Automated Clinical Decision Support for Coronary Plaques Characterization from Optical Coherence Tomography Imaging with Fused Neural Networks

Deep Neural Networks (DNNs) are nurturing clinical decision support systems for the detection and accurate modeling of coronary arterial plaques. However, efficient plaque characterization in time-constrained settings is still an open problem. The purpose of this study is to develop a novel automated classification architecture viable for the real-time clinical detection and classification of coronary artery plaques, and secondly, to use the novel dataset of OCT images for data augmentation. Further, the purpose is to validate the efficacy of transfer learning for arterial plaques classification. In this perspective, a novel time-efficient classification architecture based on DNNs is proposed. A new data set consisting of in-vivo patient Optical Coherence Tomography (OCT) images labeled by three trained experts was created and dynamically programmed. Generative Adversarial Networks (GANs) were used for populating the coronary aerial plaques dataset. We removed the fully connected layers, including softmax and the cross-entropy in the GoogleNet framework, and replaced them with the Support Vector Machines (SVMs). Our proposed architecture limits weight up-gradation cycles to only modified layers and computes the global hyper-plane in a timely, competitive fashion. Transfer learning was used for high-level discriminative feature learning. Cross-entropy loss was minimized by using the Adam optimizer for model training. A train validation scheme was used to determine the classification accuracy. Automated plaques differentiation in addition to their detection was found to agree with the clinical findings. Our customized fused classification scheme outperforms the other leading reported works with an overall accuracy of 96.84%, and multiple folds reduced elapsed time demonstrating it as a viable choice for real-time clinical settings.

Co-delivery of Curcumin and Bioperine via PLGA Nanoparticles to Prevent Atherosclerotic Foam Cell Formation

Cholesterol-rich arterial plaques characterize atherosclerosis, a significant cause of heart disease. Arterial plaques upregulate inflammatory cytokines secreted by the macrophages that finally become cholesterol-laden foam cells. Nutraceuticals have received attention over the years, demonstrating potential benefits towards treating and preventing cardiovascular diseases (CVD), including atherosclerosis. Curcumin, a potent polyphenol present in Curcuma longa, showed remarkable anti-atherosclerotic activity via anti-inflammatory and anti-oxidative properties. The bioavailability and low water solubility of curcumin limit its clinical translational purposes. These issues can be circumvented effectively by nano-drug delivery systems that can target atherosclerotic plaque sites. In this work, we chose to use curcumin and a natural bioenhancer called Bioperine (derived from Piper nigrum) inside a polymeric nano-drug delivery system for targeting atherosclerotic plaque sites. We selected two different ratios of curcumin: Bioperine to study its comparative effect on the inhibition of oxidized low-density lipoprotein (Ox-LDL) induced foam cell formation and investigated the therapeutic efficacy in THP-1 monocyte-derived macrophages via different in vitro cell studies. Our studies demonstrated that Bioperine administration alongside curcumin via PLGA nanoparticles (NPs) imparts a reduction in macrophage-mediated foam cell formation, relative cholesterol content, and the inflammatory pathways when administered as preventive medicine, highlighting the importance of natural-based compounds towards the therapeutic intervention against the atherosclerotic activity.

Familial Hypercholesterolemia and Cerebral Infarction - A Case Report

Background: Familial hypercholesterolemia has various presentations mostly including early-onset cardiovascular diseases, remarkable skin and tendon xanthomas. By comparison, Cerebral Infarction due to familial hypercholesterolemia is extremely rare. Case presentation: We present a 41-year-old man who was admitted to our hospital with dizziness, vertigo, slurred speech, weakness in his left limbs. He had family history of Hyperlipidemia in older sister . Head CT scan demonstrated multiple acute cerebral infarction in the right frontal and parietal lobes, and arterial plaques was found in the bifurcation of common carotid artery. The severe carotid stenosis was located in the initial segment of the right internal carotid artery. Histopathologic findings were consistent with xanthoma. Especially, molecular analysis of the LDLR gene was made, which identified heterozygous missense mutation in exon 12 of the LDLR gene. The final diagnosis of cerebral infarction associated with familial hypercholesterolemia was made. The patient was referred to a nutritionist for dietary advice, and was treated with Tab. Finally, the patient recovered well. The symptoms of brain infarct vanished and no recurrence occurred during follow-up.Conclusions: In the present case, the acute cerebral infarction is most likely due to hypercholesterolemia, as his family history of hypercholesterolemia, and arterial plaques and severe carotid stenosis was found by CTA. This case highlights the importance of the early diagnosis and treatment of hypercholesterolemia, which may help in preventing the development of cardiovascular and cerebrovascular diseases.

Preclinical Techniques to Investigate Exercise Training in Vascular Pathophysiology

Atherosclerosis is a dynamic process starting with endothelial dysfunction and inflammation and eventually leading to life-threatening arterial plaques. Exercise generally improves endothelial function in a dose-dependent manner by altering hemodynamics, specifically by increased arterial pressure, pulsatility, and shear stress. However, athletes who regularly participate in high-intensity training can develop arterial plaques, suggesting alternative mechanisms through which excessive exercise promotes vascular disease. Understanding the mechanisms that drive atherosclerosis in sedentary versus exercise states may lead to novel rehabilitative methods aimed at improving exercise compliance and physical activity. Preclinical tools, including in vitro cell assays, in vivo animal models, and in silico computational methods, broaden our capabilities to study the mechanisms through which exercise impacts atherogenesis, from molecular maladaptation to vascular remodeling. Here, we describe how preclinical research tools have and can be used to study exercise effects on atherosclerosis. We then propose how advanced bioengineering techniques can be used to address gaps in our current understanding of vascular pathophysiology, including integrating in vitro, in vivo, and in silico studies across multiple tissue systems and size scales. Improving our understanding of the anti-atherogenic exercise effects will enable engaging, targeted, and individualized exercise recommendations to promote cardiovascular health rather than treating cardiovascular disease that results from a sedentary lifestyle.

Bacteria Present in Carotid Arterial Plaques Are Found as Biofilm Deposits Which May Contribute to Enhanced Risk of Plaque Rupture

ABSTRACTAtherosclerosis, a disease condition resulting from the buildup of fatty plaque deposits within arterial walls, is the major underlying cause of ischemia (restriction of the blood), leading to obstruction of peripheral arteries, congestive heart failure, heart attack, and stroke in humans. Emerging research indicates that factors including inflammation and infection may play a key role in the progression of atherosclerosis. In the current work, atherosclerotic carotid artery explants from 15 patients were all shown to test positive for the presence of eubacterial 16S rRNA genes. Density gradient gel electrophoresis of 5 of these samples revealed that each contained 10 or more distinct 16S rRNA gene sequences. Direct microscopic observation of transverse sections from 5 diseased carotid arteries analyzed with a eubacterium-specific peptide nucleic acid probe revealed these to have formed biofilm deposits, with from 1 to 6 deposits per thin section of plaque analyzed. A majority, 93%, of deposits was located proximal to the internal elastic lamina and associated with fibrous tissue. In 6 of the 15 plaques analyzed, 16S rRNA genes fromPseudomonasspp. were detected.Pseudomonas aeruginosabiofilms have been shown in our lab to undergo a dispersion response when challenged with free ironin vitro. Iron is known to be released into the blood by transferrin following interaction with catecholamine hormones, such as norepinephrine. Experiments performedin vitroshowed that addition of physiologically relevant levels of norepinephrine induced dispersion ofP. aeruginosabiofilms when grown under low iron conditions in the presence but not in the absence of physiological levels of transferrin.IMPORTANCEThe association of bacteria with atherosclerosis has been only superficially studied, with little attention focused on the potential of bacteria to form biofilms within arterial plaques. In the current work, we show that bacteria form biofilm deposits within carotid arterial plaques, and we demonstrate that one species we have identified in plaques can be stimulatedin vitroto undergo a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of transferrin. Biofilm dispersion is characterized by the release of bacterial enzymes into the surroundings of biofilm microcolonies, allowing bacteria to escape the biofilm matrix. We believe these enzymes may have the potential to damage surrounding tissues and facilitate plaque rupture if norepinephrine is able to stimulate biofilm dispersionin vivo. This research, therefore, suggests a potential mechanistic link between hormonal state and the potential for heart attack and stroke.