A comparison of the ADC and T 2 mapping in an assessment of blood-clot lysability (original) (raw)
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In vitro real-time magnetic resonance imaging for quantification of thrombosis
Magnetic Resonance Materials in Physics, Biology and Medicine, 2020
Object: Thrombosis is a leading cause of failure for cardiovascular devices. While computational simulations are a powerful tool to predict thrombosis and evaluate the risk for medical devices, limited experimental data are available to validate the simulations. The aim of the current study is to provide experimental data of a growing thrombus for device-induced thrombosis. Materials and Methods: Thrombosis within a backward-facing step (BFS), or sudden expansion was investigated, using bovine and human blood circulated through the BFS model for 30 min, with a constant inflow rate of 0.76 L/min. Real-time three-dimensional flow compensated magnetic resonance imaging (MRI), supported with Magnevist, a contrast agent improving thrombus delineation, was applied to quantify thrombus deposition and growth within the model. Results: The study showed that the BFS model induced a flow recirculation region, which facilitated thrombosis. By 30 min, in comparison to bovine blood, human blood resulted in smaller thrombus formation, in terms of the length (13.3±0.6 vs. 18.1±1.3 mm), height (2.3±0.1 vs. 2.6±0.04 mm), surface area exposed to blood (0.67±0.03 vs 1.05±0.08 cm 2), and volume (0.069±0.004 vs. 0.093±0.007 cm 3), with p < 0.01. Normalization of the thrombus measurements, Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. https://www.springer.com/aamterms-v1
Thrombosis Research, 2014
Introduction: We investigated the effect of progressive haemodilution on the dynamics of fibrin clot formation and clot microstructure using a novel rheological method. The technique measures clotting time (TGP), clot strength (G`GP), and quantifies clot microstructure (df) at the incipient stages of fibrin formation. We use computational modelling to examine the relationship between structure and mass, as well as helium ion microscopy (HIM) to compare morphological changes in the fully formed clot to that of the incipient clot. Methods: This is an in vitro study; 90 healthy volunteers were recruited with informed consent and a 20ml sample of whole blood obtained from each volunteer. Five clinically relevant dilutions were investigated using 0.9w.v isotonic saline (0, 10, 20, 40 and 60%, n=18 for each dilution). The rheological method of assessing structural clot changes was compared against conventional coagulation screen and fibrinogen estimation. Results: Fractal dimension (df) and final clot microstructure both decreased with progressive dilution (significant at a dilution of 20%) with similar relationships observed for final clot characteristics in HIM images. Significant correlations were observed between df and G`GP (clot strength) (0.345, p=0.02), as well as clotting time (PT:-0.690, p>0.001; APTT:-0.672, p>0.001; TGP:-0.385, p=0.006). Conclusions: This study provides new insight into the effects of haemodilution by isotonic saline on clotting time (TGP), clot strength (GGP) and clot microstructure (df). Previous studies have 3 attempted to link clot microstructure to clot quality/strength, however this study provides a significant step in quantifying these relationships.
Thrombosis and Haemostasis, 2019
Turbidimetry is used to characterize fibrin clot properties. In purified systems, maximum absorbance (MA) directly relates to fibrin fiber cross-sectional area. However, in plasma samples there are discrepancies in the relationships between MA and fibrinogen concentration, fiber diameter, other clot properties, and cardiovascular disease outcomes, which complicate data interpretation. This study aims to advance understanding of MA of plasma clots through testing how well it relates to fundamental dependence on fibrinogen concentration and fiber diameter as predicted by light scattering theory, other clot properties and lifestyle, and biochemical variables. Plasma samples from 30 apparently healthy individuals with a fibrinogen concentration from 2.4 to 6.4 g/L were included. We performed turbidimetry, permeability, scanning electron microscopy, and rheometry on in vitro formed plasma clots. MA correlated more strongly with fibrinogen concentration (r = 0.65; p < 0.001) than with fiber diameter (r = 0.47; p = 0.01), which combined explained only 46% of the MA variance. Of additional variables measured, only low-density lipoprotein cholesterol correlated with MA (r = 0.46; p = 0.01) and clot lysis (r = 0.62; p < 0.0001) but not with fiber diameter or fibrinogen concentration. MA correlated with clot lysis time (r = 0.59; p = 0.001), storage modulus (r = 0.61; p = 0.001), and loss modulus (r = 0.59; p = 0.001), and negatively with clot permeability (r =−0.60; p = 0.001) also after adjustment for fibrinogen concentration and fiber diameter. Increased MA is indicative of a prothrombotic clot phenotype irrespective of fibrinogen concentration. MA is more indicative of overall clot density than of fiber diameter. Other plasma components can alter internal fiber density without altering fiber diameter and should be considered when interpreting MA of plasma samples.
Prediction of hemorrhagic transformation after ischemic stroke: Superiority of FLAIR-ADC
Background and Purpose-Thrombolytic treatment of stroke carries the risk of hemorrhagic transformation. Therefore, the potential of MRI for prediction of recombinant tissue plasminogen activator (rtPA)-induced bleeding is explored to identify patients in whom rtPA treatment may provoke such complications. Methods-Spontaneously hypertensive rats (SHR) (nϭ9) were submitted to middle cerebral artery (MCA) clot embolism, followed 3 hours later by intra-arterial infusion of 10 mg/kg rtPA. Untreated SHR (nϭ9) were infused with saline. MRI imaging was performed before treatment and included apparent diffusion coefficient (ADC), T2, and perfusion mapping and contrast enhancement with gadolinium-DTPA. The distribution of intracerebral hemorrhages was studied 3 days later by histological staining. Results-Clot embolism led to the rapid decline of ADC in the territory of the occluded artery. Tissue lesion volume derived from ADC imaging increased by 155Ϯ69% in the untreated animals and by 168Ϯ87% in the treated animals (PϭNS), determined on the histological sections after 3 days. This same lesion growth in both groups indicated absence of therapeutic effect after 3-hour treatment delay. Hemorrhagic transformations were significantly more frequent in treated SHR (PϽ0.05). In untreated rats, hemorrhages were found in the border zone of the ischemic territory; in treated animals, hemorrhagic transformations occurred in the ischemic core region. rtPA-induced hemorrhages were predicted by a disturbance of the blood-brain barrier in 3 of 4 animals before treatment by Gd-DTPA contrast enhancement but not by ADC, T2, or perfusion imaging. The region of contrast enhancement colocalized with subsequent bleeding in these animals. Conclusions-The disturbance of blood-brain barrier but not of other MR parameters allows risk assessment for hemorrhagic transformation induced by subsequent thrombolytic treatment. (Stroke. 2002;33:1392-1398.)
Journal of Public Health Research, 2021
Background Clot characterization is, to the present days, a multimodal approach: scanning the clot by electron microscopy (SEM) is helpful for the visualization of fibrin structure along with laboratory parameters such as the clot waveform analysis (CWA) and thrombin generation in different settings of clot abnormalities. This study aimed to assess whether the coagulative parameters were consistent with the clot images texture acquired by SEM, and therefore to propose a more generalist and integrative approach to clots classification. Design and methods In this pilot study, the examined population consists of eight healthy subjects, seven patients affected by Acquired Hemophilia A (AHA) and seven patients treated with Vitamin K Antagonists (VKAs), similar for age and gender. We studied the velocity and acceleration (1st and 2nd derivative of the aPTT) of clot formation (CWA), the thrombin generation, and the clots’ scanning by SEM. Images acquired with SEM were then analyzed with th...
Phenomenological analysis of the clotting curve
Journal of Protein Chemistry, 1991
A model-independent (phenomenological) characterization of the clotting curve is proposed. Three parameters are used to encapsulate the main features of the increase in absorbance observed at 350 nm due to the reaction of thrombin with fibrinogen that leads to clot formation: (1) the maximum increase in absorbance-per-unit time, AAm, at the inflection point of the clotting curve; (2) the time needed to reach the maximum increase in absorbance, t,,; and (3) the clotting time, t~, obtained from extrapolation of the slope at t,~ to the zero absorbance baseline° Clotting curves at low fibrinogen concentrations (0.125 + 0.250/~M), well below the K~,, where thrombin amidase activity is rate-limiting with respect to the subsequent aggregation process, have been measured under a wide variety of experimental conditions, (i.e., as a function of thrombin concentration, pH and temperature) in order to explore the basic response of each parameter to changes in solution conditions. Under all conditions examined in this study we have observed that tm and t~. are linked through a linear relationship that appears to be an important invariant property of the clotting curve, regardless of experimental conditions. No such clear relationship exists between AAm and to, with tc being associated with several possible values of AA,~ and vice versa, depending upon solution conditions. It is proposed that t~ is strictly dependent on thrombin amidase activity, while AA,~ reflects properties of the aggregation process leading to clot formation. The clotting time shows a pH and temperature dependence that closely resembles that of Kr~/Vm for synthetic amide substrates. Futhermore, tc changes linearly with either the inverse thrombin concentration and the concentration of competitive inhibitors of fibrinogen binding to thrombin, as expected for the ratio Km/Vm. We show how the analysis of clotting curves obtained at different thrombin and inhibitor concentrations yields a quantitative measure of K~ that is in excellent agreement with the value determined independently from steady-state measurements of thrombin amidase activity.