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1.
J Biomed Opt ; 29(3): 036004, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38532927

ABSTRACT

Significance: There is a significant need for the generation of virtual histological information from coronary optical coherence tomography (OCT) images to better guide the treatment of coronary artery disease (CAD). However, existing methods either require a large pixel-wise paired training dataset or have limited capability to map pathological regions. Aim: The aim of this work is to generate virtual histological information from coronary OCT images, without a pixel-wise paired training dataset while capable of providing pathological patterns. Approach: We design a structurally constrained, pathology-aware, transformer generative adversarial network, namely structurally constrained pathology-aware convolutional transformer generative adversarial network (SCPAT-GAN), to generate virtual stained H&E histology from OCT images. We quantitatively evaluate the quality of virtual stained histology images by measuring the Fréchet inception distance (FID) and perceptual hash value (PHV). Moreover, we invite experienced pathologists to evaluate the virtual stained images. Furthermore, we visually inspect the virtual stained image generated by SCPAT-GAN. Also, we perform an ablation study to validate the design of the proposed SCPAT-GAN. Finally, we demonstrate 3D virtual stained histology images. Results: Compared to previous research, the proposed SCPAT-GAN achieves better FID and PHV scores. The visual inspection suggests that the virtual histology images generated by SCPAT-GAN resemble both normal and pathological features without artifacts. As confirmed by the pathologists, the virtual stained images have good quality compared to real histology images. The ablation study confirms the effectiveness of the combination of proposed pathological awareness and structural constraining modules. Conclusions: The proposed SCPAT-GAN is the first to demonstrate the feasibility of generating both normal and pathological patterns without pixel-wisely supervised training. We expect the SCPAT-GAN to assist in the clinical evaluation of treating the CAD by providing 2D and 3D histopathological visualizations.


Subject(s)
Coronary Artery Disease , Tomography, Optical Coherence , Humans , Heart , Artifacts , Staining and Labeling , Image Processing, Computer-Assisted
2.
EuroIntervention ; 20(2): e135-e145, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38224254

ABSTRACT

BACKGROUND: There are limited data on the clinical characteristics and outcomes of patients who require prolonged mechanical circulatory support (MCS) after Impella-supported high-risk percutaneous coronary intervention (HR-PCI). AIMS: The aim of this study is to describe the contemporary clinical characteristics, outcomes, and predictors associated with prolonged MCS support after assisted HR-PCI. METHODS: Patients enrolled in the prospective, multicentre, clinical endpoint-adjudicated PROTECT III study who had undergone HR-PCI using Impella were evaluated. Patient and procedural characteristics and outcomes for those who received prolonged MCS beyond the duration of their index procedure were compared to those in whom MCS was successfully weaned and explanted at the conclusion of the index PCI. RESULTS: Among 1,155 patients who underwent HR-PCI with Impella between 2017 and 2020 and had sufficient data to confirm the duration of Impella support, 16.5% received prolonged MCS (mean duration 25.2±31.1 hours compared with 1.8±5.8 hours for those who only received intraprocedural MCS). Patients receiving prolonged support presented with more urgent indications (e.g., acute coronary syndromes [ACS], lower ejection fraction [EF], elevated baseline heart rate and lower systolic blood pressure). Use of the Impella CP, intraprocedural complications, periprocedural complications and in-hospital mortality were all more common amongst the prolonged MCS group. Prolonged MCS was associated with increased rates of major adverse cardiovascular and cerebrovascular events, cardiovascular death, and all-cause mortality at 90-day follow-up. CONCLUSIONS: Patients receiving prolonged MCS after Impella-supported HR-PCI presented with more ACS, reduced EF and less favourable haemodynamics. Additionally, they were more likely to experience intraprocedural and periprocedural complications as well as increased in-hospital and post-discharge mortality.


Subject(s)
Acute Coronary Syndrome , Percutaneous Coronary Intervention , Humans , Percutaneous Coronary Intervention/adverse effects , Aftercare , Prospective Studies , Patient Discharge
3.
Biomaterials ; 305: 122450, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38169190

ABSTRACT

In vitro atherosclerosis models are essential to evaluate therapeutics before in vivo and clinical studies, but significant limitations remain, such as the lack of three-layer vascular architecture and limited atherosclerotic features. Moreover, no scalable 3D atherosclerosis model is available for making high-throughput assays for therapeutic evaluation. Herein, we report an in vitro 3D three-layer nanomatrix vascular sheet with critical atherosclerosis multi-features (VSA), including endothelial dysfunction, monocyte recruitment, macrophages, extracellular matrix remodeling, smooth muscle cell phenotype transition, inflammatory cytokine secretion, foam cells, and calcification initiation. Notably, we present the creation of high-throughput functional assays with VSAs and the use of these assays for evaluating therapeutics for atherosclerosis treatment. The therapeutics include conventional drugs (statin and sirolimus), candidates for treating atherosclerosis (curcumin and colchicine), and potential gene therapy (miR-146a-loaded liposomes). The high efficiency and flexibility of the scalable VSA functional assays should facilitate drug discovery and development for atherosclerosis.


Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Humans , Atherosclerosis/drug therapy , Macrophages , Foam Cells , Monocytes , Gene Expression , Myocytes, Smooth Muscle
4.
ACS Biomater Sci Eng ; 9(8): 4747-4760, 2023 08 14.
Article in English | MEDLINE | ID: mdl-37480152

ABSTRACT

A recent U.S. Food and Drug Administration report presented the currently available scientific information related to biological response to metal implants. In this work, a multilevel approach was employed to assess the implant-induced and biocorrosion-related inflammation in the adjacent vascular tissue using a mouse stent implantation model. The implications of biocorrosion on peri-implant tissue were assessed at the macroscopic level via in vivo imaging and histomorphology. Elevated matrix metalloproteinase activity, colocalized with the site of implantation, and histological staining indicated that stent surface condition and implantation time affect the inflammatory response and subsequent formation and extent of neointima. Hematological measurements also demonstrated that accumulated metal particle contamination in blood samples from corroded-stetted mice causes a stronger immune response. At the cellular level, the stent-induced alterations in the nanostructure, cytoskeleton, and mechanical properties of circulating lymphocytes were investigated. It was found that cells from corroded-stented samples exhibited higher stiffness, in terms of Young's modulus values, compared to noncorroded and sham-stented samples. Nanomechanical modifications were also accompanied by cellular remodeling, through alterations in cell morphology and stress (F-actin) fiber characteristics. Our analysis indicates that surface wear and elevated metal particle contamination, prompted by corroded stents, may contribute to the inflammatory response and the multifactorial process of in-stent restenosis. The results also suggest that circulating lymphocytes could be a novel nanomechanical biomarker for peri-implant tissue inflammation and possibly the early stage of in-stent restenosis. Large-scale studies are warranted to further investigate these findings.


Subject(s)
Coronary Restenosis , United States , Humans , Coronary Restenosis/etiology , Coronary Restenosis/pathology , Coronary Vessels/pathology , Stents/adverse effects , Metals , Inflammation/complications , Inflammation/pathology
5.
Cardiovasc Revasc Med ; 57: 43-50, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37414613

ABSTRACT

BACKGROUND: The anterior-posterior fluoroscopic guidance (the AP technique) is a standard method for common femoral artery (CFA) access, but the rate of CFA access with ultrasound vs. the AP technique was not significantly different. We have shown an oblique fluoroscopic guidance (the oblique technique) with a micropuncture needle (MPN) resulted in CFA access in 100 % of patients. The outcome of the oblique vs. AP technique is unknown. We compared the utilities of the oblique vs. AP technique for CFA access with a MPN in patients undergoing coronary procedures. METHODS: A total of 200 patients were randomized to the oblique vs. AP technique. Using the oblique technique, a MPN was advanced to the mid pubis in the 20° ipsilateral right-or left anterior oblique view with fluoroscopic guidance and the CFA was punctured. In the AP technique, a MPN was advanced to the mid femoral head in the AP view with fluoroscopic guidance and the CFA was punctured. The primary endpoint was the rate of successful access to the CFA. RESULTS: The rates of first pass and CFA access were higher with the oblique vs. AP technique (82 % vs. 61 %, and 94 % vs. 81 %, respectively; P < 0.01). The number of needle punctures was lower with the oblique vs. AP technique (1.1 ± 0.39 vs. 1.4 ± 0.78, respectively; P < 0.01). In high CFA bifurcations, the rate of CFA access was higher with the oblique vs. AP technique (76 % vs. 52 %, respectively; P < 0.01). Vascular complications were lower with the oblique vs. AP technique (1 % vs. 7 %, respectively; P < 0.05). CONCLUSIONS: Our data suggest that the oblique technique, compared with the AP technique, significantly increased the rates of first pass and access to the CFA, and decreased the number of punctures and vascular complication. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03955653.


Subject(s)
Catheterization, Peripheral , Femoral Artery , Humans , Femoral Artery/diagnostic imaging , Treatment Outcome , Catheterization, Peripheral/adverse effects , Catheterization, Peripheral/methods , Needles , Punctures
6.
JACC Cardiovasc Interv ; 16(9): 1036-1038, 2023 05 08.
Article in English | MEDLINE | ID: mdl-37164600
7.
Biomater Res ; 27(1): 34, 2023 Apr 22.
Article in English | MEDLINE | ID: mdl-37087537

ABSTRACT

BACKGROUND: Capsular contracture is a critical complication of silicone implantation caused by fibrotic tissue formation from excessive foreign body responses. Various approaches have been applied, but targeting the mechanisms of capsule formation has not been completely solved. Myofibroblast differentiation through the transforming growth factor beta (TGF-ß)/p-SMADs signaling is one of the key factors for capsular contracture development. In addition, biofilm formation on implants may result chronic inflammation promoting capsular fibrosis formation with subsequent contraction. To date, there have been no approaches targeting multi-facted mechanisms of capsular contracture development. METHODS: In this study, we developed a multi-targeting nitric oxide (NO) releasing bionanomatrix coating to reduce capsular contracture formation by targeting myofibroblast differentiation, inflammatory responses, and infections. First, we characterized the bionanomatrix coating on silicon implants by conducting rheology test, scanning electron microcsopy analysis, nanoindentation analysis, and NO release kinetics evaluation. In addition, differentiated monocyte adhesion and S. epidermidis biofilm formation on bionanomatrix coated silicone implants were evaluated in vitro. Bionanomatrix coated silicone and uncoated silicone groups were subcutaneously implanted into a mouse model for evaluation of capsular contracture development for a month. Fibrosis formation, capsule thickness, TGF-ß/SMAD 2/3 signaling cascade, NO production, and inflammatory cytokine production were evaluated using histology, immunofluorescent imaging analysis, and gene and protein expression assays. RESULTS: The bionanomatrix coating maintained a uniform and smooth surface on the silicone even after mechanical stress conditions. In addition, the bionanomatrix coating showed sustained NO release for at least one month and reduction of differentiated monocyte adhesion and S. epidermidis biofilm formation on the silicone implants in vitro. In in vivo implantation studies, the bionanomatrix coated groups demonstrated significant reduction of capsule thickness surrounding the implants. This result was due to a decrease of myofibroblast differentiation and fibrous extracellular matrix production through inhibition of the TGF-ß/p-SMADs signaling. Also, the bionanomatrix coated groups reduced gene expression of M1 macrophage markers and promoted M2 macrophage markers which indicated the bionanomatrix could reduce inflammation but promote healing process. CONCLUSIONS: In conclusion, the bionanomatrix coating significantly reduced capsular contracture formation and promoted healing process on silicone implants by reducing myfibroblast differentiation, fibrotic tissue formation, and inflammation. A multi-targeting nitric oxide releasing bionanomatrix coating for silicone implant can reduce capsular contracture and improve healing process. The bionanomatrix coating reduces capsule thickness, α-smooth muscle actin and collagen synthesis, and myofibroblast differentiation through inhibition of TGF-ß/SMADs signaling cascades in the subcutaneous mouse models for a month.

8.
J Biomed Opt ; 28(3): 036008, 2023 03.
Article in English | MEDLINE | ID: mdl-36992694

ABSTRACT

Significance: Optical coherence tomography (OCT) has become increasingly essential in assisting the treatment of coronary artery disease (CAD). However, unidentified calcified regions within a narrowed artery could impair the outcome of the treatment. Fast and objective identification is paramount to automatically procuring accurate readings on calcifications within the artery. Aim: We aim to rapidly identify calcification in coronary OCT images using a bounding box and reduce the prediction bias in automated prediction models. Approach: We first adopt a deep learning-based object detection model to rapidly draw the calcified region from coronary OCT images using a bounding box. We measure the uncertainty of predictions based on the expected calibration errors, thus assessing the certainty level of detection results. To calibrate confidence scores of predictions, we implement dependent logistic calibration using each detection result's confidence and center coordinates. Results: We implemented an object detection module to draw the boundary of the calcified region at a rate of 140 frames per second. With the calibrated confidence score of each prediction, we lower the uncertainty of predictions in calcification detection and eliminate the estimation bias from various object detection methods. The calibrated confidence of prediction results in a confidence error of ∼ 0.13 , suggesting that the confidence calibration on calcification detection could provide a more trustworthy result. Conclusions: Given the rapid detection and effective calibration of the proposed work, we expect that it can assist in clinical evaluation of treating the CAD during the imaging-guided procedure.


Subject(s)
Calcinosis , Coronary Artery Disease , Humans , Tomography, Optical Coherence/methods , Calibration , Uncertainty , Predictive Value of Tests , Coronary Vessels/diagnostic imaging , Coronary Artery Disease/diagnostic imaging , Calcinosis/diagnostic imaging
9.
Nanoscale ; 15(7): 3461-3474, 2023 Feb 16.
Article in English | MEDLINE | ID: mdl-36723042

ABSTRACT

Vascular insults can create an inflammatory cascade involving endothelial cell, smooth muscle cell, and macrophage activation which can eventually lead to vascular disease such as atherosclerosis. Several studies have identified microRNA 146a's (miR-146a) anti-inflammatory potential based on its role in regulating the nuclear factor kappa beta (NF-κß) pathway. Therefore, in this study, we introduced exogenous miR-146a encapsulated by liposomes to lipopolysaccharide (LPS) stimulated vascular cells and macrophages to reduce inflammatory responses. First, the miR-146a encapsulated liposomes showed uniform size (radius 96.4 ± 4.22 nm) and round shape, long term stability (at least two months), high encapsulation efficiency (69.73 ± 0.07%), and were well transfected to human aortic endothelial cells (HAECs), human aortic smooth muscle cells (SMCs), and human differentiated monocytes (U937 cells). In addition, we demonstrated that miR-146a encapsulated liposomes reduced vascular inflammation responses in HAECs and SMCs through inhibition of ICAM-1 expression and decreased monocyte adhesion. In macrophages, miR-146a liposome treatment demonstrated decreased production of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß), as well as reduced oxidized low-density lipoprotein (ox-LDL) uptake and foam cell formation. Thus, based on these results, miR-146a encapsulated liposomes may be promising for reducing vascular inflammation by targeting its multiple associated mediators.


Subject(s)
Foam Cells , MicroRNAs , Humans , Endothelial Cells/metabolism , Foam Cells/metabolism , Foam Cells/pathology , Inflammation/metabolism , Intercellular Adhesion Molecule-1/metabolism , Liposomes , Macrophage Activation , MicroRNAs/genetics , MicroRNAs/metabolism , NF-kappa B/metabolism
10.
ACS Appl Mater Interfaces ; 14(46): 51728-51743, 2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36346768

ABSTRACT

Cardiovascular stent technologies have significantly improved over time. However, their optimal performance remains limited by restenosis, thrombosis, inflammation, and delayed re-endothelialization. Current stent designs primarily target inhibition of neointimal proliferation but do not promote functional arterial healing (pro-healing) in order to restore normal vascular reactivity. The endothelial lining that does develop with current stents appears to have loose intracellular junctions. We have developed a pro-healing nanomatrix coating for stents that enhances healing while limiting neointimal proliferation. This builds on our prior work evaluating the effects of the pro-healing nanomatrix coating on cultures of vascular endothelial cells (ECs), smooth muscle cells (SMCs), monocytes, and platelets. However, when a stent is deployed in an artery, multiple vascular cell types interact, and their interactions affect stent performance. Thus, in our current study, an in vitro vascular double-layer (VDL) system was used to observe stent effects on communication between different vascular cell types. Additionally, we assessed the pro-healing ability and vascular cell interactions after stent deployment in the VDL system and in a rabbit model, evaluating the nanomatrix-coated stent compared to a commercial bare metal stent (BMS) and a drug eluting stent (DES). In vitro results indicated that, in a layered vascular structure, the pro-healing nanomatrix-coated stent could (1) improve endothelialization and endothelial functions, (2) regulate SMC phenotype to reduce SMC proliferation and migration, (3) suppress inflammation through a multifactorial manner, and (4) reduce foam cell formation, extracellular matrix remodeling, and calcification. Consistent with this, in vivo results demonstrated that, compared with commercial BMS and DES, this pro-healing nanomatrix-coated stent enhanced re-endothelialization with negligible restenosis, inflammation, or thrombosis. Thus, these findings indicate the unique pro-healing features of this nanomatrix stent coating with superior efficacy over commercial BMS and DES.


Subject(s)
Drug-Eluting Stents , Thrombosis , Animals , Rabbits , Endothelial Cells/metabolism , Stents , Neointima , Thrombosis/metabolism , Inflammation/metabolism
11.
IEEE Trans Biomed Eng ; 69(12): 3667-3677, 2022 12.
Article in English | MEDLINE | ID: mdl-35594212

ABSTRACT

Coronary artery disease (CAD) is a cardiovascular condition with high morbidity and mortality. Intravascular optical coherence tomography (IVOCT) has been considered as an optimal imagining system for the diagnosis and treatment of CAD. Constrained by Nyquist theorem, dense sampling in IVOCT attains high resolving power to delineate cellular structures/features. There is a trade-off between high spatial resolution and fast scanning rate for coronary imaging. In this paper, we propose a viable spectral-spatial acquisition method that down-scales the sampling process in both spectral and spatial domain while maintaining high quality in image reconstruction. The down-scaling schedule boosts data acquisition speed without any hardware modifications. Additionally, we propose a unified multi-scale reconstruction framework, namely Multiscale-Spectral-Spatial-Magnification Network (MSSMN), to resolve highly down-scaled (compressed) OCT images with flexible magnification factors. We incorporate the proposed methods into Spectral Domain OCT (SD-OCT) imaging of human coronary samples with clinical features such as stent and calcified lesions. Our experimental results demonstrate that spectral-spatial down-scaled data can be better reconstructed than data that are down-scaled solely in either spectral or spatial domain. Moreover, we observe better reconstruction performance using MSSMN than using existing reconstruction methods. Our acquisition method and multi-scale reconstruction framework, in combination, may allow faster SD-OCT inspection with high resolution during coronary intervention.


Subject(s)
Coronary Artery Disease , Deep Learning , Humans , Tomography, Optical Coherence/methods , Coronary Artery Disease/diagnostic imaging , Stents
12.
ACS Appl Mater Interfaces ; 14(17): 19104-19115, 2022 May 04.
Article in English | MEDLINE | ID: mdl-35467831

ABSTRACT

Nitric oxide (NO) is a gaseous signaling molecule, which plays crucial roles in various biological processes, including inflammatory responses, metabolism, cardiovascular functions, and cognitive function. NO bioavailability is reduced with aging and cardiometabolic disorders in humans and rodents. NO stimulates the metabolic rate by increasing the mitochondrial biogenesis and brown fat activation. Therefore, we propose a novel technology of providing exogenous NO to improve the metabolic rate and cognitive function by promoting the development of brown adipose tissue. In the present study, we demonstrate the effects of the peptide amphiphiles-NO-releasing nanomatrix gel (PANO gel) on high-fat diet-induced obesity, insulin resistance, and cognitive functions. Eight-week-old male C57BL/6 mice were subcutaneously injected in the brown fat area with the PANO gel or vehicle (PA gel) every 2 weeks for 12 weeks. The PANO gel-injected mice gained less body weight, improved glucose tolerance, and decreased fasting serum insulin and leptin levels compared with the PA gel-injected mice. Insulin signaling in the muscle, liver, and epididymal white adipose tissue was improved by the PANO gel injection. The PANO gel reduced inflammation, increased lipolysis in the epididymal white adipose tissue, and decreased serum lipids and liver triglycerides. Interestingly, the PANO gel stimulated uncoupled protein 1 gene expression in the brown and beige fat tissues. Furthermore, the PANO gel increased the cerebral blood flow and improved learning and memory abilities. Our results suggest that using the PANO gel to supply exogenous NO is a novel technology to treat metabolic disorders and cognitive dysfunctions.


Subject(s)
Insulin Resistance , Adipose Tissue, Brown/metabolism , Animals , Diet, High-Fat/adverse effects , Insulin , Insulin Resistance/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Nitric Oxide/metabolism , Obesity/drug therapy , Obesity/metabolism
13.
Biomaterials ; 280: 121254, 2022 01.
Article in English | MEDLINE | ID: mdl-34836683

ABSTRACT

Vascular access is the lifeline for hemodialysis patients and the single most important component of the hemodialysis procedure. Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis patients, but nearly 60% of AVFs created fail to successfully mature due to early intimal hyperplasia development and poor outward remodeling. There are currently no therapies available to prevent AVF maturation failure. First, we showed the important regulatory role of nitric oxide (NO) on AVF development by demonstrating that intimal hyperplasia development was reduced in an overexpressed endothelial nitric oxide synthase (NOS3) mouse AVF model. This supported the rationale for the potential application of NO to the AVF. Thus, we developed a self-assembled NO releasing nanomatrix gel and applied it perivascularly at the arteriovenous anastomosis immediately following rat AVF creation to investigate its therapeutic effect on AVF development. We demonstrated that the NO releasing nanomatrix gel inhibited intimal hyperplasia formation (more than 70% reduction), as well as improved vascular outward remodeling (increased vein diameter) and hemodynamic adaptation (lower wall shear stress approaching the preoperative level and less vorticity). Therefore, direct application of the NO releasing nanomatrix gel to the AVF anastomosis immediately following AVF creation may enhance AVF development, thereby providing long-term and durable vascular access for hemodialysis.


Subject(s)
Arteriovenous Fistula , Vascular Remodeling , Animals , Arteriovenous Fistula/therapy , Humans , Hyperplasia , Mice , Nitric Oxide , Rats , Rodentia
14.
J Invasive Cardiol ; 33(7): E532-E539, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34224382

ABSTRACT

OBJECTIVES: Optimal stent deployment by intravascular ultrasound (IVUS) improves outcome, but it can only be achieved in 50% of patients. We investigated the feasibility and effect of a new method of stent optimization on optimal stent deployment. METHODS: IVUS analyses of 168 coronary segments were performed after angiography-guided stenting (AGS) and stent optimization in 29 patients (30 lesions). Minimum stent area (MSA), stent volume index (SVI), lumen area, external elastic membrane (EEM), and plaque burden (PB) were measured. Stent optimization included post-stent dilation with a balloon sized by high-definition (HD)-IVUS to the distal reference EEM diameter for stent underexpansion or malapposition, and stenting of PB >50% or edge dissection. RESULTS: After AGS, stent deployment was suboptimal in 77% of patients. After stent optimization, MSA and SVI were significantly larger than AGS. Adequate stent expansion - defined as MSA ≥5.4 mm² or ≥90% of distal reference lumen area - was significantly higher after stent optimization vs AGS (87% vs 56%, respectively; P=.02). Optimal stent deployment - a composite of adequate stent expansion, no malapposition, PB <50% at the stent edges, and no edge dissection - was markedly higher after stent optimization vs AGS (87% vs 35%, respectively; P<.01). CONCLUSION: After stent deployment and postdilation, stent results were suboptimal in two-thirds of patients. This simple online stent optimization by HD-IVUS was feasible and resulted in optimal stent deployment in the majority of patients. Randomized studies are warranted to compare the rate of optimal stent deployment and outcomes of this strategy vs other techniques.


Subject(s)
Angioplasty, Balloon, Coronary , Ultrasonography, Interventional , Coronary Angiography , Humans , Stents , Treatment Outcome
15.
Adv Drug Deliv Rev ; 170: 142-199, 2021 03.
Article in English | MEDLINE | ID: mdl-33428994

ABSTRACT

Atherosclerosis is a chronic inflammatory disease driven by lipid accumulation in arteries, leading to narrowing and thrombosis. It affects the heart, brain, and peripheral vessels and is the leading cause of mortality in the United States. Researchers have strived to design nanomaterials of various functions, ranging from non-invasive imaging contrast agents, targeted therapeutic delivery systems to multifunctional nanoagents able to target, diagnose, and treat atherosclerosis. Therefore, this review aims to summarize recent progress (2017-now) in the development of nanomaterials and their applications to improve atherosclerosis diagnosis and therapy during the preclinical and clinical stages of the disease.


Subject(s)
Atherosclerosis , Nanostructures , Animals , Atherosclerosis/diagnosis , Atherosclerosis/drug therapy , Humans , Nanostructures/chemistry , Nanostructures/therapeutic use
16.
Front Cardiovasc Med ; 8: 790529, 2021.
Article in English | MEDLINE | ID: mdl-35155603

ABSTRACT

Atherosclerosis is the primary cause of hardening and narrowing arteries, leading to cardiovascular disease accounting for the high mortality in the United States. For developing effective treatments for atherosclerosis, considerable efforts have been devoted to developing in vitro models. Compared to animal models, in vitro models can provide great opportunities to obtain data more efficiently, economically. Therefore, this review discusses the recent progress in in vitro models for atherosclerosis studies, including traditional two-dimensional (2D) systems cultured on the tissue culture plate, 2D cell sheets, and recently emerged microfluidic chip models with 2D culture. In addition, advanced in vitro three-dimensional models such as spheroids, cell-laden hydrogel constructs, tissue-engineered blood vessels, and vessel-on-a-chip will also be covered. Moreover, the functions of these models are also summarized along with model discussion. Lastly, the future perspectives of this field are discussed.

17.
ACS Appl Bio Mater ; 4(6): 4917-4924, 2021 06 21.
Article in English | MEDLINE | ID: mdl-35007040

ABSTRACT

Blood clots (90%) originate from the left atrial appendage (LAA) in non-valvular atrial fibrillation patients and are a major cause of embolic stroke. Long-term anticoagulation therapy has been used to prevent thrombus formation, but its use is limited in patients at a high risk for bleeding complications. Thus, left atrial appendage closure (LAAC) devices for LAA occlusion are well-established as an alternative to the anticoagulation therapy. However, the anticoagulation therapy is still required for at least 45 days post-implantation to bridge the time until complete LAA occlusion by neoendocardium coverage of the device. In this study, we applied an endothelium-mimicking nanomatrix to the LAAC device membrane for delivery of nitric oxide (NO) to enhance endothelialization, with the goal of possibly being able to reduce the duration of the anticoagulation therapy. The nanomatrix was uniformly coated on the LAAC device membranes and provided sustained release of NO for up to 1 month in vitro. In addition, the nanomatrix coating promoted endothelial cell proliferation and reduced platelet adhesion compared to the uncoated device membranes in vitro. The nanomatrix-coated and uncoated LAAC devices were then deployed in a canine LAA model for 22 days as a pilot study. All LAAC devices were not completely covered by neoendocardium 22 days post-implantation. However, histology image analysis showed that the nanomatrix-coated LAAC device had thicker neoendocardium coverage compared to the uncoated device. Therefore, our in vitro and in vivo results indicate that the nanomatrix coating has the potential to enhance endothelialization on the LAAC device membrane, which could improve patient outcomes by shortening the need for extended anticoagulation treatment.


Subject(s)
Atrial Appendage/surgery , Cardiac Surgical Procedures/instrumentation , Endothelium/drug effects , Nanostructures/administration & dosage , Animals , Anticoagulants/administration & dosage , Aorta/cytology , Aspirin/administration & dosage , Cell Proliferation/drug effects , Cells, Cultured , Dogs , Endothelial Cells/drug effects , Endothelium/physiology , Humans , Membranes, Artificial , Nitric Oxide/administration & dosage , Peptides/administration & dosage , Platelet Adhesiveness/drug effects , Warfarin/administration & dosage
18.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1879-1882, 2020 07.
Article in English | MEDLINE | ID: mdl-33018367

ABSTRACT

Optical coherence tomography (OCT) has stimulated a wide range of medical image-based diagnosis and treatment. In cardiac imaging, OCT has been used in assessing plaques before and after stenting. While needed in many scenarios, high resolution comes at the costs of demanding optical design and data storage/transmission. In OCT, there are two types of resolutions to characterize image quality: optical and digital resolutions. Although multiple existing works have heavily emphasized on improving the digital resolution, the studies on improving optical resolution or both resolutions remain scarce. In this paper, we focus on improving both resolutions. In particular, we investigate a deep learning method to address the problem of generating a high-resolution (HR) OCT image from a low optical and low digital resolution (L2R) image. To this end, we have modified the existing super-resolution generative adversarial network (SR-GAN) for OCT image reconstruction. Experimental results from the human coronary OCT images have demonstrated that the reconstructed images from highly compressed data could achieve high structural similarity and accuracy in comparison with the HR images. Besides, our method has obtained better denoising performance than the block-matching and 3D filtering (BM3D) and Denoising Convolutional Neural Networks (DnCNN) denoising method.


Subject(s)
Deep Learning , Tomography, Optical Coherence , Humans , Image Processing, Computer-Assisted , Neural Networks, Computer
19.
Case Rep Cardiol ; 2020: 8845627, 2020.
Article in English | MEDLINE | ID: mdl-32855827

ABSTRACT

Myocardial injury, represented by elevated cardiac enzymes, has been associated with increased morbidity and mortality in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections. Coronavirus disease 2019 (COVID-19) has created unique challenges in approaching patients with acute ST-segment changes. We describe two distinct cases of ST elevation on electrocardiogram occurring in patients with COVID-19 and review important diagnostic and management considerations for the front-line clinician.

20.
JACC Case Rep ; 2(9): 1356-1358, 2020 Jul 15.
Article in English | MEDLINE | ID: mdl-32835279

ABSTRACT

Myocardial injury is associated with excess mortality in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections, but the mechanisms of injury are diverse. We describe a case of stress-induced cardiomyopathy in the setting of SARS-CoV-2 and influenza A coinfection. (Level of Difficulty: Intermediate.).

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