PET Imaging of Post-infarct Myocardial Inflammation.
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ABSTRACT: Purpose of review
To examine the use of positron emission tomography (PET) for imaging post-infarct myocardial inflammation and repair.Recent findings
Dysregulated immune responses after myocardial infarction are associated with adverse cardiac remodelling and an increased likelihood of ischaemic heart failure. PET imaging utilising novel tracers can be applied to visualise different components of the post-infarction inflammatory and repair processes. This approach could offer unique pathophysiological insights that could prove useful for the identification and risk-stratification of individuals who would ultimately benefit most from emerging immune-modulating therapies. PET imaging could also bridge the clinical translational gap as a surrogate measure of drug efficacy in early-stage clinical trials in patients with myocardial infarction. The use of hybrid PET/MR imaging, in particular, offers the additional advantage of simultaneous in vivo molecular imaging and detailed assessment of myocardial function, viability and tissue characterisation. Further research is needed to realise the true clinical translational value of PET imaging after myocardial infarction.
SUBMITTER: Corovic A
PROVIDER: S-EPMC8249287 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hybrid PET/MR imaging is an emerging imaging modality combining positron emission tomography (PET) and magnetic resonance imaging (MRI) in the same system. Since the introduction of clinical PET/MRI in 2011, it has had some impact (e.g., imaging the components of inflammation in myocardial infarction), but its role could be much greater. Many opportunities remain unexplored and will be highlighted in this review. The inflammatory process post-myocardial infarction has many facets at a cellular level which may affect the outcome of the patient, specifically the effects on adverse left ventricular remodeling, and ultimately prognosis. The goal of inflammation imaging is to track the process non-invasively and quantitatively to determine the best therapeutic options for intervention and to monitor those therapies. While PET and MRI, acquired separately, can image aspects of inflammation, hybrid PET/MRI has the potential to advance imaging of myocardial inflammation. This review contains a description of hybrid PET/MRI, its application to inflammation imaging in myocardial infarction and the challenges, constraints, and opportunities in designing data collection protocols. Finally, this review explores opportunities in PET/MRI: improved registration, partial volume correction, machine learning, new approaches in the development of PET and MRI pulse sequences, and the use of novel injection strategies.
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Project description:Stimulation of the nitric oxide (NO)--soluble guanylate (sGC)--protein kinase G (PKG) pathway confers protection against acute ischaemia/reperfusion injury, but more chronic effects in reducing post-myocardial infarction (MI) heart failure are less defined. The aim of this study was to not only determine whether the sGC stimulator riociguat reduces infarct size but also whether it protects against the development of post-MI heart failure.Mice were subjected to 30 min ischaemia via ligation of the left main coronary artery to induce MI and either placebo or riociguat (1.2 µmol/l) were given as a bolus 5 min before and 5 min after onset of reperfusion. After 24 hours, both, late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) and (18)F-FDG-positron emission tomography (PET) were performed to determine infarct size. In the riociguat-treated mice, the resulting infarct size was smaller (8.5 ± 2.5% of total LV mass vs. 21.8% ± 1.7%. in controls, p = 0.005) and LV systolic function analysed by MRI was better preserved (60.1% ± 3.4% of preischaemic vs. 44.2% ± 3.1% in controls, p = 0.005). After 28 days, LV systolic function by echocardiography treated group was still better preserved (63.5% ± 3.2% vs. 48.2% ± 2.2% in control, p = 0.004).Taken together, mice treated acutely at the onset of reperfusion with the sGC stimulator riociguat have smaller infarct size and better long-term preservation of LV systolic function. These findings suggest that sGC stimulation during reperfusion therapy may be a powerful therapeutic treatment strategy for preventing post-MI heart failure.
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Project description:BackgroundPerfluoropropane droplets formulated from commercial microbubbles exhibit different acoustic characteristics than their parent microbubbles, most likely from enhanced endothelial permeability. This enhanced permeability may permit delayed echo-enhancement imaging (DEEI) similar to delayed enhancement magnetic resonance imaging (DE-MRI). We hypothesized this would allow detection and quantification of myocardial scar.MethodsIn 15 pigs undergoing 90 minutes of left anterior descending ischemia by either balloon (n = 13) or thrombotic occlusion (n = 2), DE-MRI was performed at 2-24 days postocclusion. Delayed echo-enhancement imaging was performed at 2-4 minutes following an intravenous injection of 1 mL of 50% Definity (Lantheus Medical) compressed into 180 nm droplets; DEEI was attempted in all pigs with single-pulse harmonic imaging at 1.7 transmit/3.4 MHz receive. Myocardial defects observed with DEEI were quantified (percentage of infarct area) and compared with DE-MRI as well as postmortem staining. In six pigs, multipulse low-mechanical index (MI) fundamental nonlinear imaging (FNLI) with intermittent high-MI impulses was performed to determine whether droplet activation within the infarct zone was achievable with a longer pulse duration.ResultsThe range of infarct size area by DE-MRI ranged from 0% to 46% of total left ventricular area. Single-pulse harmonic imaging detected a contrast defect that correlated closely with infarct area by DE-MRI (r = 0.81, P = .0001). The FNLI high-MI impulses resulted in droplet activation in both the infarct and normal zones. Harmonic subtraction of the FNLI images resulted in infarct zone enhancement that also correlated closely with infarct size (r = 0.83; P = .04). Droplets were observed on postmortem transmission electron microscopy within myocytes of the infarct and remote normal zone.ConclusionIntravenously Definity nanodroplets can be utilized to detect and quantify infarct zone at the bedside using DEEI techniques.
| S-EPMC8349868 | biostudies-literature
Project description:ObjectivesThe aim of this study was to explore post-myocardial infarction (MI) myocardial inflammation.BackgroundInnate immune cells are centrally involved in infarct healing and are emerging therapeutic targets in cardiovascular disease; however, clinical tools to assess their presence in tissue are scarce. Furthermore, it is currently not known if the nonischemic remote zone recruits monocytes.MethodsAcute inflammation was followed in mice with coronary ligation by 18-fluorodeoxyglucose ((18)FDG) positron emission tomography/magnetic resonance imaging, fluorescence-activated cell sorting, polymerase chain reaction, and histology.ResultsGd-DTPA-enhanced infarcts showed high (18)FDG uptake on day 5 after MI. Cell depletion and isolation data confirmed that this largely reflected inflammation; CD11b(+) cells had 4-fold higher (18)FDG uptake than the infarct tissue from which they were isolated (p < 0.01). Surprisingly, there was considerable monocyte recruitment in the remote myocardium (approximately 10(4)/mg of myocardium, 5.6-fold increase; p < 0.01), a finding mirrored by macrophage infiltration in the remote myocardium of patients with acute MI. Temporal kinetics of cell recruitment were slower than in the infarct, with peak numbers on day 10 after ischemia. Quantitative polymerase chain reaction showed a robust increase of recruiting adhesion molecules and chemokines in the remote myocardium (e.g., 12-fold increase of monocyte chemoattractant protein-1), although levels were always lower than in the infarct. Finally, matrix metalloproteinase activity was significantly increased in noninfarcted myocardium, suggesting that monocyte recruitment to the remote zone may contribute to post-MI dilation.ConclusionsThis study shed light on the innate inflammatory response in remote myocardium after MI.
| S-EPMC3257823 | biostudies-literature
Project description:Following myocardial infarction (MI), maladaptive upregulation of matrix metalloproteinase (MMP) alters extracellular matrix leading to cardiac remodeling. Intramyocardial hydrogel delivery provides a vehicle for local delivery of MMP tissue inhibitors (rTIMP-3) for MMP activity modulation. We evaluated swine 10-14 days following MI randomized to intramyocardial delivery of saline, degradable hyaluronic acid (HA) hydrogel, or rTIMP-3 releasing hydrogel with an MMP-targeted radiotracer (99mTc-RP805), 201Tl, and CT. Significant left ventricle (LV) wall thinning, increased wall stress, reduced circumferential wall strain occurred in the MI region of MI-Saline group along with left atrial (LA) dilation, while these changes were modulated in both hydrogel groups. 99mTc-RP805 activity increased twofold in MI-Saline group and attenuated in hydrogel animals. Infarct size significantly reduced only in rTIMP-3 hydrogel group. Hybrid SPECT/CT imaging demonstrated a therapeutic benefit of intramyocardial delivery of hydrogels post-MI and reduced remodeling of LA and LV in association with a reduction in MMP activation.
| S-EPMC10836411 | biostudies-literature
Project description:The prevalence of cardiovascular diseases (CVD) is increased in subjects with post-traumatic stress disorder (PTSD). Vascular inflammation mediates CVD and may be assessed by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging. In this pilot study, we investigated whether subjects with PTSD have enhanced vascular and systemic inflammation compared to healthy controls, as assessed by FDG PET imaging.MethodsA prospective group of 16 subjects (9 PTSD and 7 controls, age 34 ± 7) without prior history of CVD underwent FDG PET/CT imaging. The presence of PTSD symptoms at the time of the study was confirmed using PTSD checklist for DSM-5 (PCL5) questionnaire. Blood samples were collected to determine blood glucose, lipid and inflammatory biomarkers (tumor necrosis factor α, interleukin-1β, and interleukin-6) levels. FDG signal in the ascending aorta, amygdala, spleen and bone marrow was quantified.ResultsThe two groups matched closely with regards to cardiovascular risk factors. The inflammatory biomarkers were all within the normal range. There was no significant difference in FDG signal in the aorta (target to background ratio: 2.40 ± 0.29 and 2.34 ± 0.29 for control and PTSD subjects, difference: - 0.06, 95% confidence interval of difference: - 0.38 to 0.26), spleen, bone marrow, or amygdala between control and PTSD subjects. There was no significant correlation between aortic and amygdala FDG signal. However, a significant positive correlation existed between amygdala, splenic, and bone marrow FDG signal.ConclusionThis pilot, small study did not reveal any difference in vascular or systemic inflammation as assessed by FDG PET imaging between PTSD and healthy control subjects. Because of the small number of subjects, a modest increase in vascular inflammation, which requires larger scale studies to establish, cannot be excluded. The correlation between FDG signal in amygdala, spleen and bone marrow may reflect a link between amygdala activity and systemic inflammation.
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Project description:OBJECTIVE:To evaluate the frequency of artifacts in MR-based attenuation correction (AC) maps and their impact on the quantitative accuracy of PET-based flow and metabolism measurements in a cohort of consecutive heart failure patients undergoing combined PET/MR imaging. METHODS:Myocardial viability studies were performed in 20 patients following a dual-tracer protocol involving the assessment of myocardial perfusion (13N-NH3: 813 ± 86 MBq) and metabolism (18F-FDG: 335 ± 38 MBq). All acquisitions were performed using a fully-integrated PET/MR system, with standard DIXON-attenuation correction (DIXON-AC) mapping for each PET scan. All AC maps were examined for spatial misalignment with the emission data, total lung volume, susceptibility artifacts, and tissue inversion (TI). Misalignment and susceptibility artifacts were corrected using rigid co-registration and retrospective filling of the susceptibility-induced gaps, respectively. The effects of the AC artifacts were evaluated by relative difference measures and perceived changes in clinical interpretations. RESULTS:Average respiratory misalignment of (7 ± 4) mm of the PET-emission data and the AC maps was observed in 18 (90%) patients. Substantial changes in the lung volumes of the AC maps were observed in the test-retest analysis (ratio: 1.0 ± 0.2, range: 0.8-1.4). Susceptibility artifacts were observed in 10 (50%) patients, while six (30%) patients had TI artifacts. Average differences of 14 ± 10% were observed for PET images reconstructed with the artifactual AC maps. The combined artifact effects caused false-positive findings in three (15%) patients. CONCLUSION:Standard DIXON-AC maps must be examined carefully for artifacts and misalignment effects prior to AC correction of cardiac PET/MRI studies in order to avoid misinterpretation of biased perfusion and metabolism readings from the PET data.
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Project description:Calcium/calmodulin-dependent protein kinase II (CaMKII) was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. However, the specific functions of the CaMKII isoforms and splice variants in ischemia/reperfusion (I/R) injury have not been investigated yet. Thus, we studied the roles of the CaMKII isoforms and splice variants in I/R by the use of various CaMKII mutant mice. CaMKIIδC was up-regulated already one day after I/R injury but surprisingly, acute I/R injury was neither affected in CaMKIIδ-deficient mice, CaMKIIδ-deficient mice in which the splice variants CaMKIIδB and C were re-expressed nor in conditional CaMKIIδ/γ double-knockout mice (DKO). In contrast, 5 weeks after I/R, DKO mice were protected against extensive scar formation and cardiac dysfunction. Leukocyte infiltration was not altered one day but five days after I/R, explaining the late effects of CaMKII deletion on post-I/R remodeling. Other than reported before, we demonstrate that CaMKII is not critically involved in the immediate mechanisms that regulate acute I/R injury but in the process of post-infarct remodeling. We analysed 6 groups in total: 3 groups from wild-type control animals and 3 groups from CaMKII delta/gamma double-KO mice. Sham operated animals served as controls in both wild-type and KO animal groups. 2 different time points in ischia/reperfusion operated animals were investigated: 1 day and 5 days post-surgery.
2014-09-08 | E-GEOD-58486 | biostudies-arrayexpress
Project description:Matrix metalloproteinase-9 (MMP-9) deletion attenuates collagen accumulation and dilation of the left ventricle (LV) post-myocardial infarction (MI); however the biomechanical mechanisms underlying the improved outcome are poorly understood. The aim of this study was to determine the mechanisms whereby MMP-9 deletion alters collagen network composition and assembly in the LV post-MI to modulate the mechanical properties of myocardial scar tissue. Adult C57BL/6J wild-type (WT; n=88) and MMP-9 null (MMP-9(-/-); n=92) mice of both sexes underwent permanent coronary artery ligation and were compared to day 0 controls (n=42). At day 7 post-MI, WT LVs displayed a 3-fold increase in end-diastolic volume, while MMP-9(-/-) showed only a 2-fold increase (p<0.05). Biaxial mechanical testing revealed that MMP-9(-/-) infarcts were stiffer than WT infarcts, as indicated by a 1.3-fold reduction in predicted in vivo circumferential stretch (p<0.05). Paradoxically, MMP-9(-/-) infarcts had a 1.8-fold reduction in collagen deposition (p<0.05). This apparent contradiction was explained by a 3.1-fold increase in lysyl oxidase (p<0.05) in MMP-9(-/-) infarcts, indicating that MMP-9 deletion increased collagen cross-linking activity. Furthermore, MMP-9 deletion led to a 3.0-fold increase in bone morphogenetic protein-1, the metalloproteinase that cleaves pro-collagen and pro-lysyl oxidase (p<0.05) and reduced fibronectin fragmentation by 49% (p<0.05) to enhance lysyl oxidase activity. We conclude that MMP-9 deletion increases infarct stiffness and prevents LV dilation by reducing collagen degradation and facilitating collagen assembly and cross-linking through preservation of the fibronectin network and activation of lysyl oxidase.
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Project description:BackgroundI-123 meta-iodobenzylguanidine (MIBG) imaging has long been employed to noninvasively assess the integrity of human norepinephrine transporter-1 and, hence, myocardial sympathetic innervation. Positron-emitting F-18 meta-fluorobenzylguanidine (MFBG) has recently been developed for potentially superior quantitative characterization. We assessed the feasibility of MFBG imaging of myocardial sympathetic innervation.Methods16 patients were imaged with MFBG PET (30-minute dynamic imaging of chest, followed by 3 whole-body acquisitions between 30 minutes and 4-hour post-injection). Blood kinetics were assessed from multiple samples. Pharmacokinetic modeling with reversible 1- and 2-compartment models was performed. Kinetic rate constants were re-calculated from truncated datasets. All patients underwent concurrent MIBG SPECT.ResultsMFBG myocardial uptake was rapid and sustained; the mean standardized uptake value (SUV (mean ± standard deviation)) was 5.1 ± 2.2 and 3.4 ± 1.9 at 1 hour and 3-4-hour post-injection, respectively. The mean K1 and distribution volume (VT) were 1.1 ± 0.6 mL/min/g and 34 ± 22 mL/cm3, respectively. Both were reproducible when re-calculated from truncated 1-hour datasets (Intraclass Correlation Coefficient of 0.99 and 0.91, respectively). Spearman's ϱ = 0.86 between MFBG SUV and VT and 0.80 between MFBG PET-derived VT and MIBG SPECT-derived heart-to-mediastinum activity concentration ratio.ConclusionMFBG is a promising PET radiotracer for the assessment of myocardial sympathetic innervation.
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