Plaque Components Research Articles

Changes in coronary plaque component volumes comparing different virtual monoenergetic images using photon-counting computed tomography

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BV was supported by the ÚNKP-22-3-II-SE New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund. Introduction Photon-counting CT (PCCT) allows virtual monoenergetic images (VMIs) which may aid more precise assessment of coronary plaques. We aimed to analyze how plaque component volumes change on different VMIs. Methods Coronary CT angiography images were acquired using a dual-source PCCT and VMIs were reconstructed between 40–180 keV in 10 keV increments. Polychromatic images at 120 kVp (T3D) were also reconstructed and used as reference. Quantitative image quality analysis was performed on all reconstructed images. Quantitative plaque assessment was performed on T3D images and segmentation masks were copied to all VMI images. Calcified plaque (CP; >350 Hounsfield units, HU), non-calcified plaque (NCP; 30–350HU) and low-attenuation NCP (LAP; −100-30HU) volumes were calculated. Results We analyzed 51 plaques from 51 patients (67% male, mean age 65±12 years). Average attenuation and contrast-to-noise ratio (CNR) decreased significantly with increasing keV levels, with similar values observed between T3D and 70 keV images (299±209 vs 303±225 HU, p = 0.15 for mean HU; 15.5±3.7 vs. 15.8±3.5, p = 0.32 for CNR). Mean NCP volume was comparable between T3D and 100–180 keV reconstructions. There was a graded decrease in mean CP volume, with a significant difference between all VMI images and T3D (p<0.05). LAP volume increased with increasing VMI energy levels and all VMI images showed a significant difference compared to T3D, except for 50 keV (28.0±30.8 mm3 and 28.6±30.1 mm3, respectively, p = 0.63). Conclusion Fixed threshold settings result in significantly different plaque volumes when using VMIs as compared to T3D images. Normalization protocols are needed to have comparable results between future studies.

Carotid Artery Tortuosity and Internal Carotid Artery Plaque Composition.

Little is known about the association between carotid artery tortuosity and internal carotid artery atherosclerosis. This study sought to evaluate the associations between various types of arterial tortuosity and vulnerable plaque components on magnetic resonance angiography (MRA). Aretrospective review was completed of 102patients who had undergone MRA neck imaging, with intraplaque hemorrhage (IPH) present in one or both cervical internal carotid arteries (ICA). Each ICA was assessed for two categories of tortuosity: variant arterial pathway(s) (retrojugular and/or retropharyngeal) and abnormal curvature (kinks, loops, and/or coils). All ICA plaques were assessed for the presence or absence of intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), ulceration, and enhancement, as well as the volume of IPH and degree of luminal stenosis. The mean age of included patients was 73.5years (SD = 9.0 years) and 88 (86.3%) subjects were male. The left carotid plaque was significantly more likely to have IPH (68.6% vs. 47.1%; p = 0.02). The left ICA was more likely to have aretrojugular course (22% vs. 9.9%; p = 0.002) and any variant arterial course (26.5% versus 14.67%, p = 0.01). On the right there was an association between the presence of aLRNC and retropharyngeal and/or retrojugular arterial pathway (p = 0.03). On the left there was an association between the presence of any abnormal arterial curvature and IPH volume (p = 0.03). Neither association met the adjusted statistical threshold after Bonferroni correction, with alpha set at 0.0028. ICA tortuosity is not associated with carotid artery plaque composition, and likely does not play arole in the development of high-risk plaques.

Model Organisms in Neurodegenerative Diseases: Emphasis on Alzheimer’s and Polyglutamine Disease

Increase in human suffering from fatal disorders like that of Parkinson’s Disease (PD), demands the need to find an effective cure for these diseases. This can be achieved through complete understanding of the origins and mechanisms of the diseases. This is, in turn facilitated by the experiments conducted on model organisms like Drosophila melanogaster, Caenorhabditis elegans and Yeast. Drosophila melanogaster’s external characters can be easily observed which can root back to the cellular and genetic alterations, Caenorhabditis elegans on the other hand having access to fully sequential genome and Yeast which can be grown easily in lab conditions with controlled metabolisms gives all these organisms an advantage to be used as a model organism.
 Firstly, Alzheimer’s Disease was discussed in detail. It is a common neurodegenerative disease having effects of cell death, irreversible dementia and malfunctioning neurons. This is due to peptides which are the major components of the amyloid plaque created by amyloid precursor protein (APP). Since Drosophila melanogaster contains similar genes dAPPl related to AD, it is used as a model organism in AD amyloidosis pathogenesis research. Secondly, polyglutamine diseases or poly Q diseases were discussed with respect to the model organisms used to study these diseases. Poly Q diseases are characterized by gene mutations leading to accumulation of insoluble proteins in regions of brain. Among nine types of poly Q diseases documented, four were discussed in detailed namely, Huntington’s disease, Kennedy disease, Spinocerebellar ataxias and Spinal muscular atrophy. Role of drosophila in the study of each type has been discussed, with respect to different manipulations done in the organism. Finally, different model organisms used to study various neurodegenerative diseases were tabulated. Also, the genes involved and the studies related to the particular gene were also represented in the form of table.

Automatic Classification of Magnetic Resonance Histology of Peripheral Arterial Chronic Total Occlusions Using a Variational Autoencoder: A Feasibility Study.

The novel approach of our study consists in adapting and in evaluating a custom-made variational autoencoder (VAE) using two-dimensional (2D) convolutional neural networks (CNNs) on magnetic resonance imaging (MRI) images for differentiate soft vs. hard plaque components in peripheral arterial disease (PAD). Five amputated lower extremities were imaged at a clinical ultra-high field 7 Tesla MRI. Ultrashort echo time (UTE), T1-weighted (T1w) and T2-weighted (T2w) datasets were acquired. Multiplanar reconstruction (MPR) images were obtained from one lesion per limb. Images were aligned to each other and pseudo-color red-green-blue images were created. Four areas in latent space were defined corresponding to the sorted images reconstructed by the VAE. Images were classified from their position in latent space and scored using tissue score (TS) as following: (1) lumen patent, TS:0; (2) partially patent, TS:1; (3) mostly occluded with soft tissue, TS:3; (4) mostly occluded with hard tissue, TS:5. Average and relative percentage of TS was calculated per lesion defined as the sum of the tissue score for each image divided by the total number of images. In total, 2390 MPR reconstructed images were included in the analysis. Relative percentage of average tissue score varied from only patent (lesion #1) to presence of all four classes. Lesions #2, #3 and #5 were classified to contain tissues except mostly occluded with hard tissue while lesion #4 contained all (ranges (I): 0.2-100%, (II): 46.3-75.9%, (III): 18-33.5%, (IV): 20%). Training the VAE was successful as images with soft/hard tissues in PAD lesions were satisfactory separated in latent space. Using VAE may assist in rapid classification of MRI histology images acquired in a clinical setup for facilitating endovascular procedures.

QSAR Classification of Beta-Secretase 1 Inhibitor Activity in Alzheimer's Disease Using Ensemble Machine Learning Algorithms

This study focuses on the development of a machine learning ensemble approach for the classification of Beta-Secretase 1 (BACE1) inhibitors in Quantitative Structure-Activity Relationship (QSAR) analysis. BACE1 is an enzyme linked to the production of amyloid beta peptide, a significant component of Alzheimer's disease plaques. The discovery of effective BACE1 inhibitors is difficult, but QSAR modeling offers a cost-effective alternative by predicting the activity of compounds based on their chemical structures. This study evaluates the performance of four machine learning models (Random Forest, AdaBoost, Gradient Boosting, and Extra Trees) in predicting BACE1 inhibitor activity. Random Forest achieved the highest performance, with a training accuracy of 98.65% and a testing accuracy of 82.53%. In addition, it exhibited superior precision, recall, and F1-score. Random Forest's superior performance was a result of its ability to capture a wide variety of patterns and its randomized ensemble approach. Overall, this study demonstrates the efficacy of ensemble machine learning models, specifically Random Forest, in predicting the activity of BACE1 inhibitors. The findings contribute to ongoing efforts in Alzheimer's disease drug discovery research by providing a cost-effective and efficient strategy for screening and prioritizing potential BACE1 inhibitors.

Aβ43 levels determine the onset of pathological amyloid deposition

About 2% of Alzheimer's disease (AD) cases have early onset (FAD) and are caused by mutations in either Presenilins (PSEN1/2) or amyloid-β precursor protein (APP). PSEN1/2 catalyze production of Aβ peptides of different length from APP. Aβ peptides are the major components of amyloid plaques, a pathological lesion that characterizes AD. Analysis of mechanisms by which PSEN1/2 and APP mutations affect Aβ peptide compositions lead to the implication of the absolute or relative increase in Aβ42 in amyloid-β plaques formation. Here, to elucidate the formation of pathogenic Aβ cocktails leading to amyloid pathology, we utilized FAD rat knock-in models carrying the Swedish APP (Apps allele) and the PSEN1 L435F (Psen1LF allele) mutations. To accommodate the differences in the pathogenicity of rodent and human Aβ, these rat models are genetically engineered to express human Aβ species as both the Swedish mutant allele and the WT rat allele (called Apph) have been humanized in the Aβ-coding region. Analysis of the eight possible FAD mutant permutations indicates that the CNS levels of Aβ43, rather than absolute or relative increases in Aβ42, determine the onset of pathological amyloid deposition in FAD knock-in rats. Notably, Aβ43 was found in amyloid plaques in late onset AD and mild cognitive impairment cases, suggesting that the mechanisms initiating amyloid pathology in FAD knock-in rat reflect disease mechanisms driving amyloid pathology in late onset AD. This study helps clarifying the molecular determinants initiating amyloid pathology and supports therapeutic interventions targeting Aβ43 in AD.

Carotid atherosclerotic plaque segmentation in multi-weighted MRI using a two-stage neural network: advantages of training with high-resolution imaging and histology.

A reliable and automated method to segment and classify carotid artery atherosclerotic plaque components is needed to efficiently analyze multi-weighted magnetic resonance (MR) images to allow their integration into patient risk assessment for ischemic stroke. Certain plaque components such as lipid-rich necrotic core (LRNC) with hemorrhage suggest a greater likelihood of plaque rupture and stroke event. Assessment for presence and extent of LRNC could assist in directing treatment with impact upon patient outcomes. To address the need to accurately determine the presence and extent of plaque components on carotid plaque MRI, we proposed a two-staged deep-learning-based approach that consists of a convolutional neural network (CNN), followed by a Bayesian neural network (BNN). The rationale for the two-stage network approach is to account for the class imbalance of vessel wall and background by providing an attention mask to the BNN. A unique feature of the network training was to use ground truth defined by both high-resolution ex vivo MRI data and histopathology. More specifically, standard resolution 1.5 T in vivo MR image sets with corresponding high resolution 3.0 T ex vivo MR image sets and histopathology image sets were used to define ground-truth segmentations. Of these, data from 7 patients was used for training and from the remaining two was used for testing the proposed method. Next, to evaluate the generalizability of the method, we tested the method with an additional standard resolution 3.0 T in vivo data set of 23 patients obtained from a different scanner. Our results show that the proposed method yielded accurate segmentation of carotid atherosclerotic plaque and outperforms not only manual segmentation by trained readers, who did not have access to the ex vivo or histopathology data, but also three state-of-the-art deep-learning-based segmentation methods. Further, the proposed approach outperformed a strategy where the ground truth was generated without access to the high resolution ex vivo MRI and histopathology. The accurate performance of this method was also observed in the additional 23-patient dataset from a different scanner. In conclusion, the proposed method provides a mechanism to perform accurate segmentation of the carotid atherosclerotic plaque in multi-weighted MRI. Further, our study shows the advantages of using high-resolution imaging and histology to define ground truth for training deep-learning-based segmentation methods.

QiShenYiQi pill inhibits atherosclerosis by promoting reverse cholesterol transport PPARγ-LXRα/β-ABCA1 pathway

Ethnopharmacological relevanceQiShenYiQi pill (QSYQ), a Chinese compound medicine, originate from BuYangHuanWu decoction in the Qing dynasty, and has been used to treat ischemic cardiovascular diseases for more than two hundred years in China. Multi-central randomized double-blind controlled studies have proved that QSYQ has similar efficacy as enteric coated aspirin in the secondary prevention of myocardial infarction. Aim of studyThe aim of study was to explore the effect of QSYQ on reverse cholesterol transport (RCT) pathway during atherosclerosis. Materials and methodsEight-week-old male apoE−/− mice (on the gene background of C57BL/6J) were fed with a high-fat western diet and treated with low dose and high dose of QSYQ, as well as the positive control agent, liver X receptor-α (LXR-α) agonist GW3965. Eight weeks later, mice were sacrificed and the aorta was collected for atherosclerotic analysis. The aortic root was stained with Oil red O to evaluate the area of atherosclerotic lesion, and stained with immunohistochemistry to analyze the intra-plaque component and RCT protein in atherosclerotic plaque. The thoracic aorta was used to detect differentially expressed genes by comparative transcriptome RNA-seq and the protein expression of RCT pathway by western blotting. ResultsAfter eight weeks of treatment, we found that both of QSYQ and LXR-α agonist reduced atherosclerotic plaque area significantly, and decreased the intra-plaque component, including the lipid, the smooth muscle cell and the macrophage. Compared with the control group, there were 49 differentially expressed genes in low-dose QSYQ group, including 21 up-regulated genes and 28 down-regulated genes. The results of GO and KEGG analysis showed that the differentially expressed genes mainly concentrated in the negative regulation of lipid biosynthesis, positive regulation of lipid metabolism, cell response to lipids, negative regulation of lipid storage, fatty acid degradation, and glycerol ester metabolism. Both of QSYQ and LXR-α agonist reduced the protein expression of CD36 and increased the protein expression of PPARγ-LXRα/β-ABCA1 in atherosclerotic plaque. ConclusionThe anti-atherosclerotic mechanism of QSYQ was involved in inhibiting lipid phagocytosis and promoting reverse cholesterol transport, therefore reducing lipid deposition and inflammatory cells in plaque.

Transforming growth factor-β2 is associated with atherosclerotic plaque stability and lower risk for cardiovascular events.

Transforming growth factor-beta (TGF-β) exists in three isoforms TGF-β1, -β2 and -β3. TGF-β1 has been suggested to be important for maintaining plaque stability, yet the role of TGF-β2 and -β3 in atherosclerosis remains to be investigated. This study explores the association of these three isoforms of TGF-β with plaque stability in the human atherosclerotic disease. TGF-β1, -β2 and -β3 proteins were quantified in 223 human carotid plaques by immunoassays. Indications for the endarterectomy were: symptomatic carotid plaque with stenosis >70% or without symptoms and >80% stenosis. Plaque mRNA levels were assessed by RNA sequencing. Plaque components and extracellular matrix were measured histologically and biochemically. Matrix metalloproteinases were measured with ELISA. Monocyte chemoattractant protein-1 (MCP-1) was measured with immunoassays. The effect of TGF-β2 on inflammation and protease activity was investigated in vitro using THP-1 and RAW264.7 macrophages. Patients were followed longitudinally for cardiovascular events.TGF-β2 was the most abundant isoform and was increased at both protein and mRNA levels in asymptomatic plaques. TGF-β2 was the main determinant separating asymptomatic plaques in an Orthogonal Projections to Latent Structures Discriminant Analysis. TGF-β2 correlated positively to features of plaque stability and inversely to markers of plaque vulnerability. TGF-β2 was the only isoform inversely correlated to the matrix-degrading matrix metalloproteinase-9 and inflammation in the plaque tissue. In vitro, TGF-β2 pre-treatment reduced MCP-1 gene and protein levels as well as matrix metalloproteinase-9 gene levels and activity. Patients with plaques with high TGF-β2 levels had a lower risk to suffer from future cardiovascular events. TGF-β2 is the most abundant TGF-β isoform in human plaques and may maintain plaque stability by decreasing inflammation and matrix degradation.

Association of leisure-time physical activity and sedentary behavior with carotid atherosclerosis morphology: The ARIC carotid-MRI study

ObjectiveWe evaluated the prospective association of midlife leisure-time physical activity (LTPA) and sedentary behavior (SB), and their temporal patterns, with MRI-measured carotid atherosclerotic morphology. MethodsParticipants enrolled in the Carotid MRI substudy (2004–2006) of the Atherosclerosis Risk in Communities (ARIC) Study and with self-reported assessments of LTPA and SB at visits 1 (1987–1989) and 3 (1993–1995) were included in this study. LTPA was ascertained using the ARIC/Baecke physical activity questionnaire and categorized according to the American Heart Association's metric of poor, intermediate, or ideal physical activity. SB, measured as TV viewing frequency, was categorized as high, medium, and low. We used multivariable adjusted linear and logistic regression models to examine the associations between midlife (visit 3 only) and persistent (visit 1 to 3) LTPA and TV viewing with carotid artery plaque burden and components. ResultsAmong the 1,582 (mean age: 59 years, 43% male, 18% Black) participants, 45.7%, 21.7%, and 32.6% reported ideal, intermediate, or poor LTPA, respectively. High TV viewing was reported in 33.8% of participants, with 46.4% and 19.8% reporting medium or low TV viewing, respectively. Compared to poor LTPA, ideal LTPA in midlife was not associated with total wall volume (ß=0.01, 95% CI: -0.01, 0.03), maximum carotid wall thickness (ß=0.06, 95% CI: -0.08, 0.21), normalized wall index (ß=-0.01, 95% CI: -0.03, 0.01), or maximum stenosis (ß=-0.11, 95% CI: -1.98, 1.76). Low or middle, compared to high, TV viewing was also not associated with carotid artery measures of plaque burden. Compared to poor LTPA or high TV viewing, ideal LTPA (odds ratio (OR): 0.82, 95% CI: 0.55, 1.23) and low TV viewing (OR=0.90, 95% CI: 0.56, 1.44) was not associated with odds of lipid core presence, respectively. ConclusionOverall, this study does not provide strong evidence for an association between LTPA and SB with carotid plaque measures.

Label-Free Characterization of Atherosclerotic Plaques Via High-Resolution Multispectral Fluorescence Lifetime Imaging Microscopy.

Autofluorescence lifetime (AFL) imaging, a robust technique that enables label-free molecular investigation of biological tissues, is being introduced into the field of cardiovascular diagnostics. However, detailed AFL characteristics of coronary arteries remain elusive and there is a lack of methodology enabling such characterization. We developed multispectral fluorescence lifetime imaging microscopy (FLIM) based on analog-mean-delay. Freshly sectioned coronary arteries and atheromas, harvested from 5 swine models, were imaged using FLIM and stained to label lipids, macrophages, collagen, and smooth muscle cells. The components were quantitated from digitized histological images and compared with the corresponding FLIM. Multispectral AFL parameters derived from 2 different spectral bands (390 nm and 450 nm) were analyzed. FLIM provided a wide field-of-view, high-resolution AFL imaging of frozen sections. Principal compositions of coronary arteries, such as tunica media, tunica adventitia, elastic laminas, smooth muscle cell-enriched fibrous plaque, lipid-rich core, and foamy macrophages, were well visualized in FLIM images and were found to have each different AFL spectra. In particular, proatherogenic components including lipids and foamy macrophages exhibited significantly different AFL values compared with plaque-stabilizing collagen- or smooth muscle cell-enriched tissues (P<0.0001). Pairwise comparisons showed that each composition was distinguishable from another by the difference in multispectral AFL parameters. Pixel-level analysis based on coregistered FLIM-histology dataset showed that each component of atherosclerosis (lipids, macrophages, collagen, and smooth muscle cells) had distinct correlation pattern with AFL parameters. Random forest regressors trained with the dataset allowed automated, simultaneous visualization of the key atherosclerotic components with high accuracy (r>0.87). FLIM provided detailed pixel-level AFL investigation of the complex composition of coronary artery and atheroma. Our FLIM strategy enabling an automated, comprehensive visualization of multiple plaque components from unlabeled sections will be highly useful to efficiently evaluate ex vivo samples without the need for histological staining and analysis.

Identification of vulnerable carotid plaque with histologically validated CT-derived plaque maps.

Ruptured carotid plaque causes stroke, but differentiating rupture-prone necrotic core from fibrous tissue with CT is limited by overlap of X-ray attenuation. We investigated the ability of CT-derived plaque maps created from ratios of plaque/contrast attenuation to identify histologically proven vulnerable plaques. Seventy patients underwent carotid CT angiography and carotid endarterectomy. A derivation cohort of 20 patients had CT images matched with histology and carotid plaque components attenuation defined. In a validation cohort of 50 patients, CT-derived plaque maps were compared in 43 symptomatic vs 40 asymptomatic carotid plaques and accuracy detecting vulnerable plaques calculated. In 250 plaque areas co-registered with histology, the median attenuation (HU) of necrotic core 43(26-63), fibrous plaque 127(110-162) and calcified plaque 964 (816-1207) created significantly different ratios of plaque/contrast attenuation. CT-derived plaque maps revealed symptomatic plaques had larger necrotic core than asymptomatic (13.5%(5.9-33.3) vs 7.4%(2.3-14.3), p = 0.004) with large necrotic core predicting symptoms (area under ROC curve 0.68, p = 0.004). Twenty-four of 47 carotid plaques were histologically classified as most vulnerable (Starry-Type VI). Plaque maps revealed Type VI plaques had a greater necrotic core volume than Type IV/V plaques and a necrotic core/fibrous plaque ratio >0.5 distinguished Type VI plaques with sensitivity 75.0% (55.1-88.0) and specificity of 39.1% (22.2-59.2). Carotid plaque components can be differentiated by CT using a ratio of plaque/contrast attenuation. CT-derived plaque map volumes of necrotic core help distinguished the most vulnerable plaques. CT-derived plaque maps based on plaque/contrast attenuation may provide new markers of carotid plaque vulnerability.

Hypochlorite-induced oxidation promotes aggregation and reduces toxicity of amyloid beta 1-42

Exacerbated hypochlorite (OCl−) production is linked to neurodegenerative processes, but there is growing evidence that lower levels of hypochlorite activity are important to protein homeostasis. In this study we characterise the effects of hypochlorite on the aggregation and toxicity of amyloid beta peptide 1–42 (Aβ1-42), a major component of amyloid plaques that form in the brain in Alzheimer's disease. Our results demonstrate that treatment with hypochlorite promotes the formation of Aβ1-42 assemblies ≥100 kDa that have reduced surface exposed hydrophobicity compared to the untreated peptide. This effect is the result of the oxidation of Aβ1-42 at a single site as determined by mass spectrometry analysis. Although treatment with hypochlorite promotes the aggregation of Aβ1-42, the solubility of the peptide is enhanced and amyloid fibril formation is inhibited as assessed by filter trap assay, thioflavin T assay and transmission electron microscopy. The results of in vitro assays using SH-SY5Y neuroblastoma cells show that pre-treatment of Aβ1-42 with a sub-stoichiometric amount of hypochlorite substantially reduces its toxicity. The results of flow cytometry analysis and internalisation assays indicate that hypochlorite-induced modification of Aβ1-42 reduces its toxicity via at least two-distinct mechanism, reducing the total binding of Aβ1-42 to the surface of cells and facilitating the cell surface clearance of Aβ1-42 to lysosomes. Our data is consistent with a model in which tightly regulated production of hypochlorite in the brain is protective against Aβ-induced toxicity.

Associations between the serum triglyceride-glucose index and pericoronary adipose tissue attenuation and plaque features using dual-layer spectral detector computed tomography: a cross-sectional study.

The triglyceride-glucose (TyG) index is a reliable alternative marker for insulin resistance (IR). Pericoronary adipose tissue (PCAT) can indirectly reflect coronary inflammation. IR and coronary inflammation play a key role in the development and progression of coronary atherosclerosis. Therefore, this study investigated the relationships between the TyG index, PCAT and atherosclerotic plaque characteristics to explore whether IR might lead to coronary artery atherosclerosis progression by inducing coronary inflammation. We retrospectively collected data on patients with chest pain who underwent coronary computed tomography angiography using spectral detector computed tomography at our institution from June to December 2021. The patients were grouped based on their TyG index levels: T1 (low), T2 (medium), and T3 (high). Each patient was assessed for total plaque volume, plaque load, maximum stenosis, the plaque component volume proportion, high-risk plaques(HRPs), and plaque characteristics (including low attenuation plaques, positive remodeling, a napkin ring sign, and spot calcification). PCAT quantification was performed on the proximal right coronary artery using the fat attenuation index (FAI) measured from a conventional multicolor computed tomography image (FAI120kVp), a spectral virtual single-energy image (FAI40keV), and the slope of the spectral HU curve (λHU). We enrolled 201 patients. The proportion of patients with maximum plaque stenosis, positive remodeling, low-density plaques, and HRPs increased as the TyG index level increased. Moreover, the FAI40keV and λHU significantly differed among the three groups, and we identified good positive correlations between FAI40keV and λHU and the TyG index (r = 0.319, P <0.01 and r = 0.325, P <0.01, respectively). FAI120kVp did not significantly differ among the groups. FAI40keV had the highest area under the curve, with an optimal cutoff value of -130.5 HU for predicting a TyG index value of ≥9.13. The multivariate linear regression analysis demonstrated that FAI40keV and λHU were independently positively related to a high TyG index level (standardized regression coefficients: 0.117 [P <0.001] and 0.134 [P <0.001], respectively). Patients with chest pain and a higher TyG index level were more likely to have severe stenosis and HRPs. Moreover, FAI40keV and λHU had good correlations with the serum TyG index, which may noninvasively reflect PCAT inflammation under insulin resistance. These results could help explain the mechanism of plaque progression and instability in patients with insulin resistance might be related to IR-induced coronary inflammation.

Comparison between different approaches to evaluate fibrous cap thickness in sequential optical coherence tomography studies.

In this in-vivo human study we tested the reproducibility for optical coherence tomography (OCT) assessment of lumen area (LA) and plaque components measurements, such as lipid arc extension and fibrous cap thickness (FCt). We tested the variability of LA, lipid arc and FCt assessments in two repeated OCT pullbacks from the same diseased coronary segment matched using fiduciary anatomical landmarks. In particular, for the reliability of minimal FCt measurement we compared four different approaches based on continuous (longitudinal) or segmental (spot) individuation of smaller thickness: 1) comparison of single minimal FCt individuated alongside all plaque extension in the two pullbacks (Longitudinal (L)-spot minimal FCt value); 2) comparison of the mean FCt values of the plaque in the two pullbacks (L-plot mean FCt value); 3) comparison between the single minimal FCt value obtained in the first pullback and the single FCt obtained in the matched CS of second pullback (L-spot CS matched FCt value); 4) comparison of measurements obtained by visual selection of CS with minimal FCt s in the two pullbacks (single-spot minimal FCt value). From the paired analyses of 20 non culprit lesions (accounting for a total of 387 matched CS), we found a suboptimal in-segment correlation for LA (Intra-Class Coefficient [ICC] 0.731), but a good in-segment correlation for lipid arc (ICC 0.963). Regarding FCt measurement, a high reproducibility was obtained applying continuous assessment; in particular, the best correlation was observed with L-spot minimal FCt value and the L-plot mean FCt (ICC 0.893 and 0.952, respectively) with small inter-pullback differences (confidence intervals less than 0.04 mm). In this methodological study we observed a good reproducibility for quantitative plaque measurements with OCT confirming its reliability for serial assessment. In particular, longitudinal measurement in multiple adjacent frames seems to be the more accurate and reproducible approach for sequential FCt assessment.

Abstract 139: Semi-automated Classification Of Peripheral Artery Disease Lesion Composition From Multi-Contrast Magnetic Resonance Histology At 9.4 Tesla With A 2 Dimensional Convolutional Neural Network Variational AutoEncoder Algorithm

Introduction: Using artificial intelligence (AI)-assisted methods on MRI histology may help endovascular peripheral artery disease (PAD) treatment planning. Objectives: To evaluate soft vs. hard PAD plaque components and crossability using multi-contrast high-resolution MRI, AI algorithm, and histologic samples. Methods: PAD lesions were harvested from 6 patients (one of each) after amputation and imaged using a 9.4T ultra-high resolution MRI scanner with 3 contrasts: T1-weighted (T1w), T2-weighted (T2w) and Ultrashort Echo Time (UTE). 3D imaging volumes were spatially registered and pseudo-color composites (T1w: red, T2w: green, UTE:blue) were created. Custom 2D variational autoencoder (VAE) classification AI algorithm using convolutional neural networks for image recognition classified and scored cross-sections as lumen occluded with soft tissue (tissue score (TS)=10), with soft and hard tissue (TS=30) and with hard tissue (TS= 50). 2 readers performed visual assessment of crossability (crossable/non-crossable) on preselected MRI slices compared to histologic samples (Fig1a), percent agreement was calculated for inter-rater reliability. Results: MRI multi-contrast registration succeeded for all section (pseudo-colors: smooth muscle cells- pink/red, fatty lesions-green, collagen-dark blue, calcification-black). VAE separated axial sections based on plaque composition (Fig1b), average TS per tissue segments ranged from 10 to 48.1 and corresponded well to the composition of tissues inspected visually.20 slices showed appropriate alignment, for the evaluation of crossability 11 were excluded due to lack of sufficient histological sample, inter-rater reliability was 100% on 9 slices (7 crossable, 2 non-crossable). Conclusion: AI algorithm for image recognition successfully distinguished lesion composition. AI-aided analysis may help rapid evaluation of lesion crossability in planning endovascular interventions.

Sex Differences in the Density of Lipidic Plaque Materials: Insights From the REASSURE-NIRS MultiCenter Registry.

Intravascular imaging has shown better response of coronary atheroma to statin-mediated lowering of low-density lipoprotein cholesterol in women. However, its detailed mechanism remains to be determined yet. Modifiability of coronary atheroma under lipid-lowering therapies is partly driven by lipidic plaque component. Given a smaller plaque volume in women, lipidic plaque features including their density may differ between sex. Therefore, the current study sought to characterize sex-related differences in the density of lipidic plaque. We analyzed 1429 coronary lesions (culprit/nonculprit lesions=825/604) in 758 coronary artery disease patients (men/women=608/150) from the REASSURE-NIRS multicenter registry (Revelation of Pathophysiological Phenotypes of Vulnerable Lipid-Rich Plaque on Near-Infrared Spectroscopy). Total atheroma volume at 4-mm segment, maximum 4-mm-lipid-core burden index, and lipid plaque density index (=maximum 4-mm-lipid-core burden index/total atheroma volume at 4-mm segment) on near-infrared spectroscopy/intravascular ultrasound imaging at culprit and nonculprit lesions were compared in men and women. Statin and high-intensity statin were used in 72.4 (P=0.81) and 22.9% (P=0.32) of study subjects, respectively. Women exhibited a smaller adjusted total atheroma volume at 4-mm segment (culprit lesions: 50.3±0.4 versus 54.2±0.3mm3, P<0.001, nonculprit lesions: 31.5±3.0 versus 44.4±2.1mm3, P<0.001), whereas their adjusted maximum 4-mm-lipid-core burden index did not differ between sex (culprit lesions: 544.7±29.9 versus 501.7±19.1, P=0.11, nonculprit lesions: 288.8±26.7 versus 272.7±18.9, P=0.51). Furthermore, a greater adjusted lipid plaque density index was observed in women (culprit lesions: 18.2±0.9 versus 9.8±0.6, P<0.001, nonculprit lesions: 23.0±2.0 versus 7.8±1.4, P<0.001). These adjustments of total atheroma volume at 4-mm segment, maximum 4-mm-lipid-core burden index, and lipid plaque density index included age, body mass index, hypertension, dyslipidemia, diabetes, smoking, a history of myocardial infarction and chronic kidney disease, low-density lipoprotein cholesterol level, statin and ezetimibe use, vessel volume, and hospital unit. The aforementioned plaque features consistently existed in both acute coronary syndrome and stable coronary artery disease subjects. Women harbored greater condensed lipidic plaque features, accompanied by smaller atheroma volume. These observations indicate potentially better modifiable disease in women, which underscores the need to intensify their lipid-lowering therapies for further improving their outcomes. URL: https://www. gov/; Unique identifier: NCT04864171.

A Vision for Treating Alzheimer's Disease

Ais a type of amyloid that is the main component of the senile plaques found in the brains of people with Alzheimer's disease. It is generally thought to be associated with various neurodegenerative behaviors. At the same time, cellular autophagy disorders have also been observed in large numbers in Alzheimer's patients. However, due to technical obstacles, humans have not been very clear about the specific mechanism of Alzheimer's. Previously, the mainstream view has been that A causes autophagy disorder, which leads to Alzheimer's disease. However, emerging evidence points to the fact that A is actually a downstream event of autophagy disorder. In the experiment, they observed the specific process of autophagy in the brain by using a dual fluorescent labeling method and a variety of high-end imaging techniques at the same time. In addition, through this method, they also found that A accumulates in the cell in the early stage of the disease, rather than outside the cell as we generally think. So our goal should also shift from A removal to how to prevent autophagy disorder. While describing this situation, this paper also proposes some possible methods that have been discovered so far to prevent autophagy disorders.

The impact of baseline calcified plaque volume on coronary rapid plaque progression by serial coronary computed tomography angiography in patients with type 2 diabetes

Objectives Patients with type 2 diabetes mellitus (T2DM) are susceptible to coronary artery disease (CAD), and coronary outcomes in these patients are heterogeneous. However, the impact of coronary plaque compositions on rapid plaque progression (RPP) in patients with T2DM has rarely been reported. This study aimed to investigate the association of coronary plaque compositions with rapid lesion volume progression in patients with T2DM. Materials and Methods A total of 159 subjects (aged 62.51 ± 10.3 years, 68.6% were male) who underwent serial coronary computed tomography angiography (CCTA) with type 2 diabetic status were enrolled. Annual change of plaque volume (PV) (mm3/year) was defined as PV change divided by inter-scan period. RPP was defined as the progression of plaque burden (PV divided by vessel volume multiplied by 100) ≥0.59%/year. Plaque components were compared between RPP and no RPP groups. Then all patients were divided into 3 groups according to the baseline calcified plaque volume tertiles. The outcome was whether RPP occurred. Results The median inter-scan period was 2.09 (range 1.41–3.33) years. The overall incidence of RPP was 61.0%. The calcified plaque volume decreased significantly in the RPP group as compared to the no RPP group. The risk of RPP (odds ratio [OR] 0.39; 95% confidence interval [CI]: 0.17-0.88; p = 0.024) was reduced in tertiles III as compared to that in tertiles I even after adjustment for baseline variables (OR 0.21; 95% CI: 0.07–0.63; p = 0.005). Moreover, adding the calcified plaque volume significantly raised the predictive value for the RPP (0.370, p = 0.030, and 0.059, p = 0.025, NRI, and IDI respectively) as compared to traditional factors. Conclusion The baseline calcified plaque volume is an independent protective factor for the rapid progression of coronary atherosclerosis in patients with T2DM.

The cell origins of foam cell and lipid metabolism regulated by mechanical stress in atherosclerosis.

Atherosclerosis is an inflammatory disease initiated by endothelial activation, in which lipoprotein, cholesterol, extracellular matrix, and various types of immune and non-immune cells are accumulated and formed into plaques on the arterial wall suffering from disturbed flow, characterized by low and oscillating shear stress. Foam cells are a major cellular component in atherosclerotic plaques, which play an indispensable role in the occurrence, development and rupture of atherosclerotic plaques. It was previously believed that foam cells were derived from macrophages or smooth muscle cells, but recent studies have suggested that there are other sources of foam cells. Many studies have found that the distribution of atherosclerotic plaques is not random but distributed at the bend and bifurcation of the arterial tree. The development and rupture of atherosclerotic plaque are affected by mechanical stress. In this review, we reviewed the advances in foam cell formation in atherosclerosis and the regulation of atherosclerotic plaque and lipid metabolism by mechanical forces. These findings provide new clues for investigating the mechanisms of atherosclerotic plaque formation and progression.