Yann Le Fur

Aix-Marseille Université, Marsiglia, Provence-Alpes-Côte d'Azur, France

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Publications (192)506.32 Total impact

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    ABSTRACT: Because it leads to a rapid and massive muscle hypertrophy, postnatal blockade of the activin type IIB receptor (ActRIIB) is a promising therapeutic strategy for counteracting muscle wasting. However, the functional consequences remain very poorly documented in vivo. Here, we have investigated the impact of 8-week ActRIIB blockade with soluble receptor (sActRIIB-Fc) on gastrocnemius muscle anatomy, energy metabolism and force-generating capacity in wild-type mice using totally noninvasive magnetic resonance (MR) imaging and dynamic 31-phosphorus MR spectroscopy. Compared to vehicle (PBS) control, sActRIIB-Fc treatment resulted in a dramatic increase in body weight (+29%) and muscle volume (+58%) calculated from hindlimb MR imaging, but did not alter fiber-type distribution determined via myosin heavy chain isoforms analysis. In resting muscle, sActRIIB-Fc treatment induced acidosis and PCr depletion, thereby suggesting reduced tissue oxygenation. During an in vivo fatiguing exercise (6-min of repeated maximal isometric contraction electrically-induced at a frequency of 1.7 Hz), maximal and total absolute forces were larger in sActRIIB-Fc treated animals (+26% and +12%, respectively) whereas specific force and fatigue resistance were lower (-30% and 37%, respectively). Treatment with sActRIIB-Fc further decreased the maximal rate of oxidative ATP synthesis (-42%) and the oxidative capacity (-34%), but did not alter the bioenergetics status in contracting muscle. Our findings demonstrate in vivo that sActRIIB-Fc treatment increases absolute force-generating capacity and reduces mitochondrial function in glycolytic gastrocnemius muscle, but this reduction does not compromise energy status during sustained activity. Overall, these data support the clinical interest of postnatal ActRIIB blockade.
    No preview · Article · Feb 2016 · AJP Endocrinology and Metabolism
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    ABSTRACT: Purpose: To detect local metabolic abnormalities over the complete human brain in multiple sclerosis (MS) patients, we used optimized fast volumic echo planar spectroscopic imaging (3D-EPSI). Materials and methods: Weighted mean combination of two 3D-EPSI covering the whole brain acquired at 3T in AC-PC and AC-PC+15° axial planes was performed to obtain high-quality metabolite maps for five metabolites: N-acetyl aspartate (NAA), glutamate+glutamine (Glx), choline (Cho), myo-inositol (m-Ins), and creatine+phosphocreatine (tCr). After spatial normalization, maps from 19 patients suffering from relapsing-remitting MS were compared to 19 matched controls using statistical mapping analyses to determine the topography of metabolic abnormalities. Probabilistic white matter (WM) T2 lesion maps and gray matter (GM) atrophy maps were also generated. Results: Two-group analysis of variance (ANOVA) (SPM8, P < 0.005, false discovery rate [FDR]-corrected P < 0.05 at the cluster level with age and sex as confounding covariates) comparing patients and controls matched for age and sex showed clusters of abnormal metabolite levels with 1) decreased NAA (around -15%) and Glx (around 20%) predominantly in GM within prefrontal cortices, motor cortices, bilateral thalami, and mesial temporal cortices in line with neuronal/neuro-astrocytic dysfunction; 2) increased m-Ins (around + 20%) inside WM T2 lesions and in the normal-appearing WM of temporal-occipital lobes, suggesting glial activation. Conclusion: We demonstrate the ability to noninvasively map over the complete brain-from vertex to cerebellum-with a validated sequence, the metabolic abnormalities associated with MS, for characterizing the topography of pathological processes affecting widespread areas of WM and GM and its functional impact. J. Magn. Reson. Imaging 2016.
    Full-text · Article · Jan 2016 · Journal of Magnetic Resonance Imaging
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    ABSTRACT: Objective: To quantify individual muscle volume in rat leg MR images using a fully automatic multi-atlas-based segmentation method. Materials and methods: We optimized a multi-atlas-based segmentation method to take into account the voxel anisotropy of numbers of MRI acquisition protocols. We mainly tested an image upsampling process along Z and a constraint on the nonlinear deformation in the XY plane. We also evaluated a weighted vote procedure and an original implementation of an artificial atlas addition. Using this approach, we measured gastrocnemius and plantaris muscle volumes and compared the results with manual segmentation. The method reliability for volume quantification was evaluated using the relative overlap index. Results: The most accurate segmentation was obtained using a nonlinear registration constrained in the XY plane by zeroing the Z component of the displacement and a weighted vote procedure for both muscles regardless of the number of atlases. The performance of the automatic segmentation and the corresponding volume quantification outperformed the interoperator variability using a minimum of three original atlases. Conclusion: We demonstrated the reliability of a multi-atlas segmentation approach for the automatic segmentation and volume quantification of individual muscles in rat leg and found that constraining the registration in plane significantly improved the results.
    No preview · Article · Dec 2015 · MAGMA Magnetic Resonance Materials in Physics Biology and Medicine
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    ABSTRACT: Introduction: Endurance training elicits tremendous adaptations of the mitochondrial energetic capacity. Yet, the effects of training or physical fitness on mitochondrial efficiency during exercise are still unclear. Accordingly, the purpose of the present study was to examine in vivo the differences in mitochondrial efficiency and ATP cost of contraction during exercise in two groups of adults differing in their aerobic capacity. Method: We simultaneously assessed the ATP synthesis and O2 fluxes with P-Magnetic Resonance Spectroscopy and pulmonary gas exchange measurements in 7 endurance-trained (ET, VO2max: 67±8 ml.min.kg) and 7 recreationally active (RA, VO2max: 43±7 ml.min.kg) subjects during 6 min of dynamic moderate-intensity knee-extension. Results: The ATP cost of dynamic contraction was not significantly different between ET and RA (P>0.05). Similarly, end-exercise O2 consumption was not significantly different between groups (ET: 848±155 ml.min and RA: 760±131 ml.min, P>0.05). During the recovery period, the PCr offset time constant was significantly faster in ET compared to RA (ET: 32±8 s and RA: 43±10 s, P<0.05) thus indicating an increased mitochondrial capacity for ATP synthesis in the quadriceps of ET. In contrast, the estimated mitochondrial efficiency during exercise was not significantly different (P/O, ET: 2.0±1.0 and RA: 1.8±0.4, P>0.05). Consequently, the higher mitochondrial capacity for ATP synthesis in ET likely originated from an elevated mitochondrial volume density, mitochondria-specific respiratory capacity and/or slower post-exercise inactivation of oxidative phosphorylation by the parallel activation mechanism. Conclusion: Together, these findings reveal that 1) mitochondrial and contractile efficiency are unaltered by several years of endurance-training in young adults, and 2) the training-induced improvement in mitochondrial energetic capacity appears to be independent from changes in mitochondrial coupling.
    No preview · Article · Dec 2015 · Medicine & Science in Sports & Exercise
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    ABSTRACT: Conventional (CONV) neuromuscular electrical stimulation (NMES) (i.e., short pulse duration, low frequencies) induces a higher energetic response as compared to voluntary contractions (VOL). In contrast, wide-pulse, high-frequency (WPHF) NMES might elicit-at least in some subjects (i.e., responders)-a different motor unit recruitment compared to CONV that resembles the physiological muscle activation pattern of VOL. We therefore hypothesized that for these responder subjects, the metabolic demand of WPHF would be lower than CONV and comparable to VOL. 18 healthy subjects performed isometric plantar flexions at 10% of their maximal voluntary contraction force for CONV (25 Hz, 0.05 ms), WPHF (100 Hz, 1 ms) and VOL protocols. For each protocol, force time integral (FTI) was quantified and subjects were classified as responders and non-responders to WPHF based on k-means clustering analysis. Furthermore, a fatigue index based on FTI loss at the end of each protocol compared with the beginning of the protocol was calculated. Phosphocreatine depletion (ΔPCr) was assessed using 31P magnetic resonance spectroscopy. Responders developed four times higher FTI's during WPHF (99 ± 37 ×103 N.s) than non-responders (26 ± 12 ×103 N.s). For both responders and non-responders, CONV was metabolically more demanding than VOL when ΔPCr was expressed relative to the FTI. Only for the responder group, the ∆PCr/FTI ratio of WPHF (0.74 ± 0.19 M/N.s) was significantly lower compared to CONV (1.48 ± 0.46 M/N.s) but similar to VOL (0.65 ± 0.21 M/N.s). Moreover, the fatigue index was not different between WPHF (-16%) and CONV (-25%) for the responders. WPHF could therefore be considered as the less demanding NMES modality-at least in this subgroup of subjects-by possibly exhibiting a muscle activation pattern similar to VOL contractions.
    Full-text · Article · Nov 2015 · PLoS ONE
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    ABSTRACT: Two-dimensional spectroscopy offers the possibility to unambiguously distinguish metabolites by spreading out the multiplet structure of J-coupled spin systems into a second dimension. Quantification methods that perform parametric fitting of the 2D MRS signal have recently been proposed for resolved PRESS (JPRESS) but not explicitly for Localized Correlation Spectroscopy (LCOSY). Here, through a whole metabolite quantification approach, correlation spectroscopy quantification performances are studied. The ability to quantify metabolite relaxation constant times is studied for three localized 2D MRS sequences (LCOSY, LCTCOSY and the JPRESS) in vitro on preclinical MR systems. The issues encountered during implementation and quantification strategies are discussed with the help of the Fisher matrix formalism. The described parameterized models enable the computation of the lower bound for error variance - generally known as the Cramér Rao bounds (CRBs), a standard of precision - on the parameters estimated from these 2D MRS signal fittings. LCOSY has a theoretical net signal loss of two per unit of acquisition time compared to JPRESS. A rapid analysis could point that the relative CRBs of LCOSY compared to JPRESS (expressed as a percentage of the concentration values) should be doubled but we show that this is not necessarily true. Finally, the LCOSY quantification procedure has been applied on data acquired in vivo on a mouse brain.
    No preview · Article · Oct 2015 · Journal of Magnetic Resonance
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    ABSTRACT: Aim: To quantify the wrist cartilage cross-sectional area in humans from a 3D magnetic resonance imaging (MRI) dataset and to assess the corresponding reproducibility. Methods: The study was conducted in 14 healthy volunteers (6 females and 8 males) between 30 and 58 years old and devoid of articular pain. Subjects were asked to lie down in the supine position with the right hand positioned above the pelvic region on top of a home-built rigid platform attached to the scanner bed. The wrist was wrapped with a flexible surface coil. MRI investigations were performed at 3T (Verio-Siemens) using volume interpolated breath hold examination (VIBE) and dual echo steady state (DESS) MRI sequences. Cartilage cross sectional area (CSA) was measured on a slice of interest selected from a 3D dataset of the entire carpus and metacarpal-phalangeal areas on the basis of anatomical criteria using conventional image processing radiology software. Cartilage cross-sectional areas between opposite bones in the carpal region were manually selected and quantified using a thresholding method. Results: Cartilage CSA measurements performed on a selected predefined slice were 292.4 ± 39 mm(2) using the VIBE sequence and slightly lower, 270.4 ± 50.6 mm(2), with the DESS sequence. The inter (14.1%) and intra (2.4%) subject variability was similar for both MRI methods. The coefficients of variation computed for the repeated measurements were also comparable for the VIBE (2.4%) and the DESS (4.8%) sequences. The carpus length averaged over the group was 37.5 ± 2.8 mm with a 7.45% between-subjects coefficient of variation. Of note, wrist cartilage CSA measured with either the VIBE or the DESS sequences was linearly related to the carpal bone length. The variability between subjects was significantly reduced to 8.4% when the CSA was normalized with respect to the carpal bone length. Conclusion: The ratio between wrist cartilage CSA and carpal bone length is a highly reproducible standardized measurement which normalizes the natural diversity between individuals.
    Full-text · Article · Sep 2015 · World Journal of Orthopaedics
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    ABSTRACT: Paragangliomas (PGLs) can be associated with mutations in genes of the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase mutations (SDHx) are the prime examples of genetically determined TCA cycle defects with accumulation of succinate. Succinate, which acts as an oncometabolite, can be detected by ex-vivo metabolomics approaches. The aim of this study was to evaluate the potential role of proton MR spectroscopy (167 H-MRS) for identifying SDHx-related PGLs in vivo and non-invasively. Eight patients were prospectively evaluated with single voxel 168 H-MRS. MR spectra from 8 tumors (4 SDHx-related PGLs, 2 sporadic PGLs, 1 cervical schwannoma, and 1 cervical neurofibroma) were acquired and interpreted qualitatively. Compared to other tumors, a succinate resonance peak was detected only in SDHx72 related tumor patients. Spectra quality was considered good in 3 cases, medium in 2 cases, poor in 2 cases, and uninterpretable in the latter case. Smaller lesions had lower spectra quality compared to larger lesions. Jugular PGLs also exihibited a poorer spectra quality compared to other locations. 176 H-MRS has always been challenging in terms of its technical requisites. This is even more true for the evaluation of head and neck tumors. However, 177 H-MRS might be added to the classical MR sequences for metabolomic characterization of PGLs. In vivo detection of succinate might guide genetic testing, characterize SDHx variants of unknown significance (in the absence of available tumor sample), and even optimize a selection of appropriate therapies.
    Full-text · Article · Jun 2015 · Endocrine Related Cancer
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    ABSTRACT: Currently, the physiological factors responsible for exercise intolerance and bioenergetic alterations with age are poorly understood due, at least in part, to the confounding effect of reduced physical activity in the elderly. Thus, in 40 healthy young (22 ± 2 yrs) and old (74 ± 8 yrs) activity matched subjects, we assessed the impact of age on: 1) the relative contribution of the three major pathways of ATP synthesis (oxidative ATP synthesis, glycolysis, and the creatine kinase reaction) and 2) the ATP cost of contraction during high-intensity exercise. Specifically, during supra-maximal plantar flexion (120% of maximal aerobic power), to stress the functional limits of the skeletal muscle energy systems, we used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to assess metabolism. Although glycolytic activation was delayed in the old, ATP synthesis from the main energy pathways were not significantly different between groups. Similarly, the inferred peak rate of mitochondrial ATP synthesis was not significantly different between the young (25 ± 8 mM.min(-1)) and old (24 ± 6 mM.min(-1)). In contrast, the ATP cost of contraction was significantly elevated in the old compared to the young (5.1 ± 2.0 and 3.7 ± 1.7 mM.min(-1).W(-1), respectively; P<0.05). Overall, these findings suggest that, when young and old subjects are activity matched, there is no evidence of age-related mitochondrial and glycolytic dysfunction. However, this study does confirm an abnormal elevation in exercise-induced skeletal muscle metabolic demand in the old that may contribute to the decline in exercise capacity with advancing age. Copyright © 2014, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    No preview · Article · Jun 2015 · AJP Regulatory Integrative and Comparative Physiology
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    ABSTRACT: Purpose: Although it has been largely acknowledged that isometric neuromuscular electrostimulation (NMES) exercise induces larger muscle damage than voluntary contractions, the corresponding effects on muscle energetics remain to be determined. Voluntary exercise-induced muscle damage (EIMD) has been reported to have minor slight effects on muscle metabolic response to subsequent dynamic exercise, but the magnitude of muscle energetics alterations for NMES EIMD has never been documented. Methods: ³¹P magnetic resonance spectroscopy measurements were performed in 13 young healthy males during a standardized rest-exercise-recovery protocol before (D0) and 2 d (D2) and 4 d (D4) after NMES EIMD on knee extensor muscles. Changes in kinetics of phosphorylated metabolite concentrations (i.e., phosphocreatine [PCr], inorganic phosphate [Pi], and adenosine triphosphate [ATP]) and pH were assessed to investigate aerobic and anaerobic rates of ATP production and energy cost of contraction (Ec). Results: Resting [Pi]/[PCr] ratio increased at D2 (+39%) and D4 (+29%), mainly owing to the increased [Pi] (+43% and +32%, respectively), whereas a significant decrease in resting pH was determined (-0.04 pH unit and -0.03 pH unit, respectively). PCr recovery rate decreased at D2 (-21%) and D4 (-23%) in conjunction with a significantly decreased total rate of ATP production at D4 (-18%) mainly owing to an altered aerobic ATP production (-19%). Paradoxically, Ec was decreased at D4 (-21%). Conclusion: Overall, NMES EIMD led to intramuscular acidosis in resting muscle and mitochondrial impairment in exercising muscle. Alterations of noncontractile processes and/or adaptive mechanisms to muscle damage might account for the decreased Ec during the dynamic exercise.
    Full-text · Article · Jun 2015 · Medicine & Science in Sports & Exercise
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    ABSTRACT: 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.
    Preview · Article · Jun 2015 · PLoS ONE
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    Full-text · Dataset · May 2015
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    ABSTRACT: Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage. (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage. No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4). The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
    Full-text · Article · Mar 2015 · Clinical Nutrition
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    ABSTRACT: Exercise efficiency is an important determinant of exercise capacity. However, little is known about the physiological factors that can modulate muscle efficiency during exercise. Accordingly, we examined whether improved O2 availability would 1) impair mitochondrial efficiency and shift the energy production toward aerobic ATP synthesis, 2) reduce the ATP cost of dynamic contraction owing to an improved neuromuscular efficiency, such that 3) whole-body O2 cost would remain unchanged. We used (31)P-Magnetic Resonance Spectroscopy ((31)P-MRS), surface electromyography and pulmonary VO2 measurements in eight active subjects during 6 min of dynamic knee-extension exercise under different fractions of inspired O2 (FiO2, normoxia: 0.21; hyperoxia: 1.0). Pulmonary VO2 (755 ± 111 ml.min(-1) in normoxia and 799 ± 188 ml.min(-1) in hyperoxia, P>0.05) and O2 cost (P>0.05) were not significantly different between normoxia and hyperoxia. In contrast, the total ATP synthesis rate and the ATP cost of dynamic contraction were significantly lower in hyperoxia compared to normoxia (P<0.05). As a result, the ratio between the rate of oxidative ATP synthesis from the quadriceps and pulmonary VO2 was lower in hyperoxia compared to normoxia, but did not reach statistical significance (ATP/VO2: 16 ± 3 mM.ml(-1) in normoxia and 12 ± 5 mM.ml (-1) in hyperoxia, P=0.07). Together, these findings reveal dynamic and independent regulations of mitochondrial and contractile efficiency as a consequence of O2 availability in young active individuals. Furthermore, muscle efficiency appears to be already optimized under normoxic condition and is unlikely to contribute to the well-established improvement in exercise capacity induced by hyperoxia. Copyright © 2014, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    No preview · Article · Feb 2015 · AJP Regulatory Integrative and Comparative Physiology
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    ABSTRACT: Background To improve the extent over which whole brain quantitative three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) maps can be obtained and be used to explore brain metabolism in a population of healthy volunteers.Methods Two short echo time (20 ms) acquisitions of 3D echo planar spectroscopic imaging at two orientations, one in the anterior commissure–posterior commissure (AC-PC) plane and the second tilted in the AC-PC +15° plane were obtained at 3 Tesla in a group of 10 healthy volunteers. B1+, B1−, and B0 correction procedures and normalization of metabolite signals with quantitative water proton density measurements were performed. A combination of the two spatially normalized 3D-MRSI, using a weighted mean based on the pixel wise standard deviation metabolic maps of each orientation obtained from the whole group, provided metabolite maps for each subject allowing regional metabolic profiles of all parcels of the automated anatomical labeling (AAL) atlas to be obtained.ResultsThe combined metabolite maps derived from the two acquisitions reduced the regional intersubject variance. The numbers of AAL regions showing N-acetyl aspartate (NAA) SD/Mean ratios lower than 30% increased from 17 in the AC-PC orientation and 41 in the AC-PC+15° orientation, to a value of 76 regions of 116 for the combined NAA maps. Quantitatively, regional differences in absolute metabolite concentrations (mM) over the whole brain were depicted such as in the GM of frontal lobes (cNAA = 10.03 + 1.71; cCho = 1.78 ± 0.55; cCr = 7.29 ± 1.69; cmIns = 5.30 ± 2.67) and in cerebellum (cNAA = 5.28 ± 1.77; cCho = 1.60 ± 0.41; cCr = 6.95 ± 2.15; cmIns = 3.60 ± 0.74).ConclusionA double-angulation acquisition enables improved metabolic characterization over a wide volume of the brain. J. Magn. Reson. Imaging 2014.
    Full-text · Article · Nov 2014 · Journal of Magnetic Resonance Imaging
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    ABSTRACT: Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosinslow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8–9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in vitro muscle force might be related to alterations occuring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in vivo. These results clearly point out that in vitro alterations are muscle-dependent and do not necessarily translate into similar changes in vivo.
    Full-text · Article · Sep 2014 · PLoS ONE
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    ABSTRACT: Purpose: This study compared the metabolic and activation changes induced by electrically evoked (neuromuscular electrical stimulation (NMES)) and voluntary (VOL) contractions performed at the same submaximal intensity using P chemical shift imaging (CSI) and T2 mapping investigations. Methods: Fifteen healthy subjects were asked to perform both NMES and VOL protocols with the knee extensors (i.e., 232 isometric contractions at 30% of maximal force) inside a 3-T scanner for two experimental sessions. During the first session, metabolic variations, i.e., phosphocreatine (PCr), inorganic phosphate (Pi), and pH, were recorded using localized P CSI. During a second session, T2 maps of the knee extensors were obtained at rest and immediately after each exercise. Voxels of interest were selected from the directly stimulated vastus lateralis and from the nondirectly stimulated rectus femoris/vastus intermedius muscles. Results: PCr depletion recorded throughout the NMES session was significantly larger in the vastus lateralis as compared with the rectus femoris/vastus intermedius muscles for both conditions (VOL and NMES). A higher occurrence of Pi splitting and a greater acidosis was found during NMES as compared with VOL exercise, illustrating the heterogeneous activation of both slow and fast muscle fibers. T2 changes were greater after NMES as compared with VOL for both muscles but were not necessarily related to the localized metabolic demand. Conclusion: We provided direct evidence that the metabolic demand was strongly related to both the exercise modality and the site of stimulation. On the basis of the occurrence of Pi splitting, we suggested that NMES can activate fast muscle fibers even at low force levels.
    Full-text · Article · Sep 2014 · Medicine & Science in Sports & Exercise
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    ABSTRACT: Studies examining the effect of aging on skeletal muscle oxidative capacity have yielded equivocal results; however, these investigations may have been confounded by differences in oxygen (O2) delivery, physical activity, and small numbers of participants. Therefore, we evaluated skeletal muscle oxidative capacity and O2 delivery in a relatively large group (N = 40) of young (22 ± 2 years) and old (73 ± 7 years) participants matched for physical activity. After submaximal dynamic plantar flexion exercise, phosphocreatine (PCr) resynthesis (31P magnetic resonance spectroscopy), muscle reoxygenation (near-infrared spectroscopy), and popliteal artery blood flow (Doppler ultrasound) were measured. The phosphocreatine recovery time constant (Tau) (young: 33 ± 16; old: 30 ± 11 seconds), maximal rate of adenosine triphosphate (ATP) synthesis (young: 25 ± 9; old: 27 ± 8 mM/min), and muscle reoxygenation rates determined by the deoxyhemoglobin/myoglobin recovery Tau (young: 48 ± 5; old: 47 ± 9 seconds) were similar between groups. Similarly, although tending to be higher in the old, there were no significant age-related differences in postexercise popliteal blood flow (area under the curve: young: 1,665 ± 227 vs old: 2,404 ± 357mL, p = .06) and convective O2 delivery (young: 293 ± 146 vs old: 404 ± 191 mL, p = .07). In conclusion, when physical activity and O2 delivery are similar, oxidative capacity in the plantar flexors is not affected by aging. These findings reveal that diminished skeletal muscle oxidative capacity is not an obligatory accompaniment to the aging process.
    Full-text · Article · Aug 2014 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences
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    ABSTRACT: Although skeletal muscle work efficiency likely plays a key role in limiting mobility of the elderly, the physiological mechanisms responsible for this diminished function remain incompletely understood. Thus, in the quadriceps of young (n=9) and old (n=10) subjects, we measured the cost of muscle contraction (ATP cost) with 31P-magnetic resonance spectroscopy (31P-MRS) during 1) maximal intermittent contractions to elicit a metabolic demand from both cross-bridge cycling and ion pumping and 2) a continuous maximal contraction to predominantly tax cross-bridge cycling. The ATP cost of the intermittent contractions was significantly greater in the old (0.30 ± 0.22 mM.min-1.N m-1) compared to the young (0.13 ± 0.03 mM.min-1.N m-1, P<0.05). In contrast, at the end of the continuous contraction protocol, the ATP cost in the old (0.10 ± 0.07 mM.min-1.N m-1) was not different from the young (0.06 ± 0.02 mM.min-1.N m-1, P=0.2). In addition, the ATP cost of the intermittent contractions correlated significantly with the single leg peak power of the knee-extensors assessed during incremental dynamic exercise (r = -0.55; P<0.05,). Overall, this study reveals an age-related increase in the ATP cost of contraction, likely mediated by an excessive energy demand from ion pumping, which probably contributes to both the decline in muscle efficiency and functional capacity associated with aging.
    No preview · Article · Aug 2014 · Clinical Science
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    ABSTRACT: Background Although Magnetic Resonance Imaging has been widely used as a diagnostic tool in neuromuscular disorders, the analysis of images has remained essentially qualitative. Objectives Even if visual scores of deterioration have been proposed and achieve a good sensitivity their specificity remain low. The calculation and mapping of T2 relaxation time, a quantitative index of fat and muscle physical characteristics, can provide reliable information regarding fatty infiltration and inflammatory signs in neuromuscular disorders. Methods In addition to routine images acquired using T1 and STIR sequences, T2 mapping has been obtained from the dominant thigh of 55 patients with various muscle diseases (myositis, myopathies, rhabdomyolysis) and 36 control subjects. Based on the T2 values, we have developed an automatic segmentation method in order to distinguish muscle from fat. Two variables have been defined i.e. the most frequent T2 values (T2mf) and the numbers of T2 values ranging from 60 ms (the upper limit of normal muscle) to 75 ms (the lower limit of fat) expressed as a surface (NT2 60-75ms). Results We observed large T2 variations in patients and controls with a clear positive effect of age (0.23 p<0.001) and no relation to sex. T2mf and NT260–75ms values reduced this variation and were significantly affected by muscle diseases (Table 1). They increased from rabdomyolysis, myositis, to myopathies (Table 2). A diagnostic strategy obtained from a CHAID analysis shows that if STIR images analyses were not convincing to conclude, T2mf and NT260–75ms variable allowed to distinguish patients from controls. Conclusions T2 mapping is a quantitative approach more robust than the sole visual inspection to characterize changes in the muscles of patients with neuromuscular diseases. Additional indices such as T2mf and NT260–75ms provide alternative measures of disease activity which could be used for diagnosis, investigation of the natural history of muscle diseases and the effects of therapeutic strategies. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1602
    No preview · Article · Jun 2014 · Annals of the Rheumatic Diseases

Publication Stats

3k Citations
506.32 Total Impact Points

Institutions

  • 2006-2016
    • Aix-Marseille Université
      • Centre de Résonance Magnétique Biologique et Médicale (UMR 7339 CRMBM)
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 1980-2011
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • Etablissement Français du Sang Alsace
      Strasburg, Alsace, France
  • 2001
    • University of Liverpool
      Liverpool, England, United Kingdom
  • 1993-1999
    • University Joseph Fourier - Grenoble 1
      • Grenoble Institut des Neurosciences
      Grenoble, Rhône-Alpes, France