Vandœuvre-lès-Nancy, France
Vandœuvre-lès-Nancy, France

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Imbert L.,Nancy Research Center for Automatic Control | Imbert L.,Center Alexis Vautrin | Imbert L.,Nancy University Hospital Center | Poussier S.,Nancyclotep Experimental Imaging Platform | And 15 more authors.
Journal of Nuclear Medicine | Year: 2012

Differences in the performance of cadmium-zinc-telluride (CZT) cameras or collimation systems that have recently been commercialized for myocardial SPECT remain unclear. In the present study, the performance of 3 of these systems was compared by a comprehensive analysis of phantom and human SPECT images. Methods: We evaluated the Discovery NM 530c and DSPECT CZT cameras, as well as the Symbia Anger camera equipped with an astigmatic (IQ·SPECT) or parallel-hole (conventional SPECT) collimator. Physical performance was compared on reconstructed SPECT images from a phantom and from comparable groups of healthy subjects. Results: Classifications were as follows, in order of performance. For count sensitivity on cardiac phantom images (counts·s-1·MBq-1), DSPECT had a sensitivity of 850; Discovery NM 530c, 460; IQ·SPECT, 390; and conventional SPECT, 130. This classification was similar to that of myocardial counts normalized to injected activities from human images (respective mean values, in counts·s-1·MBq-1: 11.4 ± 2.6, 5.6 ± 1.4, 2.7 ± 0.7, and 0.6 ± 0.1). For central spatial resolution: Discovery NM 530c was 6.7 mm; DSPECT, 8.6 mm; IQ·SPECT, 15.0 mm; and conventional SPECT, 15.3 mm, also in accordance with the analysis of the sharpness of myocardial contours on human images (in cm-1: 1.02 ± 0.17, 0.92 ± 0.11, 0.64 ± 0.12, and 0.65 ± 0.06, respectively). For contrast-to-noise ratio on the phantom: Discovery NM 530c had a ratio of 4.6; DSPECT, 4.1; IQ·SPECT, 3.9; and conventional SPECT, 3.5, similar to ratios documented on human images (5.2 ± 1.0, 4.5 ± 0.5, 3.9 ± 0.6, and 3.4 ± 0.3, respectively). Conclusion: The performance of CZT cameras is dramatically higher than that of Anger cameras, even for human SPECT images. However, CZT cameras differ in that spatial resolution and contrast-to-noise ratio are better with the Discovery NM 530c, whereas count sensitivity is markedly higher with the DSPECT. Copyright © 2012 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Introduction: Inter-ictal 18F-2-fluoro-deoxy-D-glucose-positron emission tomography (FDG-PET) plays a key role for the preoperative evaluation of patients with pharmacoresistant temporal lobe epilepsy. PET images are usually analyzed visually, a way that is reported to provide a high diagnostic value but that remains subjective, depending on the expertise and experience of the observer. By contrast, the voxel-based quantitative analyses, such as statistical parametric mapping (SPM), are objective and therefore, observer independent methods of analyses. In this study, the accuracy of the analyses of brain FDG-PET images to lateralize the temporal lobe epileptogenic zone was compared between: (1) a conventional visual method, (2) a quantitative SPM analysis, and (3) a visual analysis of inter-hemispheric asymmetry (IHA) obtained after images substraction. Materials and methods: FDG-PET scans of 31patients presenting a severe temporal epilepsy and whom the temporal foci had been accurately lateralized (successful subsequent surgical treatment) were retrospectively analysed by (1) a consensual visual analysis from two experienced observers; (2) SPM analysis with voxel-wise comparisons of FDG-PET images of patients with those of age-matched healthy controls, using various statistical threshold (P) and cluster (k) values; and (3) visual assessment by the two same observers of images obtained for assessing the IHA. For this purpose, a flipped image was initially obtained by reversing in the left-right direction the FDG-PET images, which had been previously spacially normalized with the SPM template. Then, flipped and non-flipped images were substracted. Results: The temporal hypometabolic area was accurately identified: (1) by the conventional visual analysis in 87% of patients and with a satisfactory interobserver reproducibility (interobserver Cohen's coefficient=0.79); (2) by SPM analysis, in 90% of patients (when using optimal thresholds of 0.01for P value and of 50voxels (400mm3) for k value); and (3) with the visual analysis of IHA in 97% of patients with an excellent interobserver reproductibility (interobserver Cohen's coefficient=1). Conclusion: In patients presenting severe temporal epilepsy, visual assessment of FDG-PET images from IHA seems more accurate for lateralizing the epileptogenic temporal areas when compared with either conventional visual or quantitative SPM analyses. Moreover, this method is very easy to use in clinical practice, contrary to the quantitative method using SPM. © 2014 Elsevier Masson SAS.

Imbert L.,University of Lorraine | Imbert L.,Institute Of Cancerologie Of Lorraine | Imbert L.,Nancy University Hospital Center | Perrin M.,Nancy University Hospital Center | And 7 more authors.
Clinical and Translational Imaging | Year: 2016

Myocardial perfusion SPECT imaging (MPI) is able to provide a physiological assessment during physical exercise and is widely used for diagnosing coronary artery disease and assessing cardiac risk. Until recently, however, MPI needed to provide a lower radiation exposure, especially for the growing number of patients referred for repeated ionizing procedures throughout the course of their life. This goal has been partly attained with the advent of new imaging systems dedicated to nuclear cardiology and equipped with semiconductor cadmium zinc telluride (CZT) detectors, new collimation systems, and novel reconstruction software. Two CZT cameras are currently commercially available and when compared with conventional Anger cameras, they offer much higher energy resolutions and count sensitivities, allowing image quality to be improved as well as acquisition times and injected activities to be markedly reduced. Low-dose protocols have already been assessed with these CZT cameras, leading to a mean effective dose not exceeding 9 mSv per patient and thus, at a much lower level than that currently achieved with single-day protocols on conventional cameras (around 14 mSv). These doses can furthermore be reduced to less than 4 mSv, on average, owing to the use of a stress-first protocol, where the normality of stress images may lead to avoiding rest imaging. In the near future, effective doses will likely be further decreased to a lower level with technical improvements leading to minimizing the reconstructed noise and attenuation artifacts while at the same time optimizing and better tailoring the injection protocols to the individual patient. © 2015, Italian Association of Nuclear Medicine and Molecular Imaging.

Imbert L.,Nancy Research Center for Automatic Control | Imbert L.,Institute Of Cancerologie Of Lorraine | Imbert L.,Nancy University Hospital Center | Galbrun E.,Nancy Research Center for Automatic Control | And 13 more authors.
Physics in Medicine and Biology | Year: 2015

Geant4 application for tomographic emission (GATE), a Monte-Carlo simulation platform, has previously been used for optimizing tomoscintigraphic images recorded with scintillation Anger cameras but not with the new-generation heart-centric cadmium-zinc-telluride (CZT) cameras. Using the GATE platform, this study aimed at simulating the SPECT recordings from one of these new CZT cameras and to assess this simulation by direct comparison between simulated and actual recorded data, ranging from point sources to human images. Geometry and movement of detectors, as well as their respective energy responses, were modeled for the CZT 'D.SPECT' camera in the GATE platform. Both simulated and actual recorded data were obtained from: (1) point and linear sources of 99mTc for compared assessments of detection sensitivity and spatial resolution, (2) a cardiac insert filled with a 99mTc solution for compared assessments of contrast-to-noise ratio and sharpness of myocardial borders and (3) in a patient with myocardial infarction using segmented cardiac magnetic resonance imaging images. Most of the data from the simulated images exhibited high concordance with the results of actual images with relative differences of only: (1) 0.5% for detection sensitivity, (2) 6.7% for spatial resolution, (3) 2.6% for contrast-to-noise ratio and 5.0% for sharpness index on the cardiac insert placed in a diffusing environment. There was also good concordance between actual and simulated gated-SPECT patient images for the delineation of the myocardial infarction area, although the quality of the simulated images was clearly superior with increases around 50% for both contrast-to-noise ratio and sharpness index. SPECT recordings from a new heart-centric CZT camera can be simulated with the GATE software with high concordance relative to the actual physical properties of this camera. These simulations may be conducted up to the stage of human SPECT-images even if further refinement is needed in this setting. © 2015 Institute of Physics and Engineering in Medicine.

Bousquenaud M.,Laboratory of Cardiovascular Research | Maskali F.,Nancyclotep Experimental Imaging Platform | Poussier S.,Nancyclotep Experimental Imaging Platform | Marie P.-Y.,Nancyclotep Experimental Imaging Platform | And 6 more authors.
International Journal of Cardiovascular Imaging | Year: 2012

The ratmyocardial infarction (MI)model is widely used to study left ventricular (LV) remodeling. In this study, acipimox-enhanced 18F-Fluorodeoxyglucose (FDG) gated-positron emission tomography (PET) was assessed for characterizing and predicting early remodeling in the rat infarctmodel.NineteenWistar rats had surgical occlusion of the left anterior descending coronary artery and 7 were sham-operated. PET was scheduled 48 h and 2 weeks later for quantifying MI area and LV function. Segments with<50% of FDG uptake had histological evidence of MI (74 ± 9% decrease in parietal thickness, fibrosis development). At 48 h, MI area was large (>35% of LV) in 6 rats, moderate (15-35% of LV) in 8 rats, limited (<15% of LV) in 5 rats and absent in the 7 sham rats. LV remodeling, assessed through the 2 weeks increase in end-diastolic volume, increased between rats with limited, moderate and large MI (+72 ± 25, +109 ± 56, +190 ± 69 μl, respectively, P = 0.007). This 3-groups classification allowed predicting 44% of the 2weeks increase in end-diastolic volume, and additional 34%were predicted by heart rate at 48 h. The acipimoxenhanced FDG gated-PET technique provides efficient characterization and prediction of early remodeling in the rat infarct model. © Springer Science+Business Media, B.V. 2011.

Zangrando J.,CRP Sante | Zhang L.,CRP Sante | Vausort M.,CRP Sante | Maskali F.,Nancyclotep Experimental Imaging Platform | And 4 more authors.
BMC Genomics | Year: 2014

Background: Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs. LncRNAs regulate gene expression, thus having the possibility to modulate disease progression. In this study, we investigated the changes of lncRNAs expression in the heart after myocardial infarction (MI).Results: Adult male C57/BL6 mice were subjected to coronary ligation or sham operation. In a derivation group of 4 MI and 4 sham-operated mice sacrificed 24 hours after surgery, microarray analysis showed that MI was associated with up-regulation of 20 lncRNAs and down-regulation of 10 lncRNAs (fold-change >2). Among these, 2 lncRNAs, called myocardial infarction-associated transcript 1 (MIRT1) and 2 (MIRT2), showed robust up-regulation in the MI group: 5-fold and 13-fold, respectively. Up-regulation of these 2 lncRNAs after MI was confirmed by quantitative PCR in an independent validation group of 8 MI and 8 sham-operated mice (9-fold and 16-fold for MIRT1 and MIRT2, P < 0.001). In a time-course analysis involving 21 additional MI mice, the expression of both lncRNAs peaked 24 hours after MI and returned to baseline after 2 days. In situ hybridization revealed an up-regulation of MIRT1 expression in the left ventricle of MI mice. Expression of MIRT1 and MIRT2 correlated with the expression of multiple genes known to be involved in left ventricular remodeling. Mice with high level of expression of MIRT1 and MIRT2 had a preserved ejection fraction.Conclusion: Myocardial infarction induces important changes in the expression of lncRNAs in the heart. This study motivates further investigation of the role of lncRNAs in left ventricular remodeling. © 2014 Zangrando et al.; licensee BioMed Central Ltd.

Rolland-Turner M.,CRP Sante | Goretti E.,CRP Sante | Bousquenaud M.,CRP Sante | Leonard F.,CRP Sante | And 7 more authors.
PLoS ONE | Year: 2013

Background: Administration of endothelial progenitor cells (EPC) represents a promising option to regenerate the heart after myocardial infarction, but is limited because of low recruitment and engraftment in the myocardium. Mobilization and migration of EPC are mainly controlled by stromal cell-derived factor 1α (SDF-1α) and its receptor CXCR4. We hypothesized that adenosine, a cardioprotective molecule, may improve the recruitment of EPC to the heart. Methods: EPC were obtained from peripheral blood mononuclear cells of healthy volunteers. Expression of chemokines and their receptors was evaluated using microarrays, quantitative PCR, and flow cytometry. A Boyden chamber assay was used to assess chemotaxis. Recruitment of EPC to the infarcted heart was evaluated in rats after permanent occlusion of the left anterior descending coronary artery. Results: Microarray analysis revealed that adenosine modulates the expression of several members of the chemokine family in EPC. Among these, CXCR4 was up-regulated by adenosine, and this result was confirmed by quantitative PCR (3-fold increase, P<0.001). CXCR4 expression at the cell surface was also increased. This effect involved the A2B receptor. Pretreatment of EPC with adenosine amplified their migration towards recombinant SDF-1α or conditioned medium from cardiac fibroblasts. Both effects were abolished by CXCR4 blocking antibodies. Adenosine also increased CXCR4 under ischemic conditions, and decreased miR-150 expression. Binding of miR-150 to the 3′ untranslated region of CXCR4 was verified by luciferase assay. Addition of pre-miR-150 blunted the effect of adenosine on CXCR4. Administration of adenosine to rats after induction of myocardial infarction stimulated EPC recruitment to the heart and enhanced angiogenesis. Conclusion: Adenosine increases the migration of EPC. The mechanism involves A2B receptor activation, decreased expression of miR-150 and increased expression of CXCR4. These results suggest that adenosine may be used to enhance the capacity of EPC to revascularize the ischemic heart. © 2013 Rolland-Turner et al.

Bousquenaud M.,Laboratory of Cardiovascular Research | Maskali F.,Nancyclotep Experimental Imaging Platform | Poussier S.,Nancyclotep Experimental Imaging Platform | Zangrando J.,Laboratory of Cardiovascular Research | And 8 more authors.
EJNMMI Research | Year: 2013

Background: Adenosine may have beneficial effects on left ventricular function after myocardial infarction (MI), but the magnitude of this effect on remote and MI areas is controversial. We assessed the long-term effects of adenosine after MI using electrocardiogram-triggered 18 F-fluorodeoxyglucose positron emission tomography. Methods: Wistar rats were subjected to coronary ligation and randomized into three groups treated daily for 2 months by NaCl (control; n = 7), 2-chloroadenosine (CADO; n = 8) or CADO with 8-sulfophenyltheophilline, an antagonist of adenosine receptors (8-SPT; n = 8). Results: After 2 months, control rats exhibited left ventricular remodelling, with increased end-diastolic volume and decreased ejection fraction. Left ventricular remodelling was not significantly inhibited by CADO. Segmental contractility, as assessed by the change in myocardial thickening after 2 months, was improved in CADO rats compared to control rats (+1.6% ± 0.8% vs. -2.3% ± 0.8%, p < 0.001). This improvement was significant in border (+5.6% ± 0.8% vs. +1.5% ± 0.8%, p < 0.001) and remote (-4.0% ± 1.0% vs. -10.4% ± 1.3%, p < 0.001) segments, but absent in MI segments. Histological analyses revealed that CADO reduced fibrosis, cardiomyocyte hypertrophy and apoptosis. Protective effects of CADO were blunted by 8-SPT. Conclusion: Long-term administration of adenosine protects the left ventricle from contractile dysfunction following MI. © 2013 Bousquenaud et al.; licensee Springer.

Devaux Y.,Laboratory of Cardiovascular Research | Bousquenaud M.,Laboratory of Cardiovascular Research | Rodius S.,Laboratory of Cardiovascular Research | Marie P.-Y.,Nancyclotep Experimental Imaging Platform | And 5 more authors.
BMC Medical Genomics | Year: 2011

Background: Prediction of left ventricular (LV) remodeling after acute myocardial infarction (MI) is clinically important and would benefit from the discovery of new biomarkers. Methods. Blood samples were obtained upon admission in patients with acute ST-elevation MI who underwent primary percutaneous coronary intervention. Messenger RNA was extracted from whole blood cells. LV function was evaluated by echocardiography at 4-months. Results: In a test cohort of 32 MI patients, integrated analysis of microarrays with a network of protein-protein interactions identified subgroups of genes which predicted LV dysfunction (ejection fraction ≤40%) with areas under the receiver operating characteristic curve (AUC) above 0.80. Candidate genes included transforming growth factor beta receptor 1 (TGFBR1). In a validation cohort of 115 MI patients, TGBFR1 was up-regulated in patients with LV dysfunction (P < 0.001) and was associated with LV function at 4-months (P = 0.003). TGFBR1 predicted LV function with an AUC of 0.72, while peak levels of troponin T (TnT) provided an AUC of 0.64. Adding TGFBR1 to the prediction of TnT resulted in a net reclassification index of 8.2%. When added to a mixed clinical model including age, gender and time to reperfusion, TGFBR1 reclassified 17.7% of misclassified patients. TGFB1, the ligand of TGFBR1, was also up-regulated in patients with LV dysfunction (P = 0.004), was associated with LV function (P = 0.006), and provided an AUC of 0.66. In the rat MI model induced by permanent coronary ligation, the TGFB1-TGFBR1 axis was activated in the heart and correlated with the extent of remodeling at 2 months. Conclusions: We identified TGFBR1 as a new candidate prognostic biomarker after acute MI. © 2011 Devaux et al; licensee BioMed Central Ltd.

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