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Journal Article

  • Béchir, N, Pecchi, É, Vilmen, C, Bernard, M, Bendahan, D & Giannesini, B 2018, “ActRIIB blockade does not limit ATP supply in mouse skeletal muscle in vivo”, Muscle & Nerve.
    Résumé : INTRODUCTION: Postnatal activin/myostatin type IIB receptor (ActRIIB) blockade increases skeletal muscle mass and strength, but also increases muscle fatigability and impairs oxidative metabolism. The aim of this study was to determine in vivo whether this increased fatigability is due to energy supply limitation. METHODS: The impact of 8-week ActRIIB blockade with soluble receptor (sActRIIB-Fc) upon muscle function and ATP fluxes was investigated noninvasively using multimodal magnetic resonance and indirect calorimetry measurements in wild-type mice. RESULTS: ActRIIB blockade reduced (-41%) the muscle apparent mitochondrial capacity and increased (+11%) the basal body energy expenditure. During a fatiguing exercise, ActRIIB blockade decreased both oxidative ATP production rate (-32%) and fatigue resistance (-36%) but these changes affected neither the total ATP production rate nor the contractile ATP cost. DISCUSSION: These findings demonstrate that the increased fatigability following ActRIIB blockade is not due to limitation in energy supply and/or disturbance in contractile ATP cost. This article is protected by copyright. All rights reserved.
    Mots-clés : Activin myostatin receptor, crmbm, Energy expenditure, Exercise, Fatigue, msk, Muscle wasting therapy, Oxidative capacity.

  • Benacchio, S, Doutres, O, Le Troter, A, Varoquaux, A, Wagnac, E, Callot, V & Sgard, F 2018, “Estimation of the ear canal displacement field due to in-ear device insertion using a registration method on a human-like artificial ear”, Hearing Research, vol. 365, p. 16-27.
    Résumé : Passive and active in-ear devices (IED) occluding the ear canal are commonly used to (i) protect people from high noise levels (earplugs), (ii) assist people suffering from hearing impairment (hearing aids) or (iii) help people in listening from their sound systems (earbuds). However, the usability and/or efficiency of IEDs can be greatly affected by several discomfort components (physical, acoustical and functional). The mechanical pressure exerted by the IED onto the ear canal walls is greatly suspected to affect the aforementioned comfort components. This physical characteristic is closely related to the displacement field induced by the IED insertion, which has to be known for a better understanding of perceived discomfort. Thus, this paper proposes to validate a method based on medical images to estimate the displacement field of the ear canal walls due to the insertion of an IED. The approach is validated on a human-like artificial ear with canal geometry deformed using two custom molded IEDs with controlled shapes. These geometries are obtained using computed tomography imaging and the displacement field is computed using a registration method. The errors due to the ear canal segmentation and to the registration steps are small enough to compute a relevant estimation of the expected displacement field. Results show that the amplitude of the displacement and its location into the ear canal can be evaluated with an accuracy of ± 0.2 mm and ± 0.4 mm respectively. Preliminary results on images with a degraded resolution indicate that the proposed approach used to assess the displacement field of the ear canal walls using computed tomography images could be applied on magnetic resonance images, which is a preferred method to image human subject ear canals for future investigations.
    Mots-clés : crmbm, Deformation, Displacement, Ear canal, Earbud, Earplug, Hearing aids, snc.

  • 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.

  • Chatel, B, Messonnier, LA & Bendahan, D 2018, “Do we have to consider acidosis induced by exercise as deleterious in sickle cell disease?”, Experimental Physiology.
    Résumé : Sickle cell disease (SCD) is an inherited haemoglobin (Hb) disorder and the most common monogenic disease in the world. The root cause of this pathology is the synthesis of an abnormal Hb (HbS) that polymerizes in deoxygenated conditions, leading to the sickling of red blood cells (RBC). Acidosis is well-recognized as a promoter of HbS polymerisation, and thereby RBC sickling. Indeed, it has been shown in vitro that the relative amount of sickled RBC increased markedly from 1% at pH 7.4 to more than 90% at pH 7.0. Nevertheless, no study has directly tested if exercise-induced acidosis could favour SCD complications. Yet, increased knowledge of the effects of metabolic acidosis during exercise could be of importance given the conclusions reached in several studies that proposed regular physical exercise as a therapeutic strategy in managing SCD. In this review, we discuss the potential consequences of exercise-induced acidosis on the pathophysiology of SCD. We also propose some potential therapeutic interventions aiming at reducing the metabolic acidosis related to exercise. This article is protected by copyright. All rights reserved.
    Mots-clés : crmbm, exercise therapy, msk, pH, Sickle cell anaemia, vaso-occlusive crisis.

  • Choquet, C, Nguyen, THM, Sicard, P, Buttigieg, E, Tran, TT, Kober, F, Varlet, I, Sturny, R, Costa, MW, Harvey, RP, Nguyen, C, Rihet, P, Richard, S, Bernard, M, Kelly, RG, Lalevée, N & Miquerol, L 2018, “Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy”, PLoS genetics, vol. 14, no. 7, p. e1007502.
    Résumé : Left ventricular non-compaction (LVNC) is a rare cardiomyopathy associated with a hypertrabeculated phenotype and a large spectrum of symptoms. It is still unclear whether LVNC results from a defect of ventricular trabeculae development and the mechanistic basis that underlies the varying severity of this pathology is unknown. To investigate these issues, we inactivated the cardiac transcription factor Nkx2-5 in trabecular myocardium at different stages of trabecular morphogenesis using an inducible Cx40-creERT2 allele. Conditional deletion of Nkx2-5 at embryonic stages, during trabecular formation, provokes a severe hypertrabeculated phenotype associated with subendocardial fibrosis and Purkinje fiber hypoplasia. A milder phenotype was observed after Nkx2-5 deletion at fetal stages, during trabecular compaction. A longitudinal study of cardiac function in adult Nkx2-5 conditional mutant mice demonstrates that excessive trabeculation is associated with complex ventricular conduction defects, progressively leading to strain defects, and, in 50% of mutant mice, to heart failure. Progressive impaired cardiac function correlates with conduction and strain defects independently of the degree of hypertrabeculation. Transcriptomic analysis of molecular pathways reflects myocardial remodeling with a larger number of differentially expressed genes in the severe versus mild phenotype and identifies Six1 as being upregulated in hypertrabeculated hearts. Our results provide insights into the etiology of LVNC and link its pathogenicity with compromised trabecular development including compaction defects and ventricular conduction system hypoplasia.
    Mots-clés : crmbm, cvs.

  • Combès, B, Kerbrat, A, Ferré, JC, Callot, V, Maranzano, J, Badji, A, Le Page, E, Labauge, P, Ayrignac, X, Carra Dallière, C, de Champfleur, NM, Pelletier, J, Maarouf, A, de Seze, J, Collongues, N, Brassat, D, Durand-Dubief, F, Barillot, C, Bannier, E, Edan, G & EMISEP Study Group, 2018, “Focal and diffuse cervical spinal cord damage in patients with early relapsing-remitting MS: A multicentre magnetisation transfer ratio study”, Multiple Sclerosis (Houndmills, Basingstoke, England), p. 1352458518781999.
    Résumé : BACKGROUND: Studies including patients with well-established multiple sclerosis (MS) have shown a significant and disability-related reduction in the cervical spinal cord (SC) magnetisation transfer ratio (MTR). OBJECTIVES: The objectives are to (1) assess whether MTR reduction is already measurable in the SC of patients with early relapsing-remitting multiple sclerosis (RRMS) and (2) describe its spatial distribution. METHODS: We included 60 patients with RRMS <12  months and 34 age-matched controls at five centres. Axial T2*w, sagittal T2w, sagittal phase-sensitive inversion recovery (PSIR), 3DT1w, and axial magnetisation transfer (MT) images were acquired from C1 to C7. Lesions were manually labelled and mean MTR values computed both for the whole SC and for normal-appearing SC in different regions of interest. RESULTS: Mean whole SC MTR was significantly lower in patients than controls (33.7 vs 34.9  pu, p  =  0.00005), even after excluding lesions (33.9  pu, p  =  0.0003). We observed a greater mean reduction in MTR for vertebral levels displaying the highest lesion loads (C2-C4). In the axial plane, we observed a greater mean MTR reduction at the SC periphery and barycentre. CONCLUSION: Cervical SC tissue damage measured using MTR is not restricted to macroscopic lesions in patients with early RRMS and is not homogeneously distributed.
    Mots-clés : crmbm, magnetisation transfer imaging, Quantitative MRI, relapsing–remitting multiple sclerosis, snc, Spinal cord.

  • De Leener, B, Fonov, VS, Collins, DL, Callot, V, Stikov, N & Cohen-Adad, J 2018, “PAM50: Unbiased multimodal template of the brainstem and spinal cord aligned with the ICBM152 space”, NeuroImage, vol. 165, p. 170-179.
    Résumé : Template-based analysis of multi-parametric MRI data of the spinal cord sets the foundation for standardization and reproducibility, thereby helping the discovery of new biomarkers of spinal-related diseases. While MRI templates of the spinal cord have been recently introduced, none of them cover the entire spinal cord. In this study, we introduced an unbiased multimodal MRI template of the spinal cord and the brainstem, called PAM50, which is anatomically compatible with the ICBM152 brain template and uses the same coordinate system. The PAM50 template is based on 50 healthy subjects, covers the full spinal cord (C1 to L2 vertebral levels) and the brainstem, is available for T1-, T2-and T2*-weighted MRI contrasts and includes a probabilistic atlas of the gray matter and white matter tracts. Template creation accuracy was assessed by computing the mean and maximum distance error between each individual spinal cord centerline and the PAM50 centerline, after registration to the template. Results showed high accuracy for both T1- (mean = 0.37 ± 0.06 mm; max = 1.39 ± 0.58 mm) and T2-weighted (mean = 0.11 ± 0.03 mm; max = 0.71 ± 0.27 mm) contrasts. Additionally, the preservation of the spinal cord topology during the template creation process was verified by comparing the cross-sectional area (CSA) profile, averaged over all subjects, and the CSA profile of the PAM50 template. The fusion of the PAM50 and ICBM152 templates will facilitate group and multi-center studies of combined brain and spinal cord MRI, and enable the use of existing atlases of the brainstem compatible with the ICBM space.
    Mots-clés : Atlas, crmbm, ICBM, MRI, Spinal cord, Template.

  • Fouré, A, Ogier, AC, Le Troter, A, Vilmen, C, Feiweier, T, Guye, M, Gondin, J, Besson, P & Bendahan, D 2018, “Diffusion Properties and 3D Architecture of Human Lower Leg Muscles Assessed with Ultra-High-Field-Strength Diffusion-Tensor MR Imaging and Tractography: Reproducibility and Sensitivity to Sex Difference and Intramuscular Variability”, Radiology, vol. 287, no. 2, p. 592-607.
    Résumé : Purpose To demonstrate the reproducibility of the diffusion properties and three-dimensional structural organization measurements of the lower leg muscles by using diffusion-tensor imaging (DTI) assessed with ultra-high-field-strength (7.0-T) magnetic resonance (MR) imaging and tractography of skeletal muscle fibers. On the basis of robust statistical mapping analyses, this study also aimed at determining the sensitivity of the measurements to sex difference and intramuscular variability. Materials and Methods All examinations were performed with ethical review board approval; written informed consent was obtained from all volunteers. Reproducibility of diffusion tensor indexes assessment including eigenvalues, mean diffusivity, and fractional anisotropy (FA) as well as muscle volume and architecture (ie, fiber length and pennation angle) were characterized in lower leg muscles (n = 8). Intramuscular variability and sex differences were characterized in young healthy men and women (n = 10 in each group). Student t test, statistical parametric mapping, correlation coefficients (Spearman rho and Pearson product-moment) and coefficient of variation (CV) were used for statistical data analysis. Results High reproducibility of measurements (mean CV ± standard deviation, 4.6% ± 3.8) was determined in diffusion properties and architectural parameters. Significant sex differences were detected in FA (4.2% in women for the entire lower leg; P = .001) and muscle volume (21.7% in men for the entire lower leg; P = .008), whereas architecture parameters were almost identical across sex. Additional differences were found independently of sex in diffusion properties and architecture along several muscles of the lower leg. Conclusion The high-spatial-resolution DTI assessed with 7.0-T MR imaging allows a reproducible assessment of structural organization of superficial and deep muscles, giving indirect information on muscle function. ©RSNA, 2018 Online supplemental material is available for this article.
    Mots-clés : crmbm, msk.

  • Fournely, M, Petit, Y, Wagnac, É, Laurin, J, Callot, V & Arnoux, P-J 2018, “High-speed video analysis improves the accuracy of spinal cord compression measurement in a mouse contusion model”, Journal of Neuroscience Methods, vol. 293, p. 1-5.
    Résumé : BACKGROUND: Animal models of spinal cord injuries aim to utilize controlled and reproducible conditions. However, a literature review reveals that mouse contusion studies using equivalent protocols may show large disparities in the observed impact force vs. cord compression relationship. The overall purpose of this study was to investigate possible sources of bias in these measurements. The specific objective was to improve spinal cord compression measurements using a video-based setup to detect the impactor-spinal cord time-to-contact. NEW METHOD: A force-controlled 30kDyn unilateral contusion at C4 vertebral level was performed in six mice with the Infinite Horizon impactor (IH). High-speed video was used to determine the time-to-contact between the impactor tip and the spinal cord and to compute the related displacement of the tip into the tissue: the spinal cord compression and the compression ratio. RESULTS & COMPARISON WITH EXISTING METHOD(S): Delayed time-to-contact detection with the IH device led to an underestimation of the cord compression. Compression values indicated by the IH were 64% lower than those based on video analysis (0.33mm vs. 0.88mm). Consequently, the mean compression ratio derived from the device was underestimated when compared to the value derived from video analysis (22% vs. 61%). CONCLUSIONS: Default time-to-contact detection from the IH led to significant errors in spinal cord compression assessment. Accordingly, this may explain some of the reported data discrepancies in the literature. The proposed setup could be implemented by users of contusion devices to improve the quantative description of the primary injury inflicted to the spinal cord.
    Mots-clés : Compression ratio, Contusion device, crmbm, High-speed video analysis, Mouse model, snc, Spinal cord injury.

  • Gineste, C & Fouré, A 2018, “Heterogeneity of energy metabolism within the tibialis anterior. Is it just an outcome of a specific muscle activation, architecture and composition?”, The Journal of Physiology.

  • Gros, C, De Leener, B, Dupont, SM, Martin, AR, Fehlings, MG, Bakshi, R, Tummala, S, Auclair, V, McLaren, DG, Callot, V, Cohen-Adad, J & Sdika, M 2018, “Automatic spinal cord localization, robust to MRI contrasts using global curve optimization”, Medical Image Analysis, vol. 44, p. 215-227.
    Résumé : During the last two decades, MRI has been increasingly used for providing valuable quantitative information about spinal cord morphometry, such as quantification of the spinal cord atrophy in various diseases. However, despite the significant improvement of MR sequences adapted to the spinal cord, automatic image processing tools for spinal cord MRI data are not yet as developed as for the brain. There is nonetheless great interest in fully automatic and fast processing methods to be able to propose quantitative analysis pipelines on large datasets without user bias. The first step of most of these analysis pipelines is to detect the spinal cord, which is challenging to achieve automatically across the broad range of MRI contrasts, field of view, resolutions and pathologies. In this paper, a fully automated, robust and fast method for detecting the spinal cord centerline on MRI volumes is introduced. The algorithm uses a global optimization scheme that attempts to strike a balance between a probabilistic localization map of the spinal cord center point and the overall spatial consistency of the spinal cord centerline (i.e. the rostro-caudal continuity of the spinal cord). Additionally, a new post-processing feature, which aims to automatically split brain and spine regions is introduced, to be able to detect a consistent spinal cord centerline, independently from the field of view. We present data on the validation of the proposed algorithm, known as "OptiC", from a large dataset involving 20 centers, 4 contrasts (T2-weighted n = 287, T1-weighted n = 120, T2∗-weighted n = 307, diffusion-weighted n = 90), 501 subjects including 173 patients with a variety of neurologic diseases. Validation involved the gold-standard centerline coverage, the mean square error between the true and predicted centerlines and the ability to accurately separate brain and spine regions. Overall, OptiC was able to cover 98.77% of the gold-standard centerline, with a mean square error of 1.02 mm. OptiC achieved superior results compared to a state-of-the-art spinal cord localization technique based on the Hough transform, especially on pathological cases with an averaged mean square error of 1.08 mm vs. 13.16 mm (Wilcoxon signed-rank test p-value < .01). Images containing brain regions were identified with a 99% precision, on which brain and spine regions were separated with a distance error of 9.37 mm compared to ground-truth. Validation results on a challenging dataset suggest that OptiC could reliably be used for subsequent quantitative analyses tasks, opening the door to more robust analysis on pathological cases.
    Mots-clés : crmbm, Detection, Global optimization, Machine learning, MRI, Segmentation, Spinal cord.

  • Lutz, NW & Bernard, M 2018, “Multiparametric quantification of heterogeneity of metal ion concentrations, as demonstrated for [Mg2+] by way of 31P MRS”, Journal of Magnetic Resonance (San Diego, Calif.: 1997), vol. 294, p. 71-82.
    Résumé : Magnesium(II) is the second most abundant intracellular cation in mammals. Non-invasive 31P MRS is currently used to measure intracellular free Mg2+ levels in studies of magnesium deficiency disorders. However, this technique only provides one [Mg2+] value for a given tissue volume (or voxel), based on the chemical shift of the ATP-β (or NTP-β) resonance. We present here an approach for quantifying tissue heterogeneity in regard to [Mg2+], by way of multiple 31P MRS-derived descriptors characterizing the statistical intra-volume distribution of free [Mg2+] values. Our novel paradigm exploits the fact that the lineshape of the ATP-β 31P MRS resonance reflects the statistical distribution of [Mg2+] values within the observed volume (or voxel). Appropriate lineshape analysis reveals multiple quantitative statistical parameters (descriptors) characterizing the [Mg2+] distribution. First, the ATP-β 31P MRS resonance is transformed into a [Mg2+] curve that is used to construct a histogram with our specially developed algorithms. From this histogram, at least eight [Mg2+] descriptors are computed: weighted mean concentration and median concentration, standard deviation of concentration, range of concentration, concentration mode(s), concentration kurtosis, concentration skewness, and concentration entropy. Comprehensive evaluation based on in silico and experimental models demonstrates the validity of this new method. This basic feasibility study should open new avenues for future in vivo studies in physiology and medicine.
    Mots-clés : (31)P NMR, crmbm, Free Mg(2+) concentration, Heterogeneity descriptors, Histograms, Lineshape analysis, Statistical distributions.

  • 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.

  • Massire, A, Rasoanandrianina, H, Taso, M, Guye, M, Ranjeva, J-P, Feiweier, T & Callot, V 2018, “Feasibility of single-shot multi-level multi-angle diffusion tensor imaging of the human cervical spinal cord at 7T”, Magnetic Resonance in Medicine, vol. 80, no. 3, p. 947-957.
    Résumé : PURPOSE: Diffusion tensor imaging (DTI), which is frequently used to characterize microstructure impairments in many spinal cord diseases at clinical fields, may benefit from 7T investigations. Yet, it presents specific technical challenges, such as increased magnetic susceptibility-induced image distortions. METHODS: Eight healthy volunteers were scanned at 7T using a prototype diffusion multi-slice multi-angle (MSMA) single-shot spin-echo echo planar imaging (EPI) sequence developed to explore the whole cervical spinal cord while limiting the partial volume effects related to the cord curvature. To mitigate the increased susceptibility-induced distortions encountered at 7T, a reverse phase-encoding strategy was also used. Images acquired from C1-to-C7 were registered to the AMU40 template to automatically extract DTI metrics in gray matter/white matter regions of interest. Effects of B1+ inhomogeneities on the DTI metrics and repeatability of the measurements were also investigated. Lastly, a DTI acquisition with a 400-µm in-plane resolution was acquired on one volunteer to push forward 7T potentialities. RESULTS: The MSMA sequence allowed accessing to high-resolution axial diffusion images sampling the whole cord within a single acquisition. DTI metrics were found in agreement with literature at lower field, stable along a 50-120% relative B1+ variation range, with a mean inter-scan coefficient of variation of 8%. The two--fold spatial-resolution increase of the additional DTI acquisition enabled main white matter tracts visualization on a single-subject basis. CONCLUSION: Although C7-level imaging needs some improvement, this preliminary study shows that transverse 7T DTI of the whole cervical spinal cord is feasible, laying the groundwork for improved multi-parametric MR investigations and microstructure characterization of the spinal cord. Magn Reson Med 80:947-957, 2018. © 2018 International Society for Magnetic Resonance in Medicine.
    Mots-clés : 7T, crmbm, diffusion tensor imaging, multi-slice multi-angle acquisitions, snc, ultra-high-field MRI.

  • Mathieu, C, Desrois, M, Kober, F, Lalevée, N, Lan, C, Fourny, N, Iché-Torres, M, Tran, TT, Lê, LT, Singer, M, Mège, J-L, Bernard, M & Leone, M 2018, “Sex-Mediated Response to the Beta-Blocker Landiolol in Sepsis: An Experimental, Randomized Study”, Critical Care Medicine.
    Résumé : OBJECTIVES: To investigate any gender effect of the beta-1 adrenergic blocker, landiolol, on cardiac performance and energy metabolism in septic rats, and to explore the expression of genes and proteins involved in this process. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female Wistar rats. INTERVENTIONS: One hour after cecal ligation and puncture, male and female rats were randomly allocated to the following groups: sham male, cecal ligation and puncture male, cecal ligation and puncture + landiolol male, sham female, cecal ligation and puncture female, and cecal ligation and puncture + landiolol female. Cardiac MRI was carried out 18 hours after cecal ligation and puncture to assess in vivo cardiac function. Ex vivo cardiac function measurement and P magnetic resonance spectroscopy were subsequently performed using an isovolumic isolated heart preparation. Finally, we assessed cardiac gene and protein expression. MEASUREMENTS AND MAIN RESULTS: In males, landiolol increased indexed stroke volume by reversing the indexed end-diastolic volume reduction without affecting left ventricle ejection fraction. In females, landiolol did not increase indexed stroke volume and indexed end-diastolic volume but decreased left ventricle ejection fraction. Landiolol had no effect on ex vivo cardiac function and on high-energy phosphate compounds. The effect of landiolol on the gene expression of natriuretic peptide receptor 3 and on protein expression of phosphorylated-AKT:AKT ratio and endothelial nitric oxide synthase was different in males and females. CONCLUSIONS: Landiolol improved the in vivo cardiac performance of septic male rats while deleterious effects were reported in females. Expression of natriuretic peptide receptor 3, phosphorylated-AKT:AKT, and endothelial nitric oxide synthase are signaling pathways to investigate to better understand the sex differences in sepsis.
    Mots-clés : crmbm, cvs.

  • Maurice, F, Dutour, A, Vincentelli, C, Abdesselam, I, Bernard, M, Dufour, H, Le Fur, Y, Graillon, T, Kober, F, Cristofari, P, Jouve, E, Pini, L, Fernandez, R, Chagnaud, C, Brue, T, Castinetti, F & Gaborit, B 2018, “Active cushing syndrome patients have increased ectopic fat deposition and bone marrow fat content compared to cured patients and healthy subjects: a pilot 1H-MRS study”, European Journal of Endocrinology.
    Résumé : OBJECTIVE: Glucocorticoid excess is one of the most important causes of bone disorders. Bone marrow fat (BMF) has been identified as a l new mediator of bone metabolism. Cushing syndrome (CS), is a main regulator of adipose tissue distribution but its impact on BMF is unknown. The objective of the study was to evaluate the effect of chronic hypercortisolism on BMF. DESIGN: This was a cross-sectional study. Seventeen active and seventeen cured ACTH-dependent CS patients along with seventeen controls (matched with the active group for age and sex) were included. METHODS: the BMF content of the femoral neck and L3 vertebrae were measured by 1H-MRS on a 3-Tesla wide-bore magnet. BMD was evaluated in patients using dual-energy X-ray absorptiometry. RESULTS: Active CS patients had higher BMF content both in the femur (82.5±2.6%) and vertebrae (70.1±5.1%) compared to the controls (70.8±3.6%, p=0.013 and 49.0±3.7% p=0.005, respectively). In cured CS patients (average remission time of 43 months), BMF content was not different from controls at both sites (72.3±2.9% (femur) and 46.7%±5.3% (L3)). BMF content was positively correlated with age, fasting plasma glucose, HbA1c, triglycerides and visceral adipose tissue in the whole cohort and negatively correlated with BMD values in the CS patients . CONCLUSIONS: Accumulation of BMF is induced by hypercortisolism. In remission patients BMF reached values of controls. Further studies are needed to determine whether this increase in marrow adiposity in CS is associated with bone loss.
    Mots-clés : crmbm, cvs.

  • Mchinda, S, Varma, G, Prevost, VH, Le Troter, A, Rapacchi, S, Guye, M, Pelletier, J, Ranjeva, J-P, Alsop, DC, Duhamel, G & Girard, OM 2018, “Whole brain inhomogeneous magnetization transfer (ihMT) imaging: Sensitivity enhancement within a steady-state gradient echo sequence”, Magnetic Resonance in Medicine, vol. 79, no. 5, p. 2607-2619.
    Résumé : PURPOSE: To implement, characterize, and optimize an interleaved inhomogeneous magnetization transfer (ihMT) gradient echo sequence allowing for whole-brain imaging within a clinically compatible scan time. THEORY AND METHODS: A general framework for ihMT modelling was developed based on the Provotorov theory of radiofrequency saturation, which accounts for the dipolar order underpinning the ihMT effect. Experimental studies and numerical simulations were performed to characterize and optimize the ihMT-gradient echo dependency with sequence timings, saturation power, and offset frequency. The protocol was optimized in terms of maximum signal intensity and the reproducibility assessed for a nominal resolution of 1.5 mm isotropic. All experiments were performed on healthy volunteers at 1.5T. RESULTS: An important mechanism driving signal optimization and leading to strong ihMT signal enhancement that relies on the dynamics of radiofrequency energy deposition has been identified. By taking advantage of the delay allowed for readout between ihMT pulse bursts, it was possible to boost the ihMT signal by almost 2-fold compared to previous implementation. Reproducibility of the optimal protocol was very good, with an intra-individual error < 2%. CONCLUSION: The proposed sensitivity-boosted and time-efficient steady-state ihMT-gradient echo sequence, implemented and optimized at 1.5T, allowed robust high-resolution 3D ihMT imaging of the whole brain within a clinically compatible scan time. Magn Reson Med 79:2607-2619, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
    Mots-clés : crmbm, dipolar order, dual frequency RF saturation, ihMT, inhomogeneous magnetization transfer, magnetization transfer model, myelin, Provotorov theory of radiofrequency saturation, snc.

  • Messineo, AM, Gineste, C, Sztal, TE, McNamara, EL, Vilmen, C, Ogier, AC, Hahne, D, Bendahan, D, Laing, NG, Bryson-Richardson, RJ, Gondin, J & Nowak, KJ 2018, “L-tyrosine supplementation does not ameliorate skeletal muscle dysfunction in zebrafish and mouse models of dominant skeletal muscle α-actin nemaline myopathy”, Scientific Reports, vol. 8, no. 1, p. 11490.
    Résumé : L-tyrosine supplementation may provide benefit to nemaline myopathy (NM) patients, however previous studies are inconclusive, with no elevation of L-tyrosine levels in blood or tissue reported. We evaluated the ability of L-tyrosine treatments to improve skeletal muscle function in all three published animal models of NM caused by dominant skeletal muscle α-actin (ACTA1) mutations. Highest safe L-tyrosine concentrations were determined for dosing water and feed of wildtype zebrafish and mice respectively. NM TgACTA1D286G-eGFP zebrafish treated with 10 μM L-tyrosine from 24 hours to 6 days post fertilization displayed no improvement in swimming distance. NM TgACTA1D286G mice consuming 2% L-tyrosine supplemented feed from preconception had significant elevations in free L-tyrosine levels in sera (57%) and quadriceps muscle (45%) when examined at 6-7 weeks old. However indicators of skeletal muscle integrity (voluntary exercise, bodyweight, rotarod performance) were not improved. Additionally no benefit on the mechanical properties, energy metabolism, or atrophy of skeletal muscles of 6-7 month old TgACTA1D286G and KIActa1H40Y mice eventuated from consuming a 2% L-tyrosine supplemented diet for 4 weeks. Therefore this study yields important information on aspects of the clinical utility of L-tyrosine for ACTA1 NM.
    Mots-clés : crmbm, msk.

  • Petracca, M, Zaaraoui, W, Cocozza, S, Vancea, R, Howard, J, Heinig, MM, Fleysher, L, Oesingmann, N, Ranjeva, J-P & Inglese, M 2018, “An MRI evaluation of grey matter damage in African Americans with MS”, Multiple Sclerosis and Related Disorders, vol. 25, p. 29-36.
    Résumé : OBJECTIVE: Multiple sclerosis (MS) is less prevalent in African Americans (AAs) than Caucasians (CAs) but in the former the disease course tends to be more severe. In order to clarify the MRI correlates of disease severity in AAs, we performed a multimodal brain MRI study to comprehensively assess the extent of grey matter (GM) damage and the degree of functional adaptation to structural damage in AAs with MS. METHODS: In this cross-sectional study, we characterized GM damage in terms of focal lesions and volume loss and functional adaptation during the execution of a simple motor task on a sample of 20 AAs and 20 CAs with MS and 20 healthy controls (CTRLs). RESULTS: In AAs, we observed a wider range of EDSS scores than CAs, with multisystem involvement being more likely in AAs (p < 0.01). While no significant differences were detected in lesion loads and global brain volumes, AAs showed regional atrophy in the posterior lobules of cerebellum, temporo-occipital and frontal regions in comparison with CAs (p < 0.01), with cerebellar atrophy being the best metric in differentiating AAs from CAs (p = 0.007, AUC = 0.96 and p = 0.005, AUC = 0.96, respectively for right and left cerebellar clusters). In AAs, the functional analysis of cortical activations showed an increase in task-related activation of areas involved in high level processing and a decreased activation in the medial prefrontal cortex compared to CAs. INTERPRETATION: In our study, the direct comparison of AAs and CAs points to cerebellar atrophy as the main difference between subgroups.
    Mots-clés : African Americans, crmbm, Grey matter, Multiple Sclerosis, snc.

  • Ridley, B, Nagel, AM, Bydder, M, Maarouf, A, Stellmann, J-P, Gherib, S, Verneuil, J, Viout, P, Guye, M, Ranjeva, J-P & Zaaraoui, W 2018, “Distribution of brain sodium long and short relaxation times and concentrations: a multi-echo ultra-high field23Na MRI study”, Scientific Reports, vol. 8, no. 1, p. 4357.
    Résumé : Sodium (23Na) MRI proffers the possibility of novel information for neurological research but also particular challenges. Uncertainty can arise in in vivo23Na estimates from signal losses given the rapidity of T2* decay due to biexponential relaxation with both short (T2*short) and long (T2*long) components. We build on previous work by characterising the decay curve directly via multi-echo imaging at 7 T in 13 controls with the requisite number, distribution and range to assess the distribution of both in vivo T2*shortand T2*longand in variation between grey and white matter, and subregions. By modelling the relationship between signal and reference concentration and applying it to in vivo23Na-MRI signal,23Na concentrations and apparent transverse relaxation times of different brain regions were measured for the first time. Relaxation components and concentrations differed substantially between regions of differing tissue composition, suggesting sensitivity of multi-echo23Na-MRI toward features of tissue composition. As such, these results raise the prospect of multi-echo23Na-MRI as an adjunct source of information on biochemical mechanisms in both physiological and pathophysiological states.
    Mots-clés : crmbm, snc.

  • Van Obberghen, E, Mchinda, S, le Troter, A, Prevost, VH, Viout, P, Guye, M, Varma, G, Alsop, DC, Ranjeva, J-P, Pelletier, J, Girard, O & Duhamel, G 2018, “Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis”, AJNR. American journal of neuroradiology, vol. 39, no. 4, p. 634-641.
    Résumé : BACKGROUND AND PURPOSE: Inhomogeneous magnetization transfer is a new endogenous MR imaging contrast mechanism that has demonstrated high specificity for myelin. Here, we tested the hypothesis that inhomogeneous magnetization transfer is sensitive to pathology in a population of patients with relapsing-remitting MS in a way that both differs from and complements conventional magnetization transfer. MATERIALS AND METHODS: Twenty-five patients with relapsing-remitting MS and 20 healthy volunteers were enrolled in a prospective MR imaging research study, whose protocol included anatomic imaging, standard magnetization transfer, and inhomogeneous magnetization transfer imaging. Magnetization transfer and inhomogeneous magnetization transfer ratios measured in normal-appearing brain tissue and in MS lesions of patients were compared with values measured in control subjects. The potential association of inhomogeneous magnetization transfer ratio variations with the clinical scores (Expanded Disability Status Scale) of patients was further evaluated. RESULTS: The magnetization transfer ratio and inhomogeneous magnetization transfer ratio measured in the thalami and frontal, occipital, and temporal WM of patients with MS were lower compared with those of controls (P < .05). The mean inhomogeneous magnetization transfer ratio measured in lesions was lower than that in normal-appearing WM (P < .05). Significant (P < .05) negative correlations were found between the clinical scores and inhomogeneous magnetization transfer ratio measured in normal-appearing WM structures. Weaker nonsignificant correlation trends were found for the magnetization transfer ratio. CONCLUSIONS: The sensitivity of the inhomogeneous magnetization transfer technique for MS was highlighted by the reduction in the inhomogeneous magnetization transfer ratio in MS lesions and in normal-appearing WM of patients compared with controls. Stronger correlations with the Expanded Disability Status Scale score were obtained with the inhomogeneous magnetization transfer ratio compared with the standard magnetization transfer ratio, which may be explained by the higher specificity of inhomogeneous magnetization transfer for myelin.
    Mots-clés : crmbm, ihMT, snc.


Journal Article

  • Besson, P, Bandt, SK, Proix, T, Lagarde, S, Jirsa, VK, Ranjeva, J-P, Bartolomei, F & Guye, M 2017, “Anatomic consistencies across epilepsies: a stereotactic-EEG informed high-resolution structural connectivity study”, Brain: A Journal of Neurology, vol. 140, no. 10, p. 2639-2652.
    Mots-clés : Brain networks, crmbm, diffusion weighted imaging, Epilepsy, SEEG, snc, structural connectivity.

  • Bydder, M, Rapacchi, S, Girard, O, Guye, M & Ranjeva, J-P 2017, “Trimmed autocalibrating k-space estimation based on structured matrix completion”, Magnetic Resonance Imaging, vol. 43, p. 88-94.
    Résumé : PURPOSE: Parallel imaging allows the reconstruction of undersampled data from multiple coils. This provides a means to reject and regenerate corrupt data (e.g. from motion artefact). The purpose of this work is to approach this problem using the SAKE parallel imaging method. THEORY AND METHODS: Parallel imaging methods typically require calibration by fully sampling the center of k-space. This is a challenge in the presence of corrupted data, since the calibration data may be corrupted which leads to an errors-in-variables problem that cannot be solved by least squares or even iteratively reweighted least squares. The SAKE method, based on matrix completion and structured low rank approximation, was modified to detect and trim these errors from the data. RESULTS: Simulated and actual corrupted datasets were reconstructed with SAKE, the proposed approach and a more standard reconstruction method (based on solving a linear equation) with a data rejection criterion. The proposed approach was found to reduce artefacts considerably in comparison to the other two methods. CONCLUSION: SAKE with data trimming improves on previous methods for reconstructing images from grossly corrupted data.
    Mots-clés : Artefacts, crmbm, IRLS, Parallel imaging, Robust, snc, Structured low rank approximation.

  • 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.

  • Chatel, B, Messonnier, LA & Bendahan, D 2017, “Exacerbated in vivo metabolic changes suggestive of a spontaneous muscular vaso-occlusive crisis in exercising muscle of a sickle cell mouse”, Blood Cells, Molecules, and Diseases, vol. 65, p. 56-59, viewed 18August,2017, .
    Résumé : While sickle cell disease (SCD) is characterized by frequent vaso-occlusive crisis (VOC), no direct observation of such an event in skeletal muscle has been performed in vivo. The present study reported exacerbated in vivo metabolic changes suggestive of a spontaneous muscular VOC in exercising muscle of a sickle cell mouse. Using magnetic resonance spectroscopy of phosphorus 31, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured throughout two standardized protocols of rest – exercise – recovery at two different intensities in ten SCD mice. Among these mice, one single mouse presented divergent responses. A statistical analysis (based on confidence intervals) revealed that this single mouse presented slower phosphocreatine resynthesis and inorganic phosphate disappearance during the post-stimulation recovery of one of the protocols, what could suggest an ischemia. This study described, for the first time in a sickle cell mouse in vivo, exacerbated metabolic changes triggered by an exercise session that would be suggestive of a live observation of a muscular VOC. However, no evidence of a direct cause-effect relationship between exercise and VOC has been put forth.
    Mots-clés : crmbm, HbS polymerization, Magnetic resonance spectroscopy of phosphorus 31, msk, Physical activity, Red blood cell sickling.

  • De Leener, B, Levy, S, Dupont, SM, Fonov, VS, Stikov, N, Collins, DL, Callot, V & Cohen-Adad, J 2017, “SCT: Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data”, Neuroimage, vol. 145, p. 24-43.
    Résumé : For the past 25 years, the field of neuroimaging has witnessed the development of several software packages for processing multi-parametric magnetic resonance imaging (mpMRI) to study the brain. These software packages are now routinely used by researchers and clinicians, and have contributed to important breakthroughs for the understanding of brain anatomy and function. However, no software package exists to process mpMRI data of the spinal cord. Despite the numerous clinical needs for such advanced mpMRI protocols (multiple sclerosis, spinal cord injury, cervical spondylotic myelopathy, etc.), researchers have been developing specific tools that, while necessary, do not provide an integrative framework that is compatible with most usages and that is capable of reaching the community at large. This hinders cross-validation and the possibility to perform multi-center studies. In this study we introduce the Spinal Cord Toolbox (SCT), a comprehensive software dedicated to the processing of spinal cord MRI data. SCT builds on previously-validated methods and includes state-of-the-art MM templates and atlases of the spinal cord, algorithms to segment and register new data to the templates, and motion correction methods for diffusion and functional time series. SCT is tailored towards standardization and automation of the processing pipeline, versatility, modularity, and it follows guidelines of software development and distribution. Preliminary applications of SCT cover a variety of studies, from cross-sectional area measures in large databases of patients, to the precise quantification of mpMRI metrics in specific spinal pathways. We anticipate that SCT will bring together the spinal cord neuroimaging community by establishing standard templates and analysis procedures.
    Mots-clés : 3 tesla, age, Atlas, automatic segmentation, Brain, crmbm, diffeomorphic image registration, In-vivo, magnetization-transfer, matter segmentation, MRI, multiple-sclerosis, of-the-art, open-source, snc, Software, Spinal cord, Template.

  • 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.

  • Donadieu, M, Le Fur, Y, Maarouf, A, Gherib, S, Ridley, B, Pini, L, Rapacchi, S, Confort-Gouny, S, Guye, M, Schad, LR, Maudsley, AA, Pelletier, J, Audoin, B, Zaaraoui, W & Ranjeva, J-P 2017, “Metabolic counterparts of sodium accumulation in multiple sclerosis: A whole brain (23)Na-MRI and fast (1)H-MRSI study”, Multiple Sclerosis (Houndmills, Basingstoke, England), p. 1352458517736146.
    Résumé : BACKGROUND: Increase of brain total sodium concentrations (TSC) is present in multiple sclerosis (MS), but its pathological involvement has not been assessed yet. OBJECTIVE: To determine in vivo the metabolic counterpart of brain sodium accumulation. MATERIALS/METHODS: Whole brain (23)Na-MR imaging and 3D-(1)H-EPSI data were collected in 21 relapsing-remitting multiple sclerosis (RRMS) patients and 20 volunteers. Metabolites and sodium levels were extracted from several regions of grey matter (GM), normal-appearing white matter (NAWM) and white matter (WM) T2 lesions. Metabolic and ionic levels expressed as Z-scores have been averaged over the different compartments and used to explain sodium accumulations through stepwise regression models. RESULTS: MS patients showed significant (23)Na accumulations with lower choline and glutamate-glutamine (Glx) levels in GM; (23)Na accumulations with lower N-acetyl aspartate (NAA), Glx levels and higher Myo-Inositol (m-Ins) in NAWM; and higher (23)Na, m-Ins levels with lower NAA in WM T2 lesions. Regression models showed associations of TSC increase with reduced NAA in GM, NAWM and T2 lesions, as well as higher total-creatine, and smaller decrease of m-Ins in T2 lesions. GM Glx levels were associated with clinical scores. CONCLUSION: Increase of TSC in RRMS is mainly related to neuronal mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM is linked to clinical scores.
    Mots-clés : 23Na-MRI, crmbm, demyelination, MRSI, Multiple sclerosis, neurodegeneration, snc, stepwise regression.

  • Fatehi, F, Salort-Campana, E, Le Troter, A, Lareau-Trudel, E, Bydder, M, Fouré, A, Guye, M, Bendahan, D & Attarian, S 2017, “Long-term follow-up of MRI changes in thigh muscles of patients with Facioscapulohumeral dystrophy: A quantitative study”, PloS One, vol. 12, no. 8, p. e0183825.
    Résumé : Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common hereditary muscular disorders. Currently FSHD has no known effective treatment and detailed data on the natural history are lacking. Determination of the efficacy of a given therapeutic approach might be difficult in FSHD given the slow and highly variable disease progression. Magnetic resonance imaging (MRI) has been widely used to qualitatively and quantitatively evaluate in vivo the muscle alterations in various neuromuscular disorders. The main aim of the present study was to investigate longitudinally the time-dependent changes occurring in thigh muscles of FSHD patients using quantitative MRI and to assess the potential relationships with the clinical findings. Thirty-five FSHD1 patients (17 females) were enrolled. Clinical assessment tools including manual muscle testing using medical research council score (MRC), and motor function measure (MFM) were recorded each year for a period ranging from 1 to 2 years. For the MRI measurements, we used a new quantitative index, i.e., the mean pixel intensity (MPI) calculated from the pixel-intensity distribution in T1 weighted images. The corresponding MPI scores were calculated for each thigh, for each compartment and for both thighs totally (MPItotal). The total mean pixel intensity (MPItotal) refers to the sum of each pixel signal intensity divided by the corresponding number of pixels. An increased MPItotal indicates both a raised fat infiltration together with a reduced muscle volume thereby illustrating disease progression. Clinical scores did not change significantly over time whereas MPItotal increased significantly from an initial averaged value of 39.6 to 41.1 with a corresponding rate of 0.62/year. While clinical scores and MPItotal measured at the start of the study were significantly related, no correlation was found between the rate of MPItotal and MRC sum score changes, MFMtotal and MFM subscores. The relative rate of MPItotal change was 2.3% (0.5-4.3)/year and was significantly higher than the corresponding rates measured for MRCS 0% (0-1.7) /year and MFMtotal 0% (0-2.0) /year (p = 0.000). On the basis of these results, we suggested that muscle MRI and more particularly the MPItotal index could be used as a reliable biomarker and outcome measure of disease progression. In slowly progressive myopathies such as FSHD, the MPItotal index might reveal subclinical changes, which could not be evidenced using clinical scales over a short period of time.
    Mots-clés : crmbm, Humans, Magnetic Resonance Imaging, msk, Muscle, Skeletal, Muscular Dystrophy, Facioscapulohumeral.

  • Fouré, A & Bendahan, D 2017, “Is Branched-Chain Amino Acids Supplementation an Efficient Nutritional Strategy to Alleviate Skeletal Muscle Damage? A Systematic Review”, Nutrients, vol. 9, no. 10.
    Résumé : Amino acids and more precisely, branched-chain amino acids (BCAAs), are usually consumed as nutritional supplements by many athletes and people involved in regular and moderate physical activities regardless of their practice level. BCAAs have been initially shown to increase muscle mass and have also been implicated in the limitation of structural and metabolic alterations associated with exercise damage. This systematic review provides a comprehensive analysis of the literature regarding the beneficial effects of BCAAs supplementation within the context of exercise-induced muscle damage or muscle injury. The potential benefit of a BCAAs supplementation was also analyzed according to the supplementation strategy-amount of BCAAs, frequency and duration of the supplementation-and the extent of muscle damage. The review protocol was registered prospectively with Prospective Register for Systematic Reviews (registration number CRD42017073006) and followed Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Literature search was performed from the date of commencement until August 2017 using four online databases (Medline, Cochrane library, Web of science and ScienceDirect). Original research articles: (i) written in English; (ii) describing experiments performed in Humans who received at least one oral BCAAs supplementation composed of leucine, isoleucine and valine mixture only as a nutritional strategy and (iii) reporting a follow-up of at least one day after exercise-induced muscle damage, were included in the systematic review analysis. Quality assessment was undertaken independently using the Quality Criteria Checklist for Primary Research. Changes in indirect markers of muscle damage were considered as primary outcome measures. Secondary outcome measures were the extent of change in indirect markers of muscle damage. In total, 11 studies were included in the analysis. A high heterogeneity was found regarding the different outcomes of these studies. The risk of bias was moderate considering the quality ratings were positive for six and neutral for three. Although a small number of studies were included, BCAAs supplementation can be efficacious on outcomes of exercise-induced muscle damage, as long as the extent of muscle damage was low-to-moderate, the supplementation strategy combined a high daily BCAAs intake (>200 mg kg-1 day-1) for a long period of time (>10 days); it was especially effective if taken prior to the damaging exercise.
    Mots-clés : branched-chain amino acids (BCAAs), crmbm, exercise-induced muscle damage, msk, nutritional strategy, skeletal muscle.

  • Fouré, A, Duhamel, G, Vilmen, C, Bendahan, D, Jubeau, M & Gondin, J 2017, “Fast measurement of the quadriceps femoris muscle transverse relaxation time at high magnetic field using segmented echo-planar imaging”, Journal of magnetic resonance imaging: JMRI, vol. 45, no. 2, p. 356-368.
    Résumé : PURPOSE: To assess and validate a technique for transverse relaxation time (T2 ) measurements of resting and recovering skeletal muscle following exercise with a high temporal resolution and large volume coverage using segmented spin-echo echo-planar imaging (sSE-EPI). MATERIALS AND METHODS: Experiments were performed on a 3T magnetic resonance imaging (MRI) scanner using a multislice sSE-EPI technique applied at different echo times (TEs). T2 measurements were first validated in vitro in calibrated T2 phantoms (range: 25-152 ms) by comparing sSE-EPI, standard spin-echo (SE), and multislice multiecho (MSME) techniques (using a fitting procedure or a 2-TEs calculation). In vivo measurements of resting T2 quadriceps femoris (QF) muscle were performed with both sSE-EPI and MSME sequences. Finally, sSE-EPI was used to quantify T2 changes in recovering muscle after an exercise. RESULTS: T2 values measured in vitro with sSE-EPI were similar to those assessed with SE (P > 0.05). In vitro and in vivo T2 measurements obtained with sSE-EPI were independent of the T2 determination procedure (P > 0.05). In contrast, both in vitro and in vivo T2 values derived from MSME were significantly different when using 2-TEs calculation as compared to the fitting procedure (P < 0.05). sSE-EPI allowed the detection of increased T2 values in the QF muscle immediately after exercise (+14 ± 9%), while lower T2 values were recorded less than 2 min afterwards (P < 0.05). CONCLUSION: sSE-EPI sequence is a relevant method to monitor exercise-induced T2 changes of skeletal muscles over large volume coverage and to detect abnormal patterns of muscle activation. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:356-368.
    Mots-clés : crmbm, Exercise, MRI, msk, skeletal muscle, spin-echo sequence, T2.

  • Girard, OM, Callot, V, Prevost, VH, Robert, B, Taso, M, Ribeiro, G, Varma, G, Rangwala, N, Alsop, DC & Duhamel, G 2017, “Magnetization transfer from inhomogeneously broadened lines (ihMT): Improved imaging strategy for spinal cord applications”, Magnetic Resonance in Medicine, vol. 77, p. 581-591, viewed 10March,2016, .
    Résumé : Purpose Inhomogeneous magnetization transfer (ihMT) shows great promise for specific imaging of myelinated tissues. Whereas the ihMT technique has been previously applied in brain applications, the current report presents a strategy for cervical spinal cord (SC) imaging free of cerebrospinal fluid (CSF) pulsatility artifacts. Methods A pulsed ihMT preparation was combined with a single-shot HASTE readout. Electrocardiogram (ECG) synchronization was used to acquire all images during the quiescent phase of SC motion. However ihMT signal quantification errors may occur when a variable recovery delay is introduced in the sequence as a consequence of variable cardiac cycle. A semiautomatic retrospective correction algorithm, based on repetition time (TR) -matching, is proposed to correct for signal variations of long T1-components (e.g., CSF). Results The proposed strategy combining ECG synchronization and retrospective data pairing led to clean SC images free of CSF artifacts. Lower variability of the ihMT metrics were obtained with the correction algorithm, and allowed for shorter TR to be used, hence improving signal-to-noise ratio efficiency. Conclusion The proposed methodology enabled faster acquisitions, while offering robust ihMT quantification and exquisite SC image quality. This opens great perspectives for widening the in vivo characterization of SC physiopathology using MRI, such as studying white matter tracts microstructure or impairment in degenerative pathologies. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.
    Mots-clés : crmbm, CSF pulsatility, ECG synchronization, ihMT, inhomogeneous magnetization transfer, motion correction, myelin, snc, Spinal cord, White Matter.

  • 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.

  • Jubeau, M & Gondin, J 2017, “Methodological considerations for investigating the influence of neuromuscular electrical stimulation on pH heterogeneity”, Magnetic Resonance in Medicine, vol. 77, no. 2, p. 465.

  • Kerbrat, A, Combès, B, Commowick, O, Maarouf, A, Bannier, E, Ferré, JC, Tourbah, A, Ranjeva, J-P, Barillot, C & Edan, G 2017, “USPIO-positive MS lesions are associated with greater tissue damage than gadolinium-positive-only lesions during 3-year follow-up”, Multiple Sclerosis (Houndmills, Basingstoke, England), p. 1352458517736148.
    Résumé : BACKGROUND: Identifying in vivo the processes that determine lesion severity in multiple sclerosis (MS) remains a challenge. OBJECTIVES: To describe the dynamics of ultrasmall superparamagnetic iron oxide (USPIO) enhancement in MS lesions and the relationship between USPIO enhancement and microstructural changes over 3 years. METHODS: Lesion development was assessed at baseline, Months 3, 6, and 9, using magnetic resonance imaging (MRI) with gadolinium and USPIO. Microstructural changes were assessed at baseline, Months 3, 6, 9, 12, 18, 24, and 36, using relaxometry, magnetization transfer, and diffusion-weighted imaging. RESULTS: We included 15 patients with clinically isolated syndrome. In the 52 MRI scans acquired with USPIO, 22 lesions were USPIO and gadolinium positive, and 44 were USPIO negative but gadolinium positive. Lesions no longer exhibited sustained USPIO enhancement 3 months later. At baseline, lesions that were both USPIO and gadolinium positive had lower magnetization transfer ratio values (common language effect size = 0.84, p = 0.0005) and lower fractional anisotropy values (0.83, p = 0.001) than gadolinium-positive-only lesions. USPIO-positive lesions remained associated with greater damage than gadolinium-positive-only lesions throughout the 3-year follow-up. CONCLUSION: USPIO enhancement, mainly reflecting monocyte infiltration, is transient and is associated with persistent tissue damage after 3 years.
    Mots-clés : clinically isolated syndrome, crmbm, diffusion tensor imaging, Gadolinium, Magnetic Resonance Imaging, magnetization transfer imaging, Multiple sclerosis, snc, USPIO.

  • Laroche, M, Almeras, L, Pecchi, E, Bechah, Y, Raoult, D, Viola, A & Parola, P 2017, “MALDI-TOF MS as an innovative tool for detection of Plasmodium parasites in Anopheles mosquitoes”, Malaria Journal, vol. 16, no. 1, p. 5.
    Résumé : BACKGROUND: Malaria is still a major public health issue worldwide, and one of the best approaches to fight the disease remains vector control. The current methods for mosquito identification include morphological methods that are generally time-consuming and require expertise, and molecular methods that require laboratory facilities with relatively expensive running costs. Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) technology, routinely used for bacterial identification, has recently emerged in the field of entomology. The aim of the present study was to assess whether MALDI-TOF MS could successfully distinguish Anopheles stephensi mosquitoes according to their Plasmodium infection status. METHODS: C57BL/6 mice experimentally infected with Plasmodium berghei were exposed to An. stephensi bites. For the determination of An. stephensi infection status, mosquito cephalothoraxes were dissected and submitted to mass spectrometry analyses and DNA amplification for molecular analysis. Spectra were grouped according to mosquitoes' infection status and spectra quality was validated based on intensity and reproducibility within each group. The in-lab MALDI-TOF MS arthropod reference spectra database, upgraded with representative spectra from both groups (infected/non-infected), was subsequently queried blindly with cephalothorax spectra from specimens of both groups. RESULTS: The MALDI TOF MS profiles generated from protein extracts prepared from the cephalothorax of An. stephensi allowed distinction between infected and uninfected mosquitoes. Correct classification was obtained in blind test analysis for (79/80) 98.75% of all mosquitoes tested. Only one of 80 specimens, an infected mosquito, was misclassified in the blind test analysis. CONCLUSIONS: Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry appears to be a promising, rapid and reliable tool for the epidemiological surveillance of Anopheles vectors, including their identification and their infection status.
    Mots-clés : crmbm, sasnc.

  • Leporq, B, Troter, AL, Fur, YL, Salort-Campana, E, Guye, M, Beuf, O, Attarian, S & Bendahan, D 2017, “Combined quantification of fatty infiltration, T1-relaxation times and T2*-relaxation times in normal-appearing skeletal muscle of controls and dystrophic patients”, Magnetic Resonance Materials in Physics, Biology and Medicine, vol. 30, no. 4, p. 407-415, viewed 18August,2017, .
    Résumé : ObjectivesTo evaluate the combination of a fat–water separation method with an automated segmentation algorithm to quantify the intermuscular fatty-infiltrated fraction, the relaxation times, and the microscopic fatty infiltration in the normal-appearing muscle.Materials and methodsMR acquisitions were performed at 1.5T in seven patients with facio-scapulo-humeral dystrophy and eight controls. Disease severity was assessed using commonly used scales for the upper and lower limbs. The fat–water separation method provided proton density fat fraction (PDFF) and relaxation times maps (T2* and T1). The segmentation algorithm distinguished adipose tissue and normal-appearing muscle from the T2* map and combined active contours, a clustering analysis, and a morphological closing process to calculate the index of fatty infiltration (IFI) in the muscle compartment defined as the relative amount of pixels with the ratio between the number of pixels within IMAT and the total number of pixels (IMAT + normal appearing muscle).ResultsIn patients, relaxation times were longer and a larger fatty infiltration has been quantified in the normal-appearing muscle. T2* and PDFF distributions were broader. The relaxation times were correlated to the Vignos scale whereas the microscopic fatty infiltration was linked to the Medwin-Gardner-Walton scale. The IFI was linked to a composite clinical severity scale gathering the whole set of scales.ConclusionThe MRI indices quantified within the normal-appearing muscle could be considered as potential biomarkers of dystrophies and quantitatively illustrate tissue alterations such as inflammation and fatty infiltration.
    Mots-clés : crmbm, Magnetic Resonance Imaging, msk, Muscle dystrophies, Segmentation.

  • 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.

  • Maarouf, A, Audoin, B, Pariollaud, F, Gherib, S, Rico, A, Soulier, E, Confort-Gouny, S, Guye, M, Schad, L, Pelletier, J, Ranjeva, J-P & Zaaraoui, W 2017, “Increased total sodium concentration in gray matter better explains cognition than atrophy in MS”, Neurology, vol. 88, no. 3, p. 289-295, viewed 18August,2017, .
    Résumé : Objective: To investigate whether brain total sodium accumulation assessed by 23Na MRI is associated with cognitive deficit in relapsing-remitting multiple sclerosis (RRMS). Methods: Eighty-nine participants were enrolled in the study (58 patients with RRMS with a disease duration ≤10 years and 31 matched healthy controls). Patients were classified as cognitively impaired if they failed at least 2 tasks on the Brief Repeatable Battery. MRI was performed at 3T using 23Na MRI to obtain total sodium concentration (TSC) in the different brain compartments (lesions, normal-appearing white matter [NAWM], gray matter [GM]) and 1H- magnetization-prepared rapid gradient echo to assess GM atrophy (GM fraction). Results: The mean disease duration was 3.1 years and the median Expanded Disability Status Scale score was 1 (range 0–4.5). Thirty-seven patients were classified as cognitively preserved and 21 as cognitively impaired. TSC was increased in GM and NAWM in cognitively impaired patients compared to cognitively preserved patients and healthy controls. Voxel-wise analysis demonstrated that sodium accumulation was mainly located in the neocortex in cognitively impaired patients. Regression analysis evidenced than the 2 best independent predictors of cognitive impairment were GM TSC and age. Receiver operating characteristic analyses demonstrated that sensitivity and specificity of the GM TSC to classify patients according to their cognitive status were 76% and 71%, respectively. Conclusions: This study provides 2 main findings. (1) In RRMS, total sodium accumulation in the GM is better associated with cognitive impairment than GM atrophy; and (2) total sodium accumulation in patients with cognitive impairment is mainly located in the neocortex.
    Mots-clés : crmbm, snc.

  • Ogier, A, Sdika, M, Foure, A, Le Troter, A & Bendahan, D 2017, “Individual muscle segmentation in MR images: A 3D propagation through 2D non-linear registration approaches”, Conference proceedings: .. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, vol. 2017, p. 317-320.
    Résumé : Manual and automated segmentation of individual muscles in magnetic resonance images have been recognized as challenging given the high variability of shapes between muscles and subjects and the discontinuity or lack of visible boundaries between muscles. In the present study, we proposed an original algorithm allowing a semi-automatic transversal propagation of manually-drawn masks. Our strategy was based on several ascending and descending non-linear registration approaches which is similar to the estimation of a Lagrangian trajectory applied to manual masks. Using several manually-segmented slices, we have evaluated our algorithm on the four muscles of the quadriceps femoris group. We mainly showed that our 3D propagated segmentation was very accurate with an averaged Dice similarity coefficient value higher than 0.91 for the minimal manual input of only two manually-segmented slices.
    Mots-clés : crmbm, msk.

  • Prevost, VH, Girard, OM, Mchinda, S, Varma, G, Alsop, DC & Duhamel, G 2017, “Optimization of inhomogeneous magnetization transfer (ihMT) MRI contrast for preclinical studies using dipolar relaxation time (T1D) filtering”, NMR in Biomedicine, vol. 30, no. 6, viewed 18August,2017, .

  • Rasoanandrianina, H, Grapperon, A-M, Taso, M, Girard, OM, Duhamel, G, Guye, M, Ranjeva, J-P, Attarian, S, Verschueren, A & Callot, V 2017, “Region-specific impairment of the cervical spinal cord (SC) in amyotrophic lateral sclerosis: A preliminary study using SC templates and quantitative MRI (diffusion tensor imaging/inhomogeneous magnetization transfer)”, NMR in biomedicine, vol. 30, no. 12.
    Résumé : In this preliminary study, our objective was to investigate the potential of high-resolution anatomical imaging, diffusion tensor imaging (DTI) and conventional/inhomogeneous magnetization transfer imaging [magnetization transfer (MT)/inhomogeneous magnetization transfer (ihMT)] at 3 T, analyzed with template-extracted regions of interest, to measure the atrophy and structural changes of white (WM) and gray (GM) matter spinal cord (SC) occurring in patients with amyotrophic lateral sclerosis (ALS). Ten patients with ALS and 20 age-matched healthy controls were recruited. SC GM and WM areas were automatically segmented using dedicated templates. Atrophy indices were evaluated from T2 *-weighted images at each vertebral level from cervical C1 to C6. DTI and ihMT metrics were quantified within the corticospinal tract (CST), posterior sensory tract (PST) and anterior GM (aGM) horns at the C2 and C5 levels. Clinical disabilities of patients with ALS were evaluated using the Revised ALS Functional Rating Scale, upper motor neuron (UMN) and Medical Research Council scorings, and correlated with MR metrics. Compared with healthy controls, GM and WM atrophy was observed in patients with ALS, especially at lower cervical levels, where a strong correlation was also observed between GM atrophy and the UMN score (R = -0.75, p = 0.05 at C6). Interestingly, a significant decrease in ihMT ratio was found in all regions of interest (p < 0.0008), fractional anisotropy (FA) and MT ratios decreased significantly in CST, especially at C5 (p < 0.005), and λ// (axial diffusivity) decreased significantly in CST (p = 0.0004) and PST (p = 0.003) at C2. Strong correlations between MRI metrics and clinical scores were also found (0.47 < |R| < 0.87, p < 0.05). Altogether, these preliminary results suggest that high-resolution anatomical imaging and ihMT imaging, in addition to DTI, are valuable for the characterization of SC tissue impairment in ALS. In this study, in addition to an important SC WM demyelination, we also observed, for the first time in ALS, impairments of cervical aGM.
    Mots-clés : ALS, crmbm, diffusion tensor imaging, GM atrophy, inhomogeneous magnetization transfer, motor neuron, Spinal cord, spinal cord templates.

  • Ridley, B, Marchi, A, Wirsich, J, Soulier, E, Confort-Gouny, S, Schad, L, Bartolomei, F, Ranjeva, J-P, Guye, M & Zaaraoui, W 2017, “Brain sodium MRI in human epilepsy: Disturbances of ionic homeostasis reflect the organization of pathological regions”, NeuroImage, vol. 157, p. 173-183.
    Résumé : In light of technical advancements supporting exploration of MR signals other than (1)H, sodium ((23)Na) has received attention as a marker of ionic homeostasis and cell viability. Here, we evaluate for the first time the possibility that (23)Na-MRI is sensitive to pathological processes occurring in human epilepsy. A normative sample of 27 controls was used to normalize regions of interest (ROIs) from 1424 unique brain locales on quantitative (23)Na-MRI and high-resolution (1)H-MPRAGE images. ROIs were based on intracerebral electrodes in ten patients undergoing epileptic network mapping. The stereo-EEG gold standard was used to define regions as belonging to primarily epileptogenic, secondarily irritative and to non-involved regions. Estimates of total sodium concentration (TSC) on (23)Na-MRI and cerebrospinal fluid (CSF) on (1)H imaging were extracted for each patient ROI, and normalized against the same region in controls. ROIs with disproportionate CSF contributions (ZCSF≥1.96) were excluded. TSC levels were found to be elevated in patients relative to controls except in one patient, who suffered non-convulsive seizures during the scan, in whom we found reduced TSC levels. In the remaining patients, an ANOVA (F1100= 12.37, p<0.0001) revealed a highly significant effect of clinically-defined zones (F1100= 11.13, p<0.0001), with higher normalized TSC in the epileptogenic zone relative to both secondarily irritative (F1100= 11, p=0.0009) and non-involved regions (F1100= 17.8, p<0.0001). We provide the first non-invasive, in vivo evidence of a chronic TSC elevation alongside ZCSF levels within the normative range, associated with the epileptogenic region even during the interictal period in human epilepsy, and the possibility of reduced TSC levels due to seizure. In line with modified homeostatic mechanisms in epilepsy - including altered mechanisms underlying ionic gating, clearance and exchange - we provide the first indication of (23)Na-MRI as an assay of altered sodium concentrations occurring in epilepsy associated with the organization of clinically relevant divisions of pathological cortex.
    Mots-clés : Cortical localisation, crmbm, Epilepsy, Epilepsy surgery, Intracranial EEG, Ionic imaging, snc, Sodium MRI.

  • Wegrzyk, J, Ranjeva, J-P, Fouré, A, Kavounoudias, A, Vilmen, C, Mattei, J-P, Guye, M, Maffiuletti, NA, Place, N, Bendahan, D & Gondin, J 2017, “Specific brain activation patterns associated with two neuromuscular electrical stimulation protocols”, Scientific Reports, vol. 7, no. 1, p. 2742.
    Résumé : The influence of neuromuscular electrical stimulation (NMES) parameters on brain activation has been scarcely investigated. We aimed at comparing two frequently used NMES protocols - designed to vary in the extent of sensory input. Whole-brain functional magnetic resonance imaging was performed in sixteen healthy subjects during wide-pulse high-frequency (WPHF, 100 Hz-1 ms) and conventional (CONV, 25 Hz-0.05 ms) NMES applied over the triceps surae. Each protocol included 20 isometric contractions performed at 10% of maximal force. Voluntary plantar flexions (VOL) were performed as control trial. Mean force was not different among the three protocols, however, total current charge was higher for WPHF than for CONV. All protocols elicited significant activations of the sensorimotor network, cerebellum and thalamus. WPHF resulted in lower deactivation in the secondary somatosensory cortex and precuneus. Bilateral thalami and caudate nuclei were hyperactivated for CONV. The modulation of the NMES parameters resulted in differently activated/deactivated regions related to total current charge of the stimulation but not to mean force. By targeting different cerebral brain regions, the two NMES protocols might allow for individually-designed rehabilitation training in patients who can no longer execute voluntary movements.
    Mots-clés : crmbm, msk.

  • Wirsich, J, Ridley, B, Besson, P, Jirsa, V, Bénar, C, Ranjeva, J-P & Guye, M 2017, “Complementary contributions of concurrent EEG and fMRI connectivity for predicting structural connectivity”, NeuroImage, vol. 161, p. 251-260.
    Résumé : While averaged dynamics of brain function are known to estimate the underlying structure, the exact relationship between large-scale function and structure remains an unsolved issue in network neuroscience. These complex functional dynamics, measured by EEG and fMRI, are thought to arise from a shared underlying structural architecture, which can be measured by diffusion MRI (dMRI). While simulation and data transformation (e.g. graph theory measures) have been proposed to refine the understanding of the underlying function-structure relationship, the potential complementary and/or independent contribution of EEG and fMRI to this relationship is still poorly understood. As such, we explored this relationship by analyzing the function-structure correlation in fourteen healthy subjects with simultaneous resting-state EEG-fMRI and dMRI acquisitions. We show that the combination of EEG and fMRI connectivity better explains dMRI connectivity and that this represents a genuine model improvement over fMRI-only models for both group-averaged connectivity matrices and at the individual level. Furthermore, this model improves the prediction within each resting-state network. The best model fit to underlying structure is mediated by fMRI and EEG-δ connectivity in combination with Euclidean distance and interhemispheric connectivity with more local contributions of EEG-γ at the scale of resting-state networks. This highlights that the factors mediating the relationship between functional and structural metrics of connectivity are context and scale dependent, influenced by topological, geometric and architectural features. It also suggests that fMRI studies employing simultaneous EEG measures may characterize additional and essential parts of the underlying neuronal activity of the resting-state, which might be of special interest for both clinical studies and the investigation of resting-state dynamics.
    Mots-clés : Brain connectivity, Connectome, crmbm, Multimodal, Network theory, snc.

  • Wybrecht, D, Reuter, F, Pariollaud, F, Zaaraoui, W, Le Troter, A, Rico, A, Confort-Gouny, S, Soulier, E, Guye, M, Maarouf, A, Ranjeva, J-P, Pelletier, J & Audoin, B 2017, “New brain lesions with no impact on physical disability can impact cognition in early multiple sclerosis: A ten-year longitudinal study”, PloS One, vol. 12, no. 11, p. e0184650.
    Résumé : OBJECTIVE: In early multiple sclerosis, although brain T2 lesions accrual are hallmark of the disease, only weak correlations were found between T2 lesions accrual and EDSS progression, the disability scale commonly used in multiple sclerosis studies. This may be related to the very poor sensitivity of EDSS to cognitive dysfunctions that may occur and progress from the first stage of the disease. In the present study, we aimed to demonstrate that cognitive deficits progress during the first ten years of MS and are significantly impacted by new T2 lesions. METHODS: EDSS and extensive neuropsychological battery (22 measures) exploring memory, attention/speed of information processing and executive functions were assessed at baseline, Year 1 and Year 10 in 26 patients enrolled after their first clinical attack. To limit the bias of test-retest effect, only measures obtained at Year 1 and Year 10 were reported in the analysis. Raw scores of patients were transformed into z-scores using published normative data when available or scores of matched controls. Lesion probability mapping was used to assess the potential relationships between T2 lesions accumulation, cognitive decline and EDSS progression (P<0.05, FWE-corrected). RESULTS: At Year 1, 27% of patients showed attention/speed of information processing deficits, 11.5% executive dysfunction and 11.5% memory impairment. During the follow-up, frequency and severity of executive dysfunction increased (from 11.5% of patients at Year 1 to 42% at Year 10, p<0.01) while no significant changes were evidenced for the other cognitive domains. Median EDSS increased from 0.5 [range: 0-3] at Year 1 to 2.5 [range: 0-6.5] at Year 10 (p<0.001). During the ten-year follow-up, lesions accumulation in the left cerebellum and semi-ovale centers was associated with EDSS progression. In contrast, most lesions accumulation in the frontal, parietal and temporal lobes were associated with cognitive decline but had no effect on EDSS progression. CONCLUSION: The present study provides strong evidence that clinically silent T2 lesions impact cognition in early MS. In daily practice, early prevention of T2 lesions accrual may be useful to limit cognitive decline.
    Mots-clés : crmbm, snc.


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.

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