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GUYE Maxime

Director of CEMEREM
7T MRI Scientific Director
Professor of Biophysics - MD, PhD
Medicine School, Aix-Marseille University
University Hospital of Marseille (AP-HM)

maxime.guye@ap-hm.fr
tel : +33 4 91 38 84 64

Key Words
- Multimodal MRI and electrophysiology in Epilepsy and Neurodegenerative diseases
- Brain connectivity
- Ultra-high field MRI

Biosketch

Maxime Guye is the director of the medical site (i.e. CEMEREM) of the CRMBM located at the University Hospital of “La Timone” in Marseille. This site hosts 3 MRI systems dedicated to clinical research (i.e. 1.5, 3T and 7T whole body MRI). He is professor of Biophysics at the school of Medicine of Aix-Marseille University. He is consultant in Neurology/Epileptology at the Clinical Neuroscience Department of the University Hospital, APHM. He holds a PhD in Neuroscience and has been trained in MR Physics and Electrophysiology. He has held a research position at the University College of London (Institute of Neurology) after his residency in Neurology in Marseille. He is the current President of the French Society for Magnetic Resonance in Biology and Medicine. He is a member of the Scientific Committee of the French Society of Clinical Neurophysiology. He has been an elected member of the National Committee for Scientific Research (CNRS).

Current Research Interest and projects

  • Human 7T MRI
  • Developing and applying innovative MR methods in neurological and psychiatric diseases in order to improve patient care
  • Studying node interactions in pathological brain networks and their consequences on cognitive networks
  • Combining and comparing multimodal MRI techniques and electrophysiological recordings

Publications

2018

Journal Article

  • 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.

2017

Journal Article

  • 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.

  • 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.

  • 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.

  • 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.

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

  • Jirsa, VK, Proix, T, Perdikis, D, Woodman, MM, Wang, H, Gonzalez-Martinez, J, Bernard, C, Benar, C, Guye, M, Chauvel, P & Bartolomei, F 2017, “The Virtual Epileptic Patient: Individualized whole-brain models of epilepsy spread”, Neuroimage, vol. 145, p. 377-388.
    Résumé : Individual variability has clear effects upon the outcome of therapies and treatment approaches. The customization of healthcare options to the individual patient should accordingly improve treatment results. We propose a novel approach to brain interventions based on personalized brain network models derived from non-invasive structural data of individual patients. Along the example of a patient with bitemporal epilepsy, we show step by step how to develop a Virtual Epileptic Patient (VEP) brain model and integrate patient-specific information such as brain connectivity, epileptogenic zone and MRI lesions. Using high-performance computing, we systematically carry out parameter space explorations, fit and validate the brain model against the patient's empirical stereotactic EEG (SEEG) data and demonstrate how to develop novel personalized strategies towards therapy and intervention. (C) 2016 The Authors. Published by Elsevier Inc.
    Mots-clés : Diffusion MRI, eeg, Functional connectivity, network dynamics, resting brain, snc, spherical-deconvolution, structural connectivity, surgery, temporal-lobe epilepsy, tractography.


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


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

  • Proix, T, Bartolomei, F, Guye, M & Jirsa, VK 2017, “Individual brain structure and modelling predict seizure propagation”, Brain: A Journal of Neurology, vol. 140, no. 3, p. 641-654.
    Résumé : See Lytton (doi:10.1093/awx018) for a scientific commentary on this article.Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions.
    Mots-clés : brain network models, connectomes, Epilepsy, individualized medicine, seizure propagation, snc.

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

  • Ridley, B, Wirsich, J, Bettus, G, Rodionov, R, Murta, T, Chaudhary, U, Carmichael, D, Thornton, R, Vulliemoz, S, McEvoy, A, Wendling, F, Bartolomei, F, Ranjeva, J-P, Lemieux, L & Guye, M 2017, “Simultaneous Intracranial EEG-fMRI Shows Inter-Modality Correlation in Time-Resolved Connectivity Within Normal Areas but Not Within Epileptic Regions”, Brain Topography, vol. 30, no. 5, p. 639-655.
    Résumé : For the first time in research in humans, we used simultaneous icEEG-fMRI to examine the link between connectivity in haemodynamic signals during the resting-state (rs) and connectivity derived from electrophysiological activity in terms of the inter-modal connectivity correlation (IMCC). We quantified IMCC in nine patients with drug-resistant epilepsy (i) within brain networks in 'healthy' non-involved cortical zones (NIZ) and (ii) within brain networks involved in generating seizures and interictal spikes (IZ1) or solely spikes (IZ2). Functional connectivity (h 2 ) estimates for 10 min of resting-state data were obtained between each pair of electrodes within each clinical zone for both icEEG and fMRI. A sliding window approach allowed us to quantify the variability over time of h 2 (vh 2) as an indicator of connectivity dynamics. We observe significant positive IMCC for h 2 and vh 2, for multiple bands in the NIZ only, with the strongest effect in the lower icEEG frequencies. Similarly, intra-modal h 2 and vh 2 were found to be differently modified as a function of different epileptic processes: compared to NIZ, [Formula: see text] was higher in IZ1, but lower in IZ2, while [Formula: see text] showed the inverse pattern. This corroborates previous observations of inter-modal connectivity discrepancies in pathological cortices, while providing the first direct invasive and simultaneous comparison in humans. We also studied time-resolved FC variability multimodally for the first time, finding that IZ1 shows both elevated internal [Formula: see text] and less rich dynamical variability, suggesting that its chronic role in epileptogenesis may be linked to greater homogeneity in self-sustaining pathological oscillatory states.

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

  • Wirsich, J, Rey, M, Guye, M, Bénar, C, Lanteaume, L, Ridley, B, Confort-Gouny, S, Cassé-Perrot, C, Soulier, E, Viout, P, Rouby, F, Lefebvre, M-N, Audebert, C, Truillet, R, Jouve, E, Payoux, P, Bartrés-Faz, D, Bordet, R, Richardson, JC, Babiloni, C, Rossini, PM, Micallef, J, Blin, O, Ranjeva, J-P & Pharmacog Consortium, 2017, “Brain Networks are Independently Modulated by Donepezil, Sleep, and Sleep Deprivation”, Brain Topography.
    Résumé : Resting-state connectivity has been widely studied in the healthy and pathological brain. Less well-characterized are the brain networks altered during pharmacological interventions and their possible interaction with vigilance. In the hopes of finding new biomarkers which can be used to identify cortical activity and cognitive processes linked to the effects of drugs to treat neurodegenerative diseases such as Alzheimer's disease, the analysis of networks altered by medication would be particularly interesting. Eleven healthy subjects were recruited in the context of the European Innovative Medicines Initiative 'PharmaCog'. Each underwent five sessions of simultaneous EEG-fMRI in order to investigate the effects of donepezil and memantine before and after sleep deprivation (SD). The SD approach has been previously proposed as a model for cognitive impairment in healthy subjects. By applying network based statistics (NBS), we observed altered brain networks significantly linked to donepezil intake and sleep deprivation. Taking into account the sleep stages extracted from the EEG data we revealed that a network linked to sleep is interacting with sleep deprivation but not with medication intake. We successfully extracted the functional resting-state networks modified by donepezil intake, sleep and SD. We observed donepezil induced whole brain connectivity alterations forming a network separated from the changes induced by sleep and SD, a result which shows the utility of this approach to check for the validity of pharmacological resting-state analysis of the tested medications without the need of taking into account the subject specific vigilance.
    Mots-clés : Donepezil, EEG-fMRI, Functional connectivity, Memantine, Sleep, snc.

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

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

2016

Journal Article

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

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

  • Donadieu, M, Le Fur, Y, Confort-Gouny, S, Le Troter, A, Guye, M & Ranjeva, J-P 2016, “Evidencing different neurochemical profiles between thalamic nuclei using high resolution 2D-PRESS semi-LASER (1)H-MRSI at 7 T”, Magma (New York, N.Y.), vol. 29, no. 3, p. 491-501.
    Résumé : OBJECTIVE: To demonstrate that high resolution (1)H semi-LASER MRSI acquired at 7 T permits discrimination of metabolic patterns of different thalamic nuclei. MATERIALS AND METHODS: Thirteen right-handed healthy volunteers were explored at 7 T using a high-resolution 2D-semi-LASER (1)H-MRSI sequence to determine the relative levels of N-Acetyl Aspartate (NAA), choline (Cho) and creatine-phosphocreatine (Cr) in eight VOIs (volume <0.3 ml) centered on four different thalamic nuclei located on the Oxford thalamic connectivity atlas. Post-processing was done using the CSIAPO software. Chemical shift displacement of metabolites was evaluated on a phantom and correction factors were applied to in vivo data. RESULTS: The global assessment (ANOVA p < 0.05) of the neurochemical profiles (NAA, Cho and Cr levels) with thalamic nuclei and hemispheres as factors showed a significant global effect (F = 11.98, p < 0.0001), with significant effect of nucleus type (p < 0.0001) and hemisphere (p < 0.0001). Post hoc analyses showed differences in neurochemical profiles between the left and the right hemisphere (p < 0.05), and differences in neurochemical profiles between nuclei within each hemisphere (p < 0.05). CONCLUSION: For the first time, using high resolution 2D-PRESS semi-LASER (1)H-MRSI acquired at 7 T, we demonstrated that the neurochemical profiles were different between thalamic nuclei, and that these profiles were dependent on the brain hemisphere.
    Mots-clés : 1H-MRSI, Adult, Analysis of Variance, Aspartic Acid, Brain, Choline, Connectivity atlas, Creatine, crmbm, Female, Healthy Volunteers, Humans, Lasers, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Neurochemical profiles, Neurodegenerative Diseases, Phantoms, Imaging, Phosphocreatine, snc, Software, Spectrophotometry, Thalamic nuclei, Thalamus, Ultra high field, Young Adult.

  • Donadieu, M, Le Fur, Y, Lecocq, A, Maudsley, AA, Gherib, S, Soulier, E, Confort-Gouny, S, Pariollaud, F, Ranjeva, M-P, Pelletier, J, Guye, M, Zaaraoui, W, Audoin, B & Ranjeva, J-P 2016, “Metabolic voxel-based analysis of the complete human brain using fast 3D-MRSI: Proof of concept in multiple sclerosis”, Journal of magnetic resonance imaging: JMRI, vol. 44, no. 2, p. 411-419.
    Résumé : PURPOSE: To detect local metabolic abnormalities over the complete human brain in multiple sclerosis (MS) patients, we used optimized fast volumic echo planar spectroscopic imaging (3D-EPSI). MATERIALS AND METHODS: Weighted mean combination of two 3D-EPSI covering the whole brain acquired at 3T in AC-PC and AC-PC+15° axial planes was performed to obtain high-quality metabolite maps for five metabolites: N-acetyl aspartate (NAA), glutamate+glutamine (Glx), choline (Cho), myo-inositol (m-Ins), and creatine+phosphocreatine (tCr). After spatial normalization, maps from 19 patients suffering from relapsing-remitting MS were compared to 19 matched controls using statistical mapping analyses to determine the topography of metabolic abnormalities. Probabilistic white matter (WM) T2 lesion maps and gray matter (GM) atrophy maps were also generated. RESULTS: Two-group analysis of variance (ANOVA) (SPM8, P < 0.005, false discovery rate [FDR]-corrected P < 0.05 at the cluster level with age and sex as confounding covariates) comparing patients and controls matched for age and sex showed clusters of abnormal metabolite levels with 1) decreased NAA (around -15%) and Glx (around 20%) predominantly in GM within prefrontal cortices, motor cortices, bilateral thalami, and mesial temporal cortices in line with neuronal/neuro-astrocytic dysfunction; 2) increased m-Ins (around + 20%) inside WM T2 lesions and in the normal-appearing WM of temporal-occipital lobes, suggesting glial activation. CONCLUSION: We demonstrate the ability to noninvasively map over the complete brain-from vertex to cerebellum-with a validated sequence, the metabolic abnormalities associated with MS, for characterizing the topography of pathological processes affecting widespread areas of WM and GM and its functional impact. J. Magn. Reson. Imaging 2016;44:411-419.

  • Faivre, A, Robinet, E, Guye, M, Rousseau, C, Maarouf, A, Le Troter, A, Zaaraoui, W, Rico, A, Crespy, L, Soulier, E, Confort-Gouny, S, Pelletier, J, Achard, S, Ranjeva, J-P & Audoin, B 2016, “Depletion of brain functional connectivity enhancement leads to disability progression in multiple sclerosis: A longitudinal resting-state fMRI study”, Multiple Sclerosis (Houndmills, Basingstoke, England), vol. 22, no. 13, p. 1695-1708.
    Résumé : BACKGROUND: The compensatory effect of brain functional connectivity enhancement in relapsing-remitting multiple sclerosis (RRMS) remains controversial. OBJECTIVE: To characterize the relationships between brain functional connectivity changes and disability progression in RRMS. METHODS: Long-range connectivity, short-range connectivity, and density of connections were assessed using graph theoretical analysis of resting-state functional magnetic resonance imaging (fMRI) data acquired in 38 RRMS patients (disease duration: 120 ± 32 months) and 24 controls. All subjects were explored at baseline and all patients and six controls 2 years later. RESULTS: At baseline, levels of long-range and short-range brain functional connectivity were higher in patients compared to controls. During the follow-up, decrease in connections' density was inversely correlated with disability progression. Post-hoc analysis evidenced differential evolution of brain functional connectivity metrics in patients according to their level of disability at baseline: while patients with lowest disability at baseline experienced an increase in all connectivity metrics during the follow-up, patients with higher disability at baseline showed a decrease in the connectivity metrics. In these patients, decrease in the connectivity metrics was associated with disability progression. CONCLUSION: The study provides two main findings: (1) brain functional connectivity enhancement decreases during the disease course after reaching a maximal level, and (2) decrease in brain functional connectivity enhancement participates in disability progression.

  • Fouré, A, Nosaka, K, Gastaldi, M, Mattei, J-P, Boudinet, H, Guye, M, Vilmen, C, Le Fur, Y, Bendahan, D & Gondin, J 2016, “Effects of branched-chain amino acids supplementation on both plasma amino acids concentration and muscle energetics changes resulting from muscle damage: A randomized placebo controlled trial”, Clinical Nutrition (Edinburgh, Scotland), vol. 35, no. 1, p. 83-94.
    Résumé : BACKGROUND & AIMS: Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage. METHODS: (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage. RESULTS: No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4). CONCLUSIONS: The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage.
    Mots-clés : crmbm, Double blind randomized placebo controlled trial, Exercise induced-muscle damage, Magnetic Resonance Spectroscopy, msk.

  • Le Troter, A, Fouré, A, Guye, M, Confort-Gouny, S, Mattei, J-P, Gondin, J, Salort-Campana, E & Bendahan, D 2016, “Volume measurements of individual muscles in human quadriceps femoris using atlas-based segmentation approaches”, Magma (New York, N.Y.), vol. 29, no. 2, p. 245-257.
    Résumé : OBJECTIVES: Atlas-based segmentation is a powerful method for automatic structural segmentation of several sub-structures in many organs. However, such an approach has been very scarcely used in the context of muscle segmentation, and so far no study has assessed such a method for the automatic delineation of individual muscles of the quadriceps femoris (QF). In the present study, we have evaluated a fully automated multi-atlas method and a semi-automated single-atlas method for the segmentation and volume quantification of the four muscles of the QF and for the QF as a whole. SUBJECTS AND METHODS: The study was conducted in 32 young healthy males, using high-resolution magnetic resonance images (MRI) of the thigh. The multi-atlas-based segmentation method was conducted in 25 subjects. Different non-linear registration approaches based on free-form deformable (FFD) and symmetric diffeomorphic normalization algorithms (SyN) were assessed. Optimal parameters of two fusion methods, i.e., STAPLE and STEPS, were determined on the basis of the highest Dice similarity index (DSI) considering manual segmentation (MSeg) as the ground truth. Validation and reproducibility of this pipeline were determined using another MRI dataset recorded in seven healthy male subjects on the basis of additional metrics such as the muscle volume similarity values, intraclass coefficient, and coefficient of variation. Both non-linear registration methods (FFD and SyN) were also evaluated as part of a single-atlas strategy in order to assess longitudinal muscle volume measurements. The multi- and the single-atlas approaches were compared for the segmentation and the volume quantification of the four muscles of the QF and for the QF as a whole. RESULTS: Considering each muscle of the QF, the DSI of the multi-atlas-based approach was high 0.87 ± 0.11 and the best results were obtained with the combination of two deformation fields resulting from the SyN registration method and the STEPS fusion algorithm. The optimal variables for FFD and SyN registration methods were four templates and a kernel standard deviation ranging between 5 and 8. The segmentation process using a single-atlas-based method was more robust with DSI values higher than 0.9. From the vantage of muscle volume measurements, the multi-atlas-based strategy provided acceptable results regarding the QF muscle as a whole but highly variable results regarding individual muscle. On the contrary, the performance of the single-atlas-based pipeline for individual muscles was highly comparable to the MSeg, thereby indicating that this method would be adequate for longitudinal tracking of muscle volume changes in healthy subjects. CONCLUSION: In the present study, we demonstrated that both multi-atlas and single-atlas approaches were relevant for the segmentation of individual muscles of the QF in healthy subjects. Considering muscle volume measurements, the single-atlas method provided promising perspectives regarding longitudinal quantification of individual muscle volumes.
    Mots-clés : crmbm, Fusion, Individual muscle volume measurements, MRI, msk, Multi-atlas-based segmentation, Non-linear registration, Quadriceps femoris muscle.

  • Marsot, A, Boucherie, Q, Kheloufi, F, Riff, C, Braunstein, D, Dupouey, J, Guilhaumou, R, Zendjidjian, X, Bonin-Guillaume, S, Fakra, E, Guye, M, Jirsa, V, Azorin, J-M, Belzeaux, R, Adida, M, Micallef, J & Blin, O 2016, “[What can we expect from clinical trials in psychiatry?]”, L'Encephale, vol. 42, no. 6S, p. S2-S6.
    Résumé : Clinical trials in psychiatry allow to build the regulatory dossiers for market authorization but also to document the mechanism of action of new drugs, to build pharmacodynamics models, evaluate the treatment effects, propose prognosis, efficacy or tolerability biomarkers and altogether to assess the impact of drugs for patient, caregiver and society. However, clinical trials have shown some limitations. Number of recent dossiers failed to convince the regulators. The clinical and biological heterogeneity of psychiatric disorders, the pharmacokinetic and pharmacodynamics properties of the compounds, the lack of translatable biomarkers possibly explain these difficulties. Several breakthrough options are now available: quantitative system pharmacology analysis of drug effects variability, pharmacometry and pharmacoepidemiology, Big Data analysis, brain modelling. In addition to more classical approaches, these opportunities lead to a paradigm change for clinical trials in psychiatry.
    Mots-clés : Cerveau virtuel, Clinical trials, Essais cliniques, Pharmacoépidémiologie, Pharmacoepidemiology, Pharmacogenetics, Pharmacogenétique, Pharmacologie quantitative des systèmes, Quantitative system pharmacologie, snc, Virtual brain.

  • Martin, A, Grosprêtre, S, Vilmen, C, Guye, M, Mattei, J-P, LE Fur, Y, Bendahan, D & Gondin, J 2016, “The Etiology of Muscle Fatigue Differs between Two Electrical Stimulation Protocols”, Medicine and Science in Sports and Exercise, vol. 48, no. 8, p. 1474-1484.
    Résumé : PURPOSE: This study aimed at investigating the mechanisms involved in the force reduction induced by two electrical stimulation (ES) protocols that were designed to activate motor units differently. METHODS: The triceps surae of 11 healthy subjects (8 men; age, ~28 yr) was activated using ES applied over the tibial nerve. Two ES protocols (conventional [CONV]: 20 Hz, 0.05 ms vs wide-pulse high-frequency [WPHF]: 80 Hz, 1 ms) were performed and involved 40 trains (6 s on-6 s off) delivered at an intensity (IES) evoking 20% of maximal voluntary contraction. To analyze the mechanical properties of the motor units activated at IES, force-frequency relation was evoked before and after each protocol. H-reflex and M-wave responses evoked by the last stimulation pulse were also assessed during each ES protocol. Electromyographic responses (∑EMG) were recorded after each train to analyze the behavior of the motor units activated at IES. Metabolic variables, including relative concentrations of phosphocreatine and inorganic phosphate as well as intracellular pH, were assessed using P-MR spectroscopy during each protocol. RESULTS: Larger H-reflex amplitudes were observed during WPHF as compared with CONV, whereas opposite findings were observed for M-wave amplitudes. Despite this difference, both the force reduction (-26%) and metabolic changes were similar between the two protocols. The CONV protocol induced a rightward shift of the force-frequency relation, whereas a significant reduction of the ∑EMG evoked at IES was observed only for the WPHF. CONCLUSIONS: These results suggest that a decreased number of active motor units mainly contributed to WPHF-induced force decrease, whereas intracellular processes were most likely involved in the force reduction occurring during CONV stimulation.
    Mots-clés : crmbm, msk.

  • Massire, A, Taso, M, Besson, P, Guye, M, Ranjeva, J-P & Callot, V 2016, “High-resolution multi-parametric quantitative magnetic resonance imaging of the human cervical spinal cord at 7T”, NeuroImage, vol. 143, p. 58-69.
    Résumé : Quantitative MRI techniques have the potential to characterize spinal cord tissue impairments occurring in various pathologies, from both microstructural and functional perspectives. By enabling very high image resolution and enhanced tissue contrast, ultra-high field imaging may offer further opportunities for such characterization. In this study, a multi-parametric high-resolution quantitative MRI protocol is proposed to characterize in vivo the human cervical spinal cord at 7T. Multi-parametric quantitative MRI acquizitions including T1, T2(*) relaxometry mapping and axial diffusion MRI were performed on ten healthy volunteers with a whole-body 7T system using a commercial prototype coil-array dedicated to cervical spinal cord imaging. Automatic cord segmentation and multi-parametric data registration to spinal cord templates enabled robust regional studies within atlas-based WM tracts and GM horns at the C3 cervical level. T1 value, cross-sectional area and GM/WM ratio evolutions along the cervical cord were also reported. An original correction method for B1(+)-biased T1 mapping sequence was additionally proposed and validated on phantom. As a result, relaxometry and diffusion parameters derived from high-resolution quantitative MRI acquizitions were reported at 7T for the first time. Obtained images, with unmatched resolutions compared to lower field investigations, provided exquisite anatomical details and clear delineation of the spinal cord substructures within an acquisition time of 30min, compatible with clinical investigations. Regional statistically significant differences were highlighted between WM and GM based on T1 and T2* maps (p<10(-3)), as well as between sensory and motor tracts based on diffusion tensor imaging maps (p<0.05). The proposed protocol demonstrates that ultra-high field spinal cord high-resolution quantitative MRI is feasible and lays the groundwork for future clinical investigations of degenerative spinal cord pathologies.
    Mots-clés : crmbm, diffusion tensor imaging, Quantitative MRI, Relaxometry mapping, snc, Spinal cord, Template-based segmentation, Ultra-high field.

  • Ridley, B, Beltramone, M, Wirsich, J, Le Troter, A, Tramoni, E, Aubert, S, Achard, S, Ranjeva, J-P, Guye, M & Felician, O 2016, “Alien Hand, Restless Brain: Salience Network and Interhemispheric Connectivity Disruption Parallel Emergence and Extinction of Diagonistic Dyspraxia”, Frontiers in Human Neuroscience, vol. 10, p. 307.
    Résumé : Diagonistic dyspraxia (DD) is by far the most spectacular manifestation reported by sufferers of acute corpus callosum (CC) injury (so-called "split-brain"). In this form of alien hand syndrome, one hand acts at cross purposes with the other "against the patient's will". Although recent models view DD as a disorder of motor control, there is still little information regarding its neural underpinnings, due to widespread connectivity changes produced by CC insult, and the obstacle that non-volitional movements represent for task-based functional neuroimaging studies. Here, we studied patient AM, the first report of DD in patient with complete developmental CC agenesis. This unique case also offers the opportunity to study the resting-state connectomics of DD in the absence of diffuse changes subsequent to CC injury or surgery. AM developed DD following status epilepticus (SE) which resolved over a 2-year period. Whole brain functional connectivity (FC) was compared (Crawford-Howell [CH]) to 16 controls during the period of acute DD symptoms (Time 1) and after remission (Time 2). Whole brain graph theoretical models were also constructed and topological efficiency examined. At Time 1, disrupted FC was observed in inter-hemispheric and intra-hemispheric right edges, involving frontal superior and midline structures. Graph analysis indicated disruption of the efficiency of salience and right frontoparietal (FP) networks. At Time 2, after remission of diagnostic dyspraxia symptoms, FC and salience network changes had resolved. In sum, longitudinal analysis of connectivity in AM indicates that DD behaviors could result from disruption of systems that support the experience and control of volitional movements and the ability to generate appropriate behavioral responses to salient stimuli. This also raises the possibility that changes to large-scale functional architecture revealed by resting-state functional magnetic resonance imaging (fMRI) (rs-fMRI) may provide relevant information on the evolution of behavioral syndromes in addition to that provided by structural and task-based functional imaging.
    Mots-clés : alien hand, callosal agenesis, crmbm, disconnection syndrome, Epilepsy, Functional connectivity, graph theory, resting-state, snc.

  • Taso, M, Girard, OM, Duhamel, G, Le Troter, A, Feiweier, T, Guye, M, Ranjeva, J-P & Callot, V 2016, “Tract-specific and age-related variations of the spinal cord microstructure: a multi-parametric MRI study using diffusion tensor imaging (DTI) and inhomogeneous magnetization transfer (ihMT)”, NMR in biomedicine, vol. 29, no. 6, p. 817-832.
    Résumé : Being able to finely characterize the spinal cord (SC) microstructure and its alterations is a key point when investigating neural damage mechanisms encountered in different central nervous system (CNS) pathologies, such as multiple sclerosis, amyotrophic lateral sclerosis or myelopathy. Based on novel methods, including inhomogeneous magnetization transfer (ihMT) and dedicated SC probabilistic atlas post-processing, the present study focuses on the in vivo characterization of the healthy SC tissue in terms of regional microstructure differences between (i) upper and lower cervical vertebral levels and (ii) sensory and motor tracts, as well as differences attributed to normal aging. Forty-eight healthy volunteers aged from 20 to 70 years old were included in the study and scanned at 3 T using axial high-resolution T2 *-w imaging, diffusion tensor imaging (DTI) and ihMT, at two vertebral levels (C2 and C5). A processing pipeline with minimal user intervention, SC segmentation and spatial normalization into a reference space was implemented in order to assess quantitative morphological and structural parameters (cross-sectional areas, scalar DTI and MT/ihMT metrics) in specific white and gray matter regions of interest. The multi-parametric MRI metrics collected allowed upper and lower cervical levels to be distinguished, with higher ihMT ratio (ihMTR), higher axial diffusivity (λ∥ ) and lower radial diffusivity (λ⊥ ) at C2 compared with C5. Significant differences were also observed between white matter fascicles, with higher ihMTR and lower λ∥ in motor tracts compared with posterior sensory tracts. Finally, aging was found to be associated with significant metric alterations (decreased ihMTR and λ∥ ). The methodology proposed here, which can be easily transferred to the clinic, provides new insights for SC characterization. It bears great potential to study focal and diffuse SC damage in neurodegenerative and demyelinating diseases. Copyright © 2016 John Wiley & Sons, Ltd.
    Mots-clés : aging, crmbm, diffusion tensor imaging (DTI), ihMT, inhomogeneous magnetization transfer (ihMT), microstructure, Multi-parametric MRI, snc, Spinal cord.


  • Wirsich, J, Perry, A, Ridley, B, Proix, T, Golos, M, Bénar, C, Ranjeva, J-P, Bartolomei, F, Breakspear, M, Jirsa, V & Guye, M 2016, “Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy”, NeuroImage: Clinical, vol. 11, p. 707-718, viewed 7June,2016, .
    Résumé : The in vivo structure-function relationship is key to understanding brain network reorganization due to pathologies. This relationship is likely to be particularly complex in brain network diseases such as temporal lobe epilepsy, in which disturbed large-scale systems are involved in both transient electrical events and long-lasting functional and structural impairments. Herein, we estimated this relationship by analyzing the correlation between structural connectivity and functional connectivity in terms of analytical network communication parameters. As such, we targeted the gradual topological structure-function reorganization caused by the pathology not only at the whole brain scale but also both in core and peripheral regions of the brain. We acquired diffusion (dMRI) and resting-state fMRI (rsfMRI) data in seven right-lateralized TLE (rTLE) patients and fourteen healthy controls and analyzed the structure-function relationship by using analytical network communication metrics derived from the structural connectome. In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information) in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.
    Mots-clés : crmbm, Functional connectivity, Network based statistics, Network communication, rich club, snc, structural connectivity, Temporal lobe epilepsy.

2015

Journal Article

  • Fouré, A, Le Troter, A, Guye, M, Mattei, J-P, Bendahan, D & Gondin, J 2015, “Localization and quantification of intramuscular damage using statistical parametric mapping and skeletal muscle parcellation”, Scientific Reports, vol. 5, p. 18580.
    Résumé : In the present study, we proposed an original and robust methodology which combines the spatial normalization of skeletal muscle images, the statistical parametric mapping (SPM) analysis and the use of a specific parcellation in order to accurately localize and quantify the extent of skeletal muscle damage within the four heads of the quadriceps femoris. T2 maps of thigh muscles were characterized before, two (D2) and four (D4) days after 40 maximal isometric electrically-evoked contractions in 25 healthy young males. On the basis of SPM analysis of coregistrated T2 maps, the alterations were similarly detected at D2 and D4 in the superficial and distal regions of the vastus medialis (VM) whereas the proportion of altered muscle was higher in deep muscle regions of the vastus lateralis at D4 (deep: 35 ± 25%, superficial: 23 ± 15%) as compared to D2 (deep: 18 ± 13%, superficial: 17 ± 13%). The present methodology used for the first time on skeletal muscle would be of utmost interest to detect subtle intramuscular alterations not only for the diagnosis of muscular diseases but also for assessing the efficacy of potential therapeutic interventions and clinical treatment strategies.
    Mots-clés : crmbm, msk.

  • Lecocq, A, Le Fur, Y, Amadon, A, Vignaud, A, Cozzone, PJ, Guye, M & Ranjeva, J-P 2015, “Fast water concentration mapping to normalize (1)H MR spectroscopic imaging”, Magma (New York, N.Y.), vol. 28, no. 1, p. 87-100.
    Résumé : OBJECT: To propose a fast and robust acquisition and post-processing pipeline that is time-compatible with clinical explorations to obtain a proton density (ρ) map used as a reference for metabolic map normalization. This allows inter-subject and inter-group comparisons of magnetic resonance spectroscopic imaging (MRSI) data and longitudinal follow-up for single subjects. MATERIALS AND METHODS: A multi-echo T 2 (*) mapping sequence, the XEP sequence for B 1 (+) -mapping and Driven Equilibrium Single Pulse Observation of T 1-an optimized variable flip angle method for T 1 mapping used for both B 1 (-) -mapping and M 0 calculation-were used to determine correction factors leading to quantitative water proton density maps at 3T. Normalized metabolite maps were obtained on a phantom and nine healthy volunteers. To show the potential use of this technique at the individual level, we also explored one patient with low-grade glioma. RESULTS: Accurate ρ maps were obtained both on phantom and volunteers. After signal normalization with the generated ρ maps, metabolic concentrations determined by the present method differed from theory by <7 % in the phantom and were in agreement with data from the literature for the healthy controls. Using these normalized metabolic values, it was possible to demonstrate in the patient with brain glioma, metabolic abnormalities in normalized N-acetyl aspartate, choline and creatine levels; illustrating the potential for direct use of this technique in clinical studies. CONCLUSION: The proposed combination of sequences provides a robust ρ map that can be used to normalize metabolic maps in clinical MRSI studies.
    Mots-clés : crmbm, snc.

  • Lecocq, A, Le Fur, Y, Maudsley, AA, Le Troter, A, Sheriff, S, Sabati, M, Donadieu, M, Confort-Gouny, S, Cozzone, PJ, Guye, M & Ranjeva, J-P 2015, “Whole-brain quantitative mapping of metabolites using short echo three-dimensional proton MRSI”, Journal of magnetic resonance imaging: JMRI, vol. 42, no. 2, p. 280-289.
    Résumé : BACKGROUND: To improve the extent over which whole brain quantitative three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) maps can be obtained and be used to explore brain metabolism in a population of healthy volunteers. METHODS: Two short echo time (20 ms) acquisitions of 3D echo planar spectroscopic imaging at two orientations, one in the anterior commissure-posterior commissure (AC-PC) plane and the second tilted in the AC-PC +15° plane were obtained at 3 Tesla in a group of 10 healthy volunteers. B1 (+) , B1 (-) , and B0 correction procedures and normalization of metabolite signals with quantitative water proton density measurements were performed. A combination of the two spatially normalized 3D-MRSI, using a weighted mean based on the pixel wise standard deviation metabolic maps of each orientation obtained from the whole group, provided metabolite maps for each subject allowing regional metabolic profiles of all parcels of the automated anatomical labeling (AAL) atlas to be obtained. RESULTS: The combined metabolite maps derived from the two acquisitions reduced the regional intersubject variance. The numbers of AAL regions showing N-acetyl aspartate (NAA) SD/Mean ratios lower than 30% increased from 17 in the AC-PC orientation and 41 in the AC-PC+15° orientation, to a value of 76 regions of 116 for the combined NAA maps. Quantitatively, regional differences in absolute metabolite concentrations (mM) over the whole brain were depicted such as in the GM of frontal lobes (cNAA  = 10.03 + 1.71; cCho  = 1.78 ± 0.55; cCr  = 7.29 ± 1.69; cmIns  = 5.30 ± 2.67) and in cerebellum (cNAA  = 5.28 ± 1.77; cCho  = 1.60 ± 0.41; cCr  = 6.95 ± 2.15; cmIns  = 3.60 ± 0.74). CONCLUSION: A double-angulation acquisition enables improved metabolic characterization over a wide volume of the brain. J. Magn. Reson. Imaging 2015;42:280-289.
    Mots-clés : crmbm, snc.

  • Maarouf, A, Ferré, J-C, Zaaraoui, W, Le Troter, A, Bannier, E, Berry, I, Guye, M, Pierot, L, Barillot, C, Pelletier, J, Tourbah, A, Edan, G, Audoin, B & Ranjeva, J-P 2015, “Ultra-small superparamagnetic iron oxide enhancement is associated with higher loss of brain tissue structure in clinically isolated syndrome”, Multiple Sclerosis (Houndmills, Basingstoke, England).
    Résumé : BACKGROUND: Macrophages are important components of inflammatory processes in multiple sclerosis, closely linked to axonal loss, and can now be observed in vivo using ultra-small superparamagnetic iron oxide (USPIO). In the present 1-year longitudinal study, we aimed to determine the prevalence and the impact on tissue injury of macrophage infiltration in patients after the first clinical event of multiple sclerosis. METHODS: Thirty-five patients, 32 years mean age, were imaged in a mean of 66 days after their first event using conventional magnetic resonance imaging, gadolinium (Gd) to probe blood-brain barrier integrity, USPIO to study macrophage infiltration and magnetization transfer ratio (MTR) to assess tissue structure integrity. Statistics were performed using two-group repeated-measures ANOVA. Any patient received treatment at baseline. RESULTS: At baseline, patients showed 17 USPIO-positive lesions reflecting infiltration of macrophages present from the onset. This infiltration was associated with local higher loss of tissue structure as emphasized by significant lower MTRnorm values (p<0.03) in USPIO(+)/Gd(+) lesions (n=16; MTRnormUSPIO(+)/Gd(+)=0.78 at baseline, MTRnormUSPIO(+)/Gd(+)=0.81 at M12) relative to USPIO(-)/Gd(+) lesions (n=67; MTRnormUSPIO(-)/Gd(+)=0.82 at baseline, MTRnormUSPIO(-)/Gd(+)=0.85 at M12). No interaction in MTR values was observed during the 12 months follow-up (lesion type × time). CONCLUSION: Infiltration of activated macrophages evidenced by USPIO enhancement, is present at the onset of multiple sclerosis and is associated with higher and persistent local loss of tissue structure. Macrophage infiltration affects more tissue structure while tissue recovery during the following year has a similar pattern for USPIO and Gd-enhanced lesions, leading to relative higher persistent local loss of tissue structure in lesions showing USPIO enhancement at baseline.

  • Ridley, BGY, Rousseau, C, Wirsich, J, Le Troter, A, Soulier, E, Confort-Gouny, S, Bartolomei, F, Ranjeva, J-P, Achard, S & Guye, M 2015, “Nodal approach reveals differential impact of lateralized focal epilepsies on hub reorganization”, NeuroImage, vol. 118, p. 39-48.
    Résumé : The impact of the hemisphere affected by impairment in models of network disease is not fully understood. Among such models, focal epilepsies are characterised by recurrent seizures generated in epileptogenic areas also responsible for wider network dysfunction between seizures. Previous work focusing on functional connectivity within circumscribed networks suggests a divergence of network integrity and compensatory capacity between epilepsies as a function of the laterality of seizure onset. We evaluated the ability of complex network theory to reveal changes in focal epilepsy in global and nodal parameters using graph theoretical analysis of functional connectivity data obtained with resting-state fMRI. Graphs of functional connectivity networks were derived from 19 right and 13 left focal epilepsy patients and 15 controls. Topological metrics (degree, local efficiency, global efficiency and modularity) were computed for a whole-brain, atlas-defined network. We also calculated a hub disruption index for each graph metric, measuring the capacity of the brain network to demonstrate increased connectivity in some nodes for decreased connectivity in others. Our data demonstrate that the patient group as a whole is characterised by network-wide pattern of reorganization, even while global parameters fail to distinguish between groups. Furthermore, multiple metrics indicate that epilepsies with differently lateralized epileptic networks are asymmetric in their burden on functional brain networks; with left epilepsy patients being characterised by reduced efficiency and modularity, while in right epilepsy patients we provide the first evidence that functional brain networks are characterised by enhanced connectivity and efficiency at some nodes whereas reduced in others.
    Mots-clés : crmbm, Epilepsy, Functional connectivity, graph theory, Hemispheric asymmetry, Network modelling, resting-state, snc.

  • Taso, M, Le Troter, A, Sdika, M, Cohen-Adad, J, Arnoux, P-J, Guye, M, Ranjeva, J-P & Callot, V 2015, “A reliable spatially normalized template of the human spinal cord - Applications to automated white matter/gray matter segmentation and tensor-based morphometry (TBM) mapping of gray matter alterations occurring with age”, NeuroImage, vol. 117, p. 20-28.
    Résumé : Recently, a T2*-weighted template and probabilistic atlas of the white and gray matter (WM, GM) of the spinal cord (SC) have been reported. Such template can be used as tissue-priors for automated WM/GM segmentation but can also provide a common reference and normalized space for group studies. Here, a new template has been created (AMU40), and accuracy of automatic template-based WM/GM segmentation was quantified. The feasibility of tensor-based morphometry (TBM) for studying voxel-wise morphological differences of SC between young and elderly healthy volunteers was also investigated. Sixty-five healthy subjects were divided into young (n=40, age<40years old, mean age 28±5years old) and elderly (n=25, age>50years old, mean age 57±5years old) groups and scanned at 3T using an axial high-resolution T2*-weighted sequence. Inhomogeneity correction and affine intensity normalization of the SC and cerebrospinal fluid (CSF) signal intensities across slices were performed prior to both construction of the AMU40 template and WM/GM template-based segmentation. The segmentation was achieved using non-linear spatial normalization of T2*-w MR images to the AMU40 template. Validation of WM/GM segmentations was performed with a leave-one-out procedure by calculating DICE similarity coefficients between manual and automated WM/GM masks. SC morphological differences between young and elderly healthy volunteers were assessed using the same non-linear spatial normalization of the subjects' MRI to a common template, derivation of the Jacobian determinant maps from the warping fields, and a TBM analysis. Results demonstrated robust WM/GM automated segmentation, with mean DICE values greater than 0.8. Concerning the TBM analysis, an anterior GM atrophy was highlighted in elderly volunteers, demonstrating thereby, for the first time, the feasibility of studying local structural alterations in the SC using tensor-based morphometry. This holds great promise for studies of morphological impairment occurring in several central nervous system pathologies.
    Mots-clés : crmbm, snc.

  • Varoquaux, A, le Fur, Y, Imperiale, A, Reyre, A, Montava, M, Fakhry, N, Namer, I-J, Moulin, G, Pacak, K, Guye, M & Taïeb, D 2015, “Magnetic resonance spectroscopy of paragangliomas: new insights into in vivo metabolomics”, Endocrine-Related Cancer, vol. 22, no. 4, p. M1-8.
    Résumé : Paragangliomas (PGLs) can be associated with mutations in genes of the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase (SDHx) mutations are the prime examples of genetically determined TCA cycle defects with accumulation of succinate. Succinate, which acts as an oncometabolite, can be detected by ex vivo metabolomics approaches. The aim of this study was to evaluate the potential role of proton magnetic resonance (MR) spectroscopy ((1)H-MRS) for identifying SDHx-related PGLs in vivo and noninvasively. Eight patients were prospectively evaluated with single voxel (1)H-MRS. MR spectra from eight tumors (four SDHx-related PGLs, two sporadic PGLs, one cervical schwannoma, and one cervical neurofibroma) were acquired and interpreted qualitatively. Compared to other tumors, a succinate resonance peak was detected only in SDHx-related tumor patients. Spectra quality was considered good in three cases, medium in two cases, poor in two cases, and uninterpretable in the latter case. Smaller lesions had lower spectra quality compared to larger lesions. Jugular PGLs also exhibited a poorer spectra quality compared to other locations. (1)H-MRS has always been challenging in terms of its technical requisites. This is even more true for the evaluation of head and neck tumors. However, (1)H-MRS might be added to the classical MR sequences for metabolomic characterization of PGLs. In vivo detection of succinate might guide genetic testing, characterize SDHx variants of unknown significance (in the absence of available tumor sample), and even optimize a selection of appropriate therapies.
    Mots-clés : Adult, Aged, Female, Humans, Male, Metabolomics, Middle Aged, MR-spectroscopy, Paraganglioma, Positron-Emission Tomography, Proton Magnetic Resonance Spectroscopy, snc, Succinate Dehydrogenase, Tumor Burden.

  • Wegrzyk, J, Fouré, A, Le Fur, Y, Maffiuletti, NA, Vilmen, C, Guye, M, Mattei, J-P, Place, N, Bendahan, D & Gondin, J 2015, “Responders to Wide-Pulse, High-Frequency Neuromuscular Electrical Stimulation Show Reduced Metabolic Demand: A 31P-MRS Study in Humans”, PloS One, vol. 10, no. 11, p. e0143972.
    Résumé : Conventional (CONV) neuromuscular electrical stimulation (NMES) (i.e., short pulse duration, low frequencies) induces a higher energetic response as compared to voluntary contractions (VOL). In contrast, wide-pulse, high-frequency (WPHF) NMES might elicit-at least in some subjects (i.e., responders)-a different motor unit recruitment compared to CONV that resembles the physiological muscle activation pattern of VOL. We therefore hypothesized that for these responder subjects, the metabolic demand of WPHF would be lower than CONV and comparable to VOL. 18 healthy subjects performed isometric plantar flexions at 10% of their maximal voluntary contraction force for CONV (25 Hz, 0.05 ms), WPHF (100 Hz, 1 ms) and VOL protocols. For each protocol, force time integral (FTI) was quantified and subjects were classified as responders and non-responders to WPHF based on k-means clustering analysis. Furthermore, a fatigue index based on FTI loss at the end of each protocol compared with the beginning of the protocol was calculated. Phosphocreatine depletion (ΔPCr) was assessed using 31P magnetic resonance spectroscopy. Responders developed four times higher FTI's during WPHF (99 ± 37 ×103 N.s) than non-responders (26 ± 12 ×103 N.s). For both responders and non-responders, CONV was metabolically more demanding than VOL when ΔPCr was expressed relative to the FTI. Only for the responder group, the ∆PCr/FTI ratio of WPHF (0.74 ± 0.19 M/N.s) was significantly lower compared to CONV (1.48 ± 0.46 M/N.s) but similar to VOL (0.65 ± 0.21 M/N.s). Moreover, the fatigue index was not different between WPHF (-16%) and CONV (-25%) for the responders. WPHF could therefore be considered as the less demanding NMES modality-at least in this subgroup of subjects-by possibly exhibiting a muscle activation pattern similar to VOL contractions.
    Mots-clés : crmbm, msk.

2014

Journal Article


  • Gour, N, Felician, O, Didic, M, Koric, L, Gueriot, C, Chanoine, V, Confort-Gouny, S, Guye, M, Ceccaldi, M & Ranjeva, JP 2014, “Functional connectivity changes differ in early and late-onset alzheimer's disease”, Human Brain Mapping, vol. 35, no. 7, p. 2978-2994, viewed 29October,2014, .
    Résumé : At a similar stage, patients with early onset Alzheimer's disease (EOAD) have greater neocortical but less medial temporal lobe dysfunction and atrophy than the late-onset form of the disease (LOAD). Whether the organization of neural networks also differs has never been investigated. This study aims at characterizing basal functional connectivity (FC) patterns of EOAD and LOAD in two groups of 14 patients matched for disease duration and severity, relative to age-matched controls. All subjects underwent an extensive neuropsychological assessment. Magnetic resonance imaging was used to quantify atrophy and resting-state FC focusing on : the default mode network (DMN), found impaired in earlier studies on AD, and the anterior temporal network (ATN) and dorso-lateral prefrontal network (DLPFN), respectively involved in declarative memory and executive functions. Patterns of atrophy and cognitive impairment in EOAD and LOAD were in accordance with previous reports. FC within the DMN was similarly decreased in both EOAD and LOAD relative to controls. However, a double-dissociated pattern of FC changes in ATN and DLPFN was found. EOAD exhibited decreased FC in the DLPFN and increased FC in the ATN relative to controls, while the reverse pattern was found in LOAD. In addition, ATN and DLPFN connectivity correlated respectively with memory and executive performances, suggesting that increased FC is here likely to reflect compensatory mechanisms. Thus, large-scale neural network changes in EOAD and LOAD endorse both common features and differences, probably related to a distinct distribution of pathological changes. Hum Brain Mapp 35:2978–2994, 2014. © 2013 Wiley Periodicals, Inc.
    Mots-clés : Age of Onset, Aged, Alzheimer Disease, Atrophy, Brain Mapping, Case-Control Studies, Cerebral Cortex, crmbm, early onset Alzheimer disease, Executive Function, Female, Humans, Image Processing, Computer-Assisted, late onset Alzheimer disease, Magnetic Resonance Imaging, Male, Memory, Mental Status Schedule, Middle Aged, Models, Neurological, Nerve Net, neural networks, Neuropsychological Tests, Oxygen, Statistics as Topic.


  • Grapperon, A-M, Verschueren, A, Duclos, Y, Confort-Gouny, S, Soulier, E, Loundou, AD, Guye, M, Cozzone, PJ, Pouget, J, Ranjeva, J-P & Attarian, S 2014, “Association between structural and functional corticospinal involvement in amyotrophic lateral sclerosis assessed by diffusion tensor MRI and triple stimulation technique”, Muscle & Nerve, vol. 49, no. 4, p. 551-557, viewed 29October,2014, .
    Résumé : Introduction: We investigated the functional and structural integrity of the corticospinal tract (CST) using diffusion tensor imaging (DTI) and the triple stimulation technique (TST) in patients with amyotrophic lateral sclerosis (ALS). Methods: Fourteen patients with ALS, 13 healthy controls (HCs), and 6 patients with lower motor neuron (LMN) syndrome underwent DTI and TST. Results: The mean diffusivity was higher in ALS patients than HCs (P < 0.01). The TST ratio was lower in ALS patients compared with HCs (P < 0.001) and in LMN patients compared with HCs (P < 0.05). The increase in the mean diffusivity was correlated with the decrease in the TST ratio (P < 0.01). Conclusions: Significant correlations exist between the DTI and TST results, indicating both structural and functional involvement of the CST in patients with ALS. Muscle Nerve 49:551–557, 2014
    Mots-clés : Adult, Aged, Amyotrophic Lateral Sclerosis, brain MRI, Diffusion Magnetic Resonance Imaging, diffusion tensor imaging, Female, Humans, Male, Middle Aged, Pyramidal Tracts, Transcranial Magnetic Stimulation, triple stimulation technique.


  • Maarouf, A, Audoin, B, Konstandin, S, Rico, A, Soulier, E, Reuter, F, Troter, AL, Confort-Gouny, S, Cozzone, PJ, Guye, M, Schad, LR, Pelletier, J, Ranjeva, J-P & Zaaraoui, W 2014, “Topography of brain sodium accumulation in progressive multiple sclerosis”, Magnetic Resonance Materials in Physics, Biology and Medicine, vol. 27, no. 1, p. 53-62, viewed 30October,2014, .
    Résumé : Object Sodium accumulation is involved in neuronal injury occurring in multiple sclerosis (MS). We aimed to assess sodium accumulation in progressive MS, known to suffer from severe neuronal injury. Materials and methods 3D-23Na-MRI was obtained on a 3T-MR-scanner in 20 progressive MS patients [11 primary-progressive (PPMS) and nine secondary-progressive (SPMS)] and 15 controls. Total sodium concentrations (TSC) within grey matter (GM), normal-appearing white matter (WM) and lesions were extracted. Statistical mapping analyses of TSC abnormalities were also performed. Results Progressive MS patients presented higher GM–TSC values (48.8 ± 3.1 mmol/l wet tissue vol, p < 0.001) and T2lesions-TSC values (50.9 ± 2.2 mmol/l wet tissue vol, p = 0.01) compared to GM and WM of controls. Statistical mapping analysis showed TSC increases in PPMS patients confined to motor and somatosensory cortices, prefrontal cortices, pons and cerebellum. In SPMS, TSC increases were associated with areas involving: primary motor, premotor and somatosensory cortices; prefrontal, cingulate and visual cortices; the corpus callosum, thalami, brainstem and cerebellum. Anterior prefrontal and premotor cortices TSC were correlated with disability. Conclusion Sodium accumulation is present in progressive MS patients, more restricted to the motor system in PPMS and more widespread in SPMS. Local brain sodium accumulation appears as a promising marker to monitor patients with progressive MS.
    Mots-clés : Adult, Aged, Biomedical Engineering, Brain, Brain Mapping, Case-Control Studies, Computer Appl. in Life Sciences, crmbm, Disability, Female, Grey matter, Health Informatics, Humans, Imaging / Radiology, Magnetic Resonance Imaging, Male, Middle Aged, MRI, Multiple sclerosis, Nerve Fibers, Myelinated, Neurons, Progressive multiple sclerosis, Sodium, Solid State Physics.

  • Pedreira, C, Vaudano, AE, Thornton, RC, Chaudhary, UJ, Vulliemoz, S, Laufs, H, Rodionov, R, Carmichael, DW, Lhatoo, SD, Guye, M, Quian Quiroga, R & Lemieux, L 2014, “Classification of EEG abnormalities in partial epilepsy with simultaneous EEG-fMRI recordings”, NeuroImage, vol. 99, p. 461-476.
    Résumé : Scalp EEG recordings and the classification of interictal epileptiform discharges (IED) in patients with epilepsy provide valuable information about the epileptogenic network, particularly by defining the boundaries of the "irritative zone" (IZ), and hence are helpful during pre-surgical evaluation of patients with severe refractory epilepsies. The current detection and classification of epileptiform signals essentially rely on expert observers. This is a very time-consuming procedure, which also leads to inter-observer variability. Here, we propose a novel approach to automatically classify epileptic activity and show how this method provides critical and reliable information related to the IZ localization beyond the one provided by previous approaches. We applied Wave_clus, an automatic spike sorting algorithm, for the classification of IED visually identified from pre-surgical simultaneous Electroencephalogram-functional Magnetic Resonance Imagining (EEG-fMRI) recordings in 8 patients affected by refractory partial epilepsy candidate for surgery. For each patient, two fMRI analyses were performed: one based on the visual classification and one based on the algorithmic sorting. This novel approach successfully identified a total of 29 IED classes (compared to 26 for visual identification). The general concordance between methods was good, providing a full match of EEG patterns in 2 cases, additional EEG information in 2 other cases and, in general, covering EEG patterns of the same areas as expert classification in 7 of the 8 cases. Most notably, evaluation of the method with EEG-fMRI data analysis showed hemodynamic maps related to the majority of IED classes representing improved performance than the visual IED classification-based analysis (72% versus 50%). Furthermore, the IED-related BOLD changes revealed by using the algorithm were localized within the presumed IZ for a larger number of IED classes (9) in a greater number of patients than the expert classification (7 and 5, respectively). In contrast, in only one case presented the new algorithm resulted in fewer classes and activation areas. We propose that the use of automated spike sorting algorithms to classify IED provides an efficient tool for mapping IED-related fMRI changes and increases the EEG-fMRI clinical value for the pre-surgical assessment of patients with severe epilepsy.

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


  • Wirsich, J, Bénar, C, Ranjeva, J-P, Descoins, M, Soulier, E, Le Troter, A, Confort-Gouny, S, Liégeois-Chauvel, C & Guye, M 2014, “Single-trial EEG-informed fMRI reveals spatial dependency of BOLD signal on early and late IC-ERP amplitudes during face recognition”, NeuroImage, vol. 100, p. 325-336, viewed 4August,2014, .
    Résumé : Simultaneous EEG-fMRI has opened up new avenues for improving the spatio-temporal resolution of functional brain studies. However, this method usually suffers from poor EEG quality, especially for evoked potentials (ERPs), due to specific artifacts. As such, the use of EEG-informed fMRI analysis in the context of cognitive studies has particularly focused on optimizing narrow ERP time windows of interest, which ignores the rich diverse temporal information of the EEG signal. Here, we propose to use simultaneous EEG-fMRI to investigate the neural cascade occurring during face recognition in 14 healthy volunteers by using the successive ERP peaks recorded during the cognitive part of this process. N170, N400 and P600 peaks, commonly associated with face recognition, were successfully and reproducibly identified for each trial and each subject by using a group independent component analysis (ICA). For the first time we use this group ICA to extract several independent components (IC) corresponding to the sequence of activation and used single-trial peaks as modulation parameters in a general linear model (GLM) of fMRI data. We obtained an occipital–temporal–frontal stream of BOLD signal modulation, in accordance with the three successive IC-ERPs providing an unprecedented spatio-temporal characterization of the whole cognitive process as defined by BOLD signal modulation. By using this approach, the pattern of EEG-informed BOLD modulation provided improved characterization of the network involved than the fMRI-only analysis or the source reconstruction of the three ERPs; the latter techniques showing only two regions in common localized in the occipital lobe.
    Mots-clés : crmbm, Evoked Potentials, Face recognition, ICA, Simultaneous EEG-fMRI, Ventral visual pathway.

2013

Journal Article

  • Bartolomei, F, Bettus, G, Stam, CJ & Guye, M 2013, “Interictal network properties in mesial temporal lobe epilepsy: A graph theoretical study from intracerebral recordings”, Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology, vol. 124, no. 12, p. 2345-2353.
    Résumé : OBJECTIVE: Graph theoretical analysis of functional connectivity data has demonstrated a small-world topology of brain networks. There is increasing evidence that the topology of brain networks is changed in epilepsy. Here we investigated the basal properties of epileptogenic networks by applying graph analysis to intracerebral EEG recordings of patients presenting with drug-resistant partial epilepsies during the interictal period. METHODS: Interictal EEG activity was recorded in mesial temporal lobe of 11 patients with mesial temporal lobe epilepsy (MTLE group) and compared with a "control" group of 8 patients having neocortical epilepsies (non MTLE group) in whom depth-EEG recordings eventually showed an ictal onset outside the MTL structures. Synchronization likelihood (SL) was calculated between selected intracerebral electrodes contacts to obtain SL-weighted graphs. Mean normalized clustering index, average path length and small world index S were calculated to characterize network organization. RESULTS: Broadband SL values were higher in the MTLE group. Although a small-world pattern was found in the two groups, normalized clustering index and to a lesser extend average path length were higher in the MTLE group. CONCLUSIONS: We demonstrated a trend toward a more regular (less random) configuration of interictal epileptogenic networks. In addition S index was found to correlate with epilepsy duration. SIGNIFICANCE: These topological alterations might be a surrogate marker of human focal epilepsy and disclose some changes over time.


  • Faget-Agius, C, Boyer, L, Lançon, C, Richieri, R, Fassio, E, Soulier, E, Chanoine, V, Auquier, P, Ranjeva, JP & Guye, M 2013, “Structural and functional reorganization of working memory system during the first decade in schizophrenia. A cross-sectional study”, Schizophrenia Research, vol. 151, no. 1, p. 48-60, viewed 29October,2014, .
    Résumé : Introduction Progressive atrophy occurs in brain regions involved in the working memory network along the schizophrenia's course, but without parallel evolution of working memory impairment. We investigated the functional organization inside this network at different stages of the disease. Methods Twenty-eight patients with schizophrenia (16 with long disease duration (>60 months) and 12 with short disease duration (<60 months)) and eleven healthy controls underwent structural and functional MRI during an n-back task to determine atrophy and activation patterns. Results At similar n-back performances and relative to short disease duration patients, long disease duration patients activated more frontal temporal parietal and frontal network during 0-back and 1-back tasks respectively. n-back scores were correlated to atrophy in the frontal–temporal areas. Discussion Functional reorganization in the working memory network may play a compensatory role during the first ten years of schizophrenia.
    Mots-clés : crmbm, Disease duration, Functional MRI, Schizophrenia, snc, Working memory.

  • Koric, L, Ranjeva, J-P, Felician, O, Guye, M, de Anna, F, Soulier, E, Didic, M & Ceccaldi, M 2013, “Cued recall measure predicts the progression of gray matter atrophy in patients with amnesic mild cognitive impairment”, Dementia and geriatric cognitive disorders, vol. 36, no. 3-4, p. 197-210.
    Résumé : Amnesic mild cognitive impairment (aMCI) is a heterogeneous syndrome that could be subdivided into distinct neuropsychological variants. To investigate relationships between the neuropsychological profile of memory impairment at baseline and the neuroimaging pattern of grey matter (GM) loss over 18 months, we performed a prospective volumetric brain study on 31 aMCI patients and 29 matched controls. All subjects were tested at baseline using a standardized neuropsychological battery, which included the Free and Cued Selective Recall Reminding Test (FCSRT) for the assessment of verbal declarative memory. Over 18 months, patients with impaired free recall but normal total recall (high index of cueing) on the FCSRT developed subcortical and frontal GM loss, while patients with impaired free and total recall (low index of cueing) developed GM atrophy within the left anterior and lateral temporal lobe. In summary, cued recall deficits are associated with a progression of atrophy that closely parallels the spatiotemporal distribution of neurofibrillary degeneration in early Alzheimer's disease (AD), indicating possible AD pathological changes.
    Mots-clés : crmbm.

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