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Director of CRMBM
Coordinator France Life Imaging
tel : +33 4 91 32 48 18
Key Words
- Cardiovascular magnetic resonance (imaging and spectroscopy)
- Isolated perfused heart
- Animal models, Human cardiovascular pathologies
- Cardiac Transplantation, Cardiomyopathies
- Diabetes, obesity

Current Research Interest and projects

My current research interests are focused on the study of metabolic, physiological and functional alterations during cardiovascular pathologies related to diffuse or localized ischemia (atherosclerosis, diabetic and obesity related cardiomyopathy, atrial fibrillation, ischemia during transplantation). Magnetic resonance techniques with both spectroscopy (MRS, 31P, 23Na and 1H) and imaging (MRI) are combined to biochemical analyses (HPLC, enzymatic analyses) and molecular biology methods (protein expressions). Experimental models include the isolated perfused murine heart or the whole animal and studies are extended to human pathologies. Microcirculatory and metabolic aspects are emphasized in relation to endothelial dysfunction and alterations of the energetic and lipid metabolism but are part of a multimodal approach aiming at a complete characterization of the myocardium.



Journal Article

  • Chatel, B, Messonnier, LA, Barge, Q, Vilmen, C, Noirez, P, Bernard, M, Pialoux, V & Bendahan, D 2018, “Endurance training reduces exercise-induced acidosis and improves muscle function in a mouse model of sickle cell disease”, Molecular Genetics and Metabolism, vol. 123, no. 3, p. 400-410.
    Résumé : Sickle cell disease (SCD) mice (Townes model of SCD) presented exacerbated exercise-induced acidosis and fatigability as compared to control animals. We hypothesize that endurance training could represent a valuable approach to reverse these muscle defects. Endurance-trained HbAA (HbAA-END, n=10), HbAS (HbAS-END, n=11) and HbSS (HbSS-END, n=8) mice were compared to their sedentary counterparts (10 HbAA-SED, 10 HbAS-SED and 9 HbSS-SED mice) during two rest - exercise - recovery protocols during which muscle energetics and function were measured. In vitro analyses of some proteins involved in muscle energetics, pH regulation and oxidative stress were also performed. Exercise-induced acidosis was lower in HbSS-END mice as compared to their sedentary counterparts during both moderate (p<0.001) and intense (p<0.1) protocols. The total force production measured during both protocols was higher in trained mice compared to sedentary animals. In vitro analyses revealed that enolase/citrate synthase ratio was reduced in HbSS-END (p<0.001) and HbAS-END (p<0.01) mice compared to their sedentary counterparts. In addition, malondialdehyde concentration was reduced in trained mice (p<0.05). In conclusion, endurance training would reverse the more pronounced exercise-induced acidosis, reduce oxidative stress and ameliorate some of the muscle function parameters in SCD mice.
    Mots-clés : crmbm, msk, Muscle energetics, Muscle force production, pH, Physical activity.

  • Macia, M, Pecchi, E, Desrois, M, Lan, C, Vilmen, C, Portha, B, Bernard, M, Bendahan, D & Giannesini, B 2018, “Exercise training impacts exercise tolerance and bioenergetics in gastrocnemius muscle of non-obese type-2 diabetic Goto-Kakizaki rat in vivo”, Biochimie.
    Résumé : The functional and bioenergetics impact of regular physical activity upon type-2 diabetic skeletal muscle independently of confounding factors of overweight remains undocumented. Here, gastrocnemius muscle energy fluxes, mitochondrial capacity and mechanical performance were assessed noninvasively and longitudinally in non-obese diabetic Goto-Kakizaki rats using magnetic resonance (MR) imaging and dynamic 31-phosphorus MR spectroscopy (31P-MRS) throughout a 6-min fatiguing bout of exercise performed before, in the middle (4-week) and at the end of an 8-week training protocol consisting in 60-min daily run on a treadmill. The training protocol reduced plasmatic insulin level (-61%) whereas blood glucose and non-esterified fatty acids levels remained unaffected, thereby indicating an improvement of insulin sensitivity. It also increased muscle mitochondrial citrate synthase activity (+45%) but this increase did not enhance oxidative ATP synthesis capacity in working muscle in vivo while glycolytic ATP production was increased (+33%). On the other hand, the training protocol impaired maximal force-generating capacity (-9%), total amount of force produced (-12%) and increased ATP cost of contraction (+32%) during the fatiguing exercise. Importantly, these deleterious effects were transiently worsened in the middle of the 8-week period, in association with reduced oxidative capacity and increased basal [Pi]/[PCr] ratio (an in vivo biomarker of muscle damage). These data demonstrate that the beneficial effect of regular training on insulin sensitivity in non-obese diabetic rat occurs separately from any improvement in muscle mitochondrial function and might be linked to an increased capacity for metabolizing glucose through anaerobic process in exercising muscle.
    Mots-clés : crmbm, cvs, Diabetes, Mitochondrial capacity, msk, Nuclear magnetic resonance, Regular physical activity, Skeletal muscle function.


Journal Article

  • Chatel, B, Hourdé, C, Gondin, J, Fouré, A, Le Fur, Y, Vilmen, C, Bernard, M, Messonnier, LA & Bendahan, D 2017, “Impaired muscle force production and higher fatigability in a mouse model of sickle cell disease”, Blood Cells, Molecules & Diseases, vol. 63, p. 37-44.
    Résumé : Skeletal muscle function has been scarcely investigated in sickle cell disease (SCD) so that the corresponding impact of sickle hemoglobin is still a matter of debate. The purpose of this study was to investigate muscle force production and fatigability in SCD and to identify whether exercise intensity could have a modulatory effect. Ten homozygous sickle cell (HbSS), ten control (HbAA) and ten heterozygous (HbAS) mice were submitted to two stimulation protocols (moderate and intense) to assess force production and fatigability. We showed that specific maximal tetanic force was lower in HbSS mice as compared to other groups. At the onset of the stimulation period, peak force was reduced in HbSS and HbAS mice as compared to HbAA mice. Contrary to the moderate protocol, the intense stimulation protocol was associated with a larger decrease in peak force and rate of force development in HbSS mice as compared to HbAA and HbAS mice. These findings provide in vivo evidence of impaired muscle force production and resistance to fatigue in SCD. These changes are independent of muscle mass. Moreover, SCD is associated with muscle fatigability when exercise intensity is high.
    Mots-clés : crmbm, Exercise intensity, msk, Muscle mass, Muscle volume, Rate of force development.

  • Desrois, M, Lan, C, Movassat, J & Bernard, M 2017, “Reduced up-regulation of the nitric oxide pathway and impaired endothelial and smooth muscle functions in the female type 2 diabetic goto-kakizaki rat heart”, Nutrition & Metabolism, vol. 14, p. 6.
    Résumé : BACKGROUND: Type 2 diabetes is associated with greater relative risk of cardiovascular diseases in women than in men, which is not well understood. Consequently, we have investigated if male and female displayed differences in cardiac function, energy metabolism, and endothelial function which could contribute to increased cardiovascular complications in type 2 diabetic female. METHODS: Male and female Control and type 2 diabetic Goto-Kakizaki (GK) isolated rat hearts were perfused during 28 min with a physiological buffer before freeze-clamping for biochemical assays. High energy phosphate compounds and intracellular pH were followed using (31)P magnetic resonance spectroscopy with simultaneous measurement of contractile function. Nitric oxide (NO) pathway and endothelium-dependent and independent vasodilatations were measured as indexes of endothelial function. Results were analyzed via two-way ANOVA, p < 0.05 was considered as statistically significant. RESULTS: Myocardial function was impaired in male and female diabetic versus Control groups (p < 0.05) without modification of energy metabolism. Coronary flow was decreased in both diabetic versus Control groups but to a higher extent in female GK versus male GK rat hearts (p < 0.05). NO production was up-regulated in diabetic groups but to a less extent in female GK rat hearts (p < 0.05). Endothelium-dependent and independent vasodilatations were impaired in female GK rat compared with male GK (p < 0.05) and female Control (p < 0.05) rat hearts. CONCLUSIONS: We reported here an endothelial damage characterized by a reduced up-regulation of the NO pathway and impaired endothelial and smooth muscle functions, and coronary flow rates in the female GK rat hearts while energy metabolism was normal. Whether these results are related to the higher risk of cardiovascular complications among type 2 diabetic female needs to be further elicited in the future.
    Mots-clés : Cardiac function, crmbm, cvs, Endothelial function, Energy Metabolism, Gender differences, Type 2 diabetic heart.

  • Guenoun, D, Fouré, A, Pithioux, M, Guis, S, Le Corroller, T, Mattei, J-P, Pauly, V, Guye, M, Bernard, M, Chabrand, P, Champsaur, P & Bendahan, D 2017, “Correlative Analysis of Vertebral Trabecular Bone Microarchitecture and Mechanical Properties: A Combined Ultra-high Field (7 Tesla) MRI and Biomechanical Investigation”, Spine, vol. 42, no. 20, p. E1165-E1172.
    Résumé : STUDY DESIGN: High-resolution imaging and biomechanical investigation of ex-vivo vertebrae. OBJECTIVE: The aim of this study was to assess bone microarchitecture of cadaveric vertebrae using ultra-high field (UHF) 7 Tesla magnetic resonance imaging (MRI) and to determine whether the corresponding microarchitecture parameters were related to bone mineral density (BMD) and bone strength assessed by dual-energy x-ray absorptiometry (DXA) and mechanical compression tests. SUMMARY OF BACKGROUND DATA: Limitations of DXA for the assessment of bone fragility and osteoporosis have been recognized and criteria of microarchitecture alteration have been included in the definition of osteoporosis. Although vertebral fracture is the most common osteoporotic fracture, no study has assessed directly vertebral trabecular bone microarchitecture. METHODS: BMD of 24 vertebrae (L2, L3, L4) from eight cadavers was investigated using DXA. The bone volume fraction (BVF), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp) of each vertebra were quantified using UHF MRI. Measurements were performed by two operators to characterize the inter-rater reliability. The whole set of specimens underwent mechanical compression tests to failure and the corresponding failure stress was calculated. RESULTS: The inter-rater reliability for bone microarchitecture parameters was good with intraclass correlation coefficients ranging from 0.82 to 0.94. Failure load and stress were significantly correlated with BVF, Tb.Sp, and BMD (P < 0.05). Tb.Th was only correlated with the failure stress (P < 0.05). Multiple regression analysis demonstrated that the combination of BVF and BMD improved the prediction of the failure stress from an adjusted R = 0.384 for BMD alone to an adjusted R = 0.414. CONCLUSION: We demonstrated for the first time that the vertebral bone microarchitecture assessed with UHF MRI was significantly correlated with biomechanical parameters. Our data suggest that the multimodal assessment of BMD and trabecular bone microarchitecture with UHF MRI provides additional information on the risk of vertebral bone fracture and might be of interest for the future investigation of selected osteoporotic patients. LEVEL OF EVIDENCE: N /A.
    Mots-clés : crmbm, msk.

  • Lutz, NW & Bernard, M 2017, “Multiparametric quantification of thermal heterogeneity within aqueous materials by water 1H NMR spectroscopy: Paradigms and algorithms”, PLOS ONE, vol. 12, no. 5, p. e0178431, viewed 18August,2017, .
    Résumé : Processes involving heat generation and dissipation play an important role in the performance of numerous materials. The behavior of (semi-)aqueous materials such as hydrogels during production and application, but also properties of biological tissue in disease and therapy (e.g., hyperthermia) critically depend on heat regulation. However, currently available thermometry methods do not provide quantitative parameters characterizing the overall temperature distribution within a volume of soft matter. To this end, we present here a new paradigm enabling accurate, contactless quantification of thermal heterogeneity based on the line shape of a water proton nuclear magnetic resonance (1H NMR) spectrum. First, the 1H NMR resonance from water serving as a "temperature probe" is transformed into a temperature curve. Then, the digital points of this temperature profile are used to construct a histogram by way of specifically developed algorithms. We demonstrate that from this histogram, at least eight quantitative parameters describing the underlying statistical temperature distribution can be computed: weighted median, weighted mean, standard deviation, range, mode(s), kurtosis, skewness, and entropy. All mathematical transformations and calculations are performed using specifically programmed EXCEL spreadsheets. Our new paradigm is helpful in detailed investigations of thermal heterogeneity, including dynamic characteristics of heat exchange at sub-second temporal resolution.
    Mots-clés : Algorithms, crmbm, cvs, Distribution curves, Entropy, Gels, NMR spectroscopy, Nuclear magnetic resonance, Skewness, Statistical distributions.


Journal Article

  • Abdesselam, I, Dutour, A, Kober, F, Ancel, P, Bege, T, Darmon, P, Lesavre, N, Bernard, M & Gaborit, B 2016, “Time Course of Change in Ectopic Fat Stores After Bariatric Surgery”, Journal of the American College of Cardiology, vol. 67, no. 1, p. 117-119.

  • Bal-Theoleyre, L, Lalande, A, Kober, F, Giorgi, R, Collart, F, Piquet, P, Habib, G, Avierinos, J-F, Bernard, M, Guye, M & Jacquier, A 2016, “Aortic Function's Adaptation in Response to Exercise-Induced Stress Assessing by 1.5T MRI: A Pilot Study in Healthy Volunteers”, PloS One, vol. 11, no. 6, p. e0157704.
    Résumé : AIM: Evaluation of the aortic "elastic reserve" might be a relevant marker to assess the risk of aortic event. Our aim was to compare regional aortic elasticity at rest and during supine bicycle exercise at 1.5 T MRI in healthy individuals. METHODS: Fifteen volunteers (8 men), with a mean age of 29 (23-41) years, completed the entire protocol. Images were acquired immediately following maximal exercise. Retrospective cine sequences were acquired to assess compliance, distensibility, maximum rates of systolic distension and diastolic recoil at four different locations: ascending aorta, proximal descending aorta, distal descending aorta and aorta above the coeliac trunk level. Segmental aortic pulse wave velocity (PWV) was assessed by through plane velocity-encoded MRI. RESULTS: Exercise induced a significant decrease of aortic compliance and distensibility, and a significant increase of the absolute values of maximum rates of systolic distension and diastolic recoil at all sites (p<10-3). At rest and during stress, ascending aortic compliance was statistically higher compared to the whole descending aorta (p≤0.0007). We found a strong correlation between the rate pressure product and aortic distensibility at all sites (r = - 0.6 to -0.75 according to the site, p<10-4). PWV measured at the proximal and distal descending aorta increased significantly during stress (p = 0.02 and p = 0.008, respectively). CONCLUSION: Assessment of regional aortic function during exercise is feasible using MRI. During stress, aortic elasticity decreases significantly in correlation with an increase of the PWV. Further studies are required to create thresholds for ascending aorta dysfunction among patients with aneurysms, and to monitor the impact of medication on aortic remodeling.
    Mots-clés : Adaptation, Physiological, Adult, Aorta, Aorta, Thoracic, crmbm, cvs, Diastole, Elasticity, Exercise, Female, Healthy Volunteers, Humans, Magnetic Resonance Imaging, Male, Pilot Projects, Pulse Wave Analysis, Stress, Physiological, Supine Position, Systole, Vascular Stiffness.

  • Béchir, N, Pecchi, E, Vilmen, C, Le Fur, Y, Amthor, H, Bernard, M, Bendahan, D & Giannesini, B 2016, “ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo”, FASEB journal: official publication of the Federation of American Societies for Experimental Biology, vol. 30, no. 10, p. 3551-3562.
    Résumé : Postnatal blockade of the activin type IIB receptor (ActRIIB) represents a promising therapeutic strategy for counteracting dystrophic muscle wasting. However, its impact on muscle function and bioenergetics remains poorly documented in physiologic conditions. We have investigated totally noninvasively the effect of 8-wk administration of either soluble ActRIIB signaling inhibitor (sActRIIB-Fc) or vehicle PBS (control) on gastrocnemius muscle force-generating capacity, energy metabolism, and anatomy in dystrophic mdx mice using magnetic resonance (MR) imaging and dynamic [(31)P]-MR spectroscopy ([(31)P]-MRS) in vivo ActRIIB inhibition increased muscle volume (+33%) without changing fiber-type distribution, and increased basal animal oxygen consumption (+22%) and energy expenditure (+23%). During an in vivo standardized fatiguing exercise, maximum and total absolute contractile forces were larger (+40 and 24%, respectively) in sActRIIB-Fc treated animals, whereas specific force-generating capacity and fatigue resistance remained unaffected. Furthermore, sActRIIB-Fc administration did not alter metabolic fluxes, ATP homeostasis, or contractile efficiency during the fatiguing bout of exercise, although it dramatically reduced the intrinsic mitochondrial capacity for producing ATP. Overall, sActRIIB-Fc treatment increased muscle mass and strength without altering the fundamental weakness characteristic of dystrophic mdx muscle. These data support the clinical interest of ActRIIB blockade for reversing dystrophic muscle wasting.-Béchir, N., Pecchi, E., Vilmen, C., Le Fur, Y., Amthor, H., Bernard, M., Bendahan, D., Giannesini, B. ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo.
    Mots-clés : crmbm, Duchenne muscular dystrophy, msk, Muscle Fatigue, myostatin inhibition, skeletal muscle hypertrophy.

  • Bernard, M, Maixent, J-M, Gerbi, A, Lan, C, Cozzone, PJ, Pieroni, G, Armand, M & Coste, TC 2016, “Dietary docosahexaenoic acid-enriched glycerophospholipids exert cardioprotective effects in ouabain-treated rats via physiological and metabolic changes”, Food & Function, vol. 7, no. 2, p. 798-804.
    Résumé : Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 × 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analysed by gas chromatography. DHA accretion in the heart was dose-dependent (+8%, +30% and +45% for DHA10, DHA35 and DHA60, respectively). The cardiac phosphocreatine content significantly increased at the baseline in DHA35 (+45%) and DHA60 groups (+85%), and at the different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups versus control (+150%, +122.5% and +135% for DHA10, DHA35 and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional food, and possibly as a co-treatment with digitalis drugs in humans.
    Mots-clés : crmbm, snc.

  • Bricq, S, Frandon, J, Bernard, M, Guye, M, Finas, M, Marcadet, L, Miquerol, L, Kober, F, Habib, G, Fagret, D, Jacquier, A & Lalande, A 2016, “Semiautomatic detection of myocardial contours in order to investigate normal values of the left ventricular trabeculated mass using MRI”, Journal of magnetic resonance imaging: JMRI, vol. 43, no. 6, p. 1398-1406.
    Résumé : PURPOSE: To propose, assess, and validate a semiautomatic method allowing rapid and reproducible measurement of trabeculated and compacted left ventricular (LV) masses from cardiac magnetic resonance imaging (MRI). MATERIALS AND METHODS: We developed a method to automatically detect noncompacted, endocardial, and epicardial contours. Papillary muscles were segmented using semiautomatic thresholding and were included in the compacted mass. Blood was removed from trabeculae using the same threshold tool. Trabeculated, compacted masses and ratio of noncompacted to compacted (NC:C) masses were computed. Preclinical validation was performed on four transgenic mice with hypertrabeculation of the LV (high-resolution cine imaging, 11.75T). Then analysis was performed on normal cine-MRI examinations (steady-state free precession [SSFP] sequences, 1.5T or 3T) obtained from 60 healthy participants (mean age 49 ± 16 years) with 10 men and 10 women for each of the following age groups: [20,39], [40,59], and [60,79]. Interobserver and interexamination segmentation reproducibility was assessed by using Bland-Altman analysis and by computing the correlation coefficient. RESULTS: In normal participants, noncompacted and compacted masses were 6.29 ± 2.03 g/m(2) and 62.17 ± 11.32 g/m(2) , respectively. The NC:C mass ratio was 10.26 ± 3.27%. Correlation between the two observers was from 0.85 for NC:C ratio to 0.99 for end-diastolic volume (P < 10(-5) ). The bias between the two observers was -1.06 ± 1.02 g/m(2) for trabeculated mass, -1.41 ± 2.78 g/m(2) for compacted mass, and -1.51 ± 1.77% for NC:C ratio. CONCLUSION: We propose a semiautomatic method based on region growing, active contours, and thresholding to calculate the NC:C mass ratio. This method is highly reproducible and might help in the diagnosis of LV noncompaction cardiomyopathy. J. Magn. Reson. Imaging 2016;43:1398-1406.
    Mots-clés : cardiovascular magnetic resonance imaging, crmbm, cvs, left ventricle, noncompaction, papillary muscles, trabeculae.

  • Dutour, A, Abdesselam, I, Ancel, P, Kober, F, Mrad, G, Darmon, P, Ronsin, O, Pradel, V, Lesavre, N, Martin, JC, Jacquier, A, Lefur, Y, Bernard, M & Gaborit, B 2016, “Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: a prospective randomized clinical trial using magnetic resonance imaging and spectroscopy”, Diabetes, Obesity & Metabolism, vol. 18, no. 9, p. 882-891.
    Résumé : AIM: To conduct a prospective randomized trial to investigate the effect of glucagon-like peptide-1 (GLP-1) analogues on ectopic fat stores. METHODS: A total of 44 obese subjects with type 2 diabetes uncontrolled on oral antidiabetic drugs were randomly assigned to receive exenatide or reference treatment according to French guidelines. Epicardial adipose tissue (EAT), myocardial triglyceride content (MTGC), hepatic triglyceride content (HTGC) and pancreatic triglyceride content (PTGC) were assessed 45 min after a standardized meal with 3T magnetic resonance imaging and proton magnetic resonance spectroscopy before and after 26 weeks of treatment. RESULTS: The study population had a mean glycated haemoglobin (HbA1c) level of 7.5 ± 0.2% and a mean body mass index of 36.1 ± 1.1 kg/m(2) . Ninety five percent had hepatic steatosis at baseline (HTGC ≥ 5.6%). Exenatide and reference treatment led to a similar improvement in HbA1c (-0.7 ± 0.3% vs. -0.7 ± 0.4%; p = 0.29), whereas significant weight loss was observed only in the exenatide group (-5.5 ± 1.2 kg vs. -0.2 ± 0.8 kg; p = 0.001 for the difference between groups). Exenatide induced a significant reduction in EAT (-8.8 ± 2.1%) and HTGC (-23.8 ± 9.5%), compared with the reference treatment (EAT: -1.2 ± 1.6%, p = 0.003; HTGC: +12.5 ± 9.6%, p = 0.007). No significant difference was observed in other ectopic fat stores, PTGC or MTGC. In the group treated with exenatide, reductions in liver fat and EAT were not associated with homeostatic model assessment of insulin resistance index, adiponectin, HbA1c or fructosamin change, but were significantly related to weight loss (r = 0.47, p = 0.03, and r = 0.50, p = 0.018, respectively). CONCLUSION: Our data indicate that exenatide is an effective treatment to reduce liver fat content and epicardial fat in obese patients with type 2 diabetes, and these effects are mainly weight loss dependent.
    Mots-clés : crmbm, cvs, epicardial adipose tissue, glucagon-like peptide 1 receptor agonist, hepatic triglyceride content, Magnetic Resonance Imaging, magnetic-resonance imaging, myocardial triglyceride content, Obesity, pancreatic triglyceride content, Proton Magnetic Resonance Spectroscopy, proton magnetic-resonance spectroscopy, type 2 diabetes.

  • Galant, D, Gaborit, B, Desgrouas, C, Abdesselam, I, Bernard, M, Levy, N, Merono, F, Coirault, C, Roll, P, Lagarde, A, Bonello-Palot, N, Bourgeois, P, Dutour, A & Badens, C 2016, “A Heterozygous ZMPSTE24 Mutation Associated with Severe Metabolic Syndrome, Ectopic Fat Accumulation, and Dilated Cardiomyopathy”, Cells, vol. 5, no. 2.
    Résumé : ZMPSTE24 encodes the only metalloprotease, which transforms prelamin into mature lamin A. Up to now, mutations in ZMPSTE24 have been linked to Restrictive Dermopathy (RD), Progeria or Mandibulo-Acral Dysplasia (MAD). We report here the phenotype of a patient referred for severe metabolic syndrome and cardiomyopathy, carrying a mutation in ZMPSTE24. The patient presented with a partial lipodystrophic syndrome associating hypertriglyceridemia, early onset type 2 diabetes, and android obesity with truncal and abdominal fat accumulation but without subcutaneous lipoatrophy. Other clinical features included acanthosis nigricans, liver steatosis, dilated cardiomyopathy, and high myocardial and hepatic triglycerides content. Mutated fibroblasts from the patient showed increased nuclear shape abnormalities and premature senescence as demonstrated by a decreased Population Doubling Level, an increased beta-galactosidase activity and a decreased BrdU incorporation rate. Reduced prelamin A expression by siRNA targeted toward LMNA transcripts resulted in decreased nuclear anomalies. We show here that a central obesity without subcutaneous lipoatrophy is associated with a laminopathy due to a heterozygous missense mutation in ZMPSTE24. Given the high prevalence of metabolic syndrome and android obesity in the general population, and in the absence of familial study, the causative link between mutation and phenotype cannot be formally established. Nevertheless, altered lamina architecture observed in mutated fibroblasts are responsible for premature cellular senescence and could contribute to the phenotype observed in this patient.
    Mots-clés : cvs, laminopathy, metabolic syndrome, nuclear anomalies, premature senescence, ZMPSTE24.


Book Section

  • Bernard, M, Kober, F & Caus, T 2015, “Assessing Cardiac Transplant Viability with MRS”, in eMagRes, John Wiley & Sons, Ltd, viewed 18November,2015, .
    Résumé : Heart transplantation remains the treatment of choice for severe heart failure and end-stage cardiac disease. In a context of organ shortage and increasing inclusion of marginal donors, it is important to safely use the available grafts but without overestimating myocardial injury, which could result in discarding viable grafts. The development of biomarkers to assess cardiac graft viability before transplantation is thus of major interest. An important indicator of graft quality is given by high-energy phosphate compound concentrations that can be assessed noninvasively using 31P magnetic resonance spectroscopy. This method is also of use in assessing graft viability after transplantation when cardiac allograft vasculopathy can develop, which is associated with diffuse perfusion defects that potentially affect energy metabolism.
    Mots-clés : 31P MRS, cardiac, cardiac allograft vasculopathy, crmbm, cvs, early graft failure, graft viability, transplantation.
Journal Article

  • Capron, T, Troalen, T, Robert, B, Jacquier, A, Bernard, M & Kober, F 2015, “Myocardial perfusion assessment in humans using steady-pulsed arterial spin labeling”, Magnetic Resonance in Medicine, vol. 74, no. 4, p. 990-998, viewed 5October,2015, .
    Résumé : Purpose Although arterial spin labeling (ASL) has become a routinely performed method in the rodent heart, its application to the human heart remains challenged by low tissue blood flow and cardiac and respiratory motion. We hypothesized that an alternative steady-pulsed ASL (spASL) method would provide more efficient perfusion signal averaging by driving the tissue magnetization into a perfusion-dependent steady state. Methods We evaluated the feasibility of spASL in the human heart by combining pulsed labeling in the aortic root with a balanced steady state free precession sequence. The spASL scheme was applied to 13 subjects under free breathing. Breathing motion was addressed using retrospective image exclusion based on a contour-based cross-correlation algorithm. Results The measured signal with spASL was due to labeled blood. We found that the perfusion signal was larger than that obtained with the earlier flow-sensitive alternating inversion recovery (FAIR) method. Averaged myocardial blood flow (MBF) over four myocardial regions was 1.28 ± 0.36 mL·g−1·min−1. Conclusion spASL was able to quantify MBF in healthy subjects under free breathing. Because quantification with ASL is more direct than with first-pass perfusion MRI, it appears particularly suited for pathologies with diffuse microvascular alterations, MBF reserve, and follow-up studies. Magn Reson Med 74:990–998, 2015. © 2014 Wiley Periodicals, Inc.
    Mots-clés : arterial spin labeling, Blood Flow, cine-ASL, crmbm, cvs, myocardial perfusion, steady state, steady-pulsed.

  • Gaborit, B, Abdesselam, I, Kober, F, Jacquier, A, Ronsin, O, Emungania, O, Lesavre, N, Alessi, M-C, Martin, JC, Bernard, M & Dutour, A 2015, “Ectopic fat storage in the pancreas using 1H-MRS: importance of diabetic status and modulation with bariatric surgery-induced weight loss”, International Journal of Obesity (2005), vol. 39, no. 3, p. 480-487.
    Résumé : OBJECTIVES: Recent literature suggests that ectopic fat deposition in the pancreas may contribute to endocrine and exocrine organ dysfunction, such as type 2 diabetes (T2D), pancreatitis or pancreatic cancer. The aim of this study was to determine factors associated with pancreatic triglyceride content (PTGC), and to investigate the impact of bariatric surgery on ectopic fat pads, pancreatic fat (PTGC) and hepatic fat (HTGC). SUBJECTS: In all, 45 subjects (13 lean, 13 obese nondiabetics and 19 T2D, matched for age and gender) underwent 1H-magnetic resonance spectroscopy, computed tomography of the visceral abdominal fat, metabolic and lipidomic analysis, including insulin-resistance homeostasis model assessment (HOMA-IR), insulin-secretion homeostasis model assessment (HOMA-B) and plasma fatty-acid composition. Twenty obese subjects were reassessed 6 months after the bariatric surgery. RESULTS: PTGC was significantly higher in type 2 diabetic subjects (23.8±3.2%) compared with obese (14.0±3.3; P=0.03) and lean subjects (7.5±0.9%; P=0.0002). PTGC remained significantly associated with T2D after adjusting for age and sex (β=0.47; P=0.004) or even after adjusting for waist circumference, triglycerides and HOMA-IR (β=0.32; P=0.04). T2D, C18:1n-9 (oleic acid), uric acid, triglycerides and plasminogen activator inhibitor-1 were the five more important parameters involved in PTGC prediction (explained 80% of PTGC variance). Bariatric surgery induced a huge reduction of both HTGC (-51.2±7.9%) and PTGC (-43.8±7.0%) reaching lean levels, whereas body mass index remained greatly elevated. An improvement of insulin resistance HOMA-IR and no change in HOMA-B were observed after bariatric surgery. The PTGC or HTGC losses were not correlated, suggesting tissue-specific mobilization of these ectopic fat stores. CONCLUSION: Pancreatic fat increased with T2D and drastically decreased after the bariatric surgery. This suggests that decreased PTGC may contribute to improved beta cell function seen after the bariatric surgery. Further, long-term interventional studies are warranted to examine this hypothesis and to determine the degree to which ectopic fat mobilization may mediate the improvement in endocrine and exocrine pancreatic functions.
    Mots-clés : crmbm, cvs.

  • Macia, M, Pecchi, E, Vilmen, C, Desrois, M, Lan, C, Portha, B, Bernard, M, Bendahan, D & Giannesini, B 2015, “Insulin Resistance Is Not Associated with an Impaired Mitochondrial Function in Contracting Gastrocnemius Muscle of Goto-Kakizaki Diabetic Rats In Vivo”, PloS One, vol. 10, no. 6, p. e0129579.
    Résumé : Insulin resistance, altered lipid metabolism and mitochondrial dysfunction in skeletal muscle would play a major role in type 2 diabetes mellitus (T2DM) development, but the causal relationships between these events remain conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in Goto-Kakizaki (GK) rats, a non-obese T2DM model developing peripheral insulin resistant without abnormal level of plasma non-esterified fatty acids (NEFA). Wistar rats were used as controls. Mechanical performance and energy metabolism were assessed strictly non-invasively using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Compared with control group, plasma insulin and glucose were respectively lower and higher in GK rats, but plasma NEFA level was normal. In resting GK muscle, phosphocreatine content was reduced whereas glucose content and intracellular pH were both higher. However, there were not differences between both groups for basal oxidative ATP synthesis rate, citrate synthase activity, and intramyocellular contents for lipids, glycogen, ATP and ADP (an important in vivo mitochondrial regulator). During a standardized fatiguing protocol (6 min of maximal repeated isometric contractions electrically induced at a frequency of 1.7 Hz), mechanical performance and glycolytic ATP production rate were reduced in diabetic animals whereas oxidative ATP production rate, maximal mitochondrial capacity and ATP cost of contraction were not changed. These findings provide in vivo evidence that insulin resistance is not caused by an impairment of mitochondrial function in this diabetic model.
    Mots-clés : crmbm, cvs, msk.

  • Masi, B, Perles-Barbacaru, T-A, Laprie, C, Dessein, H, Bernard, M, Dessein, A & Viola, A 2015, “In Vivo MRI Assessment of Hepatic and Splenic Disease in a Murine Model of Schistosomiasis [corrected]”, PLoS neglected tropical diseases, vol. 9, no. 9, p. e0004036.
    Résumé : BACKGROUND: Schistosomiasis (or bilharzia), a major parasitic disease, affects more than 260 million people worldwide. In chronic cases of intestinal schistosomiasis caused by trematodes of the Schistosoma genus, hepatic fibrosis develops as a host immune response to the helminth eggs, followed by potentially lethal portal hypertension. In this study, we characterized hepatic and splenic features of a murine model of intestinal schistosomiasis using in vivo magnetic resonance imaging (MRI) and evaluated the transverse relaxation time T2 as a non-invasive imaging biomarker for monitoring hepatic fibrogenesis. METHODOLOGY/PRINCIPAL FINDINGS: CBA/J mice were imaged at 11.75 T two, six and ten weeks after percutaneous infection with Schistosoma mansoni. In vivo imaging studies were completed with histology at the last two time points. Anatomical MRI allowed detection of typical manifestations of the intestinal disease such as significant hepato- and splenomegaly, and dilation of the portal vein as early as six weeks, with further aggravation at 10 weeks after infection. Liver multifocal lesions observed by MRI in infected animals at 10 weeks post infection corresponded to granulomatous inflammation and intergranulomatous fibrosis with METAVIR scores up to A2F2. While most healthy hepatic tissue showed T2 values below 14 ms, these lesions were characterized by a T2 greater than 16 ms. The area fraction of increased T2 correlated (rS = 0.83) with the area fraction of Sirius Red stained collagen in histological sections. A continuous liver T2* decrease was also measured while brown pigments in macrophages were detected at histology. These findings suggest accumulation of hematin in infected livers. CONCLUSIONS/SIGNIFICANCE: Our multiparametric MRI approach confirms that this murine model replicates hepatic and splenic manifestations of human intestinal schistosomiasis. Quantitative T2 mapping proved sensitive to assess liver fibrogenesis non-invasively and may therefore constitute an objective imaging biomarker for treatment monitoring in diseases involving hepatic fibrosis.
    Mots-clés : crmbm, sasnc.

  • Mlih, M, Host, L, Martin, S, Niederhoffer, N, Monassier, L, Terrand, J, Messaddeq, N, Radke, M, Gotthardt, M, Bruban, V, Kober, F, Bernard, M, Canet-Soulas, E, Abt-Jijon, F, Boucher, P & Matz, RL 2015, “The Src Homology and Collagen A (ShcA) Adaptor Protein Is Required for the Spatial Organization of the Costamere/Z-disk Network during Heart Development”, The Journal of Biological Chemistry, vol. 290, no. 4, p. 2419-2430.
    Résumé : Src homology and collagen A (ShcA) is an adaptor protein that binds to tyrosine kinase receptors. Its germ line deletion is embryonic lethal with abnormal cardiovascular system formation, and its role in cardiovascular development is unknown. To investigate its functional role in cardiovascular development in mice, ShcA was deleted in cardiomyocytes and vascular smooth muscle cells by crossing ShcA flox mice with SM22a-Cre transgenic mice. Conditional mutant mice developed signs of severe dilated cardiomyopathy, myocardial infarctions, and premature death. No evidence of a vascular contribution to the phenotype was observed. Histological analysis of the heart revealed aberrant sarcomeric Z-disk and M-band structures, and misalignments of T-tubules with Z-disks. We find that not only the ErbB3/Neuregulin signaling pathway but also the baroreceptor reflex response, which have been functionally associated, are altered in the mutant mice. We further demonstrate that ShcA interacts with Caveolin-1 and the costameric protein plasma membrane Ca(2+)/calmodulin-dependent ATPase (PMCA), and that its deletion leads to abnormal dystrophin signaling. Collectively, these results demonstrate that ShcA interacts with crucial proteins and pathways that link Z-disk and costamere.
    Mots-clés : crmbm, cvs.

  • Rapetti-Mauss, R, Lacoste, C, Picard, V, Guitton, C, Lombard, E, Loosveld, M, Nivaggioni, V, Dasilva, N, Salgado, D, Desvignes, J-P, Béroud, C, Viout, P, Bernard, M, Soriani, O, Vinti, H, Lacroze, V, Feneant-Thibault, M, Thuret, I, Guizouarn, H & Badens, C 2015, “A mutation in the Gardos channel is associated with hereditary xerocytosis”, Blood, vol. 126, no. 11, p. 1273-1280.
    Résumé : The Gardos channel is a Ca(2+)-sensitive, intermediate conductance, potassium selective channel expressed in several tissues including erythrocytes and pancreas. In normal erythrocytes, it is involved in cell volume modification. Here, we report the identification of a dominantly inherited mutation in the Gardos channel in 2 unrelated families and its association with chronic hemolysis and dehydrated cells, also referred to as hereditary xerocytosis (HX). The affected individuals present chronic anemia that varies in severity. Their red cells exhibit a panel of various shape abnormalities such as elliptocytes, hemighosts, schizocytes, and very rare stomatocytic cells. The missense mutation concerns a highly conserved residue among species, located in the region interacting with Calmodulin and responsible for the channel opening and the K(+) efflux. Using 2-microelectrode experiments on Xenopus oocytes and patch-clamp electrophysiology on HEK293 cells, we demonstrated that the mutated channel exhibits a higher activity and a higher Ca(2+) sensitivity compared with the wild-type (WT) channel. The mutated channel remains sensitive to inhibition suggesting that treatment of this type of HX by a specific inhibitor of the Gardos channel could be considered. The identification of a KCNN4 mutation associated with chronic hemolysis constitutes the first report of a human disease caused by a defect of the Gardos channel.
    Mots-clés : Adult, Amino Acid Sequence, Anemia, Hemolytic, Congenital, Animals, Child, Preschool, cvs, Erythrocytes, Abnormal, Female, Genes, Dominant, HEK293 Cells, Humans, Hydrops Fetalis, In Vitro Techniques, Infant, Infant, Newborn, Intermediate-Conductance Calcium-Activated Potassium Channels, Male, Models, Molecular, Molecular Sequence Data, Mutant Proteins, Mutation, Missense, Oocytes, Osmotic Fragility, Patch-Clamp Techniques, Pedigree, Pregnancy, Recombinant Proteins, Sequence Homology, Amino Acid, Xenopus laevis.

  • Yashiro, K, Tonson, A, Pecchi, É, Vilmen, C, Le Fur, Y, Bernard, M, Bendahan, D & Giannesini, B 2015, “Capsiate Supplementation Reduces Oxidative Cost of Contraction in Exercising Mouse Skeletal Muscle In Vivo”, PloS One, vol. 10, no. 6, p. e0128016.
    Résumé : Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the Km of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.
    Mots-clés : crmbm, cvs.


Journal Article

  • Bernard, M, Jacquier, A & Kober, F 2014, “Cardiovascular magnetic resonance in ischemic heart disease”, Future Cardiology, vol. 10, no. 4, p. 487-496.
    Résumé : Ischemic heart disease is the major cause of death in developed countries. Recently, cardiovascular magnetic resonance (CMR) has appeared as a powerful technique for diagnosis and prognosis of ischemia, as well as for postischemic therapy follow-up. The objective of this chapter is to provide an overview of the role of CMR in assessing ischemic myocardium. It reviews the most recent studies in this field and includes CMR parameters that are already well established in the clinical setting as well as promising or emerging parameters in clinical use.
    Mots-clés : crmbm.

  • Desrois, M, Piccardo, A, Zogheib, E, Dalmasso, C, Lan, C, Fourré, D, Cozzone, PJ, Caus, T & Bernard, M 2014, “Heart donation after cardiac death: preliminary study on an isolated, perfused Swine heart after 20 minutes of normothermic ischemia”, Transplantation Proceedings, vol. 46, no. 10, p. 3314-3318.
    Résumé : BACKGROUND: We measured the functional and metabolic status of hearts submitted to normothermic ischemia before preservation through the use of an ex vivo pig heart model to assess the feasibility of donation after cardiac death (DCD) in heart transplantation. METHODS: Ten pigs were separated into 2 groups: control (n = 6, brain-dead group) and DCD (n = 4, heart donation after cardiac death). In the control group, hearts were excised 20 minutes after the brachiocephalic trunk cross-clamping and were immediately reperfused. In DCD, hearts were excised 20 minutes after exsanguination and asphyxia, stored in the Centre de Résonance Magnétique Biologique et Médicale (CRMBM) solution for 2 hours, and then were reperfused. Cardioplegic arrest was induced with the use of 1 L of CRMBM solution (4°C) and the heart was reperfused for 60 minutes through the use of an ex vivo perfusion system in Langendorff mode with normothermic autologous blood. During reperfusion, functional parameters were analyzed. Biochemical assays were performed in myocardial effluents and freeze-clamped hearts. RESULTS: No electromechanical activity was found in DCD compared with control. Creatine kinase (CK) was higher at 2 minutes of reperfusion in DCD versus control (P = .005). Adenosine triphosphate was lower in DCD versus control (P = .0019). Malondialdehyde, an oxidative stress index, was present only in DCD. The nitric oxide (NO) pathway was impaired in DCD versus control, with lower eNOS expression (P < .0001) and total nitrate concentration content (P = .04). CONCLUSIONS: We reported no cardiac functional and metabolic recovery in the DCD group after normothermic ischemia and reperfusion, which indicates that a single immersion of the cardiac graft during storage does not provide an optimal protection. New strategies in heart preservation are necessary for recruiting heart donation after cardiac death.
    Mots-clés : crmbm.

  • Desrois, M, Kober, F, Lan, C, Dalmasso, C, Cole, M, Clarke, K, Cozzone, PJ & Bernard, M 2014, “Effect of isoproterenol on myocardial perfusion, function, energy metabolism and nitric oxide pathway in the rat heart – a longitudinal MR study”, NMR in Biomedicine, vol. 27, no. 5, p. 529-538, viewed 20February,2014, .
    Résumé : The chronic administration of the β-adrenoreceptor agonist isoproterenol (IsoP) is used in animals to study the mechanisms of cardiac hypertrophy and failure associated with a sustained increase in circulating catecholamines. Time-dependent changes in myocardial blood flow (MBF), morphological and functional parameters were assessed in rats in vivo using multimodal cardiac MRI. Energy metabolism, oxidative stress and the nitric oxide (NO) pathway were evaluated in isolated perfused rat hearts following 7 days of treatment. Male Wistar rats were infused for 7 days with IsoP or vehicle using osmotic pumps. Cine-MRI and arterial spin labeling were used to determine left ventricular morphology, function and MBF at days 1, 2 and 7 after pump implantation. Isolated hearts were then perfused, and high-energy phosphate compounds and intracellular pH were followed using 31P MRS with simultaneous measurement of contractile function. Total creatine and malondialdehyde (MDA) contents were measured by high-performance liquid chromatography. The NO pathway was evaluated by NO synthase isoform expression and total nitrate concentration (NOx). In IsoP-treated rats, left ventricular mass was increased at day 1 and maintained. Wall thickness was increased with a peak at day 2 and a tendency to return to baseline values at day 7. MBF was markedly increased at day 1 and returned to normal values between days 1 and 2. The rate–pressure product and phosphocreatine/adenosine triphosphate ratio in perfused hearts were reduced. MDA, endothelial NO synthase expression and NOx were increased. Sustained high cardiac function and normal MBF after 24 h of IsoP infusion indicate imbalance between functional demand and blood flow, leading to morphological changes. After 1 week, cardiac hypertrophy and decreased function were associated with impaired phosphocreatine, increased oxidative stress and up-regulation of the NO pathway. These results provide supplemental information on the evolution of the different contributing factors leading to morphological and functional changes in this model of cardiac hypertrophy and failure. Copyright © 2014 John Wiley & Sons, Ltd.
    Mots-clés : cine-MRI, crmbm, Function, Heart, isoproterenol, Metabolism, nitric oxide pathway, Perfusion, rat.

  • Kazuya, Y, Tonson, A, Pecchi, E, Dalmasso, C, Vilmen, C, Fur, YL, Bernard, M, Bendahan, D & Giannesini, B 2014, “A single intake of capsiate improves mechanical performance and bioenergetics efficiency in contracting mouse skeletal muscle”, American Journal of Physiology. Endocrinology and Metabolism, vol. 306, no. 10, p. E1110-1119.
    Résumé : Capsiate is known to increase whole body oxygen consumption possibly via the activation of uncoupling processes, but its effect at the skeletal muscle level remains poorly documented and conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated in mice 2 h after a single intake of either vehicle (control) or purified capsiate (at 10 or 100 mg/kg body wt) through a multidisciplinary approach combining in vivo and in vitro measurements. Mechanical performance and energy pathway fluxes were assessed strictly noninvasively during a standardized electrostimulation-induced exercise, using an original device implementing 31-phosphorus magnetic resonance spectroscopy, and mitochondrial respiration was evaluated in isolated saponin-permeabilized fibers. Compared with control, both capsiate doses produced quantitatively similar effects at the energy metabolism level, including an about twofold decrease of the mitochondrial respiration sensitivity for ADP. Interestingly, they did not alter either oxidative phosphorylation or uncoupling protein 3 gene expression at rest. During 6 min of maximal repeated isometric contractions, both doses reduced the amount of ATP produced from glycolysis and oxidative phosphorylation but increased the relative contribution of oxidative phosphorylation to total energy turnover (+28 and +21% in the 10- and 100-mg groups, respectively). ATP cost of twitch force generation was further reduced in the 10- (-35%) and 100-mg (-45%) groups. Besides, the highest capsiate dose also increased the twitch force-generating capacity. These data present capsiate as a helpful candidate to enhance both muscle performance and oxidative phosphorylation during exercise, which could constitute a nutritional approach for improving health and preventing obesity and associated metabolic disorders.
    Mots-clés : Animals, Biomechanical Phenomena, Capsaicin, Cells, Cultured, crmbm, Electric Stimulation, Energy Metabolism, Male, Mice, Mice, Inbred C57BL, Muscle Contraction, Muscle, Skeletal, Physical Conditioning, Animal.
    Attachment Full Text PDF 307.6 kb (source)

  • Kober, F, Troalen, T & Bernard, M 2014, “Recent Developments in Small Animal Cardiovascular MRI”, Current Cardiovascular Imaging Reports, vol. 7, no. 2, p. 1-10, viewed 16January,2014, .
    Résumé : This review is intended to give a comprehensive overview over new cardiovascular magnetic resonance (CMR) method developments and refinements dedicated to the fully non-invasive in vivo exploration of the rodent heart. Unlike other cardiovascular imaging techniques, CMR techniques exist in many modalities giving access to parameters characterizing morphology, global and regional function, blood flow, myocardial structure, cell damage, metabolism and other molecular processes in mouse and rat models of human disease. But even in healthy animals, small animal CMR techniques can help exploring general physiological and biochemical mechanisms in vivo. New magnetic resonance imaging methods and imaging protocols are actively being developed by the entire CMR community with the goal of widening the spectrum of observable and measurable myocardial properties. This report also includes a selection of application studies using recent CMR methodology in this field. Beyond giving new insights into pathophysiologic processes, these studies underline the growing usefulness of CMR in a small animal research context.
    Mots-clés : arterial spin labeling, Cardiology, Cardiovascular magnetic resonance, crmbm, Diagnostic Radiology, flow, Function, Imaging / Radiology, Interventional radiology, Mouse, MRI, Nuclear Medicine, Perfusion, Rodent, Self-gating, T1 mapping, T2 mapping, T2* mapping, Ultrasound.

  • Marcotorchino, J, Tourniaire, F, Astier, J, Karkeni, E, Canault, M, Amiot, M-J, Bendahan, D, Bernard, M, Martin, J-C, Giannesini, B & Landrier, J-F 2014, “Vitamin D protects against diet-induced obesity by enhancing fatty acid oxidation”, The Journal of Nutritional Biochemistry, vol. 25, no. 10, p. 1077-1083.
    Résumé : Prospective studies reported an inverse correlation between 25-hydroxyvitamin D [25(OH)D] plasma levels and prevalence of obesity and type 2 diabetes. In addition, 25(OH)D status may be a determinant of obesity onset. However, the causality between these observations is not yet established. We studied the preventive effect of vitamin D3 (VD3) supplementation (15,000IU/kg of food for 10weeks) on onset of obesity in a diet-induced obesity mouse model. We showed that the VD3 supplementation limited weight gain induced by high-fat diet, which paralleled with an improvement of glucose homeostasis. The limitation of weight gain could further be explained by an increased lipid oxidation, possibly due to an up-regulation of genes involved in fatty acid oxidation and mitochondrial metabolism, leading to increased energy expenditure. Altogether, these data show that VD3 regulates energy expenditure and suggest that VD3 supplementation may represent a strategy of preventive nutrition to fight the onset of obesity and associated metabolic disorders.

  • Odelin, G, Faure, E, Kober, F, Maurel-Zaffran, C, Théron, A, Coulpier, F, Guillet, B, Bernard, M, Avierinos, J-F, Charnay, P, Topilko, P & Zaffran, S 2014, “Loss of Krox20 results in aortic valve regurgitation and impaired transcriptional activation of fibrillar collagen genes”, Cardiovascular Research, vol. 104, no. 3, p. 443-455.
    Résumé : AIMS: Heart valve maturation is achieved by the organization of extracellular matrix (ECM) and the distribution of valvular interstitial cells. However, the factors that regulate matrix components required for valvular structure and function are unknown. Based on the discovery of its specific expression in cardiac valves, we aimed to uncover the role of Krox20 (Egr-2) during valve development and disease. METHODS AND RESULTS: Using series of mouse genetic tools, we demonstrated that loss of function of Krox20 caused significant hyperplasia of the semilunar valves, while atrioventricular valves appeared normal. This defect was associated with an increase in valvular interstitial cell number and ECM volume. Echo Doppler analysis revealed that adult mutant mice had aortic insufficiency. Defective aortic valves (AoVs) in Krox20(-/-) mice had features of human AoV disease, including excess of proteoglycan deposition and reduction of collagen fibres. Furthermore, examination of diseased human AoVs revealed decreased expression of KROX20. To identify downstream targets of Krox20, we examined expression of fibrillar collagens in the AoV leaflets at different stages in the mouse. We found significant down-regulation of Col1a1, Col1a2, and Col3a1 in the semilunar valves of Krox20 mutant mice. Utilizing in vitro and in vivo experiments, we demonstrated that Col1a1 and Col3a1 are direct targets of Krox20 activation in interstitial cells of the AoV. CONCLUSION: This study identifies a previously unknown function of Krox20 during heart valve development. These results indicate that Krox20-mediated activation of fibrillar Col1a1 and Col3a1 genes is crucial to avoid postnatal degeneration of the AoV leaflets.

  • Sagui, E, Abriat, A, Kozak-Ribbens, G, Foutrier-Morello, C, Bernard, M, Canini, F, Brosset, C & Bendahan, D 2014, “Is muscle energy production disturbed in exertional heat stroke?”, Military Medicine, vol. 179, no. 3, p. 342-345.
    Résumé : BACKGROUND: Exertional heat stroke (EHS) is a life-threatening disease that shares some clinical similarities with malignant hyperthermia (MH). By use of (31)Phosphorus magnetic resonance spectroscopy (MRS), EHS patients with MH susceptibility and MH patients shared common metabolic abnormalities. The aim of this study was to determine whether subjects who suffered from an EHS episode had disturbed muscle energetics. METHOD: This retrospective study was performed within the French database of military subjects that were explored from 2004 to 2010 after they suffered an EHS. All subjects had both in vitro contracture test to determine their MH susceptibility and (31)Phosphorus MRS at 4.7 Tesla to assess muscle energetics by means of MRS score, a composite score corresponding to the sum of metabolic abnormalities recorded during a standardized rest-exercise-recovery protocol. RESULTS: 437 subjects were investigated and 32.5% of them exhibited abnormal MRS score. MRS score did not segregate subjects on demographic, clinical, or biological grounds. No clear correlation could be done between MH status and MRS score. DISCUSSION: These results did not confirm the potential relationship between calcium homeostasis and muscle energetics previously reported. However, muscle energy production was disturbed in a significant number of EHS subjects.
    Mots-clés : crmbm.

  • Taso, M, Le Troter, A, Sdika, M, Ranjeva, J-P, Guye, M, Bernard, M & Callot, V 2014, “Construction of an in vivo human spinal cord atlas based on high-resolution MR images at cervical and thoracic levels: preliminary results”, Magma (New York, N.Y.), vol. 27, no. 3, p. 257-267.
    Résumé : OBJECT: Our goal was to build a probabilistic atlas and anatomical template of the human cervical and thoracic spinal cord (SC) that could be used for segmentation algorithm improvement, parametric group studies, and enrichment of biomechanical modelling. MATERIALS AND METHODS: High-resolution axial T2*-weighted images were acquired at 3T on 15 healthy volunteers using a multi-echo-gradient-echo sequence (1 slice per vertebral level from C1 to L2). After manual segmentation, linear and affine co-registrations were performed providing either inter-individual morphometric variability maps, or substructure probabilistic maps [CSF, white and grey matter (WM/GM)] and anatomical SC template. RESULTS: The larger inter-individual morphometric variations were observed at the thoraco-lumbar levels and in the posterior GM. Mean SC diameters were in agreement with the literature and higher than post-mortem measurements. A representative SC MR template was generated and values up to 90 and 100% were observed on GM and WM-probability maps. CONCLUSION: This work provides a probabilistic SC atlas and a template that could offer great potentialities for parametrical MRI analysis (DTI/MTR/fMRI) and group studies, similar to what has already been performed using a brain atlas. It also offers great perspective for biomechanical models usually based on post-mortem or generic data. Further work will consider integration into an automated SC segmentation pipeline.
    Mots-clés : award_ESMRMB13, crmbm.

  • Troalen, T, Capron, T, Bernard, M & Kober, F 2014, “In vivo characterization of rodent cyclic myocardial perfusion variation at rest and during adenosine-induced stress using cine-ASL cardiovascular magnetic resonance”, Journal of Cardiovascular Magnetic Resonance, vol. 16, no. 1, p. 18, viewed 19February,2014, .
    Résumé : Assessment of cyclic myocardial blood flow (MBF) variations can be an interesting addition to the characterization of microvascular function and its alterations. To date, totally non-invasive in vivo methods with this capability are still lacking. As an original technique, a cine arterial spin labeling (ASL) cardiovascular magnetic resonance approach is demonstrated to be able to produce dynamic MBF maps across the cardiac cycle in rats.
    Mots-clés : crmbm.


Journal Article

  • Capron, T, Troalen, T, Cozzone, PJ, Bernard, M & Kober, F 2013, “Cine-ASL: a steady-pulsed arterial spin labeling method for myocardial perfusion mapping in mice. Part II. Theoretical model and sensitivity optimization”, Magnetic Resonance in Medicine, vol. 70, no. 5, p. 1399-1408.
    Résumé : In small rodent myocardial perfusion studies, the most widely used method is based on Look-Locker measurements of the magnetization recovery after FAIR preparation, which bears limitations regarding acquisition efficiency due to the pulsed arterial spin labeling nature of the sequence. To improve efficiency, this two-article set proposes a new steady-pulsed arterial spin labeling scheme using a cine readout incorporating one tagging pulse per heart cycle. In this part, we derive a theoretical description of the magnetization time evolution in such a scheme. The combination of steady-pulsed labeling and cine readout drives tissue magnetization into a stationary regime that explicitly depends on perfusion. In comparison with dedicated experiments on the mouse heart, the model is discussed and validated for perfusion quantification. The model predicts that in this regime, signal is independent of irregular dynamics occurring during acquisition, such as heart rate variations or arterial input function. Optimization of the sequence offers the possibility to increase the signal to noise ratio by efficient signal averaging. The sensitivity of this new method is shown to be more than three times larger than previously used techniques.
    Mots-clés : crmbm.

  • Conductier, G, Brau, F, Viola, A, Langlet, F, Ramkumar, N, Dehouck, B, Lemaire, T, Chapot, R, Lucas, L, Rovère, C, Maitre, P, Hosseiny, S, Petit-Paitel, A, Adamantidis, A, Lakaye, B, Risold, P-Y, Prévot, V, Meste, O, Nahon, J-L & Guyon, A 2013, “Melanin-concentrating hormone regulates beat frequency of ependymal cilia and ventricular volume”, Nature Neuroscience, vol. 16, no. 7, p. 845-847.
    Résumé : Ependymal cell cilia help move cerebrospinal fluid through the cerebral ventricles, but the regulation of their beat frequency remains unclear. Using in vitro, high-speed video microscopy and in vivo magnetic resonance imaging in mice, we found that the metabolic peptide melanin-concentrating hormone (MCH) positively controlled cilia beat frequency, specifically in the ventral third ventricle, whereas a lack of MCH receptor provoked a ventricular size increase.
    Mots-clés : Adenosine Triphosphate, Animals, Brain, Calcium, Cerebral Ventricles, Cerebrospinal Fluid, Cilia, Electric Stimulation, Ependyma, Female, Hormone Antagonists, Hypothalamic Hormones, In Vitro Techniques, Male, Melanins, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Neurons, Pituitary Hormones, Receptors, Somatostatin, Serotonin.
  • Garcia, C, Duan, RD, Brévaut-Malaty, V, Gire, C, Millet, V, Simeoni, U, Bernard, M & Armand, M 2013, “Bioactive compounds in human milk and intestinal health and maturity in preterm newborn: an overview”, Cellular and Molecular Biology (Noisy-Le-Grand, France), vol. 59, no. 1, p. 108-131.
    Résumé : Premature births are increasing worldwide (about 15 millions per year) due to several reasons (an advanced maternal age, fertility treatments, stress, smoking, nutritional deficiencies) and lead to a high societal overall cost. Among neonatal care procedures, the clinical nutrition practices are essential to promote the development and to minimize the sequelae. Premature newborns are at major risk of death by infections due to the immaturity of their intestine. Human milk provides not only nutrients but also a plethora of biologically active components that are tailored to contribute to the development of the intestinal tract early in postnatal life. Among them, some bioactive molecules exhibit trophic effects (LC—PUFA, sphingomyelin, IGF—I and IGF—II, EGF, insulin, leptin, adiponectin, lactoferrin, lactadherin, probiotics, prebiotics, miRNA) or are part of the intestinal cell membranes (PUFA, LC—PUFA, phospholipids, sphingolipids, cholesterol), others educate the intestine for innate microbial recognition (sCD14, sTLR—2, miRNA), many of them display direct fighting against pathogens (some fatty acids and monoglycerides, some phospholipids and sphingolipids, BSSL, insulin, lactoferrin, sIgAs, MUC—1, lactadherin, probiotics, prebiotics), or contribute to establish the gut microbiota (LC—PUFA, lactoferrin, probiotics, prebiotics). A synergetic action exists between several bioactive molecules. All together these precious agents regulate the maturation of the intestinal mucosal barrier, and might program early in postnatal life the future adult intestinal health. This review lists the main bioactive compounds and addresses their plausible roles and mechanisms of action.
    Mots-clés : crmbm, Health, Humans, Infant, Newborn, Intestines, Macromolecular Substances, Milk, Human, Premature Birth.

  • Giannesini, B, Vilmen, C, Amthor, H, Bernard, M & Bendahan, D 2013, “Lack of myostatin impairs mechanical performance and ATP cost of contraction in exercising mouse gastrocnemius muscle in vivo”, American journal of physiology. Endocrinology and metabolism, vol. 305, no. 1, p. E33-40.
    Résumé : Although it is well established that the lack of myostatin (Mstn) promotes skeletal muscle hypertrophy, the corresponding changes regarding force generation have been studied mainly in vitro and remain conflicting. Furthermore, the metabolic underpinnings of these changes are very poorly documented. To clarify this issue, we have investigated strictly noninvasively in vivo the impact of the lack of Mstn on gastrocnemius muscle function and energetics in Mstn-targeted knockout (Mstn-/-) mice using ¹H-magnetic resonance (MR) imaging and ³¹P-MR spectroscopy during maximal repeated isometric contractions induced by transcutaneous electrostimulation. In Mstn-/- animals, although body weight, gastrocnemius muscle volume, and absolute force were larger (+38, +118, and +34%, respectively) compared with wild-type (Mstn+/+) mice, specific force (calculated from MR imaging measurements) was significantly lower (-36%), and resistance to fatigue was decreased. Besides, Mstn deficiency did not affect phosphorylated compound concentrations and intracellular pH at rest but caused a large increase in ATP cost of contraction (up to +206% compared with Mstn+/+) throughout the stimulation period. Further, Mstn deficiency limits the shift toward oxidative metabolism during muscle activity despite the fact that oxidative ATP synthesis capacity was not altered. Our data demonstrate in vivo that the absence of Mstn impairs both mechanical performance and energy cost of contraction in hypertrophic muscle. These findings must be kept in mind when considering Mstn as a potential therapeutic target for increasing muscle mass in patients suffering from muscle-wasting disorders.
    Mots-clés : Adenosine Triphosphate, Animals, Biomechanics, crmbm, Electric Stimulation, Energy Metabolism, Female, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Contraction, Muscle, Skeletal, Muscular Atrophy, Myostatin, Physical Conditioning, Animal.

  • Troalen, T, Capron, T, Cozzone, PJ, Bernard, M & Kober, F 2013, “Cine-ASL: a steady-pulsed arterial spin labeling method for myocardial perfusion mapping in mice. Part I. Experimental study”, Magnetic Resonance in Medicine, vol. 70, no. 5, p. 1389-1398.
    Résumé : Arterial spin labeling has been developed and used for the quantitative and completely noninvasive assessment of myocardial perfusion in vivo. Here we propose a novel arterial spin labeling method called cine-ASL, which is based on an electrocardiogram-gated steady-pulsed labeling approach combined with simultaneous readout over the cardiac cycle using cine-fast low-angle shot. This method led to shorter acquisition times than the previously used Look-Locker flow-sensitive alternating inversion recovery gradient-echo technique while preserving spatial resolution and robustness with respect to cardiac motion. High resolution perfusion mapping (in-plane resolution = 195 μm × 391 μm) was carried out with both techniques at 4.7 T in a group of 14 healthy mice. Mean perfusion values were 5.0 ± 0.8 mL g(-1) min(-1) with cine-ASL and 5.9 ± 1.4 mL g(-1) min(-1) with Look-Locker flow-sensitive alternating inversion recovery. In one animal, physiological stress was induced with higher anesthetic concentration to evaluate the response of both methods under vasodilation. Global myocardial perfusion increased from 5.6 to 16.0 mL g(-1) min(-1) with cine-ASL and from 6.3 to 18.7 mL g(-1) min(-1) with Look-Locker flow-sensitive alternating inversion recovery. Although this original scheme requires a separate T1 measurement to be fully quantitative, it improves arterial spin labeling sensitivity while maintaining compatibility with motion constraints in cardiac MRI in small rodents.
    Mots-clés : crmbm.
  • Zink, J, Souteyrand, P, Guis, S, Chagnaud, C, Le Fur, Y, Militianu, D, Mattei, JP, Rozenbaum, M, Rosner, I, Boudinet, H, Bernard, M & Bendahan, D 2013, “Semi-Automatic Quantitative Investigation of Wrist Cartilage in Humans Using 3t Mri”, Annals of the Rheumatic Diseases, vol. 72, p. 1018-1019.


Journal Article

  • Bartoli, MA, Kober, F, Cozzone, P, Thompson, RW, Alessi, MC & Bernard, M 2012, “In vivo assessment of murine elastase-induced abdominal aortic aneurysm with high resolution magnetic resonance imaging”, European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery, vol. 44, no. 5, p. 475-481.
    Résumé : OBJECTIVES: There are, to date, no published non-invasive or longitudinal studies performed in mice to measure aortic diameter and wall thickness in an elastase-induced abdominal aortic aneurysm. This MRI study at 11.75 T aimed at evaluating the reliability of longitudinal in vivo aortic diameter and wall thickness measurements in this particular model. METHODS: Adult male C57BL/6 mice underwent transient elastase or heat-inactivated elastase perfusion (controls). Aortic dilatation was measured before, during and immediately after elastase perfusion, and again 14 days after, with a calibrated ocular grid. MRI was performed just before initial surgery and at day 14 before harvest using an 11.75 T MR microscopy imager. RESULTS: Aortic diameter was significantly greater in elastase-perfused mice compared to controls as measured by optic grid (1.150 ± 0.153 mm vs 0.939 ± 0.07 mm, P = 0.038) and according to MRI measurement of the outer diameter on spin echo images (1.203 ± 0.105 mm vs 1070 ± 0.048 mm, P = 0.0067). Aortic wall thickness was found to be significantly increased in elastase-perfused mice at day 14. CONCLUSIONS: This study demonstrates in the mouse elastase-induced aneurysm model that characterization of aneurysm development by its inner and outer vessel diameter and vessel wall thickness can be carried out longitudinally using high resolution MRI without significant mortality.
    Mots-clés : AAA, Animals, Aorta, Abdominal, Aortic Aneurysm, Abdominal, crmbm, Dilatation, Pathologic, Disease Models, Animal, High resolution MRI, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred C57BL, Murine elastase-induced abdominal aortic aneurysm, Pancreatic Elastase, Time Factors.

  • Bun, S-S, Kober, F, Jacquier, A, Espinosa, L, Kalifa, J, Bonzi, M-F, Kopp, F, Lalevee, N, Zaffran, S, Deharo, J-C, Cozzone, PJ & Bernard, M 2012, “Value of in vivo T2 measurement for myocardial fibrosis assessment in diabetic mice at 11.75 T”, Investigative radiology, vol. 47, no. 5, p. 319-323.
    Résumé : OBJECTIVE: The aim of the study was to assess the value of in vivo T2 measurements to noninvasively quantify myocardial fibrosis in diabetic mice at 11.75 T. Diabetic cardiomyopathy is characterized by extracellular matrix alteration and microcirculation impairment. These conditions might provide electrical heterogeneity, which is a substrate for arrhythmogenesis. T1 mapping has been proposed to quantify diffuse myocardial fibrosis in cardiac diseases but has several limitations. T2 measurement may represent an alternative for fibrosis quantification at high magnetic field. MATERIALS AND METHODS: A magnetic resonance imaging protocol including in vivo T2 measurements at 11.75 T was performed in 9 male C57BL/6J mice after 8 weeks of streptozotocin-induced diabetes and in 9 control mice. Programmed ventricular stimulation was performed in both groups. T2 measurements were compared with histologic quantification of fibrosis using picrosirius red staining. RESULTS: Myocardial T2 was significantly lower in diabetic mice (13.8 ± 2.8 ms) than in controls (18.9 ± 2.3 ms, P < 0.001). There was a good correlation between T2 and fibrosis area obtained by histopathology (R = 0.947, P < 0.001). During programmed ventricular stimulation, 3 nonsustained ventricular tachycardias were induced in diabetic mice versus none in the control group. CONCLUSIONS: The in vivo T2 relaxation time strongly correlated with myocardial fibrosis area assessed with histologic staining in diabetic mice.
    Mots-clés : Animals, crmbm, Diabetes Mellitus, Experimental, Endomyocardial Fibrosis, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred C57BL, Reproducibility of Results, Sensitivity and Specificity, Streptozocin.
    Note Note
    The following values have no corresponding Zotero field:<br/>Author Address: Centre de Resonance Magnetique Biologique et Medicale-UMR 6612 CNRS, Universite de la Mediterranee, Faculte de Medecine, Marseille, France.<br/>ET - 2012/04/11<br/>
    Note Note
    <p>Bun, Sok-Sithikun <br />Kober, Frank <br />Jacquier, Alexis <br />Espinosa, Leon <br />Kalifa, Jerome <br />Bonzi, Marie-France <br />Kopp, Francis <br />Lalevee, Nathalie <br />Zaffran, Stephane <br />Deharo, Jean-Claude <br />Cozzone, Patrick J <br />Bernard, Monique <br />Research Support, Non-U.S. Gov't <br />United States <br />Investigative radiology <br />Invest Radiol. 2012 May;47(5):319-23. doi: 10.1097/RLI.0b013e318243e062.</p>

  • Fabre, J-B, Martin, V, Gondin, J, Cottin, F & Grelot, L 2012, “Effect of playing surface properties on neuromuscular fatigue in tennis”, Medicine and science in sports and exercise, vol. 44, no. 11, p. 2182-2189.
    Résumé : PURPOSE: The aim of this study was to evaluate the effect of the playing surface properties on the development of neuromuscular fatigue in tennis. METHODS: Ten subjects played randomly two tennis matches on hard court (HARD) and clay court (CLAY) for an effective playing duration of 45 min (i.e., corresponding approximately to a 3-h game). Before and after each match, the maximal voluntary contraction (MVC) force of the plantar flexors, the maximal voluntary activation level, the maximal compound muscle action characteristic, and the EMG activity were determined on the soleus (SOL) and lateralis gastrocnemius (LG) muscles. Tetanic and single stimulations were also delivered to evaluate the presence of low-frequency fatigue and contractile impairment. Finally, reflex responses were evoked on the relaxed muscle (H-reflex) and during MVC (H-reflex and V-wave). RESULTS: Statistical analysis did not reveal any significant difference between playing surfaces. MVC was similarly reduced after the game (HARD, -9.1% ± 8.7%; CLAY, -4.3% ± 19.9%) and was associated with alterations of the contractile properties of the plantar flexor muscles. The implication of central factors was less clear, as evidenced by the significant reduction (P < 0.05) of the H-reflex on the relaxed LG (HARD, -16.2% ± 33.3%; CLAY, -23.9% ± 54.0%) and SOL (HARD, -16.1% ± 48.9%; CLAY, -34.9% ± 35.9%) and the nonsignificant reduction of the activation level. In addition, the reflex responses evoked during MVC were not significantly modified by the exercise. CONCLUSION: These results suggest that the ground surface properties influence neither the extent nor the origin of neuromuscular fatigue in tennis. The moderate force decrement observed in the current study was mainly associated with peripheral fatigue.
    Mots-clés : Adult, crmbm, Electromyography, Floors and Floorcoverings, H-Reflex, Humans, Isometric Contraction, Male, Muscle Contraction, Muscle Fatigue, Neuromuscular Monitoring, Tennis, Young Adult.

  • Flavian, A, Carta, F, Thuny, F, Bernard, M, Kober, F, Moulin, G, Varoquaux, A & Jacquier, A 2012, “Cardiac MRI in the diagnosis of complications of myocardial infarction”, Diagnostic and interventional imaging, vol. 93, no. 7-8, p. 578-585.
    Résumé : The improvement in revascularization techniques and medicine treatment during infarction has substantially reduced mortality during the acute phase of this condition. Since the advent of kinetic sequences and the concomitant development of gadolinium chelates and delayed enhancement sequences, cardiac MRI has become the second-line reference examination for ischemic heart disease. The technique of delayed enhancement with the inversion recovery sequence performed after injection has been validated for numerous indications in ischemic disease. Delayed enhancement sequences make it possible in particular to look for "no-reflow" areas (microvascular obstructions), to quantify the infarction area, and to assess prognosis. MRI also allows us to define the area at risk, that is, the area with edema, and to look for and assess the mechanical complications of the infarction. The aim of this review is to summarize current knowledge about: the pharmacokinetic principles that regulate myocardial enhancement; the different sequences available to acquire delayed enhancement images, and; the value of cardiac MRI in the diagnosis of complications of myocardial infarction.
    Mots-clés : Cardiac Imaging Techniques, crmbm, Heart Diseases, Humans, Magnetic Resonance Imaging, Myocardial infarction.

  • Gaborit, B, Kober, F, Jacquier, A, Moro, PJ, Cuisset, T, Boullu, S, Dadoun, F, Alessi, M-C, Morange, P, Clément, K, Bernard, M & Dutour, A 2012, “Assessment of epicardial fat volume and myocardial triglyceride content in severely obese subjects: relationship to metabolic profile, cardiac function and visceral fat”, International journal of obesity (2005), vol. 36, no. 3, p. 422-430.
    Résumé : OBJECTIVE: To assess epicardial fat volume (EFV), myocardial TG content (MTGC) and metabolic profile in severely obese patients, and to determine whether ectopic fat depots are linked to metabolic disorders or myocardial function. RESEARCH DESIGN AND METHODS: Sixty-three subjects with normal LV function and no coronary artery disease, including 33 lean (BMI: 21.4 ± 2.0 kg m(-2)) and 30 obese (BMI: 41.8 ± 6 kg m(-2)) patients, underwent 3-T cardiovascular MRI, and anthropometric, biological and visceral abdominal fat (VAT) assessments. EFV was measured by short-axis slice imaging and myocardial (intra-myocellular) TG content was measured by proton magnetic resonance spectroscopy. RESULTS: EFV and MTGC were positively correlated (r=0.52, P<0.0001), and were both strongly correlated with age, BMI, waist circumference and VAT, but not with severity of obesity. EFV and MTGC were significantly higher in obese patients than in lean controls (141 ± 18 versus 79 ± 7 ml, P=0.0001; 1.0 ± 0.1 versus 0.6 ± 0.1%, P=0.01, respectively), but some differences were found between the two cardiac depots: EFV was higher in diabetic obese subjects as compared with that in non-diabetic obese subjects (213 ± 34 versus 141 ± 18 ml, P=0.03), and was correlated with parameters of glucose tolerance (fasting plasma glucose, insulin and HOMA-IR), whereas MTGC was not. EFV and MTGC were both associated with parameters of lipid profile or inflammation (TGs, CRP). Remarkably, this was VAT-dependent, as only VAT remained independently associated with metabolic parameters (P<0.01). Concerning myocardial function, MTGC was the only parameter independently associated with stroke volume (β=-0.38, P=0.01), suggesting an impact of cardiac steatosis in cardiac function. CONCLUSIONS: These data show that VAT dominates the relationship between EFV, MTGC and metabolic measures, and uncover specific partitioning of cardiac ectopic lipid deposition.
    Mots-clés : Adult, crmbm, Diabetes Mellitus, Type 2, Female, Humans, Intra-Abdominal Fat, Lipid Metabolism, Magnetic Resonance Spectroscopy, Male, Metabolome, Obesity, Morbid, Pericardium, Triglycerides, Ventricular Dysfunction, Left.
  • Gaborit, B, Jacquier, A, Kober, F, Abdesselam, I, Cuisset, T, Boullu-Ciocca, S, Emungania, O, Alessi, MC, Clement, K, Bernard, M & Dutour, A 2012, “Bariatric surgery induces an improvement of left ventricular function and differential effects on cardiac ectopic fat deposition”, Fundamental & Clinical Pharmacology, vol. 26, p. 3-4.

  • Gaborit, B, Jacquier, A, Kober, F, Abdesselam, I, Cuisset, T, Boullu-Ciocca, S, Emungania, O, Alessi, M-C, Clément, K, Bernard, M & Dutour, A 2012, “Effects of bariatric surgery on cardiac ectopic fat: lesser decrease in epicardial fat compared to visceral fat loss and no change in myocardial triglyceride content”, Journal of the American College of Cardiology, vol. 60, no. 15, p. 1381-1389.
    Résumé : OBJECTIVES: This study investigated the effect of bariatric surgery (BS)-induced weight loss on cardiac ectopic fat using 3T magnetic resonance imaging in morbid obesity. BACKGROUND: Heart disease is one of the leading causes of mortality and morbidity in obese patients. Deposition of cardiac ectopic fat has been related to increased heart risk. Whether sustained weight loss can modulate epicardial fat or myocardial fat is unknown. METHODS: Twenty-three morbidly obese patients underwent 1H-magnetic resonance spectroscopy to determine myocardial triglyceride content (MTGC), magnetic resonance imaging to assess epicardial fat volume (EFV), cardiac function, and computed tomography visceral abdominal fat (VAF) measurements at baseline and 6 months after BS. RESULTS: The BS reduced body mass index significantly, from 43.1±4.5 kg/m2 to 32.3±4.0 kg/m2, subcutaneous fat from 649±162 cm2 to 442±127 cm2, VAF from 190±83 cm2 to 107±44 cm2, and EFV from 137±37 ml to 98±25 ml (all p<0.0001). There was no significant change in MTGC: 1.03±0.2% versus 1.1±0.2% (p=0.85). A significant reduction in left ventricular mass (118±24 g vs. 101±18 g) and cardiac output (7.1±1.6 l/min vs. 5.4±1.0 l/min) was observed and was statistically associated with weight loss (p<0.05). The loss in EFV was limited (-27±11%) compared to VAF diminution (-40±19%). The EFV variation was not correlated with percentage of body mass index or VAF loss (p=0.007). The ratio of %EFV to %VAF loss decreased with sleep apnea syndrome (1.34±0.3 vs. 0.52±0.08, p<0.05). CONCLUSIONS: Six-month BS modulates differently cardiac ectopic fat deposition, with a significant decrease in epicardial fat and no change in myocardial fat. Epicardial fat volume loss was limited in patients with sleep apnea. (Impact of Bariatric Surgery on Epicardial Adipose Tissue and on Myocardial Function; NCT01284816).
    Mots-clés : Adult, Bariatric Surgery, Body Mass Index, crmbm, Female, Follow-Up Studies, Heart Diseases, Humans, Intra-Abdominal Fat, Lipid Metabolism, Magnetic Resonance Imaging, Cine, Magnetic Resonance Spectroscopy, Male, Myocardium, Obesity, Morbid, Pericardium, Retrospective Studies, Risk Factors, Tomography, X-Ray Computed, Triglycerides.
    Note Note
    <p>Gaborit, Benedicte<br />Jacquier, Alexis<br />Kober, Frank<br />Abdesselam, Ines<br />Cuisset, Thomas<br />Boullu-Ciocca, Sandrine<br />Emungania, Olivier<br />Alessi, Marie-Christine<br />Clement, Karine<br />Bernard, Monique<br />Dutour, Anne<br />Journal article<br />Journal of the American College of Cardiology<br />J Am Coll Cardiol. 2012 Oct 9;60(15):1381-1389. doi: 10.1016/j.jacc.2012.06.016. Epub 2012 Aug 29.</p>
    Note Note
    The following values have no corresponding Zotero field:<br/>Author Address: Department of Endocrinology, Metabolic Diseases and Nutrition, Centre Hospitalier Universitaire Nord, Marseille, France; Institut National de la Sante et de la Recherche Medicale, Unite Mixte de Recherche 1062 and Institut National de la Recherche Agronomique, Unite Mixte de Recherche 1260, Marseille, France; Centre de Resonance Magnetique Biologique et Medicale, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6612, Marseille, France; Centre d'investigation Clinique, Hopital Nord, Marseille, France. Electronic address:<br/>Label: A<br/>DOI: ACL<br/>C2 - Heart<br/>ET - 2012/09/04<br/>

  • Gaborit, B, Kober, F, Jacquier, A, Moro, PJ, Flavian, A, Quilici, J, Cuisset, T, Simeoni, U, Cozzone, P, Alessi, M-C, Clément, K, Bernard, M & Dutour, A 2012, “Epicardial fat volume is associated with coronary microvascular response in healthy subjects: a pilot study”, Obesity (Silver Spring, Md.), vol. 20, no. 6, p. 1200-1205.
    Résumé : Epicardial fat (EF) is an active ectopic fat depot, which has been associated with coronary atherosclerosis, and which could early influence endothelial function. We thus investigated the relationship between EF and endothelium-dependent vasoreactivity of the coronary microcirculation, in highly selected healthy volunteers. Myocardial blood flow (MBF) was determined by measuring coronary sinus flow with velocity-encoded cine magnetic resonance imaging (MRI) at 3T. We measured MBF at baseline and in response to sympathetic stimulation by cold pressor testing (CPT) in 30 healthy volunteers with normal left ventricular (LV) function (age 22 ± 4 years, BMI = 21.3 ± 2.8 kg/m(2)). EF volume was volumetrically assessed by manual delineation on short-axis views. CPT was applied by immersing one foot in ice water for 4 min. Mean EF volume was 56 ± 26 ml and mean LV mass 100 ± 28 g. CPT significantly increased heart rate (HR) by 32 ± 19%, systolic blood pressure by 14 ± 10%, and rate-pressure product by 45 ± 25%, P < 0.0001. The increase in HR, reflecting sympathetic stimulation, was not influenced by sex, age or EF volume. CPT induced a decrease in coronary vascular resistance (135 ± 72 vs. 100 ± 42 mm, P = 0.0006), and a significant increase in MBF (0.81 ± 0.37 vs. 1.24 ± 0.56 ml.min(-1).g(-1), P < 0.0001). Interestingly, we found a significant negative correlation between EF volume and ΔMBF (r= - 0.40, P = 0.03), which remained significant after adjusting for ΔHR. ΔMBF was also associated with adiponectin (r = 0.41, P = 0.046), but not with waist circumference, BMI, C-reactive protein, lipid or glycemic parameters. In multivariate analysis, adiponectin and EF volume remained both independently associated with ΔMBF. A high EF amount is associated with a lower coronary microvascular response, suggesting that EF could early influence endothelial function.
    Mots-clés : Adolescent, Adult, Blood pressure, Cold Temperature, Coronary Artery Disease, Coronary Circulation, Coronary Vessels, crmbm, Endothelium, Vascular, Female, Humans, Male, Microcirculation, Pilot Projects, Reproducibility of Results, Ventricular Function, Left, Young Adult.

  • Garcia, C, Lutz, NW, Confort-Gouny, S, Cozzone, PJ, Armand, M & Bernard, M 2012, “Phospholipid fingerprints of milk from different mammalians determined by 31P NMR: towards specific interest in human health”, Food Chemistry, vol. 135, no. 3, p. 1777-1783.
    Résumé : Our objective was to identify and quantify phospholipids in milk from different species (human HM, cow CoM, camel CaM, and mare MM) using an optimised (31)P NMR spectroscopy procedure. The phospholipid fingerprints were species-specific with a broader variety of classes found in HM and MM; HM and CaM were richer in sphingomyelin (78.3 and 117.5μg/ml) and plasmalogens (27.3 and 24μg/ml), possibly important for infant development. Total phospholipid content was higher in CaM (0.503mM) and lower in MM (0.101mM) compared to HM (0.324mM) or CoM (0.265mM). Our optimised method showed good sensitivity, high resolution, and easy sample preparation with minimal loss of target molecules. It is suitable for determining the accurate composition of a large number of bioactive phospholipids with putative health benefits, including plasmalogens, and should aid in selecting appropriate ingredient sources for infant milk substitutes or fortifiers, and for functional foods dedicated to adults.
    Mots-clés : Animals, Camels, crmbm, Humans, Magnetic Resonance Spectroscopy, Milk, Milk, Human, Phospholipids.

  • Kober, F, Bernard, M, Troalen, T & Capron, T 2012, “Cardiovascular Magnetic Resonance of Myocardial Structure, Function, and Perfusion in Mouse and Rat Models”, Current Cardiovascular Imaging Reports, vol. 5, no. 2, p. 109-115, viewed 5July,2013, .
    Résumé : This review summarizes small-animal cardiovascular magnetic resonance (CMR) techniques that are being actively developed at present. Taking into account with few exceptions only literature of the past 2 years it shows that small-animal CMR has become an important and versatile analysis tool in many biomedical studies. The relatively complex signal formation and detection in magnetic resonance offers numerous ways of creating and modulating image contrast as a function of the specific needs. Although most new small-animal CMR developments are done within the scientific MR community, the MR manufacturers have readily contributed in making these techniques robust and available for routine application studies. Unlike other cardiovascular imaging techniques, CMR is used in many facets to assess morphology, global and regional function, blood flow, myocardial structure, cell damage, metabolism, and other molecular processes for studying mouse and rat models of human disease as well as general biochemical mechanisms in vivo.
    Mots-clés : Cardiology, Cardiovascular magnetic resonance, crmbm, Diagnostic Radiology, Function, Imaging / Radiology, Interventional radiology, Late-enhancement, MRI, Nuclear Medicine, Perfusion, Self-gating, T1-mapping, Ultrasound.


Journal Article

  • Jacquier, A, Kober, F, Bun, S, Giorgi, R, Cozzone, PJ & Bernard, M 2011, “Quantification of myocardial blood flow and flow reserve in rats using arterial spin labeling MRI: comparison with a fluorescent microsphere technique”, NMR in biomedicine, vol. 24, no. 9, p. 1047-1053.
    Résumé : To quantify noninvasively myocardial blood flow (MBF) and MBF reserve in isoflurane-anesthetized rats using the Look-Locker flow-alternating inversion recovery gradient-echo arterial spin labeling technique (LLFAIRGE-ASL), and to compare the results with the fluorescent microsphere (FM) technique. Male Wistar rats (weight = 200-240 g, n = 21) were anesthetized with 2.0% isoflurane. Hemodynamic parameters were recorded. In seven rats, MBF was assessed on a Bruker Biospec 4.7T MR system using an ECG- and respiration-gated LLFAIRGE-ASL (pixel size = 234 × 468µm(2) , TE = 1.52ms) at rest and during adenosine infusion (140 µg/kg/min). A mixture of 200 000 FM was injected into a second group of rats at rest and during adenosine infusion (n = 7 each), under similar physiologic conditions. Hearts and skeletal muscle samples were processed for fluorescence spectroscopy. Two-tailed unpaired, paired Student's t-test and ANOVA were used to compare groups. MBF measured with LLFAIRGE-ASL was 5.2 ± 1.0 mL/g/min at rest and 13.3 ± 3.0 mL/g/min during adenosine infusion. Results obtained with fluorescent microspheres yielded 5.9 ± 2.3 mL/g/min (nonsignificant vs. LLFAIRGE-ASL, p = 0.9) at rest and 13.1 ± 2.1 mL/g/min (nonsignificant vs. LLFAIRGE-ASL, p = 0.4) during adenosine infusion. Myocardial blood flow reserve measured using LLFAIRGE-ASL and FM were not significantly different (2.5 ± 0.6 vs. 2.4 ± 0.9, respectively; p = 0.8). Hemodynamic parameters during the experiments were not different between the groups. The myocardial blood flow reserve determined under isoflurane anesthesia was 2.5 ± 0.6, which was not different from the value obtained with FM. LLFAIRGE-ASL provided MBF maps with high spatial resolution in rats under isoflurane anesthesia. LLFAIRGE-ASL is a noninvasive measure to assess myocardial blood flow reserve and provides an interesting tool for cardiovascular research.
    Mots-clés : Adenosine, Animals, Arteries, Coronary Circulation, crmbm, Fluorescence, Heart, Heart Ventricles, Hemodynamics, Magnetic Resonance Imaging, Magnetic Resonance Imaging, Cine, Male, Microspheres, Myocardium, Rats, Rats, Sprague-Dawley, Spin Labels, Ventricular Function.
    Note Note
    <p>Jacquier, Alexis<br/>Kober, Frank<br/>Bun, Soksithikun<br/>Giorgi, Roch<br/>Cozzone, Patrick J<br/>Bernard, Monique<br/>Research Support, Non-U.S. Gov't<br/>England<br/>NMR in biomedicine<br/>NMR Biomed. 2011 Nov;24(9):1047-53. doi: 10.1002/nbm.1645. Epub 2011 Jan 25.</p>
    Note Note
    The following values have no corresponding Zotero field:<br/>Author Address: Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR 6612 CNRS/Universite de la Mediterranee, Faculte de Medecine, Marseille, France.<br/>ET - 2011/01/26<br/>
    Note Note
    <p>Journal article <br/>NMR in biomedicine <br/>NMR Biomed. 2011 Jan 25. doi: 10.1002/nbm.1645.</p>
    Note Note
    <p>The following values have no corresponding Zotero field:<br />Author Address: Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR 6612 CNRS/Universite de la Mediterranee, Faculte de Medecine, Marseille, France; Service de Radiologie Cardiovasculaire, Centre Hospitalo Universitaire la Timone, Marseille, France.<br />ET - 2011/01/26</p>

  • Moro, P-J, Flavian, A, Jacquier, A, Kober, F, Quilici, J, Gaborit, B, Bonnet, J-L, Moulin, G, Cozzone, PJ & Bernard, M 2011, “Gender differences in response to cold pressor test assessed with velocity-encoded cardiovascular magnetic resonance of the coronary sinus”, Journal of cardiovascular magnetic resonance: official journal of the Society for Cardiovascular Magnetic Resonance, vol. 13, p. 54.
    Résumé : BACKGROUND: Gender-specific differences in cardiovascular risk are well known, and current evidence supports an existing role of endothelium in these differences. The purpose of this study was to assess non invasively coronary endothelial function in male and female young volunteers by myocardial blood flow (MBF) measurement using coronary sinus (CS) flow quantification by velocity encoded cine cardiovascular magnetic resonance (CMR) at rest and during cold pressor test (CPT). METHODS: Twenty-four healthy volunteers (12 men, 12 women) underwent CMR in a 3 Tesla MR imager. Coronary sinus flow was measured at rest and during CPT using non breath-hold velocity encoded phase contrast cine-CMR. Myocardial function and morphology were acquired using a cine steady-state free precession sequence. RESULTS: At baseline, mean MBF was 0.63 ± 0.23 mL·g⁻¹·min⁻¹ in men and 0.79 ± 0.21 mL·g⁻¹·min⁻¹ in women. During CPT, the rate pressure product in men significantly increased by 49 ± 36% (p < 0.0001) and in women by 52 ± 22% (p < 0.0001). MBF increased significantly in both men and women by 0.22 ± 0.19 mL·g⁻¹·min⁻¹ (p = 0.0022) and by 0.73 ± 0.43 mL·g⁻¹·min⁻¹ (p = 0.0001), respectively. The increase in MBF was significantly higher in women than in men (p = 0.0012). CONCLUSION: CMR coronary sinus flow quantification for measuring myocardial blood flow revealed a higher response of MBF to CPT in women than in men. This finding may reflect gender differences in endothelial-dependent vasodilatation in these young subjects. This non invasive rest/stress protocol may become helpful to study endothelial function in normal physiology and in physiopathology.
    Mots-clés : Adolescent, Adult, Blood Flow Velocity, Blood pressure, Cold Temperature, Coronary Circulation, Coronary Sinus, crmbm, Endothelium, Vascular, Female, France, Hand, Heart Rate, Humans, Immersion, Magnetic Resonance Imaging, Cine, Male, Myocardial Perfusion Imaging, Observer Variation, Predictive Value of Tests, Reproducibility of Results, Sex Factors, Ventricular Function, Left, Young Adult.


Journal Article

  • Desrois, M, Clarke, K, Lan, C, Dalmasso, C, Cole, M, Portha, B, Cozzone, PJ & Bernard, M 2010, “Upregulation of eNOS and unchanged energy metabolism in increased susceptibility of the aging type 2 diabetic GK rat heart to ischemic injury”, American Journal of Physiology - Heart and Circulatory Physiology, vol. 299, no. 5, p. H1679-H1686, viewed 21November,2013, .
    Résumé : We investigated the tolerance of the insulin-resistant diabetic heart to ischemic injury in the male Goto-Kakizaki (GK) rat, a model of type 2 diabetes. Changes in energy metabolism, nitric oxide (NO) pathway, and cardiac function were assessed in the presence of physiological substrates. Age-matched control Wistar (n = 19) and GK (n = 18) isolated rat hearts were perfused with 0.4 mM palmitate, 3% albumin, 11 mM glucose, 3 U/l insulin, 0.2 mM pyruvate, and 0.8 mM lactate for 24 min before switching to 1.2 mM palmitate (11 rats/group) during 32 min low-flow (0.5 ml·min−1·g wet wt−1) ischemia. Next, flow was restored with 0.4 mM palmitate buffer for 32 min. A subset of hearts from each group (n = 8 for control and n = 7 for GK groups) were freeze-clamped for determining baseline values after the initial perfusion of 24 min. ATP, phosphocreatine (PCr), and intracellular pH (pHi) were followed using 31P magnetic resonance spectroscopy with simultaneous measurement of contractile function. The NO pathway was determined by nitric oxide synthase (NOS) isoform expression and total nitrate concentration (NOx) in hearts. We found that coronary flow was 26% lower (P < 0.05) during baseline conditions and 61% lower (P < 0.05) during reperfusion in GK vs. control rat hearts. Rate pressure product was lower during reperfusion in GK vs. control rat hearts (P < 0.05). ATP, PCr, and pHi during ischemia-reperfusion were similar in both groups. Endothelial NOS expression was increased in GK rat hearts during baseline conditions (P < 0.05). NOx was increased during baseline conditions (P < 0.05) and after reperfusion (P < 0.05) in GK rat hearts. We report increased susceptibility of type 2 diabetic GK rat heart to ischemic injury that is not associated with impaired energy metabolism. Reduced coronary flow, upregulation of eNOS expression, and increased total NOx levels confirm NO pathway modifications in this model, presumably related to increased oxidative stress. Modifications in the NO pathway may play a major role in ischemia-reperfusion injury of the type 2 diabetic GK rat heart.
    Mots-clés : aging, Animals, Coronary Vessels, crmbm, Diabetes Mellitus, Type 2, Disease Models, Animal, Energy Metabolism, Heart, Male, Myocardial Reperfusion Injury, Nitric Oxide, Nitric Oxide Synthase Type III, Rats, Rats, Mutant Strains, Rats, Wistar, Regional Blood Flow, Up-Regulation.

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