127 research outputs found

    Diabetes mellitus and the metabolic syndrome do not abolish, but might reduce, the cardioprotective effect of ischemic postconditioning

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    ObjectiveIschemic preconditioning fails to protect the diabetic heart against lethal reperfusion injury. Because the pathways of ischemic pre- and postconditioning partially overlap, we evaluated the cardioprotective effect of ischemic postconditioning in mouse models of type 2 diabetes (ObOb) and the metabolic syndrome (DKO).MethodsMice (C57BL/6J, ObOb, and DKO; aged 24 weeks; n = 24, n = 28, and n = 18, respectively) underwent reperfusion after 30 minutes of coronary occlusion with or without ischemic postconditioning (3 cycles of 10 seconds reperfusion–reocclusion). Left ventricular contractility and infarct size were assessed 60 minutes later with pressure conductance analysis and 2,3,5-triphenyl-tetrazolium chloride staining, respectively. In a second cohort (C57BL/6J and DKO; aged 12 weeks; n = 31 and n = 24, respectively) cardiac cine magnetic resonance imaging was performed after 1 and 10 weeks, followed by pressure conductance analysis and Sirius red staining.ResultsIn the C57BL6/J mice, the infarct size was lower (40%, P < 10−5) and the load independent preload recruitable stroke work was greater after ischemic postconditioning (P < .05). In the ObOb and DKO mice, ischemic postconditioning reduced the infarct size by 24% (P < 10−5). In the C57BL/6J mice, the ejection fraction was greater and the myocardial mass was lower 10 weeks after ischemic postconditioning (P < .05). Tagging grid deformation was increased after ischemic postconditioning in both infarcted and remote areas. After ischemic postconditioning, the survival and ejection fraction were greater in the DKO mice (67% vs 17% and 44% ± 11% vs 59% ± 2%, P < .05 for both), and the collagen content was lower for both C57BL/6J and DKO mice (P < .05 for both).ConclusionsThe cardioprotective effect of ischemic postconditioning was sustained in C57BL/6J mice after 10 weeks and protected against adverse left ventricular remodeling. In mouse models of type 2 diabetes, protection against lethal reperfusion injury is present, leading to increased survival after ischemia and reperfusion

    Imaging ischemic and reperfusion injury in acute myocardial infarction putting the pieces together with CMR

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    rom the a Department of Imaging and Pathology, KU Leuven – University of Leuven, Leuven, Belgium; b Lab on Cardiovascular Imaging and Dynamics, Department of Cardiovascular Sciences, KU Leuven – University of Leuven, Leuven, Belgium; c Life and Health Sciences Research Institute/Biomaterials, Biodegradables and Biomimetics Research Group — Portugal Government Associate Laboratory, Braga/Guimarães, Portugal; d Instituto de Engenharia Mecânica e Gestão Industrial, Faculdade de Engenharia, Universidade do Porto, Porto, Portugal; and the e Medical Imaging Research Center, ESAT-PSI, Processing Speech and Images (PSI), Department of Electrical Engineering (ESAT), KU Leuven, Leuven, Belgium. Dr. Morais has received funding for his PhD scholarship (FCT — Fundacão para a Ciência e a Tecnologia, Portugal, for funding support through the Programa Operacional Capital Humano in the scope of the PhD grant SFRH/BD/95438/2013). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.info:eu-repo/semantics/publishedVersio

    PET imaging of TSPO in a rat model of local neuroinflammation induced by intracerebral injection of lipopolysaccharide.

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    OBJECTIVE: The goal of this study was to measure functional and structural aspects of local neuroinflammation induced by intracerebral injection of lipopolysaccharide (LPS) in rats using TSPO microPET imaging with [(18)F]DPA-714, magnetic resonance imaging (MRI), in vitro autoradiography and immunohistochemistry (IHC) in order to characterize a small animal model for screening of new PET tracers targeting neuroinflammation. METHODS: Rats were injected stereotactically with LPS (50 μg) in the right striatum and with saline in the left striatum. [(18)F]DPA-714 microPET, MRI, in vitro autoradiography and IHC studies were performed at different time points after LPS injection for 1 month. RESULTS: Analysis of the microPET data demonstrated high uptake of the tracer in the LPS injected site with an affected-to-non-affected side-binding potential ratio (BPright-to-left) of 3.0 at 3 days after LPS injection. This BP ratio decreased gradually over time to 0.9 at 30 days after LPS injection. In vitro autoradiography ([(18)F]DPA-714) and IHC (CD68, GFAP and TSPO) confirmed local neuroinflammation in this model. Dynamic contrast enhanced (DCE) MRI demonstrated BBB breakdown near the LPS injection site at day 1, which gradually resolved over time and was absent at 1 month after LPS injection. CONCLUSION: The LPS model is useful for first screening of newly developed tracers because of the easy design and the robust, unilateral inflammatory reaction allowing the use of the contralateral region as control. Additionally, this model can be used to test and follow up the benefits of anti-inflammatory therapies by non-invasive imaging

    Quantitative Assessment of Age-Associated Alterations in Brain Vasculature in Wild-Type Mice and in Bigenic Mice that Model Alzheimer's Disease

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    PURPOSE: Vascular dysfunction is a major hallmark of Alzheimer's disease (AD). However, studies that investigated vascular dysfunction in mice modeling AD using magnetic resonance angiography (MRA) are typically limited to qualitative and/or scoring-based paradigms, which are labor-intensive and observer-dependent. PROCEDURES: We developed and validated a semi-automatic MRA processing pipeline and applied this to high-resolution in vivo MRA images acquired on a 9.4T small animal MRI scanner. We assessed vascular morphology at 3, 6, and 12 months in wild-type (WT) and bigenic (APP.V717IxTau.P301L: biAT) mice. RESULTS: Vessel radius or length can increase with age regardless of genotype depending on the respective vessel. We also observed significantly lower internal carotid artery length in biAT mice compared to WT. CONCLUSIONS: The results demonstrate that even subtle changes in vessel morphology can be noninvasively quantified. This is of great interest for AD, but also to other models of neurodegenerative diseases involving macrovascular dysfunction.status: publishe

    Magnetic resonance imaging and spectroscopy methods for molecular imaging

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    Magnetic resonance imaging (MRI), one of the most powerful imaging modalities available for clinical diagnosis, has contributed significantly to phenotyping of transgenic organisms and to cellular imaging and is now gaining importance in the field of molecular imaging. Its advantage is the ability to provide in vivo information with high resolution and good soft tissue contrast as compared to established other molecular imaging methods. MRI can non-invasively report on cell localisation and migration with detailed anatomical background information, which is of great interest in cellular therapies. Recent technological advances and contrast generation strategies aim to bring MRI beyond cellular imaging to the detection of functional changes in vivo. MR based monitoring of molecular processes, requires the development of contrast agents and targeting methods as well as improvements in the methods sensitivity. Here, an overview is provided on advanced MR technologies and contrast generation strategies for this purpose. This includes MRI and MR spectroscopic methods for molecular imaging and various approaches for targeted and responsive contrast generation to visualize functional changes of particular cells. A description of different methods is provided, as well as the potentials and challenges of MR techniques for the visualization of molecular processes in vivo.status: publishe

    Quantitative and qualitative assessment of acute myocardial injury by CMR at multiple time points after acute myocardial infarction

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    BACKGROUND: Recent experimental studies have shown a dynamic time course of myocardial edema with an initial wave of edematous reaction within hours after reperfusion which almost resolved at 24 h. However, this dynamic pattern appears to be absent in clinical cohort studies. Thus far, no studies have combined a quantitative and qualitative assessment of acute myocardial injury in a large clinical cohort to explain these divergent findings. METHODS: A cohort of 225 patients (59 ± 11 years, 83% men) with successfully reperfused STEMI within 12 h of symptom onset were included. Quantitative measurements of myocardial damage such as T1 mapping and T2 triple short-tau inversion recovery (STIR), contrast-to-noise ratio (CNR) and their impact on area-at-risk (AAR), infarct size (IS), and myocardial salvage index (MSI) were assessed at different time points. One-way analysis of variance (ANOVA) and linear regression analysis was used to compare myocardial damage at the different time points. RESULTS: A small fraction of patients underwent CMR within 24 h of reperfusion (17/225, 7.6%). No significant variations in AAR, IS, MSI, T2 STIR CNR, or native T1 maps were observed between the different time points after reperfusion. Time of CMR was not a significant predictor of AAR (P = 0.90), IS (P = 0.27), MSI (P = 0.23) or T2 STIR CNR (P = 0.23). CONCLUSIONS: The majority of CMR exams in STEMI patients are performed outside the dynamic time window of early post-MI edema. The stable pattern of markers of acute myocardial damage at different time points suggests these markers are reliable for the prognostication of patients after STEMI.status: publishe

    Increased cortical volume revealed by atlas-based volumetry in a bigenic mouse model of alzheimer's disease

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    Govaerts K., Rangarajan J.R., Struys T., Van Leuven F., Dresselaers T., Himmelreich U., ''Increased cortical volume revealed by atlas-based volumetry in a bigenic mouse model of alzheimer's disease'', 7th annual meeting of the ISMRM Benelux Chapter, January 16, 2015, Ghent, Belgium.status: publishe
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