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Journal Article

  • 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.

  • Benzaquen, M, Flachaire, B, Rouby, F, Berbis, P & Guis, S 2018, “Paradoxical pustular psoriasis induced by ustekinumab in a patient with Crohn's disease-associated spondyloarthropathy”, Rheumatology International.
    Résumé : Palmoplantar pustular psoriasis (PPP) is a clinical form of psoriasis, for which tumor necrosis factor alpha inhibitors (TNFi) or interleukins 12/23 inhibitor (ustekinumab) can be a therapeutic option. Paradoxical psoriatic reactions induced by TNFi are now well known. We present the exceptional case of a paradoxical PPP appeared under ustekinumab in a patient with Crohn's disease-associated spondyloarthropathy. A 58-year-old woman presented with recent peripheral inflammatory arthralgias appeared in the context of a Crohn's disease diagnosed in 2008. Three weeks after the first injection of ustekinumab 390 mg for a refractory Crohn's disease, a slight pruritic erythematous and pustular dermatosis appeared on the right hand palm. The clinical aspect was strongly in favor of a PPP. Ustekinumab was discontinued and replaced by golimumab, leading to a complete healing of PPP after 15 days of discontinuation. Causality assessment calculated using the French method was plausible for ustekinumab in the induction of PPP. It was based on a compatible chronology according to time to onset associated with complete recovery 2 weeks after cessation of treatment, and on the negative assessment of an alternative etiology (nor bacterial or viral infection, nor other treatment taken by the patient, nor previous history of psoriasis). The worsening of underlying psoriasis under ustekinumab through the appearance of generalized or palmoplantar pustules has already been reported in five cases. We describe to our knowledge the first case of paradoxical PPP under ustekinumab in a patient with no known underlying psoriasis.
    Mots-clés : Crohn’s disease, msk, Paradoxical, Pustular psoriasis, Spondyloarthropathy, Ustekinumab.

  • 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.

  • 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.

  • Durozard, P, Maarouf, A, Boutiere, C, Ruet, A, Brochet, B, Vukusic, S, Carra-Dalliere, C, Labauge, P, Mathey, G, Debouverie, M, Papeix, C, Maillart, E, Lubetzki, C, Bensa, C, Gout, O, Giannesini, C, Stankoff, B, Ciron, J, Brassat, D, Pelletier, J, Rico Lamy, A, Audoin, B & SFSEP and OFSEP groups, 2018, “Efficacy of rituximab in refractory RRMS”, Multiple Sclerosis (Houndmills, Basingstoke, England), p. 1352458518772748.
    Résumé : OBJECTIVE: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT). METHODS: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts. RESULTS: A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5-6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab ( p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4-18.4) months after rituximab ( p < 0.0001). CONCLUSION: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.
    Mots-clés : disease-modifying therapies, Multiple sclerosis, relapsing/remitting, second-line treatment, snc, treatment response.

  • 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.

  • Hart, CR, Layec, G, Trinity, JD, Le Fur, Y, Gifford, JR, Clifton, HL & Richardson, RS 2018, “Oxygen availability and skeletal muscle oxidative capacity in patients with peripheral arterial disease: Implications from in vivo and in vitro assessments”, American Journal of Physiology. Heart and Circulatory Physiology.
    Résumé : Evidence suggests that peak skeletal muscle mitochondrial ATP synthesis rate (Vmax) in patients with peripheral arterial disease (PAD) may be attenuated due to disease-related impairments in oxygen (O2) supply. However, in vitro assessments suggest intrinsic deficits in mitochondrial respiration despite ample O2 availability. To address this conundrum, Doppler ultrasound, near infrared spectroscopy (NIRS), phosphorus magnetic resonance spectroscopy (31P-MRS), and high-resolution respirometry were combined to assess convective O2 delivery, tissue oxygenation, Vmax, and skeletal muscle mitochondrial capacity (Complex I+II, State 3 respiration), respectively, in the gastrocnemius muscle of 10 patients with early-stage PAD and 11 physical activity-matched healthy controls (HC). All subjects were studied in free-flow control conditions (FF) and with reactive hyperemia (RH), induced by a period of brief ischemia during the last 30s of submaximal plantar flexion exercise. The patients with PAD repeated the FF and RH trials under hyperoxic conditions (FF+100%O2 and RH+100%O2). Compared to the HC, the patients with PAD exhibited attenuated O2 delivery at the same absolute work rate, and attenuated tissue re-oxygenation and Vmax after relative intensity-matched exercise. Compared to the FF condition, only RH+100%O2 significantly increased convective O2 delivery (~44%), tissue re-oxygenation (~54%), and Vmax (~60%) in PAD (p&lt;0.05) such that Vmax was now not different from the HC. Furthermore, there was no evidence of an intrinsic mitochondrial deficit in PAD, assessed in vitro with adequate O2. Thus, in combination, this comprehensive in vivo and in vitro investigation implicates O2 supply as the predominant factor limiting mitochondrial oxidative capacity in early-stage PAD.
    Mots-clés : Blood Flow, Exercise, Metabolism, Mitochondria, msk, Peripheral Vascular Disease.

  • Lefèvre, J, Pepe, A, Muscato, J, De Guio, F, Girard, N, Auzias, G & Germanaud, D 2018, “SPANOL (SPectral ANalysis of Lobes): A Spectral Clustering Framework for Individual and Group Parcellation of Cortical Surfaces in Lobes”, Frontiers in Neuroscience, vol. 12, p. 354.
    Résumé : Understanding the link between structure, function and development in the brain is a key topic in neuroimaging that benefits from the tremendous progress of multi-modal MRI and its computational analysis. It implies, inter alia, to be able to parcellate the brain volume or cortical surface into biologically relevant regions. These parcellations may be inferred from existing atlases (e.g., Desikan) or sets of rules, as would do a neuroanatomist for lobes, but also directly driven from the data (e.g., functional or structural connectivity) with minimum a priori. In the present work, we aimed at using the intrinsic geometric information contained in the eigenfunctions of Laplace-Beltrami Operator to obtain parcellations of the cortical surface based only on its description by triangular meshes. We proposed a framework adapted from spectral clustering, which is general in scope and suitable for the co-parcellation of a group of subjects. We applied it to a dataset of 62 adults, optimized it and revealed a striking agreement between parcels produced by this unsupervised clustering and Freesurfer lobes (Desikan atlas), which cannot be explained by chance. Constituting the first reported attempt of spectral-based fully unsupervised segmentation of neuroanatomical regions such as lobes, spectral analysis of lobes (Spanol) could conveniently be fitted into a multimodal pipeline to ease, optimize or speed-up lobar or sub-lobar segmentation. In addition, we showed promising results of Spanol on smoother brains and notably on a dataset of 15 fetuses, with an interest for both the understanding of cortical ontogeny and the applicative field of perinatal computational neuroanatomy.
    Mots-clés : cortical parcellation, fetal MRI, group-wise analysis, Laplace-Beltrami operator, snc, spectral clustering.

  • 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.

  • 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.

  • Proix, T, Jirsa, VK, Bartolomei, F, Guye, M & Truccolo, W 2018, “Predicting the spatiotemporal diversity of seizure propagation and termination in human focal epilepsy”, Nature Communications, vol. 9, no. 1, p. 1088.
    Résumé : Recent studies have shown that seizures can spread and terminate across brain areas via a rich diversity of spatiotemporal patterns. In particular, while the location of the seizure onset area is usually invariant across seizures in an individual patient, the source of traveling (2-3 Hz) spike-and-wave discharges during seizures can either move with the slower propagating ictal wavefront or remain stationary at the seizure onset area. Furthermore, although many focal seizures terminate synchronously across brain areas, some evolve into distinct ictal clusters and terminate asynchronously. Here, we introduce a unifying perspective based on a new neural field model of epileptic seizure dynamics. Two main mechanisms, the co-existence of wave propagation in excitable media and coupled-oscillator dynamics, together with the interaction of multiple time scales, account for the reported diversity. We confirm our predictions in seizures and tractography data obtained from patients with pharmacologically resistant epilepsy. Our results contribute toward patient-specific seizure modeling.
    Mots-clés : 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.

  • Salaun, E, Clavel, M-A, Rodés-Cabau, J & Pibarot, P 2018, “Bioprosthetic aortic valve durability in the era of transcatheter aortic valve implantation”, Heart (British Cardiac Society).
    Résumé : The main limitation of bioprosthetic valves is their limited durability, which exposes the patient to the risk of aortic valve reintervention. Transcatheter aortic valve implantation (TAVI) is considered a reasonable alternative to surgical aortic valve replacement (SAVR) in patients with intermediate or high surgical risk. TAVI is now rapidly expanding towards the lower risk populations. Although the results of midterm durability of the transcatheter bioprostheses are encouraging, their long-term durability remains largely unknown. The objective of this review article is to present the definition, mechanisms, incidence, outcome and management of structural valve deterioration of aortic bioprostheses with specific emphasis on TAVI. The structural valve deterioration can be categorised into three stages: stage 1: morphological abnormalities (fibrocalcific remodelling and tear) of bioprosthesis valve leaflets without hemodynamic valve deterioration; stage 2: morphological abnormalities and moderate hemodynamic deterioration (increase in gradient and/or new onset of transvalvular regurgitation); and stage 3: morphological abnormalities and severe hemodynamic deterioration. Several specifics inherent to the TAVI including valve oversizing, manipulation, delivery, positioning and deployment may cause injuries to the valve leaflets and increase leaflet mechanical stress, which may limit the long-term durability of transcatheter bioprostheses. The selection of the type of aortic valve replacement and bioprosthesis should thus take into account the ratio between the demonstrated durability of the bioprostheses versus the life expectancy of the patient. Pending the publication of robust data on long-term durability of transcatheter bioprostheses, it appears reasonable to select SAVR with a bioprosthesis model that has well-established long-term durability in patients with low surgical risk and long life expectancy.
    Mots-clés : aortic regurgitation, aortic stenosis, cardiac computer tomographic (CT) imaging, cvs, echocardiography, prosthetic heart valves.

  • Salaun, E, Sportouch, L, Barral, P-A, Hubert, S, Lavoute, C, Casalta, A-C, Pradier, J, Ouk, D, Casalta, J-P, Lambert, M, Gouriet, F, Gaubert, J-Y, Dehaene, A, Jacquier, A, Tessonnier, L, Haentjens, J, Theron, A, Riberi, A, Cammilleri, S, Grisoli, D, Jaussaud, N, Collart, F, Bonnet, J-L, Camoin, L, Renard, S, Cuisset, T, Avierinos, J-F, Lepidi, H, Mundler, O, Raoult, D & Habib, G 2018, “Diagnosis of Infective Endocarditis After TAVR: Value of a Multimodality Imaging Approach”, JACC. Cardiovascular imaging, vol. 11, no. 1, p. 143-146.
    Mots-clés : infective endocarditis, multi-imaging, PET/CT, TAVI, TAVR.

  • Tourbah, A, Gout, O, Vighetto, A, Deburghgraeve, V, Pelletier, J, Papeix, C, Lebrun-Frenay, C, Labauge, P, Brassat, D, Toosy, A, Laplaud, D-A, Outteryck, O, Moreau, T, Debouverie, M, Clavelou, P, Heinzlef, O, De Sèze, J, Defer, G, Sedel, F & Arndt, C 2018, “MD1003 (High-Dose Pharmaceutical-Grade Biotin) for the Treatment of Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study”, CNS drugs.
    Résumé : BACKGROUND: Chronic visual loss is a disabling feature in patients with multiple sclerosis (MS). It was recently shown that MD1003 (high-dose pharmaceutical-grade biotin or hdPB) may improve disability in patients with progressive MS. OBJECTIVE: The aim of this study was to evaluate whether MD1003 improves vision compared with placebo in MS patients with chronic visual loss. METHODS: The MS-ON was a 6-month, randomized, double-blind, placebo-controlled study with a 6-month open-label extension phase. Adult patients with MS-related chronic visual loss of at least one eye [visual acuity (VA) below 0.5 decimal chart] were randomized 2:1 to oral MD1003 300 mg/day or placebo. The selected eye had to show worsening of VA within the past 3 years following either acute optic neuritis (AON) or slowly progressive optic neuropathy (PON). The primary endpoint was the mean change from baseline to month 6 in VA measured in logarithm of the minimum angle of resolution (logMAR) at 100% contrast of the selected eye. Visually evoked potentials, visual field, retinal nerve fiber layer (RNFL) thickness, and health outcomes were also assessed. RESULTS: Ninety-three patients received MD1003 (n = 65) or placebo (n = 28). The study did not meet its primary endpoint, as the mean change in the primary endpoint was nonsignificantly larger (p = 0.66) with MD1003 (- 0.061 logMAR, + 3.1 letters) than with placebo (- 0.036 logMAR, + 1.8 letters). Pre-planned subgroup analyses showed that 100% contrast VA improved by a mean of + 2.8 letters (- 0.058 logMAR) with MD1003 and worsened by - 1.5 letters (+ 0.029 logMAR) with placebo (p = 0.45) in the subgroup of patients with PON. MD1003-treated patients also had nonsignificant improvement in logMAR at 5% contrast and in RNFL thickness and health outcome scores when compared with placebo-treated patients. There was no superiority of MD1003 vs placebo in patients with AON. The safety profile of MD1003 was similar to that of placebo. CONCLUSIONS: MD1003 did not significantly improve VA compared with placebo in patients with MS experiencing chronic visual loss. An interesting trend favoring MD1003 was observed in the subgroup of patients with PON. Treatment was overall well tolerated. TRIAL REGISTRATION: EudraCT identifier 2013-002112-27. Identifier: NCT02220244 FUNDING: MedDay Pharmaceuticals.
    Mots-clés : snc.

  • Tuleasca, C, Najdenovska, E, Régis, J, Witjas, T, Girard, N, Champoudry, J, Faouzi, M, Thiran, J-P, Bach Cuadra, M, Levivier, M & Van De Ville, D 2018, “Pretherapeutic functional neuroimaging predicts tremor arrest after thalamotomy”, Acta Neurologica Scandinavica.
    Résumé : OBJECTIVE: Essential tremor (ET) represents the most common movement disorder. Drug-resistant ET can benefit from standard stereotactic procedures (deep brain stimulation or radiofrequency thalamotomy) or alternatively minimally invasive high-focused ultrasound or radiosurgery. All aim at same target, thalamic ventro-intermediate nucleus (Vim). METHODS: The study included a cohort of 17 consecutive patients, with ET, treated only with left unilateral stereotactic radiosurgical thalamotomy (SRS-T) between September 2014 and August 2015. The mean time to tremor improvement was 3.32 months (SD 2.7, 0.5-10). Neuroimaging data were collected at baseline (n = 17). Standard tremor scores, including activities of daily living (ADL) and tremor score on treated hand (TSTH), were completed pretherapeutically and 1 year later. We further correlate these scores with baseline inter-connectivity in twenty major large-scale brain networks. RESULTS: We report as predictive three networks, with the interconnected statistically significant clusters: primary motor cortex interconnected with inferior olivary nucleus, bilateral thalamus interconnected with motor cerebellum lobule V2 (ADL), and anterior default-mode network interconnected with Brodmann area 103 (TSTH). For all, more positive pretherapeutic interconnectivity correlated with higher drop in points on the respective scores. Age, disease duration, or time-to-response after SRS-T were not statistically correlated with pretherapeutic brain connectivity measures (P > .05). The same applied to pretherapeutic tremor scores, after using the same methodology described above. CONCLUSIONS: Our findings have clinical implications for predicting clinical response after SRS-T. Here, using pretherapeutic magnetic resonance imaging and data processing without prior hypothesis, we show that pretherapeutic network(s) interconnectivity strength predicts tremor arrest in drug-naïve ET, following stereotactic radiosurgical thalamotomy.
    Mots-clés : fMRI, Resting state, snc, Thalamotomy.

  • Tuleasca, C, Najdenovska, E, Régis, J, Witjas, T, Girard, N, Champoudry, J, Faouzi, M, Thiran, J-P, Cuadra, MB, Levivier, M & Van De Ville, D 2018, “Clinical response to Vim's thalamic stereotactic radiosurgery for essential tremor is associated with distinctive functional connectivity patterns”, Acta Neurochirurgica, vol. 160, no. 3, p. 611-624.
    Résumé : INTRODUCTION: Essential tremor (ET) is the most common movement disorder. Drug-resistant ET can benefit from standard surgical stereotactic procedures (deep brain stimulation, thalamotomy) or minimally invasive high-intensity focused ultrasound (HIFU) or stereotactic radiosurgical thalamotomy (SRS-T). Resting-state fMRI (rs-fMRI) is a non-invasive imaging method acquired in absence of a task. We examined whether rs-fMRI correlates with tremor score on the treated hand (TSTH) improvement 1 year after SRS-T. METHODS: We included 17 consecutive patients treated with left unilateral SRS-T in Marseille, France. Tremor score evaluation and rs-fMRI were acquired at baseline and 1 year after SRS-T. Resting-state data (34 scans) were analyzed without a priori hypothesis, in Lausanne, Switzerland. Based on degree of improvement in TSTH, to consider SRS-T at least as effective as medication, we separated two groups: 1, ≤ 50% (n = 6, 35.3%); 2, > 50% (n = 11, 64.7%). They did not differ statistically by age (p = 0.86), duration of symptoms (p = 0.41), or lesion volume at 1 year (p = 0.06). RESULTS: We report TSTH improvement correlated with interconnectivity strength between salience network with the left claustrum and putamen, as well as between bilateral motor cortices, frontal eye fields and left cerebellum lobule VI with right visual association area (the former also with lesion volume). Longitudinal changes showed additional associations in interconnectivity strength between right dorsal attention network with ventro-lateral prefrontal cortex and a reminiscent salience network with fusiform gyrus. CONCLUSIONS: Brain connectivity measured by resting-state fMRI relates to clinical response after SRS-T. Relevant networks are visual, motor, and attention. Interconnectivity between visual and motor areas is a novel finding, revealing implication in movement sensory guidance.
    Mots-clés : fMRI, Independent component analysis, Radiosurgery, resting-state, snc, Thalamotomy, Ventro-intermediate nucleus.

  • Tuleasca, C, Najdenovska, E, Régis, J, Witjas, T, Girard, N, Champoudry, J, Faouzi, M, Thiran, J-P, Cuadra, MB, Levivier, M & Van De Ville, D 2018, “Ventro-lateral motor thalamus abnormal connectivity in essential tremor before and after thalamotomy: a resting-state fMRI study”, World Neurosurgery.
    Résumé : OBJECTIVE: To evaluate functional connectivity (FC) of the ventro-lateral thalamus, a common target for drug-resistant essential tremor (ET), resting-state data were analyzed before and 1 year after stereotactic radiosurgical thalamotomy (SRS-T), and compared against healthy controls (HC). METHODS: 17 consecutive patients and 10 HC were enrolled. Tremor network was investigated using ventro-lateral ventral (VLV) nucleus as region-of-interest (ROI), extracted using automated segmentation from pretherapeutic diffusion MRI. Temporal correlations of VLV at whole brain level were evaluated by comparing drug-naïve ET with HC, and longitudinally, 1 year after SRS-T. Thalamotomy volume was always located inside VLV, and did not correlate with any of FC measures (p>0.05). This suggested presence of longitudinal changes in VLV FC independently of thalamotomy volume. RESULTS: Pretherapeutic ET displayed altered VLV FC with left primary sensory-motor cortex, pedunculopontine nucleus, dorsal anterior cingulate, left visual association and left superior parietal areas. Pretherapeutic negative FC with primary somatosensory cortex and pedunculopontine nucleus correlated with poorer baseline tremor scores (Spearmann=0.04 and 0.01). Longitudinal study displayed changes within right dorsal attention (frontal eye-fields and posterior parietal) and salience (anterior insula) networks, as well as areas involved in hand movement planning or language production. CONCLUSION: Our results demonstrated that ET and HC differ in their VLV FC to primary somatosensory and supplementary motor, visual association, or brainstem areas (pedunculopontine nucleus). Longitudinal changes display reorganization of dorsal attention and salience networks after thalamotomy. Beside attentional gateway, they are also known for their major role in facilitating a rapid access to the motor system.
    Mots-clés : fMRI, motor thalamus, resting-state, snc, Thalamotomy, Ventro-intermediate nucleus.

  • Tuleasca, C, Najdenovska, E, Régis, J, Witjas, T, Girard, N, Champoudry, J, Faouzi, M, Thiran, J-P, Cuadra, MB, Levivier, M & Van De Ville, D 2018, “Pretherapeutic motor thalamus resting-state functional connectivity with visual areas predicts tremor arrest after thalamotomy for essential tremor: tracing the cerebello-thalamo-visuo-motor network”, World Neurosurgery.
    Résumé : BACKGROUND: Essential tremor (ET) is a common movement disorder. Resting state fMRI (rs-fMRI) is non-invasive neuroimaging method acquired in absence of task. OBJECTIVE: Our study aims at correlating pretherapeutic ventro-lateral thalamus functional connectivity (FC) with clinical result 1 year after stereotactic radiosurgical thalamotomy (SRS-T) for drug-resistant ET. Data from 12 healthy controls was included. METHODS: Resting-state was acquired for 17 consecutive (right handed) patients, before and after left unilateral SRS-T. Standard tremor scores were evaluated pretherapeutically and 1 year after SRS-T. Tremor network was investigated using region-of-interest (ROI), left ventro-lateral ventral (VLV) cluster, obtained from pretherapeutic diffusion MRI. Seed-based functional connectivity (FC) was obtained as correlations between the VLV's time courses and the one of every voxel. The seed-connectivity maps were obtained pretherapeutically and correlated across all patients with clinical outcome 1 year after SRS-T. One-year MR-signature volume was always located inside VLV and did not correlate with reported seed-FC measures (p>0.05). RESULTS: We report statistically significant correlations between pretherapeutic seed-FC with clinical outcome for: 1). right visual association area (Brodmann area, BA 19) predicting 1 year activities of daily living (ADL) drop (punc=0.02); 2). left fusiform gyrus (BA 37) predicting 1 year head tremor score improvement (punc=0.04); 3). posterior cingulate (left BA 23, puncor=0.009), lateral temporal cortex (right BA 21, punc=0.02) predicting time to tremor arrest . CONCLUSIONS: Our results suggest that pretherapeutic resting-state seed-FC of left VLV predicts tremor arrest after SRS-T for ET. Visual areas are identified as the main regions in this correlation.
    Mots-clés : essential tremor, fMRI, radiosurgery, resting-state, seed-based approach, snc, thalamotomy, ventro-intermediate nucleus.

  • Tuleasca, C, Régis, J, Najdenovska, E, Witjas, T, Girard, N, Champoudry, J, Faouzi, M, Thiran, J-P, Cuadra, MB, Levivier, M & Van De Ville, D 2018, “Pretherapeutic Functional Imaging Allows Prediction of Head Tremor Arrest After Thalamotomy for Essential Tremor: The Role of Altered Interconnectivity Between Thalamolimbic and Supplementary Motor Circuits”, World Neurosurgery.
    Résumé : OBJECTIVE: To correlate pretherapeutic resting-state functional magnetic resonance imaging (rs-fMRI) measures with pretherapeutic head tremor presence and/or further improvement 1 year after stereotactic radiosurgical thalamotomy (SRS-T) for essential tremor (ET). METHODS: We prospectively collected head tremor scores (range, 0-3) and rs-fMRI data for a cohort of 17 consecutive ET patients in pretherapeutic and 1 year after SRS-T states. We additionally acquired rs-fMRI data for a healthy control (HC) group (n = 12). Group-level independent component analysis (n = 17 for pretherapeutic rs-fMRI) was applied to decompose neuroimaging data into 20 large-scale brain networks using a standard approach. Through spatial regression, we projected 1 year after SRS-T and HC rs-fMRI time points, on the same 20 brain networks. RESULTS: Pretherapeutic interconnectivity (IC) strength between the network including bilateral thalamus and limbic system with left supplementary motor area predicted head tremor improvement at 1 year after SRS-T (family-wise corrected P < 0.001, cluster size Kc = 146). For the statistically significant cluster, IC strength was strongest in HCs (mean, 4.6; median, 3.8) compared with pre- (mean, 0.1; median, 0.2) or posttherapeutic (mean, -0.2; median, 0.09) states. CONCLUSIONS: Baseline measures of IC between bilateral thalamus and limbic system with left supplementary motor area may predict head tremor arrest after thalamotomy. However, procedures such as SRS-T, for this particular clinical feature, do not align patients to HCs in terms of functional brain connectivity. We postulate that supplementary motor area is modulating head tremor appearance, by abnormal connectivity with the thalamolimbic system.
    Mots-clés : fMRI, Head tremor, Resting state, snc, Thalamotomy, Ventrointermediate nucleus.

  • Tuleasca, C, Régis, J, Najdenovska, E, Witjas, T, Girard, N, Thiran, J-P, Bach Cuadra, M, Levivier, M & Van De Ville, D 2018, “Visually-sensitive networks in essential tremor: evidence from structural and functional imaging”, Brain: A Journal of Neurology.

  • Tuleasca, C, Witjas, T, Van de Ville, D, Najdenovska, E, Verger, A, Girard, N, Champoudry, J, Thiran, J-P, Cuadra, MB, Levivier, M, Guedj, E & Régis, J 2018, “Right Brodmann area 18 predicts tremor arrest after Vim radiosurgery: a voxel-based morphometry study”, Acta Neurochirurgica, vol. 160, no. 3, p. 603-609.
    Résumé : INTRODUCTION: Drug-resistant essential tremor (ET) can benefit from open standard stereotactic procedures, such as deep-brain stimulation or radiofrequency thalamotomy. Non-surgical candidates can be offered either high-focused ultrasound (HIFU) or radiosurgery (RS). All procedures aim to target the same thalamic site, the ventro-intermediate nucleus (e.g., Vim). The mechanisms by which tremor stops after Vim RS or HIFU remain unknown. We used voxel-based morphometry (VBM) on pretherapeutic neuroimaging data and assessed which anatomical site would best correlate with tremor arrest 1 year after Vim RS. METHODS: Fifty-two patients (30 male, 22 female; mean age 71.6 years, range 49-82) with right-sided ET benefited from left unilateral Vim RS in Marseille, France. Targeting was performed in a uniform manner, using 130 Gy and a single 4-mm collimator. Neurological (pretherapeutic and 1 year after) and neuroimaging (baseline) assessments were completed. Tremor score on the treated hand (TSTH) at 1 year after Vim RS was included in a statistical parametric mapping analysis of variance (ANOVA) model as a continuous variable with pretherapeutic neuroimaging data. Pretherapeutic gray matter density (GMD) was further correlated with TSTH improvement. No a priori hypothesis was used in the statistical model. RESULTS: The only statistically significant region was right Brodmann area (BA) 18 (visual association area V2, p = 0.05, cluster size Kc = 71). Higher baseline GMD correlated with better TSTH improvement at 1 year after Vim RS (Spearman's rank correlation coefficient = 0.002). CONCLUSIONS: Routine baseline structural neuroimaging predicts TSTH improvement 1 year after Vim RS. The relevant anatomical area is the right visual association cortex (BA 18, V2). The question whether visual areas should be included in the targeting remains open.

  • 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.
    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.

  • Zhou, Z, Han, F, Yu, S, Yu, D, Rapacchi, S, Song, HK, Wang, DJJ, Hu, P & Yan, L 2018, “Accelerated noncontrast-enhanced 4-dimensional intracranial MR angiography using golden-angle stack-of-stars trajectory and compressed sensing with magnitude subtraction”, Magnetic Resonance in Medicine, vol. 79, no. 2, p. 867-878.
    Résumé : PURPOSE: To evaluate the feasibility and performance of compressed sensing (CS) with magnitude subtraction regularization in accelerating non-contrast-enhanced dynamic intracranial MR angiography (NCE-dMRA). METHODS: A CS algorithm was introduced in NCE-dMRA by exploiting the sparsity of the magnitude difference of the control and label images. The NCE-dMRA data were acquired using golden-angle stack-of-stars trajectory on six healthy volunteers and one patient with arteriovenous fistula. Images were reconstructed using (i) the proposed magnitude-subtraction CS (MS-CS); (ii) complex-subtraction CS; (iii) independent CS; and (iv) view-sharing with k-space weighted image contrast (KWIC). The dMRA image quality was compared across the four reconstruction strategies. The proposed MS-CS method was further compared with KWIC for temporal fidelity of depicting dynamic flow. RESULTS: The proposed MS-CS method was able to reconstruct NCE-dMRA images with detailed vascular structures and clean background. It provided better subjective image quality than the other two CS strategies (P < 0.05). Compared with KWIC, MS-CS showed similar image quality, but reduced temporal blurring in delineating the fine distal arteries. CONCLUSIONS: The MS-CS method is a promising CS technique for accelerating NCE-dMRA acquisition without compromising image quality and temporal fidelity. Magn Reson Med 79:867-878, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
    Mots-clés : arterial spin labeling, compressed sensing, KWIC, magnitude subtraction, noncontrast MR angiography, view sharing.


Journal Article

  • Achenbach, S, Paul, J-F, Laurent, F, Becker, H-C, Rengo, M, Caudron, J, Leschka, S, Vignaux, O, Knobloch, G, Benea, G, Schlosser, T, Andreu, J, Cabeza, B, Jacquier, A, Souto, M, Revel, D, Qanadli, SD, Cademartiri, F & X-ACT Study Group, 2017, “Erratum to: Comparative assessment of image quality for coronary CT angiography with iobitridol and two contrast agents with higher iodine concentrations: iopromide and iomeprol. A multicentre randomized double-blind trial”, European Radiology, vol. 27, no. 2, p. 831.

  • Albi, A, Pasternak, O, Minati, L, Marizzoni, M, Bartres-Faz, D, Bargallo, N, Bosch, B, Rossini, PM, Marra, C, Mueller, B, Fiedler, U, Wiltfang, J, Roccatagliata, L, Picco, A, Nobili, FM, Blin, O, Sein, J, Ranjeva, J-P, Didic, M, Bombois, S, Lopes, R, Bordet, R, Gros-Dagnac, H, Payoux, P, Zoccatelli, G, Alessandrini, F, Beltramello, A, Ferretti, A, Caulo, M, Aiello, M, Cavaliere, C, Soricelli, A, Parnetti, L, Tarducci, R, Floridi, P, Tsolaki, M, Constantinidis, M, Drevelegas, A, Frisoni, G & Jovicich, J 2017, “Free water elimination improves test-retest reproducibility of diffusion tensor imaging indices in the brain: A longitudinal multisite study of healthy elderly subjects”, Human Brain Mapping, vol. 38, no. 1, p. 12-26.
    Résumé : Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test-retest reproducibility. This study compares a bi-tensor model for FWE with DTI by extending a previous longitudinal-reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55-80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white-matter regions of the JHU-ICBM-DTI-81 white-matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12-26, 2017. (c) 2016 Wiley Periodicals, Inc.
    Mots-clés : alzheimers-disease, brain diffusion tensor imaging, cerebral white-matter, false discovery rate, free-water imaging, healthy elderly, longitudinal, MRI, multisite diffusion MRI, parkinsons-disease, reliability, Schizophrenia, snc, spatial statistics, substantia-nigra, test-retest reproducibility, tracking.

  • Allen, LA, Harper, RM, Kumar, R, Guye, M, Ogren, JA, Lhatoo, SD, Lemieux, L, Scott, CA, Vos, SB, Rani, S & Diehl, B 2017, “Dysfunctional Brain Networking among Autonomic Regulatory Structures in Temporal Lobe Epilepsy Patients at High Risk of Sudden Unexpected Death in Epilepsy”, Frontiers in Neurology, vol. 8, p. 544.
    Résumé : BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is common among young people with epilepsy. Individuals who are at high risk of SUDEP exhibit regional brain structural and functional connectivity (FC) alterations compared with low-risk patients. However, less is known about network-based FC differences among critical cortical and subcortical autonomic regulatory brain structures in temporal lobe epilepsy (TLE) patients at high risk of SUDEP. METHODS: 32 TLE patients were risk-stratified according to the following clinical criteria: age of epilepsy onset, duration of epilepsy, frequency of generalized tonic-clonic seizures, and presence of nocturnal seizures, resulting in 14 high-risk and 18 low-risk cases. Resting-state functional magnetic resonance imaging (rs-fMRI) signal time courses were extracted from 11 bilateral cortical and subcortical brain regions involved in autonomic and other regulatory processes. After computing all pairwise correlations, FC matrices were analyzed using the network-based statistic. FC strength among the 11 brain regions was compared between the high- and low-risk patients. Increases and decreases in FC were sought, using high-risk > low-risk and low-risk > high-risk contrasts (with covariates age, gender, lateralization of epilepsy, and presence of hippocampal sclerosis). RESULTS: High-risk TLE patients showed a subnetwork with significantly reduced FC (t = 2.5, p = 0.029) involving the thalamus, brain stem, anterior cingulate, putamen and amygdala, and a second subnetwork with significantly elevated FC (t = 2.1, p = 0.031), which extended to medial/orbital frontal cortex, insula, hippocampus, amygdala, subcallosal cortex, brain stem, thalamus, caudate, and putamen. CONCLUSION: TLE patients at high risk of SUDEP showed widespread FC differences between key autonomic regulatory brain regions compared to those at low risk. The altered FC revealed here may help to shed light on the functional correlates of autonomic disturbances in epilepsy and mechanisms involved in SUDEP. Furthermore, these findings represent possible objective biomarkers which could help to identify high-risk patients and enhance SUDEP risk stratification via the use of non-invasive neuroimaging, which would require validation in larger cohorts, with extension to patients with other epilepsies and subjects who succumb to SUDEP.
    Mots-clés : Functional connectivity, graph theory, hippocampus, insula, Resting state, snc.

  • Alory, A, Jacquier, A, Gentien, D, de la Grange, P & Haase, G 2017, “[Neurotrophic factors for motor neurons: an à la carte menu]”, Medecine Sciences: M/S, vol. 33, no. 10, p. 835-839.

  • Armand, M, Bernard, JY, Forhan, A, Heude, B, Charles, M-A & EDEN mother-child cohort study group, 2017, “Maternal nutritional determinants of colostrum fatty acids in the EDEN mother-child cohort”, Clinical Nutrition (Edinburgh, Scotland).
    Résumé : BACKGROUND & AIMS: Programming of infant development and later health may depend on early-milk polyunsaturated fatty acids (PUFA) contents, that are very variable between women for reasons not well elucidated. Indeed, a high n-6/n-3 PUFA in milk was associated with higher adiposity, arterial pressure and lower psychomotor scores in childhood. We aimed to explore the respective contribution of several maternal and perinatal factors to the variability of linoleic (LA), α-linolenic (ALA), arachidonic (AA), and docosahexaenoic (DHA) acid levels in early milk. METHODS: Fatty acids of 934 colostrum samples from the EDEN mother-child cohort were analyzed by gas chromatography. The dietary intakes during the last trimester of pregnancy were estimated using a quantitative food frequency questionnaire. Relationship between milk PUFA and dietary fatty acids, and other maternal or pregnancy variables were analyzed by multiple linear regression. RESULTS: The means (±SD) of colostrum LA, ALA, AA and DHA levels were, respectively, 9.85 ± 1.85, 0.65 ± 0.22, 0.86 ± 0.16, and 0.64 ± 0.19% of total fatty acids. Obese mothers colostrum contained the highest level of LA and AA and the lowest level of ALA and DHA. Colostrum LA, AA and DHA levels were higher in primiparous women. Mother's age was positively associated with colostrum AA and DHA. Dietary n-6 PUFA were associated with higher LA and lower DHA levels in colostrum, while dietary n-3 PUFA were related to higher LA and lower AA levels. Contrary to what was observed for DHA, AA level in colostrum was not related to its dietary intake. High dietary AA/DHA and total n-6/n-3 ratios were critical for the content of DHA in colostrum lipids. CONCLUSIONS: Our study brings new insights in the understanding of the main maternal factors involved in PUFA levels variability in early milk. These data are important to consider for dietary counseling for women prior to and during pregnancy.
    Mots-clés : BMI class, Cohort study, Colostrum PUFA, cvs, Maternal determinants, Pregnant women diet.

  • Aziz, A-L, Giusiano, B, Joubert, S, Duprat, L, Didic, M, Gueriot, C, Koric, L, Boucraut, J, Felician, O, Ranjeva, J-P, Guedj, E & Ceccaldi, M 2017, “Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease”, Neurobiology of Aging, vol. 54, p. 22-30.
    Résumé : Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions.
    Mots-clés : Age of Onset, Alzheimer's disease, Magnetic Resonance Imaging, Neuroimaging biomarkers, Positron emission tomography imaging, snc.

  • Barral, P-A, De Masi-Jacquier, M, Gaudry, M, Boutboul, D, Bartoli, J-M, Jacquier, A & Piquet, P 2017, “Three-Dimensional to Three-Dimensional Image Fusion-Guided Thoracic Endovascular Aortic Repair without Iodine Injection”, Journal of vascular and interventional radiology: JVIR, vol. 28, no. 8, p. 1201-1203.

  • Bartolomei, F, Lagarde, S, Wendling, F, McGonigal, A, Jirsa, V, Guye, M & Bénar, C 2017, “Defining epileptogenic networks: Contribution of SEEG and signal analysis”, Epilepsia, vol. 58, no. 7, p. 1131-1147.
    Résumé : Epileptogenic networks are defined by the brain regions involved in the production and propagation of epileptic activities. In this review we describe the historical, methodologic, and conceptual bases of this model in the analysis of electrophysiologic intracerebral recordings. In the context of epilepsy surgery, the determination of cerebral regions producing seizures (i.e., the "epileptogenic zone") is a crucial objective. In contrast with a traditional focal vision of focal drug-resistant epilepsies, the concept of epileptogenic networks has been progressively introduced as a model better able to describe the complexity of seizure dynamics and realistically describe the distribution of epileptogenic anomalies in the brain. The concept of epileptogenic networks is historically linked to the development of the stereoelectroencephalography (SEEG) method and subsequent introduction of means of quantifying the recorded signals. Seizures, and preictal and interictal discharges produce clear patterns on SEEG. These patterns can be analyzed utilizing signal analysis methods that quantify high-frequency oscillations or changes in functional connectivity. Dramatic changes in SEEG brain connectivity can be described during seizure genesis and propagation within cortical and subcortical regions, associated with the production of different patterns of seizure semiology. The interictal state is characterized by networks generating abnormal activities (interictal spikes) and also by modified functional properties. The introduction of novel approaches to large-scale modeling of these networks offers new methods in the goal of better predicting the effects of epilepsy surgery. The epileptogenic network concept is a key factor in identifying the anatomic distribution of the epileptogenic process, which is particularly important in the context of epilepsy surgery.
    Mots-clés : Algorithms, Brain, Brain Mapping, Brain networks, Cerebral Cortex, Electrocorticography, Electrodes, Implanted, Electroencephalography, Epilepsies, Partial, Epilepsy, Evoked Potentials, Focal epilepsies, Functional connectivity, Humans, Malformations of Cortical Development, Models, Theoretical, Nerve Net, Signal processing, Signal Processing, Computer-Assisted, Stereoelectroencephalography.

  • 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.

  • Besson, P, Carrière, N, Bandt, SK, Tommasi, M, Leclerc, X, Derambure, P, Lopes, R & Tyvaert, L 2017, “Whole-Brain High-Resolution Structural Connectome: Inter-Subject Validation and Application to the Anatomical Segmentation of the Striatum”, Brain Topography, vol. 30, no. 3, p. 291-302, viewed 18August,2017, .
    Résumé : The present study describes extraction of high-resolution structural connectome (HRSC) in 99 healthy subjects, acquired and made available by the Human Connectome Project. Single subject connectomes were then registered to the common surface space to allow assessment of inter-individual reproducibility of this novel technique using a leave-one-out approach. The anatomic relevance of the surface-based connectome was examined via a clustering algorithm, which identified anatomic subdivisions within the striatum. The connectivity of these striatal subdivisions were then mapped on the cortical and other subcortical surfaces. Findings demonstrate that HRSC analysis is robust across individuals and accurately models the actual underlying brain networks related to the striatum. This suggests that this method has the potential to model and characterize the healthy whole-brain structural network at high anatomic resolution.
    Mots-clés : Connectome, Diffusion Magnetic Resonance Imaging, High-resolution, snc, Striatum clustering, Surface-based connectivity.

  • Boutière, C, Rey, C, Zaaraoui, W, Le Troter, A, Rico, A, Crespy, L, Achard, S, Reuter, F, Pariollaud, F, Wirsich, J, Asquinazi, P, Confort-Gouny, S, Soulier, E, Guye, M, Pelletier, J, Ranjeva, J-P & Audoin, B 2017, “Improvement of spasticity following intermittent theta burst stimulation in multiple sclerosis is associated with modulation of resting-state functional connectivity of the primary motor cortices”, Multiple Sclerosis (Houndmills, Basingstoke, England), vol. 23, no. 6, p. 855-863.
    Résumé : BACKGROUND: Intermittent theta burst stimulation (iTBS) of the primary motor cortex improves transiently lower limbs spasticity in multiple sclerosis (MS). However, the cerebral mechanisms underlying this effect have never been investigated. OBJECTIVE: To assess whether modulation of spasticity induced by iTBS is underlined by functional reorganization of the primary motor cortices. METHODS: A total of 17 patients with MS suffering from lower limbs spasticity were randomized to receive real iTBS or sham iTBS during the first half of a 5-week indoor rehabilitation programme. Spasticity was assessed using the Modified Ashworth Scale and the Visual Analogue Scale at baseline, after the stimulation session and at the end of the rehabilitation programme. Resting-state functional magnetic resonance imaging (fMRI) was performed at the three time points, and brain functional networks topology was analysed using graph-theoretical approach. RESULTS: At the end of stimulation, improvement of spasticity was greater in real iTBS group than in sham iTBS group ( p = 0.026). iTBS had a significant effect on the balance of the connectivity degree between the stimulated and the homologous primary motor cortex ( p = 0.005). Changes in inter-hemispheric balance were correlated with improvement of spasticity (rho = 0.56, p = 0.015). CONCLUSION: This longitudinal resting-state fMRI study evidences that functional reorganization of the primary motor cortices may underlie the effect of iTBS on spasticity in MS.

  • 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.

  • De Leener, B, Mangeat, G, Dupont, S, Martin, AR, Callot, V, Stikov, N, Fehlings, MG & Cohen-Adad, J 2017, “Topologically preserving straightening of spinal cord MRI”, Journal of magnetic resonance imaging: JMRI, vol. 46, no. 4, p. 1209-1219.
    Résumé : PURPOSE: To propose a robust and accurate method for straightening magnetic resonance (MR) images of the spinal cord, based on spinal cord segmentation, that preserves spinal cord topology and that works for any MRI contrast, in a context of spinal cord template-based analysis. MATERIALS AND METHODS: The spinal cord curvature was computed using an iterative Non-Uniform Rational B-Spline (NURBS) approximation. Forward and inverse deformation fields for straightening were computed by solving analytically the straightening equations for each image voxel. Computational speed-up was accomplished by solving all voxel equation systems as one single system. Straightening accuracy (mean and maximum distance from straight line), computational time, and robustness to spinal cord length was evaluated using the proposed and the standard straightening method (label-based spline deformation) on 3T T2 - and T1 -weighted images from 57 healthy subjects and 33 patients with spinal cord compression due to degenerative cervical myelopathy (DCM). RESULTS: The proposed algorithm was more accurate, more robust, and faster than the standard method (mean distance = 0.80 vs. 0.83 mm, maximum distance = 1.49 vs. 1.78 mm, time = 71 vs. 174 sec for the healthy population and mean distance = 0.65 vs. 0.68 mm, maximum distance = 1.28 vs. 1.55 mm, time = 32 vs. 60 sec for the DCM population). CONCLUSION: A novel image straightening method that enables template-based analysis of quantitative spinal cord MRI data is introduced. This algorithm works for any MRI contrast and was validated on healthy and patient populations. The presented method is implemented in the Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1209-1219.
    Mots-clés : deformation field, MR image analysis, NURBS, SCT, snc, Spinal cord, straightening.

  • 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.

  • Doche, E, Lecocq, A, Maarouf, A, Duhamel, G, Soulier, E, Confort-Gouny, S, Rico, A, Guye, M, Audoin, B, Pelletier, J, Ranjeva, J-P & Zaaraoui, W 2017, “Hypoperfusion of the thalamus is associated with disability in relapsing remitting multiple sclerosis”, Journal of Neuroradiology. Journal De Neuroradiologie, vol. 44, no. 2, p. 158-164.
    Résumé : BACKGROUND: While gray matter (GM) perfusion abnormalities have been evidenced in multiple sclerosis (MS) patients, the relationships with disability still remain unclear. Considering that atrophy is known to impact on perfusion, we aimed to assess perfusion abnormalities in GM of MS patients, outside atrophic regions and investigate relationships with disability. METHODS: Brain perfusion of 23 relapsing remitting MS patients and 16 matched healthy subjects were assessed at 3T using the pseudo-continuous arterial spin labeling magnetic resonance imaging technique. In order to locate potential GM perfusion abnormalities in regions spared by atrophy, we combined voxelwise comparisons of GM cerebral blood flow (CBF) maps (cortex and deep GM) (P<0.005, FWE-corrected) and voxel-based-morphometry analysis (P<0.005, FDR-corrected) to exclude atrophic regions. Disability was assessed using the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite score (MSFC). RESULTS: In patients, significant GM hypoperfusion outside atrophic regions was depicted only in bilateral thalami. No other cluster was found to be hypoperfused compared to controls. Perfusion of thalami was correlated to MSFC (P=0.011, rho=0.523). A trend of correlation was found between perfusion of thalami and EDSS (P=0.061, rho=-0.396). CONCLUSION: In relapsing remitting MS, perfusion abnormalities in thalamic regions contribute to disability. These findings suggest that functional impairments of thalami, representing a major brain hub, may disturb various cerebral functions even before structural damage.

  • 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.

  • Dupont, SM, De Leener, B, Taso, M, Le Troter, A, Nadeau, S, Stikov, N, Callot, V & Cohen-Adad, J 2017, “Fully-integrated framework for the segmentation and registration of the spinal cord white and gray matter”, NeuroImage, vol. 150, p. 358-372.
    Résumé : The spinal cord white and gray matter can be affected by various pathologies such as multiple sclerosis, amyotrophic lateral sclerosis or trauma. Being able to precisely segment the white and gray matter could help with MR image analysis and hence be useful in further understanding these pathologies, and helping with diagnosis/prognosis and drug development. Up to date, white/gray matter segmentation has mostly been done manually, which is time consuming, induces a bias related to the rater and prevents large-scale multi-center studies. Recently, few methods have been proposed to automatically segment the spinal cord white and gray matter. However, no single method exists that combines the following criteria: (i) fully automatic, (ii) works on various MRI contrasts, (iii) robust towards pathology and (iv) freely available and open source. In this study we propose a multi-atlas based method for the segmentation of the spinal cord white and gray matter that addresses the previous limitations. Moreover, to study the spinal cord morphology, atlas-based approaches are increasingly used. These approaches rely on the registration of a spinal cord template to an MR image, however the registration usually doesn't take into account the spinal cord internal structure and thus lacks accuracy. In this study, we propose a new template registration framework that integrates the white and gray matter segmentation to account for the specific gray matter shape of each individual subject. Validation of segmentation was performed in 24 healthy subjects using T2*-weighted images, in 8 healthy subjects using diffusion weighted images (exhibiting inverted white-to-gray matter contrast compared to T2*-weighted), and in 5 patients with spinal cord injury. The template registration was validated in 24 subjects using T2*-weighted data. Results of automatic segmentation on T2*-weighted images was in close correspondence with the manual segmentation (Dice coefficient in the white/gray matter of 0.91/0.71 respectively). Similarly, good results were obtained in data with inverted contrast (diffusion-weighted image) and in patients. When compared to the classical template registration framework, the proposed framework that accounts for gray matter shape significantly improved the quality of the registration (comparing Dice coefficient in gray matter: p=9.5×10-6). While further validation is needed to show the benefits of the new registration framework in large cohorts and in a variety of patients, this study provides a fully-integrated tool for quantitative assessment of white/gray matter morphometry and template-based analysis. All the proposed methods are implemented in the Spinal Cord Toolbox (SCT), an open-source software for processing spinal cord multi-parametric MRI data.

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