Pierre-Yves Marie

Electroanatomic Characterization of Post-Infarct Scars Comparison With 3-Dimensional Myocardial Scar Reconstruction Based on Magnetic Resonance Imaging

OBJECTIVESnThis study was designed to compare electroanatomic mapping (EAM) and magnetic resonance imaging (MRI) with delayed contrast enhancement (DCE) data for delineation of post-infarct scars.nnnBACKGROUNDnElectroanatomic substrate mapping is an important step in the post-infarct ventricular tachycardia (VT) ablation strategy, but this technique has not yet been compared with a gold-standard noninvasive tool informing on the topography and transmural extent of myocardial scars in humans.nnnMETHODSnTen patients (9 men, age 71 +/- 10 years) admitted for post-infarct VT ablation underwent both a left ventricle DCE MRI and a sinus-rhythm 3-dimensional (3D) (CARTO) EAM (Biosense Webster, Johnson & Johnson, Diamond Bar, California). A 3D color-coded MRI-reconstructed left ventricular endocardial shell was generated to display scar data (intramural location and transmural extent). A matching process allocated any CARTO point to its corresponding position on the MRI map. Electrogram (EGM) characteristics were then evaluated in relation to scar data.nnnRESULTSnA spiky EGM morphology, a reduced unipolar or bipolar EGM voltage amplitude (<6.52 and <1.54 mV, respectively), as well as a longer bipolar EGM duration (>56 ms) independently correlated with the presence of scar whatever its intramural position. Endocardial scars had a larger degree of signal reduction than intramural or epicardial scars. None of the parameters was correlated with transmural scar depth. A clear mismatch in infarct surface between CARTO and MRI maps was observed in one-third of infarct zones.nnnCONCLUSIONSnSinus-rhythm EAM helps identify the limits of post-infarct scars. However, the accuracy of EAM for precise scar delineation is limited. This limit might be circumvented using anatomical information provided by 3D MRI data.

Compared Performance of High-Sensitivity Cameras Dedicated to Myocardial Perfusion SPECT: A Comprehensive Analysis of Phantom and Human Images

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.

Generalized Reconstruction by Inversion of Coupled Systems (GRICS) applied to free-breathing MRI

A reconstruction strategy is proposed for physiological motion correction, which overcomes many limitations of existing techniques. The method is based on a general framework allowing correction for arbitrary motion–nonrigid or affine, making it suitable for cardiac or abdominal imaging, in the context of multiple coil, arbitrarily sampled acquisition. A model is required to predict motion in the field of view at each sample time point, based on prior knowledge provided by external sensors. A theoretical study is carried out to analyze the influence of motion prediction errors. Small errors are shown to propagate linearly in that reconstruction algorithm, and thus induce a reconstruction residue that is bounded (stability). Furthermore, optimization of the motion model is proposed in order to minimize this residue. This leads to reformulating reconstruction as two inverse problems which are coupled: motion‐compensated reconstruction (known motion) and model optimization (known image). A fixed‐point multiresolution scheme is described for inverting these two coupled systems. This framework is shown to allow fully autocalibrated reconstructions, as coil sensitivities and motion model coefficients are determined directly from the corrupted raw data. The theory is validated with real cardiac and abdominal data from healthy volunteers, acquired in free‐breathing. Magn Reson Med 60:146–157, 2008.

Methyl donor deficiency induces cardiomyopathy through altered methylation/acetylation of PGC-1α by PRMT1 and SIRT1.

Cardiomyopathies occur by mechanisms that involve inherited and acquired metabolic disorders. Both folate and vitamin B12 deficiencies are associated with left ventricular dysfunction, but mechanisms that underlie these associations are not known. However, folate and vitamin B12 are methyl donors needed for the synthesis of S‐adenosylmethionine, the substrate required for the activation by methylation of regulators of energy metabolism. We investigated the consequences of a diet lacking methyl donors in the myocardium of weaning rats from dams subjected to deficiency during gestation and lactation. Positron emission tomography (PET), microscope and metabolic examinations evidenced a myocardium hypertrophy, with cardiomyocyte enlargement, disturbed mitochondrial alignment, lipid droplets, decreased respiratory activity of complexes I and II and decreased S‐adenosylmethionine:S‐adenosylhomocysteine ratio. The increased concentrations of triglycerides and acylcarnitines were consistent with a deficit in fatty acid oxidation. These changes were explained by imbalanced acetylation/methylation of PGC‐1α, through decreased expression of SIRT1 and PRMT1 and decreased S‐adenosylmethionine:S‐adenosylhomocysteine ratio, and by decreased expression of PPARα and ERRα. The main changes of the myocardium proteomic study were observed for proteins regulated by PGC‐1α, PPARs and ERRα. These proteins, namely trifunctional enzyme subunit α‐complex, short chain acylCoA dehydrogenase, acylCoA thioesterase 2, fatty acid binding protein‐3, NADH dehydrogenase (ubiquinone) flavoprotein 2, NADH dehydrogenase (ubiquinone) 1α‐subunit 10 and Hspd1 protein, are involved in fatty acid oxidation and mitochondrial respiration. In conclusion, the methyl donor deficiency produces detrimental effects on fatty acid oxidation and energy metabolism of myocardium through imbalanced methylation/acetylation of PGC‐1α and decreased expression of PPARα and ERRα. These data are of pathogenetic relevance to perinatal cardiomyopathies. Copyright

Beige differentiation of adipose depots in mice lacking prolactin receptor protects against high-fat-diet-induced obesity

Stimulating conversion of white fat to metabolically active adipocytes (beige fat) constitutes a promising strategy against weight gain and its deleterious associated‐disorders. We provide direct evidence that prolactin (PRL), best known for its actions on the mammary gland, plays a pivotal role in energy balance through the control of adipocyte differentiation and fate. Here we show that lack of prolactin receptor (PRLR) causes resistance to high‐fat‐diet‐induced obesity due to enhanced energy expenditure and increased metabolic rate. Mutant mice displayed reduced fat mass associated with appearance of massive brown‐like adipocyte foci in perirenal and subcutaneous but not in gonadal fat depots under a high‐fat diet. Positron emission tomography imaging further demonstrated the occurrence of these thermogenic brown fat depots in adult mice, providing additional support for recruitable brown‐like adipocytes (beigeing) in white fat depots. Consistent with the activation of brown adipose tissue, PRLR inactivation increases expression of master genes controlling brown adipocyte fate (PRDM16) and mitochondrial function (PGC1α, UCP1). Altered pRb/Foxc2 expression suggests that this PRL‐regulated pathway may contribute to beige cell commitment. Together, these results provide direct genetic evidence that PRLR affects energy balance and metabolic adaptation in rodents via effects on brown adipose tissue differentiation and function.—Auffret, J., Viengchareun, S., Carré, N., Denis, R. G. P., Magnan, C., Marie, P.‐Y., Muscat, A., Fève, B., Lombès, M., Binart, N. Beige differentiation of adipose depots in mice lacking prolactin receptor protects against high‐fat‐diet‐induced obesity. FASEB J. 26, 3728–3737 (2012). www.fasebj.org

Short-term heart retention and distribution of intramyocardial delivered mesenchymal cells within necrotic or intact myocardium.

Cell therapy with bone marrow mesenchymal stem cells (BMSCs) is a new strategy for treating ischemic heart failure, but data concerning the distribution and retention of transplanted cells remain poor. We investigated the short-term myocardial retention of BMSCs when these cells are directly injected within necrotic or intact myocardium. 111Indium-oxine-labeled autologous BMSCs were injected within either 1-month-old infarction (n = 6) or normal myocardium (n = 6) from rats. Serial in vivo pinhole scintigraphy was scheduled during 1 week in order to track the implanted cells. The myocardial retention of BMSCs was definitely higher in myocardial infarction than in normal myocardial area (estimated percent retention at 2 h: 63 ± 3% vs. 25 ± 4%, p < 0.001) and the estimated cardiac retention values were unchanged in both groups along the 7 days of follow-up. On heart sections at day 7, labeled BMSCs were still around the injection site and appeared confined to the scarred tissue corresponding either to the infarct area or to the myocardium damaged by needle insertion. BMSCs have a higher retention when they are injected in necrotic than in normal myocardial areas and these cells appear to stay around the injection site for at least a 7-day period.

Aortic inflammation, as assessed by hybrid FDG-PET/CT imaging, is associated with enhanced aortic stiffness in addition to concurrent calcification

PurposeTo analyse the relationship between: (i) aortic pulse wave velocity (PWV), an index of aortic stiffness with strong prognostic significance, and (ii) aortic calcification and inflammation, which were quantified by hybrid imaging with X-ray computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET).MethodsCentral aortic (carotid-femoral) and peripheral (carotid-brachial and femoral-tibial) PWV were recorded in 26 patients, who had been routinely referred for dual FDG-PET/CT imaging.ResultsIn univariate analyses, central aortic PWV was strongly linked to the volume of calcifications (VCa) and an enhanced FDG activity, when determined by averaging standardized uptake values (SUVmax). By multivariate stepwise analysis including age and gender, both VCa (pu2009<u20090.0001) and SUVmax (pu2009<u20090.01) were significant determinants of PWV explaining 61% and 11% of its variability.ConclusionAortic inflammation, assessed by hybrid FDG-PET/CT imaging, is associated with an enhanced aortic stiffness, in addition to the concurrent impact of calcifications.

Combined SEEG and source localisation study of temporal lobe schizencephaly and polymicrogyria.

OBJECTIVESnType 1 schizencephaly (SZ) is a cerebral malformation characterised by a cleft lined and surrounded by a polymicrogyric cortex, extending from the pial region to the peri-ventricular heterotopia. Our purpose was to combine and compare dipole source imaging technique and Stereo-EEG (SEEG) technique in determining the irritative and epileptogenic zones in a case of type 1 schizencephaly.nnnMETHODSnHigh-resolution (64-channel) video-EEG with electrical source imaging and SEEG recordings were performed during a pre-surgical evaluation for medically intractable epilepsy.nnnRESULTSnAnatomo-electro-clinical correlations based on SEEG and source localisation identified two irritative and epileptogenic zones partially overlapping the polymicrogyric cortex surrounding the SZ: an anterior medio-lateral network primarily involving dysplasic limbic structures and a lateral network involving the anterior and middle part of the cleft and polymicrogyric cortex. The most posterior part (at the temporo-parieto-occipital junction) displayed a normal background activity.nnnCONCLUSIONSnBoth epileptogenic and electrophysiologically normal cortices coexisted within the same widespread malformation: only the anterior part belonged to the anterior medio-lateral epileptogenic network defined by the SEEG.nnnSIGNIFICANCEnIn cases of widespread cortical malformation such as SZ, source localization techniques can help to define the irritative zone and relevant targets for SEEG.

Assessment of right ventricle volumes and function by cardiac MRI: quantification of the regional and global interobserver variability.

Reproducibility of the manual assessment of right ventricle volumes by short‐axis cine‐MRI remains low and is often attributed to the difficulty in separating the right atrium from the ventricle. This study was designed to evaluate the regional interobserver variability of the right ventricle volume assessment to identify segmentation zones with the highest interobserver variability. Short‐axis views of 90 right ventricles (30 hypertrophic, 30 dilated, and 30 normal) were acquired with 2D steady‐state free precession sequences at 1.5 T and were manually segmented by two observers. The two segmentations were compared and the variations were quantified with a variation score based on the Hausdorff distance between the two segmentations and the interobserver 95% limits of concordance of the global volumes. The right ventricles were semiautomatically split into four subregions: apex, mid‐ventricle, tricuspid zone, and infundibulum. These four subregions represented 11%, 34%, 36%, and 19% of the volume but, respectively, yielded variation scores of 8%, 16%, 42%, and 34%. The infundibulum yielded the highest interobserver regional variability although its variation score remained comparable to the tricuspid zone due to its lower volume. These results emphasize the importance of standardizing the segmentation of the infundibulum and the tricuspid zone to improve reproducibility. Magn Reson Med, 2011.

3D myocardial T1 mapping at 3T using variable flip angle method: Pilot study

Myocardial T1 mapping is an emerging technique that could improve cardiovascular magnetic resonance diagnostic accuracy. In this study, a variable flip angle approach with B1 correction is proposed at 3T on the myocardium, employing standard 3D spoiled fast gradient echo and echo planar imaging sequences.