotid atherosclerotic plaque neovascularization diagnostics by CEUS. The added value of CEUS in the characterization of atherosclerotic plaque is that it indicates regions with high neovascularization and visualizes ulcerations on plaque surfaces, suggestive of increased instability risk.

3-D transesophageal echocardiography aids in assessment of embolic stroke due to aortic atherosclerotic plaque: A case series.

Atherosclerosis is the most common cause of heart disease and stroke. Plaque thickness ≥4 mm in the ascending aorta or aortic arch is strongly correlated with cerebral embolic events and ischemic stroke. However, despite imaging workup, the cause of embolic stroke remains unidentified in many patients. Transesophageal echocardiography (TEE) is the preferred echocardiographic method for the evaluation of cardiac source of emboli. 2D TEE imaging evaluates aortic root and aortic arch in a single plane or two planes with biplane imaging. However, 2D TEE often fails to detect mobile or complex components in the ascending aorta and aortic arch plaques. The routine availability of 3D TEE in current ultrasound systems may significantly improve the assessment of aortic plaques as a potential embolic source. In this case series, we present four consecutive patients with stroke who underwent TEE by a single cardiologist for possible cardioembolic source. Some of these patients may have been labelled as "cryptogenic stroke" or "embolic stroke of undetermined source" (ESUS) due to the presence of insignificant or nonmobile ascending aortic or aortic arch plaques on 2D TEE imaging. In our four consecutive patients with ESUS who underwent TEE by a single operator, 3D TEE showed complex aortic arch plaques with ulceration with mobile components and established these plaques as the likely source of embolic stroke.

The accuracy of detailed analysis of optical coherence tomography in detection of plaque lipid content: dual-imaging study with optical coherence tomography and near-infrared spectroscopy.

BACKGROUND: Lipid-rich plaque covered by a thin fibrous cap (FC) has been identified as a frequent morphological substrate for the development of acute coronary syndrome. Optical coherence tomography (OCT) permits the identification and measurement of the FC. Near-infrared spectroscopy (NIRS) has been approved for detection of coronary lipids. AIMS: We aimed to assess the ability of detailed OCT analysis to identify coronary lipids, using NIRS as the reference method. METHODS: In total, 40 patients with acute coronary syndrome underwent imaging of a non-culprit lesion by both NIRS and OCT. For each segment, the NIRS-derived 4 mm segment with maximal lipid core burden index (maxLCBI4mm) was assessed. OCT analysis was performed using a semi-automated method including measurement of the fibrous cap thickness (FCT) of all detected fibroatheromas. Subsequent quantitative volumetric evaluation furnished FCT, FC surface area (FC SA), lipid arc, and FC (fibrous cap) volume data. OCT features of lipid plaques were compared with maxLCBI4mm. Predictors of maxLCBI4mm >400 was assessed by using univariable and multivariable analysis. RESULTS: OCT features (mean FCT, total FC SA, FC volume, maximal, mean, and total lipid arcs) strongly correlated with the maxLCBI4mm (p = 0.012 for the mean FCT, respectively p < 0.001 for all other aforementioned features). The strongest predictors of maxLCBI4mm >400 were the maximal (p = 0.002) and mean (p = 0.002) lipid arc, and total FC SA (p = 0.012). CONCLUSIONS: We found a strong correlation between the OCT-derived features and NIRS findings. Detailed OCT analysis may be reliably used for detection of the presence of coronary lipids.

In Situ Imaging of GGT and HOBr-Triggered Atherosclerotic Plaque Rupture via Activating the RunX2/Col IV Signaling Pathway.

Calcification and abnormal collagen deposition within blood vessels constitute causative factors for atherosclerotic plaque rupture, and their occurrence is intimately linked with γ-glutamyltranspeptidase (GGT) and hypobromous acid (HOBr). However, the underlying regulatory mechanisms of GGT and HOBr in plaque rupture remain unclear. Hence, we developed a dual-responsive near-infrared (NIR) fluorescent probe (BOC-H) that effectively avoids spectral crosstalk for the in situ visualization of the fluctuations in GGT and HOBr levels during atherosclerotic plaque rupture. We found that both GGT and HOBr contents increase significantly in the calcification models of cells and animals. The overexpressed GGT participated in intracellular oxygen-promoting behavior, which obviously upregulated the expression of RunX2 and Col IV by facilitating H2O2 and HOBr secretion. This process triggered calcification and abnormal collagen deposition within the plaque, which raised the risk of plaque rupture. PM2.5-induced arteriosclerotic calcification models further verified the results that GGT and HOBr accelerate plaque rupture via activation of the RunX2/Col IV signaling pathway. Moreover, the assessment of GGT and HOBr in serum samples from patients with acute myocardial infarction further confirmed the co-regulation of GGT and HOBr in the plaque rupture. Together, our studies highlight the involvement of GGT and HOBr in driving plaque rupture and offer new targets for the prevention and treatment of acute cardiovascular disease.

Tailoring Zinc Ferrite Nanoparticle Surface Coating for Macrophage-Affinity Magnetic Resonance Imaging of Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease characterized by the formation of atherosclerotic plaques, while macrophages as key players in plaque progression and destabilization are promising targets for atherosclerotic plaque imaging. Contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a powerful noninvasive imaging technique for the evaluation of atherosclerotic plaques within arterial walls. However, the visualization of macrophages within atherosclerotic plaques presents considerable challenges due to the intricate pathophysiology of the disease and the dynamic behavior of these cells. Biocompatible ferrite nanoparticles with diverse surface ligands possess the potential to exhibit distinct relaxivity and cellular affinity, enabling improved imaging capabilities for macrophages in atherosclerosis. In this work, we report macrophage-affinity nanoparticles for magnetic resonance imaging (MRI) of atherosclerosis via tailoring nanoparticle surface coating. The ultrasmall zinc ferrite nanoparticles (Zn0.4Fe2.6O4) as T1 contrast agents were synthesized and modified with dopamine, 3,4-dihydroxyhydrocinnamic acid, and phosphorylated polyethylene glycol to adjust their surface charges to be positively, negatively, and neutrally charged, respectively. In vitro MRI evaluation shows that the T1 relaxivity for different surface charged Zn0.4Fe2.6O4 nanoparticles was three higher than that of the clinically used Gd-DTPA. Furthermore, in vivo atherosclerotic plaque MR imaging indicates that positively charged Zn0.4Fe2.6O4 showed superior MRI efficacy on carotid atherosclerosis than the other two, which is ascribed to high affinity to macrophages of positively charged nanoparticles. This work provides improved diagnostic capability and a better understanding of the molecular imaging of atherosclerosis.

Establishment of a hybrid model of atherosclerosis and acute colitis in ApoE-/- mice.

Inflammatory bowel disease (IBD) and atherosclerosis (AS) are both common chronic inflammatory diseases with similar pathophysiological mechanisms. Some studies have shown that IBD patients are at increased risk for early atherosclerosis, myocardial infarction and venous thrombosis. Here we set up a hybrid mouse model associated with atherosclerosis and acute colitis in order to investigate the interplay of the two diseases. We fed ApoE-/- mice with high fat diet to establish atherosclerosis model, and used animal ultrasound machine to detect the artery of mice noninvasively. Then a new hybrid model of atherosclerosis and acute colitis was prepared by drinking water for 7 days. At the end of the experiment, the hybrid model mice showed typically pathological and intuitionistic changes of atherosclerosis and acute colitis. We found the shortened colon length, high histopathological scores of the colon with mucosal erosion and necrosis, hyperlipidemia, a plaque-covered mouse aorta and plaque with foam cells and lipid deposition in the hybrid model group, which proved that the hybrid model was successfully established. At the same time, ultrasonic detection showed that the end-diastolic blood flow velocity and the relative dilation value were decreased, while systolic time / diastolic time, the wall thickness, systolic diameters as well as diastolic diameters were gradually increased, and statistical significance appeared as early as 8 weeks. We clearly described the process of establishing a hybrid model of atherosclerosis and acute colitis, which might provide a repeatable platform for the interaction mechanism exploring and drug screening of atherosclerosis and inflammatory bowel disease in preclinical study.

Multiple plaque ruptures healing assessed by serial optical coherence tomography.

A 30-year-old man with hypertension presented to the emergency department with a 30-minute episode of diaphoresis and chest pain, acute inferior myocardial infarction was diagnosed on electrocardiogram.

Accumulation of Iron Oxide-Based Contrast Agents in Rabbit Atherosclerotic Plaques in Relation to Plaque Age and Vulnerability Features.

Purpose: In this study, a detailed characterization of a rabbit model of atherosclerosis was performed to assess the optimal time frame for evaluating plaque vulnerability using superparamagnetic iron oxide nanoparticle (SPION)-enhanced magnetic resonance imaging (MRI). Methods: The progression of atherosclerosis induced by ballooning and a high-cholesterol diet was monitored using angiography, and the resulting plaques were characterized using immunohistochemistry and histology. Morphometric analyses were performed to evaluate plaque size and vulnerability features. The accumulation of SPIONs (novel dextran-coated SPIONDex and ferumoxytol) in atherosclerotic plaques was investigated by histology and MRI and correlated with plaque age and vulnerability. Toxicity of SPIONDex was evaluated in rats. Results: Weak positive correlations were detected between plaque age and intima thickness, and total macrophage load. A strong negative correlation was observed between the minimum fibrous cap thickness and plaque age as well as the mean macrophage load. The accumulation of SPION in the atherosclerotic plaques was detected by MRI 24 h after administration and was subsequently confirmed by Prussian blue staining of histological specimens. Positive correlations between Prussian blue signal in atherosclerotic plaques, plaque age, and macrophage load were detected. Very little iron was observed in the histological sections of the heart and kidney, whereas strong staining of SPIONDex and ferumoxytol was detected in the spleen and liver. In contrast to ferumoxytol, SPIONDex administration in rabbits was well tolerated without inducing hypersensitivity. The maximum tolerated dose in rat model was higher than 100 mg Fe/kg. Conclusion: Older atherosclerotic plaques with vulnerable features in rabbits are a useful tool for investigating iron oxide-based contrast agents for MRI. Based on the experimental data, SPIONDex particles constitute a promising candidate for further clinical translation as a safe formulation that offers the possibility of repeated administration free from the risks associated with other types of magnetic contrast agents.

Near-Infrared Persistent Luminescence Nanoprobe for Early Detection of Atherosclerotic Plaque.

Atherosclerosis (AS) is a crucial contributor to various cardiovascular diseases (CVDs), which seriously threaten human life and health. Early and accurate recognition of AS plaques is essential for the prevention and treatment of CVD. Herein, we introduce an AS-targeting nanoprobe based on near-infrared (NIR) persistent luminescence nanoparticles (PLNPs), developing a highly sensitive NIR persistent luminescence (PersL) AS plaque imaging technique and successfully realizing early AS plaque detection. The nanoprobe exhibits good monodispersity and regular spherical morphology and also owns exceptional NIR PersL performance upon repetitive irradiation by biological window light. The surface-conjugated antibody (anti-osteopontin) endowed nanoprobe excellent targeting ability to foam cells within plaques. After intravenously injected nanoprobe into AS model mice, the highly sensitive PersL imaging technique can accurately detect AS plaques prior to ultrasonography (US) and magnetic resonance imaging (MRI). Specifically, the NIR PersL imaging reveals AS plaques at the earliest within 2 weeks, with higher signal-to-background ratio (SBR) up to 5.72. Based on this technique, the nanoprobe has great potential for applications in the prevention and treatment of CVD, the study of AS pathogenesis, and the screening of anti-AS drugs.