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Sample records for plaque rupture current

  1. Fatigue crack propagation analysis of plaque rupture.

    PubMed

    Pei, Xuan; Wu, Baijian; Li, Zhi-Yong

    2013-10-01

    Rupture of atheromatous plaque is the major cause of stroke or heart attack. Considering that the cardiovascular system is a classic fatigue environment, plaque rupture was treated as a chronic fatigue crack growth process in this study. Fracture mechanics theory was introduced to describe the stress status at the crack tip and Paris' law was used to calculate the crack growth rate. The effect of anatomical variation of an idealized plaque cross-section model was investigated. The crack initiation was considered to be either at the maximum circumferential stress location or at any other possible locations around the lumen. Although the crack automatically initialized at the maximum circumferential stress location usually propagated faster than others, it was not necessarily the most critical location where the fatigue life reached its minimum. We found that the fatigue life was minimum for cracks initialized in the following three regions: the midcap zone, the shoulder zone, and the backside zone. The anatomical variation has a significant influence on the fatigue life. Either a decrease in cap thickness or an increase in lipid pool size resulted in a significant decrease in fatigue life. Comparing to the previously used stress analysis, this fatigue model provides some possible explanations of plaque rupture at a low stress level in a pulsatile cardiovascular environment, and the method proposed here may be useful for further investigation of the mechanism of plaque rupture based on in vivo patient data. PMID:23897295

  2. Multimodality Intravascular Imaging Assessment of Plaque Erosion versus Plaque Rupture in Patients with Acute Coronary Syndrome

    PubMed Central

    Kwon, Jee Eun; Mintz, Gary S.; Hong, Young Joon; Lee, Sung Yun; Kim, Ki Seok; Hahn, Joo-Yong; Kumar, Kaup Sharath; Won, Hoyoun; Hyeon, Seong Hyeop; Shin, Seung Yong; Lee, Kwang Je; Kim, Tae Ho; Kim, Chee Jeong; Kim, Sang Wook

    2016-01-01

    Background and Objectives We assessed plaque erosion of culprit lesions in patients with acute coronary syndrome in real world practice. Subjects and Methods Culprit lesion plaque rupture or plaque erosion was diagnosed with optical coherence tomography (OCT). Intravascular ultrasound (IVUS) was used to determine arterial remodeling. Positive remodeling was defined as a remodeling index (lesion/reference EEM [external elastic membrane area) >1.05. Results A total of 90 patients who had plaque rupture showing fibrous-cap discontinuity and ruptured cavity were enrolled. 36 patients showed definite OCT-plaque erosion, while 7 patients had probable OCT-plaque erosion. Overall, 26% (11/43) of definite/probable plaque erosion had non-ST elevation myocardial infarction (NSTEMI) while 35% (15/43) had ST elevation myocardial infarction (STEMI). Conversely, 14.5% (13/90) of plaque rupture had NSTEMI while 71% (64/90) had STEMI (p<0.0001). Among plaque erosion, white thrombus was seen in 55.8% (24/43) of patients and red thrombus in 27.9% (12/43) of patients. Compared to plaque erosion, plaque rupture more often showed positive remodeling (p=0.003) with a larger necrotic core area examined by virtual histology (VH)-IVUS, while negative remodeling was prominent in plaque erosion. Overall, 65% 28/43 of plaque erosions were located in the proximal 30 mm of a culprit vessel-similar to plaque ruptures (72%, 65/90, p=0.29). Conclusion Although most of plaque erosions show nearly normal coronary angiogram, modest plaque burden with negative remodeling and an uncommon fibroatheroma might be the nature of plaque erosion. Multimodality intravascular imaging with OCT and VH-IVUS showed fundamentally different pathoanatomic substrates underlying plaque rupture and erosion. PMID:27482258

  3. miRNAs in atherosclerotic plaque initiation, progression, and rupture.

    PubMed

    Andreou, Ioannis; Sun, Xinghui; Stone, Peter H; Edelman, Elazer R; Feinberg, Mark W

    2015-05-01

    Atherosclerosis is a chronic immune-inflammatory disorder that integrates multiple cell types and a diverse set of inflammatory mediators. miRNAs are emerging as important post-transcriptional regulators of gene expression in most, if not all, vertebrate cells, and constitute central players in many physiological and pathological processes. Rapidly accumulating experimental studies reveal their key role in cellular and molecular processes related to the development of atherosclerosis. We review current evidence for the involvement of miRNAs in early atherosclerotic lesion formation and in plaque rupture and erosion. We conclude with a perspective on the clinical relevance, therapeutic opportunities, and future challenges of miRNA biology in understanding the pathogenesis of this complex disease. PMID:25771097

  4. miRNAs in atherosclerotic plaque initiation, progression, and rupture

    PubMed Central

    Andreou, Ioannis; Sun, Xinghui; Stone, Peter H.; Edelman, Elazer R.; Feinberg, Mark W.

    2015-01-01

    Atherosclerosis is a chronic immune-inflammatory disorder that integrates multiple cell types and a diverse set of inflammatory mediators. miRNAs are emerging as important post-transcriptional regulators of gene expression in most, if not all, vertebrate cells and constitute central players in many physiological and pathological processes. Rapidly accumulating experimental studies reveal their key role in cellular and molecular processes related to the development of atherosclerosis. Here, we review the current evidence for the involvement of miRNAs in early atherosclerotic lesion formation to plaque rupture and erosion. We conclude with a perspective on the clinical relevance, therapeutic opportunities, and future challenges of miRNA biology in the pathogenesis of this complex disease. PMID:25771097

  5. Changing Views of the Biomechanics of Vulnerable Plaque Rupture, a Review

    PubMed Central

    Cardoso, Luis; Weinbaum, Sheldon

    2013-01-01

    This review examines changing perspectives on the biomechanics of vulnerable plaque rupture over the past 25 years from the first FEA showing that the presence of a lipid pool significantly increases the local tissue stress in the atheroma cap to the latest imaging and 3D FEA studies revealing numerous microcalcifications in the cap proper and a new paradigm for cap rupture. The first part of the review summarizes studies describing the role of the fibrous cap thickness, tissue properties and lesion geometry as main determinants of the risk of rupture. Advantages and limitations of current imaging technologies for assessment of vulnerable plaques are also discussed. However, the basic paradoxes as to why ruptures frequently did not coincide with location of PCS and why caps > 65 μm thickness could rupture at tissue stresses significantly below the 300 kPa critical threshold still remained unresolved. The second part of the review describes recent studies in the role of microcalcifications, their origin, shape and clustering in explaining these unresolved issues including the actual mechanism of rupture due to the explosive growth of tiny voids (cavitation) in locals regions of high stress concentration between closely spaced microinclusions oriented along their tensile axis. PMID:23842694

  6. Optical measurement of arterial mechanical properties: from atherosclerotic plaque initiation to rupture

    PubMed Central

    2013-01-01

    Abstract. During the pathogenesis of coronary atherosclerosis, from lesion initiation to rupture, arterial mechanical properties are altered by a number of cellular, molecular, and hemodynamic processes. There is growing recognition that mechanical factors may actively drive vascular cell signaling and regulate atherosclerosis disease progression. In advanced plaques, the mechanical properties of the atheroma influence stress distributions in the fibrous cap and mediate plaque rupture resulting in acute coronary events. This review paper explores current optical technologies that provide information on the mechanical properties of arterial tissue to advance our understanding of the mechanical factors involved in atherosclerosis development leading to plaque rupture. The optical approaches discussed include optical microrheology and traction force microscopy that probe the mechanical behavior of single cell and extracellular matrix components, and intravascular imaging modalities including laser speckle rheology, optical coherence elastography, and polarization-sensitive optical coherence tomography to measure the mechanical properties of advanced coronary lesions. Given the wealth of information that these techniques can provide, optical imaging modalities are poised to play an increasingly significant role in elucidating the mechanical aspects of coronary atherosclerosis in the future. PMID:24296995

  7. Is Cadmium Exposure Associated with the Burden, Vulnerability and Rupture of Human Atherosclerotic Plaques?

    PubMed Central

    Sallsten, Gerd; Lundh, Thomas; Barregard, Lars

    2015-01-01

    The general population is exposed to cadmium from food and smoking. Cadmium is a widely spread toxic pollutant that seems to be associated with cardiovascular diseases, although little is known if it contributes to the occurrence of atherosclerotic plaques and the process whereby plaques become vulnerable and are prone to rupture. We tested the hypotheses that cadmium exposure is associated not only with an increased subclinical burden of atherosclerotic plaques in different vascular territories and early signs of plaque vulnerability, but also with cadmium content and plaque-rupture in the clinical phase of the disease. Ultrasound technique was used to measure plaque prevalence and echogenicity in the carotid and femoral arteries in a population sample of women (n = 599) in whom blood cadmium was measured. In addition cadmium was measured in snap-frozen endarterectomies and whole blood obtained from patients who were referred to surgery because of symptomatic carotid plaques (n = 37). Sixteen endarterectomies were divided into three parts corresponding to different flow conditions and plaque vulnerability. In the population sample blood cadmium was associated with the number of vascular territories with plaques (p = 0.003 after adjustment for potential confounders). The cadmium concentrations in symptomatic plaques were 50-fold higher in plaque tissue than in blood. Cadmium levels in blood and plaque correlated, also after adjustment for smoking and other cardiovascular risk factors (p<0.001). Compared with the other parts of the plaque, the cadmium content was double as high in the part where plaque rupture usually occurs. In conclusion, the results show that cadmium exposure is associated with the burden of subclinical atherosclerosis in middle-aged women with different degrees of glucose tolerance, and that the content of cadmium in symptomatic plaques in patients is related to that in blood, but much higher, and preferentially located in the part of plaque

  8. Detection of plaque rupture using 64-slice multidetector row computed tomography

    PubMed Central

    Reimann, Anja J; Beck, Torsten; Heuschmid, Martin; Brodoefel, Harald; Burgstahler, Christof; Schröder, Stephen; Kopp, Andreas F

    2008-01-01

    The present case report describes a 37-year-old man who presented to the emergency room with symptoms of a myocardial infarction but no high-grade stenosis on conventional catheter angiography. Consecutive multi-detector row computed tomography of the coronary arteries showed an intimal flap along a fibrous plaque formation in the left anterior descending artery. This finding was found to represent a plaque rupture, and the lesion was treated with an 18 mm stent. Multidetector row computed tomography helped to correctly position the stent by identifying the exact location of the rupture along the long plaque formation. PMID:18340394

  9. Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture

    PubMed Central

    Lee, K.; Santibanez-Koref, M.; Polvikoski, T.; Birchall, D.; Mendelow, A.D.; Keavney, B.

    2013-01-01

    Objective Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. Methods and results We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptured human atherosclerotic plaques. Plaques present in carotid endarterectomy specimens were designated as stable or ruptured using clinical, radiological and histopathological criteria. Macrophage-rich regions were excised from 5 ruptured and 6 stable plaques by laser micro-dissection. Transcriptional profiling was performed using Affymetrix microarrays. The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences (p < 0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine signaling pathway were the most significantly upregulated in ruptured compared to stable plaques (p = 5.4 × 10−7). Two key components of the pathway, fatty-acid binding-protein 4 (FABP4) and leptin, showed nine-fold (p = 0.0086) and five-fold (p = 0.0012) greater expression respectively in macrophages from ruptured plaques. Conclusions We found differences in gene expression signatures between macrophages isolated from stable and ruptured human atheromatous plaques. Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential. PMID:23122912

  10. The Fat-Fed Apolipoprotein E Knockout Mouse Brachiocephalic Artery in the Study of Atherosclerotic Plaque Rupture

    PubMed Central

    Bond, Andrew R.; Jackson, Christopher L.

    2011-01-01

    Atherosclerosis has been studied in animals for almost a century, yet the events leading up to the rupture of an atherosclerotic plaque (the underlying cause of the majority of fatal thrombosis formation) have only been studied in the past decade, due in part to the development of a mouse model of spontaneous plaque rupture. Apolipoprotein E knockout mice, when fed a high-fat diet, consistently develop lesions in the brachiocephalic artery that rupture at a known time point. It is therefore now possible to observe the development of lesions to elucidate the mechanisms behind the rupture of plaques. Critics argue that the model does not replicate the appearance of human atherosclerotic plaque ruptures. The purpose of this review is to highlight the reasons why we should be looking to the apolipoprotein E knockout mouse to further our understanding of plaque rupture. PMID:21076539

  11. Atherosclerosis and atheroma plaque rupture: imaging modalities in the visualization of vasa vasorum and atherosclerotic plaques.

    PubMed

    Sun, Zhonghua

    2014-01-01

    Invasive angiography has been widely accepted as the gold standard to diagnose cardiovascular pathologies. Despite its superior resolution of demonstrating atherosclerotic plaque in terms of degree of lumen stenosis, the morphological assessment for the plaque is insufficient for the analysis of plaque components, and therefore, unable to predict the risk status or vulnerability of atherosclerotic plaque. There is an increased body of evidence to show that the vasa vasorum play an important role in the initiation, progression, and complications of atherosclerotic plaque leading to major adverse cardiac events. This paper provides an overview of the evidence-based reviews of various imaging modalities with regard to their potential value for comprehensive characterization of the composition, burden, and neovascularization of atherosclerotic plaque. PMID:24688380

  12. Atherosclerosis and Atheroma Plaque Rupture: Imaging Modalities in the Visualization of Vasa Vasorum and Atherosclerotic Plaques

    PubMed Central

    2014-01-01

    Invasive angiography has been widely accepted as the gold standard to diagnose cardiovascular pathologies. Despite its superior resolution of demonstrating atherosclerotic plaque in terms of degree of lumen stenosis, the morphological assessment for the plaque is insufficient for the analysis of plaque components, and therefore, unable to predict the risk status or vulnerability of atherosclerotic plaque. There is an increased body of evidence to show that the vasa vasorum play an important role in the initiation, progression, and complications of atherosclerotic plaque leading to major adverse cardiac events. This paper provides an overview of the evidence-based reviews of various imaging modalities with regard to their potential value for comprehensive characterization of the composition, burden, and neovascularization of atherosclerotic plaque. PMID:24688380

  13. Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism.

    PubMed

    Abela, Oliver G; Ahsan, Chowdhury H; Alreefi, Fadi; Salehi, Negar; Baig, Imran; Janoudi, Abed; Abela, George S

    2016-06-01

    Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis-often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy. PMID:27091328

  14. Biomechanical modeling and morphology analysis indicates plaque rupture due to mechanical failure unlikely in atherosclerosis-prone mice.

    PubMed

    Campbell, Ian C; Weiss, Daiana; Suever, Jonathan D; Virmani, Renu; Veneziani, Alessandro; Vito, Raymond P; Oshinski, John N; Taylor, W Robert

    2013-02-01

    Spontaneous plaque rupture in mouse models of atherosclerosis is controversial, although numerous studies have discussed so-called "vulnerable plaque" phenotypes in mice. We compared the morphology and biomechanics of two acute and one chronic murine model of atherosclerosis to human coronaries of the thin-cap fibroatheroma (TCFA) phenotype. Our acute models were apolipoprotein E-deficient (ApoE(-/-)) and LDL receptor-deficient (LDLr(-/-)) mice, both fed a high-fat diet for 8 wk with simultaneous infusion of angiotensin II (ANG II), and our chronic mouse model was the apolipoprotein E-deficient strain fed a regular chow diet for 1 yr. We found that the mouse plaques from all three models exhibited significant morphological differences from human TCFA plaques, including the plaque burden, plaque thickness, eccentricity, and amount of the vessel wall covered by lesion as well as significant differences in the relative composition of plaques. These morphological differences suggested that the distribution of solid mechanical stresses in the walls may differ as well. Using a finite-element analysis computational solid mechanics model, we computed the relative distribution of stresses in the walls of murine and human plaques and found that although human TCFA plaques have the highest stresses in the thin fibrous cap, murine lesions do not have such stress distributions. Instead, local maxima of stresses were on the media and adventitia, away from the plaque. Our results suggest that if plaque rupture is possible in mice, it may be driven by a different mechanism than mechanics. PMID:23203971

  15. In Vivo Detection of Activated Platelets Allows Characterizing Rupture of Atherosclerotic Plaques with Molecular Magnetic Resonance Imaging in Mice

    PubMed Central

    Wiens, Kristina; Neudorfer, Irene; Zirlik, Andreas; Meissner, Mirko; Tilly, Peg; Charles, Anne-Laure; Bode, Christoph; Peter, Karlheinz; Fabre, Jean-Etienne

    2012-01-01

    Background Early and non-invasive detection of platelets on micro atherothrombosis provides a means to identify unstable plaque and thereby allowing prophylactic treatment towards prevention of stroke or myocardial infarction. Molecular magnetic resonance imaging (mMRI) of activated platelets as early markers of plaque rupture using targeted contrast agents is a promising strategy. In this study, we aim to specifically image activated platelets in murine atherothrombosis by in vivo mMRI, using a dedicated animal model of plaque rupture. Methods An antibody targeting ligand-induced binding sites (LIBS) on the glycoprotein IIb/IIIa-receptor of activated platelets was conjugated to microparticles of iron oxide (MPIO) to form the LIBS-MPIO contrast agent causing a signal-extinction in T2*-weighted MRI. ApoE−/− mice (60 weeks-old) were fed a high fat diet for 5 weeks. Using a small needle, the surface of their carotid plaques was scratched under blood flow to induce atherothrombosis. In vivo 9.4 Tesla MRI was performed before and repetitively after intravenous injection of either LIBS-MPIO versus non-targeted-MPIO. Results LIBS-MPIO injected animals showed a significant signal extinction (p<0.05) in MRI, corresponding to the site of plaque rupture and atherothrombosis in histology. The signal attenuation was effective for atherothrombosis occupying ≥2% of the vascular lumen. Histology further confirmed significant binding of LIBS-MPIO compared to control-MPIO on the thrombus developing on the surface of ruptured plaques (p<0.01). Conclusion in vivo mMRI detected activated platelets on mechanically ruptured atherosclerotic plaques in ApoE−/− mice with a high sensititvity. This imaging technology represents a unique opportunity for noninvasive detection of atherothrombosis and the identification of unstable atherosclerotic plaques with the ultimate promise to prevent strokes and myocardial infarctions. PMID:23028736

  16. A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture.

    PubMed

    Maldonado, Natalia; Kelly-Arnold, Adreanne; Vengrenyuk, Yuliya; Laudier, Damien; Fallon, John T; Virmani, Renu; Cardoso, Luis; Weinbaum, Sheldon

    2012-09-01

    The role of microcalcifications (μCalcs) in the biomechanics of vulnerable plaque rupture is examined. Our laboratory previously proposed (Ref. 44), using a very limited tissue sample, that μCalcs embedded in the fibrous cap proper could significantly increase cap instability. This study has been greatly expanded. Ninety-two human coronary arteries containing 62 fibroatheroma were examined using high-resolution microcomputed tomography at 6.7-μm resolution and undecalcified histology with special emphasis on calcified particles <50 μm in diameter. Our results reveal the presence of thousands of μCalcs, the vast majority in lipid pools where they are not dangerous. However, 81 μCalcs were also observed in the fibrous caps of nine of the fibroatheroma. All 81 of these μCalcs were analyzed using three-dimensional finite-element analysis, and the results were used to develop important new clinical criteria for cap stability. These criteria include variation of the Young's modulus of the μCalc and surrounding tissue, μCalc size, and clustering. We found that local tissue stress could be increased fivefold when μCalcs were closely spaced, and the peak circumferential stress in the thinnest nonruptured cap (66 μm) if no μCalcs were present was only 107 kPa, far less than the proposed minimum rupture threshold of 300 kPa. These results and histology suggest that there are numerous μCalcs < 15 μm in the caps, not visible at 6.7-μm resolution, and that our failure to find any nonruptured caps between 30 and 66 μm is a strong indication that many of these caps contained μCalcs. PMID:22777419

  17. Is the carotid plaque rupture a pivotal event in stroke pathogenesis? Update on the role of the intraplaque inflammatory processes.

    PubMed

    Pende, Aldo; Dallegri, Franco

    2015-01-01

    Stroke, a leading cause of death or disability worldwide, is frequently dependent on the rupture of carotid atherosclerotic plaques. It is therefore extremely important to study the mechanisms of formation, progression and eventually rupture of the plaques. Vulnerability of the plaque, the intrinsic tendency to lose its integrity and consequently to induce a dramatic atherothrombotic or embolic event, is still an elusive concept because many players are involved and the clinical picture is frequently the sum of different contrasting (pro-inflammatory and anti-inflammatory) phenomena. This review will discuss recent advancements in the comprehension of this topic. In particular inflammatory activation at the level of the carotid plaque will be described in the attempt to underline the main factors for the formation, the chronic persistence and the risk of rupture. Since these topics can be studied in humans only with plaque samples obtained following endarterectomy, research has tried to evaluate the role of different biomarkers which could be useful for the definition of the vulnerability of a carotid plaque, or, with more clinical relevance, of a patient; some recent results from our group will be discussed. A significant help for clinical decisions may also come from imaging tools, both well established ultrasound and more sophisticated options, such as magnetic resonance and positron emission tomography. This large amount of scientific information should allow the development of new therapeutic approaches for the effective prevention of cerebrovascular events. PMID:24188488

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

    PubMed Central

    Lanter, Bernard B.; Sauer, Karin

    2014-01-01

    ABSTRACT Atherosclerosis, 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 from Pseudomonas spp. were detected. Pseudomonas aeruginosa biofilms have been shown in our lab to undergo a dispersion response when challenged with free iron in vitro. Iron is known to be released into the blood by transferrin following interaction with catecholamine hormones, such as norepinephrine. Experiments performed in vitro showed that addition of physiologically relevant levels of norepinephrine induced dispersion of P. aeruginosa biofilms when grown under low iron conditions in the presence but not in the absence of physiological levels of transferrin. PMID:24917599

  19. The vulnerable plaque: current concepts and future perspectives on coronary morphology, composition and wall stress imaging.

    PubMed

    Silva Marques, João; Pinto, Fausto J

    2014-02-01

    Cardiovascular imaging plays an important role in the identification and characterization of the vulnerable plaque. A major goal is the ability to identify individuals at risk of plaque rupture and developing an acute coronary syndrome. Early recognition of rupture-prone atherosclerotic plaques may lead to the development of pharmacologic and interventional strategies to reduce acute coronary events. We review state-of-the-art cardiovascular imaging for identification of the vulnerable plaque. There is ample evidence of a close relationship between plaque morphology and patient outcome, but molecular imaging can add significant information on tissue characterization, inflammation and subclinical thrombosis. Additionally, identifying arterial wall exposed to high shear stress may further identify rupture-prone arterial segments. These new modalities may help reduce the individual, social and economic burden of cardiovascular disease. PMID:24513090

  20. Emergent surgical embolectomy for middle cerebral artery occlusion due to carotid plaque rupture followed by elective carotid endarterectomy.

    PubMed

    Kiyofuji, Satoshi; Inoue, Tomohiro; Hasegawa, Hirotaka; Tamura, Akira; Saito, Isamu

    2014-09-01

    Embolic intracranial large artery occlusion with severe neurological deficit is associated with an extremely poor prognosis. The safest and most effective treatment strategy has not yet been determined when such emboli are associated with unstable proximal carotid plaque. The authors performed emergent surgical embolectomy for left middle cerebral artery (MCA) occlusion, and the patient experienced marked neurological recovery without focal deficit and regained premorbid activity. Postoperative investigation revealed "vulnerable plaque" of the left internal carotid artery without apparent evidence of cardiac embolism, such as would be seen with atrial fibrillation. Specimens from subsequent elective carotid endarterectomy (CEA) showed ruptured vulnerable plaque that was histologically consistent as a source of the intracranial embolic specimen. Surgical embolectomy for MCA occlusion due to carotid plaque rupture followed by CEA could be a safer and more effective alternative to endovascular treatment from the standpoint of obviating the risk of secondary embolism that could otherwise occur as a result of the manipulation of devices through an extremely unstable portion of plaque. Further, this strategy is associated with a high probability of complete recanalization with direct removal of hard and large, though fragile, emboli. PMID:24905562

  1. From vulnerable plaque to atherothrombosis.

    PubMed

    Thim, T; Hagensen, M K; Bentzon, J F; Falk, E

    2008-05-01

    Plaque rupture precipitates approximately 75% of all fatal coronary thrombi. Therefore, the plaque prone to rupture is the primary focus of this review. The lipid-rich core and fibrous cap are pivotal in the understanding of plaque rupture. Plaque rupture is a localized process within the plaque caused by degradation of a tiny fibrous cap rather than by diffuse inflammation of the plaque. Atherosclerosis is a multifocal disease, but plaques prone to rupture seem to be oligofocal at most. PMID:18410594

  2. Effect of culprit-lesion remodeling versus plaque rupture on three-year outcome in patients with acute coronary syndrome.

    PubMed

    Okura, Hiroyuki; Kobayashi, Yoshio; Sumitsuji, Satoru; Terashima, Mitsuyasu; Kataoka, Toru; Masutani, Motomaru; Ohyanagi, Mitsumasa; Shimada, Kenei; Taguchi, Haruyuki; Yasuga, Yuji; Takeda, Yoshihiro; Ohashi, Yoshitaka; Awano, Kojiro; Fujii, Kenichi; Mintz, Gary S

    2009-03-15

    To investigate intravascular ultrasound predictors of long-term clinical outcome in patients with acute coronary syndrome, 94 patients with a first acute coronary syndrome with both preintervention intravascular ultrasound imaging and long-term follow-up were enrolled in this study. Remodeling index was defined as external elastic membrane cross-sectional area at the target lesion divided by that at the proximal reference. Arterial remodeling was defined as either positive (PR: remodeling index >1.05) or intermediate/negative remodeling (remodeling index < or =1.05). Clinical events were death, myocardial infarction, and target-lesion revascularization. Patients were followed up for a mean of 3 years. PR was observed in 50 (53%), and intermediate/negative remodeling, in 44 (47%). During the 3-year follow-up, there were 20 target-lesion revascularization events and 5 deaths (2 cardiac and 3 noncardiac), but no myocardial infarctions. Patients with PR showed significantly lower major adverse cardiac event (MACE; death, myocardial infarction, and target-lesion revascularization)-free survival (log-rank p = 0.03). However, patients with plaque rupture showed a nonsignificant trend toward lower MACE-free survival (p = 0.13), but there were no significant differences in MACE-free survival between those with single versus multiple plaque ruptures. Using multivariate logistic regression analysis, only culprit lesion PR was an independent predictor of MACEs (p = 0.04). In conclusion, culprit-lesion remodeling rather than the presence or absence of culprit-lesion plaque rupture was a strong predictor of long-term (3-year) clinical outcome in patients with acute coronary syndrome. PMID:19268733

  3. Cholesterol-independent effects of atorvastatin prevent cardiovascular morbidity and mortality in a mouse model of atherosclerotic plaque rupture.

    PubMed

    Roth, Lynn; Rombouts, Miche; Schrijvers, Dorien M; Martinet, Wim; De Meyer, Guido R Y

    2016-05-01

    Because cholesterol-independent effects of statins are difficult to determine in patients, we studied these pleiotropic effects in apolipoprotein E-deficient (ApoE(-/-)) mice with a mutation in the fibrillin-1 gene (Fbn1(C1039G+/-)). These mice develop exacerbated atherosclerosis and spontaneous plaque ruptures, accompanied by myocardial infarctions (MI) and sudden death. ApoE(-/-)Fbn1(C1039G+/-) mice were fed a Western diet (WD). At week 10 of WD, mice were divided in a control (WD), atorvastatin (10mg/kg/day + WD) and cholesterol withdrawal group (cholW, normal chow). The latter was included to compare the effects of atorvastatin with dietary lipid lowering. Fifteen weeks later, the mice were sacrificed. CholW, but not atorvastatin, reduced plasma cholesterol. Survival increased from 50% to 90% both in cholW and atorvastatin treated mice. CholW as well as atorvastatin treatment increased plaque collagen and fibrous cap thickness, but they did not affect the amount of plaque macrophages and T cells. MMP-2 and MMP-9 activity was significantly lower and the expression of MMP-12, TNF-α and IL-1β was strongly reduced in both treatment groups. Blood monocytes and neutrophils returned to baseline levels (ApoE(-/-) mice before the onset of atherosclerosis). Importantly, atorvastatin but not cholW significantly reduced coronary stenosis (from 50 to 28%) and the occurrence of MI (from 43 to 10%). In conclusion, independent of cholesterol lowering, atorvastatin significantly reduced mortality, plaque vulnerability and inflammation to the same extent as cholW. In addition, atorvastatin but not cholW reduced coronary stenosis and the occurrence of MI. These data unequivocally illustrate the significance of the pleiotropic effects of atorvastatin in the prevention of cardiovascular morbidity and mortality. PMID:26826559

  4. Vulnerable Plaque

    MedlinePlus

    ... all vulnerable plaque ruptures, and researchers at the Texas Heart Institute are looking at ways to determine ... comments. Terms of Use and Privacy Policy © Copyright Texas Heart Institute All rights reserved.

  5. Atherosclerosis and atheroma plaque rupture: normal anatomy of vasa vasorum and their role associated with atherosclerosis.

    PubMed

    Sun, Zhonghua

    2014-01-01

    Atherosclerosis is primarily a degenerative disorder related to aging with a chronic inflammatory component. There are differences in expression among different vascular beds, inflicting a range of vascular diseases. The majority of studies focus on the inner and medial vascular layers, which are affected at the development of atherosclerosis. Recent evidence shows that the outer layer of blood vessels, composed of the adventitial layer and the vasa vasorum, not only plays a significant role in maintaining vessel integrity, but also reacts to atheroma. What is not clear is the extent of contribution of the outer layer to the process of atherosclerosis. Is it involved in the initiation, progression, and clinical expression of atheroma? Is the inflammation associated with atheroma limited to being merely reactive or is there a proactive element? This paper provides an overview of the normal anatomy of vasa vasorum and potential mechanism of plaque formation due to vascular injury (vasa vasorum) and microhemorrhage. PMID:24790560

  6. Atherosclerosis and Atheroma Plaque Rupture: Normal Anatomy of Vasa Vasorum and Their Role Associated with Atherosclerosis

    PubMed Central

    2014-01-01

    Atherosclerosis is primarily a degenerative disorder related to aging with a chronic inflammatory component. There are differences in expression among different vascular beds, inflicting a range of vascular diseases. The majority of studies focus on the inner and medial vascular layers, which are affected at the development of atherosclerosis. Recent evidence shows that the outer layer of blood vessels, composed of the adventitial layer and the vasa vasorum, not only plays a significant role in maintaining vessel integrity, but also reacts to atheroma. What is not clear is the extent of contribution of the outer layer to the process of atherosclerosis. Is it involved in the initiation, progression, and clinical expression of atheroma? Is the inflammation associated with atheroma limited to being merely reactive or is there a proactive element? This paper provides an overview of the normal anatomy of vasa vasorum and potential mechanism of plaque formation due to vascular injury (vasa vasorum) and microhemorrhage. PMID:24790560

  7. Imaging unstable plaque.

    PubMed

    Sriranjan, Rouchelle S; Tarkin, Jason M; Evans, Nicholas R; Chowdhury, Mohammed M; Rudd, James H

    2016-09-01

    Recent advances in imaging technology have enabled us to utilise a range of diagnostic approaches to better characterise high-risk atherosclerotic plaque. The aim of this article is to review current and emerging techniques used to detect and quantify unstable plaque in the context of large and small arterial systems and will focus on both invasive and non-invasive imaging techniques. While the diagnosis of clinically relevant atherosclerosis still relies heavily on anatomical assessment of arterial luminal stenosis, evolving multimodal cross-sectional imaging techniques that encompass novel molecular probes can provide added information with regard to plaque composition and overall disease burden. Novel molecular probes currently being developed to track precursors of plaque rupture such as inflammation, micro-calcification, hypoxia and neoangiogenesis are likely to have translational applications beyond diagnostics and have the potential to play a part in quantifying early responses to therapeutic interventions and more accurate cardiovascular risk stratification. PMID:27273430

  8. Plaque Size Is Decreased but M1 Macrophage Polarization and Rupture Related Metalloproteinase Expression Are Maintained after Deleting T-Bet in ApoE Null Mice

    PubMed Central

    Tsaousi, Aikaterini; Hayes, Elaine M.; Di Gregoli, Karina; Bond, Andrew R.; Bevan, Laura

    2016-01-01

    Background Thelper1 (Th1) lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1) macrophage activation or production of matrix degrading metalloproteinases (MMPs) and their tissue inhibitors, TIMPs. Methods & Results We studied the effect of T-bet deletion in apolipoproteinE (ApoE) knockout mice fed a high fat diet (HFD) or normal chow diet (ND). Transcript levels of M1/M2 macrophage polarization markers, selected MMPs and TIMPs were measured by RT-qPCR in macrophages isolated from subcutaneous granulomas or in whole aortae. Immunohistochemistry of aortic sinus (AS) and brachiocephalic artery (BCA) plaques was conducted to quantify protein expression of the same factors. Deletion of T-bet decreased mRNA for the M1 marker NOS-2 in granuloma macrophages but levels of M2 markers (CD206, arginase-1 and Ym-1), MMPs-2, -9, -12, -13, -14 and -19 or TIMPs-1 to -3 were unchanged. No mRNA differences were observed in aortic extracts from mice fed a HFD for 12 weeks. Moreover, AS and BCA plaques were similarly sized between genotypes, and had similar areas stained for NOS-2, COX-2, MMP-12 and MMP-14 proteins. T-bet deletion increased MMP-13, MMP-14 and arginase-1 in AS plaques. After 35 weeks of ND, T-bet deletion reduced the size of AS and BCA plaques but there were no differences in the percentage areas stained for M1 or M2 markers, MMPs-12, -13, -14, or TIMP-3. Conclusions Absence of Th1 lymphocytes is associated with reduced plaque size in ApoE knockout mice fed a normal but not high fat diet. In either case, M1 macrophage polarization and expression of several MMPs related to plaque instability are either maintained or increased. PMID:26886778

  9. MRI-based biomechanical parameters for carotid artery plaque vulnerability assessment.

    PubMed

    Speelman, Lambert; Teng, Zhongzhao; Nederveen, Aart J; van der Lugt, Aad; Gillard, Jonathan H

    2016-02-29

    Carotid atherosclerotic plaques are a major cause of ischaemic stroke. The biomechanical environment to which the arterial wall and plaque is subjected to plays an important role in the initiation, progression and rupture of carotid plaques. MRI is frequently used to characterize the morphology of a carotid plaque, but new developments in MRI enable more functional assessment of carotid plaques. In this review, MRI based biomechanical parameters are evaluated on their current status, clinical applicability, and future developments. Blood flow related biomechanical parameters, including endothelial wall shear stress and oscillatory shear index, have been shown to be related to plaque formation. Deriving these parameters directly from MRI flow measurements is feasible and has great potential for future carotid plaque development prediction. Blood pressure induced stresses in a plaque may exceed the tissue strength, potentially leading to plaque rupture. Multi-contrast MRI based stress calculations in combination with tissue strength assessment based on MRI inflammation imaging may provide a plaque stress-strength balance that can be used to assess the plaque rupture risk potential. Direct plaque strain analysis based on dynamic MRI is already able to identify local plaque displacement during the cardiac cycle. However, clinical evidence linking MRI strain to plaque vulnerability is still lacking. MRI based biomechanical parameters may lead to improved assessment of carotid plaque development and rupture risk. However, better MRI systems and faster sequences are required to improve the spatial and temporal resolution, as well as increase the image contrast and signal-to-noise ratio. PMID:26791734

  10. Cap buckling as a potential mechanism of atherosclerotic plaque vulnerability.

    PubMed

    Abdelali, Maria; Reiter, Steven; Mongrain, Rosaire; Bertrand, Michel; L'Allier, Philippe L; Kritikou, Ekaterini A; Tardif, Jean-Claude

    2014-04-01

    Plaque rupture in atherosclerosis is the primary cause of potentially deadly coronary events, yet about 40% of ruptures occur away from the plaque cap shoulders and cannot be fully explained with the current biomechanical theories. Here, cap buckling is considered as a potential destabilizing factor which increases the propensity of the atherosclerotic plaque to rupture and which may also explain plaque failure away from the cap shoulders. To investigate this phenomenon, quasistatic 2D finite element simulations are performed, considering the salient geometrical and nonlinear material properties of diverse atherosclerotic plaques over the range of physiological loads. The numerical results indicate that buckling may displace the location of the peak von Mises stresses in the deflected caps. Plaque buckling, together with its deleterious effects is further observed experimentally in plaque caps using a physical model of deformable mock coronary arteries with fibroatheroma. Moreover, an analytical approach combining quasistatic equilibrium equations with the Navier-Bresse formulas is used to demonstrate the buckling potential of a simplified arched slender cap under intraluminal pressure and supported by foundations. This analysis shows that plaque caps - calcified, fibrotic or cellular - may buckle in specific undulated shapes once submitted to critical loads. Finally, a preliminary analysis of intravascular ultrasonography recordings of patients with atherosclerotic coronary arteries corroborates the numerical, experimental and theoretical findings and shows that various plaque caps buckle in vivo. By displacing the sites of high stresses in the plaque cap, buckling may explain the atherosclerotic plaque cap rupture at various locations, including cap shoulders. PMID:24491969

  11. Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes: a role for CD40 signaling in plaque rupture?

    PubMed

    Schönbeck, U; Mach, F; Sukhova, G K; Murphy, C; Bonnefoy, J Y; Fabunmi, R P; Libby, P

    1997-09-01

    Physical disruption of an atheromatous lesion often underlies acute coronary syndromes. Matrix-degrading enzymes, eg, matrix metalloproteinases (MMPs), may cause loss in mechanical integrity of plaque tissue that favors rupture. T lymphocytes accumulate at sites where atheromata rupture, but the mechanisms by which these immune cells may contribute to plaque destabilization are unknown. This study tested the hypothesis that the T-lymphocyte surface molecule CD40 ligand (CD40L), recently localized in atherosclerotic plaques, regulates the expression of MMPs in human vascular smooth muscle cells (SMCs), the most numerous cell type in arteries. We report here that stimulated human T lymphocytes induced the expression of the matrix-degrading enzymes, ie, interstitial collagenase (MMP-1), stromelysin (MMP-3), gelatinase B (MMP-9), and activated gelatinase A (MMP-2), in human vascular SMCs by cell contact via CD40 ligation, as demonstrated by Western blot analysis, zymography, and antibody neutralization. Recombinant human CD40L (rCD40L) induced de novo synthesis of MMP-1, MMP-3, and MMP-9 on vascular SMCs and stimulated the expression of these enzymes to a greater extent than did maximally effective concentrations of tumor necrosis factor-alpha or interleukin-1beta, established agonists of MMP expression. Interferon gamma, another T-lymphocyte- derived cytokine, inhibited the induction of MMPs by rCD40L. Immunohistochemical analysis of human coronary atheromata colocalized MMP-1 and MMP-3 with CD40-positive SMCs. These results demonstrated that CD40 ligand, expressed on T lymphocytes, promoted the expression of matrix-degrading enzymes in vascular SMCs and thus established a new pathway of immune-modulated destabilization in human atheromata. PMID:9285647

  12. The human HDL proteome displays high inter-individual variability and is altered dynamically in response to angioplasty-induced atheroma plaque rupture.

    PubMed

    Jorge, Inmaculada; Burillo, Elena; Mesa, Raquel; Baila-Rueda, Lucía; Moreno, Margoth; Trevisan-Herraz, Marco; Silla-Castro, Juan Carlos; Camafeita, Emilio; Ortega-Muñoz, Mariano; Bonzon-Kulichenko, Elena; Calvo, Isabel; Cenarro, Ana; Civeira, Fernando; Vázquez, Jesús

    2014-06-25

    Recent findings support potential roles for HDL in cardiovascular pathophysiology not related to lipid metabolism. We address whether HDL proteome is dynamically altered in atheroma plaque rupture. We used immunoaffinity purification of HDL samples from coronary artery disease patients before and after percutaneous transluminal coronary angioplasty (PTCA), a model of atheroma plaque disruption. Samples were analyzed by quantitative proteomics using stable isotope labeling and results were subjected to statistical analysis of protein variance using a novel algorithm. We observed high protein variability in HDL composition between individuals, indicating that HDL protein composition is highly patient-specific. However, intra-individual protein variances remained at low levels, confirming the reproducibility of the method used for HDL isolation and protein quantification. A systems biology analysis of HDL protein alterations induced by PTCA revealed an increase in two protein clusters that included several apolipoproteins, fibrinogen-like protein 1 and other intracellular proteins, and a decrease in antithrombin-III, annexin A1 and several immunoglobulins. Our results support the concept of HDL as dynamic platforms that donate and receive a variety of molecules and provide an improved methodology to use HDL proteome for the systematic analysis of differences among individuals and the search for cardiovascular biomarkers. Biological significance The HDL proteome is an interesting model of clinical relevance and has been previously described to be dynamically altered in response to pathophysiological conditions and cardiovascular diseases. Our study suggests that interindividual variability of HDL proteome is higher than previously thought and provided the detection of a set of proteins that changed their abundance in response to plaque rupture, supporting the concept of HDL as dynamic platforms that donate and receive a variety of molecules. PMID:24747125

  13. Impact of arterial remodelling and plaque rupture on target and non‐target lesion revascularisation after stent implantation in patients with acute coronary syndrome: an intravascular ultrasound study

    PubMed Central

    Okura, Hiroyuki; Taguchi, Haruyuki; Kubo, Tomoichiro; Toda, Iku; Yoshiyama, Minoru; Yoshikawa, Junichi; Yoshida, Kiyoshi

    2007-01-01

    Objectives To investigate the impact of arterial remodelling on long‐term clinical outcome after stent implantation in patients with acute coronary syndrome (ACS). Methods 134 patients with ACS were enrolled. External elastic membrane (EEM) cross‐sectional area (CSA) and lumen CSA were measured. Plaque and media CSA was calculated as EEM minus lumen CSA. Final minimal stent area (MSA) was also measured after stenting. Positive remodelling (PR) was defined as the ratio of the EEM CSA at the target lesion to that at the proximal reference of >1.05, and intermediate or negative remodelling (IR/NR) was defined as that of ⩽1.05. Results Although final MSA was similar, target lesion revascularisation (TLR) rates at 2 years were significantly higher in patients with PR (33.7%) than in those with IR/NR (13.7%; p = 0.01). In addition, non‐TLR rates were also significantly higher in patients with PR (42.2%) than in those with IR/NR (23.5%; p = 0.03). Cardiac event‐free survival (for events such as death, myocardial infarction, TLR and non‐TLR) was significantly lower in patients with PR than in those with IR/NR (log rank, p = 0.001). By multivariate logistic regression analysis, PR (χ2 6.57, OR 2.70; 95% CI, 1.27 to 5.78; p = 0.01) and plaque rupture (χ2 4.17, OR 2.38; 95% CI, 1.04 to 5.45; p = 0.04) were independent predictors of cardiac events. Conclusion In patients with ACS, PR and intravascular ultrasound findings that may correspond with plaque rupture predict cardiac events including both TLR and non‐TLR at 2 years. PMID:17395673

  14. [Achilles tendon rupture : Current diagnostic and therapeutic standards].

    PubMed

    Hertel, G; Götz, J; Grifka, J; Willers, J

    2016-08-01

    A superior life expectancy and an increased activity in the population result in an increase in degenerative diseases, such as Achilles tendon ruptures. The medical history and physical examinations are the methods of choice to diagnose Achilles tendon ruptures. Ultrasound and radiography represent reasonable extended diagnostic procedures. In order to decide on the medical indications for the therapy concept, the advantages and disadvantages of conservative and surgical treatment options have to be weighed up on an indivdual basis. There are explicit contraindications for both treatment options. For the surgical treatment concept open suture techniques, minimally invasive methods and reconstructive procedures are available. The postoperative management of the patient is as important as the choice of surgical technique. With the correct medical indications and supervision of the patient it is possible to achieve extremely satisfying results for the patient with both conservative and surgical treatment options. PMID:27405457

  15. Comparison by optical coherence tomography of the frequency of lipid coronary plaques in current smokers, former smokers, and nonsmokers.

    PubMed

    Abtahian, Farhad; Yonetsu, Taishi; Kato, Koji; Jia, Haibo; Vergallo, Rocco; Tian, Jinwei; Hu, Sining; McNulty, Iris; Lee, Hang; Yu, Bo; Jang, Ik-Kyung

    2014-09-01

    Smoking is associated with high incidence of cardiovascular events including acute coronary syndrome. We sought to characterize coronary plaques in patients with ongoing smoking using optical coherence tomography (OCT) compared with former smokers and nonsmokers. We identified 465 coronary plaques from 182 subjects who underwent OCT imaging for all 3 coronary arteries. Subjects were divided into 3 groups: current smokers (n = 41), former smokers (n = 67), and nonsmokers (n = 74). OCT analysis included the presence of lipid-rich plaque, thin-cap fibroatheroma (TCFA), calcification, maximum lipid arc, lipid core length, lipid index, and fibrous cap thickness. Lipid index was defined by mean lipid arc multiplied by lipid core length. Compared with former smokers and nonsmokers, the incidence of lipid plaques and TCFA was significantly higher in current smokers (lipid plaques: 68.0% vs 45.9% and 52.6%, p = 0.002; TCFA: 18.4% vs 7.6% and 9.9%, p = 0.018). There was a trend for higher plaque disruption in current smokers. Former smokers were more likely to have calcified plaques than current and nonsmokers (52.9% vs 32.0% and 38.0%, p = 0.001). In a multivariate analysis, current smoking, low-density lipoprotein, and presentation with acute coronary syndrome were independently associated with the presence of TCFAs. In conclusion, current smokers are more likely to have lipid plaques and OCT-defined vulnerable plaques (TCFAs). Former smokers have increased number of calcified plaques. These results may explain the increased risk of acute cardiac events among smokers. PMID:25048344

  16. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    PubMed Central

    Goel, Sunny; Miller, Avraham; Agarwal, Chirag; Zakin, Elina; Acholonu, Michael; Gidwani, Umesh; Sharma, Abhishek; Kulbak, Guy; Shani, Jacob; Chen, On

    2015-01-01

    Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level. PMID:26798515

  17. The Vulnerable Plaque: the Real Villain in Acute Coronary Syndromes

    PubMed Central

    Liang, Michael; Puri, Aniket; Devlin, Gerard

    2011-01-01

    The term "vulnerable plaque" refers to a vascular lesion that is prone to rupture and may result in life-threatening events which include myocardial infarction. It consists of thin-cap fibroatheroma and a large lipid core which is highly thrombogenic. Acute coronary syndromes often result from rupture of vulnerable plaques which frequently are only moderately stenosed and not visible by conventional angiography. Several invasive and non-invasive strategies have been developed to assess the burden of vulnerable plaques. Intravascular ultrasound provides a two-dimensional cross-sectional image of the arterial wall and can help assess the plaque burden and composition. Optical coherent tomography offers superior resolution over intravascular ultrasound. High-resolution magnetic resonance imaging provides non-invasive imaging for visualizing fibrous cap thickness and rupture in plaques. In addition, it may be of value in assessing the effects of treatments, such as lipid-lowering therapy. Technical issues however limit its clinical applicability. The role of multi-slice computed tomography, a well established screening tool for coronary artery disease, remains to be determined. Fractional flow reserve (FFR) may provide physiological functional assessment of plaque vulnerability; however, its role in the management of vulnerable plaque requires further studies. Treatment of the vulnerable patient may involve systemic therapy which currently include statins, ACE inhibitors, beta-blockers, aspirin, and calcium-channel blockers and in the future local therapeutic options such as drug-eluting stents or photodynamic therapy. PMID:21673834

  18. Impaired gait pattern as a sensitive tool to assess hypoxic brain damage in a novel mouse model of atherosclerotic plaque rupture.

    PubMed

    Roth, Lynn; Van Dam, Debby; Van der Donckt, Carole; Schrijvers, Dorien M; Lemmens, Katrien; Van Brussel, Ilse; De Deyn, Peter P; Martinet, Wim; De Meyer, Guido R Y

    2015-02-01

    Apolipoprotein E deficient (ApoE(-/-)) mice with a heterozygous mutation in the fibrillin-1 gene (Fbn1(C1039G+/-)) show spontaneous atherosclerotic plaque ruptures, disturbances in cerebral flow and sudden death when fed a Western-type diet (WD). The present study focused on motor coordination and spatial learning of ApoE(-/-) Fbn1(C1039G+/-) mice on WD for 20 weeks (n=21). ApoE(-/-) mice on WD (n=24) and ApoE(-/-) Fbn1(C1039G+/-) mice on normal diet (ND, n=21) served as controls. Starting from 10 weeks of diet, coordination was assessed every two weeks by the following tests: gait analysis, stationary beam, wire suspension and accelerating rotarod. The Morris water maze test was performed after 13 weeks of diet to study spatial learning. At the end of the experiment (20 weeks of WD), the mice were sacrificed and the brachiocephalic artery and brain were isolated. From 12 weeks onward, gait analysis of ApoE(-/-) Fbn1(C1039G+/-) mice on WD revealed a progressive increase in track width as compared to ApoE(-/-) mice on WD and ApoE(-/-) Fbn1(C1039G+/-) mice on ND (at 20 weeks: 29.8±0.6 mm vs. 25.8±0.4 mm and 26.0±0.5 mm). Moreover, the stationary beam test showed a decrease in motor coordination of ApoE(-/-) Fbn1(C1039G+/-) mice on WD at 18 and 20 weeks. The wire suspension test and accelerating rotarod could not detect signs of motor impairment. Spatial learning was also not affected. Histological analysis of the brachiocephalic artery showed larger and more stenotic plaques in ApoE(-/-) Fbn1(C1039G+/-) mice on WD. Furthermore, the parietal cortex of ApoE(-/-) Fbn1(C1039G+/-) mice on WD showed pyknotic nuclei as a sign of hypoxia and the percentage of pyknosis correlated with track width. In conclusion, gait analysis may be an efficient method for analyzing hypoxic brain damage in the ApoE(-/-) Fbn1(C1039G+/-) mouse model. This test could be of value to assess the effect of potential anti-atherosclerotic therapies in mice. PMID:25449385

  19. Investigation of the composition of arterial plaques based on arterial waveforms and material properties.

    PubMed

    Feng, J; Rajeswaran, T; He, S; Wilkinson, F L; Serracino-Inglott, F; Azzawi, M; Parikh, V; Miraftab, M; Alexander, M Y

    2015-08-01

    Stroke is mainly caused by a narrowing of the carotid artery from a build-up of plaque. The risk of plaque rupture and subsequent stroke is dependent on plaque composition. Advances in imaging modalities offer a non-invasive means to assess the health of blood vessels and detect damage. However, the current diagnosis fails to identify patients with soft lipid plaque that are more susceptible to fissure, resulting in stroke. The aim of this study was to use waveform analysis to identify plaque composition and the risk of rupture. We have investigated pressure and flow by combining an artificial blood flow circuit with tubing containing different materials, to simulate plaques in a blood vessel. We used fat and bone to model lipid and calcification respectively to determine if the composition of plaques can be identified by arterial waveforms. We demonstrate that the arterial plaque models with different percentages of calcification and fat, results in significantly different arterial waveforms. These findings imply that arterial waveform analysis has the potential for further development to identify the vulnerable plaques prone to rupture. These findings could have implications for improved patient prognosis by speed of detection and a more appropriate treatment strategy. PMID:26736431

  20. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis

    PubMed Central

    Wang, Yi; Qiu, Juhui; Luo, Shisui; Xie, Xiang; Zheng, Yiming; Zhang, Kang; Ye, Zhiyi; Liu, Wanqian; Gregersen, Hans; Wang, Guixue

    2016-01-01

    Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions. PMID:27482467

  1. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis.

    PubMed

    Wang, Yi; Qiu, Juhui; Luo, Shisui; Xie, Xiang; Zheng, Yiming; Zhang, Kang; Ye, Zhiyi; Liu, Wanqian; Gregersen, Hans; Wang, Guixue

    2016-12-01

    Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions. PMID:27482467

  2. Quantification of plaque stiffness by Brillouin microscopy in experimental thin cap fibroatheroma.

    PubMed

    Antonacci, Giuseppe; Pedrigi, Ryan M; Kondiboyina, Avinash; Mehta, Vikram V; de Silva, Ranil; Paterson, Carl; Krams, Rob; Török, Peter

    2015-11-01

    Plaques vulnerable to rupture are characterized by a thin and stiff fibrous cap overlaying a soft lipid-rich necrotic core. The ability to measure local plaque stiffness directly to quantify plaque stress and predict rupture potential would be very attractive, but no current technology does so. This study seeks to validate the use of Brillouin microscopy to measure the Brillouin frequency shift, which is related to stiffness, within vulnerable plaques. The left carotid artery of an ApoE(-/-)mouse was instrumented with a cuff that induced vulnerable plaque development in nine weeks. Adjacent histological sections from the instrumented and control arteries were stained for either lipids or collagen content, or imaged with confocal Brillouin microscopy. Mean Brillouin frequency shift was 15.79 ± 0.09 GHz in the plaque compared with 16.24 ± 0.15 (p < 0.002) and 17.16 ± 0.56 GHz (p < 0.002) in the media of the diseased and control vessel sections, respectively. In addition, frequency shift exhibited a strong inverse correlation with lipid area of -0.67 ± 0.06 (p < 0.01) and strong direct correlation with collagen area of 0.71 ± 0.15 (p < 0.05). This is the first study, to the best of our knowledge, to apply Brillouin spectroscopy to quantify atherosclerotic plaque stiffness, which motivates combining this technology with intravascular imaging to improve detection of vulnerable plaques in patients. PMID:26559685

  3. Pathophysiology of Atherosclerotic Plaque Development.

    PubMed

    Rognoni, Andrea; Cavallino, Chiara; Veia, Alessia; Bacchini, Sara; Rosso, Roberta; Facchini, Manuela; Secco, Gioel G; Lupi, Alessandro; Nardi, Federico; Rametta, Francesco; Bongo, Angelo S

    2015-01-01

    Cardiovascular diseases and in particular coronary atherosclerotic disease are the leading cause of mortality and morbidity in the industrialized countries. Coronary atherosclerosis has been recognized for over a century and it was the subject of various studies. Pathophysiological studies have unravelled the interactions of molecular and cellular elements involved in atherogenesis; during the last decades the basic research has focused on the study of the instability of atherosclerotic plaque. Plaque rupture and resulting intracoronary thrombosis are thought to account for most acute coronary syndromes including ST - segment elevation myocardial infarction and non ST - segment elevation myocardial infarction. This is a brief review of the pathophysiology of atherosclerotic plaque development. PMID:25544119

  4. Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation

    PubMed Central

    Tang, Jun; Lobatto, Mark E.; Hassing, Laurien; van der Staay, Susanne; van Rijs, Sarian M.; Calcagno, Claudia; Braza, Mounia S.; Baxter, Samantha; Fay, Francois; Sanchez-Gaytan, Brenda L.; Duivenvoorden, Raphaël; Sager, Hendrik B.; Astudillo, Yaritzy M.; Leong, Wei; Ramachandran, Sarayu; Storm, Gert; Pérez-Medina, Carlos; Reiner, Thomas; Cormode, David P.; Strijkers, Gustav J.; Stroes, Erik S. G.; Swirski, Filip K.; Nahrendorf, Matthias; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2015-01-01

    Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E–deficient mice (Apoe−/−) with advanced atherosclerotic plaques. This resulted in the rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an 8-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis. PMID:26295063

  5. Contemporary carotid imaging: from degree of stenosis to plaque vulnerability.

    PubMed

    Brinjikji, Waleed; Huston, John; Rabinstein, Alejandro A; Kim, Gyeong-Moon; Lerman, Amir; Lanzino, Giuseppe

    2016-01-01

    Carotid artery stenosis is a well-established risk factor of ischemic stroke, contributing to up to 10%-20% of strokes or transient ischemic attacks. Many clinical trials over the last 20 years have used measurements of carotid artery stenosis as a means to risk stratify patients. However, with improvements in vascular imaging techniques such as CT angiography and MR angiography, ultrasonography, and PET/CT, it is now possible to risk stratify patients, not just on the degree of carotid artery stenosis but also on how vulnerable the plaque is to rupture, resulting in ischemic stroke. These imaging techniques are ushering in an emerging paradigm shift that allows for risk stratifications based on the presence of imaging features such as intraplaque hemorrhage (IPH), plaque ulceration, plaque neovascularity, fibrous cap thickness, and presence of a lipid-rich necrotic core (LRNC). It is important for the neurosurgeon to be aware of these new imaging techniques that allow for improved patient risk stratification and outcomes. For example, a patient with a low-grade stenosis but an ulcerated plaque may benefit more from a revascularization procedure than a patient with a stable 70% asymptomatic stenosis with a thick fibrous cap. This review summarizes the current state-of-the-art advances in carotid plaque imaging. Currently, MRI is the gold standard in carotid plaque imaging, with its high resolution and high sensitivity for identifying IPH, ulceration, LRNC, and inflammation. However, MRI is limited due to time constraints. CT also allows for high-resolution imaging and can accurately detect ulceration and calcification, but cannot reliably differentiate LRNC from IPH. PET/CT is an effective technique to identify active inflammation within the plaque, but it does not allow for assessment of anatomy, ulceration, IPH, or LRNC. Ultrasonography, with the aid of contrast enhancement, is a cost-effective technique to assess plaque morphology and characteristics, but it is

  6. Noninvasive In Vivo Characterization of Human Carotid Plaques with Acoustic Radiation Force Impulse (ARFI) Ultrasound: Comparison with Histology Following Endarterectomy

    PubMed Central

    Czernuszewicz, Tomasz J.; Homeister, Jonathon W.; Caughey, Melissa C.; Farber, Mark A.; Fulton, Joseph J.; Ford, Peter F.; Marston, William A.; Vallabhaneni, Raghuveer; Nichols, Timothy C.; Gallippi, Caterina M.

    2014-01-01

    Ischemic stroke from thromboembolic sources is linked to carotid artery atherosclerotic disease with a trend toward medical management in asymptomatic patients. Extent of disease is currently diagnosed by noninvasive imaging techniques that measure luminal stenosis, but it has been suggested that a better biomarker for determining risk of future thromboembolic events is plaque morphology and composition. Specifically, plaques that are composed of mechanically-soft lipid/necrotic regions covered by thin fibrous caps are the most vulnerable to rupture. An ultrasound technique that noninvasively interrogates the mechanical properties of soft tissue, called acoustic radiation force impulse (ARFI) imaging, has been developed as a new modality for atherosclerotic plaque characterization using phantoms and atherosclerotic pigs, but the technique has yet to be validated in vivo in humans. In this preliminary study, in vivo ARFI imaging is presented in a case-study format from four patients undergoing clinically-indicated carotid endarterectomy and compared to histology. In two type Va plaques, characterized by lipid/necrotic cores covered by fibrous caps, mean ARFI displacements in focal regions were high relative to the surrounding plaque material, suggesting soft features covered by stiffer layers within the plaques. In two type Vb plaques, characterized by heavy calcification, mean ARFI peak displacements were low relative to the surrounding plaque and arterial wall, suggesting stiff tissue. This pilot study demonstrates the feasibility and challenges of transcutaneous ARFI for characterizing the material and structural composition of carotid atherosclerotic plaques via mechanical properties, in humans, in vivo. PMID:25619778

  7. Radionuclide imaging - A molecular key to the atherosclerotic plaque

    PubMed Central

    Langer, Harald Franz; Haubner, Roland; Pichler, Bernd Juergen; Gawaz, Meinrad

    2008-01-01

    Despite primary and secondary prevention, serious cardiovascular events like unstable angina or myocardial infarction still account for one third of all deaths worldwide. Therefore, identifying individual patients with vulnerable plaques at high risk for plaque rupture is a central challenge in cardiovascular medicine. Several non-invasive techniques, such as MRI, multislice computed tomography and electron beam tomography are currently being tested for their ability to identify such patients by morphological criteria. In contrast, molecular imaging techniques use radiolabeled molecules to detect functional aspects in atherosclerotic plaques by visualizing its biological activity. Based upon the knowledge about the pathophysiology of atherosclerosis, various studies in vitro, in vivo and the first clinical trials have used different tracers for plaque imaging studies, including radioactive labelled lipoproteins, components of the coagulation system, cytokines, mediators of the metalloproteinase system, cell adhesion receptors and even whole cells. This review gives an update on the relevant non-invasive plaque imaging approaches using nuclear imaging techniques to detect atherosclerotic vascular lesions. PMID:18582628

  8. Ultrafast optical-ultrasonic system and miniaturized catheter for imaging and characterizing atherosclerotic plaques in vivo

    PubMed Central

    Li, Jiawen; Ma, Teng; Mohar, Dilbahar; Steward, Earl; Yu, Mingyue; Piao, Zhonglie; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Patel, Pranav M.; Chen, Zhongping

    2015-01-01

    Atherosclerotic coronary artery disease (CAD) is the number one cause of death worldwide. The majority of CAD-induced deaths are due to the rupture of vulnerable plaques. Accurate assessment of plaques is crucial to optimize treatment and prevent death in patients with CAD. Current diagnostic techniques are often limited by either spatial resolution or penetration depth. Several studies have proved that the combined use of optical and ultrasonic imaging techniques increase diagnostic accuracy of vulnerable plaques. Here, we introduce an ultrafast optical-ultrasonic dual-modality imaging system and flexible miniaturized catheter, which enables the translation of this technology into clinical practice. This system can perform simultaneous optical coherence tomography (OCT)-intravascular ultrasound (IVUS) imaging at 72 frames per second safely in vivo, i.e., visualizing a 72 mm-long artery in 4 seconds. Results obtained in atherosclerotic rabbits in vivo and human coronary artery segments show that this ultrafast technique can rapidly provide volumetric mapping of plaques and clearly identify vulnerable plaques. By providing ultrafast imaging of arteries with high resolution and deep penetration depth simultaneously, this hybrid IVUS-OCT technology opens new and safe opportunities to evaluate in real-time the risk posed by plaques, detect vulnerable plaques, and optimize treatment decisions. PMID:26678300

  9. Ruptured eardrum

    MedlinePlus

    Tympanic membrane perforation; Eardrum - ruptured or perforated; Perforated eardrum ... Buttaravoli P, Leffler SM. Perforated tympanic membrane (ruptured eardrum). ... PA: Mosby Elsevier; 2012:chap 37. Kerschner JE. Otitis ...

  10. Reflection spectroscopy of atherosclerotic plaque

    NASA Astrophysics Data System (ADS)

    Lilledahl, Magnus B.; Haugen, Olav A.; Barkost, Marianne; Svaasand, Lars O.

    2006-03-01

    Heart disease is the primary cause of death in the western world. Many of these deaths are caused by the rupture of vulnerable plaque. Vulnerable plaques are characterized by a large lipid core covered by a thin fibrous cap. One method for detecting these plaques is reflection spectroscopy. Several studies have investigated this method using statistical methods. A more analytic and quantitative study might yield more insight into the sensitivity of this detection modality. This is the approach taken in this work. Reflectance spectra in the spectral region from 400 to 1700 nm are collected from 77 measurement points from 23 human aortas. A measure of lipid content in a plaque based on reflection spectra is presented. The measure of lipid content is compared with the thickness of the lipid core, determined from histology. Defining vulnerable plaque as having a lipid core >500 µm and fibrous cap <500 µm, vulnerable plaques are detected with a sensitivity of 88% and a specificity of 94%. Although the method can detect lipid content, it is not very sensitive to the thickness of the fibrous cap. Another detection modality is necessary to detect this feature.

  11. Collagenases and cracks in the plaque

    PubMed Central

    Libby, Peter

    2013-01-01

    The core of an atheromatous plaque contains lipids, macrophages, and cellular debris, typically covered by a fibrous cap that separates the thrombogenic core from the blood. Rupture of the fibrous cap causes most fatal myocardial infarctions. Interstitial collagen confers tensile strength on the cap, as it does in skin and tendons. In 1994, Peter Libby and colleagues demonstrated overexpression of collagenolytic enzymes in atheromatous plaques and implicated MMPs in the destabilization of these lesions. PMID:23908120

  12. Fishbowl Plaques.

    ERIC Educational Resources Information Center

    Lambert, Phyllis Gilchrist

    1998-01-01

    Presents an elementary art activity that successfully teaches the process of slabbing by having students create fishbowl plaques. Explains the process step-by-step beginning with a demonstration to the students along with showing previous examples. Endorses a type of clay that fires white because the glaze colors are much more vibrant. (CMK)

  13. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models.

    PubMed

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE(-/-) and ApoE(-/-)Fbn1C1039G(+/-) mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  14. Emerging applications of nanotechnology for the diagnosis and management of vulnerable atherosclerotic plaques.

    PubMed

    Yu, Shann S; Ortega, Ryan A; Reagan, Brendan W; McPherson, John A; Sung, Hak-Joon; Giorgio, Todd D

    2011-01-01

    An estimated 16 million people in the United States have coronary artery disease (CAD), and approximately 325,000 people die annually from cardiac arrest. About two-thirds of unexpected cardiac deaths occur without prior recognition of cardiac disease. A vast majority of these deaths are attributable to the rupture of 'vulnerable atherosclerotic plaques'. Clinically, plaque vulnerability is typically assessed through imaging techniques, and ruptured plaques leading to acute myocardial infarction are treated through angioplasty or stenting. Despite significant advances, it is clear that current imaging methods are insufficiently capable for elucidating plaque composition--which is a key determinant of vulnerability. Further, the exciting improvement in the treatment of CAD afforded by stenting procedures has been buffered by significant undesirable host-implant effects, including restenosis and late thrombosis. Nanotechnology has led to some potential solutions to these problems by yielding constructs that interface with plaque cellular components at an unprecedented size scale. By leveraging the innate ability of macrophages to phagocytose nanoparticles, contrast agents can now be targeted to plaque inflammatory activity. Improvements in nano-patterning procedures have now led to increased ability to regenerate tissue isotropy directly on stents, enabling gradual regeneration of normal, physiologic vascular structures. Advancements in immunoassay technologies promise lower costs for biomarker measurements, and in the near future, may enable the addition of routine blood testing to the clinician's toolbox--decreasing the costs of atherosclerosis-related medical care. These are merely three examples among many stories of how nanotechnology continues to promise advances in the diagnosis and treatment of vulnerable atherosclerotic plaques. PMID:21834059

  15. Comprehensive plaque assessment by coronary CT angiography.

    PubMed

    Maurovich-Horvat, Pál; Ferencik, Maros; Voros, Szilard; Merkely, Béla; Hoffmann, Udo

    2014-07-01

    Most acute coronary syndromes are caused by sudden luminal thrombosis due to atherosclerotic plaque rupture or erosion. Preventing such an event seems to be the only effective strategy to reduce mortality and morbidity of coronary heart disease. Coronary lesions prone to rupture have a distinct morphology compared with stable plaques, and provide a unique opportunity for noninvasive imaging to identify vulnerable plaques before they lead to clinical events. The submillimeter spatial resolution and excellent image quality of modern computed tomography (CT) scanners allow coronary atherosclerotic lesions to be detected, characterized, and quantified. Large plaque volume, low CT attenuation, napkin-ring sign, positive remodelling, and spotty calcification are all associated with a high risk of acute cardiovascular events in patients. Computation fluid dynamics allow the calculation of lesion-specific endothelial shear stress and fractional flow reserve, which add functional information to plaque assessment using CT. The combination of morphologic and functional characteristics of coronary plaques might enable noninvasive detection of vulnerable plaques in the future. PMID:24755916

  16. ACTIVATION OF T LYMPHOCYTES IN ATHEROSCLEROTIC PLAQUES

    PubMed Central

    Grivel, Jean-Charles; Ivanova, Oxana; Pinegina, Natalia; Blank, Paul S.; Shpektor, Alexander; Margolis, Leonid B.; Vasilieva, Elena

    2011-01-01

    Objective To decipher the immunological mechanisms of plaque maturation and rupture, it is necessary to analyze the phenotypes and distribution of individual lymphocytes which migrate to the plaques as well as their activation at different stages of plaque formation. Methods and Results We developed a protocol to isolate plaque-residing immune cells and analyze their status using polychromatic flow cytometry. We found that the composition and phenotype of T lymphocytes in the plaques differs from that in blood. CD4 and, in particular, CD8+ T cells in plaques are highly activated; the fraction of CD8 T cells co-expressing CD25 and HLA-DR in plaques was 10 times larger than in blood. Conclusions The first flow-cytoanalysis of individual T cells in atherosclerotic plaques indicates that plaques represent a separate immunological compartment from blood with lymphocytes characterized by a high level of T cells activation, which is compatible with the presence of antigen(s) that trigger infiltration activation of these cells. The ability to isolate and characterize these cells may lead to the identification of such antigens. PMID:21960562

  17. Multiphoton microscopy of atheroslcerotic plaques

    NASA Astrophysics Data System (ADS)

    Lilledahl, Magnus B.; de Lange Davies, Catharina; Haugen, Olav A.; Svaasand, Lars O.

    2007-02-01

    Multiphoton microscopy is a techniques that fascilitates three dimensional imaging of intact, unstained tissue. Especially connective tissue has a relatively strong nonlinear optical response and can easily be imaged. Atherosclerosis is a disease where lipids accumulate in the vessel wall and there is a thickening of the intima by growth of a cap of connective tissue. The mechanical strength of this fibrous cap is of clinically importance. If the cap ruptures a thrombosis forms which can block a coronary vessel and therby causing myocardial infarction. Multiphoton microscopy can be used to image the fibrous cap and thereby determine the thickness of the cap and the structure of the connective fibres. This could possibly be developed into a diagnostic and clincal tool to monitor the vulnerability of a plaque and also to better understand the development of a plaque and effects of treatment. We have collected multiphoton microscopy images from atherosclerotic plaque in human aorta, both two photon excited fluorescens and second harmonic generated signal. The feasability of using this technique to determine the state of the plaque is explored.

  18. Targeting the vulnerable plaque: the evolving role of nuclear imaging.

    PubMed

    Davies, John R; Rudd, James F; Fryer, Tim D; Weissberg, Peter L

    2005-01-01

    The majority of acute ischemic events relating to atherosclerosis are caused by plaque rupture and ensuing thrombosis. The risk of plaque rupture is dictated in part by plaque morphology, which in turn is influenced by pathophysiologic mechanisms at the cellular and molecular level. Anatomic imaging modalities such as intravascular ultrasound, high-resolution magnetic resonance imaging, and multislice computed tomography can identify morphologic features of the vulnerable plaque, such as a large lipid core and thin fibrous cap, but give little or no information regarding molecular and cellular mechanisms, such as endothelial function, macrophage activation, lipid transport and metabolism, and cell death. Recent studies suggest that nuclear imaging may be able to provide images of sufficient quality to identify and quantify some of these molecular and cellular pathophysiologic processes. In the future this could allow for the early identification and noninvasive monitoring of vulnerable plaque. PMID:15812381

  19. Vascular MR segmentation: wall and plaque

    NASA Astrophysics Data System (ADS)

    Yang, Fuxing; Holzapfel, Gerhard; Schulze-Bauer, Christian; Stollberger, Rudolf; Thedens, Daniel; Bolinger, Lizann; Stolpen, Alan; Sonka, Milan

    2003-05-01

    Cardiovascular events frequently result from local rupture of vulnerable atherosclerotic plaque. Non-invasive assessment of plaque vulnerability is needed to allow institution of preventive measures before heart attack or stroke occur. A computerized method for segmentation of arterial wall layers and plaque from high-resolution volumetric MR images is reported. The method uses dynamic programming to detect optimal borders in each MRI frame. The accuracy of the results was tested in 62 T1-weighted MR images from 6 vessel specimens in comparison to borders manually determined by an expert observer. The mean signed border positioning errors for the lumen, internal elastic lamina, and external elastic lamina borders were -0.12+/-0.14 mm, 0.04+/-0.12mm, and -0.15+/-0.13 mm, respectively. The presented wall layer segmentation approach is one of the first steps towards non-invasive assessment of plaque vulnerability in atherosclerotic subjects.

  20. Effect of Transmural Transport Properties on Atheroma Plaque Formation and Development.

    PubMed

    Cilla, M; Martínez, M A; Peña, E

    2015-07-01

    We propose a mathematical model of atheroma plaque initiation and early development in coronary arteries using anisotropic transmural diffusion properties. Our current approach is on the process on plaque initiation and intimal thickening rather than in severe plaque progression and rupture phenomena. The effect of transport properties, in particular the anisotropy of diffusion properties of the artery, on plaque formation and development is investigated using the proposed mathematical model. There is not a strong influence of the anisotropic transmural properties on LDL, SMCs and collagen distribution and concentrations along the artery. On the contrary, foam cells distribution strongly depends on the value of the radial diffusion coefficient of the substances [Formula: see text] and the ratio [Formula: see text]. Decreasing [Formula: see text] or diffusion coefficients ratio means a higher concentration of the foam cells close to the intima. Due to the fact that foam cells concentration is associated to the necrotic core formation, the final distribution of foam cells is critical to evolve into a vulnerable or fibrotic plaque. PMID:25814436

  1. Investigation of fibrous cap stresses on vulnerable plaques leading to heart attacks.

    PubMed

    Hsiao, Hao-Ming; Wu, Yi-Yu; Tsai, Bo-Chian; Chen, Yung-Chi; Cheng, Yu-Han

    2015-01-01

    Rupture-prone plaques in the coronary arteries, called ``vulnerable plaques'', are recognized as the key factor in acute myocardial infarction. Vulnerable plaques have a thin fibrous cap over a large fatty core and are highly susceptible to rupture. In general, this type of plaque rupture is mainly associated with stress concentrated on the fibrous cap. Fibrous cap stresses are counted among the most important factors in the plaque rupture process and must be taken into consideration when assessing the plaque vulnerability leading to heart attacks. The objective of this paper was to investigate the effects of nitinol stent deployment on the morphological changes of vulnerable plaques and then to propose a new stent design concept for effectively reducing fibrous cap stresses and the associated rupture risk. The deployment of a self-expanding nitinol stent was modeled, and the resulting stress distribution on the fibrous cap was investigated. The fibrous cap stresses were more uniformly distributed and the maximum stress was reduced by 13% when the crown number of the stent was increased. This study demonstrates an excellent approach to stent design that could effectively reduce the risk of a vulnerable plaque rupturing and causing a heart attack. PMID:26684564

  2. Rupture disc

    DOEpatents

    Newton, Robert G.

    1977-01-01

    The intermediate heat transport system for a sodium-cooled fast breeder reactor includes a device for rapidly draining the sodium therefrom should a sodium-water reaction occur within the system. This device includes a rupturable member in a drain line in the system and means for cutting a large opening therein and for positively removing the sheared-out portion from the opening cut in the rupturable member. According to the preferred embodiment of the invention the rupturable member includes a solid head seated in the end of the drain line having a rim extending peripherally therearound, the rim being clamped against the end of the drain line by a clamp ring having an interior shearing edge, the bottom of the rupturable member being convex and extending into the drain line. Means are provided to draw the rupturable member away from the drain line against the shearing edge to clear the drain line for outflow of sodium therethrough.

  3. Growth of Necrotic Cores in Vulnerable Plaque

    NASA Astrophysics Data System (ADS)

    Fok, Pak-Wing

    2011-03-01

    Plaques are fatty deposits that grow mainly in arteries and develop as a result of a chronic inflammatory response. Plaques are called vulnerable when they are prone to mechanical rupture. Vulnerable Plaques (VPs) are characterized by lipid-rich, necrotic cores that are heavily infiltrated with macrophages. The rupture of VPs releases thrombogenic agents into the bloodstream, usually resulting in myocardial infarctions. We propose a quantitative model to predict the development of a plaque's necrotic core. By solving coupled reaction-diffusion equations for macrophages and dead cells, we explore the joint effects of hypoxic cell death and chemo-attraction to Ox-LDL, a molecule that is strongly linked to atherosclerosis. Our model predicts cores that have approximately the right size and shape. Normal mode analysis and subsequent calculation of the smallest eigenvalues allow us to compute the times required for the system to reach its steady state. This study allows us to make quantitative predictions for how quickly vulnerable plaques develop and how their growth depends on system parameters such as chemotactic coefficients and cell death rates.

  4. The Spatial Distribution of Plaque Vulnerabilities in Patients with Acute Myocardial Infarction

    PubMed Central

    Zheng, Guian; Li, Yuxin; Takayama, Tadateru; Nishida, Toshihiko; Sudo, Mitsumasa; Haruta, Hironori; Fukamachi, Daisuke; Okubo, Kimie; Higuchi, Yoshiharu; Hiro, Takafumi; Saito, Satoshi; Hirayama, Atsushi

    2016-01-01

    Objective Although the plaque characteristics have been recognized in patients with acute myocardial infarction (AMI), the plaque spatial distribution is not well clarified. Using color-mapping intravascular ultrasound (iMAP-IVUS), we examined culprit lesions to clarify plaque morphology, composition and spatial distribution of the sites of potential vulnerability. Methods Sixty-eight culprit lesions in 64 consecutive AMI patients who underwent angiography and IVUS examinations before intervention were analyzed. Plaque morphology and composition were quantified with iMAP-IVUS. The spatial distribution of the sites of potential vulnerability was assessed with longitudinal reconstruction of the consecutive IVUS images. The plaque characteristics were also compared between ruptured and non-ruptured lesions, and between totally occlusive (TO) and non-TO lesions. Results The sites with maximum necrotic area (maxNA), maximum plaque burden (maxPB) and most severely narrowed (minimal luminal area, MLA) were recognized vulnerability. In the majority of cases, maxNA sites were proximal to the maxPB sites, and MLA sites were distal to the maxNA and maxPB sites. Ruptures usually occurred close to maxNA sites and proximal to maxPB and MLA sites. The average distance from the site of rupture to the maxNA site was 0.33 ± 4.04 mm. Ruptured lesions showed significant vessel remodeling, greater plaque volume, and greater lipidic volume compared to those of non-ruptured lesions. Both the length and plaque burden (PB) of TO lesions were greater than those of non-TO lesions. Conclusions Instead of overlapping on maxPB sites, most maxNA sites are proximal to the maxPB sites and are the sites most likely to rupture. Plaque morphology and composition play critical roles in plaque rupture and coronary occlusion. PMID:27031514

  5. The nature of iron deposits differs between symptomatic and asymptomatic carotid atherosclerotic plaques

    DOE PAGESBeta

    Kopriva, David; Kisheev, Anastasye; Meena, Deiter; Pelle, Shaneen; Karnitsky, Max; Lavoie, Andrea; Buttigieg, Josef; Hagemeyer, Christoph E.

    2015-11-25

    Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophagesmore » with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R2 = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. Moreover, the abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin.« less

  6. The nature of iron deposits differs between symptomatic and asymptomatic carotid atherosclerotic plaques

    SciTech Connect

    Kopriva, David; Kisheev, Anastasye; Meena, Deiter; Pelle, Shaneen; Karnitsky, Max; Lavoie, Andrea; Buttigieg, Josef; Hagemeyer, Christoph E.

    2015-11-25

    Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophages with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R2 = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. Moreover, the abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin.

  7. The Nature of Iron Deposits Differs between Symptomatic and Asymptomatic Carotid Atherosclerotic Plaques

    PubMed Central

    Kopriva, David; Kisheev, Anastasye; Meena, Deiter; Pelle, Shaneen; Karnitsky, Max; Lavoie, Andrea; Buttigieg, Josef

    2015-01-01

    Iron within atherosclerotic plaque has been implicated as a catalyst of oxidative stress that causes progression of plaque, and plaque rupture. Iron is believed to accumulate within plaque by incorporation of erythrocytes following plaque rupture and hemorrhage. There is only indirect evidence to support this hypothesis. Plaque specimens were obtained from ten symptomatic and fifteen asymptomatic patients undergoing carotid endarterectomy at a single institution. Plaques were sectioned for study using synchrotron radiation induced X-ray fluorescence the study the distribution of zinc, calcium and iron. Histologic staining was carried out with Prussian Blue, and immunohistochemical staining was done to localize macrophages with CD68. Data were compared against patient clinical variables. Ten symptomatic (15 ± 10 days between index symptoms and surgery) and fifteen asymptomatic carotid plaques were studied. Zinc and calcium co-localized in mineralized areas of symptomatic and asymptomatic plaque. Iron was identified away from zinc and calcium in both symptomatic and asymptomatic plaques. Within the symptomatic plaques, iron was found within the thrombus associated with plaque rupture and hemorrhage. It did not stain with Prussian Blue, but was found in association with CD68 positive macrophages. In symptomatic plaques, the abundance of iron showed an association with the source patient’s LDL cholesterol (R2 = 0.39, Significance F = 0.05). Iron in asymptomatic plaque was present as hemosiderin/ferritin that stained positive with Prussian Blue, and was observed in association with CD68 positive macrophages. Iron in acutely symptomatic plaques is found within thrombus, in the presence of macrophages. The abundance of iron in symptomatic plaques is associated with the source patient’s LDL cholesterol. Within asymptomatic plaques, iron is found in association with macrophages, as hemosiderin/ferritin. PMID:26606178

  8. Assessment of coronary plaque collagen with polarization sensitive optical coherence tomography (PS-OCT)

    NASA Astrophysics Data System (ADS)

    Giattina, Susanne D.; Courtney, Brian K.; Herz, Paul R.; Harman, Michelle; Shortkroff, Sonya; Stamper, Debra L.; Liu, Bin; Fujimoto, James G.; Brezinski, Mark E.

    2006-02-01

    Current evidence indicates that most plaques classified as vulnerable or ruptured plaques do not lead to unstable angina or myocardial infarction. Improved methods are needed to risk stratify plaques to identify those which lead to most acute coronary syndromes. Collagen depletion in the intima overlying lipid collections appears to be a critical component of unstable plaques. In this study, we use polarization sensitive optical coherence tomography (PS-OCT) for the assessment of coronary plaque collagen. Collagen is birefringent, meaning that different polarization states travel through it at different velocities. Changes in PS-OCT images are a measure of tissue birefringence. Twenty-two coronary artery segments were imaged with PS-OCT and analyzed by picrosirius staining (a measure of collagen intensity and fiber size) and trichrome blue. The regression plot between PS-OCT changes and measured collagen yielded a correlation coefficient value of 0.475 (p<0.002). Good correlation was noted between two blinded investigators both with respect to PS-OCT measurements as well as luminosity as assessed by picrosirius. The predictive value of a PS-OCT measurement of negligible birefringence (less than 33% change) for minimal collagen was 93% while the predictive value of high birefringence (greater than 66% change) for high collagen concentrations was 89%. The effect of fiber type (chemical composition) was minimal relative to the effect due to fiber concentration. The capability of PS-OCT to assess plaque collagen content, in addition to its ability to generate high resolution structural assessments, make it a potentially powerful technology for identifying high risk plaques.

  9. Development of a quantitative mechanical test of atherosclerotic plaque stability.

    PubMed

    Wang, Ying; Ning, Jinfeng; Johnson, John A; Sutton, Michael A; Lessner, Susan M

    2011-09-01

    Atherosclerotic plaque rupture is the main cause of myocardial infarction and stroke. Both clinical and computational studies indicate that the shoulder region, where a plaque joins the vessel wall, is rupture-prone. Previous mechanistic studies focused on mechanical properties of the fibrous cap and tensile stresses, which could lead to tearing of the cap. Based on clinical observations of "mobile floating plaques," we postulate that de-adhesion between the fibrous cap and the underlying vessel wall may also play a role in plaque failure. Thus, measuring adhesive strength of the bond between plaque and vascular wall may provide useful new insights into plaque stability. Delamination experiments, widely used in examining inter-laminar adhesive strength of biological materials, were used to measure adhesive strength of advanced plaques in apolipoprotein E-knockout (apoE-KO) mice after 8 months on Western diet. We measured adhesive strength in terms of local energy release rate, G, during controlled plaque delamination. As a measure of the fracture energy required to delaminate a unit area of plaque from the underlying internal elastic lamina (IEL), G provides a quantitative measure of local adhesive strength of the plaque-IEL interface. The values for G acquired from 16 plaques from nine apoE-KO mouse aortas formed a positively skewed distribution with a mean of 24.5 J/m(2), median of 19.3 J/m(2), first quartile of 10.8 J/m(2), and third quartile of 34.1 J/m(2). These measurements are in the lower range of values reported for soft tissues. Histological studies confirmed delamination occurred at the interface between plaque and IEL. PMID:21757197

  10. Evaluation of collagen in atherosclerotic plaques: the use of two coherent laser-based imaging methods

    PubMed Central

    Nadkarni, Seemantini K.; Bouma, Brett E.; de Boer, Johannes; Tearney, Guillermo J.

    2009-01-01

    Acute coronary events such as myocardial infarction are frequently caused by the rupture of unstable atherosclerotic plaque. Collagen plays a key role in determining plaque stability. Methods to measure plaque collagen content are invaluable in detecting unstable atherosclerotic plaques. Recently, novel coherent laser-based imaging techniques, such as polarization-sensitive optical coherence tomography (PSOCT) and laser speckle imaging (LSI) have been investigated, and they provide a wealth of information related to collagen content and plaque stability. Additionally, given their potential for intravascular use, these technologies will be invaluable for improving our understanding of the natural history of plaque development and rupture and, hence, enable the detection of unstable plaques. In this article we review recent developments in these techniques and potential challenges in translating these methods into intra-arterial use in patients. PMID:18386093

  11. Experimental determination of circumferential properties of fresh carotid artery plaques.

    PubMed

    Lawlor, Michael G; O'Donnell, Michael R; O'Connell, Barry M; Walsh, Michael T

    2011-06-01

    Carotid endarterectomy (CEA) is currently accepted as the gold standard for interventional revascularisation of diseased arteries belonging to the carotid bifurcation. Despite the proven efficacy of CEA, great interest has been generated in carotid angioplasty and stenting (CAS) as an alternative to open surgical therapy. CAS is less invasive compared with CEA, and has the potential to successfully treat lesions close to the aortic arch or distal internal carotid artery (ICA). Following promising results from two recent trials (CREST; Carotid revascularisation endarterectomy versus stenting trial, and ICSS; International carotid stenting study) it is envisaged that there will be a greater uptake in carotid stenting, especially amongst the group who do not qualify for open surgical repair, thus creating pressure to develop computational models that describe a multitude of plaque models in the carotid arteries and their reaction to the deployment of such interventional devices. Pertinent analyses will require fresh human atherosclerotic plaque material characteristics for different disease types. This study analysed atherosclerotic plaque characteristics from 18 patients tested on site, post-surgical revascularisation through endarterectomy, with 4 tissue samples being excluded from tensile testing based on large width-length ratios. According to their mechanical behaviour, atherosclerotic plaques were separated into 3 grades of stiffness. Individual and group material coefficients were then generated analytically using the Yeoh strain energy function. The ultimate tensile strength (UTS) of each sample was also recorded, showing large variation across the 14 atherosclerotic samples tested. Experimental Green strains at rupture varied from 0.299 to 0.588 and the Cauchy stress observed in the experiments was between 0.131 and 0.779 MPa. It is expected that this data may be used in future design optimisation of next generation interventional medical devices for the

  12. Ultrafast laser ablation for targeted atherosclerotic plaque removal

    NASA Astrophysics Data System (ADS)

    Lanvin, Thomas; Conkey, Donald B.; Descloux, Laurent; Frobert, Aurelien; Valentin, Jeremy; Goy, Jean-Jacques; Cook, Stéphane; Giraud, Marie-Noelle; Psaltis, Demetri

    2015-07-01

    Coronary artery disease, the main cause of heart disease, develops as immune cells and lipids accumulate into plaques within the coronary arterial wall. As a plaque grows, the tissue layer (fibrous cap) separating it from the blood flow becomes thinner and increasingly susceptible to rupturing and causing a potentially lethal thrombosis. The stabilization and/or treatment of atherosclerotic plaque is required to prevent rupturing and remains an unsolved medical problem. Here we show for the first time targeted, subsurface ablation of atherosclerotic plaque using ultrafast laser pulses. Excised atherosclerotic mouse aortas were ablated with ultrafast near-infrared (NIR) laser pulses. The physical damage was characterized with histological sections of the ablated atherosclerotic arteries from six different mice. The ultrafast ablation system was integrated with optical coherence tomography (OCT) imaging for plaque-specific targeting and monitoring of the resulting ablation volume. We find that ultrafast ablation of plaque just below the surface is possible without causing damage to the fibrous cap, which indicates the potential use of ultrafast ablation for subsurface atherosclerotic plaque removal. We further demonstrate ex vivo subsurface ablation of a plaque volume through a catheter device with the high-energy ultrafast pulse delivered via hollow-core photonic crystal fiber.

  13. Nanoparticle uptake by macrophages in vulnerable plaques for atherosclerosis diagnosis.

    PubMed

    Melzer, Susanne; Ankri, Rinat; Fixler, Dror; Tarnok, Attila

    2015-11-01

    The composition of atherosclerotic (AS) plaques is crucial concerning rupture, thrombosis and clinical events. Two plaque types are distinguished: stable and vulnerable plaques. Vulnerable plaques are rich in inflammatory cells, mostly only M1 macrophages, and are highly susceptible to rupture. These plaques represent a high risk particularly with the standard invasive diagnosis by coronary angiography. So far there are no non-invasive low-risk clinical approaches available to detect and distinguish AS plaque types in vivo. The perspective review introduces a whole work-flow for a novel approach for non-invasive detection and classification of AS plaques using the diffusion reflection method with gold nanoparticle loaded macrophages in combination with flow and image cytometric analysis for quality assurance. Classical biophotonic methods for AS diagnosis are summarized. Phenotyping of monocytes and macrophages are discussed for specific subset labelling by nanomaterials, as well as existing studies and first experimental proofs of concept for the novel approach are shown. In vitro and in vivo detection of NP loaded macrophages (MΦ). Different ways of MΦ labelling include (1) in vitro labelling in suspension (whole blood or buffy coat) or (2) labelling of short-term MΦ cultures with re-injection of MΦ-NP into the animal to detect migration of the cells in the plaques and (3) in vivo injection of NP into the organism. PMID:26110589

  14. Imaging Atherosclerosis and Vulnerable Plaque

    PubMed Central

    Sadeghi, Mehran M.; Glover, David K.; Lanza, Gregory M.; Fayad, Zahi A.; Johnson, Lynne L.

    2010-01-01

    Identifying patients at high risk for an acute cardiovascular event such as myocardial infarction or stroke and assessing the total atherosclerotic burden are clinically important. Currently available imaging modalities can delineate vascular wall anatomy and, with novel probes, target biologic processes important in plaque evolution and plaque stability. Expansion of the vessel wall involving remodeling of the extracellular matrix can be imaged, as can angiogenesis of the vasa vasorum, plaque inflammation, and fibrin deposits on early nonocclusive vascular thrombosis. Several imaging platforms are available for targeted vascular imaging to acquire information on both anatomy and pathobiology in the same imaging session using either hybrid technology (nuclear combined with CT) or MRI combined with novel probes targeting processes identified by molecular biology to be of importance. This article will discuss the current state of the art of these modalities and challenges to clinical translation. PMID:20395341

  15. Reducing dental plaque formation and caries development. A review of current methods and implications for novel pharmaceuticals.

    PubMed

    Kalesinskas, Povilas; Kačergius, Tomas; Ambrozaitis, Arvydas; Pečiulienė, Vytautė; Ericson, Dan

    2014-01-01

    Dental caries is an oral disease, which has a high worldwide prevalence despite the availability of various prophylactic means, including the daily use of fluoride toothpastes, water fluoridation, dental sealants, oral health educational programs and various antiseptic mouth-rinses. One important reason for this is uncontrolled increase in consumption of foods containing considerable sucrose concentration, especially among children. Sucrose is easily metabolized by oral bacteria (mostly streptococci) to acids and, subsequently, causing tooth decay or dental caries. In the oral ecosystem, streptococci principally reside on tooth surfaces forming biofilm. Important structural and binding materials of biofilm are glucan polymers synthesized by several isoforms of glucosyltransferase enzyme present in certain species of oral bacteria, including mutans group streptococci - Streptococcus mutans and Streptococcus sobrinus, which preferably colonize humans. Thus, there is a constant need to develop the methods and chemotherapeutics for improving oral health care and decreasing teeth decay through the suppression of cariogenic biofilm formation in the oral cavity. The aim of this paper was to review literature related to the pathogenesis of dental caries as well as currently existing and experimental pharmaceutical substances used for prevention of this process. PMID:25209226

  16. Direct association between diet and the stability of human atherosclerotic plaque.

    PubMed

    Gonçalves, Isabel; Andersson Georgiadou, Elisavet; Mattsson, Sören; Skog, Göran; Pedro, Luís; Fernandes E Fernandes, José; Dias, Nuno; Engström, Gunnar; Nilsson, Jan; Stenström, Kristina

    2015-01-01

    Mediterranean diet has been suggested to explain why coronary heart disease mortality is lower in southern than northern Europe. Dietary habits can be revealed by isotope ratio mass spectrometry (IRMS) measurement of carbon (δ(13)C) and nitrogen (δ(15)N) in biological tissues. To study if diet is associated with human plaque stability, atherosclerotic plaques from carotid endarterectomy on 56 patients (21 Portuguese and 35 Swedish) were analysed by IRMS and histology. Plaque components affecting rupture risk were measured. Swedish plaques had more apoptosis, lipids and larger cores, as well as fewer proliferating cells and SMC than the Portuguese, conferring the Swedish a more rupture-prone phenotype. Portuguese plaques contained higher δ(13)C and δ(15)N than the Swedish, indicating that Portuguese plaques were more often derived from marine food. Plaque δ(13)C correlated with SMC and proliferating cells, and inversely with lipids, core size, apoptosis. Plaque δ(15)N correlated with SMC and inversely with lipids, core size and apoptosis. This is the first observational study showing that diet is reflected in plaque components associated with its vulnerability. The Portuguese plaques composition is consistent with an increased marine food intake and those plaques are more stable than those from Swedish patients. Marine-derived food is associated with plaque stability. PMID:26490319

  17. Direct association between diet and the stability of human atherosclerotic plaque

    PubMed Central

    Gonçalves, Isabel; Andersson Georgiadou, Elisavet; Mattsson, Sören; Skog, Göran; Pedro, Luís; Fernandes e Fernandes, José; Dias, Nuno; Engström, Gunnar; Nilsson, Jan; Stenström, Kristina

    2015-01-01

    Mediterranean diet has been suggested to explain why coronary heart disease mortality is lower in southern than northern Europe. Dietary habits can be revealed by isotope ratio mass spectrometry (IRMS) measurement of carbon (δ13C) and nitrogen (δ15N) in biological tissues. To study if diet is associated with human plaque stability, atherosclerotic plaques from carotid endarterectomy on 56 patients (21 Portuguese and 35 Swedish) were analysed by IRMS and histology. Plaque components affecting rupture risk were measured. Swedish plaques had more apoptosis, lipids and larger cores, as well as fewer proliferating cells and SMC than the Portuguese, conferring the Swedish a more rupture-prone phenotype. Portuguese plaques contained higher δ13C and δ15N than the Swedish, indicating that Portuguese plaques were more often derived from marine food. Plaque δ13C correlated with SMC and proliferating cells, and inversely with lipids, core size, apoptosis. Plaque δ15N correlated with SMC and inversely with lipids, core size and apoptosis. This is the first observational study showing that diet is reflected in plaque components associated with its vulnerability. The Portuguese plaques composition is consistent with an increased marine food intake and those plaques are more stable than those from Swedish patients. Marine-derived food is associated with plaque stability. PMID:26490319

  18. 3D MRI-based multicomponent FSI models for atherosclerotic plaques.

    PubMed

    Tang, Dalin; Yang, Chun; Zheng, Jie; Woodard, Pamela K; Sicard, Gregorio A; Saffitz, Jeffrey E; Yuan, Chun

    2004-07-01

    A three-dimensional (3D) MRI-based computational model with multicomponent plaque structure and fluid-structure interactions (FSI) is introduced to perform mechanical analysis for human atherosclerotic plaques and identify critical flow and stress/strain conditions which may be related to plaque rupture. Three-dimensional geometry of a human carotid plaque was reconstructed from 3D MR images and computational mesh was generated using Visualization Toolkit. Both the artery wall and the plaque components were assumed to be hyperelastic, isotropic, incompressible, and homogeneous. The flow was assumed to be laminar, Newtonian, viscous, and incompressible. The fully coupled fluid and structure models were solved by ADINA, a well-tested finite element package. Results from two-dimensional (2D) and 3D models, based on ex vivo MRI and histological images (HI), with different component sizes and plaque cap thickness, under different pressure and axial stretch conditions, were obtained and compared. Our results indicate that large lipid pools and thin plaque caps are associated with both extreme maximum (stretch) and minimum (compression when negative) stress/strain levels. Large cyclic stress/strain variations in the plaque under pulsating pressure were observed which may lead to artery fatigue and possible plaque rupture. Large-scale patient studies are needed to validate the computational findings for possible plaque vulnerability assessment and rupture predictions. PMID:15298432

  19. Atherosclerotic plaque detection by confocal Brillouin and Raman microscopies

    NASA Astrophysics Data System (ADS)

    Meng, Zhaokai; Basagaoglu, Berkay; Yakovlev, Vladislav V.

    2015-02-01

    Atherosclerosis, the development of intraluminal plaque, is a fundamental pathology of cardiovascular system and remains the leading cause of morbidity and mortality worldwide. Biomechanical in nature, plaque rupture occurs when the mechanical properties of the plaque, related to the morphology and viscoelastic properties, are compromised, resulting in intraluminal thrombosis and reduction of coronary blood flow. In this report, we describe the first simultaneous application of confocal Brillouin and Raman microscopies to ex-vivo aortic wall samples. Such a non-invasive, high specific approach allows revealing a direct relationship between the biochemical and mechanical properties of atherosclerotic tissue.

  20. Mechanical modeling of cholesterol crystallization in atherosclerotic plaques base on Micro-OCT images (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Luo, Yuemei; Liu, Xinyu; Chen, Si; Cui, Dongyao; Wang, Xianghong; Liu, Linbo

    2016-02-01

    Plaque rupture is the critical cause of cardiovascular thrombosis but this process is still under discussion. Recent studies show that, during crystallization, cholesterol crystals in atheromatous plaques accumulate rapidly in a limited space and may result in plaque rupture. However, the actual role of cholesterol crystals on plaque rupture remains unclear due to the lack of detailed morphological information of cholesterol crystals. In this study, we used a Micro-optical coherence tomography (µOCT) setup with 1-2 µm spatial resolution to extract the geometry of cholesterol crystals from human atherosclerotic artery ex vivo firstly. With measured dimensions of cholesterol crystals by this µOCT system (the average length and thickness of 269.1±80.16 µm and 3.0±0.33 µm), we developed a two-dimensional mechanical model in which rectangular shaped cholesterol crystals distribute at different locations spatially. We predicted the stress on the thin cap induced by the expansion of cholesterol crystals by use of finite-element method. Since a large portion of plaques (58%) rupture at points of peak circumferential stress (PCS), we used PCS as the primary indicator of plaque stability with blood pressure of 14.6 kPa on the lumen. The results demonstrate that loading of the concentrated crystals especially at the cap shoulder destabilize the plaque by proportionally increasing the PCS, while evenly distributed crystals loading along the cap might impose less PCS to the plaque than the concentrated case.

  1. Aortic atherosclerotic plaque detection using a multiwavelength handheld photoacoustic imaging system

    NASA Astrophysics Data System (ADS)

    Hirano, Susumu; Namita, Takeshi; Kondo, Kengo; Yamakawa, Makoto; Shiina, Tsuyoshi

    2016-03-01

    Patients affected by diseases caused by arteriosclerosis are increasing. Atherosclerosis, which is becoming an especially difficult health problem, forms plaques from lipids such as cholesterol located in walls of the aorta, cerebral artery, and coronary artery. Because lipid-rich plaques are vulnerable and because arterial rupture causes acute vascular occlusion, early detection is crucially important to prevent plaque growth and rupture. Ultrasound systems can detect plaques but cannot discriminate between vulnerable and equable plaques. To evaluate plaques non-invasively and easily, we developed a handheld photoacoustic imaging device. Its usefulness was verified in phantom experiments with a bovine aorta in which mimic plaque had been embedded. Photoacoustic images taken at wavelengths that produce high light absorbance by lipids show strong photoacoustic signals from the boundary of the mimic plaque. Results confirmed that our system can evaluate plaque properties by analysis with the photoacoustic spectrum. The effects of surrounding tissues and tissue components on plaque evaluation were investigated using a layered phantom. The mimic plaque located under a 6 mm blood layer was also evaluated. Results of these analyses demonstrate the system's usefulness.

  2. Application of infrared fiber optic imaging in atherosclerotic plaques

    NASA Astrophysics Data System (ADS)

    Guo, Bujin; Casscells, S. W.; Bearman, Gregory H.; McNatt, Janice; Naghevi, Morteza; Malik, Basit A.; Gul, Khawar; Willerson, James T.

    1999-07-01

    Rupture of atherosclerotic plaques - the main cause of heart attach and stokes - is not predictable. Hence even treadmill stress tests fail to detect many persons at risk. Fatal plaques are found at autopsies to be associated with active inflammatory cells. Classically, inflammation is detected by its swelling, red color, pain and heat. We have found that heat accurately locates the dangerous plaques that are significantly warmer then atherosclerotic plaques without the same inflammation. In order to develop a non-surgical method of locating these plaques, an IR fiber optic imaging system has been developed in our laboratory to evalute the causes and effect of heat in atherosclerotic plaques. The fiber optical imagin bundle consists of 900 individual As2S3 chalcogenide glass fibers which transmit IR radiation from 0.7 micrometers 7 micrometers with little energy loss. By combining that with a highly sensitive Indium Antimonide IR focal plane array detector, we are able to obtain thermal graphic images in situ. The temperature heterogeneity of atherosclerotic plaques developed in the arteral of the experimental animal models is under study with the new device. The preliminary experimental results from the animal model are encouraging. The potential of using this new technology in diagnostic evaluation of the vulnerable atherosclerotic plaques is considerable.

  3. Aterofisiol® in carotid plaque evolution

    PubMed Central

    Amato, Bruno; Compagna, Rita; Amato, Maurizio; Gallelli, Luca; de Franciscis, Stefano; Serra, Raffaele

    2015-01-01

    Background In patients with carotid stenosis, the risk of plaque rupture is related to the composition of the atherosclerotic plaque rather than to its magnitude. In this regard, we evaluated the effects of a supplement, Aterofisiol,® containing omega-3 (EPA [eicosapen acid] DHA [docosahexaenoic acid]), vitamin K2, vitamin B6, vitamin B12, oligomeric proanthocyanidins (OPC) and resveratrol on the composition of atherosclerotic plaque and on neurological symptoms in patients with carotid stenosis undergoing carotid endarterectomy. Methods The study was randomized, prospective, and double-blinded. Eligible patients were of both sexes, with carotid stenosis >70% who underwent endarterectomy. Enrolled patients were randomly allocated to receive either one tablet of acetylsalicylic acid 100 mg (Cardioaspirin®) + one tablet of Aterofisiol every 24 hours or one tablet of Cardioaspirin + one tablet of placebo every 24 hours. Each treatment was started 30 days before the surgery and was stopped 5 days before the surgery. The plaques were removed “en bloc” using standard surgical technique. Results During the study period, 214 patients (135 men and 79 women) were enrolled for intent-to-treat and randomized in two groups: Group A: 107 patients (68 men and 39 women) were treated with Cardioaspirin + Aterofisiol. Group B: 107 patients (67 men and 40 women) were treated with Cardioaspirin + placebo. At the end of the study, 202 patients participated fully (103 patients in Group A and 99 patients in Group B), making up the protocol evaluation population (94.4%). The mean lipid content of removed plaques was significantly lower (P<0.05) in Group A. We recorded a significantly lower incidence of neurological symptoms in Group A in comparison with Group B (P<0.05). Conclusion In the study, Aterofisiol showed to be effective in reducing the amounts of cholesterol and lipids in the plaques and in reducing adverse neurological events in the study group with respect to controls

  4. Biomechanics of Atherosclerotic Coronary Plaque: Site, Stability and In Vivo Elasticity Modeling

    PubMed Central

    Ohayon, Jacques; Finet, Gérard; Le Floc’h, Simon; Cloutier, Guy; Gharib, Ahmed M.; Heroux, Julie; Pettigrew, Roderic I.

    2016-01-01

    Coronary atheroma develop in local sites that are widely variable among patients and are considerably variable in their vulnerability for rupture. This article summarizes studies conducted by our collaborative laboratories on predictive biomechanical modeling of coronary plaques. It aims to give insights into the role of biomechanics in the development and localization of atherosclerosis, the morphologic features that determine vulnerable plaque stability, and emerging in vivo imaging techniques that may detect and characterize vulnerable plaque. Composite biomechanical and hemodynamic factors that influence the actual site of development of plaques have been studied. Plaque vulnerability, in vivo, is more challenging to assess. Important steps have been made in defining the biomechanical factors that are predictive of plaque rupture and the likelihood of this occurring if characteristic features are known. A critical key in defining plaque vulnerability is the accurate quantification of both the morphology and the mechanical properties of the diseased arteries. Recently, an early IVUS based palpography technique developed to assess local strain, elasticity and mechanical instabilities has been successfully revisited and improved to account for complex plaque geometries. This is based on an initial best estimation of the plaque components’ contours, allowing subsequent iteration for elastic modulus assessment as a basis for plaque stability determination. The improved method has also been preliminarily evaluated in patients with successful histologic correlation. Further clinical evaluation and refinement are on the horizon. PMID:24043605

  5. Monocytes and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques

    PubMed Central

    Tavora, Fabio R; Ripple, Mary; Li, Ling; Burke, Allen P

    2009-01-01

    Background Myeloperoxidase (MPO) -containing macrophages and neutrophils have been described at sites of plaque rupture. The presence of these cells in precursor lesions to acute rupture (thin cap atheroma, or vulnerable plaque) and within thrombi adjacent to ruptures has not been described, nor an association with iron-containing macrophages within unstable plaques. Methods We studied 61 acute ruptures, 15 organizing ruptures, 31 thin cap fibroatheromas, and 28 fibroatheromas from 72 sudden coronary death victims by immunohistochemical and histochemical techniques. Inflammatory cells were typed with anti-CD68 (macrophages), anti-BP-30 (neutrophil bactericidal glycoprotein), and anti-MPO. Iron was localized by Mallory's Prussian blue stain. In selected plaques alpha smooth muscle actin (DAKO, Carpinteria, CA, clone M0851) was performed. Results MPO positive cells were present in 79% of ruptured caps, 28% of thin cap fibroatheroma, and no fibroatheromas; neutrophils were present in 72% of ruptures, 8% of thin cap fibroatheromas, and no fibroatheromas. Iron containing foam cells were present in the caps of 93% of acute ruptures, of 85% of organizing ruptures, 20% of thin cap atheromas, and 10% of fibroatheromas. MPO positive cells were more frequent in occlusive than non-occlusive thrombi adjacent to ruptures (p = .006) and were more numerous in diabetics compared to non-diabetics (p = .002) Conclusion Unstable fibrous caps are more likely to contain MPO-positive cells, neutrophils, and iron-containing macrophages than fibrous caps of stable fibroatheromas. MPO-positive cells in thrombi adjacent to disrupted plaques are associated with occlusive thrombi and are more numerous in diabetic patients. PMID:19549340

  6. Morphometric analysis of atherosclerotic plaques in human carotid arteries.

    PubMed

    Shishkina, V S; Kashirina, S V; Sirotkin, V N; Il'inskaya, O P; Tararak, E M

    2012-03-01

    Morphometric analysis of 35 biopsy specimens from patients with stable (n=10) and unstable (n=25) atherosclerotic lesions was carried out. The structure of the plaques and their connective tissue caps was studied by various methods of histological sections staining. A new morphometric approach to quantitative evaluation of atherosclerotic lesions instability is suggested. It consists in calculation of the morphological "rigidity" coefficient, due to which the plaque is characterized more accurately. The proportion of areas of the "rigid" (connective tissue and calcium salt deposition areas) to "soft" (atheronecrotic nuclei, microvessels, clots and hemorrhages) structures of the plaque is evaluated. Plaque instability (liability of a to rupture) is associated with changes in the extracellular matrix components in the cap: accumulation of collagen and reduction of elastic fiber content reducing vessel elasticity and making its locally more rigid. PMID:22803155

  7. Intracoronary Imaging in the Detection of Vulnerable Plaques.

    PubMed

    Batty, Jonathan A; Subba, Shristy; Luke, Peter; Gigi, Li Wing Chi; Sinclair, Hannah; Kunadian, Vijay

    2016-03-01

    Coronary artery disease is the result of atherosclerotic changes to the coronary arterial wall, comprising endothelial dysfunction, vascular inflammation and deposition of lipid-rich macrophage foam cells. Certain high-risk atherosclerotic plaques are vulnerable to disruption, leading to rupture, thrombosis and the clinical sequelae of acute coronary syndrome. Though recognised as the gold standard for evaluating the presence, distribution and severity of atherosclerotic lesions, invasive coronary angiography is incapable of identifying non-stenotic, vulnerable plaques that are responsible for adverse cardiovascular events. The recognition of such limitations has impelled the development of intracoronary imaging technologies, including intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy, which enable the detailed evaluation of the coronary wall and atherosclerotic plaques in clinical practice. This review discusses the present status of invasive imaging technologies; summarises up-to-date, evidence-based clinical guidelines; and addresses questions that remain unanswered with regard to the future of intracoronary plaque imaging. PMID:26879196

  8. Imaging of coronary atherosclerosis and identification of the vulnerable plaque

    PubMed Central

    de Feyter, P.J.; Serruys, P. W.; Nieman, K.; Mollet, N.; Cademartiri, F.; van Geuns, R. J.; Slager, C.; van der Steen, A.F.W.; Krams, R.; Schaar, J.A.; Wielopolski, P.; Pattynama, P.M.T.; Arampatzis, A.; van der Lugt, A.; Regar, E.; Ligthart, J.; Smits, P.

    2003-01-01

    Identification of the vulnerable plaque responsible for the occurrence of acute coronary syndromes and acute coronary death is a prerequisite for the stabilisation of this vulnerable plaque. Comprehensive coronary atherosclerosis imaging in clinical practice should involve visualisation of the entire coronary artery tree and characterisation of the plaque, including the three-dimensional morphology of the plaque, encroachment of the plaque on the vessel lumen, the major tissue components of the plaque, remodelling of the vessel and presence of inflammation. Obviously, no single diagnostic modality is available that provides such comprehensive imaging and unfortunately no diagnostic tool is available that unequivocally identifies the vulnerable plaque. The objective of this article is to discuss experience with currently available diagnostic modalities for coronary atherosclerosis imaging. In addition, a number of evolving techniques will be briefly discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7 PMID:25696244

  9. SPECT/CT Imaging of High-Risk Atherosclerotic Plaques using Integrin-Binding RGD Dimer Peptides

    PubMed Central

    Sun Yoo, Jung; Lee, Jonghwan; Ho Jung, Jae; Seok Moon, Byung; Kim, Soonhag; Chul Lee, Byung; Eun Kim, Sang

    2015-01-01

    Vulnerable atherosclerotic plaques with unique biological signatures are responsible for most major cardiovascular events including acute myocardial infarction and stroke. However, current clinical diagnostic approaches for atherosclerosis focus on anatomical measurements such as the degree of luminal stenosis and wall thickness. An abundance of neovessels with elevated expression of integrin αvβ3 is closely associated with an increased risk of plaque rupture. Herein we evaluated the potential of an αvβ3 integrin-targeting radiotracer, 99mTc-IDA-D-[c(RGDfK)]2, for SPECT/CT imaging of high-risk plaque in murine atherosclerosis models. In vivo uptake of 99mTc-IDA-D-[c(RGDfK)]2 was significantly higher in atherosclerotic aortas than in relatively normal aortas. Comparison with the negative-control peptide, 99mTc-IDA-D-[c(RADfK)]2, proved specific binding of 99mTc-IDA-D-[c(RGDfK)]2 for plaque lesions in in vivo SPECT/CT and ex vivo autoradiographic imaging. Histopathological characterization revealed that a prominent SPECT signal of 99mTc-IDA-D-[c(RGDfK)]2 corresponded to the presence of high-risk plaques with a large necrotic core, a thin fibrous cap, and vibrant neoangiogenic events. Notably, the RGD dimer based 99mTc-IDA-D-[c(RGDfK)]2 showed better imaging performance in comparison with the common monomeric RGD peptide probe 123I-c(RGDyV) and fluorescence tissue assay corroborated this. Our preclinical data demonstrated that 99mTc-IDA-D-[c(RGDfK)]2 SPECT/CT is a sensitive tool to noninvasively gauge atherosclerosis beyond vascular anatomy by assessing culprit plaque neovascularization. PMID:26123253

  10. Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results

    PubMed Central

    2015-01-01

    Background Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue. Methods Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue. Results Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen. Conclusions Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large

  11. Markers of inflammation associated with plaque progression and instability in patients with carotid atherosclerosis.

    PubMed

    Ammirati, Enrico; Moroni, Francesco; Norata, Giuseppe Danilo; Magnoni, Marco; Camici, Paolo G

    2015-01-01

    Atherosclerosis is the focal expression of a systemic disease affecting medium- and large-sized arteries, in which traditional cardiovascular risk factor and immune factors play a key role. It is well accepted that circulating biomarkers, including C-reactive protein and interleukin-6, reliably predict major cardiovascular events, including myocardial infarction or death. However, the relevance of biomarkers of systemic inflammation to atherosclerosis progression in the carotid artery is less established. The large majority of clinical studies focused on the association between biomarkers and subclinical atherosclerosis, that is, carotid intima-media thickening (cIMT), which represents an earlier stage of the disease. The aim of this work is to review inflammatory biomarkers that were associated with a higher atherosclerotic burden, a faster disease progression, and features of plaque instability, such as inflammation or neovascularization, in patients with carotid atherosclerotic plaque, which represents an advanced stage of disease compared with cIMT. The association of biomarkers with the occurrence of cerebrovascular events, secondary to carotid plaque rupture, will also be presented. Currently, the degree of carotid artery stenosis is used to predict the risk of future cerebrovascular events in patients affected by carotid atherosclerosis. However, this strategy appears suboptimal. The identification of suitable biomarkers could provide a useful adjunctive criterion to ensure better risk stratification and optimize management. PMID:25960621

  12. Comparison of two murine models of thrombosis induced by atherosclerotic plaque injury.

    PubMed

    Hechler, Béatrice; Gachet, Christian

    2011-05-01

    Arterial thrombosis occurs at sites of erosion or rupture of atherosclerotic vascular lesions. To better study the pathophysiology of this complex phenomenon, there is a need for animal models of localised thrombosis at sites of atherosclerotic lesions with closer resemblance to the human pathology as compared to commonly used thrombosis models in healthy vessels. In the present study, we describe and compare a new model of thrombosis induced by atherosclerotic plaque rupture in the carotid artery from ApoE-/- mice using a suture needle to a milder model of ultrasound-induced plaque injury. Needle injury induces atherosclerotic plaque rupture with exposure of plaque material and formation of a thrombus that is larger, nearly occlusive and more stable as compared to that formed by application of ultrasounds. These two models have common features such as the concomitant involvement of platelet activation, thrombin generation and fibrin formation, which translates into sensitivity toward both antiplatelet drugs and anticoagulants. On the other hand, they display differences with respect to the role of the platelet collagen receptor GPVI, the plaque rupture model being less sensitive to its inhibition as compared to the ultrasound-induced injury, which may be related to the amount of thrombin generated. These models represent an improvement as compared to models in healthy vessels and may help identify specific plaque triggers of thrombosis. They should therefore be useful to evaluate new antithrombotic targets. PMID:21479341

  13. Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin

    PubMed Central

    Li, Dongye; Wu, Weiheng; Gong, Lei; Li, Yong; Zhang, Qingdui; Zhang, Tao; Zhang, Chao; Zhang, Yu

    2015-01-01

    Background Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI). Methods Atherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10) were controls. VP was established in groups B (n = 10) and C (n = 10) using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured. Results DMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05). Conclusion After successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels. PMID:25973795

  14. Plaque, plaque model systems and pH.

    PubMed

    Sissons, C

    1998-06-01

    Four interlocking lines of research carried out during the Directorship of Dr TW Cutress in the Dental Research Unit were: plaque urea metabolism, which led to the study of plaque pH responses and their control; development of plaque-like biofilm model systems; plaque mineralisation to calculus; and plaque demineralisation of tooth tissue in caries. New modes of regulation of oral bacterial urea metabolism and its role in the mouth were discovered, especially a role as a pH-rise factor and in mineralisation processes. The development of microcosm plaques, consortia of major plaque species, and of the multi-plaque artificial mouth with the ability to measure pH continuously, has substantiated the theory that plaque thickness and fluid flow are important in determining plaque pH. For the first time, formation of large pH gradients inside plaque have been demonstrated and plaque pH experimentally controlled. Plaque growth curves can be accurately measured and procedures established for measuring antiplaque and anticaries agents. These studies exemplify the value of the fundamental approach adopted by Dr Cutress--that integrated, basic, applied, and public-health lines of research reinforce each other. PMID:9676473

  15. Assessment of vulnerable and unstable carotid atherosclerotic plaques on endarterectomy specimens

    PubMed Central

    BUTCOVAN, DOINA; MOCANU, VERONICA; BARAN, DANA; CIURESCU, DIANA; TINICA, GRIGORE

    2016-01-01

    The types of lesion instability responsible for the majority of acute coronary events frequently include plaque disruption and plaque erosion with superimposed thrombosis. The term ‘vulnerable plaque is used to describe atherosclerotic (ATS) plaques that are particularly prone to rupture and susceptible to thrombus formation, such as the thin-cap fibroatheroma (TCFA). The aim of the present study was to assess the morphological and histological differences between plaques that are unstable and those that are vulnerable to instability. Carotid artery endarterectomy specimens were obtained from 26 patients with carotid artery stenosis, consisting of 20 men and 6 women (age range, 35–80 years). Histological and morphometric methods were used to visualize and characterize the ATS plaques. Among the 26 carotid ATS plaques, 23% were stable, 23% were unstable and 54% were vulnerable. With regard to morphometric characteristics, the following mean values were obtained for the TCFA and unstable plaques, respectively: Fibrous cap thickness, 21.91 and 11.66 µM; proportion of necrotic core area in the total plaque area, 25.90 and 22.03%; and the proportion of inflammatory area in the total plaque area, 8.41 and 3.04%. No plaque calcification was observed in any of them. Since ATS coronary artery disease is considerably widespread and fatal, it is crucial to further study ATS lesions to obtain an improved understanding of the nature of vulnerable and unstable plaques. The methods used to detect plaque size, necrotic core area and fibrous cap thickness are considered to be particularly useful for identifying vulnerable and unstable plaques. PMID:27168846

  16. Dental plaque identification at home

    MedlinePlus

    ... your teeth. Plaque is the major cause of tooth decay and gum disease ( gingivitis ). It is hard to ... the plaque is not removed, it can cause tooth decay or cause the gums to bleed easily (gingivitis) ...

  17. Aetiology of pleural plaques

    PubMed Central

    Rous, V.; Studeny, J.

    1970-01-01

    Pleural plaques were found in 644 (6·6%) of 9,760 photofluorograms taken in 1965 in a region of Pelhřimov district; the incidence was highest in the age group 66-70 years. The advanced age of those affected may be explained by the greater frequency of the causative agent in the past. The disorder was known in Pelhřimov district as early as 1930; it was then thought to be posttuberculous. The past history of the cases was uninformative; as a rule, the only common previous disease was pleurisy with effusion, occurring in 9·7%. The general condition of those affected was excellent; only 8% were aware of the fact that pleural lesions were present. The disorder was found mainly in farmers, familial incidence was common, and if two generations of one family suffered from the condition, the older generation was affected in 100%. Pleural plaques consist morphologically of limited areas of hyalinized collagenous connective tissue with calcium salt deposits. Tubercle bacilli could not be cultivated from the lesions. Mineralological analysis showed no evidence of silicates in the pleural plaques and a normal content in the lungs. The aetiological factor responsible for the development of pleural plaques in Pelhřimov district is not known, but asbestos cannot be implicated. The unknown noxious agent is carried to the pleura by the lymph and blood stream. Pleural plaques are an endemic disorder. The traditional view that lesions are post-tuberculous appears, in the region submitted to this study, to be a possible explanation. Images PMID:5465601

  18. Premature rupture of membranes

    MedlinePlus

    ... When the water breaks early, it is called premature rupture of membranes (PROM). Most women will go ... th week of pregnancy, it is called preterm premature rupture of membranes (PPROM). The earlier your water ...

  19. MR Imaging of Coronary Arteries and Plaques.

    PubMed

    Dweck, Marc R; Puntman, Valentina; Vesey, Alex T; Fayad, Zahi A; Nagel, Eike

    2016-03-01

    Cardiac magnetic resonance offers the promise of radiation-free imaging of the coronary arteries, providing information with respect to luminal stenosis, plaque burden, high-risk plaque characteristics, and disease activity. In combination, this would provide a comprehensive, individualized assessment of coronary atherosclerosis that could be used to improve patient risk stratification and to guide treatment. However, the technical challenges involved with delivering upon this promise are considerable, requiring sophisticated approaches to both data acquisition and post-processing. In this review, we describe the current status of this technology, its capabilities, its limitations, and what will be required in the future to translate this technology into routine clinical practice. PMID:26965732

  20. Identifying Vulnerable Plaques with Acoustic Radiation Force Impulse Imaging

    NASA Astrophysics Data System (ADS)

    Doherty, Joshua Ryan

    The rupture of arterial plaques is the most common cause of ischemic complications including stroke, the fourth leading cause of death and number one cause of long term disability in the United States. Unfortunately, because conventional diagnostic tools fail to identify plaques that confer the highest risk, often a disabling stroke and/or sudden death is the first sign of disease. A diagnostic method capable of characterizing plaque vulnerability would likely enhance the predictive ability and ultimately the treatment of stroke before the onset of clinical events. This dissertation evaluates the hypothesis that Acoustic Radiation Force Impulse (ARFI) imaging can noninvasively identify lipid regions, that have been shown to increase a plaque's propensity to rupture, within carotid artery plaques in vivo. The work detailed herein describes development efforts and results from simulations and experiments that were performed to evaluate this hypothesis. To first demonstrate feasibility and evaluate potential safety concerns, finite- element method simulations are used to model the response of carotid artery plaques to an acoustic radiation force excitation. Lipid pool visualization is shown to vary as a function of lipid pool geometry and stiffness. A comparison of the resulting Von Mises stresses indicates that stresses induced by an ARFI excitation are three orders of magnitude lower than those induced by blood pressure. This thesis also presents the development of a novel pulse inversion harmonic tracking method to reduce clutter-imposed errors in ultrasound-based tissue displacement estimates. This method is validated in phantoms and was found to reduce bias and jitter displacement errors for a marked improvement in image quality in vivo. Lastly, this dissertation presents results from a preliminary in vivo study that compares ARFI imaging derived plaque stiffness with spatially registered composition determined by a Magnetic Resonance Imaging (MRI) gold standard

  1. How Does Calcification Influence Plaque Vulnerability? Insights from Fatigue Analysis

    PubMed Central

    Wu, Baijian; Pei, Xuan; Li, Zhi-Yong

    2014-01-01

    Background. Calcification is commonly believed to be associated with cardiovascular disease burden. But whether or not the calcifications have a negative effect on plaque vulnerability is still under debate. Methods and Results. Fatigue rupture analysis and the fatigue life were used to evaluate the rupture risk. An idealized baseline model containing no calcification was first built. Based on the baseline model, we investigated the influence of calcification on rupture path and fatigue life by adding a circular calcification and changing its location within the fibrous cap area. Results show that 84.0% of calcified cases increase the fatigue life up to 11.4%. For rupture paths 10D far from the calcification, the life change is negligible. Calcifications close to lumen increase more fatigue life than those close to the lipid pool. Also, calcifications in the middle area of fibrous cap increase more fatigue life than those in the shoulder area. Conclusion. Calcifications may play a positive role in the plaque stability. The influence of the calcification only exists in a local area. Calcifications close to lumen may be influenced more than those close to lipid pool. And calcifications in the middle area of fibrous cap are seemly influenced more than those in the shoulder area. PMID:24955401

  2. Characterising human atherosclerotic carotid plaque tissue composition and morphology using combined spectroscopic and imaging modalities

    PubMed Central

    2015-01-01

    Calcification is a marked pathological component in carotid artery plaque. Studies have suggested that calcification may induce regions of high stress concentrations therefore increasing the potential for rupture. However, the mechanical behaviour of the plaque under the influence of calcification is not fully understood. A method of accurately characterising the calcification coupled with the associated mechanical plaque properties is needed to better understand the impact of calcification on the mechanical behaviour of the plaque during minimally invasive treatments. This study proposes a comparison of biochemical and structural characterisation methods of the calcification in carotid plaque specimens to identify plaque mechanical behaviour. Biochemical analysis, by Fourier Transform Infrared (FTIR) spectroscopy, was used to identify the key components, including calcification, in each plaque sample. However, FTIR has a finite penetration depth which may limit the accuracy of the calcification measurement. Therefore, this FTIR analysis was coupled with the identification of the calcification inclusions located internally in the plaque specimen using micro x-ray computed tomography (μX-CT) which measures the calcification volume fraction (CVF) to total tissue content. The tissue characterisation processes were then applied to the mechanical material plaque properties acquired from experimental circumferential loading of human carotid plaque specimen for comparison of the methods. FTIR characterised the degree of plaque progression by identifying the functional groups associated with lipid, collagen and calcification in each specimen. This identified a negative relationship between stiffness and 'lipid to collagen' and 'calcification to collagen' ratios. However, μX-CT results suggest that CVF measurements relate to overall mechanical stiffness, while peak circumferential strength values may be dependent on specific calcification geometries. This study

  3. Bi-modal imaging of atherosclerotic plaques: Automated method for co-registration between fluorescence lifetime imaging and intravascular ultrasound data

    NASA Astrophysics Data System (ADS)

    Gorpas, Dimitris; Fatakdawala, Hussain; Bec, Julien; Ma, Dinglong; Yankelevich, Diego R.; Bishop, John W.; Qi, Jinyi; Marcu, Laura

    2014-03-01

    The risk of atherosclerosis plaque rupture cannot be assessed by the current imaging systems and thus new multi-modal technologies are under investigation. This includes combining a new fluorescence lifetime imaging (FLIm) technique, which is sensitive to plaque biochemical features, with conventional intravascular ultrasound (IVUS), which provides information on plaque morphology. In this study we present an automated method allowing for the co-registration of imaging data acquired based on these two techniques. Intraluminal studies were conducted in ex-vivo segments of human coronaries with a multimodal catheter integrating a commercial IVUS (40 MHz) and a rotational side-viewing fiber based multispectral FLIm system (355 nm excitation, 390+/-20, 452+/-22 and 542+/-25 nm acquisition wavelengths). The proposed method relies on the lumen/intima boundary extraction from the IVUS polar images. Image restoration is applied for the noise reduction and edge enhancement, while gray-scale peak tracing over the A-lines of the IVUS polar images is applied for the lumen boundary extraction. The detection of the guide-wire artifact is used for the angular registration between FLIm and IVUS data, after which the lifetime values can be mapped onto the segmented lumen/intima interface. The segmentation accuracy has been assessed against manual tracings, providing 0.120+/-0.054 mm mean Hausdorff distance. This method makes the bi-modal FLIm and IVUS approach feasible for comprehensive intravascular diagnostic by providing co-registered biochemical and morphological information about atherosclerotic plaques.

  4. Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice.

    PubMed

    Ulrich, Victoria; Rotllan, Noemi; Araldi, Elisa; Luciano, Amelia; Skroblin, Philipp; Abonnenc, Mélanie; Perrotta, Paola; Yin, Xiaoke; Bauer, Ashley; Leslie, Kristen L; Zhang, Pei; Aryal, Binod; Montgomery, Rusty L; Thum, Thomas; Martin, Kathleen; Suarez, Yajaira; Mayr, Manuel; Fernandez-Hernando, Carlos; Sessa, William C

    2016-01-01

    Abnormal remodeling of atherosclerotic plaques can lead to rupture, acute myocardial infarction, and death. Enhancement of plaque extracellular matrix (ECM) may improve plaque morphology and stabilize lesions. Here, we demonstrate that chronic administration of LNA-miR-29 into an atherosclerotic mouse model improves indices of plaque morphology. This occurs due to upregulation of miR-29 target genes of the ECM (col1A and col3A) resulting in reduced lesion size, enhanced fibrous cap thickness, and reduced necrotic zones. Sustained LNA-miR-29 treatment did not affect circulating lipids, blood chemistry, or ECM of solid organs including liver, lung, kidney, spleen, or heart. Collectively, these data support the idea that antagonizing miR-29 may promote beneficial plaque remodeling as an independent approach to stabilize vulnerable atherosclerotic lesions. PMID:27137489

  5. Directional spatial frequency analysis of lipid distribution in atherosclerotic plaque

    NASA Astrophysics Data System (ADS)

    Korn, Clyde; Reese, Eric; Shi, Lingyan; Alfano, Robert; Russell, Stewart

    2016-04-01

    Atherosclerosis is characterized by the growth of fibrous plaques due to the retention of cholesterol and lipids within the artery wall, which can lead to vessel occlusion and cardiac events. One way to evaluate arterial disease is to quantify the amount of lipid present in these plaques, since a higher disease burden is characterized by a higher concentration of lipid. Although therapeutic stimulation of reverse cholesterol transport to reduce cholesterol deposits in plaque has not produced significant results, this may be due to current image analysis methods which use averaging techniques to calculate the total amount of lipid in the plaque without regard to spatial distribution, thereby discarding information that may have significance in marking response to therapy. Here we use Directional Fourier Spatial Frequency (DFSF) analysis to generate a characteristic spatial frequency spectrum for atherosclerotic plaques from C57 Black 6 mice both treated and untreated with a cholesterol scavenging nanoparticle. We then use the Cauchy product of these spectra to classify the images with a support vector machine (SVM). Our results indicate that treated plaque can be distinguished from untreated plaque using this method, where no difference is seen using the spatial averaging method. This work has the potential to increase the effectiveness of current in-vivo methods of plaque detection that also use averaging methods, such as laser speckle imaging and Raman spectroscopy.

  6. The effects of plaque morphology and material properties on peak cap stress in human coronary arteries.

    PubMed

    Akyildiz, Ali C; Speelman, Lambert; Nieuwstadt, Harm A; van Brummelen, Harald; Virmani, Renu; van der Lugt, Aad; van der Steen, Anton F W; Wentzel, Jolanda J; Gijsen, Frank J H

    2016-01-01

    Heart attacks are often caused by rupture of caps of atherosclerotic plaques in coronary arteries. Cap rupture occurs when cap stress exceeds cap strength. We investigated the effects of plaque morphology and material properties on cap stress. Histological data from 77 coronary lesions were obtained and segmented. In these patient-specific cross sections, peak cap stresses were computed by using finite element analyses. The finite element analyses were 2D, assumed isotropic material behavior, and ignored residual stresses. To represent the wide spread in material properties, we applied soft and stiff material models for the intima. Measures of geometric plaque features for all lesions were determined and their relations to peak cap stress were examined using regression analyses. Patient-specific geometrical plaque features greatly influence peak cap stresses. Especially, local irregularities in lumen and necrotic core shape as well as a thin intima layer near the shoulder of the plaque induce local stress maxima. For stiff models, cap stress increased with decreasing cap thickness and increasing lumen radius (R = 0.79). For soft models, this relationship changed: increasing lumen radius and increasing lumen curvature were associated with increased cap stress (R = 0.66). The results of this study imply that not only accurate assessment of plaque geometry, but also of intima properties is essential for cap stress analyses in atherosclerotic plaques in human coronary arteries. PMID:26237279

  7. Self-Rupturing Hermetic Valve

    NASA Technical Reports Server (NTRS)

    Tucker, Curtis E., Jr.; Sherrit, Stewart

    2011-01-01

    For commercial, military, and aerospace applications, low-cost, small, reliable, and lightweight gas and liquid hermetically sealed valves with post initiation on/off capability are highly desirable for pressurized systems. Applications include remote fire suppression, single-use system-pressurization systems, spacecraft propellant systems, and in situ instruments. Current pyrotechnic- activated rupture disk hermetic valves were designed for physically larger systems and are heavy and integrate poorly with portable equipment, aircraft, and small spacecraft and instrument systems. Additionally, current pyrotechnically activated systems impart high g-force shock loads to surrounding components and structures, which increase the risk of damage and can require additional mitigation. The disclosed mechanism addresses the need for producing a hermetically sealed micro-isolation valve for low and high pressure for commercial, aerospace, and spacecraft applications. High-precision electrical discharge machining (EDM) parts allow for the machining of mated parts with gaps less than a thousandth of an inch. These high-precision parts are used to support against pressure and extrusion, a thin hermetically welded diaphragm. This diaphragm ruptures from a pressure differential when the support is removed and/or when the plunger is forced against the diaphragm. With the addition of conventional seals to the plunger and a two-way actuator, a derivative of this design would allow nonhermetic use as an on/off or metering valve after the initial rupturing of the hermetic sealing disk. In addition, in a single-use hermetically sealed isolation valve, the valve can be activated without the use of potential leak-inducing valve body penetrations. One implementation of this technology is a high-pressure, high-flow-rate rupture valve that is self-rupturing, which is advantageous for high-pressure applications such as gas isolation valves. Once initiated, this technology is self

  8. Glass rupture disk

    DOEpatents

    Glass, S. Jill; Nicolaysen, Scott D.; Beauchamp, Edwin K.

    2002-01-01

    A frangible rupture disk and mounting apparatus for use in blocking fluid flow, generally in a fluid conducting conduit such as a well casing, a well tubing string or other conduits within subterranean boreholes. The disk can also be utilized in above-surface pipes or tanks where temporary and controllable fluid blockage is required. The frangible rupture disk is made from a pre-stressed glass with controllable rupture properties wherein the strength distribution has a standard deviation less than approximately 5% from the mean strength. The frangible rupture disk has controllable operating pressures and rupture pressures.

  9. Array Measurements of Earthquake Rupture.

    NASA Astrophysics Data System (ADS)

    Goldstein, Peter

    Accurate measurements of earthquake rupture are an essential step in the development of an understanding of the earthquake source process. In this dissertation new array analysis techniques are developed and used to make the first measurements of two-dimensional earthquake rupture propagation. In order to measure earthquake rupture successfully it is necessary to account for the nonstationary behavior of seismic waves and nonplanar wavefronts due to time delays caused by local heterogeneities. Short time windows are also important because they determine the precision with which it is possible to measure rupture times of earthquake sources. The subarray spatial averaging and seismogram alignment methods were developed for these reasons. The basic algorithm which is used to compute frequency-wavenumber power spectra is the multiple signal characterization (MUSIC) method. Although a variety of methods could be applied with subarray spatial averaging and seismogram alignment, MUSIC is used because it has better resolution of multiple sources than other currently available methods and it provides a unique solution. Power spectra observed at the array are converted into source locations on the fault plane by tracing rays through a layered medium. A dipping layer correction factor is introduced to account for a laterally varying basin structure such as that found beneath the SMART 1 array in Taiwan. A framework is presented that allows for the estimation of precision and resolution of array measurements of source locations and can be used to design an optimum array for a given source. These methods are used to show that the November 14th 1986, M_{L} = 7.0 Hualien, Taiwan earthquake began as a shallow event with unilateral rupture from southwest to northeast. A few seconds later a second, deeper and larger event began rupturing from below the hypocentral region from southwest to northeast slightly down-dip. Energy density estimates indicate larger energy sources at greater

  10. [Present status and research train of thoughts in integrative medicine on unstable plaque].

    PubMed

    Zhang, Jing-chun; Chen, Ke-ji; Ahang, Wen-gao

    2005-10-01

    The changing of atherosclerosis (AS) plaque from stable to unstable is closely related to the incidence of cardio-cerebrovascular events. So, to stabilize AS plaque become the hot point of the modern study on prevention and treatment of cardio-cerebrovascular diseases. The formation of AS plaque is a very long and complicated process with the participation of many factors. However, inflammation reaction plays an important role in the formation and rupture of unstable plaque. Traditional Chinese medicine (TCM) shows latent therapeutic advantages in stabilizing AS plaque with its characteristics of multi-way, multi-link, and multi-target point and all-sided treatment as well as its rather milder adverse reactions. The paper gives a comparatively systematic retrospection of study on unstable plaque treated by integrated Chinese and Western medicine conducted in recent years. Combined with the related topics conducted by the authors, they raise the theory of "unstable plaque is induced by toxinduced by toxin and stagnation", and introduce the study on the intervention of unstable plaque by removing toxic substances and activating blood flow. They believe that the explorative study can provide objective experimental and clinical basis for TCM therapeutic method in stabilizing AS plaque. PMID:16313104

  11. Multimodal spectroscopy detects features of vulnerable atherosclerotic plaque

    PubMed Central

    Šćepanović, Obrad R.; Fitzmaurice, Maryann; Miller, Arnold; Kong, Chae-Ryon; Volynskaya, Zoya; Dasari, Ramachandra R.; Kramer, John R.; Feld, Michael S.

    2011-01-01

    Early detection and treatment of rupture-prone vulnerable atherosclerotic plaques is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy—termed multimodal spectroscopy (MMS)—provides detailed biochemical information about tissue and can detect vulnerable plaque features: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), and thrombus. Ex vivo MMS spectra are collected from 12 patients that underwent carotid endarterectomy or femoral bypass surgery. Data are collected by means of a unitary MMS optical fiber probe and a portable clinical instrument. Blinded histopathological analysis is used to assess the vulnerability of each spectrally evaluated artery lesion. Modeling of the ex vivo MMS spectra produce objective parameters that correlate with the presence of vulnerable plaque features: TFC with fluorescence parameters indicative of collagen presence; NC∕SFC with a combination of diffuse reflectance β-carotene∕ceroid absorption and the Raman spectral signature of lipids; and thrombus with its Raman signature. Using these parameters, suspected vulnerable plaques can be detected with a sensitivity of 96% and specificity of 72%. These encouraging results warrant the continued development of MMS as a catheter-based clinical diagnostic technique for early detection of vulnerable plaques. PMID:21280896

  12. Multimodal spectroscopy detects features of vulnerable atherosclerotic plaque

    NASA Astrophysics Data System (ADS)

    Šćepanović, Obrad R.; Fitzmaurice, Maryann; Miller, Arnold; Kong, Chae-Ryon; Volynskaya, Zoya; Dasari, Ramachandra R.; Kramer, John R.; Feld, Michael S.

    2011-01-01

    Early detection and treatment of rupture-prone vulnerable atherosclerotic plaques is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy-termed multimodal spectroscopy (MMS)-provides detailed biochemical information about tissue and can detect vulnerable plaque features: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), and thrombus. Ex vivo MMS spectra are collected from 12 patients that underwent carotid endarterectomy or femoral bypass surgery. Data are collected by means of a unitary MMS optical fiber probe and a portable clinical instrument. Blinded histopathological analysis is used to assess the vulnerability of each spectrally evaluated artery lesion. Modeling of the ex vivo MMS spectra produce objective parameters that correlate with the presence of vulnerable plaque features: TFC with fluorescence parameters indicative of collagen presence; NC/SFC with a combination of diffuse reflectance β-carotene/ceroid absorption and the Raman spectral signature of lipids; and thrombus with its Raman signature. Using these parameters, suspected vulnerable plaques can be detected with a sensitivity of 96% and specificity of 72%. These encouraging results warrant the continued development of MMS as a catheter-based clinical diagnostic technique for early detection of vulnerable plaques.

  13. A finite element study of balloon expandable stent for plaque and arterial wall vulnerability assessment

    NASA Astrophysics Data System (ADS)

    Karimi, Alireza; Navidbakhsh, Mahdi; Razaghi, Reza

    2014-07-01

    The stresses induced within plaque tissues and arterial layers during stent expansion inside an atherosclerotic artery can be exceeded from the yield stresses of those tissues and, consequently, lead to plaque or arterial layer rupture. The distribution and magnitude of the stresses in each component involved in stenting might be clearly different for different plaque types and different arterial layers. In this study, a nonlinear finite element simulation was employed to investigate the effect of plaque composition (calcified, cellular, and hypocellular) on the stresses induced in the arterial layers (intima, media, and adventitia) during implantation of a balloon expandable coronary stent into a stenosed artery. The atherosclerotic artery was assumed to consist of a plaque and normal/healthy arterial tissues on its outer side. The results indicated a significant influence of plaque types on the maximum stresses induced within the plaque wall and arterial layers during stenting but not when computing maximum stress on the stent. The stress on the stiffest calcified plaque wall was in the fracture level (2.38 MPa), whereas cellular and hypocellular plaques remain stable owing to less stress on their walls. Regardless of plaque types, the highest von Mises stresses were observed on the stiffest intima layer, whereas the lowest stresses were seen to be located in less stiff media layer. The computed stresses on the intima layer were found to be high enough to initiate a rupture in this stiff layer. These findings suggest a higher risk of arterial vascular injury for the intima layer, while a lower risk of arterial injury for the media and adventitia layers.

  14. Imaging Atherosclerotic Plaque Calcification: Translating Biology.

    PubMed

    Bailey, Grant; Meadows, Judith; Morrison, Alan R

    2016-08-01

    Calcification of atherosclerotic lesions was long thought to be an age - related, passive process, but increasingly data has revealed that atherosclerotic calcification is a more active process, involving complex signaling pathways and bone-like genetic programs. Initially, imaging of atherosclerotic calcification was limited to gross assessment of calcium burden, which is associated with total atherosclerotic burden and risk of cardiovascular mortality and of all cause mortality. More recently, sophisticated molecular imaging studies of the various processes involved in calcification have begun to elucidate information about plaque calcium composition and consequent vulnerability to rupture, leading to hard cardiovascular events like myocardial infarction. As such, there has been renewed interest in imaging calcification to advance risk assessment accuracy in an evolving era of precision medicine. Here we summarize recent advances in our understanding of the biologic process of atherosclerotic calcification as well as some of the molecular imaging tools used to assess it. PMID:27339750

  15. La pelade par plaques

    PubMed Central

    Spano, Frank; Donovan, Jeff C.

    2015-01-01

    Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre l’épidémiologie, la pathogenèse, l’histologie et l’approche clinique au diagnostic de la pelade par plaques. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant la pathogenèse, le diagnostic et le pronostic de la pelade par plaques. Message principal La pelade par plaques est une forme de perte pileuse auto-immune dont la prévalence durant une vie est d’environ 2 %. Des antécédents personnels ou familiaux de troubles auto-immuns concomitants, comme le vitiligo ou une maladie de la thyroïde, peuvent être observés dans un petit sous-groupe de patients. Le diagnostic peut souvent être posé de manière clinique en se fondant sur la perte de cheveux non cicatricielle et circulaire caractéristique, accompagnée de cheveux en « point d’exclamation » en périphérie chez ceux dont le problème en est aux premiers stades. Le diagnostic des cas plus complexes ou des présentations inhabituelles peut être facilité par une biopsie et un examen histologique. Le pronostic varie largement et de mauvais résultats sont associés à une apparition à un âge précoce, une perte importante, la variante ophiasis, des changements aux ongles, des antécédents familiaux ou des troubles auto-immuns concomitants. Conclusion La pelade par plaques est une forme auto-immune de perte de cheveux périodiquement observée en soins primaires. Les médecins de famille sont bien placés pour identifier la pelade par plaques, déterminer la gravité de la maladie et poser le diagnostic différentiel approprié. De plus, ils sont en mesure de renseigner leurs patients à propos de l’évolution clinique de la maladie ainsi que du pronostic général selon le sous-type de patients.

  16. La pelade par plaques

    PubMed Central

    Spano, Frank; Donovan, Jeff C.

    2015-01-01

    Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre les schémas thérapeutiques et les résultats des traitements pour la pelade par plaques, de même que les aider à identifier les patients pour qui une demande de consultation en dermatologie pourrait s’imposer. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant le traitement de la pelade par plaques. Message principal La pelade par plaques est une forme auto-immune de perte pileuse qui touche à la fois les enfants et les adultes. Même s’il n’y a pas de mortalité associée à la maladie, la morbidité découlant des effets psychologiques de la perte des cheveux peut être dévastatrice. Lorsque la pelade par plaques et le sous-type de la maladie sont identifiés, un schéma thérapeutique approprié peut être amorcé pour aider à arrêter la chute des cheveux et possiblement faire commencer la repousse. Les traitements de première intention sont la triamcinolone intralésionnelle avec des corticostéroïdes topiques ou du minoxidil ou les 2. Les médecins de famille peuvent prescrire ces traitements en toute sécurité et amorcer ces thérapies. Les cas plus avancés ou réfractaires pourraient avoir besoin de diphénylcyclopropénone topique ou d’anthraline topique. On peut traiter la perte de cils avec des analogues de la prostaglandine. Les personnes ayant subi une perte de cheveux abondante peuvent recourir à des options de camouflage ou à des prothèses capillaires. Il est important de surveiller les troubles psychiatriques en raison des effets psychologiques profonds de la perte de cheveux. Conclusion Les médecins de famille verront de nombreux patients qui perdent leurs cheveux. La reconnaissance de la pelade par plaques et la compréhension du processus pathologique sous-jacent permettent d’amorcer un schéma thérapeutique approprié. Les cas plus graves ou r

  17. Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.; Tawakol, Ahmed; Castano, Ana P.; Gad, Faten; Zahra, Touqir; Ahmadi, Atosa; Stern, Jeremy; Ortel, Bernhard; Chirico, Stephanie; Shirazi, Azadeh; Syed, Sakeena; Muller, James E.

    2003-06-01

    Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular

  18. Biological plaque control: novel therapeutic approach to periodontal disease.

    PubMed

    Sugano, Naoyuki

    2012-03-01

    Despite its important role in the control of periodontal disease, mechanical plaque control is not properly practiced by most individuals. Therefore, adjunctive chemical plaque control using chlorhexidine and antibiotics has also been suggested as an additional therapeutic strategy to augment mechanical plaque control. However, the additional effects of adjunctive antibiotic therapy are small, and topical chlorhexidine therapy is not without side effects. Given current limitations, new approaches for the control of biofilm are required. The new therapeutic approaches discussed in this review are divided into two categories: probiotics and vaccines. Probiotics is an interesting new field of periodontology research that aims to achieve biological plaque control by eliminating pathogenic bacteria. In addition, passive immunization using egg yolk antibody raised against periodontal pathogens may be an effective approach for the treatment of periodontitis. Further study to evaluate the possible effects of these biological plaque control methods against periodontal disease is warranted. PMID:22466880

  19. Non-pulsed electrochemical impregnation of flexible metallic battery plaques

    DOEpatents

    Maskalick, Nicholas J.

    1982-01-01

    A method of loading active battery material into porous, flexible, metallic battery plaques, comprises the following steps: precipitating nickel hydroxide active material within the plaque, by making the plaque cathodic, at a high current density, in an electro-precipitation cell also containing a consumable nickel anode and a solution comprising nickel nitrate, having a pH of between 2.0 and 2.8; electrochemically oxidizing the precipitate in caustic formation solution; and repeating the electro-precipitation step at a low current density.

  20. Chronic intermittent mental stress promotes atherosclerotic plaque vulnerability, myocardial infarction and sudden death in mice.

    PubMed

    Roth, Lynn; Rombouts, Miche; Schrijvers, Dorien M; Lemmens, Katrien; De Keulenaer, Gilles W; Martinet, Wim; De Meyer, Guido R Y

    2015-09-01

    Vulnerable atherosclerotic plaques are prone to plaque rupture leading to acute cardiovascular syndromes and death. Elucidating the risk of plaque rupture is important to define better therapeutic or preventive strategies. In the present study, we investigated the effect of chronic intermittent mental stress on atherosclerotic plaque stability and cardiovascular mortality in apolipoprotein E-deficient (ApoE(-/-)) mice with a heterozygous mutation in the fibrillin-1 gene (Fbn1(C1039G+/)(-)). This mouse model displays exacerbated atherosclerosis with spontaneous plaque ruptures, myocardial infarction and sudden death, when fed a Western-type diet (WD). Female ApoE(-/-)Fbn1(C1039G+/-) mice were fed a WD for up to 25 weeks. After 10 weeks WD, mice were divided in a control (n = 27) and mental stress (n = 29) group. The chronic intermittent mental stress protocol consisted of 3 triggers: water avoidance, damp bedding and restraint stress, in a randomly assigned order lasting 6 h every weekday for 15 weeks. Chronic intermittent mental stress resulted in a significant increase in the amount of macrophages in atherosclerotic plaques of the proximal ascending aorta, whereas type I collagen and fibrous cap thickness were decreased. The coronary arteries of mental stress-treated mice showed larger plaques, more stenosis, and an increased degree of perivascular fibrosis. Moreover, myocardial infarctions occurred more frequently in the mental stress group. As compared to the control group, the survival of stressed ApoE(-/-)Fbn1(C1039G+/-) mice decreased from 67% to 52% at 25 weeks WD, presumably due to myocardial infarctions. In conclusion, chronic intermittent mental stress promotes plaque instability, myocardial infarctions, and mortality of ApoE(-/-)Fbn1(C1039G+/-) mice. PMID:26233915

  1. Ex vivo identification of atherosclerotic plaque calcification by a 31P solid-state magnetic resonance imaging technique.

    PubMed

    Hallock, Kevin J; Hamilton, James A

    2006-12-01

    Calcified tissue is a common component of atherosclerotic plaques, and occurs most often in mature plaques. The process of calcification is a poorly understood risk factor that may contribute to a plaque's vulnerability to sudden rupture. In this study a solid-state imaging sequence, termed single-point imaging (SPI), was used to observe calcification directly in ex vivo atherosclerotic plaques. Standards were used to validate the ability of (31)P SPI to detect and differentiate calcification from crystalline cholesterol, phospholipids, and other plaque components. After suitable experimental parameters were found, human carotid specimens obtained by endarterectomy were imaged ex vivo by (31)P solid-state imaging and standard (1)H methods. In contrast to (1)H imaging methods, (31)P imaging detected only the calcification in the plaque. PMID:17089379

  2. Methodical study on plaque characterization using integrated vascular ultrasound, strain and spectroscopic photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Graf, Iulia M.; Su, Jimmy; Yeager, Doug; Amirian, James; Smalling, Richard; Emelianov, Stanislav

    2011-03-01

    Carotid atherosclerosis has been identified as a potential risk factor for cerebrovascular events, but information about its direct effect on the risk of recurrent stroke is limited due to incomplete diagnosis. The combination of vascular ultrasound, strain rate and spectroscopic photoacoustics could improve the timely diagnosis of plaque status and risk of rupturing. Current ultrasound techniques can noninvasively image the anatomy of carotid arteries. The spatio-temporal variation in displacement of different regions within the arterial wall can be derived from ultrasound radio frequency data; therefore an ultrasound based strain rate imaging modality can be used to reveal changes in arterial mechanical properties. Additionally, spectroscopic photoacoustic imaging can provide information on the optical absorption properties of arterial tissue and it can be used to identify the location of specific tissue components, such as lipid pools. An imaging technique combining ultrasound, strain rate and spectroscopic photoacoustics was tested on an excised atherosclerotic rabbit aorta. The ultrasound image illustrates inhomogeneities in arterial wall thickness, the strain rate indicates the arterial segment with reduced elasticity and the spectroscopic photoacoustic image illustrates the accumulation of lipids. The results demonstrated that ultrasound, strain rate and spectroscopic photoacoustic imaging are complementary. Thus the integration of the three imaging modalities advances the characterization of atherosclerotic plaques.

  3. Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques

    PubMed Central

    Cui, Dongyao; Yu, Xiaojun; Chen, Si; Liu, Xinyu; Tang, Hongying; Wang, Xianghong; Liu, Linbo

    2016-01-01

    Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals. PMID:27149381

  4. Influence of Cigarette Smoking on Burden and Characteristics of Coronary Artery Plaques in Chinese Men

    PubMed Central

    Sun, Yujiao; Yu, Xin; Zhi, Ying; Geng, Song; Li, Hua; Liu, Ting; Xu, Ke; Qi, Guoxian

    2015-01-01

    Background It is generally well-known that smoking has a substantial impact on general health, and cardiovascular health in particular. The purpose of this study was to analyze the effects of different smoking status on the burden and characteristics of coronary artery plaques in Chinese men. Methods Our study enrolled 1920 individuals with suspected coronary artery disease undergoing 256-detector-row computed tomography scan after clinical assessment. These study participants were stratified into three groups: never smoker, current smoker, and former smoker, according to their smoking status. Thereafter, the associations of different smoking status with the coronary artery plaques were assessed using both univariable and multivariable logistic regression. Results The prevalences of any plaque, significant stenosis and coronary artery calcium score (CACS) ≥ 10 were highest in the current smokers (all p < 0.05). The proportion of calcified plaques was the lowest and the prevalence of non-calcified plaques was the highest in current smokers (p = 0.004). The higher pack-years group had significantly elevated percentages of any plaque, significant stenosis, ≥ 2/LM vessel disease and CACS ≥ 10 than the lower pack-years group (all p < 0.001). The percent of calcified plaques was lower and the percent of non-calcified plaques was higher in the higher (> 20) pack-years group than in the lower pack-years group (≤ 20) (p = 0.024). Current smoking with higher pack-years was the independent risk factor for any plaque, significant stenosis, CACS ≥ 10, non-calcified and mixed plaques (all p < 0.05) after multivariate adjustments. Conclusions The current smokers had the most serious burden of coronary artery plaques and the highest percentage of non-calcified plaques. Current smoking with higher pack-years was a significant risk factor for coronary artery plaque burden and non-calcified and mixed plaques. PMID:27122899

  5. Knockdown of mTOR by lentivirus‑mediated RNA interference suppresses atherosclerosis and stabilizes plaques via a decrease of macrophages by autophagy in apolipoprotein E‑deficient mice.

    PubMed

    Wang, Xiaochuang; Li, Lingxia; Li, Manxiang; Dang, Xiaoyan; Wan, Lin; Wang, Ni; Bi, Xiaoju; Gu, Changwei; Qiu, Suijuan; Niu, Xiaolin; Zhu, Xinye; Wang, Lina

    2013-11-01

    Atherosclerotic plaque destabilization and rupture leads to acute coronary syndromes which cause serious damage to human health worldwide. However, there is currently a lack of efficient therapeutic methods. Mammalian target of rapamycin (mTOR) has been suggested to be involved in the development of atherosclerotic plaques and serves as a therapeutic target. The present study was performed to determine whether RNA interference (RNAi) of mTOR in vivo by LV‑mediated small hairpin RNA (shRNA) was capable of inhibiting the progression of atherosclerotic plaques. LV‑mediated shRNA against mTOR (LV‑shmTOR) was designed and obtained. Male apolipoprotein E‑deficient mice were fed a high‑fat diet and a constrictive collar was placed around the right carotid arteries of these mice to induce plaque formation. Eight weeks after surgery, mice were randomly divided into the mTOR RNA interference (LV‑shmTOR) group, receiving treatment with LV‑mTOR‑shRNA; the LV‑shCON group, receiving treatment with LV‑non‑specific‑shRNA; and the control group, receiving treatment with phosphate‑buffered saline. Following transfection, the mice were sacrificed to evaluate the effects of mTOR expression silencing on atherosclerosis. Transfection of LV‑mTOR‑shRNA markedly inhibited the mRNA and protein expression levels. Knockdown of mTOR ameliorated dysregulated blood lipid metabolism and stabilized aortic atherosclerotic plaques by decreasing the plaque area and increasing the fibrous cap and cap‑to‑core ratio. Furthermore, macrophages were decreased by silencing mTOR in atherosclerotic plaques. In addition, western blot analysis revealed that the knockdown of mTOR increased autophagy‑related protein 13 (Atg13) dephosphorylation and light chain 3‑I/light chain 3‑II (LC3‑I/LC3‑II) ratios, both of which were associated with a high activity of autophagy, suggesting an increase of autophagy in atherosclerotic plaques. Moreover, genes including matrix

  6. Low dose tunicamycin enhances atherosclerotic plaque stability by inducing autophagy.

    PubMed

    Ma, Meijuan; Song, Liqiang; Yan, Hao; Liu, Min; Zhang, Le; Ma, Ying; Yuan, Jian; Hu, Jianhua; Ji, Zhaole; Zhang, Rongqing; Li, Congye; Wang, Haichang; Tao, Ling; Zhang, Yingmei; Li, Yan

    2016-01-15

    After decades of indolent progression, atherosclerosis may cause unheralded events, such as myocardial infarction, acute coronary syndrome and stroke due to sudden rupture of atherosclerotic plaques, and pharmacologically modulating plaque stability would reduce the risk of cardiovascular diseases. Endoplasmic reticulum stress (ERS) is responsible for the vulnerability of plaques. However, the underlying mechanism has not been fully elucidated. In this work, ApoE(-/-) mice underwent perivascular carotid collar placement surgeries or sham operations were given higher (3.0mg/kg) and lower (0.3mg/kg) doses of tunicamycin (TM), and plaque stability was evaluated. It was shown that lower TM-treated animals exhibited reduced plaque areas and necrotic cores as well as fibrous cap thickness accompanied by a lower percentage of infiltrates and foam cells than the sham-operated and higher TM treated animals. Lower TM had a profound inhibitory effect on plasma inflammatory response and lipid profile in atherosclerotic ApoE(-/-) mice. In addition, we found that the ApoE(-/-) mice presented higher autophagy activity in response to lower TM administration while apoptosis was reduced. An in vitro study in murine macrophages revealed that lower TM could markedly reduce lipid uptake and accumulation and cell apoptosis while significantly upregulated the expression of Atg7. However, higher TM had adverse effects. Finally, mild induction of ERS by lower TM inhibits AKT-TSC-mTOR cascades to increase cellular autophagy. However, high TM failed to enhance autophagy and equilibrate elevated CHOP-mediated cell death in spite of the inhibition of AKT-TSC-mTOR signaling. In conclusion, lower TM stabilized plaques by activating autophagy through AKT-TSC-mTOR signaling. PMID:26616221

  7. Imaging of the Fibrous Cap in Atherosclerotic Carotid Plaque

    SciTech Connect

    Saba, Luca; Potters, Fons; Lugt, Aad van der; Mallarini, Giorgio

    2010-08-15

    In the last two decades, a substantial number of articles have been published to provide diagnostic solutions for patients with carotid atherosclerotic disease. These articles have resulted in a shift of opinion regarding the identification of stroke risk in patients with carotid atherosclerotic disease. In the recent past, the degree of carotid artery stenosis was the sole determinant for performing carotid intervention (carotid endarterectomy or carotid stenting) in these patients. We now know that the degree of stenosis is only one marker for future cerebrovascular events. If one wants to determine the risk of these events more accurately, other parameters must be taken into account; among these parameters are plaque composition, presence and state of the fibrous cap (FC), intraplaque haemorrhage, plaque ulceration, and plaque location. In particular, the FC is an important structure for the stability of the plaque, and its rupture is highly associated with a recent history of transient ischaemic attack or stroke. The subject of this review is imaging of the FC.

  8. Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque.

    PubMed

    Janoudi, Abed; Shamoun, Fadi E; Kalavakunta, Jagadeesh K; Abela, George S

    2016-07-01

    Evolution of plaque that is prone to rupture is characterized by inflammation and physical changes. Accumulation of low-density lipoprotein in the sub-intima provides esterified cholesterol (ESC) to macrophages and smooth muscle cells that convert it into free cholesterol (FRC) by cholesteryl ester hydrolases (CEHs). Membrane-bound cholesterol carriers transport FRC to high-density lipoprotein (HDL). Impaired HDL transport function and altered composition can lead to extracellular accumulation of FRC, whereas impaired membrane carrier activity can lead to intracellular FRC accumulation. Saturation of FRC can result in cholesterol crystallization with cell death and intimal injury. Disequilibrium between ESC and FRC can impact foam cell and cholesterol crystal (CC) formation. Cholesterol crystals initiate inflammation via NLRP3 inflammasome leading to interleukin-1β (IL-1β) production inducing C-reactive protein. Eventually, crystals growing from within the plaque and associated inflammation destabilize the plaque. Thus, inhibition of inflammation by antagonists to IL-1β or agents that dissolve or prevent CC formation may stabilize vulnerable plaques. PMID:26705388

  9. Composition and genesis of calcium deposits in atheroma plaques.

    PubMed

    Lara, María Jesús; Ros, Eduardo; Sierra, Manuel; Dorronsoro, Carlos; Aguilar, José

    2014-05-01

    The composition of atheromatous plaque determines its progression toward rupture or thrombosis. Although its histopathological structure has been widely studied, little attention has been paid to its structural and chemical composition and even less to its mineral component. Thirty-three atheromatous plaques were obtained by carotid thromboendarterectomy. Three types of materials were observed under polarized light microscopy: apatite crystals in the form of glomeruli (dark with plane polarized illumination and greensh with cross-polarized illumination); fibrous-like cholesterol (uncolored or grayish with plane-polarized illumination); and amorphous organic material as brownish deposits. SEM-EDX analysis showed an abundance of phosphorus and calcium in sufficient quantities to form calcium phosphates, and appreciably reduced levels of sodium. X-ray diffraction results differentiated samples into three groups: group I with predominance of hydroxyapatite-type crystals, group II with crystalline material containing an amorphous component, and group III with wholly amorphous material. The most abundant mineral in atheromatous plaque is hydroxyapatite, on which crystals of cholesterol and lipid nuclei are deposited, stratifying the plaque into layers that reflect the different stages of its formation. The difference in calcium and sodium concentrations between arteries with and without atheromata may indicate an important relationship in the pathophysiological development of calcium deposits. PMID:24134634

  10. Assessment of carotid plaque neovascularization by contrast-enhanced ultrasound and high sensitivity C-reactive protein test in patients with acute cerebral infarction: a comparative study.

    PubMed

    Xu, Rong; Yin, Xiaohua; Xu, Weixin; Jin, Lin; Lu, Min; Wang, Yingchun

    2016-07-01

    Vulnerable carotid plaque easily ruptures and causes cerebral infarction. Plaque inflammation and neovascularization have both been shown as important characteristics in vulnerable plaque. We assessed neovascularization within carotid plaque using contrast-enhanced ultrasound, and also assessed inflammation, using high sensitivity C-reactive protein (hs-CRP) testing, in acute cerebral infarction patients. A total of 106 patients with acute cerebral infarction and 40 controls were enrolled in the study. All subjects had been previously found to have carotid atherosclerotic plaques, and the plaques were classified as soft plaque, hard plaque, mixed plaque, and calcified plaque, using carotid artery ultrasound. Contrast-enhanced ultrasound was performed on the plaques for quantitative analysis and hs-CRP levels were measured. The results showed that plaque enhancement was present in 81.1 % of cerebral infarction patients and 40.0 % of controls. The contrast parameters for cerebral infarction patients were significantly different from controls. For cerebral infarction patients, soft plaque showed the highest enhanced percentage, 95.1 %, with contrast parameters significantly different to other types of plaque. The hs-CRP levels of enhanced cerebral infarction patients were higher than in non-enhanced patients. Correlation analysis in cerebral infarction patients showed that hs-CRP levels were closely related to the contrast parameters. Acute cerebral infarction patients showed intense contrast enhancement and inflammation in carotid plaque, and different types of plaque had various degrees of enhancement, suggesting that contrast-enhanced ultrasound and hs-CRP might be used for plaque risk stratification. PMID:27021564

  11. Pioneer F Plaque Location

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The Pioneer F spacecraft, destined to be the first man made object to escape from the solar system into interstellar space, carries this pictorial plaque. It is designed to show scientifically educated inhabitants of some other star system, who might intercept it millions of years from now, when Pioneer was launched, from where, and by what kind of beings. (Hopefully, any aliens reading the plaque will not use this knowledge to immediately invade Earth.) The design is etched into a 6 inch by 9 inch gold-anodized aluminum plate, attached to the spacecraft's attenna support struts in a position to help shield it from erosion by interstellar dust. The radiating lines at left represents the positions of 14 pulsars, a cosmic source of radio energy, arranged to indicate our sun as the home star of our civilization. The '1-' symbols at the ends of the lines are binary numbers that represent the frequencies of these pulsars at the time of launch of Pioneer F relative of that to the hydrogen atom shown at the upper left with a '1' unity symbol. The hydrogen atom is thus used as a 'universal clock,' and the regular decrease in the frequencies of the pulsars will enable another civilization to determine the time that has elapsed since Pioneer F was launched. The hydrogen is also used as a 'universal yardstick' for sizing the human figures and outline of the spacecraft shown on the right. The hydrogen wavelength, about 8 inches, multiplied by the binary number representing '8' shown next to the woman gives her height, 64 inches. The figures represent the type of creature that created Pioneer. The man's hand is raised in a gesture of good will. Across the bottom are the planets, ranging outward from the Sun, with the spacecraft trajectory arching away from Earth, passing Mars, and swinging by Jupiter.

  12. Achilles tendon rupture rehabilitation

    PubMed Central

    Kearney, R. S.; Parsons, N.; Underwood, M.; Costa, M. L.

    2015-01-01

    Objectives The evidence base to inform the management of Achilles tendon rupture is sparse. The objectives of this research were to establish what current practice is in the United Kingdom and explore clinicians’ views on proposed further research in this area. This study was registered with the ISRCTN (ISRCTN68273773) as part of a larger programme of research. Methods We report an online survey of current practice in the United Kingdom, approved by the British Orthopaedic Foot and Ankle Society and completed by 181 of its members. A total of ten of these respondents were invited for a subsequent one-to-one interview to explore clinician views on proposed further research in this area. Results The survey showed wide variations in practice, with patients being managed in plaster cast alone (13%), plaster cast followed by orthoses management (68%), and orthoses alone (19%). Within these categories, further variation existed regarding the individual rehabilitation facets, such as the length of time worn, the foot position within them and weight-bearing status. The subsequent interviews reflected this clinical uncertainty and the pressing need for definitive research. Conclusions The gap in evidence in this area has resulted in practice in the United Kingdom becoming varied and based on individual opinion. Future high-quality randomised trials on this subject are supported by the clinical community. Cite this article: Bone Joint Res 2015;4:65–9 PMID:25868938

  13. Chemical Plaque Control Strategies in the Prevention of Biofilm-associated Oral Diseases.

    PubMed

    Jafer, Mohammed; Patil, Shankargouda; Hosmani, Jagadish; Bhandi, Shilpa H; Chalisserry, Elna P; Anil, Sukumaran

    2016-01-01

    Dental plaque is a biofilm that forms naturally on the surfaces of exposed teeth and other areas of the oral cavity. It is the primary etiological factor for the most frequently occurring oral diseases, such as dental caries and periodontal diseases. Specific, nonspecific, and ecologic plaque hypothesis explains the causation of dental and associated diseases. Adequate control of biofilm accumulation on teeth has been the cornerstone of prevention of periodontitis and dental caries. Mechanical plaque control is the mainstay for prevention of oral diseases, but it requires patient cooperation and motivation; therefore, chemical plaque control agents act as useful adjuvants for achieving the desired results. Hence, it is imperative for the clinicians to update their knowledge in chemical antiplaque agents and other developments for the effective management of plaque biofilm-associated diseases. This article explores the critical analysis of various chemical plaque control strategies and the current trends in the control and prevention of dental plaque biofilm. PMID:27340170

  14. Morphological and Stress Vulnerability Indices for Human Coronary Plaques and Their Correlations with Cap Thickness and Lipid Percent: An IVUS-Based Fluid-Structure Interaction Multi-patient Study

    PubMed Central

    Wang, Liang; Zheng, Jie; Maehara, Akiko; Yang, Chun; Billiar, Kristen L.; Wu, Zheyang; Bach, Richard; Muccigrosso, David; Mintz, Gary S.; Tang, Dalin

    2015-01-01

    Plaque vulnerability, defined as the likelihood that a plaque would rupture, is difficult to quantify due to lack of in vivo plaque rupture data. Morphological and stress-based plaque vulnerability indices were introduced as alternatives to obtain quantitative vulnerability assessment. Correlations between these indices and key plaque features were investigated. In vivo intravascular ultrasound (IVUS) data were acquired from 14 patients and IVUS-based 3D fluid-structure interaction (FSI) coronary plaque models with cyclic bending were constructed to obtain plaque wall stress/strain and flow shear stress for analysis. For the 617 slices from the 14 patients, lipid percentage, min cap thickness, critical plaque wall stress (CPWS), strain (CPWSn) and flow shear stress (CFSS) were recorded, and cap index, lipid index and morphological index were assigned to each slice using methods consistent with American Heart Association (AHA) plaque classification schemes. A stress index was introduced based on CPWS. Linear Mixed-Effects (LME) models were used to analyze the correlations between the mechanical and morphological indices and key morphological factors associated with plaque rupture. Our results indicated that for all 617 slices, CPWS correlated with min cap thickness, cap index, morphological index with r = -0.6414, 0.7852, and 0.7411 respectively (p<0.0001). The correlation between CPWS and lipid percentage, lipid index were weaker (r = 0.2445, r = 0.2338, p<0.0001). Stress index correlated with cap index, lipid index, morphological index positively with r = 0.8185, 0.3067, and 0.7715, respectively, all with p<0.0001. For all 617 slices, the stress index has 66.77% agreement with morphological index. Morphological and stress indices may serve as quantitative plaque vulnerability assessment supported by their strong correlations with morphological features associated with plaque rupture. Differences between the two indices may lead to better plaque assessment schemes

  15. Making a Lightweight Battery Plaque

    NASA Technical Reports Server (NTRS)

    Reid, M. A.; Post, R. E.; Soltis, D.

    1986-01-01

    Plaque formed in porous plastic by electroless plating. Lightweight plaque prepared by electroless plating of porous plastic contains embedded wire or expanded metal grid. Plastic may or may not be filled with soluble pore former. If it contains soluble pore former, treated to remove soluble pore former and increase porosity. Porous plastic then clamped into rig that allows plating solutions to flow through plastic. Lightweight nickel plaque used as electrode substrate for alkaline batteries, chiefly Ni and Cd electrodes, and for use as electrolyte-reservoir plates for fuel cells.

  16. Noninvasive imaging modalities to visualize atherosclerotic plaques

    PubMed Central

    2016-01-01

    Atherosclerotic cardiovascular disease is becoming a major cause of death in the world due to global epidemic of diabetes and obesity. For the prevention of atherosclerotic cardiovascular disease, it is necessary to detect high-risk atherosclerotic plaques prior to events. Recent technological advances enable to visualize atherosclerotic plaques noninvasively. This ability of noninvasive imaging helps to refine cardiovascular risk assessment in various individuals, select optimal therapeutic strategy and evaluate the efficacy of medical therapies. In this review, we discuss the role of the currently available imaging modalities including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography. Advantages and disadvantages of each noninvasive imaging modality will be also summarized. PMID:27500092

  17. Noninvasive imaging modalities to visualize atherosclerotic plaques.

    PubMed

    Shishikura, Daisuke

    2016-08-01

    Atherosclerotic cardiovascular disease is becoming a major cause of death in the world due to global epidemic of diabetes and obesity. For the prevention of atherosclerotic cardiovascular disease, it is necessary to detect high-risk atherosclerotic plaques prior to events. Recent technological advances enable to visualize atherosclerotic plaques noninvasively. This ability of noninvasive imaging helps to refine cardiovascular risk assessment in various individuals, select optimal therapeutic strategy and evaluate the efficacy of medical therapies. In this review, we discuss the role of the currently available imaging modalities including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography. Advantages and disadvantages of each noninvasive imaging modality will be also summarized. PMID:27500092

  18. Distribution of nickel hydroxide in sintered nickel plaques measured by radiotracer method during electroimpregnation

    SciTech Connect

    Ng, P.K.; Schneider, E.W.

    1986-01-01

    Sintered nickel positive electrodes were prepared by electroimpregnating nickel hydroxide inside a porous nickel plaque in a nickel nitrate solution. The distribution of nickel hydroxide inside the plaque was measured using a radio-tracer method with /sup 63/Ni as the radioactivity source. Autoradiography and ..beta.. counting were used to follow qualitative and quantitative distributions, respectively, of the pore filling process. Relatively uniform distribution was observed at low current density, and the precipitation of Ni(OH)/sub 2/ extends to the center of the plaque. At high current density, most of the Ni(OH)/sub 2/ aggregated in the region just underneath the plaque surface, causing a somewhat nonuniform distribution. Nickel hydroxide also precipitates heavily on the surface of the plaque at high current density, reducing the penetration of electrolyte to the inside of the plaque.

  19. Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice

    PubMed Central

    Sastre, Cristina; Fernández-Laso, Valvanera; Madrigal-Matute, Julio; Muñoz-García, Begoña; Moreno, Juan A; Pastor-Vargas, Carlos; Llamas-Granda, Patricia; Burkly, Linda C; Egido, Jesús; Martín-Ventura, Jose L; Blanco-Colio, Luis M

    2014-01-01

    Clinical complications associated with atherosclerotic plaques arise from luminal obstruction due to plaque growth or destabilization leading to rupture. Tumour necrosis factor ligand superfamily member 12 (TNFSF12) also known as TNF-related weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine that participates in atherosclerotic plaque development, but its role in plaque stability remains unclear. Using two different approaches, genetic deletion of TNFSF12 and treatment with a TWEAK blocking mAb in atherosclerosis-prone mice, we have analysed the effect of TWEAK inhibition on atherosclerotic plaques progression and stability. Mice lacking both TNFSF12 and Apolipoprotein E (TNFSF12−/−ApoE−/−) exhibited a diminished atherosclerotic burden and lesion size in their aorta. Advanced atherosclerotic plaques of TNFSF12−/−ApoE−/− or anti-TWEAK treated mice exhibited an increase collagen/lipid and vascular smooth muscle cell/macrophage ratios compared with TNFSF12+/+ApoE−/− control mice, reflecting a more stable plaque phenotype. These changes are related with two different mechanisms, reduction of the inflammatory response (chemokines expression and secretion and nuclear factor kappa B activation) and decrease of metalloproteinase activity in atherosclerotic plaques of TNFSF12−/−ApoE−/−. A similar phenotype was observed with anti-TWEAK mAb treatment in TNFSF12+/+ApoE−/− mice. Brachiocephalic arteries were also examined since they exhibit additional features akin to human atherosclerotic plaques associated with instability and rupture. Features of greater plaque stability including augmented collagen/lipid ratio, reduced macrophage content, and less presence of lateral xanthomas, buried caps, medial erosion, intraplaque haemorrhage and calcium content were present in TNFSF12−/−ApoE−/− or anti-TWEAK treatment in TNFSF12+/+ApoE−/− mice. Overall, our data indicate that anti-TWEAK treatment has the capacity to diminish

  20. Identification of Amyloid Plaques in Retinas from Alzheimer’s Patients and Noninvasive In Vivo Optical Imaging of Retinal Plaques in a Mouse Model

    PubMed Central

    Koronyo-Hamaoui, Maya; Koronyo, Yosef; Ljubimov, Alexander V.; Miller, Carol A.; Ko, MinHee K.; Black, Keith L.; Schwartz, Michal; Farkas, Daniel L.

    2010-01-01

    Noninvasive monitoring of β-amyloid (Aβ) plaques, the neuropathological hallmarks of Alzheimer's disease (AD), is critical for AD diagnosis and prognosis. Current visualization of Aβ plaques in brains of live patients and animal models is limited in specificity and resolution. The retina as an extension of the brain portrays an appealing target for a live, noninvasive optical imaging of AD if disease pathology is manifested there. We identified retinal Aβ plaques in postmortem eyes from AD patients (n=8) and in suspected early stage cases (n=5), consistent with brain pathology and clinical reports; plaques were undetectable in age-matched non-AD individuals (n=5). In APPSWE/PS1ΔE9 transgenic mice (AD-Tg; n=18) and not in non-Tg wt mice (n=10), retinal Aβ plaques were detected following systemic administration of curcumin, a safe plaque-labeling fluorochrome. Moreover, retinal plaques were detectable earlier than in the brain and accumulated with disease progression. An immune-based therapy effective in reducing brain plaques, significantly reduced retinal Aβ plaque burden in immunized versus non-immunized AD mice (n=4 mice per group). In live AD-Tg mice (n=24), systemic administration of curcumin allowed noninvasive optical imaging of retinal Aβ plaques in vivo with high resolution and specificity; plaques were undetectable in non-Tg wt mice (n=11). Our discovery of Aβ specific plaques in retinas from AD patients, and the ability to noninvasively detect individual retinal plaques in live AD mice establish the basis for developing high resolution optical imaging for early AD diagnosis, prognosis assessment and response to therapies. PMID:20550967

  1. On the effect of calcification volume and configuration on the mechanical behaviour of carotid plaque tissue.

    PubMed

    Barrett, H E; Cunnane, E M; Kavanagh, E G; Walsh, M T

    2016-03-01

    Vascular calcification is a complex molecular process that exhibits a number of relatively characteristic morphology patterns in atherosclerotic plaques. Treatment of arterial stenosis by endovascular intervention, involving forceful circumferential expansion of the plaque, can be unpredictable in calcified lesions. The aim of this study was to determine the mechanical stretching mechanisms and define the mechanical limits for circumferentially expanding carotid plaque lesions under the influence of distinct calcification patterns. Mechanical and structural characterisation was performed on 17 human carotid plaques acquired from patients undergoing endarterectomy procedures. The mechanical properties were determined using uniaxial extension tests that stretch the lesions to complete failure along their circumferential axis. Calcification morphology of mechanically ruptured plaque lesions was characterised using high resolution micro computed tomography imaging. Scanning electron microscopy was used to examine the mechanically induced failure sites and to identify the interface boundary conditions between calcified and non-calcified tissue. The mechanical tests produced four distinct trends in mechanical behaviour which corresponded to the calcification patterns that structurally defined each mechanical group. Each calcification pattern produced unique mechanical restraining effects on the plaque tissue stretching properties evidenced by the variation in degree of stretch to failure. Resistance to failure appears to rely on interactions between calcification and non-calcified tissue. Scanning electron microscopy examination revealed structural gradations at interface boundary conditions to facilitate the transfer of stress. This study emphasises the mechanical influence of distinct calcification configurations on plaque expansion properties and highlights the importance of pre-operative lesion characterisation to optimise treatment outcomes. PMID:26655460

  2. Application of IR and NIR fiber optic imaging in thermographic and spectroscopic diagnosis of atherosclerotic vulnerable plaques: preliminary experience

    NASA Astrophysics Data System (ADS)

    Naghavi, Morteza; Khan, Tania; Gu, Bujin; Soller, Babs R.; Melling, Peter; Asif, Mohammed; Gul, Khawar; Madjid, Mohammad; Casscells, S. W.; Willerson, James T.

    2000-12-01

    Despite major advances in cardiovascular science and technology during the past three decades, approximately half of all myocardial infarctions and sudden deaths occur unexpectedly. It is widely accepted that coronary atherosclerotic plaques and thrombotic complications resulting from their rupture or erosion are the underlying causes of this major health problem. The majority of these vulnerable plaques exhibit active inflammation, a large necrotic lipid core, a thin fibrous cap, and confer a stenosis of less than 70%. These lesions are not detectable by stress testing or coronary angiography. Our group is exploring the possibility of a functional classification based on physiological variables such as plaque temperature, pH, oxygen consumption, lactate production etc. We have shown that heat accurately locates the inflamed plaques. We also demonstrated human atherosclerotic plaques are heterogeneous with regard to pH and hot plaques and are more likely to be acidic. To develop a nonsurgical method for locating the inflamed plaques, we are developing both IR fiber optic imaging and NIR spectroscopic systems in our laboratory to detect hot and acidic plaque in atherosclerotic arterial walls. Our findings introduce the possibility of an isolated/combined IR and NIR fiber optic catheter that can bring new insight into functional assessment of atherosclerotic plaque and thereby detection of active and inflamed lesions responsible for heart attacks and strokes.

  3. Disappearance of La Caille Plaque

    NASA Astrophysics Data System (ADS)

    2010-04-01

    A bronze plaque erected to the memory of N.-L. de La Caille near the site of his observatory in Central Cape Town, has been stolen by metal thieves. It was designed by the famous architect Sir Herbert Baker.

  4. Pioneer F Plaque Symbology

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The Pioneer F spacecraft, destined to be the first man made object to escape from the solar system into interstellar space, carries this pictorial plaque. It is designed to show scientifically educated inhabitants of some other star system, who might intercept it millions of years from now, when Pioneer was launched, from where, and by what kind of beings. (With the hope that they would not invade Earth.) The design is etched into a 6 inch by 9 inch gold-anodized aluminum plate, attached to the spacecraft's attenna support struts in a position to help shield it from erosion by interstellar dust. The radiating lines at left represents the positions of 14 pulsars, a cosmic source of radio energy, arranged to indicate our sun as the home star of our civilization. The '1-' symbols at the ends of the lines are binary numbers that represent the frequencies of these pulsars at the time of launch of Pioneer F relative of that to the hydrogen atom shown at the upper left with a '1' unity symbol. The hydrogen atom is thus used as a 'universal clock,' and the regular decrease in the frequencies of the pulsars will enable another civilization to determine the time that has elapsed since Pioneer F was launched. The hydrogen is also used as a 'universal yardstick' for sizing the human figures and outline of the spacecraft shown on the right. The hydrogen wavelength, about 8 inches, multiplied by the binary number representing '8' shown next to the woman gives her height, 64 inches. The figures represent the type of creature that created Pioneer. The man's hand is raised in a gesture of good will. Across the bottom are the planets, ranging outward from the Sun, with the spacecraft trajectory arching away from Earth, passing Mars, and swinging by Jupiter.

  5. Identification of High-Risk Plaques by MRI and Fluorescence Imaging in a Rabbit Model of Atherothrombosis

    PubMed Central

    Hua, Ning; Baik, Fred; Pham, Tuan; Phinikaridou, Alkystis; Giordano, Nick; Friedman, Beth; Whitney, Michael; Nguyen, Quyen T.; Tsien, Roger Y.; Hamilton, James A.

    2015-01-01

    Introduction The detection of atherosclerotic plaques at risk for disruption will be greatly enhanced by molecular probes that target vessel wall biomarkers. Here, we test if fluorescently-labeled Activatable Cell Penetrating Peptides (ACPPs) could differentiate stable plaques from vulnerable plaques that disrupt, forming a luminal thrombus. Additionally, we test the efficacy of a combined ACPP and MRI technique for identifying plaques at high risk of rupture. Methods and Results In an atherothrombotic rabbit model, disrupted plaques were identified with in vivo MRI and co-registered in the same rabbit aorta with the in vivo uptake of ACPPs, cleaved by matrix metalloproteinases (MMPs) or thrombin. ACPP uptake, mapped ex vivo in whole aortas, was higher in disrupted compared to non-disrupted plaques. Specifically, disrupted plaques demonstrated a 4.5~5.0 fold increase in fluorescence enhancement, while non-disrupted plaques showed only a 2.2~2.5 fold signal increase. Receiver operating characteristic (ROC) analysis indicates that both ACPPs (MMP and thrombin) show high specificity (84.2% and 83.2%) and sensitivity (80.0% and 85.7%) in detecting disrupted plaques. The detection power of ACPPs was improved when combined with the MRI derived measure, outward remodeling ratio. Conclusions Our targeted fluorescence ACPP probes distinguished disrupted plaques from stable plaques with high sensitivity and specificity. The combination of anatomic, MRI-derived predictors for disruption and ACPP uptake can further improve the power for identification of high-risk plaques and suggests future development of ACPPs with molecular MRI as a readout. PMID:26448434

  6. Adhesive strength of atherosclerotic plaque in a mouse model depends on local collagen content and elastin fragmentation.

    PubMed

    Wang, Ying; Johnson, John A; Fulp, Abigail; Sutton, Michael A; Lessner, Susan M

    2013-02-22

    Atherosclerotic plaque rupture is a major cause of myocardial infarction and ischemic stroke. The adhesive strength of the bond between a plaque and the vascular wall, measured as local energy release rate, G, is used for quantitative plaque stability estimation. We tested the hypothesis that adhesive strength varies with plaque composition. Matrix metalloproteinase-12 (MMP12) deficiency was previously reported to alter lesion composition. To estimate G values, peeling experiments are performed on aortic plaques from apolipoprotein E knockout (apoE KO) and apoE MMP12 double knockout (DKO) male mice after 8 months on high-fat diet. For plaques in apoE KO and apoE MMP12 DKO mice, experimental values for G differ significantly (p<0.002) between genotypes, averaging 19.2J/m(2) and 12.1J/m(2), respectively. Histology confirms that plaques delaminate along their interface with the underlying internal elastic lamina (IEL) in both genotypes. Quantitative image analysis of stained tissue sections demonstrates a significant positive correlation (p<0.05) between local collagen content of lesions and G values in both genotypes, indicating that adhesive strength of plaques depends on local collagen content. Surprisingly, macrophage content of aortic plaques is neither significantly correlated with G values nor significantly different between genotypes. The IEL underlying plaques in apoE KO mice is significantly more fragmented (number of breaks and length of breaks) than in apoE MMP12 DKO mice, suggesting that elastin fragmentation also influences adhesion strength of plaques. Overall, our results suggest that plaques adhere more strongly to the underlying IEL in apoE KO mice than in apoE MMP12 DKO mice. PMID:23261250

  7. Automatic plaque assay for the pharmaceutical industry using machine vision

    NASA Astrophysics Data System (ADS)

    Wilder, Joseph; Tsai, Augustine; Festa, J. M.

    1995-10-01

    A crucial step in the manufacture of vaccines is the verification of their potency. An assay of the potency must be carried out on every batch produced to determine the safety and efficacy of the vaccine. Currently, human inspectors count the number of plaques (holes) in a cell layer in a petri dish to estimate the potency.They must determine whether nearby plaques that have overgrown each other's borders are single or multiple plaques and distinguish between plaques and small tears in the cell layer resulting from the processing operations (the edges of tears differ in appearance from the edges of plaques). Because of the judgments required to make these subtle distinctions, human inspectors are inconsistent. In cooperation with Merck & Co., Inc., the Rutgers University Center for Computer Aids for Industrial Productivity has demonstrated the feasibility of achieving consistent automatic counting of plaques by a prototype intelligent machine vision system. The David Sarnoff Research Center developed materials handling equipment and factory information system interfaces to enable this prototype system to be installed in a quality control facility at Merck. This paper describes the overall operation of the machine vision aspects of the system, including optics, illumination, sensing, preprocessing, feature extraction and shape recognition. Results of initial tests of the system are also reported.

  8. Fault rupture segmentation

    NASA Astrophysics Data System (ADS)

    Cleveland, Kenneth Michael

    A critical foundation to earthquake study and hazard assessment is the understanding of controls on fault rupture, including segmentation. Key challenges to understanding fault rupture segmentation include, but are not limited to: What determines if a fault segment will rupture in a single great event or multiple moderate events? How is slip along a fault partitioned between seismic and seismic components? How does the seismicity of a fault segment evolve over time? How representative are past events for assessing future seismic hazards? In order to address the difficult questions regarding fault rupture segmentation, new methods must be developed that utilize the information available. Much of the research presented in this study focuses on the development of new methods for attacking the challenges of understanding fault rupture segmentation. Not only do these methods exploit a broader band of information within the waveform than has traditionally been used, but they also lend themselves to the inclusion of even more seismic phases providing deeper understandings. Additionally, these methods are designed to be fast and efficient with large datasets, allowing them to utilize the enormous volume of data available. Key findings from this body of work include demonstration that focus on fundamental earthquake properties on regional scales can provide general understanding of fault rupture segmentation. We present a more modern, waveform-based method that locates events using cross-correlation of the Rayleigh waves. Additionally, cross-correlation values can also be used to calculate precise earthquake magnitudes. Finally, insight regarding earthquake rupture directivity can be easily and quickly exploited using cross-correlation of surface waves.

  9. The rhythmic expression of clock genes attenuated in human plaque-derived vascular smooth muscle cells

    PubMed Central

    2014-01-01

    Background Acute myocardial infarction and stroke are more likely to occur in the early morning. Circadian pacemakers are considered to be involved in the process. Many peripheral tissues and cells also contain clock systems. In this study, we examined whether the primary cultured human plaque-derived vascular smooth muscle cells (VSMCs) process circadian rhythmicity; furthermore, we investigated the expression difference of clock genes between normal human carotid VSMCs and human plaque-derived VSMCs. Methods Fifty-six human carotid plaques provided the atherosclerotic tissue, and 21 samples yielded viable cultured primary VSMCs. The normal carotid VSMCs were cultured from donors’ normal carotids. The mRNA levels of the target genes were measured by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results After serum shock, both types of cells showed clear circadian expressions of Bmal1, Cry1, Cry2, Per1, Per2, Per3 and Rev-erbα mRNA; meanwhile the Clock mRNA show a rhythmic expression in plaque-derived SMCs but not in normal carotid VSMCs. The expression levels of these main clock genes were significantly attenuated in human plaque-derived VSMCs compared with normal human carotid VSMCs. The rhythm of Bmal1 mRNA in plaque-derived VSMCs was changed. Conclusion The present results demonstrate that the human plaque-derived VSMCs possess different circadian rhythmicity from that of normal carotid VSMCs. The rhythm changes of clock genes in plaque-derived VSMCs may be involved in the process of atherosclerosis and finally promote the rupture of plaque. PMID:24418196

  10. Denitrification in human dental plaque

    PubMed Central

    2010-01-01

    Background Microbial denitrification is not considered important in human-associated microbial communities. Accordingly, metabolic investigations of the microbial biofilm communities of human dental plaque have focused on aerobic respiration and acid fermentation of carbohydrates, even though it is known that the oral habitat is constantly exposed to nitrate (NO3-) concentrations in the millimolar range and that dental plaque houses bacteria that can reduce this NO3- to nitrite (NO2-). Results We show that dental plaque mediates denitrification of NO3- to nitric oxide (NO), nitrous oxide (N2O), and dinitrogen (N2) using microsensor measurements, 15N isotopic labelling and molecular detection of denitrification genes. In vivo N2O accumulation rates in the mouth depended on the presence of dental plaque and on salivary NO3- concentrations. NO and N2O production by denitrification occurred under aerobic conditions and was regulated by plaque pH. Conclusions Increases of NO concentrations were in the range of effective concentrations for NO signalling to human host cells and, thus, may locally affect blood flow, signalling between nerves and inflammatory processes in the gum. This is specifically significant for the understanding of periodontal diseases, where NO has been shown to play a key role, but where gingival cells are believed to be the only source of NO. More generally, this study establishes denitrification by human-associated microbial communities as a significant metabolic pathway which, due to concurrent NO formation, provides a basis for symbiotic interactions. PMID:20307293

  11. Incomplete Cesarean Scar Rupture

    PubMed Central

    Ahmadi, Firoozeh; Siahbazi, Shiva; Akhbari, Farnaz

    2013-01-01

    Background Uterine rupture at the site of a previous cesarean scar is an uncommon but catastrophic complication of pregnancy, which is associated with significant maternal and fetal morbidity and mortality. Case Presentation A 30-year old woman at 24th week of gestation and complaint of pain, contractions and spotting was admitted in Royan Institute in Tehran, Iran. She had a past medical history of an EP and a cesarean section delivery, respectively 4 and 2 years before hospitalization. Herniation of an amniotic membrane into the maternal bladder was found on ultrasound examination. Conclusion Risk factors of cesarean scar rupture should be considered in women undergoing subsequent pregnancies as they need extra care. Ultrasonography can be used to evaluate women with previous cesarean section to assess the risks of scar rupture during subsequent pregnancies. PMID:23926561

  12. Arachnoid cyst spontaneous rupture.

    PubMed

    Marques, Inês Brás; Vieira Barbosa, José

    2014-01-01

    Arachnoid cysts are benign congenital cerebrospinal fluid collections, usually asymptomatic and diagnosed incidentally in children or adolescents. They may become symptomatic after enlargement or complications, frequently presenting with symptoms of intracranial hypertension. We report an unusual case of progressive refractory headache in an adult patient due to an arachnoid cyst spontaneous rupture. Although clinical improvement occurred with conservative treatment, the subdural hygroma progressively enlarged and surgical treatment was ultimately needed. Spontaneous rupture is a very rare complication of arachnoid cysts. Accumulation of cerebrospinal fluid accumulation in the subdural space causes sustained intracranial hypertension that may be life-threatening and frequently requires surgical treatment. Patients with arachnoid cysts must be informed on their small vulnerability to cyst rupture and be aware that a sudden and severe headache, especially if starting after minor trauma or a Valsalva manoeuvre, always requires medical evaluation. PMID:24581205

  13. A uni-extension study on the ultimate material strength and extreme extensibility of atherosclerotic tissue in human carotid plaques

    PubMed Central

    Teng, Zhongzhao; Feng, Jiaxuan; Zhang, Yongxue; Sutcliffe, Michael P.F.; Huang, Yuan; Brown, Adam J.; Jing, Zaiping; Lu, Qingsheng; Gillard, Jonathan H.

    2015-01-01

    Atherosclerotic plaque rupture occurs when mechanical loading exceeds its material strength. Mechanical analysis has been shown to be complementary to the morphology and composition for assessing vulnerability. However, strength and stretch thresholds for mechanics-based assessment are currently lacking. This study aims to quantify the ultimate material strength and extreme extensibility of atherosclerotic components from human carotid plaques. Tissue strips of fibrous cap, media, lipid core and intraplaque hemorrhage/thrombus were obtained from 21 carotid endarterectomy samples of symptomatic patients. Uni-extension test with tissue strips was performed until they broke or slid. The Cauchy stress and stretch ratio at the peak loading of strips broken about 2 mm away from the clamp were used to characterize their ultimate strength and extensibility. Results obtained indicated that ultimate strength of fibrous cap and media were 158.3 [72.1, 259.3] kPa (Median [Inter quartile range]) and 247.6 [169.0, 419.9] kPa, respectively; those of lipid and intraplaque hemorrhage/thrombus were 68.8 [48.5, 86.6] kPa and 83.0 [52.1, 124.9] kPa, respectively. The extensibility of each tissue type were: fibrous cap – 1.18 [1.10, 1.27]; media – 1.21 [1.17, 1.32]; lipid – 1.25 [1.11, 1.30] and intraplaque hemorrhage/thrombus – 1.20 [1.17, 1.44]. Overall, the strength of fibrous cap and media were comparable and so were lipid and intraplaque hemorrhage/thrombus. Both fibrous cap and media were significantly stronger than either lipid or intraplaque hemorrhage/thrombus. All atherosclerotic components had similar extensibility. Moreover, fibrous cap strength in the proximal region (closer to the heart) was lower than that of the distal. These results are helpful in understanding the material behavior of atherosclerotic plaques. PMID:26472304

  14. Intravascular probe for detection of vulnerable plaque

    NASA Astrophysics Data System (ADS)

    Patt, Bradley E.; Iwanczyk, Jan S.; MacDonald, Lawrence R.; Yamaguchi, Yuko; Tull, Carolyn R.; Janecek, Martin; Hoffman, Edward J.; Strauss, H. William; Tsugita, Ross; Ghazarossian, Vartan

    2001-12-01

    Coronary angiography is unable to define the status of the atheroma, and only measures the luminal dimensions of the blood vessel, without providing information about plaque content. Up to 70% of heart attacks are caused by minimally obstructive vulnerable plaques, which are too small to be detected adequately by angiography. We have developed an intravascular imaging detector to identify vulnerable coronary artery plaques. The detector works by sensing beta or conversion electron radiotracer emissions from plaque-binding radiotracers. The device overcomes the technical constraints of size, sensitivity and conformance to the intravascular environment. The detector at the distal end of the catheter uses six 7mm long by 0.5mm diameter scintillation fibers coupled to 1.5m long plastic fibers. The fibers are offset from each other longitudinally by 6mm and arranged spirally around a guide wire in the catheter. At the proximal end of the catheter the optical fibers are coupled to an interface box with a snap on connector. The interface box contains a position sensitive photomultiplier tube (PSPMT) to decode the individual fibers. The whole detector assembly fits into an 8-French (2.7 mm in diameter) catheter. The PSPMT image is further decoded with software to give a linear image, the total instantaneous count rate and an audio output whose tone corresponds to the count rate. The device was tested with F-18 and Tl-204 sources. Spectrometric response, spatial resolution, sensitivity and beta to background ratio were measured. System resolution is 6 mm and the sensitivity is >500 cps / micrometers Ci when the source is 1 mm from the detector. The beta to background ratio was 11.2 for F-18 measured on a single fiber. The current device will lead to a system allowing imaging of labeled vulnerable plaque in coronary arteries. This type of signature is expected to enable targeted and cost effective therapies to prevent acute coronary artery diseases such as: unstable angina

  15. Neuroimaging of the Vulnerable Plaque

    PubMed Central

    Lovblad, Karl-Olof; Mendes-Pereira, Vitor; Garibotto, Valentina; Assal, Frédéric; Willi, Jean-Pierre; Stztajzel, Roman; Ratib, Osman; Vargas, Maria Isabel

    2015-01-01

    Plaque vulnerability due to inflammation has been shown to be a participating factor in the degenerative process in the arterial wall that contributes to stenosis and embolism. This is believed to have an important role to play also in the genesis of stroke or cerebrovascular diseases. In order to appropriately screen patients for treatment, there is an absolute need to directly or indirectly visualize both the normal carotid and the suspected plaque. This can be done with a variety of techniques ranging from ultrasound to computed tomography (CT) and magnetic resonance imaging (MRI). In addition to angiographic techniques, direct imaging of the plaque can be done either by ultrasound or by the so-called molecular imaging techniques, i.e. positron emission tomography (PET). These findings, together with other clinical and paraclinical parameters should finally guide the therapeutic choice. PMID:24188487

  16. Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors.

    PubMed

    Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, DaeGab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

    2016-01-01

    Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications. PMID:26948523

  17. Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability

    PubMed Central

    Veiner, Hilla-Lee; Gorbatov, Rostic; Vardi, Moshe; Doros, Gheorghe; Miller-Lotan, Rachel; Zohar, Yaniv; Sabo, Edmond; Asleh, Rabea; Levy, Nina S.; Goldfarb, Levi J.; Berk, Thomas A.; Haas, Tali; Shalom, Hadar; Suss-Toby, Edith; Kam, Adi; Kaplan, Marielle; Tamir, Ronit; Ziskind, Anna; Levy, Andrew P.

    2015-01-01

    Structured Abstract Objective Homozygosity for a 1.7kb intragenic duplication of the Haptoglobin (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been associated with a 2–3 fold increased incidence of atherothrombosis in individuals with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated with the Hp 2-2 genotype has been shown to be prevented with vitamin E supplementation in man. We sought to determine if there was an interaction between the Hp genotype and vitamin E on atherosclerotic plaque growth and stability in a transgenic model of the Hp polymorphism. Methods and Results Brachiocephalic artery atherosclerotic plaque volume was serially assessed by high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE−/− background. Hp 2-2 mice had more rapid plaque growth and an increased incidence of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction between the Hp genotype and vitamin E on plaque growth. Conclusions These results may help explain why vitamin E supplementation in man can prevent CVD in Hp 2-2 DM but not in non Hp 2-2 DM individuals. PMID:25618031

  18. Imaging Plaques to Predict and Better Manage Patients with Acute Coronary Events

    PubMed Central

    Garcia-Garcia, Hector M.; Jang, Ik-Kyung; Serruys, Patrick W.; Kovacic, Jason C.; Narula, Jagat; Fayad, Zahi A.

    2014-01-01

    Culprit lesions of patients who have had an acute coronary syndrome commonly are ruptured coronary plaques with superimposed thrombus. The precursor of such lesions is an inflamed thin-capped fibroatheroma. These plaques can be imaged by means of invasive techniques such as intravascular ultrasound (and derived techniques), optical coherence tomography and near-infrared spectroscopy. Very often these patients exhibit similar (multiple) plaques beyond the culprit lesion. These remote plaques can be assessed non invasively by computed tomography angiography and magnetic resonance imaging and also using invasive imaging. The detection of these remote plaques is not only feasible, but also in natural history studies have been associated with clinical coronary events. Different systemic pharmacological treatments have been studied (mostly statins) with modest success and therefore newer approaches are being tested. Local treatment for such lesions is in its infancy and larger, prospective and randomized trials are needed. This review will describe the pathological and imaging findings in culprit lesions of patients with acute coronary syndrome and as well as the assessment of remote plaques. In addition, the pharmacological and local treatment options will be reviewed. PMID:24902974

  19. Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

    PubMed Central

    Kim, Ji Bak; Park, Kyeongsoon; Ryu, Jiheun; Lee, Jae Joong; Lee, Min Woo; Cho, Han Saem; Nam, Hyeong Soo; Park, Ok Kyu; Song, Joon Woo; Kim, Tae Shik; Oh, Dong Joo; Gweon, DaeGab; Oh, Wang-Yuhl; Yoo, Hongki; Kim, Jin Won

    2016-01-01

    Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications. PMID:26948523

  20. Molecular Imaging of Plaque Vulnerability

    PubMed Central

    Tavakoli, Sina; Vashist, Aseem; Sadeghi, Mehran M.

    2014-01-01

    Over the past decade significant progress has been made in the development of novel imaging strategies focusing on the biology of the vessel wall for identification of vulnerable plaques. While the majority of these studies are still in the preclinical stage, few techniques (e.g., 18F-FDG and 18F-NaF PET imaging) have already been evaluated in clinical studies with promising results. Here, we will briefly review the pathobiology of atherosclerosis and discuss molecular imaging strategies that have been developed to target these events, with an emphasis on mechanisms that are associated with atherosclerotic plaque vulnerability. PMID:25124827

  1. Anti‐Inflammatory Immune Skewing Is Atheroprotective: Apoe−/−FcγRIIb−/− Mice Develop Fibrous Carotid Plaques

    PubMed Central

    Harmon, Erin Y.; Fronhofer, Van; Keller, Rebecca S.; Feustel, Paul J.; Zhu, Xinmei; Xu, Hao; Avram, Dorina; Jones, David M.; Nagarajan, Shanmugam; Lennartz, Michelle R.

    2014-01-01

    Background Stroke, caused by carotid plaque rupture, is a major cause of death in the United States. Whereas vulnerable human plaques have higher Fc receptor (FcγR) expression than their stable counterparts, how FcγR expression impacts plaque histology is unknown. We investigated the role of FcγRIIb in carotid plaque development and stability in apolipoprotein (Apo)e−/− and Apoe−/−FcγRIIb−/− double knockout (DKO) animals. Methods and Results Plaques were induced by implantation of a shear stress‐modifying cast around the carotid artery. Plaque length and stenosis were followed longitudinally using ultrasound biomicroscopy. Immune status was determined by flow cytometry, cytokine release, immunoglobulin G concentration and analysis of macrophage polarization both in plaques and in vitro. Surprisingly, DKO animals had lower plaque burden in both carotid artery and descending aorta. Plaques from Apoe−/− mice were foam‐cell rich and resembled vulnerable human specimens, whereas those from DKO mice were fibrous and histologically stable. Plaques from DKO animals expressed higher arginase 1 (Arg‐1) and lower inducible nitric oxide synthase (iNOS), indicating the presence of M2 macrophages. Analysis of blood and cervical lymph nodes revealed higher interleukin (IL)‐10, immune complexes, and regulatory T cells (Tregs) and lower IL‐12, IL‐1β, and tumor necrosis factor alpha (TNF‐α) in DKO mice. Similarly, in vitro stimulation produced higher IL‐10 and Arg‐1 and lower iNOS, IL‐1β, and TNF‐α in DKO versus Apoe−/− macrophages. These results define a systemic anti‐inflammatory phenotype. Conclusions We hypothesized that removal of FcγRIIb would exacerbate atherosclerosis and generate unstable plaques. However, we found that deletion of FcγRIIb on a congenic C57BL/6 background induces an anti‐inflammatory Treg/M2 polarization that is atheroprotective. PMID:25516435

  2. Ligation of Macrophage Fcγ Receptors Recapitulates the Gene Expression Pattern of Vulnerable Human Carotid Plaques

    PubMed Central

    Lennartz, Michelle R.; Aggarwal, Ankur; Michaud, Tanya M.; Feustel, Paul J.; Jones, David M.; Brosnan, M. Julia; Keller, Rebecca S.; Loegering, Daniel J.; Kreienberg, Paul B.

    2011-01-01

    Stroke is a leading cause of death in the United States. As ∼60% of strokes result from carotid plaque rupture, elucidating the mechanisms that underlie vulnerability is critical for therapeutic intervention. We tested the hypothesis that stable and vulnerable human plaques differentially express genes associated with matrix degradation. Examination established that femoral, and the distal region of carotid, plaques were histologically stable while the proximal carotid plaque regions were vulnerable. Quantitative RT-PCR was used to compare expression of 22 genes among these tissues. Distal carotid and femoral gene expression was not significantly different, permitting the distal carotid segments to be used as a paired control for their corresponding proximal regions. Analysis of the paired plaques revealed differences in 16 genes that impact plaque stability: matrix metalloproteinases (MMP, higher in vulnerable), MMP modulators (inhibitors: lower, activators: higher in vulnerable), activating Fc receptors (FcγR, higher in vulnerable) and FcγR signaling molecules (higher in vulnerable). Surprisingly, the relative expression of smooth muscle cell and macrophage markers in the three plaque types was not significantly different, suggesting that macrophage distribution and/or activation state correlates with (in)stability. Immunohistochemistry revealed that macrophages and smooth muscle cells localize to distinct and non-overlapping regions in all plaques. MMP protein localized to macrophage-rich regions. In vitro, treatment of macrophages with immune complexes, but not oxidized low density lipoprotein, C-reactive protein, or TNF-α, induced a gene expression profile similar to that of the vulnerable plaques. That ligation of FcγR recapitulates the pattern of gene expression in vulnerable plaques suggests that the FcγR → macrophage activation pathway may play a greater role in human plaque vulnerability than previously appreciated. PMID:21814555

  3. In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque

    NASA Astrophysics Data System (ADS)

    Motz, Jason T.; Fitzmaurice, Maryann; Miller, Arnold; Gandhi, Saumil J.; Haka, Abigail S.; Galindo, Luis; Dasari, Ramachandra R.; Kramer, John R., Jr.; Feld, Michael S.

    2006-03-01

    The rupture of vulnerable atherosclerotic plaque accounts for the majority of clinically significant acute cardiovascular events. Because stability of these culprit lesions is directly related to chemical and morphological composition, Raman spectroscopy may be a useful technique for their study. Recent developments in optical fiber probe technology have allowed for the real-time in vivo Raman spectroscopic characterization of human atherosclerotic plaque demonstrated in this work. We spectroscopically examine 74 sites during carotid endarterectomy and femoral artery bypass surgeries. Of these, 34 are surgically biopsied and examined histologically. Excellent signal-to-noise ratio spectra are obtained in only 1 s and fit with an established model, demonstrating accurate tissue characterization. We also report the first evidence that Raman spectroscopy has the potential to identify vulnerable plaque, achieving a sensitivity and specificity of 79 and 85%, respectively. These initial findings indicate that Raman spectroscopy has the potential to be a clinically relevant diagnostic tool for studying cardiovascular disease.

  4. Dynamic rupture processes inferred from laboratory microearthquakes

    NASA Astrophysics Data System (ADS)

    Passelègue, François. X.; Schubnel, Alexandre; Nielsen, Stefan; Bhat, Harsha S.; Deldicque, Damien; Madariaga, Raúl

    2016-06-01

    We report macroscopic stick-slip events in saw-cut Westerly granite samples deformed under controlled upper crustal stress conditions in the laboratory. Experiments were conducted under triaxial loading (σ1>σ2=σ3) at confining pressures (σ3) ranging from 10 to 100 MPa. A high-frequency acoustic monitoring array recorded particle acceleration during macroscopic stick-slip events allowing us to estimate rupture speed. In addition, we record the stress drop dynamically and we show that the dynamic stress drop measured locally close to the fault plane is almost total in the breakdown zone (for normal stress >75 MPa), while the friction f recovers to values of f > 0.4 within only a few hundred microseconds. Enhanced dynamic weakening is observed to be linked to the melting of asperities which can be well explained by flash heating theory in agreement with our postmortem microstructural analysis. Relationships between initial state of stress, rupture velocities, stress drop, and energy budget suggest that at high normal stress (leading to supershear rupture velocities), the rupture processes are more dissipative. Our observations question the current dichotomy between the fracture energy and the frictional energy in terms of rupture processes. A power law scaling of the fracture energy with final slip is observed over 8 orders of magnitude in slip, from a few microns to tens of meters.

  5. Understanding Motivation of Plaque Control.

    ERIC Educational Resources Information Center

    Beck, Kenneth H.

    1982-01-01

    A theoretical model for understanding motivation of plaque control is presented. The belief in this model is that, if people can be convinced of their ability to control a health threat, they would be encouraged to take responsibility for their health. (CJ)

  6. Dynamics of mussel plaque detachment.

    PubMed

    Desmond, Kenneth W; Zacchia, Nicholas A; Waite, J Herbert; Valentine, Megan T

    2015-09-14

    Mussels are well known for their ability to generate and maintain strong, long-lasting adhesive bonds under hostile conditions. Many prior studies attribute their adhesive strength to the strong chemical interactions between the holdfast and substrate. While chemical interactions are certainly important, adhesive performance is also determined by contact geometry, and understanding the coupling between chemical interactions and the plaque shape and mechanical properties is essential in deploying bioinspired strategies when engineering improved adhesives. To investigate how the shape and mechanical properties of the mussel's plaque contribute to its adhesive performance, we use a custom built load frame capable of fully characterizing the dynamics of the detachment. With this, we can pull on samples along any orientation, while at the same time measuring the resulting force and imaging the bulk deformations of the plaque as well as the holdfast-substrate interface where debonding occurs. We find that the force-induced yielding of the mussel plaque improves the bond strength by two orders of magnitude and that the holdfast shape improves bond strength by an additional order of magnitude as compared to other simple geometries. These results demonstrate that optimizing the contact geometry can play as important a role on adhesive performance as optimizing the chemical interactions as observed in other organisms and model systems. PMID:26223522

  7. Mathematical modeling and simulation of the evolution of plaques in blood vessels.

    PubMed

    Yang, Yifan; Jäger, Willi; Neuss-Radu, Maria; Richter, Thomas

    2016-03-01

    In this paper, a model is developed for the evolution of plaques in arteries, which is one of the main causes for the blockage of blood flow. Plaque rupture and spread of torn-off material may cause closures in the down-stream vessel system and lead to ischemic brain or myocardial infarctions. The model covers the flow of blood and its interaction with the vessel wall. It is based on the assumption that the penetration of monocytes from the blood flow into the vessel wall, and the accumulation of foam cells increasing the volume, are main factors for the growth of plaques. The dynamics of the vessel wall is governed by a deformation gradient, which is given as composition of a purely elastic tensor, and a tensor modeling the biologically caused volume growth. An equation for the evolution of the metric is derived quantifying the changing geometry of the vessel wall. To calculate numerically the solutions of the arising free boundary problem, the model system of partial differential equations is transformed to an ALE (Arbitrary Lagrangian-Eulerian) formulation, where all equations are given in fixed domains. The numerical calculations are using newly developed algorithms for ALE systems. The results of the simulations, obtained for realistic system parameters, are in good qualitative agreement with observations. They demonstrate that the basic modeling assumption can be justified. The increase of stresses in the vessel wall can be computed. Medical treatment tries to prevent critical stress values, which may cause plaque rupture and its consequences. PMID:26385578

  8. Machine learning techniques as a helpful tool toward determination of plaque vulnerability.

    PubMed

    Cilla, Myriam; Martínez, Javier; Peña, Estefanía; Martínez, Miguel Ángel

    2012-04-01

    Atherosclerotic cardiovascular disease results in millions of sudden deaths annually, and coronary artery disease accounts for the majority of this toll. Plaque rupture plays main role in the majority of acute coronary syndromes. Rupture has been usually associated with stress concentrations, which are determined mainly by tissue properties and plaque geometry. The aim of this study is develop a tool, using machine learning techniques to assist the clinical professionals on decisions of the vulnerability of the atheroma plaque. In practice, the main drawbacks of 3-D finite element analysis to predict the vulnerability risk are the huge main memories required and the long computation times. Therefore, it is essential to use these methods which are faster and more efficient. This paper discusses two potential applications of computational technologies, artificial neural networks and support vector machines, used to assess the role of maximum principal stress in a coronary vessel with atheroma plaque as a function of the main geometrical features in order to quantify the vulnerability risk. PMID:22287230

  9. Anterior cruciate ligament rupture and osteoarthritis progression.

    PubMed

    Wong, James Min-Leong; Khan, Tanvir; Jayadev, Chethan S; Khan, Wasim; Johnstone, David

    2012-01-01

    Anterior Cruciate Ligament (ACL) rupture is a common sporting injury that frequently affects young, athletic patients. Apart from the functional problems of instability, patients with ACL deficient knees also develop osteoarthritis. Although this is frequently cited as an indication for ACL reconstruction, the relationship between ACL rupture, reconstruction and the instigation and progression of articular cartilage degenerative change is controversial.The purpose of this paper is to review the published literature with regards ACL rupture and the multifactorial causes for osteoarthritis progression, and whether or not this is slowed or stopped by ACL reconstruction.There is no evidence in the published literature to support the view that ACL reconstruction prevents osteoarthritis, although it may prevent further meniscal damage. It must be recognised that this conclusion is based on the current literature which has substantial methodological limitations. PMID:22896777

  10. Ruptured, Intracranial Dermoid Cyst - A Visual Diagnosis?

    PubMed Central

    Scheer, Fabian; Andresen, Reimer

    2016-01-01

    Dermoid cysts are a very rare entity of intracranial tumours. The traumatic or non-traumatic rupture of the cyst wall is a serious complication that can be treated surgically or conservatively depending on the clinical symptoms. However, more common entities have to be considered as a differential diagnosis. We report on a female patient who was admitted with complaints of significant, prolonged headache and diffuse pain. Analysis of her blood and cerebrospinal fluid indicated no clear pathology. A CT examination of the head revealed a ruptured dermoid cyst adjacent to the left sphenoidal bone. An additional MRI was conducted to confirm the CT findings and rule out an intracranial ischemia or vasospasms. A conservative therapy was scheduled and the patient recovered well. Using current imaging techniques, especially magnetic resonance imaging, it is possible to identify a ruptured dermoid cyst by its pathognomonic signal behavior and rule out potentially life threatening complications. PMID:27190918

  11. Human coronary plaque wall thickness correlated positively with flow shear stress and negatively with plaque wall stress: an IVUS-based fluid-structure interaction multi-patient study

    PubMed Central

    2014-01-01

    Background Atherosclerotic plaque progression and rupture are believed to be associated with mechanical stress conditions. In this paper, patient-specific in vivo intravascular ultrasound (IVUS) coronary plaque image data were used to construct computational models with fluid-structure interaction (FSI) and cyclic bending to investigate correlations between plaque wall thickness and both flow shear stress and plaque wall stress conditions. Methods IVUS data were acquired from 10 patients after voluntary informed consent. The X-ray angiogram was obtained prior to the pullback of the IVUS catheter to determine the location of the coronary artery stenosis, vessel curvature and cardiac motion. Cyclic bending was specified in the model representing the effect by heart contraction. 3D anisotropic FSI models were constructed and solved to obtain flow shear stress (FSS) and plaque wall stress (PWS) values. FSS and PWS values were obtained for statistical analysis. Correlations with p < 0.05 were deemed significant. Results Nine out of the 10 patients showed positive correlation between wall thickness and flow shear stress. The mean Pearson correlation r-value was 0.278 ± 0.181. Similarly, 9 out of the 10 patients showed negative correlation between wall thickness and plaque wall stress. The mean Pearson correlation r-value was -0.530 ± 0.210. Conclusion Our results showed that plaque vessel wall thickness correlated positively with FSS and negatively with PWS. The patient-specific IVUS-based modeling approach has the potential to be used to investigate and identify possible mechanisms governing plaque progression and rupture and assist in diagnosis and intervention procedures. This represents a new direction of research. Further investigations using more patient follow-up data are warranted. PMID:24669780

  12. Quantitative Evaluation of Atherosclerotic Plaque Using Ultrasound Tissue Characterization.

    NASA Astrophysics Data System (ADS)

    Yigiter, Ersin

    Evaluation of therapeutic methods directed toward interrupting and/or delaying atherogenesis is impeded by the lack of a reliable, non-invasive means for monitoring progression or regression of disease. The ability to characterize the predominant component of plaque may be very valuable in the study of this disease's natural history. The earlier the lesion, the more likely is lipid to be the predominant component. Progression of plaque is usually by way of overgrowth of fibrous tissues around the fatty pool. Calcification is usually a feature of the older or complicated lesion. To explore the feasibility of using ultrasound to characterize plaque we have conducted measurements of the acoustical properties of various atherosclerotic lesions found in freshly excised samples of human abdominal aorta. Our objective has been to determine whether or not the acoustical properties of plaque correlate with the type and/or chemical composition of plaque and, if so, to define a measurement scheme which could be done in-vivo and non-invasively. Our current data base consists of individual tissue samples from some 200 different aortas. Since each aorta yields between 10 to 30 tissue samples for study, we have data on some 4,468 different lesions or samples. Measurements of the acoustical properties of plaque were found to correlate well with the chemical composition of plaque. In short, measurements of impedance and attenuation seem sufficient to classify plaque as to type and to composition. Based on the in-vitro studies, the parameter of attenuation was selected as a means of classifying the plaque. For these measurements, an intravascular ultrasound scanner was modified according to our specifications. Signal processing algorithms were developed which would analyze the complex ultrasound waveforms and estimate tissue properties such as attenuation. Various methods were tried to estimate the attenuation from the pulse-echo backscattered signal. Best results were obtained by

  13. Association between abdominal aortic plaque and coronary artery disease

    PubMed Central

    Li, Wei; Luo, Songyuan; Luo, Jianfang; Liu, Yuan; Huang, Wenhui; Chen, Jiyan

    2016-01-01

    Objective Currently, the association between abdominal aortic plaques and coronary artery disease (CAD) has not yet been clarified clearly. The purpose of this study was to determine the prevalence of abdominal aortic plaques by ultrasound imaging and to explore its association with CAD in patients undergoing coronary angiography. Methods Between October 2014 and June 2015, a prospective study was conducted in the Department of Cardiology at Guangdong General Hospital, Guangzhou, People’s Republic of China. Ultrasound scanning of the abdominal aortas was performed in 1,667 consecutive patients undergoing coronary angiography. Clinical characteristics and coronary profile were collected from the patients. Results Of the 1,667 study patients (male, 68.9%; mean age, 63±11 years) undergoing coronary angiography, 1,268 had CAD. Compared with 399 patients without CAD, 1,268 patients with CAD had higher prevalence of abdominal aortic plaques (37.3% vs 17%, P<0.001). In multivariate analysis, abdominal aortic plaques served as independent factors associated with the presence of CAD (odds ratio =2.08; 95% confidence interval =1.50–2.90; P<0.001). Of the 1,268 patients with CAD, the prevalence of abdominal aortic plaques was 27.0% (98/363) in patients with one-vessel disease, 35.0% (107/306) in patients with two-vessel disease, and 44.7% (268/599) in patients with three-vessel disease. Stepwise increases in the prevalence of abdominal aortic plaque was found depending on the number of stenotic coronary vessels (P<0.001; P-value for trend <0.001). In an ordinal logistic regression model, abdominal aortic plaques served as independent factors associated with the severity of CAD according to the number of stenotic coronary vessels (P<0.001). Conclusion The prevalence of abdominal aortic plaques was higher in patients with CAD than in those without CAD. Abdominal aortic plaque was an independent factor associated with the presence and severity of CAD. PMID:27279740

  14. Blunt cardiac rupture.

    PubMed

    Martin, T D; Flynn, T C; Rowlands, B J; Ward, R E; Fischer, R P

    1984-04-01

    Blunt injury to the heart ranges from contusion to disruption. This report comprises 14 patients seen during a 6-year period with cardiac rupture secondary to blunt trauma. Eight patients were injured in automobile accidents, two patients were injured in auto-pedestrian accidents, two were kicked in the chest by ungulates, and two sustained falls. Cardiac tamponade was suspected in ten patients. Five patients presented with prehospital cardiac arrest or arrested shortly after arrival. All underwent emergency department thoracotomy without survival. Two patients expired in the operating room during attempted cardiac repair; both had significant extracardiac injury. Seven patients survived, three had right atrial injuries, three had right ventricular injuries, and one had a left atrial injury. Cardiopulmonary bypass was not required for repair of the surviving patients. There were no significant complications from the cardiac repair. The history of significant force dispersed over a relatively small area of the precordium as in a kicking injury from an animal or steering wheel impact should alert the physician to possible cardiac rupture. Cardiac rupture should be considered in patients who present with signs of cardiac tamponade or persistent thoracic bleeding after blunt trauma. PMID:6708151

  15. Premature rupture of membranes.

    PubMed Central

    Poma, P. A.

    1996-01-01

    The management of patients with premature rupture of membranes has changed markedly in the past several years. The basis for this is a combination of a better understanding of newborn physiology, improved neonatal care, refinements in antibiotic therapy, and the widespread use of maternal and fetal monitoring. The best outcome for both mother and infant undoubtedly reflects data based on a combination of factors, among which are gestational age survival, evidence of fetal distress, presence or absence of labor and sepsis, and of course, the cervical condition as it is related to labor-readiness. An important recent advance is the recognition that an active observation management program is associated with less morbidity and mortality than the classic management course of delivery within 12 hours of membrane rupture. The fact that preterm premature rupture of membranes tends to recur in subsequent pregnancies offers an opportunity for prevention. Moreover, advances in perinatal and neonatal care will continue to improve the outcomes of these women and their children. PMID:8583489

  16. A Framework for Local Mechanical Characterization of Atherosclerotic Plaques: Combination of Ultrasound Displacement Imaging and Inverse Finite Element Analysis.

    PubMed

    Akyildiz, Ali C; Hansen, Hendrik H G; Nieuwstadt, Harm A; Speelman, Lambert; De Korte, Chris L; van der Steen, Antonius F W; Gijsen, Frank J H

    2016-04-01

    Biomechanical models have the potential to predict plaque rupture. For reliable models, correct material properties of plaque components are a prerequisite. This study presents a new technique, where high resolution ultrasound displacement imaging and inverse finite element (FE) modeling is combined, to estimate material properties of plaque components. Iliac arteries with plaques were excised from 6 atherosclerotic pigs and subjected to an inflation test with pressures ranging from 10 to 120 mmHg. The arteries were imaged with high frequency 40 MHz ultrasound. Deformation maps of the plaques were reconstructed by cross correlation of the ultrasound radiofrequency data. Subsequently, the arteries were perfusion fixed for histology and structural components were identified. The histological data were registered to the ultrasound data to construct FE model of the plaques. Material properties of the arterial wall and the intima of the atherosclerotic plaques were estimated using a grid search method. The computed displacement fields showed good agreement with the measured displacement fields, implying that the FE models were able to capture local inhomogeneities within the plaque. On average, nonlinear stiffening of both the wall and the intima was observed, and the wall of the atheroslcerotic porcine iliac arteries was markedly stiffer than the intima (877 ± 459 vs. 100 ± 68 kPa at 100 mmHg). The large spread in the data further illustrates the wide variation of the material properties. We demonstrated the feasibility of a mixed experimental-numerical framework to determine the material properties of arterial wall and intima of atherosclerotic plaques from intact arteries, and concluded that, due to the observed variation, plaque specific properties are required for accurate stress simulations. PMID:26399991

  17. The pathology of parietal pleural plaques

    PubMed Central

    Roberts, G. Hefin

    1971-01-01

    The incidence, morbid anatomy, histology, and relationship of hyaline pleural plaques to exposure to asbestos has been studied. Plaques were found in 12·3% of 334 hospital necropsies (in an urban population in Glasgow, 41 cases). In 85·3% (35 cases) asbestos bodies were found in the lungs. There is evidence of a dose-response relationship between the number of asbestos bodies found in the lungs and the presence of pleural plaques. The selective distribution of plaques within the pleural cavities suggests that mechanical factors play a part in their localization. Histological examination contributed little to understanding the mechanism of plaque formation; that asbestos bodies have been detected in only a few cases suggest that their presence in the parietal pleura is not essential to plaque formation. The suggested mechanisms of plaque formation are discussed. Images PMID:5556121

  18. Modeling of Experimental Atherosclerotic Plaque Delamination.

    PubMed

    Leng, Xiaochang; Chen, Xin; Deng, Xiaomin; Sutton, Michael A; Lessner, Susan M

    2015-12-01

    A cohesive zone model (CZM) approach is applied to simulate atherosclerotic plaque delamination experiments in mouse abdominal aorta specimens. A three-dimensional finite element model is developed for the experiments. The aortic wall is treated as a fiber-reinforced, highly deformable, incompressible material, and the Holzapfel-Gasser-Ogden (HGO) model is adopted for the aortic bulk material behavior. Cohesive elements are placed along the plaque-media interface along which delamination occurs. The 3D specimen geometry is created based on images from the experiments and certain simplifying approximations. A set of HGO and CZM parameter values is determined based on values suggested in the literature and through matching simulation predictions of the load vs. load-point displacement curve with experimental measurements for one loading-delamination-unloading cycle. Using this set of parameter values, simulation predictions for four other loading-delamination-unloading cycles are obtained, which show good agreement with experimental measurements. The findings of the current study demonstrate the applicability of the CZM approach in arterial tissue failure simulations. PMID:26101030

  19. Nanorose and lipid detection in atherosclerotic plaque using dual-wavelength photothermal wave imaging

    NASA Astrophysics Data System (ADS)

    Wang, Tianyi; Qiu, Jinze; Ma, Li Leo; Li, Xiankai; Sun, Jingjing; Ryoo, Seungyup; Johnston, Keith P.; Feldman, Marc D.; Milner, Thomas E.

    2010-02-01

    Atherosclerosis and specifically rupture of vulnerable plaques account for 23% of all deaths worldwide, far surpassing both infectious diseases and cancer. In atherosclerosis, macrophages can infiltrate plaques which are often associated with lipid deposits. Photothermal wave imaging is based on the periodic thermal modulation of a sample using intensity modulated light. Intensity modulated light enters the sample and is absorbed by targeted chromophores and generates a periodic thermal modulation. We report use of photothermal wave imaging to visualize nanoroses (taken up by macrophages via endocytosis) and lipids in atherosclerotic plaques. Two excitation wavelengths were selected to image nanoroses (800 nm) and lipids (1210 nm). Atherosclerotic plaque in a rabbit abdominal artery was irradiated (800 nm and 1210 nm separately) at a frequency of 4 Hz to generate photothermal waves. The radiometric temperature at the tissue surface was recorded by an infrared (IR) camera over a 10 second time period at the frame rate of 25.6 Hz. Extraction of images (256 × 256 pixels) at various frequencies was performed by Fourier transform at each pixel. Frequency amplitude images were obtained corresponding to 800 nm and 1210 nm laser irradiation. Computed images suggest that the distributions of both nanorose and lipid can be identified in amplitude images at a frequency of 4 Hz. Nanoroses taken up by macrophages are distributed at the edges of lipid deposits. Observation of high concentration of nanoroses in atherosclerotic plaque confirms that nanoroses are present at locations associated with lipid deposits.

  20. Towards coronary plaque imaging using simultaneous PET-MR: a simulation study.

    PubMed

    Petibon, Y; El Fakhri, G; Nezafat, R; Johnson, N; Brady, T; Ouyang, J

    2014-03-01

    Coronary atherosclerotic plaque rupture is the main cause of myocardial infarction and the leading killer in the US. Inflammation is a known bio-marker of plaque vulnerability and can be assessed non-invasively using fluorodeoxyglucose-positron emission tomography imaging (FDG-PET). However, cardiac and respiratory motion of the heart makes PET detection of coronary plaque very challenging. Fat surrounding coronary arteries allows the use of MRI to track plaque motion during simultaneous PET-MR examination. In this study, we proposed and assessed the performance of a fat-MR based coronary motion correction technique for improved FDG-PET coronary plaque imaging in simultaneous PET-MR. The proposed methods were evaluated in a realistic four-dimensional PET-MR simulation study obtained by combining patient water-fat separated MRI and XCAT anthropomorphic phantom. Five small lesions were digitally inserted inside the patients coronary vessels to mimic coronary atherosclerotic plaques. The heart of the XCAT phantom was digitally replaced with the patient's heart. Motion-dependent activity distributions, attenuation maps, and fat-MR volumes of the heart, were generated using the XCAT cardiac and respiratory motion fields. A full Monte Carlo simulation using Siemens mMR's geometry was performed for each motion phase. Cardiac/respiratory motion fields were estimated using non-rigid registration of the transformed fat-MR volumes and incorporated directly into the system matrix of PET reconstruction along with motion-dependent attenuation maps. The proposed motion correction method was compared to conventional PET reconstruction techniques such as no motion correction, cardiac gating, and dual cardiac-respiratory gating. Compared to uncorrected reconstructions, fat-MR based motion compensation yielded an average improvement of plaque-to-background contrast of 29.6%, 43.7%, 57.2%, and 70.6% for true plaque-to-blood ratios of 10, 15, 20 and 25:1, respectively. Channelized

  1. Towards coronary plaque imaging using simultaneous PET-MR: a simulation study

    NASA Astrophysics Data System (ADS)

    Petibon, Y.; El Fakhri, G.; Nezafat, R.; Johnson, N.; Brady, T.; Ouyang, J.

    2014-03-01

    Coronary atherosclerotic plaque rupture is the main cause of myocardial infarction and the leading killer in the US. Inflammation is a known bio-marker of plaque vulnerability and can be assessed non-invasively using fluorodeoxyglucose-positron emission tomography imaging (FDG-PET). However, cardiac and respiratory motion of the heart makes PET detection of coronary plaque very challenging. Fat surrounding coronary arteries allows the use of MRI to track plaque motion during simultaneous PET-MR examination. In this study, we proposed and assessed the performance of a fat-MR based coronary motion correction technique for improved FDG-PET coronary plaque imaging in simultaneous PET-MR. The proposed methods were evaluated in a realistic four-dimensional PET-MR simulation study obtained by combining patient water-fat separated MRI and XCAT anthropomorphic phantom. Five small lesions were digitally inserted inside the patients coronary vessels to mimic coronary atherosclerotic plaques. The heart of the XCAT phantom was digitally replaced with the patient's heart. Motion-dependent activity distributions, attenuation maps, and fat-MR volumes of the heart, were generated using the XCAT cardiac and respiratory motion fields. A full Monte Carlo simulation using Siemens mMR's geometry was performed for each motion phase. Cardiac/respiratory motion fields were estimated using non-rigid registration of the transformed fat-MR volumes and incorporated directly into the system matrix of PET reconstruction along with motion-dependent attenuation maps. The proposed motion correction method was compared to conventional PET reconstruction techniques such as no motion correction, cardiac gating, and dual cardiac-respiratory gating. Compared to uncorrected reconstructions, fat-MR based motion compensation yielded an average improvement of plaque-to-background contrast of 29.6%, 43.7%, 57.2%, and 70.6% for true plaque-to-blood ratios of 10, 15, 20 and 25:1, respectively. Channelized

  2. Towards coronary plaque imaging using simultaneous PET-MR: a simulation study

    PubMed Central

    Petibon, Y; El Fakhri, G; Nezafat, R; Johnson, N; Brady, T; Ouyang, J

    2014-01-01

    Coronary atherosclerotic plaque rupture is the main cause of myocardial infarction and the leading killer in the US. Inflammation is a known bio-marker of plaque vulnerability and can be assessed non-invasively using FDG-PET imaging. However, cardiac and respiratory motion of the heart makes PET detection of coronary plaque very challenging. Fat surrounding coronary arteries allow the use of MRI to track plaque motion during simultaneous PET-MR examination. In this study, we proposed and assessed the performance of a fat-MR based coronary motion correction technique for improved FDG-PET coronary plaque imaging in simultaneous PET-MR. The proposed methods were evaluated in a realistic four-dimensional PET-MR simulation study obtained by combining patient water-fat separated MRI and XCAT anthropomorphic phantom. Five small lesions were digitally inserted inside the patient coronary vessels to mimic coronary atherosclerotic plaques. The heart of the XCAT phantom was digitally replaced with the patient’s heart. Motion-dependent activity distributions, attenuation maps, and fat MR volumes of the heart, were generated using the XCAT cardiac and respiratory motion fields. A full Monte Carlo simulation using Siemens mMR’s geometry was performed for each motion phase. Cardiac/respiratory motion fields were estimated using non-rigid registration of the transformed fat MR volumes and incorporated directly into the system matrix of PET reconstruction along with motion-dependent attenuation maps. The proposed motion correction method was compared to conventional PET reconstruction techniques such as no motion correction, cardiac gating, and dual cardiac-respiratory gating. Compared to uncorrected reconstructions, fat-MR based motion compensation yielded an average improvement of plaque-to-background contrast (PBC) of 29.6%, 43.7%, 57.2%, and 70.6% for true plaque-to-blood ratios of 10, 15, 20 and 25:1, respectively. Channelized Hotelling Observer (CHO) Signal to Noise Ratio

  3. Ruptured tubal molar pregnancy.

    PubMed

    Yakasai, I A; Adamu, N; Galadanchi, H S

    2012-01-01

    Molar pregnancies in most instances develop within the uterine cavity, but may occur at any site. Ectopic molar pregnancy is a rare event. The objective of this study was to present a case of ruptured tubal molar gestation, discuss its clinical features and ways to improve diagnostic accuracy. A 35-year-old woman presented with features suggestive of ruptured tubal ectopic pregnancy. There was neither any evidence at the time of presentation to suspect a molar gestation, nor β human chorionic gonadotrophin (βhCG) hormone estimation was done, but only a clearview pregnancy test was carried out. She had total left salpingectomy and histological evaluation of the specimen revealed complete hydatidiform mole. The hCG level normalized within 3 weeks of follow-up. Clinical features of ectopic molar pregnancy may be indistinguishable from non-molar ectopic pregnancy. We recommend βhCG estimation as well as histological examination of the surgical specimen for all patients coming with features suggestive of ectopic pregnancy. PMID:23238205

  4. Patient-Specific Carotid Plaque Progression Simulation Using 3D Meshless Generalized Finite Difference Models with Fluid-Structure Interactions Based on Serial In Vivo MRI Data.

    PubMed

    Yang, Chun; Tang, Dalin; Atluri, Satya

    2011-01-01

    simulation adds time dimension to plaque vulnerability assessment and will improve prediction accuracy for potential plaque rupture risk. PMID:21927582

  5. Wrapped Wire Detects Rupture Of Pressure Vessel

    NASA Technical Reports Server (NTRS)

    Hunt, James B.

    1990-01-01

    Simple, inexpensive technique helps protect against damage caused by continuing operation of equipment after rupture or burnout of pressure vessel. Wire wrapped over area on outside of vessel where breakthrough most likely. If wall breaks or burns, so does wire. Current passing through wire ceases, triggering cutoff mechanism stopping flow in vessel to prevent further damage. Applied in other situations in which pipes or vessels fail due to overpressure, overheating, or corrosion.

  6. Impact of Wall Shear Stress and Pressure Variation on the Stability of Atherosclerotic Plaque

    NASA Astrophysics Data System (ADS)

    Taviani, V.; Li, Z. Y.; Sutcliffe, M.; Gillard, J.

    Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The mechanism of blood flow and plaque rupture in stenotic arteries is still not fully understood. A three dimensional rigid wall model was solved under steady and unsteady conditions assuming a time-varying inlet velocity profile to investigate the relative importance of axial forces and pressure drops in arteries with asymmetric stenosis. Flow-structure interactions were investigated for the same geometry and the results were compared with those retrieved with the corresponding one dimensional models. The Navier-Stokes equations were used as the governing equations for the fluid. The tube wall was assumed linearly elastic, homogeneous isotropic. The analysis showed that wall shear stress is small (less than 3.5%) with respect to pressure drop throughout the cycle even for severe stenosis. On the contrary, the three dimensional behavior of velocity, pressure and wall shear stress is in general very different from that predicted by one dimensional models. This suggests that the primary source of mistakes in one dimensional studies comes from neglecting the three dimensional geometry of the plaque. Neglecting axial forces only involves minor errors.

  7. Plaque and arterial vulnerability investigation in a three-layer atherosclerotic human coronary artery using computational fluid-structure interaction method

    NASA Astrophysics Data System (ADS)

    Karimi, Alireza; Navidbakhsh, Mahdi; Razaghi, Reza

    2014-08-01

    Coronary artery disease is the common form of cardiovascular diseases and known to be the main reason of deaths in the world. Fluid-Structure Interaction (FSI) simulations can be employed to assess the interactions of artery/plaque and blood to provide a more precise anticipation for rupture of arterial tissue layers and plaque tissues inside an atherosclerotic artery. To date, the arterial tissue in computational FSI simulations has been considered as a one-layer structure. However, a single layer assumption might have deeply bounded the results and, consequently, more computational simulation is needed by considering the arterial tissue as a three-layer structure. In this study, a three-dimensional computational FSI model of an atherosclerotic artery with a three-layer structure and different plaque types was established to perform a more accurate arterial wall/plaque tissue vulnerability assessment. The hyperelastic material coefficients of arterial layers were calculated and implemented in the computational model. The fully coupled fluid and structure models were solved using the explicit dynamics finite element code LS-DYNA. The results revealed the significant role of plaque types in the normal and shear stresses induced within the arterial tissue layers. The highest von Mises and shear stresses were observed on the stiffest calcified plaque with 3.59 and 3.27 MPa, while the lowest von Mises and shear stresses were seen on the hypocellular plaque with 1.15 and 0.63 MPa, respectively. Regardless of plaque types, the media and adventitia layers were played protective roles by displaying less stress on their wall, whilst the intima layer was at a high risk of rupture. The findings of this study have implications not only for determining the most vulnerable arterial layer/plaque tissue inside an atherosclerotic coronary artery but also for balloon-angioplasty, stenting, and bypass surgeries.

  8. Spontaneous rupture on irregular faults

    NASA Astrophysics Data System (ADS)

    Liu, C.

    2014-12-01

    It is now know (e.g. Robinson et al., 2006) that when ruptures propagate around bends, the rupture velocity decrease. In the extreme case, a large bend in the fault can stop the rupture. We develop a 2-D finite difference method to simulate spontaneous dynamic rupture on irregular faults. This method is based on a second order leap-frog finite difference scheme on a uniform mesh of triangles. A relaxation method is used to generate an irregular fault geometry-conforming mesh from the uniform mesh. Through this numerical coordinate mapping, the elastic wave equations are transformed and solved in a curvilinear coordinate system. Extensive numerical experiments using the linear slip-weakening law will be shown to demonstrate the effect of fault geometry on rupture properties. A long term goal is to simulate the strong ground motion near the vicinity of bends, jogs, etc.

  9. Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE(-/-) mice.

    PubMed

    Knutsson, Anki; Hsiung, Sabrina; Celik, Selvi; Rattik, Sara; Mattisson, Ingrid Yao; Wigren, Maria; Scher, Howard I; Nilsson, Jan; Hultgårdh-Nilsson, Anna

    2016-01-01

    Androgen-deprivation therapy (ADT) for prostate cancer has been associated with increased risk for development of cardiovascular events and recent pooled analyses of randomized intervention trials suggest that this primarily is the case for patients with pre-existing cardiovascular disease treated with gonadotropin-releasing hormone receptor (GnRH-R) agonists. In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE(-/-) mice. A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery. After 4 weeks of ADT, increased areas of necrosis was observed in stable plaques from leuprolide-treated mice (median and IQR plaque necrotic area in control, degarelix and leuprolide-treated mice were 0.6% (IQR 0-3.1), 0.2% (IQR 0-4.4) and 11.0% (IQR 1.0-19.8), respectively). There was also evidence of increased inflammation as assessed by macrophage immunohistochemistry in the plaques from leuprolide-treated mice, but we found no evidence of such changes in plaques from control mice or mice treated with degarelix. Necrosis destabilizes plaques and increases the risk for rupture and development of acute cardiovascular events. Destabilization of pre-existing atherosclerotic plaques could explain the increased cardiovascular risk in prostate cancer patients treated with GnRH-R agonists. PMID:27189011

  10. Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE−/− mice

    PubMed Central

    Knutsson, Anki; Hsiung, Sabrina; Celik, Selvi; Rattik, Sara; Mattisson, Ingrid Yao; Wigren, Maria; Scher, Howard I.; Nilsson, Jan; Hultgårdh-Nilsson, Anna

    2016-01-01

    Androgen-deprivation therapy (ADT) for prostate cancer has been associated with increased risk for development of cardiovascular events and recent pooled analyses of randomized intervention trials suggest that this primarily is the case for patients with pre-existing cardiovascular disease treated with gonadotropin-releasing hormone receptor (GnRH-R) agonists. In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE−/− mice. A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery. After 4 weeks of ADT, increased areas of necrosis was observed in stable plaques from leuprolide-treated mice (median and IQR plaque necrotic area in control, degarelix and leuprolide-treated mice were 0.6% (IQR 0–3.1), 0.2% (IQR 0–4.4) and 11.0% (IQR 1.0-19.8), respectively). There was also evidence of increased inflammation as assessed by macrophage immunohistochemistry in the plaques from leuprolide-treated mice, but we found no evidence of such changes in plaques from control mice or mice treated with degarelix. Necrosis destabilizes plaques and increases the risk for rupture and development of acute cardiovascular events. Destabilization of pre-existing atherosclerotic plaques could explain the increased cardiovascular risk in prostate cancer patients treated with GnRH-R agonists. PMID:27189011

  11. Spontaneous Iliac Vein Rupture

    PubMed Central

    Kim, Dae Hwan; Park, Hyung Sub; Lee, Taeseung

    2015-01-01

    Spontaneous iliac vein rupture (SIVR) is a rare entity, which usually occurs without a precipitating factor, but can be a life-threatening emergency often requiring an emergency operation. This is a case report of SIVR in a 62-year-old female who presented to the emergency room with left leg swelling. Workup with contrast-enhanced computed tomography revealed a left leg deep vein thrombosis with May-Thurner syndrome and a hematoma in the pelvic cavity without definite evidence of arterial bleeding. She was managed conservatively without surgical intervention, and also underwent inferior vena cava filter insertion and subsequent anticoagulation therapy for pulmonary thromboembolism. This case shows that SIVR can be successfully managed with close monitoring and conservative management, and anticoagulation may be safely applied despite the patient presenting with venous bleeding. PMID:26217647

  12. Short-lived Supershear Rupture

    NASA Astrophysics Data System (ADS)

    Fukuyama, E.; Xu, S.; Yamashita, F.; Mizoguchi, K.; Takizawa, S.; Kawakata, H.

    2015-12-01

    Fukuyama and Olsen (2002) computed the supershear rupture initiation, propagation and termination process due to a passage of high stress drop area (called asperity) using a boundary integral equation method. They found that supershear rupture continued to propagate after the passage through high stress drop area but it died after a certain propagation distance, which depends on the elastic energy released at the high stress drop area. Here, we could reproduce a similar phenomenon in the laboratory. We conducted large-scale biaxial friction experiments using a pair of meter-scaled metagabbro rock specimens (VP=6.9km/s, VS=3.6km/s) at the National Research institute for Earth Science and Disaster Prevention (NIED). We observed several stick slip rupture events that initiated close to an asperity and immediately became supershear ruptures. But after propagating certain distance they died out and co-existing subshear ruptures became prominent. If we look into details, during the supershear rupture, we could see a sequence of rupture acceleration, its short rest and re-acceleration. This feature reminds us of a sequential breakage of small high stress patches as predicted by Fukuyama and Madariaga (2000). These observations might be interpreted under a concept of energy balance where the energy transmission from strain energy released by the asperity to fracture energy consumed at the crack tip was not instantaneously balanced in space. This could be related to the fact that earthquake rupture velocity is rather smooth reported from the finite fault analysis of large earthquakes with seismic waveforms. References Fukuyama, E. and R. Madariaga (2000) Dynamic propagation and interaction of a rupture front on a planar fault, PAGEOPH, 257, 1959-1979. Fukuyama, E. and K.B. Olsen (2002) A condition for super-shear rupture propagation in a heterogeneous stress field, PAGEOPH, 159, 2047-2056.

  13. Migration of blood cells to β-amyloid plaques in Alzheimer’s disease

    PubMed Central

    Hohsfield, Lindsay A.; Humpel, Christian

    2015-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disease that leads to the progressive deterioration of cognitive and memory functions. The deposition of extracellular beta-amyloid (Aβ) senile plaques and intracellular tau neurofibrillary tangles are considered the cardinal pathological hallmarks of AD, however, accumulating evidence indicates that immune cells may also play an important role in disease pathogenesis. Among these immune cells, blood-derived cells and their infiltration into the CNS towards Aβ plaques have been implicated in therapeutic strategies against AD. Here, we review the current literature on blood cell migration into the AD brain and the important players involved in this selective migration towards Aβ plaques. PMID:25752742

  14. Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaques.

    PubMed

    Tu, Chuqiao; Ng, Thomas S C; Sohi, Hargun K; Palko, Heather A; House, Adrian; Jacobs, Russell E; Louie, Angelique Y

    2011-10-01

    In a number of literature reports iron oxide nanoparticles have been investigated for use in imaging atherosclerotic plaques and found to accumulate in plaques via uptake by macrophages, which are critical in the process of atheroma initiation, propagation, and rupture. However, the uptake of these agents is non-specific; thus the labeling efficiency for plaques in vivo is not ideal. We have developed targeted agents to improve the efficiency for labeling macrophage-laden plaques. These probes are based on iron oxide nanoparticles coated with dextran sulfate, a ligand of macrophage scavenger receptor type A (SR-A). We have sulfated dextran-coated iron oxide nanoparticles (DIO) with sulfur trioxide, thereby targeting our nanoparticle imaging agents to SR-A. The sulfated DIO (SDIO) remained mono-dispersed and had an average hydrodynamic diameter of 62 nm, an r(1) relaxivity of 18.1 mM(-1) s(-1), and an r(2) relaxivity of 95.8 mM(-1) s(-1) (37 °C, 1.4 T). Cell studies confirmed that these nanoparticles were nontoxic and specifically targeted to macrophages. In vivo MRI after intravenous injection of the contrast agent into an atherosclerotic mouse injury model showed substantial signal loss on the injured carotid at 4 and 24 h post-injection of SDIO. No discernable signal decrease was seen at the control carotid and only mild signal loss was observed for the injured carotid post-injection of non-sulfated DIO, indicating preferential uptake of the SDIO particles at the site of atherosclerotic plaque. These results indicate that SDIO can facilitate MRI detection and diagnosis of vulnerable plaques in atherosclerosis. PMID:21742374

  15. Uptake of 68gallium in atherosclerotic plaques in LDLR-/-ApoB100/100 mice

    PubMed Central

    2011-01-01

    Background Atherosclerosis is a chronic inflammatory disease of artery wall characterized by infiltration of monocytes into subendothelial space and their differentiation into macrophages. Since rupture-prone plaques commonly contain high amounts of activated macrophages, imaging of the macrophage content may provide a useful tool for the evaluation of plaque vulnerability. The purpose of this study was to explore the uptake of 68gallium (68Ga) in atherosclerotic plaques in mice. Methods Uptake of ionic 68Ga was investigated in atherosclerotic LDLR-/-ApoB100/100 and C57BL/6N control mice at 3 h after injection. The ex vivo biodistribution of the 68Ga was assessed and autoradiography of aortic cryosections was defined. In vivo imaging of 68Ga was performed using a small animal positron emission tomography PET/CT scanner. Results Our results revealed that the uptake of 68Ga-radioactivity was higher in atherosclerotic plaques than in healthy vessel wall (ratio 1.8 ± 0.2, p = 0.0002) and adventitia (ratio 1.3 ± 0.2, p = 0.0011). The autoradiography signal co-localized with macrophages prominently as demonstrated by Mac-3 staining. In both mice strains, the highest level of radioactivity was found in the blood. Conclusions We observed a moderate but significantly elevated 68Ga-radioactivity uptake in the aortic plaques of atherosclerotic mice, especially at the sites rich in macrophages. While the uptake of 68Ga was promising in this animal model, the slow blood clearance may limit the usability of 68Ga as a PET tracer for clinical imaging of atherosclerotic plaques. PMID:22214258

  16. Fluoride bioavailability in saliva and plaque

    PubMed Central

    2012-01-01

    Background Different fluoride formulations may have different effects on caries prevention. It was the aim of this clinical study to assess the fluoride content, provided by NaF compared to amine fluoride, in saliva and plaque. Methods Eight trained volunteers brushed their teeth in the morning for 3 minutes with either NaF or amine fluoride, and saliva and 3-day-plaque-regrowth was collected at 5 time intervals during 6 hours after tooth brushing. The amount of collected saliva and plaque was measured, and the fluoride content was analysed using a fluoride sensitive electrode. All subjects repeated all study cycles 5 times, and 3 cycles per subject underwent statistical analysis using the Wilcoxon-Mann-Whitney test. Results Immediately after brushing the fluoride concentration in saliva increased rapidly and dropped to the baseline level after 360 minutes. No difference was found between NaF and amine fluoride. All plaque fluoride levels were elevated after 30 minutes until 120 minutes after tooth brushing, and decreasing after 360 minutes to baseline. According to the highly individual profile of fluoride in saliva and plaque, both levels of bioavailability correlated for the first 30 minutes, and the fluoride content of saliva and plaque was back to baseline after 6 hours. Conclusions Fluoride levels in saliva and plaque are interindividually highly variable. However, no significant difference in bioavailability between NaF and amine fluoride, in saliva, or in plaque was found. PMID:22230722

  17. Stabilization of high-risk plaques

    PubMed Central

    Takata, Kohei; Zhang, Bo; Miura, Shin-ichiro; Saku, Keijiro

    2016-01-01

    The prevalence of atherosclerotic cardiovascular diseases (ASCVDs) is increasing globally and they have become the leading cause of death in most countries. Numerous experimental and clinical studies have been conducted to identify major risk factors and effective control strategies for ASCVDs. The development of imaging modalities with the ability to determine the plaque composition enables us to further identify high-risk plaque and evaluate the effectiveness of different treatment strategies. While intensive lipid-lowering by statins can stabilize or even regress plaque by various mechanisms, such as the reduction of lipid accumulation in a necrotic lipid core, the reduction of inflammation, and improvement of endothelial function, there are still considerable residual risks that need to be understood. We reviewed important findings regarding plaque vulnerability and some encouraging emerging approaches for plaque stabilization. PMID:27500090

  18. Pathology of human plaque vulnerability: mechanisms and consequences of intraplaque haemorrhages.

    PubMed

    Michel, Jean-Baptiste; Martin-Ventura, José Luis; Nicoletti, Antonino; Ho-Tin-Noé, Benoit

    2014-06-01

    Atherothrombotic diseases are still major causes of inability and mortality and fighting atherothrombosis remains a public health priority. The involvement of repeated intraplaque haemorrhages (IPH) in the evolution of atherothrombotic lesions towards complications was proposed as early as 1936. This important topic has been recently revisited and reviewed. Histological observations have been corroborated by magnetic resonance imaging (MRI) of human carotid atheroma, identifying IPH as the main determinant of plaque evolution towards rupture. Beside the intimal integration of asymptomatic luminal coagulum, inward sprouting of neovessels from the adventitia towards the plaque, is one source of IPH in human atheroma. We recently described that directed neo-angiogenesis from the adventitia towards the plaque, across the media, is initiated by lipid mediators generated by the plaque on the luminal side, outwardly convected to the medial VSMCs. Subsequent stimulation of VSMC PPAR-γ receptors induces VEGF expression which causes centripetal sprouting of adventitial vessels. However, this neovascularization is considered to be immature and highly susceptible to leakage. The main cellular components of IPH are Red Blood Cells (RBCs), which with their haemoglobin content and their cell membrane components, particularly enriched in unesterified cholesterol, participate in both the oxidative process and cholesterol accumulation. The presence of iron, glycophorin A and ceroids provides evidence of RBCs. IPH also convey blood leukocytes and platelets and are sites prone to weak pathogen contamination. Therefore prevention and treatment of the biological consequences of IPH pave the way to innovative preventive strategies and improved therapeutic options in human atherothrombotic diseases. PMID:24726899

  19. Assessment of atherosclerotic plaque collagen content and architecture using polarization-sensitive optical coherence tomography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Doradla, Pallavi; Villiger, Martin; Tshikudi, Diane M.; Bouma, Brett E.; Nadkarni, Seemantini K.

    2016-02-01

    Acute myocardial infarction, caused by the rupture of vulnerable coronary plaques, is the leading cause of death worldwide. Collagen is the primary extracellular matrix macromolecule that imparts the mechanical stability to a plaque and its reduction causes plaque instability. Intracoronary polarization sensitive optical coherence tomography (PS-OCT) measures the polarization states of the backscattered light from the tissue to evaluate plaque birefringence, a material property that is elevated in proteins such as collagen with an ordered structure. Here we investigate the dependence of the PS-OCT parameters on the quantity of the plaque collagen and fiber architecture. In this study, coronary arterial segments from human cadaveric hearts were evaluated with intracoronary PS-OCT and compared with Histopathological assessment of collagen content and architecture from picrosirius-red (PSR) stained sections. PSR sections were visualized with circularly-polarized light microscopy to quantify collagen birefringence, and the additional assessment of color hue indicated fibril thickness. Due to the ordered architecture of thick collagen fibers, a positive correlation between PS-OCT retardation and quantity of thick collagen fibers (r=0.54, p=0.04), and similarly with the total collagen content (r=0.51, p=0.03) was observed. In contrast, there was no perceivable relationship between PS-OCT retardation and the presence of thin collagen fibers (r=0.08, p=0.07), suggesting that thin and disorganized collagen fiber architecture did not significantly contribute to the PS-OCT retardation. Further analysis will be performed to assess the relationship between PS-OCT retardation and collagen architecture based on immunohistochemical analysis of collagen type. These results suggest that intracoronary PS-OCT may open the opportunity to assess collagen architecture in addition total collagen content, potentially enabling an improved understanding of coronary plaque rupture.

  20. Ruptured thought: rupture as a critical attitude to nursing research.

    PubMed

    Beedholm, Kirsten; Lomborg, Kirsten; Frederiksen, Kirsten

    2014-04-01

    In this paper, we introduce the notion of ‘rupture’ from the French philosopher Michel Foucault, whose studies of discourse and governmentality have become prominent within nursing research during the last 25 years. We argue that a rupture perspective can be helpful for identifying and maintaining a critical potential within nursing research. The paper begins by introducing rupture as an inheritance from the French epistemological tradition. It then describes how rupture appears in Foucault's works, as both an overall philosophical approach and as an analytic tool in his historical studies. Two examples of analytical applications of rupture are elaborated. In the first example, rupture has inspired us to make an effort to seek alternatives to mainstream conceptions of the phenomenon under study. In the second example, inspired by Foucault's work on discontinuity, we construct a framework for historical epochs in nursing history. The paper concludes by discussing the potential of the notion of rupture as a response to the methodological concerns regarding the use of Foucault-inspired discourse analysis within nursing research. We agree with the critique of Cheek that the critical potential of discourse analysis is at risk of being undermined by research that tends to convert the approach into a fixed method. PMID:24741691

  1. Dynamic Rupture Processes during Laboratory Earthquakes

    NASA Astrophysics Data System (ADS)

    Passelègue, F. X.; Schubnel, A.; Nielsen, S. B.; Bhat Suresh, H.; Madariaga, R. I.

    2014-12-01

    that, at least at the scale of asperities, the resulting dynamic stress drop could be much larger than current seismological estimates. In addition, we demonstrate that the radiation efficiency decreases with the dynamic friction coefficient, suggesting that rupture processes become more dispersive under high normal stress conditions.

  2. Fibrillar Amyloid Plaque Formation Precedes Microglial Activation

    PubMed Central

    Steinbach, Sonja; Blazquez-Llorca, Lidia; Herms, Jochen

    2015-01-01

    In Alzheimer’s disease (AD), hallmark β-amyloid deposits are characterized by the presence of activated microglia around them. Despite an extensive characterization of the relation of amyloid plaques with microglia, little is known about the initiation of this interaction. In this study, the detailed investigation of very small plaques in brain slices in AD transgenic mice of the line APP-PS1(dE9) revealed different levels of microglia recruitment. Analysing plaques with a diameter of up to 10 μm we find that only the half are associated with clear morphologically activated microglia. Utilizing in vivo imaging of new appearing amyloid plaques in double-transgenic APP-PS1(dE9)xCX3CR1+/- mice further characterized the dynamic of morphological microglia activation. We observed no correlation of morphological microglia activation and plaque volume or plaque lifetime. Taken together, our results demonstrate a very prominent variation in size as well as in lifetime of new plaques relative to the state of microglia reaction. These observations might question the existing view that amyloid deposits by themselves are sufficient to attract and activate microglia in vivo. PMID:25799372

  3. The ruptured PIP breast implant.

    PubMed

    Helyar, V; Burke, C; McWilliams, S

    2013-08-01

    Public concern erupted about the safety of Poly Implant Prothèse (PIP) breast implants when it was revealed in 2011 that they contained an inferior, unlicensed industrial-grade silicone associated with a high rate of rupture. There followed national guidance for UK clinicians, which led to a considerable increase in referrals of asymptomatic women for breast implant assessment. In this review we discuss possible approaches to screening the PIP cohort and the salient characteristics of a ruptured implant. PMID:23622796

  4. Carotid plaque characterization using CT and MRI scans for synergistic image analysis

    NASA Astrophysics Data System (ADS)

    Getzin, Matthew; Xu, Yiqin; Rao, Arhant; Madi, Saaussan; Bahadur, Ali; Lennartz, Michelle R.; Wang, Ge

    2014-09-01

    Noninvasive determination of plaque vulnerability has been a holy grail of medical imaging. Despite advances in tomographic technologies , there is currently no effective way to identify vulnerable atherosclerotic plaques with high sensitivity and specificity. Computed tomography (CT) and magnetic resonance imaging (MRI) are widely used, but neither provides sufficient information of plaque properties. Thus, we are motivated to combine CT and MRI imaging to determine if the composite information can better reflect the histological determination of plaque vulnerability. Two human endarterectomy specimens (1 symptomatic carotid and 1 stable femoral) were imaged using Scanco Medical Viva CT40 and Bruker Pharmascan 16cm 7T Horizontal MRI / MRS systems. μCT scans were done at 55 kVp and tube current of 70 mA. Samples underwent RARE-VTR and MSME pulse sequences to measure T1, T2 values, and proton density. The specimens were processed for histology and scored for vulnerability using the American Heart Association criteria. Single modality-based analyses were performed through segmentation of key imaging biomarkers (i.e. calcification and lumen), image registration, measurement of fibrous capsule, and multi-component T1 and T2 decay modeling. Feature differences were analyzed between the unstable and stable controls, symptomatic carotid and femoral plaque, respectively. By building on the techniques used in this study, synergistic CT+MRI analysis may provide a promising solution for plaque characterization in vivo.

  5. [Ligament ruptures of the lower extremity in the elderly].

    PubMed

    Herbort, M; Raschke, M J

    2011-08-01

    There is an increasing incidence of ligament ruptures of the lower extremities in older patients. This higher incidence is caused by the typical current demographic changes in the population and the higher level of activity and athletic motivation of the older people in our society. In this review we address the most important ligament ruptures of the lower extremity in the old patient. Quadriceps tendon and Achilles tendon ruptures are mostly the result of degenerative and abrasion changes. The ACL rupture on the other hand occurs spontaneously after adequate trauma and without former degenerative changes especially in highly active patients. For a differentiated treatment of the older patient with tendon ruptures, secondary diseases, an increased risk and complication profile and a potentially decreased compliance during rehabilitation must be taken into consideration before indicating operative or conservative therapy. There are no strict age-related limitations for indication of an operative treatment of tendon ruptures in the older patient. In this patient group a differentiated treatment decision is recommended. PMID:21766204

  6. Antibody-Labeled Liposomes for CT Imaging of Atherosclerotic Plaques

    PubMed Central

    Danila, Delia; Partha, Ranga; Elrod, Don B.; Lackey, Melinda; Casscells, S. Ward; Conyers, Jodie L.

    2009-01-01

    We evaluated the specific binding of anti-intercellular adhesion molecule 1 (ICAM-1) conjugated liposomes (immunoliposomes, or ILs) to activated human coronary artery endothelial cells (HCAEC) with the purpose of designing a computed tomographic imaging agent for early detection of atherosclerotic plaques. Covalent attachment of anti-ICAM-1 monoclonal antibodies to pre-formed liposomes stabilized with polyethylene glycol yielded ILs, with a coupling efficiency of the ICAM-1 to the liposomes of 10% to 24%. The anti-ICAM-1–labeled ILs had an average diameter of 136 nm as determined by dynamic light-scattering and cryogenic electron microscopy. The ILs' encapsulation of 5-[N-acetyl-(2,3-dihydroxypropyl)-amino)-N, N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-benzene-1,3-dicarboxamide (iohexol) was determined to be 18% to 19% by a dialysis technique coupled with ultraviolet detection of free iohexol. This encapsulation corresponded to 30 to 38 mg iodine per mL IL solution, and the ILs exhibited 91% to 98.5% iohexol retention at room temperature and under physiologic conditions. The specific binding of the ILs to cultured, activated HCAEC was measured using flow cytometry, enzyme-linked immunosorbent assays, and fluorescence microscopy. The immunosorbent assays demonstrated the specificity of binding of anti-ICAM-1 to ICAM-1 compared with control studies using nonspecific immunoglobulin G-labeled ILs. Flow cytometry and fluorescence microscopy experiments demonstrated the expression of ICAM-1 on the surface of activated HCAEC. Therefore, our iohexol-filled ILs demonstrated potential for implementation in computed tomographic angiography to noninvasively detect atherosclerotic plaques that are prone to rupture. PMID:19876414

  7. Rupture process of the 2013 Okhotsk deep mega earthquake from iterative backprojection and compress sensing methods

    NASA Astrophysics Data System (ADS)

    Qin, W.; Yin, J.; Yao, H.

    2013-12-01

    On May 24th 2013 a Mw 8.3 normal faulting earthquake occurred at a depth of approximately 600 km beneath the sea of Okhotsk, Russia. It is a rare mega earthquake that ever occurred at such a great depth. We use the time-domain iterative backprojection (IBP) method [1] and also the frequency-domain compressive sensing (CS) technique[2] to investigate the rupture process and energy radiation of this mega earthquake. We currently use the teleseismic P-wave data from about 350 stations of USArray. IBP is an improved method of the traditional backprojection method, which more accurately locates subevents (energy burst) during earthquake rupture and determines the rupture speeds. The total rupture duration of this earthquake is about 35 s with a nearly N-S rupture direction. We find that the rupture is bilateral in the beginning 15 seconds with slow rupture speeds: about 2.5km/s for the northward rupture and about 2 km/s for the southward rupture. After that, the northward rupture stopped while the rupture towards south continued. The average southward rupture speed between 20-35 s is approximately 5 km/s, lower than the shear wave speed (about 5.5 km/s) at the hypocenter depth. The total rupture length is about 140km, in a nearly N-S direction, with a southward rupture length about 100 km and a northward rupture length about 40 km. We also use the CS method, a sparse source inversion technique, to study the frequency-dependent seismic radiation of this mega earthquake. We observe clear along-strike frequency dependence of the spatial and temporal distribution of seismic radiation and rupture process. The results from both methods are generally similar. In the next step, we'll use data from dense arrays in southwest China and also global stations for further analysis in order to more comprehensively study the rupture process of this deep mega earthquake. Reference [1] Yao H, Shearer P M, Gerstoft P. Subevent location and rupture imaging using iterative backprojection for

  8. Evaluation of Carotid Plaque Using Ultrasound Imaging

    PubMed Central

    2016-01-01

    Traditional risk factors for predicting of cardiovascular disease are not always effective predictors for development of cardiovascular events. This review summarizes several newly developed noninvasive imaging techniques for evaluating carotid plaques and their role in cardiovascular disease risk. PMID:27358696

  9. CONFIRMED VIRUSES VERSUS UNCONFIRMED PLAQUES IN SEWAGE

    EPA Science Inventory

    Ninety-two treated and untreated sewage samples from seven wastewater treatment plants in Chicago, Illinois, Memphis, Tennessee, and Cincinnati, Ohio were examined for their virus content. Concentrated and unconcentrated samples were plaque assayed in five different cell culture ...

  10. Aneurysm flow characteristics in realistic carotid artery aneurysm models induced by proximal virtual stenotic plaques: a computational hemodynamics study

    NASA Astrophysics Data System (ADS)

    Castro, Marcelo A.; Peloc, Nora L.; Chien, Aichi; Goldberg, Ezequiel; Putman, Christopher M.; Cebral, Juan R.

    2015-03-01

    Cerebral aneurysms may rarely coexist with a proximal artery stenosis. In that small percent of patients, such coexistence poses a challenge for interventional neuroradiologists and neurosurgeons to make the best treatment decision. According to previous studies, the incidence of cerebral aneurysms in patients with internal carotid artery stenosis is no greater than five percent, where the aneurysm is usually incidentally detected, being about two percent for aneurysms and stenoses in the same cerebral circulation. Those cases pose a difficult management decision for the physician. Case reports showed patients who died due to aneurysm rupture months after endarterectomy but before aneurysm clipping, while others did not show any change in the aneurysm after plaque removal, having optimum outcome after aneurysm coiling. The aim of this study is to investigate the intra-aneurysmal hemodynamic changes before and after treatment of stenotic plaque. Virtually created moderate stenoses in vascular models of internal carotid artery aneurysm patients were considered in a number of cases reconstructed from three dimensional rotational angiography images. The strategy to create those plaques was based on parameters analyzed in a previous work where idealized models were considered, including relative distance and stenosis grade. Ipsilateral and contralateral plaques were modeled. Wall shear stress and velocity pattern were computed from finite element pulsatile blood flow simulations. The results may suggest that wall shear stress changes depend on relative angular position between the aneurysm and the plaque.

  11. [The role of the vascular-associated lymphoid tissue (VALT) network and neovascularization in atherosclerotic carotid plaque].

    PubMed

    Kawahara, Ichiro; Tsutsumi, Keisuke; Nagata, Izumi

    2013-01-01

    As you know, atherosclerosis is a serious public problem and is the leading cause of morbidity and mortality not only in Western countries but also in Asia. Cervical carotid disease is typical atherosclerosis, which is responsible for ischemic stroke. Recently, it has been well established that the risk of an acute event mediated by rupture is predicated by plaque components rather than by the degree of luminal narrowing. Preoperative evaluation of plaque components by some modalities such as magnetic resonance imaging is very important for a decision of the treatment strategy. Generally, vulnerable plaques are characterized by a large lipid core, a thin fibrous cap, and substantial infiltration with inflammatory cells. Recently, evidence is accumulating for a role of the immune system and neovascularization in the progression of atherosclerosis. Neovascularization may act as a conduit for the entry of immune and inflammatory cells. Dendritic cells, macrophages, and T-lymphocytes play a main role in the immune-inflammatory system of atherosclerotic lesions, in which they form the vascular-associated lymphoid tissue (VALT) network together. The immune-inflammatory system in the VALT network plays a role in determining the dynamic balance between collagen degradation and collagen synthesis. On the other hand, some of these consecutive mechanisms related with plaque vulnerability have not yet been clarified. To clarify them, we should keep on researching the formation process of atherosclerotic carotid plaque from the pathohistological viewpoint. PMID:23269250

  12. Detection of High-Risk Atherosclerotic Plaque

    PubMed Central

    Fleg, Jerome L.; Stone, Gregg W.; Fayad, Zahi A.; Granada, Juan F.; Hatsukami, Thomas S.; Kolodgie, Frank D.; Ohayon, Jacques; Pettigrew, Roderic; Sabatine, Marc S.; Tearney, Guillermo; Waxman, Sergio; Domanski, Michael J.; Srinivas, Pothur R.; Narula, Jagat

    2013-01-01

    The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis. PMID:22974808

  13. Utility of Combining PET and MR Imaging of Carotid Plaque.

    PubMed

    Vesey, Alex T; Dweck, Marc R; Fayad, Zahi A

    2016-02-01

    By harnessing the versatility and soft tissue imaging capabilities of MR imaging alongside the unmatched sensitivity and biomolecular flexibility of PET, the potential to provide detailed multiparametric plaque characterization in the carotid arteries is clear. The ability to acquire simultaneous, and dynamic multimodal data is perhaps PET/MR's greatest strength that will be of major interest to researchers investigating carotid and coronary atherosclerosis alike. This review summarizes the current status of dedicated hybrid PET/MR imaging; to crystallize the rationale for and advantages of this technique with respect to carotid atherosclerosis; and to discuss current limitations, challenges, and future directions. PMID:26610660

  14. Helicobacter pylori in dental plaque of Pakistanis.

    PubMed

    Butt, A K; Khan, A A; Bedi, R

    1999-07-01

    Helicobacter pylori is now generally accepted to play a key role in acid related and neoplastic pathology of gastroduodenal diseases. Recent reports have concluded that dental plaque is not an important reservoir for Helicobacter pylori, however, these studies did not consider the ethnic background of their subjects nor the amounts of dental plaque present. The aim of this study was to explore the association of Helicobacter pylori dental plaque colonisation in 125 males and 53 females (group I) attending a dental clinic in Pakistan. A simultaneous sample of 30 healthy volunteers with good orodental hygiene consisting of 17 males and 13 females was included as a control group (group II). Six dental plaque specimens were obtained from each subject with a sickle scaler; two were inoculated into CLO test gel and the remaining four were used to prepare cytology slides stained with Giemsa's stain. CLO test was positive in all specimens from group I, while cytology for Helicobacter pylori was positive in 173 cases in this group. One hundred and forty two cases had heavy plaque deposits and all of them were positive on cytology. In group II CLO test was positive in 20 and dental plaque cytology was positive in 7 cases. In conclusion, it is important that future studies into the prevalence of Helicobacter pylori in the oral cavity should take into account the levels of oral cleanliness and the ethnic background of the subjects. PMID:10833287

  15. Plaque fluid as a bacterial milieu.

    PubMed

    Edgar, W M; Higham, S M

    1990-06-01

    Studies of the extracellular, free concentrations of substrates, growth factors, inhibitors, and end-products of metabolism to which the intact plaque microflora is exposed in situ can assist in the understanding of factors controlling plaque pathogenicity. Information is becoming increasingly available from analysis of fluid separated by centrifugation of plaques collected at various intervals after an intra-oral pulse of dietary or experimental substrate, or different procedures or treatments having cariostatic potential. Such analytical results give more information than those obtained by analysis of aqueous or other extracts, because they yield values of substrate concentration representing those occurring at the bacterial cell surface. The largest body of information concerns extracellular levels of acid end-products of sugar catabolism in relation to food quality or sequence, and of amino acids and other products of nitrogen metabolism, in relation to studies of the detailed metabolic events of the Stephan curve, and of the demineralizing effect of the plaque environment. Areas where little information is available and which merit further study include plaque clearance of salivary and other components with anti-caries activity (e.g., antibodies, enzymes, fluorides, cations, other antimicrobials, etc.), and substrate concentrations to determine gradients for diffusion into and out of plaque. PMID:2191982

  16. Rupture of the tracheobronchial tree.

    PubMed Central

    Roxburgh, J C

    1987-01-01

    Eleven cases of tracheobronchial rupture are described. Nine were the result of external non-penetrating trauma and all but three had other serious injuries. The remaining two were caused by endobronchial intubation. Of the cases caused by external injury, respiratory tract injury was confined to the cervical trachea in three. Two required tracheostomy and repair and the third was managed conservatively; all made satisfactory recoveries. Intrathoracic rupture was recognised on or soon after admission in three cases. One patient died of uncontrollable pulmonary haemorrhage before he could be operated on; immediate repair gave good long term results in the other two. In three cases rupture of the main bronchus was not recognised until complete obstruction developed three, five, and 12 weeks after the accidents. The strictures were resected and the lung re-expanded. Robertshaw endobronchial tubes ruptured the left main bronchus in two patients undergoing oesophageal surgery. Uneventful recovery followed immediate repair. The difficulty of confirming rupture of a major airway is discussed and the importance of conserving the lung when the diagnosis has been missed is emphasised. Images PMID:3317977

  17. Noninvasive Detection of Macrophage-rich Atherosclerotic Plaque in Hyperlipidemic Rabbits using ‘Positive Contrast’ Magnetic Resonance Imaging

    PubMed Central

    Korosoglou, Grigorios; Weiss, Robert G.; Kedziorek, Dorota A.; Walczak, Piotr; Gilson, Wesley D.; Schär, Michael; Sosnovik, David; Kraitchman, Dara L.; Boston, Raymond C.; Bulte, Jeff W.M; Weissleder, Ralph; Stuber, Matthias

    2009-01-01

    Objectives To identify macrophage-rich atherosclerotic plaque non-invasively by the combined use of systemic administration of superparamagnetic nanoparticles with magnetic resonance imaging (MRI), using a positive contrast off-resonance imaging sequence (Inversion Recovery with ON-resonant water suppression: IRON). Background The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis would be of great potential clinical utility. Methods Experiments were conducted on a clinical 3T MRI scanner in seven heritable hyperlipidemic and four control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated intravenously (two doses of 250μmol Fe/kg), and animals underwent serial IRON-MRI before injection of the nanoparticles and serially after 1, 3 and 6 days. Results After administration of MION-47, a striking signal enhancement was found in areas of plaque only in hyperlipidemic rabbits. The magnitude of enhancement on MR-images had a high correlation with the number of macrophages determined by histology (p<0.001) and allowed for the detection of macrophage-rich plaque with high accuracy (AUC=0.92, SE=0.04, 95% CI=0.84-0.96, p<0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in controls without atherosclerosis. Conclusion IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for the noninvasive evaluation of macrophage-rich, vulnerable plaques. PMID:18672170

  18. Mechanical Interaction of an Expanding Coiled Stent with a Plaque-Containing Arterial Wall: A Finite Element Analysis.

    PubMed

    Welch, Tré R; Eberhart, Robert C; Banerjee, Subhash; Chuong, Cheng-Jen

    2016-03-01

    Wall injury is observed during stent expansion within atherosclerotic arteries, related in part to stimulation of the inflammatory process. Wall stress and strain induced by stent expansion can be closely examined by finite element analysis (FEA), thus shedding light on procedure-induced sources of inflammation. The purpose of this work was to use FEA to examine the interaction of a coiled polymer stent with a plaque-containing arterial wall during stent expansion. An asymmetric fibrotic plaque-containing arterial wall model was created from intravascular ultrasound (IVUS) images of a diseased artery. A 3D model for a coil stent at unexpanded state was generated in SolidWorks. They were imported into ANSYS for FEA of combined stent expansion and fibrotic plaque-distortion. We simulated the stent expansion in the plaqued lumen by increasing balloon pressure from 0 to 12 atm in 1 atm step. At increasing pressure, we examined how the expanding stent exerts forces on the fibrotic plaque and vascular wall components, and how the latter collectively resist and balance the expansive forces from the stent. Results show the expanding coiled stent creates high stresses within the plaque and the surrounding fibrotic capsule. Lower stresses were observed in adjacent medial and adventitial layers. High principal strains were observed in plaque and fibrotic capsule. The results suggest fibrotic capsule rupture might occur at localized regions. The FEA/IVUS method can be adapted for routine examination of the effects of the expansion of selected furled stents against IVUS-reconstructed diseased vessels, to improve stent deployment practices. PMID:26621671

  19. Differential association of visceral adipose tissue with coronary plaque characteristics in patients with and without diabetes mellitus

    PubMed Central

    2014-01-01

    Background Excess visceral adipose tissue (VAT) is closely associated with the presence of coronary artery plaques that are vulnerable to rupture. Patients with diabetes mellitus (DM) have more VAT than patients without DM, but the extent to which VAT contributes to the characteristics of coronary plaques before and after the development of DM is not fully understood. Methods We retrospectively evaluated 456 patients (60% male, age 64 ± 16 years) who were suspected to have cardiovascular disease and underwent 64-slice computed tomography angiography (CTA). Seventy-one (16%) patients had vulnerable plaques (CT density < 50 Hounsfield Units, positive remodeling index > 1.05, and adjacent spotty areas of calcification). Results Patients were divided into tertiles according to the VAT area. There were stepwise increases in noncalcified and vulnerable plaques with increasing tertiles of VAT area in patients without DM, but not in patients with DM. Multivariate analysis showed that a larger VAT area was significantly associated with a higher risk of vulnerable plaque in patients without DM (odds ratio 3.17, 95% confidence interval 1.08–9.31, p = 0.04), but not in patients with DM. Conclusions The VAT area is associated with the characteristics of coronary plaques on CTA in patients without DM, but not in patients with DM. VAT may be a significant cardiometabolic risk factor that is associated with plaque vulnerability before the development of DM. CTA findings may help to improve risk stratification in such patients. PMID:24624968

  20. Multiple plaque rupture and intracoronary thrombosis: two successful therapeutic strategies in the same patient.

    PubMed

    Tigen, Kursat; Mutlu, Bulent; Cevik, Cihan; Karavelioglu, Yusuf; Basaran, Yelda

    2008-01-01

    Interventionalists have many tools at their disposal for percutaneous revascularization and they all use every modality to restore flow. Sometimes they face challenging situations in the setting of acute coronary syndromes in which more than one strategy has to be used urgently. We are presenting a young male patient with myocardial infarction having two simultaneous occluding fresh coronary thrombi in his left anterior descending coronary artery and its diagonal side branch. Clot extraction catheter is used for aspiration of left anterior descending coronary artery thrombus and he received lytic therapy for the thrombus in the large diagonal side branch. PMID:18486083

  1. The Role of Geometric and Biomechanical Factors in Abdominal Aortic Aneurysm Rupture Risk Assessment

    PubMed Central

    Raut, Samarth S.; Chandra, Santanu; Shum, Judy; Finol, Ender A.

    2013-01-01

    The current clinical management of abdominal aortic aneurysm (AAA) disease is based to a great extent on measuring the aneurysm maximum diameter to decide when timely intervention is required. Decades of clinical evidence show that aneurysm diameter is positively associated with the risk of rupture, but other parameters may also play a role in causing or predisposing the AAA to rupture. Geometric factors such as vessel tortuosity, intraluminal thrombus volume, and wall surface area are implicated in the differentiation of ruptured and unruptured AAAs. Biomechanical factors identified by means of computational modeling techniques, such as peak wall stress, have been positively correlated with rupture risk with a higher accuracy and sensitivity than maximum diameter alone. The objective of this review is to examine these factors, which are found to influence AAA disease progression, clinical management and rupture potential, as well as to highlight on-going research by our group in aneurysm modeling and rupture risk assessment. PMID:23508633

  2. Improved treatment planning for COMS eye plaques

    SciTech Connect

    Astrahan, Melvin A. . E-mail: astrahan@usc.edu

    2005-03-15

    Purpose: A recent reanalysis of the Collaborative Ocular Melanoma Study (COMS) medium tumor trial concluded that incorporating factors to account for anisotropy, line source approximation, the gold plaque, and attenuation in the Silastic seed carrier into the dose calculations resulted in a significant and consistent reduction of calculated doses to structures of interest within the eye. The authors concluded that future eye plaque dosimetry should be 'performed using the most up-to-date parameters available.' The reason these factors are important is attributable to the low energy {sup 125}I radiation (approximately 28 keV) that is primarily absorbed by the photoelectric process. Photoelectric absorption is quite dependent on the atomic composition of the absorbing material. Being 40% silicon by weight, the effective atomic number of Silastic is significantly greater than that of water. Although the AAPM TG43 brachytherapy formalism inherently addresses the issues of source anisotropy and geometry, its parameter that accounts for scatter and attenuation, the radial dose function g(r), assumes that the source is immersed in infinite homogeneous water. In this work, factors are proposed for {sup 125}I that correct for attenuation in the Silastic carrier and scatter deficits resulting from the gold plaque and nearby air. The implications of using {sup 103}Pd seeds in COMS plaques are also discussed. Methods and materials: An existing TG43-based ophthalmic plaque planning system was modified to incorporate additional scatter and attenuation correction factors that better account for the path length of primary radiation in the Silastic seed carrier and the distance between the dose calculation point and the eye-air interface. Results: Compared with homogeneous water, the dose-modifying effects of the Silastic and gold are greatest near the plaque surface and immediately adjacent to the plaque, while being least near the center of the eye. The calculated dose

  3. Stone Morphology Suggestive of Randall's Plaque

    NASA Astrophysics Data System (ADS)

    Daudon, Michel; Traxer, Olivier; Jungers, Paul; Bazin, Dominique

    2007-04-01

    Randall's plaques are found in a number of calcium oxalate stone formers. Stones developed on a Randall's plaque typically present a small depressed zone ("umbilication") corresponding to the tip of the papilla and containing material detached from the plaque. By examining the morphology and infrared composition of 45,774 calculi referred to our laboratory over the past three decades, we identified 8,916 umbilicated calculi (19.5%). We have selected three periods of time corresponding to the first years of each decade. Over these periods, we analyzed 26,182 consecutive calculi. Among them, we identified 5,401 umbilicated calculi, of which 91.5% had an identifiable plaque. We analyzed the relative prevalence of umbilicated stones over time and the respective composition of Randall's plaque and stones. The proportion of umbilicated stones rose significantly from 10% in period 1 (1978-1984) to 21% in period 2 (1990-1993) and 22.2% in period 3 (2000-2006), with a parallel rise in the prevalence of stones with identifiable Randall's plaque. The main component of plaques was carbapatite in 90.8% of cases, whereas other components such as amorphous carbonated calcium phosphate, sodium hydrogen urate or uric acid were found in other cases. The morphology of plaques made of carbapatite was diverse, as was their carbonate content, thus suggesting variable pathophysiological mechanisms. Stones were made of whewellite as the main component in 51.4% of cases, or admixed with weddellite in 26.8%, predominant weddellite in 12.5% and other components (mainly uric acid) in 7.5% of cases. Our findings confirm that Randall's plaques are made of carbapatite in the great majority of cases, but with the stones more frequently composed of calcium oxalate monohydrate (which is associated with hyperoxaluria) than of calcium oxalate dihydrate (associated with hypercalciuria). In conclusion, in our country, stones developed on a carbapatite Randall's plaque are as frequently made of

  4. Relation between TLR4/NF-κB signaling pathway activation by 27-hydroxycholesterol and 4-hydroxynonenal, and atherosclerotic plaque instability

    PubMed Central

    Gargiulo, Simona; Gamba, Paola; Testa, Gabriella; Rossin, Daniela; Biasi, Fiorella; Poli, Giuseppe; Leonarduzzi, Gabriella

    2015-01-01

    It is now thought that atherosclerosis, although due to increased plasma lipids, is mainly the consequence of a complicated inflammatory process, with immune responses at the different stages of plaque development. Increasing evidence points to a significant role of Toll-like receptor 4 (TLR4), a key player in innate immunity, in the pathogenesis of atherosclerosis. This study aimed to determine the effects on TLR4 activation of two reactive oxidized lipids carried by oxidized low-density lipoproteins, the oxysterol 27-hydroxycholesterol (27-OH) and the aldehyde 4-hydroxynonenal (HNE), both of which accumulate in atherosclerotic plaques and play a key role in the pathogenesis of atherosclerosis. Secondarily, it examined their potential involvement in mediating inflammation and extracellular matrix degradation, the hallmarks of high-risk atherosclerotic unstable plaques. In human promonocytic U937 cells, both 27-OH and HNE were found to enhance cell release of IL-8, IL-1β, and TNF-α and to upregulate matrix metalloproteinase-9 (MMP-9) via TLR4/NF-κB-dependent pathway; these actions may sustain the inflammatory response and matrix degradation that lead to atherosclerotic plaque instability and to their rupture. Using specific antibodies, it was also demonstrated that these inflammatory cytokines increase MMP-9 upregulation, thus enhancing the release of this matrix-degrading enzyme by macrophage cells and contributing to plaque instability. These innovative results suggest that, by accumulating in atherosclerotic plaques, the two oxidized lipids may contribute to plaque instability and rupture. They appear to do so by sustaining the release of inflammatory molecules and MMP-9 by inflammatory and immune cells, for example, macrophages, through activation of TLR4 and its NF-κB downstream signaling. PMID:25757594

  5. Amyloid Plaques in PSAPP Mice Bind Less Metal than Plaques in Human Alzheimer’s Disease

    PubMed Central

    Leskovjan, Andreana C.; Lanzirotti, Antonio; Miller, Lisa M.

    2009-01-01

    Amyloid beta (Aβ) is the primary component of Alzheimer’s disease (AD) plaques, a key pathological feature of the disease. Metal ions of zinc (Zn), copper (Cu), iron (Fe), and calcium (Ca) are elevated in human amyloid plaques and are thought to be involved in neurodegeneration. Transgenic mouse models of AD also exhibit amyloid plaques, but fail to exhibit the high degree of neurodegeneration observed in humans. In this study, we imaged the Zn, Cu, Fe, and Ca ion distribution in the PSAPP transgenic mouse model representing end-stage AD (N = 6) using synchrotron X-ray fluorescence (XRF) microprobe. In order to account for differences in density in the plaques, the relative protein content was imaged with synchrotron Fourier transform infrared microspectroscopy (FTIRM) on the same samples. FTIRM results revealed a 61% increase in protein content in the plaques compared to the surrounding tissue. After normalizing to protein density, we found that the PSAPP plaques contained only a 29% increase in Zn and there was actually less Cu, Fe, and Ca in the plaque compared to the surrounding tissue. Since metal-binding to Aβ is thought to induce redox chemistry that is toxic to neurons, the reduced metal-binding in PSAPP mice is consistent with the lack of neurodegeneration in these animals. These findings were in stark contrast to the high metal ion content observed in human AD plaques, further implicating the role of metal ions in human AD pathology. PMID:19481608

  6. Amyloid Plaques in PSAPP Mice Bind Less Metal than Plaques in Human Alzheimer's Disease

    SciTech Connect

    Leskovjan, A.; Lanzirotti, A; Miller, L

    2009-01-01

    Amyloid beta (A{Beta}) is the primary component of Alzheimer's disease (AD) plaques, a key pathological feature of the disease. Metal ions of zinc (Zn), copper (Cu), iron (Fe), and calcium (Ca) are elevated in human amyloid plaques and are thought to be involved in neurodegeneration. Transgenic mouse models of AD also exhibit amyloid plaques, but fail to exhibit the high degree of neurodegeneration observed in humans. In this study, we imaged the Zn, Cu, Fe, and Ca ion distribution in the PSAPP transgenic mouse model representing end-stage AD (N = 6) using synchrotron X-ray fluorescence (XRF) microprobe. In order to account for differences in density in the plaques, the relative protein content was imaged with synchrotron Fourier transform infrared microspectroscopy (FTIRM) on the same samples. FTIRM results revealed a 61% increase in protein content in the plaques compared to the surrounding tissue. After normalizing to protein density, we found that the PSAPP plaques contained only a 29% increase in Zn and there was actually less Cu, Fe, and Ca in the plaque compared to the surrounding tissue. Since metal binding to A{beta} is thought to induce redox chemistry that is toxic to neurons, the reduced metal binding in PSAPP mice is consistent with the lack of neurodegeneration in these animals. These findings were in stark contrast to the high metal ion content observed in human AD plaques, further implicating the role of metal ions in human AD pathology.

  7. Chemical agents for the control of plaque and plaque microflora: an overview.

    PubMed

    Gaffar, A; Afflitto, J; Nabi, N

    1997-10-01

    This presentation provides an overview of the technologies available for the chemical control of plaque. It is generally accepted that the formation of dental plaque at the interfaces of tooth/gingiva is one of the major causes of gingival inflammation and dental caries. Several therapeutic approaches have been used to control dental plaque and supragingival infections. These include fluoride preparations such as stannous fluoride, oxygenating agents, anti-attachment agents, and cationic and non-cationic antibacterial agents. Among the fluoride preparations, stable stannous fluoride pastes and gels have been shown to reduce supragingival plaque, gingivitis, hypersensitivity and caries. The effect of the oxygenating agents on the supragingival plaque has been equivocal, but recent data indicate that a stable agent which provides sustained active oxygen release is effective in controlling plaque. A polymer, PVPA, which reduced attachment of bacteria to teeth was shown to significantly reduce plaque formation in humans. A new generation of antibacterials includes non-ionics such as triclosan, which in combination with a special polymer delivery system, has been shown to reduce plaque, gingivitis, supragingival calculus and dental caries in long-term studies conducted around the world. Unlike the first generation of agents, the triclosan/copolymer/sodium fluoride system is effective in long-term clinicals and does not cause staining of teeth, increase in calculus, or disturbance in the oral microbial ecology. PMID:9395116

  8. In Vitro Shear Stress Measurements Using Particle Image Velocimetry in a Family of Carotid Artery Models: Effect of Stenosis Severity, Plaque Eccentricity, and Ulceration

    PubMed Central

    Kefayati, Sarah; Milner, Jaques S.; Holdsworth, David W.; Poepping, Tamie L.

    2014-01-01

    Atherosclerotic disease, and the subsequent complications of thrombosis and plaque rupture, has been associated with local shear stress. In the diseased carotid artery, local variations in shear stress are induced by various geometrical features of the stenotic plaque. Greater stenosis severity, plaque eccentricity (symmetry) and plaque ulceration have been associated with increased risk of cerebrovascular events based on clinical trial studies. Using particle image velocimetry, the levels and patterns of shear stress (derived from both laminar and turbulent phases) were studied for a family of eight matched-geometry models incorporating independently varied plaque features – i.e. stenosis severity up to 70%, one of two forms of plaque eccentricity, and the presence of plaque ulceration). The level of laminar (ensemble-averaged) shear stress increased with increasing stenosis severity resulting in 2–16 Pa for free shear stress (FSS) and approximately double (4–36 Pa) for wall shear stress (WSS). Independent of stenosis severity, marked differences were found in the distribution and extent of shear stress between the concentric and eccentric plaque formations. The maximum WSS, found at the apex of the stenosis, decayed significantly steeper along the outer wall of an eccentric model compared to the concentric counterpart, with a 70% eccentric stenosis having 249% steeper decay coinciding with the large outer-wall recirculation zone. The presence of ulceration (in a 50% eccentric plaque) resulted in both elevated FSS and WSS levels that were sustained longer (∼20 ms) through the systolic phase compared to the non-ulcerated counterpart model, among other notable differences. Reynolds (turbulent) shear stress, elevated around the point of distal jet detachment, became prominent during the systolic deceleration phase and was widely distributed over the large recirculation zone in the eccentric stenoses. PMID:25007248

  9. Vortex dynamics in ruptured and unruptured intracranial aneurysms

    NASA Astrophysics Data System (ADS)

    Trylesinski, Gabriel

    the current hypothesized biological triggers of pathological remodeling of the artery walls. Having a good natural ratio of statuses in our IA cohort (55 unruptured vs. 19 ruptured), we were able to test the statistical significance of our predictor to fortify our findings. We also performed a distribution analysis of our cohort with respect to the number of WKV to strengthen the encouraging statistical analysis result; both analyses provided a clear good separation of the status of the aneurysms based on our predictor. Lastly, we constructed a receiver operating characteristic (ROC) curve to analyze the power different thresholds of WKV had in splitting the data in a binary way (unruptured/ruptured). The number of WKV was efficaciously able to stratify the rupture status, identifying 84.21 % of the ruptured aneurysms (with 25.45 % of false positives, i.e. unruptured IAs tagged as ruptured) when using a threshold value of 2. Our novel work undertaken to study the vortex structures in IAs brought to light interesting characteristics of the flow in the aneurysmal sac. We found that there are several distinct categories in which the aneurysm vortex topologies can be put in without relationship to the aneurysm rupture status. This first finding was in contradiction with available already-published results. Nonetheless, ruptured IAs had a statistically significant larger amount of WKV as opposed to unruptured aneurysms. This new predictor we propose to the community could very well clear a new path among the currently controversial WSS-based parameters. Although it needs to be improved to be more resilient, the first results obtained by the WKV-based parameter are promising when applied to a large dataset of 74 IAs patient-specific transient CFD simulations.

  10. DECT evaluation of noncalcified coronary artery plaque

    SciTech Connect

    Ravanfar Haghighi, Rezvan; Chatterjee, S.; Tabin, Milo; Singh, Rishi P.; Sharma, Munish; Krishna, Karthik; Sharma, Sanjiv; Jagia, Priya; Ray, Ruma; Arava, Sudhir; Yadav, Rakesh; Vani, V. C.; Lakshmi, R.; Kumar, Pratik; Mandal, Susama R.

    2015-10-15

    Purpose: Composition of the coronary artery plaque is known to have critical role in heart attack. While calcified plaque can easily be diagnosed by conventional CT, it fails to distinguish between fibrous and lipid rich plaques. In the present paper, the authors discuss the experimental techniques and obtain a numerical algorithm by which the electron density (ρ{sub e}) and the effective atomic number (Z{sub eff}) can be obtained from the dual energy computed tomography (DECT) data. The idea is to use this inversion method to characterize and distinguish between the lipid and fibrous coronary artery plaques. Methods: For the purpose of calibration of the CT machine, the authors prepare aqueous samples whose calculated values of (ρ{sub e}, Z{sub eff}) lie in the range of (2.65 × 10{sup 23} ≤ ρ{sub e} ≤ 3.64 × 10{sup 23}/cm{sup 3}) and (6.80 ≤ Z{sub eff} ≤ 8.90). The authors fill the phantom with these known samples and experimentally determine HU(V{sub 1}) and HU(V{sub 2}), with V{sub 1},V{sub 2} = 100 and 140 kVp, for the same pixels and thus determine the coefficients of inversion that allow us to determine (ρ{sub e}, Z{sub eff}) from the DECT data. The HU(100) and HU(140) for the coronary artery plaque are obtained by filling the channel of the coronary artery with a viscous solution of methyl cellulose in water, containing 2% contrast. These (ρ{sub e}, Z{sub eff}) values of the coronary artery plaque are used for their characterization on the basis of theoretical models of atomic compositions of the plaque materials. These results are compared with histopathological report. Results: The authors find that the calibration gives ρ{sub e} with an accuracy of ±3.5% while Z{sub eff} is found within ±1% of the actual value, the confidence being 95%. The HU(100) and HU(140) are found to be considerably different for the same plaque at the same position and there is a linear trend between these two HU values. It is noted that pure lipid type plaques

  11. Hyperspectral imaging of atherosclerotic plaques in vitro

    NASA Astrophysics Data System (ADS)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Olstad, Elisabeth; Haugen, Olav A.; Aksnes, Astrid; Svaasand, Lars O.

    2011-02-01

    Vulnerable plaques constitute a risk for serious heart problems, and are difficult to identify using existing methods. Hyperspectral imaging combines spectral- and spatial information, providing new possibilities for precise optical characterization of atherosclerotic lesions. Hyperspectral data were collected from excised aorta samples (n = 11) using both white-light and ultraviolet illumination. Single lesions (n = 42) were chosen for further investigation, and classified according to histological findings. The corresponding hyperspectral images were characterized using statistical image analysis tools (minimum noise fraction, K-means clustering, principal component analysis) and evaluation of reflectance/fluorescence spectra. Image analysis combined with histology revealed the complexity and heterogeneity of aortic plaques. Plaque features such as lipids and calcifications could be identified from the hyperspectral images. Most of the advanced lesions had a central region surrounded by an outer rim or shoulder-region of the plaque, which is considered a weak spot in vulnerable lesions. These features could be identified in both the white-light and fluorescence data. Hyperspectral imaging was shown to be a promising tool for detection and characterization of advanced atherosclerotic plaques in vitro. Hyperspectral imaging provides more diagnostic information about the heterogeneity of the lesions than conventional single point spectroscopic measurements.

  12. Functional expression of dental plaque microbiota.

    PubMed

    Peterson, Scott N; Meissner, Tobias; Su, Andrew I; Snesrud, Erik; Ong, Ana C; Schork, Nicholas J; Bretz, Walter A

    2014-01-01

    Dental caries remains a significant public health problem and is considered pandemic worldwide. The prediction of dental caries based on profiling of microbial species involved in disease and equally important, the identification of species conferring dental health has proven more difficult than anticipated due to high interpersonal and geographical variability of dental plaque microbiota. We have used RNA-Seq to perform global gene expression analysis of dental plaque microbiota derived from 19 twin pairs that were either concordant (caries-active or caries-free) or discordant for dental caries. The transcription profiling allowed us to define a functional core microbiota consisting of nearly 60 species. Similarities in gene expression patterns allowed a preliminary assessment of the relative contribution of human genetics, environmental factors and caries phenotype on the microbiota's transcriptome. Correlation analysis of transcription allowed the identification of numerous functional networks, suggesting that inter-personal environmental variables may co-select for groups of genera and species. Analysis of functional role categories allowed the identification of dominant functions expressed by dental plaque biofilm communities, that highlight the biochemical priorities of dental plaque microbes to metabolize diverse sugars and cope with the acid and oxidative stress resulting from sugar fermentation. The wealth of data generated by deep sequencing of expressed transcripts enables a greatly expanded perspective concerning the functional expression of dental plaque microbiota. PMID:25177549

  13. Measurement of fibrous cap thickness in atherosclerotic plaques by spatiotemporal analysis of laser speckle images

    NASA Astrophysics Data System (ADS)

    Nadkarni, Seemantini K.; Bilenca, Alberto; Bouma, Brett E.; Tearney, Guillermo J.

    2006-03-01

    Necrotic-core fibroatheromas (NCFA) with thin, mechanically weak fibrous caps overlying lipid cores comprise the majority of plaques that rupture and cause acute myocardial infarction. Laser speckle imaging (LSI) has been recently demonstrated to enable atherosclerotic plaque characterization with high accuracy. We investigate spatio-temporal analysis of LSI data, in conjunction with diffusion theory and Monte Carlo modeling of light transport, to estimate fibrous cap thickness in NCFAs. Time-varying laser speckle images of 20 NCFAs are selected for analysis. Spatio-temporal intensity fluctuations are analyzed by exponential fitting of the windowed normalized cross-correlation of sequential laser speckle patterns to obtain the speckle decorrelation time constant, τ(ρ), as a function of distance ρ from the source entry location. The distance, ρ‧, at which τ(ρ) dropped to 65% of its maximum value is recorded. Diffusion theory and Monte Carlo models are utilized to estimate the maximum photon penetration depth, zmax(ρ‧), for a distance equal to ρ‧, measured from LSI. Measurements of zmax(ρ‧) correlate well with histological measurements of fibrous cap thickness (R=0.78,p<0.0001), and paired t-tests show no significant difference between the groups (p=0.4). These results demonstrate that spatio-temporal LSI may allow the estimation of fibrous cap thickness in NCFAs, which is an important predictor of plaque stability.

  14. Rupture interaction with fault jogs

    NASA Astrophysics Data System (ADS)

    Sibson, Richard H.

    Propagation of moderate to large earthquake ruptures within major transcurrent fault systems is affected by their large-scale brittle infrastructure, comprising echelon segmentation and curvature of principal slip surfaces (PSS) within typically ˜1 km wide main fault zones. These PSS irregularities are classified into dilational and antidilational fault jogs depending on the tendency for areal increase or reduction, respectively, across the jog structures. High precision microearthquake studies show that the jogs often extend throughout the seismogenic regime to depths of around 10 km. On geomorphic evidence, the larger jogs may persist for periods >105 years. While antidilational jogs form obstacles to both short- and long-term displacements, dilational jogs appear to act as kinetic barriers capable of perturbing or arresting earthquake ruptures, but allowing time-dependent slip transfer. In the case of antidilational jogs slip transfer is accommodated by widespread subsidiary faulting, but for dilational jogs it additionally involves extensional fracture opening localized in the echelon stepover. In fluid-saturated crust, the rapid opening of linking extensional fracture systems to allow passage of earthquake ruptures is opposed by induced suctions which scale with the width of the jog. Rupture arrest at dilational jogs may then be followed by delayed slip transfer as fluid pressures reequilibrate by diffusion. Aftershock distributions associated with the different fault jogs reflect these contrasts in their internal structure and mechanical response.

  15. Quadriceps Tendon Rupture due to Postepileptic Convulsion

    PubMed Central

    Erkut, Adem; Guvercin, Yilmaz; Sahin, Rifat; Keskin, Davut

    2014-01-01

    We present a case of quadriceps tendon (QT) rupture. QT ruptures can occur in all ages. The cause is mostly traumatic in origin. Spontaneous ruptures that are thought to result from predisposing conditions are rare. Post-convulsion QT ruptures lacking traumas in their history can be overlooked in clinical examinations. This should be born in mind by the attending physician, as early diagnosis and treatment of the condition can lead to satisfactory outcomes. PMID:24944977

  16. Effect of delmopinol hydrochloride mouthrinse on plaque formation and gingivitis in "rapid" and "slow" plaque formers.

    PubMed

    Zee, K; Rundegren, J; Attström, R

    1997-07-01

    The aim of the present study was to investigate differences in the plaque and gingivitis inhibiting effect of delmopinol rinsing between "rapid" and "slow" plaque formers. 23 subjects (12 "rapid" and 11 "slow" plaque formers) were selected from 71 healthy young adults. The selection was based on the plaque index on the buccal surfaces of all premolars and 1st molars after 3-days without plaque control. The 23 subjects were randomly assigned into 3 groups with different mouthrinses, i.e., 0.1% delmopinol, 0.2% delmopinol, and placebo. The study was double-blind with parallel design between the "rapid" and "slow" plaque formers and cross-over design between 2 active periods and a placebo period. Each rinsing period lasted for 5 days. During the 3 test periods, the subjects refrained from all oral hygiene and rinsed 2x daily with either one of the 3 solutions. Gingival crevicular fluid (GCF) was collected from buccal surfaces of upper canines and premolars and bleeding on probing (BOP) recorded at 6 sites around each tooth before and after each test period. Plaque assessment, including plaque index (PI) and standardized color slides for planimetric analyses obtained from the canines and premolars, were only recorded after each test period. Results showed that the mean PI and planimetry values for both the "rapid" and "slow" plaque formers were lower than the placebo, for either the 0.1% or the 0.2% delmopinol mouthrinse. The differences between the" rapid" and "slow" plaque formers were not statistically significant. There was a small reduction in BOP in both groups for the delmopinol periods, as against a slight increase in the placebo period; the difference between the placebo group and the 2 groups of plaque formers was not statistically significant (p>0.6 for both 0.1% and 0.2% delmopinol). Results suggested that both 0.1% and 0.2% delmopinol reduce plaque formation and gingivitis to a similar extent in subjects with extreme rates of plaque formation. PMID:9226389

  17. Analyzing Single-Event Gate Ruptures In Power MOSFET's

    NASA Technical Reports Server (NTRS)

    Zoutendyk, John A.

    1993-01-01

    Susceptibilities of power metal-oxide/semiconductor field-effect transistors (MOSFET's) to single-event gate ruptures analyzed by exposing devices to beams of energetic bromine ions while applying appropriate bias voltages to source, gate, and drain terminals and measuring current flowing into or out of each terminal.

  18. Mechanics of Multifault Earthquake Ruptures

    NASA Astrophysics Data System (ADS)

    Fletcher, J. M.; Oskin, M. E.; Teran, O.

    2015-12-01

    The 2010 El Mayor-Cucapah earthquake of magnitude Mw 7.2 produced the most complex rupture ever documented on the Pacific-North American plate margin, and the network of high- and low-angle faults activated in the event record systematic changes in kinematics with fault orientation. Individual faults have a broad and continuous spectrum of slip sense ranging from endmember dextral strike slip to normal slip, and even faults with thrust sense of dip slip were commonly observed in the aftershock sequence. Patterns of coseismic slip are consistent with three-dimensional constrictional strain and show that integrated transtensional shearing can be accommodated in a single earthquake. Stress inversions of coseismic surface rupture and aftershock focal mechanisms define two coaxial, but permuted stress states. The maximum (σ1) and intermediate (σ2) principal stresses are close in magnitude, but flip orientations due to topography- and density-controlled gradients in lithostatic load along the length of the rupture. Although most large earthquakes throughout the world activate slip on multiple faults, the mechanical conditions of their genesis remain poorly understood. Our work attempts to answer several key questions. 1) Why do complex fault systems exist? They must do something that simple, optimally-oriented fault systems cannot because the two types of faults are commonly located in close proximity. 2) How are faults with diverse orientations and slip senses prepared throughout the interseismic period to fail spontaneously together in a single earthquake? 3) Can a single stress state produce multi-fault failure? 4) Are variations in pore pressure, friction and cohesion required to produce simultaneous rupture? 5) How is the fabric of surface rupture affected by variations in orientation, kinematics, total geologic slip and fault zone architecture?

  19. Intravascular MRI for Plaque Characterization: Are We Close to Reality?

    PubMed

    Cavalcante, João L; Larose, Eric

    2016-09-01

    Non-invasive external magnetic resonance imaging (MRI) of large vessel atherosclerosis is a robust and promising imaging modality that can be applied for the evaluation of the atherosclerotic process in large vessels. However, it requires expertise for setup and time for data acquisition and analysis. Intravascular MRI is a promising tool, but its use remains at the pre-clinical stage within selected research groups. In this review, the current status and future role of intravascular MRI for atherosclerotic plaque characterization are summarized, along with important challenges which will be necessary to overcome prior to the wide adoption of this technique. PMID:27448403

  20. Integrated IVUS-OCT Imaging for Atherosclerotic Plaque Characterization

    PubMed Central

    Li, Xiang; Li, Jiawen; Jing, Joe; Ma, Teng; Liang, Shanshan; Zhang, Jun; Mohar, Dilbahar; Raney, Aidan; Mahon, Sari; Brenner, Matthew; Patel, Pranav; Shung, K. Kirk; Zhou, Qifa; Chen, Zhongping

    2014-01-01

    For the diagnosis of atherosclerosis, biomedical imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed. The combined use of IVUS and OCT is hypothesized to remarkably increase diagnostic accuracy of vulnerable plaques. We have developed an integrated IVUS-OCT imaging apparatus, which includes the integrated catheter, motor drive unit, and imaging system. The dual-function imaging catheter has the same diameter of current clinical standard. The imaging system is capable for simultaneous IVUS and OCT imaging in real time. Ex vivo and in vivo experiments on rabbits with atherosclerosis were conducted to demonstrate the feasibility and superiority of the integrated intravascular imaging modality. PMID:24771992

  1. Detection of vulnerable atherosclerosis plaques with a dual-modal single-photon-emission computed tomography/magnetic resonance imaging probe targeting apoptotic macrophages.

    PubMed

    Cheng, Dengfeng; Li, Xiao; Zhang, Chunfu; Tan, Hui; Wang, Cong; Pang, Lifang; Shi, Hongcheng

    2015-02-01

    Atherosclerosis (AS), especially the vulnerable AS plaque rupture-induced acute obstructive vascular disease, is a leading cause of death. Accordingly, there is a need for an effective method to draw accurate predictions about AS progression and plaque vulnerability. Herein we report on an approach to constructing a hybrid nanoparticle system using a single-photon-emission computed tomography (SPECT)/magnetic resonance imaging (MRI) multimodal probe, aiming for a comprehensive evaluation of AS progression by achieving high sensitivity along with high resolution. Ultrasmall superparamagnetic iron oxide (USPIO) was covered by aminated poly(ethylene glycol) (PEG) and carboxylated PEG simultaneously and then functionalized with diethylenetriaminepentacetate acid for (99m)Tc coordination and subsequently Annexin V for targeting apoptotic macrophages abundant in vulnerable plaques. The in vivo accumulations of imaging probe reflected by SPECT and MRI were consistent and accurate in highlighting lesions. Intense radioactive signals detected by SPECT facilitated focus recognization and quantification, while USPIO-based T2-weighted MRI improved the focal localization and volumetry of AS plaques. For subsequent ex vivo planar images, targeting effects were further confirmed by immunohistochemistry, including CD-68 and TUNEL staining; meanwhile, the degree of concentration was proven to be statistically correlated with the Oil Red O staining results. In conclusion, these results indicated that the Annexin V-modified hybrid nanoparticle system specifically targeted the vulnerable AS plaques containing apoptotic macrophages and could be of great value in the invasively accurate detection of vulnerable plaques. PMID:25569777

  2. A Retrospective Analysis of Ruptured Breast Implants

    PubMed Central

    Baek, Woo Yeol; Lew, Dae Hyun

    2014-01-01

    Background Rupture is an important complication of breast implants. Before cohesive gel silicone implants, rupture rates of both saline and silicone breast implants were over 10%. Through an analysis of ruptured implants, we can determine the various factors related to ruptured implants. Methods We performed a retrospective review of 72 implants that were removed for implant rupture between 2005 and 2014 at a single institution. The following data were collected: type of implants (saline or silicone), duration of implantation, type of implant shell, degree of capsular contracture, associated symptoms, cause of rupture, diagnostic tools, and management. Results Forty-five Saline implants and 27 silicone implants were used. Rupture was diagnosed at a mean of 5.6 and 12 years after insertion of saline and silicone implants, respectively. There was no association between shell type and risk of rupture. Spontaneous was the most common reason for the rupture. Rupture management was implant change (39 case), microfat graft (2 case), removal only (14 case), and follow-up loss (17 case). Conclusions Saline implants have a shorter average duration of rupture, but diagnosis is easier and safer, leading to fewer complications. Previous-generation silicone implants required frequent follow-up observation, and it is recommended that they be changed to a cohesive gel implant before hidden rupture occurs. PMID:25396188

  3. 46 CFR 64.61 - Rupture disc.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Rupture disc. 64.61 Section 64.61 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Pressure Relief Devices and Vacuum Relief Devices for MPTs § 64.61 Rupture disc. If a rupture...

  4. 46 CFR 64.61 - Rupture disc.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Rupture disc. 64.61 Section 64.61 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Pressure Relief Devices and Vacuum Relief Devices for MPTs § 64.61 Rupture disc. If a rupture...

  5. 46 CFR 64.61 - Rupture disc.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Rupture disc. 64.61 Section 64.61 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Pressure Relief Devices and Vacuum Relief Devices for MPTs § 64.61 Rupture disc. If a rupture...

  6. 46 CFR 64.61 - Rupture disc.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Rupture disc. 64.61 Section 64.61 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Pressure Relief Devices and Vacuum Relief Devices for MPTs § 64.61 Rupture disc. If a rupture...

  7. 46 CFR 64.61 - Rupture disc.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Rupture disc. 64.61 Section 64.61 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Pressure Relief Devices and Vacuum Relief Devices for MPTs § 64.61 Rupture disc. If a rupture...

  8. Rupture Directivity in a Foam Rubber Physical Model

    NASA Astrophysics Data System (ADS)

    Anooshehpoor, R.; Brune, J. N.

    2003-12-01

    Understanding earthquake rupture dynamics, especially forward rupture directivity (focusing of seismic energy in the direction of rupture propagation), is crucial in determining the seismic hazard for critical structures located near major active faults. We use foam rubber modeling experiments to provide constraints on parameters that control rupture dynamics, and consequently, forward directivity effects. Numerical models currently in use have too many unconstrained parameters to allow confidence in predictions, and may not even be realistic from a physical point of view. The foam rubber model allows us to develop a deep physical understanding of an actual physical model. This in turn will allow us to better specify which physical parameters used in numerical models are critical, and establish a realistic range for their values, and to better understand and qualify particular numerical models. Three-dimensional numerical simulations of earlier experiments with excellent results provided incentive for additional funding from PEER to increase the number of recording channels in the model from 32 to 76. In particular, we have increased the number of recording sites on the fault plane from 12 to 35 to provide a better picture of the slip distribution on the fault during rupture. At the time of meeting we will present waveforms for selected events.

  9. Direct visualization of microalgae rupture by ultrasound-driven bubbles

    NASA Astrophysics Data System (ADS)

    Pommella, Angelo; Harun, Irina; Pouliopoulos, Antonis; Choi, James J.; Hellgardt, Klaus; Garbin, Valeria

    2015-11-01

    Cell rupture induced by ultrasound is central to applications in biotechnology. For instance, cell disruption is required in the production of biofuels from microalgae (unicellular species of algae). Ultrasound-induced cavitation, bubble collapse and jetting are exploited to induce sufficiently large viscous stresses to cause rupture of the cell membranes. It has recently been shown that seeding the flow with bubbles that act as cavitation nuclei significantly reduces the energy cost for cell processing. However, a fundamental understanding of the conditions for rupture of microalgae in the complex flow fields generated by ultrasound-driven bubbles is currently lacking. We perform high-speed video microscopy to visualize the miscroscale details of the interaction of Chlamydomonas reinhardtii , microalgae of about 10 μm in size, with ultrasound-driven microbubbles of 2-200 μm in diameter. We investigate the efficiency of cell rupture depending on ultrasound frequency and pressure amplitude (from 10 kPa up to 1 MPa), and the resulting bubble dynamics regimes. In particular we compare the efficiency of membrane rupture in the acoustic microstreaming flow induced by linear oscillations, with the case of violent bubble collapse and jetting. V.G. acknowledges partial support from the European Commission (FP7-PEOPLE-2013-CIG), Grant No. 618333.

  10. Dealing with a penstock rupture: A success story

    SciTech Connect

    Siminski, D.R. )

    1993-08-01

    Speed and safety are important considerations when repairing damaged penstocks. When the Control Gorge penstock in southern California ruptured, quick, successful action prevented complications. In the winter of 1991, a break occurred in the lower portion of the 8-foot-diameter Owens River Gorge penstock. The rupture created a vacuum, which caused about 1,500 feet of the pipe upstream of the break to collapse. Investigations by the Los Angeles Department of Water and Power (LADWP) indicate that pressure surges in the penstock caused by rapid opening and closing of a turbine bypass-relief valve at the Control Gorge hydro plant and a defective weld at a manway (a small access that leads into the penstock) led to the rupture. Quick emergency repairs were required owing to the limited bypass capability around the penstock, the need for water flow for fish habitat in the lower sections of the Owens River, and water needs for Los Angeles. Within ten days, LADWP employees had temporarily repaired the penstock. In less than five months, workers had replaced the collapsed and ruptured sections, and returned the penstock to full service. The penstock rupture at Owens Gorge caused LADWP to recognize that older hydro plants may have hidden defects that would not have been left in place with current construction and inspection methods. Therefore, additional care should be taken during operation of these plants to avoid placing any unnecessary stresses on plant equipment.