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Background--The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI 18F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of 18F-FDG positron emission tomography/ magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. Methods and Results--We prospectively enrolled 49 patients with ST-segment-elevation myocardial infarction and performed 18F-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, 99mTcsestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of 18F-FDG-uptake and late gadolinium enhancement showed substantial overlap (κ=0.66), whereas quantitative analysis demonstrated that 18F-FDG extent exceeded late gadolinium enhancement extent (33.2±16.2% left ventricular myocardium versus 20.4±10.6% left ventricular myocardium, P<0.0001) and corresponded to the area at risk (r=0.87, P<0.0001). The peripheral blood count of CD14high/CD16+ monocytes correlated with the infarction size and 18F-FDG signal extent (r=0.53, P<0.002 and r=0.42, P<0.02, respectively). 18F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar, and the standardized uptake valuemean was associated with left ventricular functional outcome independent of infarct size (Δ ejection fraction: P<0.04, Δ end-diastolic volume: P<0.02, Δ end-systolic volume: P<0.005). Conclusions--In this study, the intensity of 18F-FDG uptake in the myocardium after acute myocardial infarction correlated inversely with functional outcome at 6 months. Thus, 18F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury. [ABSTRACT FROM AUTHOR]

Aims F-18 fluorodeoxyglucose (FDG) myocardial PET imaging is since more than two decades considered to delineate glucose utilization in dysfunctional but viable cardiomyocytes. Late gadolinium enhancement (LGE) MRI was introduced more than a decade ago and identifies increased extravascular space in areas of infarction and scar. Although the physiological foundation differs, both approaches are valuable in the prediction of functional outcome of the left ventricle, but synergistic effects are yet unknown. We aimed to compare the improvement of LV function after 6 months based on the regional FDG uptake and the transmurality of scar by LGE in patients early after acute myocardial infarction (AMI). Methods and results Twenty-eight patients with primary AMI underwent simultaneous PET/MRI for assessment of regional FDG uptake and degree of LGE transmurality 5-7 days after PCI. Follow-up by MRI was performed in 20 patients 6 months later. Myocardium was defined 'PET viable' based on the established threshold of ≥50% FDG uptake compared with remote myocardium or as 'MRI viable' when LGE transmurality of ≤50% was present. Regional wall motion was measured by MRI. Ninety-five dysfunctional segments were further analysed regarding regional wall motion recovery. There was a substantial intermethod agreement for segmental LGE transmurality and reduction of FDG uptake (κ = 0.65). 'PET viable' and 'MRI viable' segments showed a lower wall motion abnormality score (PET: initial: 1.4 ± 0.6 vs. 1.9 ± 0.8, P < 0.008; follow-up: 0.5 ± 0.7 vs. 1.5 ± 1.0, P < 0.0001; MRI: initial: 1.5 ± 0.6 vs. 2.0 ± 0.8, P < 0.002; follow-up: 0.7 ± 0.8 vs. 1.6 ± 1.0, P < 0.0001) and a better regional wall motion improvement (PET: -0.9 ± 0.7 vs. -0.4 ± 0.7, P < 0.0007; MRI: -0.8 ± 0.7 vs. -0.4 ± 0.7, P < 0.009) compared with 'PET non-viable' or 'MRI non-viable' segments, respectively. Eighteen per cent of the dysfunctional segments showed discrepant findings ('PET non-viable' but 'MRI viable'). At follow-up, the regional wall motion of these segments was inferior compared with 'PET viable/MRI viable' segments (1.1 ± 0.8 vs. 0.5 ± 0.7, P < 0.01), had an inferior functional recovery (-0.5 ± 0.6 vs. -0.9 ± 0.7, P < 0.03), but showed no difference compared with concordant 'PET non-viable/MRI non-viable' segments. Conclusion The simultaneous assessment of LGE and FDG uptake using a hybrid PET/MRI system is feasible. The established PET and MRI 'viability' parameter prior to revascularization therapy also predicts accurately the regional outcome of wall motion after AMI. In a small proportion of segments with discrepant FDG PET and LGE MRI findings, FDG uptake was a better predictor for functional recovery. [ABSTRACT FROM AUTHOR]

Current knowledge about the molecular mechanisms of NMDA receptor (NMDAR)-independent long-term potentiation (LTP) in the hippocampus and its function for memory formation in the behaving animal is limited. NMDAR-independent LTP in the CA1 region is thought to require activity of postsynaptic L-type voltage-dependent Ca2+ channels (Cav1.x), but the underlying channel isoform remains unknown. We evaluated the function of the Cav1.2 L-type Ca2+ channel for spatial learning, synaptic plasticity, and triggering of learning-associated biochemical processes using a mouse line with an inactivation of the CACNA1C(Cav1.2) gene in the hippocampus and neocortex (Cav1.2HCKO). This model shows (1) a selective loss of protein synthesis-dependent NMDAR-independent Schaffer collateral/ CA1 late-phase LTP (L-LTP), (2) a severe impairment of hippocampus-dependent spatial memory, and (3) decreased activation of the mitogen-activated protein kinase (MAPK) pathway and reduced cAMP response element (CRE)-dependent transcription in CA1 pyramidal neurons. Our results provide strong evidence for a role of L-type Ca2+ channel-dependent, NMDAR-independent hippocampal L-LTP in the formation of spatial memory in the behaving animal and for a function of the MAPK/CREB (CRE-binding protein) signaling cascade in linking Cav1.2 channel-mediated Ca2+ influx to either process. [ABSTRACT FROM AUTHOR]

Aims: F-18 fluorodeoxyglucose (FDG) myocardial PET imaging is since more than two decades considered to delineate glucose utilization in dysfunctional but viable cardiomyocytes. Late gadolinium enhancement (LGE) MRI was introduced more than a decade ago and identifies increased extravascular space in areas of infarction and scar. Although the physiological foundation differs, both approaches are valuable in the prediction of functional outcome of the left ventricle, but synergistic effects are yet unknown. We aimed to compare the improvement of LV function after 6 months based on the regional FDG uptake and the transmurality of scar by LGE in patients early after acute myocardial infarction (AMI)., Methods and Results: Twenty-eight patients with primary AMI underwent simultaneous PET/MRI for assessment of regional FDG uptake and degree of LGE transmurality 5-7 days after PCI. Follow-up by MRI was performed in 20 patients 6 months later. Myocardium was defined 'PET viable' based on the established threshold of ≥ 50% FDG uptake compared with remote myocardium or as 'MRI viable' when LGE transmurality of ≤ 50% was present. Regional wall motion was measured by MRI. Ninety-five dysfunctional segments were further analysed regarding regional wall motion recovery. There was a substantial intermethod agreement for segmental LGE transmurality and reduction of FDG uptake (κ = 0.65). 'PET viable' and 'MRI viable' segments showed a lower wall motion abnormality score (PET: initial: 1.4 ± 0.6 vs. 1.9 ± 0.8, P < 0.008; follow-up: 0.5 ± 0.7 vs. 1.5 ± 1.0, P < 0.0001; MRI: initial: 1.5 ± 0.6 vs. 2.0 ± 0.8, P < 0.002; follow-up: 0.7 ± 0.8 vs. 1.6 ± 1.0, P < 0.0001) and a better regional wall motion improvement (PET: -0.9 ± 0.7 vs. -0.4 ± 0.7, P < 0.0007; MRI: -0.8 ± 0.7 vs. -0.4 ± 0.7, P < 0.009) compared with 'PET non-viable' or 'MRI non-viable' segments, respectively. Eighteen per cent of the dysfunctional segments showed discrepant findings ('PET non-viable' but 'MRI viable'). At follow-up, the regional wall motion of these segments was inferior compared with 'PET viable/MRI viable' segments (1.1 ± 0.8 vs. 0.5 ± 0.7, P < 0.01), had an inferior functional recovery (-0.5 ± 0.6 vs. -0.9 ± 0.7, P < 0.03), but showed no difference compared with concordant 'PET non-viable/MRI non-viable' segments., Conclusion: The simultaneous assessment of LGE and FDG uptake using a hybrid PET/MRI system is feasible. The established PET and MRI 'viability' parameter prior to revascularization therapy also predicts accurately the regional outcome of wall motion after AMI. In a small proportion of segments with discrepant FDG PET and LGE MRI findings, FDG uptake was a better predictor for functional recovery., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: Journals.permissions@oup.com.)

Current knowledge about the molecular mechanisms of NMDA receptor (NMDAR)-independent long-term potentiation (LTP) in the hippocampus and its function for memory formation in the behaving animal is limited. NMDAR-independent LTP in the CA1 region is thought to require activity of postsynaptic L-type voltage-dependent Ca2+ channels (Cav1.x), but the underlying channel isoform remains unknown. We evaluated the function of the Cav1.2 L-type Ca2+ channel for spatial learning, synaptic plasticity, and triggering of learning-associated biochemical processes using a mouse line with an inactivation of the CACNA1C (Cav1.2) gene in the hippocampus and neocortex (Cav1.2(HCKO)). This model shows (1) a selective loss of protein synthesis-dependent NMDAR-independent Schaffer collateral/CA1 late-phase LTP (L-LTP), (2) a severe impairment of hippocampus-dependent spatial memory, and (3) decreased activation of the mitogen-activated protein kinase (MAPK) pathway and reduced cAMP response element (CRE)-dependent transcription in CA1 pyramidal neurons. Our results provide strong evidence for a role of L-type Ca2+ channel-dependent, NMDAR-independent hippocampal L-LTP in the formation of spatial memory in the behaving animal and for a function of the MAPK/CREB (CRE-binding protein) signaling cascade in linking Cav1.2 channel-mediated Ca2+ influx to either process.