High Resolution Magnetic Resonance Imaging of Resected Plaque

1997 ◽  
Vol 3 (S2) ◽  
pp. 309-310
Author(s):  
D. Saloner
Keyword(s):  
Atherosclerotic Plaque ◽  
Carotid Bifurcation ◽  
Surgical Removal ◽  
Strongly Correlated ◽  
Clinical Events ◽  
Significant Events ◽  
Diseased Vessel ◽  
Clinically Significant ◽  
Substantial Interest

Atherosclerotic plaque at the carotid bifurcation is strongly correlated with the incidence of clinically significant events, such as transient ischemie attacks or stroke. Large multi-center trials have demonstrated that surgical removal of the atheroma is more effective in reducing these clinical events than is medical treatment alone. Patients are selected for surgery from an assessment of the severity of disease at the carotid bifurcation. The measure of disease severity is conventionally taken to be the degree of narrowing of the diseased vessel compared to a normal segment of vessel. However, using this criterion alone, many patients receive endarterectomy surgery who would probably not have progressed to other neurological events, while others are excluded who do progress to neurological events. For this reason, there is substantial interest in methods that could evaluate the composition of the atherosclerotic plaque in vivo, with the hope that this information would improve the predictive power of pre-surgical imaging of the diseased vessel.

scholarly journals Exploring the Relationships Between Hemodynamic Stresses in the Carotid Arteries

2021 ◽  
Vol 7 ◽  
Author(s):  
Magnus Ziegler ◽  
Jesper Alfraeus ◽  
Elin Good ◽  
Jan Engvall ◽  
Ebo de Muinck ◽  
...  
Keyword(s):  
Vessel Wall ◽  
Carotid Arteries ◽  
Carotid Bifurcation ◽  
Vessel Diameter ◽  
Atherosclerotic Plaques ◽  
Shear Stresses ◽  
Strongly Correlated ◽  
4D Flow ◽  
Bifurcation Angle

Background: Atherosclerosis manifests as a focal disease, often affecting areas with complex hemodynamics such as the carotid bifurcation. The magnitude and regularity of the hemodynamic shear stresses acting on the vessel wall are thought to generate risk patterns unique to each patient and play a role in the pathogenesis of atherosclerosis. The involvement of different expressions of shear stress in the pathogenesis of carotid atherosclerosis highlights the need to characterize and compare the differential impact of the various expressions of shear stress in the atherosclerotic carotid bifurcation. Therefore, the aim of this study is to characterize and compare hemodynamic wall shear stresses (WSS) in the carotid arteries of subjects with asymptomatic atherosclerotic plaques. Shear stresses were also compared against vessel diameter and bifurcation angle to examine the relationships with the geometry of the carotid bifurcation.Methods: 4D Flow MRI and contrast-enhanced MRA data were acquired for 245 subjects with atherosclerotic plaques of at least 2.7 mm in conjunction with the Swedish CArdioPulmonary bioImage Study (SCAPIS). Following automatic segmentation and geometric analysis, time-resolved WSS and near-wall turbulent kinetic energy (nwTKE) were derived from the 4D Flow data. Whole-cycle parameters including time-averaged WSS and nwTKE, and the oscillatory shear index (OSI) were calculated. Pairwise Spearman rank-correlation analyses were used to investigate relationships among the hemodynamic as well as geometric parameters.Results: One hundred and seventy nine subjects were successfully segmented using automated tools and subsequently geometric and hemodynamic analyses were performed. Temporally resolved WSS and nwTKE were strongly correlated, ρ = 0.64. Cycle-averaged WSS and nwTKE were moderately correlated, ρ = 0.57. Cycle-average nwTKE was weakly correlated to OSI (ρ = −0.273), revealing that nwTKE provides information about disturbed flow on the vessel wall that OSI does not. In this cohort, there was large inter-individual variation for both WSS and nwTKE. Both WSS and nwTKE varied most within the external carotid artery. WSS, nwTKE, and OSI were weakly correlated to vessel diameter and bifurcation angle.Conclusion: The turbulent and mean component of WSS were examined together in vivo for the first time, and a strong correlation was found between them. nwTKE presents the opportunity to quantify turbulent wall stresses in vivo and gain insight into the effects of disturbed flow on the vessel wall. Neither vessel diameter nor bifurcation angle were found to be strongly correlated to the turbulent or mean component of WSS in this cohort.

Atherosclerosis imaging

ESC CardioMed ◽  
2018 ◽  
pp. 524-528
Author(s):  
Chun Yuan ◽  
Zach Miller ◽  
Jianming Cai
Keyword(s):  
Atherosclerotic Plaque ◽  
Large Scale ◽  
Three Dimensional ◽  
Plaque Imaging ◽  
Fibrous Cap ◽  
Intraplaque Haemorrhage ◽  
Clinical Events ◽  
Flexible Imaging ◽  
Atherosclerosis Imaging

Atherosclerosis imaging goes beyond the simple identification of luminal stenosis. Besides stenosis measurement, there are two main motivations for atherosclerosis imaging: one is to identify the so-called vulnerable plaque, defined as atherosclerotic plaque that poses increased risk of rupture and clinical events, such as heart attack or stroke; the other is to identify ‘positively remodelled’ plaques—plaques that grow outward from the lumen but cause minimal or no stenosis. Cardiovascular magnetic resonance (CMR) has histologically validated capabilities to characterize carotid plaque features in vivo, including a lipid-rich necrotic core, fibrous cap, intraplaque haemorrhage (IPH), calcification, and inflammation. A multicontrast two-dimensional imaging approach has been used in many prospective studies relating baseline CMR characteristics of carotid atherosclerosis with plaque progression and clinical events. These studies have demonstrated the importance of detecting IPH, lipid-rich necrotic cores, and fibrous caps. Building on these findings, a number of three-dimensional CMR techniques have been recently developed that allow higher spatial resolution plaque imaging and easier application clinically with short scan times. Three-dimensional plaque imaging offers flexible imaging plane and view angle analysis, large coverage, multivascular beds capability, and is a fast and cost-effective screening for clinical use. Atherosclerosis imaging has also been applied to detect plaques in other vascular beds such as the coronary artery, intracranial artery, and peripheral artery, although each bed comes with unique imaging needs. Large-scale studies are needed to determine the impact of atherosclerotic plaque CMR on patient outcomes.

Animal models of atherosclerosis and magnetic resonance imaging for monitoring plaque progression

Vascular ◽  
2014 ◽  
Vol 22 (3) ◽  
pp. 221-237 ◽  
Author(s):  
Antoine Millon ◽  
Emmanuelle Canet-Soulas ◽  
Loic Boussel ◽  
Zahi Fayad ◽  
Philippe Douek
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Animal Models ◽  
Atherosclerotic Plaque ◽  
Atherosclerotic Plaques ◽  
Resonance Imaging ◽  
Human Atherosclerotic Plaque ◽  
Clinical Events ◽  
Vulnerable Plaques

Atherosclerosis, the main cause of heart attack and stroke, is the leading cause of death in most modern countries. Preventing clinical events depends on a better understanding of the mechanism of atherosclerotic plaque destabilization. Our knowledge on the characteristics of vulnerable plaques in humans has grown past decades. Histological studies have provided a precise definition of high-risk lesions and novel imaging methods for human atherosclerotic plaque characterization have made significant progress. However the pathological mechanisms leading from stable lesions to the formation of vulnerable plaques remain uncertain and the related clinical events are unpredictable. An animal model mimicking human plaque destablization is required as well as an in vivo imaging method to assess and monitor atherosclerosis progression. Magnetic resonance imaging (MRI) is increasingly used for in vivo assessment of atherosclerotic plaques in the human carotids. MRI provides well-characterized morphological and functional features of human atherosclerotic plaque which can be also assessed in animal models. This review summarizes the most common species used as animal models for experimental atherosclerosis, the techniques to induce atherosclerosis and to obtain vulnerable plaques, together with the role of MRI for monitoring atherosclerotic plaques in animals.

Cardiopulmonary Monitors and Clinically Significant Events in Critically Ill Children

2011 ◽  
Vol 45 (s1) ◽  
pp. 38-45 ◽  
Author(s):  
Linda B. Talley ◽  
Jeffrey Hooper ◽  
Brian Jacobs ◽  
Cathie Guzzetta ◽  
Robert McCarter ◽  
...  
Keyword(s):  
Critically Ill ◽  
False Positive ◽  
Critically Ill Children ◽  
Predictive Values ◽  
Safety Issues ◽  
Clinical Events ◽  
Significant Events ◽  
Clinically Significant ◽  
Sensitivity Specificity ◽  
Clinical Conditions

Abstract Cardiopulmonary monitors (CPMs) generate false alarm rates ranging from 85%–99% with few of these alarms actually representing serious clinical events. The overabundance of clinically insignificant alarms in hospitals desensitizes the clinician to true-positive alarms and poses significant safety issues. In this IRB-approved externally funded study, we sought to assess the clinical conditions associated with true and false-positive CPM alarms and attempted to define optimal alarm parameters that would reduce false-positive alarm rates (as they relate to clinically significant events) and thus improve overall CPM performance in critically ill children. Prior to the study, clinically significant events (CSEs) were defined and validated. Over a seven-month period in 2009, critically ill children underwent evaluation of CSEs while connected to a CPM. Comparative CPM and CSE data were analyzed with an aim to estimate sensitivity, specificity, and positive and negative predictive values for CSEs. CPM and CSE data were evaluated in 98 critically ill children. Overall, 2,245 high priority alarms were recorded with 68 CSEs noted in 45 observational days. During the course of the study, the team developed a firm understanding of CPM functionality, including the pitfalls associated with aggregation and analysis of CPM alarm data. The inability to capture all levels of CPM alarms represented a significant study challenge. Selective CPM data can be easily queried with standard reporting, however the default settings with this reporting exclude critical information necessary in compiling a coherent study denominator database. Although the association between CPM alarms and CSEs could not be comprehensively evaluated, preliminary analysis reflected poor CPM alarm specificity. This study provided the necessary considerations for the proper design of a future study that improves the positive predictive value of CPM alarms. In addition, this investigation has resulted in improved awareness of CPM alarm parameter settings and associated false-positive alarms. This information has been incorporated into nursing educational programs.

Release, Aggregation and Lysis of Human Platelets by Antilymphocyte Globulin and Antiplatelet Serum

1976 ◽  
Vol 36 (02) ◽  
pp. 411-423 ◽  
Author(s):  
Nicholas Lekas ◽  
J. C Rosenberg
Keyword(s):  
Platelet Aggregation ◽  
Gamma Globulin ◽  
Human Platelets ◽  
Plasma Medium ◽  
Release Reaction ◽  
Clinical Events ◽  
Thrombotic Complications ◽  
Platelet Release ◽  
Free Media

SummaryHuman platelets labeled with 51Cr were used to determine the contribution made by platelet lysis to the platelet release reaction and platelet aggregation induced by rabbit antihuman platelet serum (APS) and equine antihuman thymocyte globulin (ATG). Platelets were tested in both plasma (PRP) and non-plasma containing media. Antibodies directed against platelets, either as APS or ATG, induced significant amounts of platelet release and aggregation, as well as some degree of lysis, in the absence of complement. The presence of complement increased platelet lysis and aggregation, but not the release reaction. Non-immune horse gamma globulin produced different responses depending upon whether platelets were investigated in PRP or non-plasma containing media. Aggregation was seen in the latter but not the former. These differences can be explained by the presence of plasma components which prevent non-specific immune complexes from causing platelet aggregation. Since platelets in vivo are always in a plasma medium, one must be wary of utilizing data from platelet studies in synthetic plasma-free media as the basis of explaining clinical events. These observations demonstrate at least two, and possibly three, different mechanisms whereby ATG could activate platelets causing thrombotic complications and thrombocytopenia, i.e., via 1) specific and, 2) non-specific non-lytic pathways and 3) a lytic pathway.

scholarly journals Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets

2020 ◽  
Vol 318 (1) ◽  
pp. G1-G9 ◽  
Author(s):  
Richard A. Jacobson ◽  
Kiedo Wienholts ◽  
Ashley J. Williamson ◽  
Sara Gaines ◽  
Sanjiv Hyoju ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Healing Process ◽  
Abdominal Sepsis ◽  
Infectious Complications ◽  
Fibrinolytic System ◽  
Clinical Safety ◽  
High Concentrations ◽  
Clinically Significant

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing. NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

scholarly journals Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Mensch ◽  
Jade Dunot ◽  
Sandy M. Yishan ◽  
Samuel S. Harris ◽  
Aline Blistein ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strongly Correlated ◽  
App Processing ◽  
Term Potentiation ◽  
Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

scholarly journals Platelet CD36 signaling through ERK5 promotes caspase-dependent procoagulant activity and fibrin deposition in vivo

2018 ◽  
Vol 2 (21) ◽  
pp. 2848-2861 ◽  
Author(s):  
Moua Yang ◽  
Andaleb Kholmukhamedov ◽  
Marie L. Schulte ◽  
Brian C. Cooley ◽  
Na’il O. Scoggins ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Signaling Molecules ◽  
Chow Diet ◽  
Glycoprotein Vi ◽  
Platelet Signaling ◽  
Clinically Significant

Abstract Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer exposure and, subsequently, recruitment of the prothrombinase complex, resulting in the generation of fibrin from the activation of thrombin. Caspase activity was observed when platelets were stimulated with oxLDL. This was prevented by inhibiting CD36 and ERK5. Furthermore, oxLDL potentiates convulxin/glycoprotein VI–mediated fibrin formation by platelets, which was prevented when CD36, ERK5, and caspases were inhibited. Using 2 in vivo arterial thrombosis models in apoE-null hyperlipidemic mice demonstrated enhanced arterial fibrin accumulation upon vessel injury. Importantly, absence of ERK5 in platelets or mice lacking CD36 displayed decreased fibrin accumulation in high-fat diet–fed conditions comparable to that seen in chow diet–fed animals. These findings suggest that platelet signaling through CD36 and ERK5 induces a procoagulant phenotype in the hyperlipidemic environment by enhancing caspase-mediated PSer exposure.

A Novel Noninvasive Technique for Pulse-Wave Imaging and Characterization of Clinically-Significant Vascular Mechanical Properties In Vivo

2007 ◽  
Vol 29 (3) ◽  
pp. 137-154 ◽  
Author(s):  
Kana Fujikura ◽  
Jianwen Luo ◽  
Viktor Gamarnik ◽  
Mathieu Pernot ◽  
Royd Fukumoto ◽  
...  
Keyword(s):  
Aortic Wall ◽  
Pulse Wave ◽  
Distal Region ◽  
Noninvasive Technique ◽  
Abdominal Aortic ◽  
Wave Imaging ◽  
Risk Patients ◽  
Noninvasive Mapping ◽  
Clinically Significant

The pulse-wave velocity (PWV) has been used as an indicator of vascular stiffness, which can be an early predictor of cardiovascular mortality. A noninvasive, easily applicable method for detecting the regional pulse wave (PW) may contribute as a future modality for risk assessment. The purpose of this study was to demonstrate the feasibility and reproducibility of PW imaging (PWI) during propagation along the abdominal aortic wall by acquiring electrocardiography-gated (ECG-gated) radiofrequency (rf) signals noninvasively. An abdominal aortic aneurysm (AAA) was induced using a CaCl2 model in order to investigate the utility of this novel method for detecting disease. The abdominal aortas of twelve normal and five CaCl2, mice were scanned at 30 MHz and electrocardiography (ECG) was acquired simultaneously. The radial wall velocities were mapped with 8000 frames/s. Propagation of the PW was demonstrated in a color-coded ciné-loop format in all cases. In the normal mice, the wave propagated in linear fashion from a proximal to a distal region. However, in CaCl2 mice, multiple waves were initiated from several regions (i.e., most likely initiated from various calcified regions within the aortic wall). The regional PWV in normal aortas was 2.70 ± 0.54 m/s ( r2 = 0.85 ± 0.06, n = 12), which was in agreement with previous reports using conventional techniques. Although there was no statistical difference in the regional PWV between the normal and CaCl2-treated aortas (2.95 ± 0.90 m/s ( r2 = 0.51 ± 0.22, n = 5)), the correlation coefficient was found to be significantly lower in the CaCl2-treated aortas ( p<0.01). This state-of-the-art technique allows noninvasive mapping of vascular disease in vivo. In future clinical applications, it may contribute to the detection of early stages of cardiovascular disease, which may decrease mortality among high-risk patients.

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