Abstract 95: Longitudinal In Vivo Quantification of Infarct Size and Cardiac Function in a Murine Model of Myocardial Infarction using Novel Compact High-Performance MRI

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Tonya Coulthard ◽  
Jun Wu
Keyword(s):  
Cardiac Function ◽  
Infarct Size ◽  
Contrast Agents ◽  
Coronary Revascularization ◽  
Myocardial Strain ◽  
Cine Mri ◽  
Peak Strain ◽  
Contrast Imaging ◽  
Increased Sensitivity

Intro: Delayed Enhancement Imaging (DEI) characterizes MI and predicts therapeutic efficacy following coronary revascularization, stem cell transplantation, or other procedures. Typically gadolinium-based (Gd) contrast agents are injected intravenously and accumulate in the lesion, differentiating between normal and diseased myocardium. Traditionally, DEI has been explored using superconducting high-field MRI. Using a novel compact MRI at 1 Tesla, there is increased sensitivity to Gd-based contrast agents compared with higher-field MRI systems. Hypothesis: In this study, DEI on a compact MRI system was employed with spatial intensity analysis to measure infarct size. Tagged cine MRI assessed myocardial strain using the HARP method. Post-mortem histology of Masson Trichrome staining estimated infarct size. Correlation analysis determined relationships between infarct size measured via DEI and histology. Methods: C57BL/6 MI mice had ligation of the left anterior descending artery. Four sham control and five MI mice we imaged using compact MRI (ICON compact MRI, Billerica, MA) and monitored longitudinally over 21 days for infarct progression and cardiac function in vivo. DE imaging was performed 10-20 minutes post injection of 2 μL Gd contrast agent (ProHance, 0.5 mmol/ml). Images were acquired in short axis, 1 mm superior to the apex. Post-processing analysis (pcVirtue, Diagnosoft, Morrisville, NC) measured cardiac function and infarct size. Results and Conclusions: Analyses of DEI data indicate an average infarct size of 24.85 +/- 15.09 % in the left ventricle. One week after MI induction, a much lower EF was observed in MI mice with respect to control (35.3 +/- 7.567% vs. 67.3 +/- 1.6 %), with a slight recovery of cardiac function in MI mice by week 3 (EF = 45.5 +/- 3.1%). Strain analysis also indicated significantly lower average peak strain in MI vs control mice (6.9 +/- 4.3 vs. 21.5 +/- 0.4 %). Preliminary results demonstrate successful monitoring of cardiac function while performing DEI to visualize and quantify MI at 1 Tesla and leverage the benefits of the increased sensitivity of Gd-based contrast imaging with novel compact MRI. Such imaging and analysis techniques could be used to test efficacy of multiple therapeutic interventions.

scholarly journals Quantitative Evaluation On Cardiac Remodeling Mechanism After Intensive Exercise: A Preliminary Study of Non-enhanced Cardiac Cine MRI

2021 ◽  
Author(s):  
hongqin Liang ◽  
Liqiang Zhu ◽  
Bing Ji ◽  
Yongning Shang ◽  
xiaoyue Zhou ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Myocardial Strain ◽  
Strain Analysis ◽  
Exercise Group ◽  
Left Ventricular ◽  
Cine Mri ◽  
Control Group ◽  
Peak Strain ◽  
Functional Parameters ◽  
Time To Peak

Abstract Purpose: High intensity and longtime aerobic exercise may lead to the remodeling of both left and right ventricles with increased myocardial mass and cavity dilatation,which is mainly reflected in the changes of traditional cardiac function parameters.Feature tracking myocardial strain allows quantitative strain analysis of myocardial functionThe purpose was to quantitatively evaluate traditional cardiac function and feature tracking myocardial strain of exercise-induced ,andMaterials and methods: The study included 67 healthy volunteers (21 ± 2 years of age). The exercise group (n=43) who fulfilled our defined exercise criteria. The control group (n=23) who maintained a basic daily life .Noncontrast enhancement CMR scanning were performed on all the subjects using a 3T MRI scanner .Cvi42 software was used for post-processing . Left ventricular cardiac function and overall globle stress were measured.Results: Cardiac function parameters in the exercise group were significantly higher than those of the control group except for the ejection fractions (EFs) and heart rates (HRs). The GRS peak strain and GLS peak diastolic strain rates of both groups were significantly different (P＜0.05).The GRS peak strains and EFs were partly correlated (R=0.61). The GRS peak diastolic strains and cardiac Indices (CIs) were significantly correlated (R=0.68). The GCS and GRS Peak Strains showed highly negative correlations (R=–0.96). The GCS and GRS time to peak values were also highly correlated (R= 0.87). Conclusion:The initial results showed that Changes in the functional parameters were more obvious than in the myocardial strain parameters, and some strain indices were correlated with the cardiac functional parameters,when the remodeling of the heart occurs.This is a new attempt to quantitatively assessment of Cardiac function and strain by Non-contrast-enhanced magnetic resonance.

Abstract 16708: Cathelicidin Related Antimicrobial Peptide Treated Bone Marrow Derived Mononuclear Cells Improves Cardiac Function in a Mouse Model of Acute Myocardial Infarction: Potential Therapeutic Targets in Ischemic Heart Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yuri M Klyachkin ◽  
Prabhakara R Nagareddy ◽  
Ahmed Asfour ◽  
Shaojing Ye ◽  
Erhe Gao ◽  
...  
Keyword(s):  
Heart Disease ◽  
Cardiac Function ◽  
Ischemic Heart Disease ◽  
Infarct Size ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
In Vivo Studies ◽  
Boyden Chamber ◽  
Acute Ischemic Heart Disease

Introduction: Limited stem cell retention following intracoronary administration for ischemic heart disease has reduced the clinical efficacy of this novel therapy. Cathelicidins have been shown to prime BMMNC migration towards low gradients of SDF-1 suggesting a potential role in BMMNC retention. We sought to assess the safety and efficacy of BMMNC pre-treatment with CRAMP for treatment of acute ischemic heart disease. METHODS: BMMNCs isolated from GFP mice were incubated with recombinant CRAMP (2.5 μg/ml) or placebo for 1 hour followed by chemotaxis studies towards low levels of SDF-1 (2 ng/ml) using a Boyden chamber in vitro. During the in vivo studies, mice were randomized into 3 groups: AMI followed by injection of phosphate buffered saline (PBS), BMMNCs alone, or BMMNCs incubated with CRAMP. Scar size, survival and retention of injected BMNNCs were examined by immunohistochemistry at 5 weeks. Left ventricular function was measured by echocardiography at baseline, 48 hours, and 5 weeks after MI. Changes in infarct size between 5 days and 5 weeks after AMI was assessed by cardiac MRI utilizing delayed gadolinium enhancement. RESULTS: Treatment of BMNNCs with CRAMP enhanced their migration towards low, yet physiological, levels of SDF-1 (Fig 1A). In vivo, a greater proportion of cell survival and retention was observed in the BMNNC+CRAMP group than in the BMNNC-alone group (Fig 1B) and this was associated with higher percentage of BrdU positive cells (Fig 1C). Moreover, BMNNC+CRAMP administration led to significantly better survival, improvement of cardiac function (Fig 1D-H) and reduction in infarct size compared with other control groups (Fig 1I). CONCLUSIONS: Cathelicidins enhance BMMNC retention after intramyocardial administration for acute ischemic heart disease resulting in enhanced recovery. Therapies employing this strategy may represent an effective method for improving cardiac recovery and survival rate after AMI in human studies.

Developmental changes of cardiac function and mass assessed with MRI in neonatal, juvenile, and adult mice

2000 ◽  
Vol 278 (2) ◽  
pp. H652-H657 ◽  
Author(s):  
Frank Wiesmann ◽  
Jan Ruff ◽  
Karl-Heinz Hiller ◽  
Eberhard Rommel ◽  
Axel Haase ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Transgenic Mouse ◽  
Mouse Models ◽  
Age Groups ◽  
Left Ventricular ◽  
Cine Mri ◽  
Transgenic Mouse Models ◽  
Adult Mice ◽  
Lv Mass

Cardiovascular transgenic mouse models with an early phenotype or even premature death require noninvasive imaging methods that allow for accurate visualization of cardiac morphology and function. Thus the purpose of our study was to assess the feasibility of magnetic resonance imaging (MRI) to characterize cardiac function and mass in newborn, juvenile, and adult mice. Forty-five C57bl/6 mice from seven age groups (3 days to 4 mo after birth) were studied by MRI under isoflurane anesthesia. Electrocardiogram-gated cine MRI was performed with an in-plane resolution of (78–117 μm)2. Temporal resolution per cine frame was 8.6 ms. MRI revealed cardiac anatomy in mice from all age groups with high temporal and spatial resolution. There was close correlation between MRI- and autopsy-determined left ventricular (LV) mass ( r = 0.95, SE of estimate = 9.5 mg). The increase of LV mass (range 9.6–101.3 mg), cardiac output (range 1.1–14.3 ml/min), and stroke volume (range 3.2–40.2 μl) with age could be quantified by MRI measurements. Ejection fraction and cardiac index did not change with aging. However, LV mass index decreased with increasing age ( P < 0.01). High-resolution MRI allows for accurate in vivo assessment of cardiac function in neonatal, juvenile, and adult mice. This method should be useful when applied in transgenic mouse models.

scholarly journals Bone marrow-derived stromal cells home to and remain in the infarcted rat heart but fail to improve function: an in vivo cine-MRI study

2008 ◽  
Vol 295 (2) ◽  
pp. H533-H542 ◽  
Author(s):  
Carolyn A. Carr ◽  
Daniel J. Stuckey ◽  
Louise Tatton ◽  
Damian J. Tyler ◽  
Sarah J. M. Hale ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Therapy ◽  
Cardiac Function ◽  
Stromal Cells ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cine Mri ◽  
Iron Oxide Particles ◽  
Ventricular Ejection Fraction

Basic and clinical studies have shown that bone marrow cell therapy can improve cardiac function following infarction. In experimental animals, reported stem cell-mediated changes range from no measurable improvement to the complete restoration of function. In the clinic, however, the average improvement in left ventricular ejection fraction is around 2% to 3%. A possible explanation for the discrepancy between basic and clinical results is that few basic studies have used the magnetic resonance (MR) imaging (MRI) methods that were used in clinical trials for measuring cardiac function. Consequently, we employed cine-MR to determine the effect of bone marrow stromal cells (BMSCs) on cardiac function in rats. Cultured rat BMSCs were characterized using flow cytometry and labeled with iron oxide particles and a fluorescent marker to allow in vivo cell tracking and ex vivo cell identification, respectively. Neither label affected in vitro cell proliferation or differentiation. Rat hearts were infarcted, and BMSCs or control media were injected into the infarct periphery ( n = 34) or infused systemically ( n = 30). MRI was used to measure cardiac morphology and function and to determine cell distribution for 10 wk after infarction and cell therapy. In vivo MRI, histology, and cell reisolation confirmed successful BMSC delivery and retention within the myocardium throughout the experiment. However, no significant improvement in any measure of cardiac function was observed at any time. We conclude that cultured BMSCs are not the optimal cell population to treat the infarcted heart.

Anti-Apoptotic Effect of Magnolol in Myocardial Ischemia and Reperfusion Injury Requires Extracellular Signal-Regulated Kinase1/2 Pathways in Rat In Vivo

2008 ◽  
Vol 233 (10) ◽  
pp. 1280-1288 ◽  
Author(s):  
Yong Chun Jin ◽  
Kil Jung Kim ◽  
Young Min Kim ◽  
Yu Mi Ha ◽  
Hye Jung Kim ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Infarct Size ◽  
Function Analysis ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion

Magnolol, an active component extracted from Magnolia officinalis, has been reported to have protective effect on ischemia and reperfusion (I/R)-induced injury in experimental animals. The aim of the present investigation was to further evaluate the mechanism(s) by which magnolol reduces I/R-induced myocardial injury in rats in vivo. Under anesthesia, left anterior descending (LAD) coronary artery was occluded for 30 min followed by reperfusion for 24 h (for infarct size and cardiac function analysis). In some experiments, reperfusion was limited to 1 h or 6 h for analysis of biochemical and molecular events. Magnolol and DMSO solution (vehicle) were injected intra-peritoneally 1 h prior to I/R insult. The infarct size was measured by TTC technique and heart function was monitored by Millar Catheter. Apoptosis related events such as p-ERK, p-Bad, Bcl-xl and cytochrome c expression were evaluated by Western blot analysis and myocardial caspase-3 activity was also measured. Magnolol (10 mg/kg) reduced infarct size by 50% ( P < 0.01 versus vehicle), and also improved I/R-induced myocardial dysfunction. Left ventricular systolic pressure and positive and negative maximal values of the first derivative of left ventricular pressure (dP/dt) were significantly improved in magnolol-treated rats. Magnolol increased the expression of phosphor ERK and Bad which resulted in inhibition of myocardial apoptosis as evidenced by TUNEL analysis and DNA laddering experiments. Application of PD 98059, a selective MEK1/2 inhibitor, strongly antagonized the effect of magnolol. Taken together, we concluded that magnolol inhibits apoptosis through enhancing the activation of ERK1/2 and modulation of the Bcl-xl proteins which brings about reduction of infarct size and improvement of cardiac function in I/R-induced injury.

scholarly journals Ultrafast amplitude modulation for molecular and hemodynamic ultrasound imaging

2021 ◽  
Author(s):  
Claire Rabut ◽  
Di Wu ◽  
Bill Ling ◽  
Zhiyang Jin ◽  
Dina Malounda ◽  
...  
Keyword(s):  
Contrast Agents ◽  
Amplitude Modulation ◽  
Imaging Modality ◽  
Pulse Sequences ◽  
Frame Rate ◽  
Wide Field ◽  
Contrast Imaging ◽  
Rapid Discrimination

Ultrasound is playing an emerging role in molecular and cellular imaging thanks to new micro- and nanoscale contrast agents and reporter genes. Acoustic methods for the selective in vivo detection of these imaging agents are needed to maximize their impact in biology and medicine. Existing ultrasound pulse sequences use the nonlinearity in contrast agents response to acoustic pressure to distinguish them from mostly linear tissue scattering. However, such pulse sequences typically scan the sample using focused transmissions, resulting in a limited frame rate and restricted field of view. Meanwhile, existing wide-field scanning techniques based on plane wave transmissions suffer from limited sensitivity or nonlinear artifacts. To overcome these limitations, we introduce an ultrafast nonlinear imaging modality combining amplitude-modulated pulses, multiplane wave transmissions and selective coherent compounding. This technique achieves contrast imaging sensitivity comparable to much slower gold-standard amplitude modulation sequences and enables the acquisition of larger and deeper fields of view, while providing a much faster imaging framerate of 3.2kHz. Additionally, it enables simultaneous nonlinear and linear image formation, and allows concurrent monitoring of phenomena accessible only at ultrafast framerates, such as blood volume variations. We demonstrate the performance of this ultrafast amplitude modulation (uAM) technique by imaging gas vesicles, an emerging class of genetically encodable biomolecular contrast agents, in several in vitro and in vivo contexts. These demonstrations include the rapid discrimination of moving contrast agents and the real-time monitoring of phagolysosomal function in the mouse liver.

scholarly journals Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction

2021 ◽  
Vol 8 ◽  
Author(s):  
Yijin Wu ◽  
Min Wu ◽  
Jue Yang ◽  
Ying Li ◽  
Wenying Peng ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Infarct Size ◽  
Cardiac Dysfunction ◽  
Harmful Effect ◽  
Akt Pathway ◽  
Circular Rnas ◽  
Cerna Network ◽  
Myocardial Apoptosis

The ceRNA network involving circular RNAs (circRNAs) is essential in the cardiovascular system. We investigated the underlying ceRNA network involving circHIPK3 in myocardial infarction (MI). After an MI model was established, cardiac function was verified, and myocardial tissue damage in mice with MI was evaluated. A hypoxia model of cardiomyocytes was used to simulate MI in vivo, and the expression of and targeting relationships among circHIPK3, miR-93-5p, and Rac1 were verified. The apoptosis of cardiomyocyte was identified. Gain- and loss-of-functions were performed to verify the ceRNA mechanism. The MI-modeled mice showed cardiac dysfunction and enlarged infarct size. CircHIPK3 was highly expressed in mouse and cell models of MI. Silencing circHIPK3 reduced infarct size, myocardial collagen deposition, and myocardial apoptosis rate and improved cardiac function. CircHIPK3 sponged miR-93-5p, and miR-93-5p targeted Rac1. Overexpression of miR-93-5p inhibited MI-induced cardiomyocyte injury and eliminated the harmful effect of circHIPK3. CircHIPK3 acted as ceRNA to absorb miR-93-5p, thus promoting the activation of the Rac1/PI3K/AKT pathway. We highlighted that silencing circHIPK3 can upregulate miR-93-5p and then inhibit the activation of Rac1/PI3K/Akt pathway, which can improve MI-induced cardiac dysfunction.

Ultrasound -Triggered Drug Delivery with Contrast Imaging: Effect of Microencapsulation Method

1998 ◽  
Vol 550 ◽  
Author(s):  
M.A. Wheatley ◽  
D. El-Sherif ◽  
R. Basude ◽  
R. Shimp ◽  
P. Narayan
Keyword(s):  
Drug Delivery ◽  
Contrast Agents ◽  
Drug Loading ◽  
Blood Stream ◽  
Solid Core ◽  
Contrast Imaging ◽  
Fda Approval ◽  
Polymeric Microcapsules ◽  
Spray Dried

AbstractA method for preparation of hollow, biodegradable polymeric microcapsules for use as contrast agents is described, and strategies for their use in concomitant imaging and drug delivery are outlined. Compared with X-ray or magnetic resonance imaging, diagnostic ultrasound is a safe, relatively inexpensive imaging technique, which allows the physician to view real-time images. Contrast agents are being developed which will greatly enhance the contrast of the received image, when injected into the patients blood stream. We have developed hollow polymeric CA based upon the ability to microencapsulate a solid core of ammonium carbonate which is then removed by decomposition and freeze-drying. The polymer poly D,L(lactide-co-glycolide) (PLGA) was chosen for it's FDA approval, and because it has the most rapid in vivo degradation of the α-hydroxy acid series. Spray dried and solvent extraction samples were used to test the concept of concomitant drug delivery and imaging. The method of fabrication had an important effect on the drug loading by adsorption, and on the amount of drug that was released when the capsules were insonated with ultrasound in the medical imaging range. Both were greater for spray dried samples. Both frequency and pressure of insonation also influenced release. The most dramatic increase in release was after 5 minutes for the 10 Mhz low (1.25 MPa) pressure insonation, which showed 316% greater release than control, a total of 1.89 mg.

scholarly journals Hyperpolarized Magnetic Resonance Shows that the Anti-Ischemic Drug, Meldonium, Leads to Increased Flux Through Pyruvate Dehydrogenase In Vivo Resulting in Improved Post-Ischemic Function in the Diabetic Heart.

2020 ◽  
Author(s):  
Dragana Savic ◽  
Vicky Ball ◽  
Lorenz Holzner ◽  
David Hauton ◽  
Kerstin Timm ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Cardiac Function ◽  
Pyruvate Dehydrogenase ◽  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Diabetic Heart ◽  
Cine Mri ◽  
And Control ◽  
The Impact

Abstract Background: The diabetic heart has a decreased ability to metabolize glucose. The anti-ischemic drug, Meldonium, may provide a route to counteract this by reducing L-carnitine levels, resulting in improved cardiac glucose utilization. Therefore, the aim of this study was to use the novel technique of hyperpolarized magnetic resonance to investigate the in vivo effects of treatment with Meldonium on cardiac metabolism and function in control and diabetic rats. Methods: 36 male Wistar rats were injected with either placebo or streptozotocin (55mg/kg) to induce a model of type-1 diabetes. Daily treatment with either saline or Meldonium (100mg/kg/day) was undertaken for three weeks. In vivo cardiac function and metabolism were assessed with CINE MRI and hyperpolarized magnetic resonance respectively. Isolated perfused hearts were challenged with low-flow ischemia/reperfusion to assess the impact of Meldonium on post-ischemic recovery.Results: Meldonium had no significant effect on blood glucose levels or on baseline cardiac function. However, hyperpolarized magnetic resonance revealed that Meldonium treatment elevated pyruvate dehydrogenase flux by 3.1-fold and 1.2-fold in diabetic and control animals respectively, indicating an increase in cardiac glucose oxidation. Hyperpolarized magnetic resonance further demonstrated that Meldonium reduced acetylcarnitine by 2.1-fold in both diabetic and control animals. The increase in in vivo glucose oxidation was accompanied by an improvement in ex vivo post-ischemic function, where Meldonium elevated rate pressure product by 1.3-fold and 1.5-fold in the control and diabetic animals respectively. Conclusion: Meldonium improves in vivo glucose utilization in the diabetic heart, contributing to improved cardiac recovery post-ischemia.

Abstract 167: Genetic Deletion of p66Shc Adaptor Protein Leads to Increased Myocardial Infarction by Inhibiting RISK and SAFE Prosurvival Pathways

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Alexander Akhmedov ◽  
Vincent Braunersreuther ◽  
Fabrizio Montecucco ◽  
Philip Jakob ◽  
Giovanni G Camici ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Adaptor Protein ◽  
Increased Sensitivity ◽  
Genetic Deletion ◽  
Few Data ◽  
Protein Kinase Akt

Background— Formation of reactive oxygen species (ROS) contributes to many pathophysiological processes. Although ROS production is also involved in some physiological processes, the imbalance between their generation and removal, i.e. oxidative stress, plays a major role in particular in myocardial injury caused by ischemia-reperfusion (I/R). The mammalian Shc locus encodes three Shc isoforms: p46 Shc , p52 Shc and p66 Shc . The p66 Shc is not involved in mitogenic signals as p46 Shc /p52 Shc , but it functions as a critical mediator of intracellular oxidative signal transduction. Various studies relate p66 Shc to cardiovascular disease; however, few data are available on the role of p66 Shc in myocardial I/R. Methods and Results— 8-12-week-old male p66 Shc deficient ( p66 Shc-/- ) mice and corresponding C57Bl/6 wild-type (WT) control mice were subjected in vivo to different durations of ischemia (30, 45 and 60 min) followed by 24h of reperfusion. Infarct size was assessed morphologically and by MRI. After 30 min of ischemia, p66 Shc-/- mice developed markedly larger infarcts as compared to WT. This effect was confirmed by in vivo silencing of p66 Shc prior to I/R. Both genetic deletion and silencing of p66 Shc displayed increased post-ischemic levels of serum cardiac troponin I (cTnI). However, the observed effect on infarct size was limited to 30 min of ischemia since by increasing ischemia duration to either 45 or 60 min infarct size did no longer differ between p66 Shc-/- and WT mice. Moreover, differently from WT, infarct size in p66 Shc-/- was not significantly larger with increasing duration of ischemia (from 30 to 60 min). On the molecular level the observed effect was linked to the inhibition of activation by phosphorylation of protein kinase Akt and transcription factor STAT3 - two key members of prosurvival pathways RISK and SAFE, respectively. Conclusions— Our data suggest that genetic deletion of p66 Shc leads to an increased sensitivity to myocardial infarction with larger infarcts with shorter, but not prolonged ischemia, and that RISK and SAFE prosurvival pathways are involved. Therefore, activation of p66 Shc may provide resistance to ischemia and represent a novel therapeutic target in the early phase of myocardial infarction.

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