Plaque Rupture Research Articles

Accuracy of dynamic stress CT myocardial perfusion in patients with suspected non-ST elevation myocardial infarction.

Coronary CT angiography (CCTA) and dynamic stress CT myocardial perfusion (CT-MPI) are established modalities in the analysis of patients with chronic coronary syndromes. Their role in patients with suspected non-ST elevation myocardial infarction (NSTEMI) is unknown. CCTA with CT-MPI might assist in the triage of NSTEMI patients to the Cath lab. We investigated the correlation of significant epicardial lesions by CT-MPI in addition to CCTA compared to invasive coronary angiography (ICA) with fractional flow reserve (FFR) in patients with NSTEMI. Twenty NSTEMI patients scheduled for ICA were enrolled in this study with planned ICA. CCTA and CT-MPI was performed pre-ICA. For each coronary artery, the presence or absence of significant lesions was interpreted by CCTA with CT-MPI, using an FFR of ≤ 0.8 or angiographic culprit (stenosis > 90%, suspected plaque rupture) as reference. The main outcome was the per-vessel correlation. Sixteen out of 20 patients had a culprit lesion that required immediate revascularization. CCTA with ≥ 50% stenosis demonstrated a per vessel sensitivity and specificity for the detection of significant stenosis of respectively 100% (95% CI: 86-100%) and 75% (95% CI: 58-88%). CCTA with CT-MPI showed a lower sensitivity 90% (95% CI: 70-99%) but higher specificity of 100% (95% CI: 90-100%). CCTA with CT-MPI exhibits a strong correlation for identifying significant CAD in patients with NSTEMI. Thereby, it might assist in the triage of ICA in NSTEMI patients.

Emerging nanoprobes for the features visualization of vulnerable atherosclerotic plaques

AbstractAtherosclerosis (AS) is a major cause of cardiovascular disease. In particular, the unpredictable rupture of vulnerable atherosclerotic plaques (VASPs) can cause serious cardiovascular events such as myocardial infarction, stroke, and even sudden death. Therefore, early evaluation of the vulnerability of atherosclerotic plaques is of great importance. However, clinical imaging techniques are only marginally useful in the presence of severe anatomical structural changes, making it difficult to evaluate plaque vulnerability at an early stage. With the development of molecular imaging and nanotechnology, specific nanoprobes constructed for the pathological features of VASPs have attracted much attention for their ability to visualize VASPs early and noninvasively at the cellular and molecular levels. Here, we outline the pathological features of VASPs, analyze the superiority and limitations of current clinical imaging techniques, introduce the rational design principles of nanoprobes, and systematically summarize the application of nanoprobes to visualize the features of VASPs at the cellular and molecular levels. In addition, we discussed the prospects and urgent challenges in this field, and we believe it will provide new ideas for the early and accurate diagnosis of cardiovascular diseases.

Simulating atherosclerotic plaque mechanics using polyvinyl alcohol (PVA) cryogel artery phantoms, ultrasound imaging and inverse finite element analysis.

The aim of this study is to demonstrate the potential of polyvinyl alcohol phantoms to simulate atherosclerotic features. In addition, a testing and simulation framework is developed for full PVA vessel material characterization using ring tensile testing and inflation testing combined with non-invasive ultrasound imaging and computational modelling. Strain stiffening behavior was observed in PVA through ring tensile tests, particularly at high (n=6) freeze-thaw cycles. Inflation testing of bi-layered phantoms featuring lipid pool inclusions demonstrated high strains at shoulder regions. The application of an inverse finite element framework successfully recovered boundaries and determined the shear moduli for the PVA wall to lie within the range 27 kPa to 53 kPa. The imaging-modelling framework presented facilitates the use and characterization of arterial mimicking phantoms to further explore plaque rupture. It also shows translational potential for non-invasive mechanical characterization of atherosclerotic plaques to improve the identification of clinically relevant metrics of plaque vulnerability.

Coronary CT Angiography Radiomics for Identifying Coronary Artery Plaque Vulnerability: A Systematic Review

Background/objectives: Acute coronary syndrome (ACS) is a major global health issue primarily caused by the rupture or erosion of vulnerable coronary plaques. Non-invasive identification of these plaques through coronary computed tomography angiography (CCTA) can be improved with radiomics, which extracts and analyses quantitative features from medical images. This systematic review aims to comprehensively evaluate the literature surrounding the role of radiomics in assessing coronary plaques via CCTA. Methods: A systematic search of Medline, EMBASE, and Web of Science was conducted up to July 2024. Nine studies met the inclusion criteria, and their methodological quality was assessed using the radiomic quality score (RQS) and the QUADAS-2 tool. Results: All studies that evaluated radiomic models for plaque vulnerability reported area under the curve (AUC) values exceeding 0.7, indicating at least modest diagnostic performance. In the four studies that made direct comparisons, radiomic models consistently outperformed conventional CCTA markers. However, RQS scores ranged from 2.7% to 41.7%, reflecting variability in study quality and underscoring the need for more robust validation. Conclusions: Radiomics has the potential to enhance CCTA-based identification of vulnerable coronary plaques, offering a promising non-invasive approach to predicting major adverse cardiovascular events. However, the current body of research is limited by the lack of external validation, reliance on small, single-centre retrospective studies, and methodological inconsistencies, which impact the generalisability and reproducibility of findings. Future research should prioritise prospective, multi-centre studies with standardised protocols and rigorous validation frameworks to effectively incorporate radiomics into clinical practice.

The Role of Platelets in Atherosclerosis: A Historical Review.

Atherosclerosis is a chronic, multifactorial inflammatory disorder of large and medium-size arteries, which is the leading cause of cardiovascular mortality and morbidity worldwide. Although platelets in cardiovascular disease have mainly been studied for their crucial role in the thrombotic event triggered by atherosclerotic plaque rupture, over the last two decades it has become clear that platelets participate also in the development of atherosclerosis, owing to their ability to interact with the damaged arterial wall and with leukocytes. Platelets participate in all phases of atherogenesis, from the initial functional damage to endothelial cells to plaque unstabilization. Platelets deposit at atherosclerosis predilection sites before the appearance of manifest lesions to the endothelium and contribute to induce endothelial dysfunction, thus supporting leukocyte adhesion to the vessel wall. In particular, platelets release matrix metalloproteinases, which interact with protease-activated receptor 1 on endothelial cells triggering adhesion molecule expression. Moreover, P-selectin and glycoprotein Ibα expressed on the surface of vessel wall-adhering platelets bind PSGL-1 and β2 integrins on leukocytes, favoring their arrest and transendothelial migration. Platelet-leukocyte interactions promote the formation of radical oxygen species which are strongly involved in the lipid peroxidation associated with atherosclerosis. Platelets themselves actively migrate through the endothelium toward the plaque core where they release chemokines that modify the microenvironment by modulating the function of other inflammatory cells, such as macrophages. While current antiplatelet agents seem unable to prevent the contribution of platelets to atherogenesis, the inhibition of platelet secretion, of the release of MMPs, and of some specific pathways of platelet adhesion to the vessel wall may represent promising future strategies for the prevention of atheroprogression.

Mechanistic insights into the regression of atherosclerotic plaques.

Atherosclerosis is a major contributor to cardiovascular diseases and mortality globally. The progression of atherosclerotic disease results in the expansion of plaques and the development of necrotic cores. Subsequent plaque rupture can lead to thrombosis, occluding blood vessels, and end-organ ischemia with consequential ischemic injury. Atherosclerotic plaques are formed by the accumulation of lipid particles overloaded in the subendothelial layer of blood vessels. Abnormally elevated blood lipid levels and impaired endothelial function are the initial factors leading to atherosclerosis. The atherosclerosis research has never been interrupted, and the previous view was that the pathogenesis of atherosclerosis is an irreversible and chronic process. However, recent studies have found that the progression of atherosclerosis can be halted when patients' blood lipid levels are reversed to normal or lower. A large number of studies indicates that it can inhibit the progression of atherosclerosis lesions and promote the regression of atherosclerotic plaques and necrotic cores by lowering blood lipid levels, improving the repair ability of vascular endothelial cells, promoting the reverse cholesterol transport in plaque foam cells and enhancing the ability of macrophages to phagocytize and clear the necrotic core of plaque. This article reviews the progress of research on the mechanism of atherosclerotic plaque regression. Our goal is to provide guidance for developing better therapeutic approaches to atherosclerosis by reviewing and analyzing the latest scientific findings.

Abstract 4136597: Atherosclerotic plaque healing as a marker of plaque vulnerability: Insight from intracoronary polarization-sensitive optical frequency domain imaging

Background: Collagen is the major extracellular matrix that imparts mechanical strength to fibrous caps covering fibroatheromas. Intracoronary polarimetry with polarization-sensitive (PS) optical frequency domain imaging (OFDI) measures polarization properties, such as birefringence and depolarization (Figure 1). Birefringence is elevated in collagen and collagen-synthesizing smooth muscle cells, while depolarization is increased by the presence of macrophages and lipid/necrotic cores. Purpose: This study aimed to investigate polarimetric signatures of coronary lesions with healed coronary plaques (HCP) in patients with ACS and chronic coronary syndrome (CCS). Furthermore, we aimed to investigate diagnostic value for birefringence and depolarization of ACS culprit lesions discriminating from CCS target lesions. Methods: We conducted a single center prospective registry of intracoronary PS-OFDI imaging in patients with coronary artery disease (n = 50). A total of 862 OFDI frames selected from culprit or target lesions were analyzed. Coronary plaque phenotypes were assessed using conventional OFDI imaging. HCP was defined as plaques with one or more layers of different optical density and a clear demarcation from underlying components on intensity images. Birefringence and depolarization of the newer intima was measured in cross-sectional images. Birefringence and depolarization of ACS- and CCS-lesions were compared using a generalized estimating equation model. Receiver operating characteristic (ROC) analysis was used to investigate the diagnostic performance of polarimetric signatures for identifying ACS-lesions. Results: Compared to CCS-lesions, ACS-lesions featured significantly higher lipid-burden index and maximum lipid arc (both p < 0.05). Compared to the CCS-lesions, ACS-lesions exhibited significantly lower birefringence (p < 0.05) and higher depolarization (p < 0.05). In the ROC analysis for differentiating ACS-lesions from CCS-lesions, area under the curves (AUC) for birefringence and depolarization were 0.712 and 0.672, respectively. In the multivariable ROC analysis in diagnosing ACS lesions, combination of birefringence with depolarization improved the AUC to 0.755 (p ＝ 0.025). Conclusions: Intracoronary polarimetry provides quantitative assessment of plaque composition in patients. Further research is warranted to investigate whether birefringence can serve as a marker of healing failure following plaque rupture and erosion.

Abstract 4120821: Electrochemical Impedance Spectroscopy Unmasks High-Risk Atherosclerotic Features in Human Coronary Artery Disease

Background: Coronary plaque rupture remains the prominent mechanism of myocardial infarction. Accurate identification of rupture-prone plaque may improve clinical management. This study assessed the discriminatory performance of electrochemical impedance spectroscopy (EIS) in human cardiac explants to detect high-risk atherosclerotic features that portend rupture risk. Methods: In this single-center, prospective study, n=26 cardiac explants were collected for EIS interrogation of the three major coronary arteries. Vessels in which advancement of the EIS catheter without iatrogenic plaque disruption was rendered impossible were not assessed. N=61 vessels underwent EIS measurement and histological analyses. Plaques were dichotomized according to previously established high rupture-risk parameter thresholds. Diagnostic performance was determined via receiver operating characteristic areas-under-the-curve (AUC). Results: Necrotic cores were identified in n=19 vessels (median area 1.53 mm 2 ) with median fibrous cap thickness of 62 μm. Impedance was significantly greater in plaques with necrotic core area ≥1.75 mm 2 vs <1.75 mm 2 (19.8±4.4 kΩ vs 7.2±1.0 kΩ, P =0.019), fibrous cap thickness ≤65 μm vs >65 μm (19.1±3.5 kΩ vs 6.5±0.9 kΩ, P =0.004), and ≥20 macrophages per 0.3 mm-diameter high-power field (HPF) vs <20 macrophages per HPF (19.8±4.1 kΩ vs 10.2±0.9 kΩ, P=0.002). Impedance identified necrotic core area ≥1.75 mm 2 , fibrous cap thickness ≤65 μm, and ≥20 macrophages per HPF with AUCs of 0.889 (95% CI: 0.716–1.000) ( P =0.013), 0.852 (0.646—1.000) ( P =0.025), and 0.835 (0.577—1.000) ( P =0.028), respectively. Further, phase delay discriminated severe stenosis (≥70%) with an AUC of 0.767 (0.573—0.962) ( P =0.035). Conclusions: EIS discriminates high-risk atherosclerotic features that portend plaque rupture in human coronary artery disease and may serve as a complementary modality for angiography-guided atherosclerosis evaluation.

Abstract 4136274: A Case of Myocardial Infarction with Non-obstructive Coronary Arteries (MINOCA) Complicated by a Ventricular Septal Defect (VSD)

Case: A 69-year-old woman with a history of hypertension and tobacco use disorder presented with acute chest pain. The patient was found to have classic anterior ST elevation myocardial infarction (STEMI) pattern on electrocardiogram (ECG) with high-sensitivity troponin of 12,772 ng/L and was taken emergently to the catheterization laboratory. Coronary angiography showed tortuous coronary vessels though without evidence of obstructive coronary artery disease, plaque rupture, ulceration, dissection, or vasospasm. Transthoracic echocardiogram showed an apical ventricular septal defect (VSD) with normal left ventricular systolic function of 60%. Cardiac computed tomography (CT), confirmed a discrete apical VSD that was 7.93 mm in diameter and multiple small VSDs distally in the septum. Right heart catheterization revealed severe left-to-right shunting with a ratio of pulmonary blood flow to systemic blood flow (Qp:Qs) of 2.8. Early surgical repair of the apical VSD was pursued despite known high operative risk given the hemodynamic significance of the shunt. The patient developed ongoing hemodynamic instability from cardiogenic shock with inability to ween from intra-aortic balloon pump (IABP). Unfortunately, because of the location of the residual VSDs and elevated panel-reactive antibody testing of 98%, the patient was deemed to not be a candidate for percutaneous closure or heart transplantation, respectively. Discussion: An acquired ventricular septal defect (VSD) is a rare and catastrophic complication of myocardial infarction, typically with a culprit obstructive coronary artery lesion identified on coronary angiography. Acquired VSDs in myocardial infarction with nonobstructive coronary arteries (MINOCA) is an even more rare phenomenon. Possible causes include low flow, inflammation, intimal disruption, or vasospasm of coronary arteries. Our case highlights that MINOCA can present with life-threatening complications similar to obstructive STEMI. The timing of intervention and treatment approach of acquired VSDs remains an area of debate. The life-threatening effects of VSDs make it critical to manage in a multidisciplinary manner involving advanced imagers, interventional cardiologists, cardiothoracic surgeons, and heart failure specialists. This case emphasizes the importance of maintaining a high index of suspicion for abnormal coronary anatomy, even in patients with MINOCA, and prompt interdisciplinary decision making to reduce mortality.

Abstract 4132291: Assessing the Efficacy of Preventive Percutaneous Coronary Intervention vs Optimal Medical Therapy for the Treatment of Vulnerable Plaque: A Meta-analysis

Introduction: Rupture and thrombosis of lipid-rich atherosclerotic plaques (vulnerable plaques) contributes to majority of acute coronary syndrome (ACS). Current guidelines recommend optimal medical therapy (OMT) for stabilization of vulnerable plaques. Recent evidence of preventive percutaneous intervention (PCI) as a targeted treatment shows improvement in outcomes in these patients. Hypothesis/Goals/Aims: We aim to evaluate the efficacy of preventive percutaneous coronary intervention (PCI) compared to optimal medical therapy (OMT) for treatment of non-vulnerable plaque within five years of follow up from available selected randomized controlled trials (RCTs). Methods: PubMed, Cochrane, OVID, and NIH Clinical Trials were searched for RCTs evaluating preventive PCI compared to standard of care medical therapy. All trials reported primary common endpoints as death from cardiac cause and myocardial infarction (MI). Secondary outcomes included all-cause mortality, any revascularization, hospitalization for unstable and progressive angina, and composite death (any cause, MI, or any revascularization). Sub analyses for secondary outcomes were included if measured by RCT. A fixed effect model with Mantel-Haenszel statistical method was used to calculate risk ratios, Z scores, and a 95% confidence interval. Results: Ten RCTs (n=15955 patients) were included. Preventive PCI of vulnerable plaques revealed a significant benefit in lowering incidence of MI (RR: 0.86 [0.77, 0.86], p=0.01) and death from cardiac cause (RR: 0.73 [0.62, 0.86], p=0.004). Similarly, patients undergoing preventive PCI had a lower incidence of hospitalization for unstable or progressive angina (RR: 0.75 [0.62, 0.91], p<0.0001) and composite death (RR: 0.55 [0.46, 0.67], p<0.001). No difference was noted in all-cause mortality. Incidence of revascularization had a significant benefit with OMT therapy compared to preventive PCI (RR: 1.84 [1.75, 1.94], p<0.0001). Conclusion: Preventive PCI in vulnerable plaque demonstrates cardiovascular benefit as a result from lower incidence of MI, death from cardiac cause, composite death and fewer hospitalization for unstable or progressive angina.

High-risk features in non-culprit lesions and clinical outcome after NSTEMI versus STEMI.

Complete non-culprit (NC) revascularization may help reduce recurrent events after NSTEMI, especially if NC lesions would harbor high-risk plaque features similar to STEMI. The study aimed to assess differences in fractional flow reserve (FFR)-negative NC plaque morphology in patients presenting with NSTEMI versus STEMI and assess the association of high-risk plaque morphology and clinical outcome. In the prospective PECTUS-obs study, 438 patients presenting with myocardial infarction (MI) underwent optical coherence tomography (OCT) of all FFR-negative intermediate NC lesions. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE, all-cause mortality, non-fatal MI or unplanned revascularization) at two-year follow-up. Four hundred and twenty patients had at least one analyzable OCT, including 203 (48.3%) with NSTEMI and 217 (51.7%) with STEMI. The prevalence of high-risk plaques (HRP), including thin-cap fibroatheromas (TCFA), plaque rupture and thrombus, was comparable between groups. MACE occurred in 29 (14.3%) NSTEMI patients and 16 (7.4%) STEMI patients (Punivariable=0.025 and Pmultivariable=0.270). Incidence of MACE was numerically higher among patients with HRP, irrespective of the clinical presentation at index (Pinteraction=0.684). Among high-risk plaque criteria, plaque rupture was associated with MACE in both NSTEMI (p<0.001) and STEMI (p=0.020). Presence of NC HRP is comparable between NSTEMI and STEMI and leads to numerically higher event rates in both. These results call for additional research on complete revascularization in NSTEMI and treatment of HRP.

Teriparatide administration is osteoanabolic but does not impact atherosclerotic plaque calcification and progression in a mouse model of menopause

Menopause exacerbates osteoporosis and increases the risk of atherosclerotic plaque rupture, leading to cardiovascular mortality. Osteoporotic women are increasingly treated with teriparatide (TPTD, 1–34 parathyroid hormone), one of the few treatments that stimulate bone formation. Despite the fact that atherosclerotic plaque calcification is a hallmark of plaque development, the impact of TPTD administration on plaque calcification remain unclear. In this context, we sought to determine the effects of TPTD administration on atherosclerosis in ovariectomized (OVX) apolipoprotein E deficient mice (ApoE−/−), as a model of postmenopausal osteoporosis. OVX ApoE−/− mice, fed a high fat, high cholesterol diet to induce atherosclerosis, received either vehicle or TPTD daily injections (40 μg/kg/d) for 4 or 10 weeks, at which points plaques are respectively weakly and heavily calcified. After sacrifice, bone remodeling was evaluated by serum markers and bone histomorphometry. Bone architectural parameters were measured by μCT. Aortic plaques were analyzed histologically, and their calcification with von Kossa staining and the calcium tracer Osteosense. Plaque inflammation and calcification markers were measured by RT-qPCR. Intermittent TPTD increased bone volume in OVX mice, due to a higher stimulation of bone formation relatively to bone resorption. These effects were not accompanied by changes in serum levels of cholesterol, triglycerides, glucose or insulin. TPTD neither significantly affected aortic plaque size, inflammation, and calcification, even if it slightly increased vascular smooth muscle cell transdifferentiation into calcifying cells. In conclusion, TPTD exhibits osteoanabolic effects in OVX ApoE−/− mice, without significantly influencing atherosclerotic plaque progression or calcification in the short term.

Morphological characterization of coronary plaques in young indian patients with acute coronary syndrome: A multicentric study

ObjectivesThe prevalence of atherosclerosis and acute coronary syndrome (ACS) is increasing in young Indians (18–50 years of age). However, the characteristics of atherosclerotic plaques in such individuals are poorly understood, presenting distinct challenges for the management of ACS. This study aims to analyze plaque characteristics in young Indian patients with ACS who underwent percutaneous coronary intervention (PCI) using optical coherence tomography (OCT) imaging. MethodsThis was a prospective, multicentric, non-interventional study on patients aged 18–50 years presenting with ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction, or unstable angina, and were scheduled to undergo OCT-guided PCI. Major adverse cardiac events (MACE) were assessed post-procedure and at the 6-month and 12-month follow-ups. ResultsThe study included 100 ACS patients (mean age = 43.6 ± 5.2 years), with 51% presenting with STEMI. Pre-PCI OCT assessment showed that fibrous plaques (75%) were most common followed by plaques containing macrophages (27%), microchannels (20%), and calcified nodules (14%). In addition, plaque rupture, plaque erosion, and lipid-rich plaques, along with red, white, and mixed thrombi, were observed in 31%, 25%, 24%, 21%, 14%, and 17% (total thrombus occurrence = 52%) of the patients, respectively. At 12 months, the MACE (coronary artery bypass graft) rate was 1%. ConclusionsYoung Indian patients with ACS displayed a range of plaque morphologies identified through pre-PCI OCT. Among these, fibrous plaques were the most prominent type, followed by plaques containing macrophages. Additionally, plaque rupture, plaque erosion, and lipid-rich plaques were also observed in this population.

Black phosphorus nanoplatform coated with platelet membrane improves inhibition of atherosclerosis progression through macrophage targeting and efferocytosis

Plaque rupture in atherosclerosis (AS) is a major cause of acute cardiovascular events. Macrophage-induced inflammatory responses and accumulation of excess reactive oxygen species (ROS) primarily induce unstable plaques. Therefore, targeting ROS clearance and functional modulation of macrophages are clinically crucial for improving plaque stability and inhibiting AS progression. Here, we constructed a bionic nano-delivery platform, PBP@siR@PM, using platelet membranes (PM) coated with black phosphorus nanosheets (BPNSs) to target macrophages in atherosclerotic plaques. Meanwhile, PM-coated BPNSs (PBP@siR@PM) were used to deliver small interfering RNA silencing Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) into macrophages. Furthermore, macrophage efferocytosis was restored by inhibiting CaMKIIγ and increasing the expression of MerTK, a cytosolic receptor, thus promoting the clearance of apoptotic cells from plaques. This study demonstrated that intraplaque macrophage-targeted therapy using the bionic nano-delivery platform PBP@siR@PM effectively removed excess ROS from macrophages, promoted efferocytosis, cleared apoptotic cells in plaques, improved plaque stability, and largely inhibited AS progression in ApoE–/– mice after high fat diet. In summary, this study proposes a therapeutic strategy for AS and highlights the outstanding therapeutic potential of biomimetic nanomaterials in this type of chronic inflammatory disease. Statement of significanceRupture of atherosclerotic unstable plaques is a major cause of acute cardiovascular events. Macrophage-induced chronic inflammation and oxidative stress due to overloaded ROS are major contributors to plaque rupture. In this study, we focused on the improvement of macrophage efferocytosis within the plaque for the effective treatment of atherosclerosis. A bionic nano-delivery platform was constructed using platelet membranes (PM) coated black phosphorus nanosheets (BPNSs) to target macrophages in atherosclerotic plaques. In conclusion, intraplaque macrophage-targeted therapy based on the bionic nano-delivery platform PBP@siR@PM effectively scavenges overloaded ROS in macrophages, promotes efferocytosis, removes apoptotic cells from plaques, and improves plaque stability, which significantly inhibits the progression of atherosclerosis in ApoE–/– mice after a high-fat diet.

Ultrasound Strain Imaging for Characterizing Atherosclerotic Plaque in the Carotid Arteries of Asymptomatic Subjects

The rupture of vulnerable plaques in the carotid artery is a leading cause of strokes. While magnetic resonance imaging (MRI) is the standard for quantifying plaque composition, its high costs and lengthy procedure times limit large-scale use. Compound ultrasound strain imaging (CUSI) ultrasound offers a non-invasively alternative by assessing tissue deformation/strain within the arterial wall. Previous studies have demonstrated the relationship between strain values and plaque composition, primarily focusing on longitudinal acquisitions, which only image the proximal and distal parts of the wall. This study examines CUSI in transverse imaging planes, which enables visualization of the entire cross-section of the vessel wall. CUSI has already been validated on a symptomatic population. Therefore, the aim is to determine whether CUSI can differentiate plaque composition in asymptomatic individuals with an increased cardiovascular risk profile, validated by MRI. This cross-sectional study included 42 plaques in 28 participants. Ultrasound data were acquired with a Samsung Medison Accuvix V10 with an L5-13IS transducer and RF-interface. An experienced neuroradiologist classified plaques with MRI using the Siemens 3.0T MAGNETOM Skyra MRI (Erlangen, Germany) with a dedicated coil. Strain differences were compared across four plaque categories (calcified, lipid, hemorrhagic, fibrous/aspecific) and for vulnerable versus stable plaques. A difference in strain values was found between lipid and calcified plaques (Kruskal-Wallis test, p < 0.05). Additionally, vulnerable plaques exhibited higher strain values than stable plaques (independent samples test, p < 0.05). CUSI values differ between lipid and calcified and between stable and vulnerable plaques. Minor differences were found between the other plaque types.

Deep Learning and Single-Cell Sequencing Analyses Unveiling Key Molecular Features in the Progression of Carotid Atherosclerotic Plaque.

Rupture of advanced carotid atherosclerotic plaques increases the risk of ischaemic stroke, which has significant global morbidity and mortality rates. However, the specific characteristics of immune cells with dysregulated function and proven biomarkers for the diagnosis of atherosclerotic plaque progression remain poorly characterised. Our study elucidated the role of immune cells and explored diagnostic biomarkers in advanced plaque progression using single-cell RNA sequencing and high-dimensional weighted gene co-expression network analysis. We identified a subcluster of monocytes with significantly increased infiltration in the advanced plaques. Based on the monocyte signature and machine-learning approaches, we accurately distinguished advanced plaques from early plaques, with an area under the curve (AUC) of 0.899 in independent external testing. Using microenvironment cell populations (MCP) counter and non-negative matrix factorisation, we determined the association between monocyte signatures and immune cell infiltration as well as the heterogeneity of the patient. Finally, we constructed a convolutional neural network deep learning model based on gene-immune correlation, which achieved an AUC of 0.933, a sensitivity of 92.3%, and a specificity of 87.5% in independent external testing for diagnosing advanced plaques. Our findings on unique subpopulations of monocytes that contribute to carotid plaque progression are crucial for the development of diagnostic tools for clinical diseases.

A balanced sample generation method for semi-supervised carotid ultrasound image classification via pseudo-label distribution and model confidence

Abstract The rupture of carotid plaques dramatically increases the risk of stroke, making it essential to classify these plaques to promptly identify high-risk cases and assist in patient management. Deep learning-based plaque classification methods need large labeled datasets, which are often challenging to acquire. Semi-supervised learning offers a solution by enabling deep learning networks to perform well with fewer labeled images. However, this method filters pseudo-labels based on thresholds, resulting in imbalanced quantities and cognitive bias in the network. To tackle this issue, we present a Balanced Sample Generation based Pseudo-label algorithm (BSGP) for semi-supervised carotid ultrasound image classification. BSGP generates new samples based on pseudo-label distribution and model confidence in each category, reducing cognitive bias from imbalanced pseudo-label quantities. Evaluated on 1,270 ultrasound carotid plaque images, our BSGP outperformed other semi-supervised methods (FixMatch, FlexMatch, AdaMatch, FreeMatch) when using 10%, 30%, and 50% labeled data. This illustrates the efficacy of our method in leveraging unlabeled images for model training, potentially advancing the use of deep learning in ultrasound-based plaque classification and supporting clinical diagnoses.

Multimodal Intravascular Imaging of the Vulnerable Coronary Plaque.

Vulnerable coronary plaques are atherosclerotic lesions which, due to their specific phenotype, are prone to plaque rupture and to cause acute coronary syndromes, with subsequent relevant morbidity and mortality. Strategies to break the chain link between plaque vulnerability and adverse clinical events include optimized pharmacologic prevention and potentially also preemptive percutaneous coronary interventions (previously defined as "plaque sealing" or "plaque passivation"). Various morphologic features of the vulnerable plaques have been described, including aspects regarding the large necrotic lipid content, the thin fibrous cap, the presence and extent of the presence of calcifications with small size and calcification angle, and as well as the large macrophage infiltration within the plaque. The detection of these features of plaque vulnerability is possible with intravascular imaging modalities such as intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT). This review explores the peculiarities of these three imaging modalities for the detection of vulnerable coronary plaque features.

Coronary Artery Vasculitis and Encasement: Multimodality Imaging Findings and Mimics.

Coronary artery vasculitis (CAV) and coronary artery encasement are rarely diagnosed conditions that are important diagnostic considerations, particularly in patients with acute coronary syndrome without traditional cardiovascular risk factors or systemic illness. Vasculitis refers to inflammation of the blood vessel walls, which can be primary or secondary. This process should be distinguished from neoplastic involvement of the coronary arteries, termed coronary artery encasement. Prospective diagnosis of these diseases is challenging, often requiring multidisciplinary workup with careful attention to clinical presentation and multiorgan findings. While CAV and coronary artery encasement can be indistinguishable at coronary CT angiography, certain imaging features help order the differential diagnosis. CAV should be considered when there is smooth wall thickening that is circumferential and/or continuous. A diagnosis of coronary artery encasement is favored when there is irregular or nodular wall thickening that is eccentric to the vessel lumen. Epicardial fat stranding may also appear more extensive compared with CAV. Potential mimics of CAV include atherosclerosis, acute plaque rupture, coronary artery aneurysm, and spontaneous coronary artery dissection. Detection and diagnosis of CAV may help avoid complications related to accelerated atherosclerosis and infarction. Radiologists should be familiar with the range of pathologic conditions that can affect the coronary arteries beyond atherosclerosis as they may be the first to raise such diagnostic possibilities, guiding next steps in patient workup and management. ©RSNA, 2024 Supplemental material is available for this article.

Localization of Hemostasis Elements in Aspirated Coronary Thrombi at Different Stages of Evolution.

The structure of aspirated coronary thrombus in ST-segment elevation myocardial infarction (STEMI) is still being studied. Our aims were to characterize coronary thrombi of different ages, focusing on the appearance of activated protein C (APC/PC) and its relation to the elements of neutrophil extracellular traps (NETs), and the factors closely related to fibrin as factor XIII (FXIII) and α2 plasmin inhibitor (α2-PI). The thrombi of n = 24 male patients with atherosclerotic coronary plaque rupture related to native coronary artery occlusion were selected for histopathology analysis. Thrombus age was distinguished as fresh, lytic, and organized, and then analyzed by immunofluorescent staining and confocal microscopy. FXIII was present at a high level and showed a high degree of co-localization with fibrin in all stages of thrombus evolution. The amount of α2-PI was low in the fresh thrombi, which increased significantly to the lytic phase. It was evenly distributed and consistently associated with fibrin. APC/PC appeared in the fresh thrombus and remained constant during its evolution. The presence of NET marker and CD66b was most dominant in the lytic phase. APC/PC co-localization with the elements of NET formation shows its role in NET degradation. These observations suggest the importance of searching for further targeted therapeutic strategies in STEMI patients.