scholarly journals In Vivo Quantification of Myocardial Infarction in Mice Using Micro-CT and a Novel Blood Pool Agent

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Stefan Sawall ◽  
Danielle Franke ◽  
Anne Kirchherr ◽  
Jan Beckendorf ◽  
Jan Kuntz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Contrast Agent ◽  
Infarct Size ◽  
Blood Pool ◽  
Signal Enhancement ◽  
Imaging Method ◽  
Micro Ct ◽  
Contrast Agent Injection ◽  
Dependent Signal

We herein developed a micro-CT method using the innovative contrast agent ExiTron™ MyoC 8000 to longitudinally monitor cardiac processes in vivo in small animals. Experiments were performed on healthy mice and mice with myocardial infarction inflicted by ligation of the left anterior descending artery. Time-dependent signal enhancement in different tissues of healthy mice was measured and various contrast agent doses were investigated so as to determine the minimum required dose for imaging of the myocardium. Due to its ability to be taken up by healthy myocardium but not by infarct tissue, ExiTron MyoC 8000 enables detection of myocardial infarction even at a very low dose. The signal enhancement in the myocardium of infarcted mice after contrast agent injection was exploited for quantification of infarct size. The values of infarct size obtained from the imaging method were compared with those obtained from histology and showed a significant correlation (R2=0.98). Thus, the developed micro-CT method allows for monitoring of a variety of processes such as cardiac remodeling in longitudinal studies.

scholarly journals PEG-modified gadolinium nanoparticles as contrast agents for in vivo micro-CT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Charmainne Cruje ◽  
P. Joy Dunmore-Buyze ◽  
Eric Grolman ◽  
David W. Holdsworth ◽  
Elizabeth R. Gillies ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Soft Tissues ◽  
Three Dimensional ◽  
Blood Pool ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Poly Ethylene

AbstractVascular research is largely performed in rodents with the goal of developing treatments for human disease. Micro-computed tomography (micro-CT) provides non-destructive three-dimensional imaging that can be used to study the vasculature of rodents. However, to distinguish vasculature from other soft tissues, long-circulating contrast agents are required. In this study, we demonstrated that poly(ethylene glycol) (PEG)-coated gadolinium nanoparticles can be used as a vascular contrast agent in micro-CT. The coated particles could be lyophilized and then redispersed in an aqueous solution to achieve 100 mg/mL of gadolinium. After an intravenous injection of the contrast agent into mice, micro-CT scans showed blood pool contrast enhancements of at least 200 HU for 30 min. Imaging and quantitative analysis of gadolinium in tissues showed the presence of contrast agent in clearance organs including the liver and spleen and very low amounts in other organs. In vitro cell culture experiments, subcutaneous injections, and analysis of mouse body weight suggested that the agents exhibited low toxicity. Histological analysis of tissues 5 days after injection of the contrast agent showed cytotoxicity in the spleen, but no abnormalities were observed in the liver, lungs, kidneys, and bladder.

scholarly journals 4-D Micro-CT of the Mouse Heart

2005 ◽  
Vol 4 (2) ◽  
pp. 153535002005041 ◽  
Author(s):  
Cristian T. Badea ◽  
Boma Fubara ◽  
Laurence W. Hedlund ◽  
G. Allan Johnson
Keyword(s):  
Cardiac Function ◽  
Contrast Agent ◽  
Blood Pool ◽  
Kidney Cortex ◽  
Mouse Heart ◽  
Micro Ct ◽  
Maximum Enhancement ◽  
Functional Studies ◽  
Iodinated Contrast

Purpose: Demonstrate noninvasive imaging methods for in vivo characterization of cardiac structure and function in mice using a micro-CT system that provides high photon fluence rate and integrated motion control. Materials and Methods: Simultaneous cardiac- and respiratory-gated micro-CT was performed in C57BL/6 mice during constant intravenous infusion of a conventional iodinated contrast agent (Isovue-370), and after a single intravenous injection of a blood pool contrast agent (Fenestra VC). Multiple phases of the cardiac cycle were reconstructed with contrast to noise and spatial resolution sufficient for quantitative assessment of cardiac function. Results: Contrast enhancement with Isovue-370 increased over time with a maximum of ~500 HU (aorta) and 900 HU (kidney cortex). Fenestra VC provided more constant enhancement over 3 hr, with maximum enhancement of ~620 HU (aorta) and ~90 HU (kidney cortex). The maximum enhancement difference between blood and myocardium in the heart was ~250 HU for Isovue-370 and ~500 HU for Fenestra VC. In mice with Fenestra VC, volumetric measurements of the left ventricle were performed and cardiac function was estimated by ejection fraction, stroke volume, and cardiac output. Conclusion: Image quality with Fenestra VC was sufficient for morphological and functional studies required for a standardized method of cardiac phenotyping of the mouse.

scholarly journals In Vivo Detection and Measurement of Aortic Aneurysm and Dissection in Mouse Models Using Microcomputed Tomography with Contrast Agent

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Guanglang Zhu ◽  
Huiying Sun ◽  
Jiannan Wang ◽  
Zhiqing Zhao ◽  
Junmin Bao ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Aortic Dissection ◽  
Mouse Model ◽  
Contrast Agent ◽  
Time Dependent ◽  
Micro Ct ◽  
Aortic Aneurysm And Dissection ◽  
Dependent Signal ◽  
Changing Process

Objectives. The aim of this study was to evaluate the potential of microcomputed tomography (micro-CT) using the intravascular contrast agent ExiTron nano 12000 for aorta imaging and monitoring the dynamic changing process of the aorta in mouse models with aortic aneurysm and dissection. Materials and Methods. Experiments were performed on healthy mice and mice with aortic dissection. Mice that were developing aortic dissection and healthy mice underwent micro-CT imaging after injection of ExiTron nano 12000. Time-dependent signal enhancement (at 1, 2, 3, 6, and 12 hours after intravenous injection of the contrast agent, respectively) in the aorta of healthy mice was measured to confirm the optimal imaging time of aorta. Various contrast agent doses (70, 100, and 150 μl per 25 g mouse, respectively) were investigated to determine the optimal required dose for imaging of the aorta. The mice were scanned with micro-CT at 1, 14, and 28 days after onset of aneurysm and dissection to monitor the dynamic changing process of the aorta. Mouse aortas were stained with hematoxylin and eosin staining, and the diameter of the aorta was measured and compared with those obtained by micro-CT. Results. Time-dependent signal enhancement in the aorta shows that the contrast agent has a long blood half-life of 6 hours, with a peak enhancement at 2 hours after injection. Injection of 100 μl ExiTron nano 12000 per 25 g mouse allows for effective visualization of the aorta. Micro-CT combined with contrast agent can monitor the changing process of the aorta in the mouse model of aortic aneurysm and dissection dynamically. The values of the diameter of the aortas obtained from the in vivo micro-CT imaging were compared with those obtained from histology and showed a significant correlation (R2 = 0.96). Conclusions. These data demonstrate that in vivo micro-CT is an accurate and feasible technique to detect aortic aneurysm or dissection in a mouse model, and the micro-CT technique using the innovative contrast agent ExiTron nano 12000 allows for monitoring various processes dynamically such as aortic remodeling in longitudinal studies.

scholarly journals Study on Establishing Reference Safe Concentrations of MRI Contrast Agents for Optimized Images: Paramagnetic Gd-DTPA-BMEA and Superparamagnetic Ferucarbotran

2021 ◽  
Vol 11 (3) ◽  
pp. 1165
Author(s):  
Wen-Tien Hsiao ◽  
Yi-Hong Chou ◽  
Jhong-Wei Tu ◽  
Ai-Yih Wang ◽  
Lu-Han Lai
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Mri Contrast Agents ◽  
Mri Contrast Agent ◽  
In Vitro Experiments ◽  
Mri Contrast ◽  
In Vivo Experiments ◽  
Contrast Agent Injection

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%; all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 μL, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

Abstract 12: EMMPRIN-Targeted Magnetic Nanoparticles for in vivo Visualization and Regression of Acute Myocardial Infarction in a Model of Acute Coronary Artery Occlusion

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Irene Cuadrado ◽  
Maria Jose Garcia Miguel ◽  
Irene Herruzo ◽  
Mari Carmen Turpin ◽  
Ana Martin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Extracellular Matrix ◽  
Coronary Artery ◽  
Left Ventricle ◽  
Infarct Size ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Gadolinium Enhancement

Extracellular matrix metalloproteinase inducer EMMPRIN, is highly expressed in patients with acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including MMP-9 and MMP-13. To prevent Extracellular matrix degradation and cardiac cell death we targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles with an EMMPRIN binding peptide AP9 conjugated (NAP9), or an AP9 scramble peptide as a negative control (NAPSC). NAP9 binds to endogenous EMMPRIN as detected by confocal microscopy of cardiac myocytes and macrophages incubated with NAP and NAPSC in vitro, and in vivo in mouse hearts subjected to left anterior descending coronary artery occlusion (IV injection 50mγ/Kg NAP9 or NAP9SC). Administration of NAP9 at the same time or 1 hour after AMI reduced infarct size over a 20% respect to untreated and NAPSC injected mice, recovered left ventricle ejection fraction (LVEF) similar to healthy controls, and reduced EMMPRIN downstream MMP9 expression. In magnetic resonance scans of mouse hearts 2 days after AMI and injected with NAP9, we detected a significant gadolinium enhancement in the left ventricle respect to non-injected mice and to mice injected with NAPSC. Late gadolinium enhancement assays exhibited NAP9-mediated left ventricle signal enhancement as early as 30 minutes after nanoprobe injection, in which a close correlation between the MRI signal enhancement and left ventricle infarct size was detected. Taken together, these results point EMMPRIN targeted nanoprobes as a new tool for the treatment of AMI.

Inhibition of nonexocytotic norepinephrine release by desipramine reduces myocardial infarction size

2006 ◽  
Vol 84 (11) ◽  
pp. 1185-1189 ◽  
Author(s):  
Doreen Richardt ◽  
Andreas Dendorfer ◽  
Ralph Tölg ◽  
Peter Dominiak ◽  
Gert Richardt
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Coronary Occlusion ◽  
Tricyclic Antidepressant ◽  
In Vivo Model ◽  
Norepinephrine Release ◽  
Area At Risk ◽  
Transport Direction

During myocardial ischemia, a substantial accumulation of norepinephrine occurs in the ischemic zone due to a local nonexocytotic release of norepinephrine. Norepinephrine release is driven by the neuronal monoamine transporter (NET), which reverses its usual transmembrane transport direction. We investigated whether this local accumulation of norepinephrine contributes to irreversible myocardial injury in an in vivo model of myocardial infarction. Male, anaesthetized Wistar rats were subjected to 30 min coronary occlusion and subsequent 120 min reperfusion. Five minutes prior to coronary occlusion, the NET inhibitor desipramine was administered intravenously. Infarct size (IS) was determined by TTC-staining and was related to the area at risk (AAR). The influence of desipramine on cardiac norepinephrine release was investigated in isolated perfused hearts with 30 min of regional ischemia. Norepinephrine was measured in the effluent from the hearts by HPLC and electrochemical detection. Desipramine (0.1–0.8 mg/kg) dose-dependently reduced infarct size (IS/AAR) from 0.54 to 0.21 and suppressed postischemic norepinephrine release from 245 to 108 pg/mL. In summary, the data indicate that nonexocytotic release of norepinephrine in myocardial ischemia exaggerates acute ischemic damage, because suppression of ischemia-induced release of norepinephrine by the tricyclic antidepressant desipramine effectively reduces infarct size in an in vivo model of myocardial ischemia.

scholarly journals C-Reactive Protein and Complement Are Important Mediators of Tissue Damage in Acute Myocardial Infarction

1999 ◽  
Vol 190 (12) ◽  
pp. 1733-1740 ◽  
Author(s):  
M. Griselli ◽  
J. Herbert ◽  
W.L. Hutchinson ◽  
K.M. Taylor ◽  
M. Sohail ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Myocardial Injury ◽  
Peak Plasma ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Coronary Ligation

Myocardial infarction in humans provokes an acute phase response, and C-reactive protein (CRP), the classical acute phase plasma protein, is deposited together with complement within the infarct. The peak plasma CRP value is strongly associated with postinfarct morbidity and mortality. Human CRP binds to damaged cells and activates complement, but rat CRP does not activate complement. Here we show that injection of human CRP into rats after ligation of the coronary artery reproducibly enhanced infarct size by ∼40%. In vivo complement depletion, produced by cobra venom factor, completely abrogated this effect. Complement depletion also markedly reduced infarct size, even when initiated up to 2 h after coronary ligation. These observations demonstrate that human CRP and complement activation are major mediators of ischemic myocardial injury and identify them as therapeutic targets in coronary heart disease.

Morphine Enhances Pharmacological Preconditioning by Isoflurane

2003 ◽  
Vol 98 (3) ◽  
pp. 705-711 ◽  
Author(s):  
Lynda M. Ludwig ◽  
Hemal H. Patel ◽  
Garrett J. Gross ◽  
Judy R. Kersten ◽  
Paul S. Pagel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Potassium Channels ◽  
Infarct Size ◽  
Adenosine Triphosphate ◽  
Opioid Receptors ◽  
Myocardial Infarct ◽  
Coronary Artery Occlusion ◽  
Myocardial Infarct Size ◽  
Area At Risk

Background Adenosine triphosphate-regulated potassium channels mediate protection against myocardial infarction produced by volatile anesthetics and opioids. We tested the hypothesis that morphine enhances the protective effect of isoflurane by activating mitochondrial adenosine triphosphate-regulated potassium channels and opioid receptors. Methods Barbiturate-anesthetized rats (n = 131) were instrumented for measurement of hemodynamics and subjected to a 30 min coronary artery occlusion followed by 2 h of reperfusion. Myocardial infarct size was determined using triphenyltetrazolium staining. Rats were randomly assigned to receive 0.9% saline, isoflurane (0.5 and 1.0 minimum alveolar concentration [MAC]), morphine (0.1 and 0.3 mg/kg), or morphine (0.3 mg/kg) plus isoflurane (1.0 MAC). Isoflurane was administered for 30 min and discontinued 15 min before coronary occlusion. In eight additional groups of experiments, rats received 5-hydroxydecanoic acid (5-HD; 10 mg/kg) or naloxone (6 mg/kg) in the presence or absence of isoflurane, morphine, and morphine plus isoflurane. Results Isoflurane (1.0 MAC) and morphine (0.3 mg/kg) reduced infarct size (41 +/- 3%; n = 13 and 38 +/- 2% of the area at risk; n = 10, respectively) as compared to control experiments (59 +/- 2%; n = 10). Morphine plus isoflurane further decreased infarct size to 26 +/- 3% (n = 11). 5-HD and naloxone alone did not affect infarct size, but abolished cardioprotection produced by isoflurane, morphine, and morphine plus isoflurane. Conclusions Combined administration of isoflurane and morphine enhances the protection against myocardial infarction to a greater extent than either drug alone. This beneficial effect is mediated by mitochondrial adenosine triphosphate-regulated potassium channels and opioid receptors in vivo.

Optimization of a blood pool contrast agent injection protocol for MR angiography

2005 ◽  
Vol 21 (5) ◽  
pp. 611-619 ◽  
Author(s):  
Philippe Robert ◽  
Xavier Violas ◽  
Robin Santus ◽  
Denis Le Bihan ◽  
Claire Corot
Keyword(s):  
Contrast Agent ◽  
Mr Angiography ◽  
Blood Pool ◽  
Blood Pool Contrast Agent ◽  
Contrast Agent Injection ◽  
Injection Protocol
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