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RANJEVA Jean-Philippe

Professor of Neurosciences (CNU 69)

Aix Marseille Université
Medical School of Marseille, Neurosciences, Biophysics

Head of the group: ’ Human CNS ’
PI of the 7T-AMISTART project (AMIDEX)

jean-philippe.ranjeva@univ-amu.fr
tel : +33 4 91 38 84 63

Key Words
- MR exploration of Human CNS at High field (1.5T, 3T) and Ultra High Field (7T)
- MR Imaging, MR Spectroscopy, fMRI, X-nucleus MRI
- Brain Image Analysis
- Structural and functional brain connectivity
- Multiple Sclerosis, Epilepsy, Alzheimer’s disease, Schizophrenia
- EEG/fMRI, rTMS, neuronavigation
- Cognition (working memory, executive function)

Current Research Interest and projects

Using MRI/MRS/fMRI techniques but also electrophysiology, neuropsychology and clinical evaluation, we aim at characterizing the physiopathology and the morpho-functional underpinnings of neurological and psychiatric diseases.

We develop and adapt new MR methods allowing to assess one relevant problem relative to precise clinical or fundamental questions.

The main projects are focussed on the study of Multiple Sclerosis, Epilepsy, spinal cord damage, Alzheimer’s disease and Schizophrenia. These projects are conducted in close collaboration with the clinical departments specialized in each of the pathologies studied.

The activity is located mainly on the clinical site of the lab (CEMEREM) equiped with 3 MR scanners (Siemens Verio 3T, Avanto 1.5T and Siemens 7T step 2), EEG/fMRI facilities, rTMS and neuronavigation.

The CNS chapter of the 7T-AMISTART project aims at developing and validating new parameters acquired on the new whole body 7T MR scanner (Siemens Step 2) to characterize the normal and pathological Human CNS (Brain and spinal cord) to improve diagnosis, prognosis and non invasive characterization of physiopathological processes accompanying neurological diseases.

Publications

2017

Journal Article

  • ALBI A., PASTERNAK O., MINATI L., MARIZZONI M., BARTRES-FAZ D., BARGALLO N., BOSCH B., ROSSINI P. M., MARRA C., MUELLER B., FIEDLER U., WILTFANG J., ROCCATAGLIATA L., PICCO A., NOBILI F. M., BLIN O., SEIN J., RANJEVA J. - P., DIDIC M., BOMBOIS S., LOPES R., BORDET R., GROS-DAGNAC H., PAYOUX P., ZOCCATELLI G., ALESSANDRINI F., BELTRAMELLO A., FERRETTI A., CAULO M., AIELLO M., CAVALIERE C., SORICELLI A., PARNETTI L., TARDUCCI R., FLORIDI P., TSOLAKI M., CONSTANTINIDIS M., DREVELEGAS A., FRISONI G., JOVICICH J. “Free water elimination improves test-retest reproducibility of diffusion tensor imaging indices in the brain: A longitudinal multisite study of healthy elderly subjects.”. Human Brain Mapping [En ligne]. 2017. Vol. 38, n°1, p. 12-26. Disponible sur : < http://dx.doi.org/10.1002/hbm.23350 > (consulté le no date)
    Résumé : Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test-retest reproducibility. This study compares a bi-tensor model for FWE with DTI by extending a previous longitudinal-reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55-80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white-matter regions of the JHU-ICBM-DTI-81 white-matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12-26, 2017. (c) 2016 Wiley Periodicals, Inc.
    Mots-clés : alzheimers-disease, brain diffusion tensor imaging, cerebral white-matter, false discovery rate, free-water imaging, healthy elderly, longitudinal, MRI, multisite diffusion MRI, parkinsons-disease, reliability, Schizophrenia, spatial statistics, substantia-nigra, test-retest reproducibility, tracking.

  • AZIZ A. - L., GIUSIANO B., JOUBERT S., DUPRAT L., DIDIC M., GUERIOT C., KORIC L., BOUCRAUT J., FELICIAN O., RANJEVA J. - P., GUEDJ E., CECCALDI M. “Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease.”. Neurobiology of Aging [En ligne]. 2017. Vol. 54, p. 22-30. Disponible sur : < http://dx.doi.org/10.1016/j.neurobiolaging.2017.02.010 > (consulté le no date)
    Résumé : Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions.
    Mots-clés : Age of Onset, Alzheimer's disease, Magnetic Resonance Imaging, Neuroimaging biomarkers, Positron emission tomography imaging.

  • BYDDER M., RAPACCHI S., GIRARD O., GUYE M., RANJEVA J. - P. “Trimmed autocalibrating k-space estimation based on structured matrix completion.”. Magnetic Resonance Imaging [En ligne]. 2017. Vol. 43, p. 88-94. Disponible sur : < http://dx.doi.org/10.1016/j.mri.2017.07.015 > (consulté le no date)
    Résumé : PURPOSE: Parallel imaging allows the reconstruction of undersampled data from multiple coils. This provides a means to reject and regenerate corrupt data (e.g. from motion artefact). The purpose of this work is to approach this problem using the SAKE parallel imaging method. THEORY AND METHODS: Parallel imaging methods typically require calibration by fully sampling the center of k-space. This is a challenge in the presence of corrupted data, since the calibration data may be corrupted which leads to an errors-in-variables problem that cannot be solved by least squares or even iteratively reweighted least squares. The SAKE method, based on matrix completion and structured low rank approximation, was modified to detect and trim these errors from the data. RESULTS: Simulated and actual corrupted datasets were reconstructed with SAKE, the proposed approach and a more standard reconstruction method (based on solving a linear equation) with a data rejection criterion. The proposed approach was found to reduce artefacts considerably in comparison to the other two methods. CONCLUSION: SAKE with data trimming improves on previous methods for reconstructing images from grossly corrupted data.
    Mots-clés : Artefacts, crmbm, IRLS, Parallel imaging, Robust, Structured low rank approximation.


  • 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. “Increased total sodium concentration in gray matter better explains cognition than atrophy in MS.”. Neurology [En ligne]. 2017. Vol. 88, n°3, p. 289-295. Disponible sur : < http://dx.doi.org/10.1212/WNL.0000000000003511 >
    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.

  • RIDLEY B., MARCHI A., WIRSICH J., SOULIER E., CONFORT-GOUNY S., SCHAD L., BARTOLOMEI F., RANJEVA J. - P., GUYE M., ZAARAOUI W. “Brain sodium MRI in human epilepsy: Disturbances of ionic homeostasis reflect the organization of pathological regions.”. NeuroImage [En ligne]. 2017. Vol. 157, p. 173-183. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2017.06.011 > (consulté le no date)
    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, 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. “Simultaneous Intracranial EEG-fMRI Shows Inter-Modality Correlation in Time-Resolved Connectivity Within Normal Areas but Not Within Epileptic Regions.”. Brain Topography [En ligne]. 2017. Disponible sur : < http://dx.doi.org/10.1007/s10548-017-0551-5 > (consulté le no date)
    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.
    Mots-clés : connectivity, crmbm, Dynamic connectivity, Focal epilepsy, Multimodal imaging, Resting-state.

2016

Journal Article

  • 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. “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) [En ligne]. 2016. Disponible sur : < http://dx.doi.org/10.1177/1352458516661640 > (consulté le no date)
    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.
    Mots-clés : connectivity, crmbm, intermittent theta burst stimulation, Multiple Sclerosis, primary motor cortex, resting state fMRI, spasticity.

  • 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. “Hypoperfusion of the thalamus is associated with disability in relapsing remitting multiple sclerosis.”. Journal of Neuroradiology. Journal De Neuroradiologie [En ligne]. 2016. Disponible sur : < http://dx.doi.org/10.1016/j.neurad.2016.10.001 > (consulté le no date)
    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.
    Mots-clés : Atrophy, crmbm, Disability, Multiple Sclerosis, perfusion, Pseudo-continuous arterial spin labeling, Thalamus.

  • DONADIEU M., LE FUR Y., CONFORT-GOUNY S., LE TROTER A., GUYE M., RANJEVA J. - P. “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.) [En ligne]. 2016. Disponible sur : < http://dx.doi.org/10.1007/s10334-016-0556-1 > (consulté le no date)
    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, Connectivity atlas, crmbm, Neurochemical profiles, Thalamic nuclei, Ultra high field.

  • DONADIEU M., LE FUR Y., LECOCQ A., MAUDSLEY A. A., GHERIB S., SOULIER E., CONFORT-GOUNY S., PARIOLLAUD F., RANJEVA M. - P., PELLETIER J., GUYE M., ZAARAOUI W., AUDOIN B., RANJEVA J. - P. “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 [En ligne]. 2016. Vol. 44, n°2, p. 411-419. Disponible sur : < http://dx.doi.org/10.1002/jmri.25139 > (consulté le no date)
    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.
    Mots-clés : crmbm, Inflammation, Multiple Sclerosis, neurodegeneration, proton magnetic resonance spectroscopic imaging, statistical mapping analysis, whole brain.

  • 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. “Depletion of brain functional connectivity enhancement leads to disability progression in multiple sclerosis: A longitudinal resting-state fMRI study.”. Multiple Sclerosis (Houndmills, Basingstoke, England) [En ligne]. 2016. Vol. 22, n°13, p. 1695-1708. Disponible sur : < http://dx.doi.org/10.1177/1352458516628657 > (consulté le no date)
    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.
    Mots-clés : crmbm, Disability, Functional connectivity, Functional MRI, Graph theory, Multiple Sclerosis.

  • JOVICICH J., MINATI L., MARIZZONI M., MARCHITELLI R., SALA-LLONCH R., BARTRES-FAZ D., ARNOLD J., BENNINGHOFF J., FIEDLER U., ROCCATAGLIATA L., PICCO A., NOBILI F., BLIN O., BOMBOIS S., LOPES R., BORDET R., SEIN J., RANJEVA J. - P., DIDIC M., GROS-DAGNAC H., PAYOUX P., ZOCCATELLI G., ALESSANDRINI F., BELTRAMELLO A., BARGALLO N., FERRETTI A., CAULO M., AIELLO M., CAVALIERE C., SORICELLI A., PARNETTI L., TARDUCCI R., FLORIDI P., TSOLAKI M., CONSTANTINIDIS M., DREVELEGAS A., ROSSINI P. M., MARRA C., SCHOENKNECHT P., HENSCH T., HOFFMANN K. - T., KUIJER J. P., VISSER P. J., BARKHOF F., FRISONI G. B. “Longitudinal reproducibility of default-mode network connectivity in healthy elderly participants: A multicentric resting-state fMRI study.”. Neuroimage [En ligne]. 2016. Vol. 124, p. 442-454. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2015.07.010 > (consulté le no date)
    Résumé : To date, limited data are available regarding the inter-site consistency of test-retest reproducibility of functional connectivity measurements, in particular with regard to integrity of the Default Mode Network (DMN) in elderly participants. We implemented a harmonized resting-state fMRI protocol on 13 clinical scanners at 3.0 T using vendor-provided sequences. Each site scanned a group of 5 healthy elderly participants twice, at least a week apart. We evaluated inter-site differences and test-retest reproducibility of both temporal signal-to-noise ratio (tSNR) and functional connectivity measurements derived from: i) seed-based analysis (SBA) with seed in the posterior cingulate cortex (PCC), ii) group independent component analysis (ICA) separately for each site (site ICA), and iii) consortium ICA, with group ICA across the whole consortium. Despite protocol harmonization, significant and quantitatively important inter-site differences remained in the tSNR of resting-state fMRI data; these were plausibly driven by hardware and pulse sequence differences across scanners which could not be harmonized. Nevertheless, the tSNR test-retest reproducibility in the consortium was high (ICC = 0.81). The DMN was consistently extracted across all sites and analysis methods. While significant inter-site differences in connectivity scores were found, there were no differences in the associated test-retest error. Overall, ICA measurements were more reliable than PCC-SBA, with site ICA showing higher reproducibility than consortium ICA. Across the DMN nodes, the PCC yielded the most reliable measurements (approximate to 4% test-retest error, ICC = 0.85), the medial frontal cortex the least reliable (approximate to 12%, ICC = 0.82) and the lateral parietal cortices were in between (site ICA). Altogether these findings support usage of harmonized multisite studies of resting-state functional connectivity to characterize longitudinal effects in studies that assess disease progression and treatment response. (C) 2015 Elsevier Inc. All rights reserved.
    Mots-clés : clinical-applications, connectomics, Default Mode Network, disease, Functional connectivity, Functional MRI, human brain, independent component analysis, Multi-center, Multi-site MRI, optimization, physiological noise, Reproducibility, signal-to-noise, test-retest reliability.

  • MASSIRE A., TASO M., BESSON P., GUYE M., RANJEVA J. - P., CALLOT V. “High-resolution multi-parametric quantitative magnetic resonance imaging of the human cervical spinal cord at 7T.”. NeuroImage [En ligne]. 2016. Vol. 143, p. 58-69. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2016.08.055 > (consulté le no date)
    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, 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. “Alien Hand, Restless Brain: Salience Network and Interhemispheric Connectivity Disruption Parallel Emergence and Extinction of Diagonistic Dyspraxia.”. Frontiers in Human Neuroscience [En ligne]. 2016. Vol. 10, p. 307. Disponible sur : < http://dx.doi.org/10.3389/fnhum.2016.00307 > (consulté le no date)
    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.

  • TASO M., GIRARD O. M., DUHAMEL G., LE TROTER A., FEIWEIER T., GUYE M., RANJEVA J. - P., CALLOT V. “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 [En ligne]. 2016. Vol. 29, n°6, p. 817-832. Disponible sur : < http://dx.doi.org/10.1002/nbm.3530 > (consulté le no date)
    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, spinal cord.

  • VON GUMBERZ J., MAHMOUDI M., YOUNG K., SCHIPPLING S., MARTIN R., HEESEN C., SIEMONSEN S., STELLMANN J. - P. “Short-term MRI measurements as predictors of EDSS progression in relapsing-remitting multiple sclerosis: grey matter atrophy but not lesions are predictive in a real-life setting.”. PeerJ [En ligne]. 2016. Vol. 4, p. e2442. Disponible sur : < http://dx.doi.org/10.7717/peerj.2442 > (consulté le no date)
    Résumé : BACKGROUND: Magnetic resonance imaging (MRI) is the best biomarker of inflammatory disease activity in relapsing remitting Multiple Sclerosis (RRMS) so far but the association with disability is weak. Appearance of new MRI-lesions is used to evaluate response to immunotherapies in individual patients as well as being the most common primary outcome in phase-2 trials. Measurements of brain atrophy show promising outcomes in natural cohort studies and some phase-2 trials. From a theoretical perspective they might represent irreversible neurodegeneration and be more closely associated with disability. However, these atrophy measurements are not yet established as prognostic factors in real-life clinical routine. High field MRI has improved image quality and resolution and new methods to measure atrophy dynamics have become available. OBJECTIVE: To investigate the predictive value of MRI classification criteria in to high/low atrophy and inflammation groups, and to explore predictive capacity of two consecutive routine MRI scans for disability progression in RRMS in a real-life prospective cohort. METHODS: 82 RRMS-patients (40 untreated, 42 treated with immunotherapies, mean age 40 years, median Expanded Disability Status Scale (EDSS) of 2, underwent two clinically indicated MRI scans (3 Tesla) within 5-14 months, and EDSS assessment after a mean of 3.0 (1.5-4.2) years. We investigated the predictive value of predefined classifications in low/high inflammatory and atrophy groups for EDSS progression (≥1.5 if baseline EDSS = 0, ≥1.0 if baseline EDSS <5, ≥0.5 for other) by chi-square tests and by analysis of variance (ANOVA). The classifications were based on current scientific or clinical recommendation (e.g., treatment response criteria). Brain atrophy was assessed with three different methods (SIENA, SIENAX, and FreeSurfer). Post-hoc analyses aimed to explore clinical data and dynamics of MRI outcomes as predictors in multivariate linear and logit models. RESULTS: Progression was observed in 24% of patients and was independent from treatment status. None of the predefined classifications were predictive for progression. Explorative post-hoc analyses found lower baseline EDSS and higher grey matter atrophy (FreeSurfer) as best predictors (R (2) = 0.29) for EDSS progression and the accuracy was overall good (Area under the curve = 0.81). CONCLUSION: Beside EDSS at baseline, short-term grey matter atrophy is predictive for EDSS progression in treated and untreated RRMS. The development of atrophy measurements for individual risk counselling and evaluation of treatment response seems possible, but needs further validation in larger cohorts. MRI-atrophy estimates from the FreeSurfer toolbox seem to be more reliable than older methods.
    Mots-clés : Atrophy, disability progression, Lesions, MRI, Multiple Sclerosis, Predictors.


  • WIRSICH J., PERRY A., RIDLEY B., PROIX T., GOLOS M., BéNAR C., RANJEVA J. - P., BARTOLOMEI F., BREAKSPEAR M., JIRSA V., GUYE M. “Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy.”. NeuroImage: Clinical [En ligne]. 2016. Vol. 11, p. 707-718. Disponible sur : < http://dx.doi.org/10.1016/j.nicl.2016.05.010 >
    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, structural connectivity, Temporal lobe epilepsy.

2015

Journal Article


  • COMMOWICK O., MAAROUF A., FERRé J. - C., RANJEVA J. - P., EDAN G., BARILLOT C. “Diffusion MRI abnormalities detection with orientation distribution functions: A multiple sclerosis longitudinal study.”. Medical Image Analysis [En ligne]. 2015. Vol. 22, n°1, p. 114-123. Disponible sur : < http://dx.doi.org/10.1016/j.media.2015.02.005 >
    Résumé : We propose a new algorithm for the voxelwise analysis of orientation distribution functions between one image and a group of reference images. It relies on a generic framework for the comparison of diffusion probabilities on the sphere, sampled from the underlying models. We demonstrate that this method, combined to dimensionality reduction through a principal component analysis, allows for more robust detection of lesions on simulated data when compared to classical tensor-based analysis. We then demonstrate the efficiency of this pipeline on the longitudinal comparison of multiple sclerosis patients at an early stage of the disease: right after their first clinically isolated syndrome (CIS) and three months later. We demonstrate the predictive value of ODF-based scores for the early detection of lesions that will appear or heal.
    Mots-clés : Diffusion MRI, Orientation distribution functions, Patient to controls comparison.

  • FAGET-AGIUS C., CATHERINE F. - A., BOYER L., WIRSICH J., JONATHAN W., RANJEVA J. - P., JEAN-PHILIPPE R., RICHIERI R., RAPHAELLE R., SOULIER E., ELISABETH S., CONFORT-GOUNY S., SYLVIANE C. - G., AUQUIER P., PASCAL A., GUYE M., MAXIME G., LANçON C., CHRISTOPHE L. “Neural substrate of quality of life in patients with schizophrenia: a magnetisation transfer imaging study.”. Scientific Reports [En ligne]. 2015. Vol. 5, p. 17650. Disponible sur : < http://dx.doi.org/10.1038/srep17650 > (consulté le no date)
    Résumé : The aim of this study was to investigate the neural substrate underlying quality of life (QoL) and to demonstrate the microstructural abnormalities associated with impaired QoL in a large sample of patients with schizophrenia, using magnetisation transfer imaging. A total of 81 right-handed men with a diagnosis of schizophrenia and 25 age- and sex-similar healthy controls were included and underwent a 3T MRI with magnetization transfer ratio (MTR) to detect microstructural abnormalities. Compared with healthy controls, patients with schizophrenia had grey matter (GM) decreased MTR values in the temporal lobe (BA21, BA37 and BA38), the bilateral insula, the occipital lobe (BA17, BA18 and BA19) and the cerebellum. Patients with impaired QoL had lower GM MTR values relative to patients with preserved QoL in the bilateral temporal pole (BA38), the bilateral insula, the secondary visual cortex (BA18), the vermis and the cerebellum. Significant correlations between MTR values and QoL scores (p < 0.005) were observed in the GM of patients in the right temporal pole (BA38), the bilateral insula, the vermis and the right cerebellum. Our study shows that QoL impairment in patients with schizophrenia is related to the microstructural changes in an extensive network, suggesting that QoL is a bio-psychosocial marker.
    Mots-clés : Adolescent, Adult, Brain, Cerebral Cortex, crmbm, Gray matter, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neurons, Quality of Life, Radiography, Schizophrenia, Surveys and Questionnaires, Temporal Lobe.

  • JOUBERT S., GOUR N., GUEDJ E., DIDIC M., GUÉRIOT C., KORIC L., RANJEVA J. - P., FELICIAN O., GUYE M., CECCALDI M. “Early-onset and late-onset Alzheimer's disease are associated with distinct patterns of memory impairment.”. Cortex; a Journal Devoted to the Study of the Nervous System and Behavior [En ligne]. 2015. Vol. 74, p. 217-232. Disponible sur : < http://dx.doi.org/10.1016/j.cortex.2015.10.014 > (consulté le no date)
    Résumé : The goal of this study was to investigate the specific patterns of memory breakdown in patients suffering from early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Twenty EOAD patients, twenty LOAD patients, twenty matched younger controls, and twenty matched older controls participated in this study. All participants underwent a detailed neuropsychological assessment, an MRI scan, an FDG-PET scan, and AD patients had biomarkers as supporting evidence of both amyloïdopathy and neuronal injury. Results of the neuropsychological assessment showed that both EOAD and LOAD groups were impaired in the domains of memory, executive functions, language, praxis, and visuoconstructional abilities, when compared to their respective control groups. EOAD and LOAD groups, however, showed distinct patterns of memory impairment. Even though both groups were similarly affected on measures of episodic, short term and working memory, in contrast semantic memory was significantly more impaired in LOAD than in EOAD patients. The EOAD group was not more affected than the LOAD group in any memory domain. EOAD patients, however, showed significantly poorer performance in other cognitive domains including executive functions and visuoconstructional abilities. A more detailed analysis of the pattern of semantic memory performance among patient groups revealed that the LOAD was more profoundly impaired, in tasks of both spontaneous recall and semantic recognition. Voxel-Based Morphometry (VBM) analyses showed that impaired semantic performance in patients was associated with reduced gray matter volume in the anterior temporal lobe (ATL) region, while PET-FDG analyses revealed that poorer semantic performance was associated with greater hypometabolism in the left temporoparietal region, both areas reflecting key regions of the semantic network. Results of this study indicate that EOAD and LOAD patients present with distinct patterns of memory impairment, and that a genuine semantic impairment may represent one of the clinical hallmarks of LOAD.
    Mots-clés : Cognition, crmbm, Early-onset Alzheimer's disease, Late-onset Alzheimer's disease, Memory, Neuropsychological Tests, Semantic memory.

  • LECOCQ A., LE FUR Y., AMADON A., VIGNAUD A., COZZONE P. J., GUYE M., RANJEVA J. - P. “Fast water concentration mapping to normalize (1)H MR spectroscopic imaging.”. Magma (New York, N.Y.) [En ligne]. 2015. Vol. 28, n°1, p. 87-100. Disponible sur : < http://dx.doi.org/10.1007/s10334-014-0451-6 > (consulté le no date)
    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.

  • LECOCQ A., LE FUR Y., MAUDSLEY A. A., LE TROTER A., SHERIFF S., SABATI M., DONADIEU M., CONFORT-GOUNY S., COZZONE P. J., GUYE M., RANJEVA J. - P. “Whole-brain quantitative mapping of metabolites using short echo three-dimensional proton MRSI.”. Journal of magnetic resonance imaging: JMRI [En ligne]. 2015. Vol. 42, n°2, p. 280-289. Disponible sur : < http://dx.doi.org/10.1002/jmri.24809 > (consulté le no date)
    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.

  • 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. “Ultra-small superparamagnetic iron oxide enhancement is associated with higher loss of brain tissue structure in clinically isolated syndrome.”. Multiple Sclerosis (Houndmills, Basingstoke, England) [En ligne]. 2015. Disponible sur : < http://dx.doi.org/10.1177/1352458515607649 > (consulté le no date)
    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.
    Mots-clés : clinically isolated syndrome, crmbm, macrophage, MRI, Multiple Sclerosis, USPIO.

  • RIDLEY B. G. Y., ROUSSEAU C., WIRSICH J., LE TROTER A., SOULIER E., CONFORT-GOUNY S., BARTOLOMEI F., RANJEVA J. - P., ACHARD S., GUYE M. “Nodal approach reveals differential impact of lateralized focal epilepsies on hub reorganization.”. NeuroImage [En ligne]. 2015. Vol. 118, p. 39-48. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2015.05.096 > (consulté le no date)
    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.

2014

Journal Article

  • CRIMI A., COMMOWICK O., MAAROUF A., FERRé J. - C., BANNIER E., TOURBAH A., BERRY I., RANJEVA J. - P., EDAN G., BARILLOT C. “Predictive value of imaging markers at multiple sclerosis disease onset based on gadolinium- and USPIO-enhanced MRI and machine learning.”. PloS One [En ligne]. 2014. Vol. 9, n°4, p. e93024. Disponible sur : < http://dx.doi.org/10.1371/journal.pone.0093024 > (consulté le no date)
    Résumé : OBJECTIVES: A novel characterization of Clinically Isolated Syndrome (CIS) patients according to lesion patterns is proposed. More specifically, patients are classified according to the nature of inflammatory lesions patterns. It is expected that this characterization can infer new prospective figures from the earliest imaging signs of Multiple Sclerosis (MS), since it can provide a classification of different types of lesions across patients. METHODS: The method is based on a two-tiered classification. Initially, the spatio-temporal lesion patterns are classified. The discovered lesion patterns are then used to characterize groups of patients. The patient groups are validated using statistical measures and by correlations at 24-month follow-up with hypointense lesion loads. RESULTS: The methodology identified 3 statistically significantly different clusters of lesion patterns showing p-values smaller than 0.01. Moreover, these patterns defined at baseline correlated with chronic hypointense lesion volumes by follow-up with an R(2) score of 0.90. CONCLUSIONS: The proposed methodology is capable of identifying three major different lesion patterns that are heterogeneously present in patients, allowing a patient classification using only two MRI scans. This finding may lead to more accurate prognosis and thus to more suitable treatments at early stage of MS.

  • FRADET L., ARNOUX P. - J., RANJEVA J. - P., PETIT Y., CALLOT V. “Morphometrics of the entire human spinal cord and spinal canal measured from in vivo high-resolution anatomical magnetic resonance imaging.”. Spine [En ligne]. 2014. Vol. 39, n°4, p. E262-269. Disponible sur : < http://dx.doi.org/10.1097/BRS.0000000000000125 > (consulté le no date)
    Résumé : STUDY DESIGN: Measurements of cervical and thoracolumbar human spinal cord (SC) geometry based on in vivo magnetic resonance imaging and investigation of morphological "invariants." OBJECTIVE: The current work aims at providing morphological features of the complete in vivo human normal SC and at investigating possible "invariant" parameters that may serve as normative data for individualized study of SC injuries. SUMMARY OF BACKGROUND DATA: Few in vivo magnetic resonance image-based studies have described human SC morphology at the cervical level, and similar description of the entire SC only relies on postmortem studies, which may be prone to atrophy biases. Moreover, large interindividual variations currently limit the use of morphological metrics as reference for clinical applications or as modeling inputs. METHODS: Absolute metrics of SC (transverse and anteroposterior diameters, width of anterior and posterior horns, cross-sectional SC area, and white matter percentage) were measured using semiautomatic segmentation of high resolution in vivo T2*-weighted transverse images acquired at 3 T, at each SC level, on healthy young (N = 15) and older (N = 8) volunteers. Robustness of measurements, effects of subject, age, or sex, as well as comparison with previously published postmortem data were investigated using statistical analyses (separate analysis of variance, Tukey-HSD, Bland-Altman). Normalized-to-C3 parameters were evaluated as invariants using a leave-one-out analysis. Spinal canal parameters were measured and occupation ratio border values were determined. RESULTS: Metrics of SC morphology showed large intra- and interindividual variations, up to 30% and 13%, respectively, on average. Sex had no influence except on posterior horn width (P < 0.01). Age-related differences were observed for anteroposterior diameter and white matter percentage (P < 0.05) and all postmortem metrics were significantly lower than in vivo values (P < 0.001). In vivo normalized SC area and diameters seemed to be invariants (R > 0.74, root-mean-square deviation < 10%). Finally, minimal and maximal occupation ratio were 0.2 and 0.6, respectively. CONCLUSION: This study presented morphological characteristics of the complete in vivo human SC. Significant differences linked to age and postmortem state have been identified. Morphological "invariants" that could be used to calculate the normally expected morphology accurately, were also identified. These observations should benefit to biomechanical and SC pathology studies. LEVEL OF EVIDENCE: N/A.
    Mots-clés : crmbm.


  • GOUR N., FELICIAN O., DIDIC M., KORIC L., GUERIOT C., CHANOINE V., CONFORT-GOUNY S., GUYE M., CECCALDI M., RANJEVA J. P. “Functional connectivity changes differ in early and late-onset alzheimer's disease.”. Human Brain Mapping [En ligne]. 2014. Vol. 35, n°7, p. 2978-2994. Disponible sur : < http://dx.doi.org/10.1002/hbm.22379 >
    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 A. D., GUYE M., COZZONE P. J., POUGET J., RANJEVA J. - P., ATTARIAN S. “Association between structural and functional corticospinal involvement in amyotrophic lateral sclerosis assessed by diffusion tensor MRI and triple stimulation technique.”. Muscle & Nerve [En ligne]. 2014. Vol. 49, n°4, p. 551-557. Disponible sur : < http://dx.doi.org/10.1002/mus.23957 >
    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.

  • JOVICICH J., MARIZZONI M., BOSCH B., BARTRéS-FAZ D., ARNOLD J., BENNINGHOFF J., WILTFANG J., ROCCATAGLIATA L., PICCO A., NOBILI F., BLIN O., BOMBOIS S., LOPES R., BORDET R., CHANOINE V., RANJEVA J. - P., DIDIC M., GROS-DAGNAC H., PAYOUX P., ZOCCATELLI G., ALESSANDRINI F., BELTRAMELLO A., BARGALLó N., FERRETTI A., CAULO M., AIELLO M., RAGUCCI M., SORICELLI A., SALVADORI N., TARDUCCI R., FLORIDI P., TSOLAKI M., CONSTANTINIDIS M., DREVELEGAS A., ROSSINI P. M., MARRA C., OTTO J., REISS-ZIMMERMANN M., HOFFMANN K. - T., GALLUZZI S., FRISONI G. B., THE PHARMACOG CONSORTIUM. “Multisite longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging of healthy elderly subjects.”. NeuroImage [En ligne]. 2014. Vol. 101C, p. 390-403. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2014.06.075 > (consulté le no date)
    Résumé : Large-scale longitudinal neuroimaging studies with diffusion imaging techniques are necessary to test and validate models of white matter neurophysiological processes that change in time, both in healthy and diseased brains. The predictive power of such longitudinal models will always be limited by the reproducibility of repeated measures acquired during different sessions. At present, there is limited quantitative knowledge about the across-session reproducibility of standard diffusion metrics in 3T multi-centric studies on subjects in stable conditions, in particular when using tract based spatial statistics and with elderly people. In this study we implemented a multi-site brain diffusion protocol in 10 clinical 3T MRI sites distributed across 4 countries in Europe (Italy, Germany, France and Greece) using vendor provided sequences from Siemens (Allegra, Trio Tim, Verio, Skyra, Biograph mMR), Philips (Achieva) and GE (HDxt) scanners. We acquired DTI data (2×2×2mm(3), b=700s/mm(2), 5 b0 and 30 diffusion weighted volumes) of a group of healthy stable elderly subjects (5 subjects per site) in two separate sessions at least a week apart. For each subject and session four scalar diffusion metrics were considered: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial (AD) diffusivity. The diffusion metrics from multiple subjects and sessions at each site were aligned to their common white matter skeleton using tract-based spatial statistics. The reproducibility at each MRI site was examined by looking at group averages of absolute changes relative to the mean (%) on various parameters: i) reproducibility of the signal-to-noise ratio (SNR) of the b0 images in centrum semiovale, ii) full brain test-retest differences of the diffusion metric maps on the white matter skeleton, iii) reproducibility of the diffusion metrics on atlas-based white matter ROIs on the white matter skeleton. Despite the differences of MRI scanner configurations across sites (vendors, models, RF coils and acquisition sequences) we found good and consistent test-retest reproducibility. White matter b0 SNR reproducibility was on average 7±1% with no significant MRI site effects. Whole brain analysis resulted in no significant test-retest differences at any of the sites with any of the DTI metrics. The atlas-based ROI analysis showed that the mean reproducibility errors largely remained in the 2-4% range for FA and AD and 2-6% for MD and RD, averaged across ROIs. Our results show reproducibility values comparable to those reported in studies using a smaller number of MRI scanners, slightly different DTI protocols and mostly younger populations. We therefore show that the acquisition and analysis protocols used are appropriate for multi-site experimental scenarios.


  • MAAROUF A., AUDOIN B., KONSTANDIN S., RICO A., SOULIER E., REUTER F., TROTER A. L., CONFORT-GOUNY S., COZZONE P. J., GUYE M., SCHAD L. R., PELLETIER J., RANJEVA J. - P., ZAARAOUI W. “Topography of brain sodium accumulation in progressive multiple sclerosis.”. Magnetic Resonance Materials in Physics, Biology and Medicine [En ligne]. 2014. Vol. 27, n°1, p. 53-62. Disponible sur : < http://dx.doi.org/10.1007/s10334-013-0396-1 >
    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.

  • TASO M., LE TROTER A., SDIKA M., RANJEVA J. - P., GUYE M., BERNARD M., CALLOT V. “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.) [En ligne]. 2014. Vol. 27, n°3, p. 257-267. Disponible sur : < http://dx.doi.org/10.1007/s10334-013-0403-6 > (consulté le no date)
    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. “Single-trial EEG-informed fMRI reveals spatial dependency of BOLD signal on early and late IC-ERP amplitudes during face recognition.”. NeuroImage [En ligne]. 2014. Vol. 100, p. 325-336. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2014.05.075 >
    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


  • FAGET-AGIUS C., BOYER L., LANÇON C., RICHIERI R., FASSIO E., SOULIER E., CHANOINE V., AUQUIER P., RANJEVA J. P., GUYE M. “Structural and functional reorganization of working memory system during the first decade in schizophrenia. A cross-sectional study.”. Schizophrenia Research [En ligne]. 01 December 2013. Vol. 151, n°1, p. 48-60. Disponible sur : < http://dx.doi.org/10.1016/j.schres.2013.10.023 >
    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, Working memory.


  • INGLESE M., OESINGMANN N., ZAARAOUI W., RANJEVA J. P., FLEYSHER L. “Sodium imaging as a marker of tissue injury in patients with multiple sclerosis.”. Multiple Sclerosis and Related Disorders [En ligne]. 2013. Vol. 2, n°4, p. 263-269. Disponible sur : < http://dx.doi.org/10.1016/j.msard.2013.03.009 >
    Résumé : Abstract Recent studies have suggested that intra-axonal sodium accumulation contribute to axonal degeneration in patients with MS. Advances in MRI hardware and software allow acquisition of brain sodium signal in vivo. This review begins with a summary of the experimental evidence for impairment of sodium homeostasis in MS. Then, MRI methods for sodium acquisition are reviewed and the application of the techniques in patients with MS is discussed. Sodium imaging and ultra-high field MRI have the potential to provide tissue-specific markers of neurodegeneration in MS.
    Mots-clés : crmbm, Multiple Sclerosis, Multiple-quantum filtering, Sodium imaging, Ultra-high magnetic field.

  • JOVICICH J., MARIZZONI M., SALA-LLONCH R., BOSCH B., BARTRéS-FAZ D., ARNOLD J., BENNINGHOFF J., WILTFANG J., ROCCATAGLIATA L., NOBILI F., HENSCH T., TRäNKNER A., SCHöNKNECHT P., LEROY M., LOPES R., BORDET R., CHANOINE V., RANJEVA J. - P., DIDIC M., GROS-DAGNAC H., PAYOUX P., ZOCCATELLI G., ALESSANDRINI F., BELTRAMELLO A., BARGALLó N., BLIN O., FRISONI G. B., PHARMACOG CONSORTIUM. “Brain morphometry reproducibility in multi-center 3T MRI studies: A comparison of cross-sectional and longitudinal segmentations.”. NeuroImage [En ligne]. 2013. Vol. 83, p. 472-484. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2013.05.007 > (consulté le no date)
    Résumé : Large-scale longitudinal multi-site MRI brain morphometry studies are becoming increasingly crucial to characterize both normal and clinical population groups using fully automated segmentation tools. The test-retest reproducibility of morphometry data acquired across multiple scanning sessions, and for different MR vendors, is an important reliability indicator since it defines the sensitivity of a protocol to detect longitudinal effects in a consortium. There is very limited knowledge about how across-session reliability of morphometry estimates might be affected by different 3T MRI systems. Moreover, there is a need for optimal acquisition and analysis protocols in order to reduce sample sizes. A recent study has shown that the longitudinal FreeSurfer segmentation offers improved within session test-retest reproducibility relative to the cross-sectional segmentation at one 3T site using a nonstandard multi-echo MPRAGE sequence. In this study we implement a multi-site 3T MRI morphometry protocol based on vendor provided T1 structural sequences from different vendors (3D MPRAGE on Siemens and Philips, 3D IR-SPGR on GE) implemented in 8 sites located in 4 European countries. The protocols used mild acceleration factors (1.5-2) when possible. We acquired across-session test-retest structural data of a group of healthy elderly subjects (5 subjects per site) and compared the across-session reproducibility of two full-brain automated segmentation methods based on either longitudinal or cross-sectional FreeSurfer processing. The segmentations include cortical thickness, intracranial, ventricle and subcortical volumes. Reproducibility is evaluated as absolute changes relative to the mean (%), Dice coefficient for volume overlap and intraclass correlation coefficients across two sessions. We found that this acquisition and analysis protocol gives comparable reproducibility results to previous studies that used longer acquisitions without acceleration. We also show that the longitudinal processing is systematically more reliable across sites regardless of MRI system differences. The reproducibility errors of the longitudinal segmentations are on average approximately half of those obtained with the cross sectional analysis for all volume segmentations and for entorhinal cortical thickness. No significant differences in reliability are found between the segmentation methods for the other cortical thickness estimates. The average of two MPRAGE volumes acquired within each test-retest session did not systematically improve the across-session reproducibility of morphometry estimates. Our results extend those from previous studies that showed improved reliability of the longitudinal analysis at single sites and/or with non-standard acquisition methods. The multi-site acquisition and analysis protocol presented here is promising for clinical applications since it allows for smaller sample sizes per MRI site or shorter trials in studies evaluating the role of potential biomarkers to predict disease progression or treatment effects.
    Mots-clés : crmbm.

  • KORIC L., RANJEVA J. - P., FELICIAN O., GUYE M., DE ANNA F., SOULIER E., DIDIC M., CECCALDI M. “Cued recall measure predicts the progression of gray matter atrophy in patients with amnesic mild cognitive impairment.”. Dementia and geriatric cognitive disorders [En ligne]. 2013. Vol. 36, n°3-4, p. 197-210. Disponible sur : < http://dx.doi.org/10.1159/000351667 > (consulté le no date)
    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.

2012

Journal Article

  • BARBEAU E. J., DIDIC M., JOUBERT S., GUEDJ E., KORIC L., FELICIAN O., RANJEVA J. - P., COZZONE P., CECCALDI M. “Extent and neural basis of semantic memory impairment in mild cognitive impairment.”. Journal of Alzheimer's disease: JAD [En ligne]. 2012. Vol. 28, n°4, p. 823-837. Disponible sur : < http://dx.doi.org/10.3233/JAD-2011-110989 > (consulté le no date)
    Résumé : An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted.
    Mots-clés : Aged, Aged, 80 and over, Case-Control Studies, Cerebral Cortex, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Memory Disorders, Memory, Long-Term, Middle Aged, Mild Cognitive Impairment, Neuropsychological Tests, Photic Stimulation, Semantics.

  • DURANTE L., ZAARAOUI W., RICO A., CRESPY L., WYBRECHT D., FAIVRE A., REUTER F., MALIKOVA I., POMMIER G., CONFORT-GOUNY S., COZZONE P. J., RANJEVA J. - P., PELLETIER J., BOUCRAUT J., AUDOIN B. “Intrathecal synthesis of IgM measured after a first demyelinating event suggestive of multiple sclerosis is associated with subsequent MRI brain lesion accrual.”. Multiple sclerosis (Houndmills, Basingstoke, England) [En ligne]. 2012. Vol. 18, n°5, p. 587-591. Disponible sur : < http://dx.doi.org/10.1177/1352458511424589 > (consulté le no date)
    Résumé : BACKGROUND: Previous studies have demonstrated that intrathecal synthesis of IgM is observed in multiple sclerosis (MS) and correlates with a worse disease course. These results suggest that IgM participates in the formation of MS lesions. OBJECTIVE: The aim of the present study was to assess the potential association between the level of intrathecal synthesis of IgM measured after a clinically isolated syndrome (CIS) and the subsequent formation of brain lesions. METHODS: Fifty seven patients with a CIS and a high risk developing MS were enrolled in a longitudinal study. Examination of cerebrospinal fluid was performed after the CIS and included measures of intrathecal IgM and IgG synthesis. Patients were assessed with the same 1.5 Tesla magnetic resonance imaging (MRI) system at baseline and after a mean follow-up period of 49 months (range 36-60). Spearman Rank correlation was used to assess the potential correlations between levels of intrathecal immunoglobulin synthesis and MRI data. RESULTS: The level of intrathecal IgM synthesis was correlated with the number of gadolinium-enhancing lesions at baseline (p = 0.01) and with accrual of brain lesions during the follow-up period (p = 0.02). By taking into account brain sub-regions, we demonstrated that the level of intrathecal IgM synthesis was only correlated with the increased number of lesions in the periventricular regions (p = 0.004). The level of intrathecal IgG synthesis was not correlated with any MRI data. CONCLUSION: The present longitudinal study demonstrates that the level of intrathecal IgM synthesis measured after a CIS is associated with subsequent lesion accrual during the first years of MS. This result emphasizes the involvement of IgM in plaque formation.
    Mots-clés : Adult, Brain, Contrast Media, crmbm, Demyelinating Diseases, Disease Progression, Female, France, Humans, Immunoglobulin M, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Predictive Value of Tests, Severity of Illness Index, Time Factors, Young Adult.

  • FAIVRE A., RICO A., ZAARAOUI W., CRESPY L., REUTER F., WYBRECHT D., SOULIER E., MALIKOVA I., CONFORT-GOUNY S., COZZONE P. J., PELLETIER J., RANJEVA J. - P., AUDOIN B. “Assessing brain connectivity at rest is clinically relevant in early multiple sclerosis.”. Multiple sclerosis (Houndmills, Basingstoke, England) [En ligne]. 2012. Vol. 18, n°9, p. 1251-1258. Disponible sur : < http://dx.doi.org/10.1177/1352458511435930 > (consulté le no date)
    Résumé : OBJECTIVE: The present study aims to determine the clinical counterpart of brain resting-state networks reorganization recently evidenced in early multiple sclerosis. METHODS: Thirteen patients with early relapsing-remitting multiple sclerosis and 14 matched healthy controls were included in a resting state functional MRI study performed at 3 T. Data were analyzed using group spatial Independent Component Analysis using concatenation approach (FSL 4.1.3) and double regression analyses (SPM5) to extract local and global levels of connectivity inside various resting state networks (RSNs). Differences in global levels of connectivity of each network between patients and controls were assessed using Mann-Whitney U-test. In patients, relationship between clinical data (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite Score - MSFC) and global RSN connectivity were assessed using Spearman rank correlation. RESULTS: Independent component analysis provided eight consistent neuronal networks involved in motor, sensory and cognitive processes. For seven RSNs, the global level of connectivity was significantly increased in patients compared with controls. No significant decrease in RSN connectivity was found in early multiple sclerosis patients. MSFC values were negatively correlated with increased RSN connectivity within the dorsal frontoparietal network (r = -0.811, p = 0.001), the right ventral frontoparietal network (r = - 0.587, p = 0.045) and the prefronto-insular network (r = -0.615, p = 0.033). CONCLUSIONS: This study demonstrates that resting state networks reorganization is strongly associated with disability in early multiple sclerosis. These findings suggest that resting state functional MRI may represent a promising surrogate marker of disease burden.
    Mots-clés : Adult, Analysis of Variance, Brain, Brain Mapping, Case-Control Studies, Cognition, crmbm, Disability Evaluation, Female, Humans, Magnetic Resonance Imaging, Male, Motor Activity, Multiple Sclerosis, Relapsing-Remitting, Nerve Net, Neuropsychological Tests, Predictive Value of Tests, Prognosis, Regression Analysis, Rest, Sensation, Severity of Illness Index, Young Adult.

  • WYBRECHT D., REUTER F., ZAARAOUI W., FAIVRE A., CRESPY L., RICO A., MALIKOVA I., CONFORT-GOUNY S., SOULIER E., COZZONE P. J., PELLETIER J., RANJEVA J. - P., AUDOIN B. “Voxelwise analysis of conventional magnetic resonance imaging to predict future disability in early relapsing-remitting multiple sclerosis.”. Multiple sclerosis (Houndmills, Basingstoke, England) [En ligne]. 2012. Vol. 18, n°11, p. 1585-1591. Disponible sur : < http://dx.doi.org/10.1177/1352458512442991 > (consulté le no date)
    Résumé : BACKGROUND: The ability of conventional magnetic resonance imaging (MRI) to predict subsequent physical disability and cognitive deterioration after a clinically isolated syndrome (CIS) is weak. OBJECTIVES: We aimed to investigate whether conventional MRI changes over 1 year could predict cognitive and physical disability 5 years later in CIS. We performed analyses using a global approach (T(2) lesion load, number of T(2) lesions), but also a topographic approach. METHODS: This study included 38 patients with a CIS. At inclusion, 10 out of 38 patients fulfilled the 2010 revised McDonald's criteria for the diagnosis of multiple sclerosis. Expanded Disability Status Scale (EDSS) evaluation was performed at baseline, year 1 and year 5, and cognitive evaluation at baseline and year 5. T(2)-weighted MRI was performed at baseline and year 1. We used voxelwise analysis to analyse the predictive value of lesions location for subsequent disability. RESULTS: Using the global approach, no correlation was found between MRI and clinical data. The occurrence or growth of new lesions in the brainstem was correlated with EDSS changes over the 5 years of follow-up. The occurrence or growth of new lesions in cerebellum, thalami, corpus callosum and frontal lobes over 1 year was correlated with cognitive impairment at 5 years. CONCLUSION: The assessment of lesion location at the first stage of multiple sclerosis may be of value to predict future clinical disability.
    Mots-clés : crmbm.

  • ZAARAOUI W., KONSTANDIN S., AUDOIN B., NAGEL A. M., RICO A., MALIKOVA I., SOULIER E., VIOUT P., CONFORT-GOUNY S., COZZONE P. J., PELLETIER J., SCHAD L. R., RANJEVA J. - P. “Distribution of brain sodium accumulation correlates with disability in multiple sclerosis: a cross-sectional 23Na MR imaging study.”. Radiology [En ligne]. 2012. Vol. 264, n°3, p. 859-867. Disponible sur : < http://dx.doi.org/10.1148/radiol.12112680 > (consulté le no date)
    Résumé : PURPOSE: To quantify brain sodium accumulations and characterize for the first time the spatial location of sodium abnormalities at different stages of relapsing-remitting (RR) multiple sclerosis (MS) by using sodium 23 ((23)Na) magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the local committee on ethics, and written informed consent was obtained from all participants. Three-dimensional (23)Na MR imaging data were obtained with a 3.0-T unit in two groups of patients with RR MS-14 with early RR MS (disease duration <5 years) and 12 with advanced RR MS (disease duration >5 years)-and 15 control subjects. Quantitative assessment of total sodium concentration (TSC) levels within compartments (MS lesions, white matter [WM], and gray matter [GM]) as well as statistical mapping analyses of TSC abnormalities were performed. RESULTS: TSC was increased inside demyelinating lesions in both groups of patients, whereas increased TSC was observed in normal-appearing WM and GM only in those with advanced RR MS. In patients, increased TSC inside GM was correlated with disability (as determined with the Expanded Disability Status Scale [EDSS] score; P = .046, corrected) and lesion load at T2-weighted imaging (P = .003, corrected) but not with disease duration (P = .089, corrected). Statistical mapping analysis showed confined TSC increases inside the brainstem, cerebellum, and temporal poles in early RR MS and widespread TSC increases that affected the entire brain in advanced RR MS. EDSS score correlated with TSC increases inside motor networks. CONCLUSION: TSC accumulation dramatically increases in the advanced stage of RR MS, especially in the normal-appearing brain tissues, concomitant with disability. Brain sodium MR imaging may help monitor the occurrence of tissue injury and disability.
    Mots-clés : Adult, Area Under Curve, Brain, crmbm, Disability Evaluation, Female, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Regression Analysis, Sodium, Statistics, Nonparametric.

2011

Journal Article

  • BETTUS G., RANJEVA J. - P., WENDLING F., BÉNAR C. G., CONFORT-GOUNY S., RÉGIS J., CHAUVEL P., COZZONE P. J., LEMIEUX L., BARTOLOMEI F., GUYE M. “Interictal functional connectivity of human epileptic networks assessed by intracerebral EEG and BOLD signal fluctuations.”. PloS one [En ligne]. 2011. Vol. 6, n°5, p. e20071. Disponible sur : < http://dx.doi.org/10.1371/journal.pone.0020071 > (consulté le no date)
    Résumé : In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal derived from resting state functional magnetic resonance imaging (fMRI) reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG) and resting-state functional MRI (fMRI) in 5 patients suffering from intractable temporal lobe epilepsy (TLE). Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions) during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband) and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal). This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional connectivity measured by iEEG and BOLD signals give complementary but sometimes inconsistent information in TLE.
    Mots-clés : crmbm, Electroencephalography, epilepsy, Humans, Magnetic Resonance Imaging.

  • CRESPY L., ZAARAOUI W., LEMAIRE M., RICO A., FAIVRE A., REUTER F., MALIKOVA I., CONFORT-GOUNY S., COZZONE P. J., PELLETIER J., RANJEVA J. - P., AUDOIN B. “Prevalence of grey matter pathology in early multiple sclerosis assessed by magnetization transfer ratio imaging.”. PloS one [En ligne]. 2011. Vol. 6, n°9, p. e24969. Disponible sur : < http://dx.doi.org/10.1371/journal.pone.0024969 > (consulté le no date)
    Résumé : The aim of the study was to assess the prevalence, the distribution and the impact on disability of grey matter (GM) pathology in early multiple sclerosis. Eighty-eight patients with a clinically isolated syndrome with a high risk developing multiple sclerosis were included in the study. Forty-four healthy controls constituted the normative population. An optimized statistical mapping analysis was performed to compare each subject's GM Magnetization Transfer Ratio (MTR) imaging maps with those of the whole group of controls. The statistical threshold of significant GM MTR decrease was determined as the maximum p value (p<0.05 FDR) for which no significant cluster survived when comparing each control to the whole control population. Using this threshold, 51% of patients showed GM abnormalities compared to controls. Locally, 37% of patients presented abnormalities inside the limbic cortex, 34% in the temporal cortex, 32% in the deep grey matter, 30% in the cerebellum, 30% in the frontal cortex, 26% in the occipital cortex and 19% in the parietal cortex. Stepwise regression analysis evidenced significant association (p = 0.002) between EDSS and both GM pathology (p = 0.028) and T2 white matter lesions load (p = 0.019). In the present study, we evidenced that individual analysis of GM MTR map allowed demonstrating that GM pathology is highly heterogeneous across patients at the early stage of MS and partly underlies irreversible disability.
    Mots-clés : Adolescent, Adult, Brain, Brain Mapping, Case-Control Studies, crmbm, Diagnostic Imaging, Disease Progression, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Middle Aged, Multiple Sclerosis, Young Adult.

  • EDAN G., COMI G., LE PAGE E., LERAY E., ROCCA M. A., FILIPPI M., FRENCH€ITALIAN MITOXANTRONE INTERFERON-BETA-1B TRIAL GROUP. “Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial.”. Journal of neurology, neurosurgery, and psychiatry [En ligne]. 2011. Vol. 82, n°12, p. 1344-1350. Disponible sur : < http://dx.doi.org/10.1136/jnnp.2010.229724 > (consulté le no date)
    Résumé : OBJECTIVES: The long-term impact of interferon-beta-1b (IFN) might be improved by short-term immunosuppression with mitoxantrone (MITOX) in aggressive relapsing-remitting multiple sclerosis (ARMS) patients. METHODS: In this 3-year clinical and MRI study, 109 ARMS patients (two or more relapses in the previous 12 months and one or more gadolinium (Gd)-enhancing MRI lesion) were randomised into two groups: 54 patients received MITOX monthly (12 mg/m(2); maximum 20 mg) combined with 1 g of methylprednisolone (MP) for 6 months followed by IFN for the last 27 months, and 55 patients received IFN for 3 years combined with 1 g of MP monthly for the first 6 months. The primary endpoint was the time to worsen by at least one Expanded Disability Status Scale point confirmed at 3 months. RESULTS: The time to worsen by at least one Expanded Disability Status Scale point confirmed at 3 months was delayed by 18 months in the MITOX group compared with the IFN group (p<0.012). The 3-year risk of worsening disability was reduced by 65% in the MITOX group relative to the IFN group (11.8% vs 33.6%). MITOX patients had a reduced relapse rate by 61.7%, a reduced number of Gd-enhancing lesions at month 9 and a slower accumulation of new T2 lesions at each time point. CONCLUSIONS: Although there were limitations in this investigator-academic-driven study, the data do suggest that mitoxantrone induction therapy prior to INF beta-1b may have a role in aggressive disease.
    Mots-clés : Adult, Brain, Drug Administration Schedule, Drug Therapy, Combination, Female, Gadolinium, Humans, Immunologic Factors, Immunosuppressive Agents, Interferon-beta, Magnetic Resonance Imaging, Male, Methylprednisolone, Mitoxantrone, Multiple Sclerosis, Relapsing-Remitting, Neuroimaging, Severity of Illness Index.

  • GOUR N., RANJEVA J. - P., CECCALDI M., CONFORT-GOUNY S., BARBEAU E., SOULIER E., GUYE M., DIDIC M., FELICIAN O. “Basal functional connectivity within the anterior temporal network is associated with performance on declarative memory tasks.”. NeuroImage [En ligne]. 2011. Vol. 58, n°2, p. 687-697. Disponible sur : < http://dx.doi.org/10.1016/j.neuroimage.2011.05.090 > (consulté le no date)
    Résumé : Spontaneous fluctuations in the blood oxygenation level-dependent (BOLD) signal, as measured by functional magnetic resonance imaging (fMRI) at rest, exhibit a temporally coherent activity thought to reflect functionally relevant networks. Antero-mesial temporal structures are the site of early pathological changes in Alzheimer's disease and have been shown to be critical for declarative memory. Our study aimed at exploring the functional impact of basal connectivity of an anterior temporal network (ATN) on declarative memory. A heterogeneous group of subjects with varying performance on tasks assessing memory was therefore selected, including healthy subjects and patients with isolated memory complaint, amnestic Mild Cognitive Impairment (aMCI) and mild Alzheimer's disease (AD). Using Independent Component Analysis on resting-state fMRI, we extracted a relevant anterior temporal network (ATN) composed of the perirhinal and entorhinal cortex, the hippocampal head, the amygdala and the lateral temporal cortex extending to the temporal pole. A default mode network and an executive-control network were also selected to serve as control networks. We first compared basal functional connectivity of the ATN between patients and control subjects. Relative to controls, patients exhibited significantly increased functional connectivity in the ATN during rest. Specifically, voxel-based analysis revealed an increase within the inferior and superior temporal gyrus and the uncus. In the patient group, positive correlations between averaged connectivity values of ATN and performance on anterograde and retrograde object-based memory tasks were observed, while no correlation was found with other evaluated cognitive measures. These correlations were specific to the ATN, as no correlation between performance on memory tasks and the other selected networks was found. Taken together, these findings provide evidence that basal connectivity inside the ATN network has a functional role in object-related, context-free memory. They also suggest that increased connectivity at rest within the ATN could reflect compensatory mechanisms that occur in response to early pathological insult.
    Mots-clés : Aged, Alzheimer Disease, crmbm, Data Interpretation, Statistical, Educational Status, Executive Function, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Memory, Memory Disorders, Mild Cognitive Impairment, Nerve Net, Neural Pathways, Neuropsychological Tests, Principal Component Analysis, Psychomotor Performance, Temporal Lobe, Visual Perception.

  • GUEDJ E., BETTUS G., BARBEAU E. J., LIÉGEOIS-CHAUVEL C., CONFORT-GOUNY S., BARTOLOMEI F., CHAUVEL P., COZZONE P. J., RANJEVA J. - P., GUYE M. “Hyperactivation of parahippocampal region and fusiform gyrus associated with successful encoding in medial temporal lobe epilepsy.”. Epilepsia [En ligne]. 2011. Vol. 52, n°6, p. 1100-1109. Disponible sur : < http://dx.doi.org/10.1111/j.1528-1167.2011.03052.x > (consulté le no date)
    Résumé : PURPOSE: Performance in recognition memory differs among patients with medial temporal lobe epilepsy (MTLE). We aimed to determine if distinct recognition performances (normal vs. impaired) could be related to distinct patterns of brain activation during encoding. METHODS: Event-related functional magnetic resonance imaging (fMRI) activation profiles were obtained during successful encoding of non-material-specific items, in 14 MTLE patients tested for recognition of stimuli afterward. Findings were compared to those of 25 healthy subjects, and voxel-based correlations were assessed between brain activation and performance. KEY FINDINGS: Patients with left and right MTLE showed similar activations and similar performances. As a whole, the group of patients demonstrated altered recognition scores, but three of the seven patients with left MTLE and three of the seven patients with right MTLE exhibited normal performance relative to controls. In comparison to healthy subjects and patients with impaired recognition, patients with normal recognition showed weaker activations in left opercular cortex, but stronger activations in bilateral parahippocampal region/fusiform gyrus (PH/FG). By contrast, patients with impaired performance showed weaker activations in bilateral PH/FG, but stronger activations in a frontal/cingulate and parietal network. Recognition performance was correlated positively to bilateral PH/FG activations, and negatively correlated to bilateral frontal/cingulate activations, in the whole group of patients, as well as in subgroups of patients with either left or right MTLE. SIGNIFICANCE: These results suggest occurrence of effective functional compensation within bilateral PH/FG in MTLE, allowing patients to maintain recognition capability. In contrast, impairment of this perceptive-memory system may lead to alternative activation of an inefficient nonspecific attentional network in patients with altered performance.
    Mots-clés : Adolescent, Adult, crmbm, Epilepsy, Temporal Lobe, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Parahippocampal Gyrus, Prospective Studies, Psychomotor Performance, Recognition (Psychology), Young Adult.

  • LI L., PADHI A., RANJEVA S. L., DONALDSON S. C., WARF B. C., MUGAMBA J., JOHNSON D., OPIO Z., JAYARAO B., KAPUR V., POSS M., SCHIFF S. J. “Association of bacteria with hydrocephalus in Ugandan infants.”. Journal of neurosurgery. Pediatrics [En ligne]. 2011. Vol. 7, n°1, p. 73-87. Disponible sur : < http://dx.doi.org/10.3171/2010.9.PEDS10162 > (consulté le no date)
    Résumé : OBJECT: Infantile hydrocephalus in East Africa is predominantly postinfectious. The microbial origins remain elusive, since most patients present with postinfectious hydrocephalus after antecedent neonatal sepsis (NS) has resolved. METHODS: To characterize this syndrome in Ugandan infants, the authors used polymerase chain reaction targeting bacterial 16S ribosomal DNA from CSF to determine if bacterial residua from recent infections were detectable. Bacteria were identified based on the relationship of genetic sequences obtained with reference bacteria in public databases. The authors evaluated samples from patients presenting during dry and rainy seasons and performed environmental sampling in the villages of patients. RESULTS: Bacterial DNA was recovered from 94% of patients. Gram-negative bacteria in the phylum Proteobacteria were the most commonly detected. Within this phylum, Gammaproteobacteria dominated in patients presenting after infections during the rainy season, and Betaproteobacteria was most common following infections during the dry season. Acinetobacter species were identified in the majority of patients admitted after rainy season infection. CONCLUSIONS: Postinfectious hydrocephalus in Ugandan infants appears associated with predominantly enteric gram-negative bacteria. These findings highlight the need for linking these cases with antecedent NS to develop more effective treatment and prevention strategies.
    Mots-clés : Cohort Studies, DNA, Bacterial, Female, Gram-Negative Bacteria, Gram-Negative Bacterial Infections, Humans, Hydrocephalus, Infant, Male, Polymerase Chain Reaction, Proteobacteria, RNA, Ribosomal, 16S, Seasons, Uganda.

  • REUTER F., ZAARAOUI W., CRESPY L., FAIVRE A., RICO A., MALIKOVA I., CONFORT-GOUNY S., COZZONE P. J., RANJEVA J. - P., PELLETIER J., AUDOIN B. “Cognitive impairment at the onset of multiple sclerosis: relationship to lesion location.”. Multiple sclerosis (Houndmills, Basingstoke, England) [En ligne]. 2011. Vol. 17, n°6, p. 755-758. Disponible sur : < http://dx.doi.org/10.1177/1352458511398265 > (consulté le no date)
    Résumé : The impact of lesion location on cognitive functioning was assessed in a group of 97 patients with a clinically isolated syndrome. Using the Brief Repeatable Battery, we evidenced that 24% of patients showed at least one abnormal test, 20% at least two and 15% at least three. Verbal learning performances were inversely associated with presence of lesions in Broca's area, in the right frontal lobe and in the splenium while spatial learning performances were inversely correlated to the presence of lesions in the deep white matter. No associations were evidenced between lesion location and performance of tasks exploring attention and executive functions.
    Mots-clés : Adult, Attention, Brain, Case-Control Studies, Cognition, Cognition Disorders, crmbm, Demyelinating Diseases, Disability Evaluation, Executive Function, Female, France, Humans, Magnetic Resonance Imaging, Male, Memory, Multiple Sclerosis, Neuropsychological Tests, Prevalence, spinal cord, Verbal Learning, Young Adult.

  • REUTER F., ZAARAOUI W., CRESPY L., FAIVRE A., RICO A., MALIKOVA I., SOULIER E., VIOUT P., RANJEVA J. - P., PELLETIER J., AUDOIN B. “Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis.”. Journal of neurology, neurosurgery, and psychiatry [En ligne]. 2011. Vol. 82, n°10, p. 1157-1159. Disponible sur : < http://dx.doi.org/10.1136/jnnp.2010.213744 > (consulté le no date)
    Résumé : Previous studies have demonstrated that cognitive impairment is already present in patients suffering from a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). However, little is known about the course of cognitive impairment after the occurrence of a CIS. In order to characterise the early evolution of cognitive impairment, the authors assessed during a 5-year follow-up period a group of 24 CIS patients with high risk of developing MS. Longitudinal neuropsychological assessment was performed at two time points (baseline and year 5) in patients and controls (baseline and year 1). At year 5, 54% of patients showed cognitive impairment against 29% at baseline. Multiple regression models showed that patients with a higher T(2) lesion load at baseline had a higher cognitive impairment at year 5. This longitudinal study performed in CIS patients showed that the frequency of cognitive impairment increases dramatically during the first 5 years following a CIS and that the cognitive status at year 5 was predictable by conventional MRI parameters recorded at baseline.
    Mots-clés : Adult, Brain, Cognition Disorders, crmbm, Demyelinating Diseases, Disability Evaluation, Disease Progression, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Multiple Sclerosis, Neuropsychological Tests, Oligoclonal Bands, Risk Factors, spinal cord.

  • RICO A., ZAARAOUI W., FRANQUES J., ATTARIAN S., REUTER F., MALIKOVA I., CONFORT-GOUNY S., SOULIER E., POUGET J., COZZONE P. J., PELLETIER J., RANJEVA J. - P., AUDOIN B. “Motor cortical reorganization is present after a single attack of multiple sclerosis devoid of cortico-spinal dysfunction.”. Magma (New York, N.Y.) [En ligne]. 2011. Vol. 24, n°2, p. 77-84. Disponible sur : < http://dx.doi.org/10.1007/s10334-010-0232-9 > (consulté le no date)
    Résumé : OBJECT: While occurrence of motor cortical reorganization has been clearly demonstrated in patients with multiple sclerosis (MS), it is not yet clear whether this cortical reorganization constitutes a response to cortico-spinal lesions or to more diffuse damage affecting the neuronal network involved in motor act preparation, or both. We proposed to investigate the changes in the activation pattern during a simple motor task devoid of cortico-spinal dysfunction occurring in patients with clinically isolated syndrome (CIS) suggestive of MS. MATERIALS AND METHODS: Among 15 right-handed CIS patients, we selected eight patients with a preserved central motor pathway established by motor evoked potentials. Ten healthy right-handed gender- and age-matched volunteers were also included. After morphological MRI, subjects performed calibrated conjugated finger flexion and extension movements during fMRI acquisition. RESULTS: In CIS patients, simple movements of the non-dominant hand induced recruitment of the anterior cingulate cortex (BA32) usually involved in complex motor movements. This reorganization was correlated with the diffuse brain tissue damage (brain T₂ lesion load). CONCLUSION: These results suggest that at least part of the cortical reorganization observed during very simple tasks in the earliest stage of MS occurs whether or not the efferent pathways are intact.
    Mots-clés : Adult, Brain Mapping, crmbm, Demyelinating Diseases, Evoked Potentials, Motor, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Motor Activity, Motor Cortex, Multiple Sclerosis, Pyramidal Tracts, Young Adult.

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