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Focal epilepsy is characterized by repeated spontaneous seizures that originate from cortical epileptogenic zone networks (EZN). Analysis of intracerebral recordings showed that subcortical structures, and in particular the thalamus, play an important role in seizure dynamics as well, supporting their structural alterations reported in the neuroimaging literature. Nonetheless, between‐patient differences in EZN localization (e.g., temporal vs. non‐temporal lobe epilepsy) as well as extension (i.e., number of epileptogenic regions) might impact the magnitude as well as spatial distribution of subcortical structural changes. Here we used 7 Tesla MRI T1 data to provide an unprecedented description of subcortical morphological (volume, tissue deformation, and shape) and longitudinal relaxation (T1) changes in focal epilepsy patients and evaluate the impact of the EZN and other patient‐specific clinical features. Our results showed variable levels of atrophy across thalamic nuclei that appeared most prominent in the temporal lobe epilepsy group and the side ipsilateral to the EZN, while shortening of T1 was especially observed for the lateral thalamus. Multivariate analyses across thalamic nuclei and basal ganglia showed that volume acted as the dominant discriminator between patients and controls, while (posterolateral) thalamic T1 measures looked promising to further differentiate patients based on EZN localization. In particular, the observed differences in T1 changes between thalamic nuclei indicated differential involvement based on EZN localization. Finally, EZN extension was found to best explain the observed variability between patients. To conclude, this work revealed multi‐scale subcortical alterations in focal epilepsy as well as their dependence on several clinical characteristics. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate the bias in quantitative MT (qMT) measures introduced by the presence of dipolar order and on‐resonance saturation (ONRS) effects using magnetization transfer (MT) spoiled gradient‐recalled (SPGR) acquisitions, and propose changes to the acquisition and analysis strategies to remove these biases. Methods: The proposed framework consists of SPGR sequences prepared with simultaneous dual‐offset frequency‐saturation pulses to cancel out dipolar order and associated relaxation (T1D) effects in Z‐spectrum acquisitions, and a matched quantitative MT (qMT) mathematical model that includes ONRS effects of readout pulses. Variable flip angle and MT data were fitted jointly to simultaneously estimate qMT parameters (macromolecular proton fraction [MPF], T2,f, T2,b, R, and free pool T1). This framework is compared with standard qMT and investigated in terms of reproducibility, and then further developed to follow a joint single‐point qMT methodology for combined estimation of MPF and T1. Results: Bland–Altman analyses demonstrated a systematic underestimation of MPF (−2.5% and −1.3%, on average, in white and gray matter, respectively) and overestimation of T1 (47.1 ms and 38.6 ms, on average, in white and gray matter, respectively) if both ONRS and dipolar order effects are ignored. Reproducibility of the proposed framework is excellent (ΔMPF = −0.03% and ΔT1 = −19.0 ms). The single‐point methodology yielded consistent MPF and T1 values with respective maximum relative average bias of −0.15% and −3.5 ms found in white matter. Conclusion: The influence of acquisition strategy and matched mathematical model with regard to ONRS and dipolar order effects in qMT‐SPGR frameworks has been investigated. The proposed framework holds promise for improved accuracy with reproducibility. [ABSTRACT FROM AUTHOR]

Whole brain ionic and metabolic imaging has potential as a powerful tool for the characterization of brain diseases. We combined sodium MRI (23Na MRI) and 1H‐MR Spectroscopic Imaging (1H‐MRSI), assessing changes within epileptogenic networks in comparison with electrophysiologically normal networks as defined by stereotactic EEG (SEEG) recordings analysis. We applied a multi‐echo density adapted 3D projection reconstruction pulse sequence at 7 T (23Na‐MRI) and a 3D echo‐planar spectroscopic imaging sequence at 3 T (1H‐MRSI) in 19 patients suffering from drug‐resistant focal epilepsy who underwent presurgical SEEG. We investigated 23Na MRI parameters including total sodium concentration (TSC) and the sodium signal fraction associated with the short component of T2* decay (f), alongside the level of metabolites N‐acetyl aspartate (NAA), choline compounds (Cho), and total creatine (tCr). All measures were extracted from spherical regions of interest (ROIs) centered between two adjacent SEEG electrode contacts and z‐scored against the same ROI in controls. Group comparison showed a significant increase in f only in the epileptogenic zone (EZ) compared to controls and compared to patients' propagation zone (PZ) and non‐involved zone (NIZ). TSC was significantly increased in all patients' regions compared to controls. Conversely, NAA levels were significantly lower in patients compared to controls, and lower in the EZ compared to PZ and NIZ. Multiple regression analyzing the relationship between sodium and metabolites levels revealed significant relations in PZ and in NIZ but not in EZ. Our results are in agreement with the energetic failure hypothesis in epileptic regions associated with widespread tissue reorganization. [ABSTRACT FROM AUTHOR]

Purpose: Ultra‐high field 1H MR spectroscopy (MRS) is of great interest to help characterizing human spinal cord pathologies. However, very few studies have been reported so far in this small size structure at these fields due to challenging experimental difficulties caused by static and radiofrequency field heterogeneities, as well as physiological motion. In this work, in line with the recent developments proposed to strengthen spinal cord MRS feasibility at 7 T, a respiratory‐triggered acquisition approach was optimized to compensate for dynamic B0 field heterogeneities and to provide robust cervical spinal cord MRS data. Methods: A semi‐LASER sequence was purposely used, and a dedicated raw data processing algorithm was developed to enhance MR spectral quality by discarding corrupted scans. To legitimate the choices done during the optimization stage, additional tests were carried out to determine the impact of breathing, voluntary motion, body mass index, and fitting algorithm. An in‐house quantification tool was concomitantly designed for accurate estimation of the metabolite concentration ratios for choline, N‐acetyl‐aspartate (NAA), myo‐inositol and glutathione. The method was tested on a cohort of 14 healthy volunteers. Results: Average water linewidth and NAA signal‐to‐noise ratio reached 0.04 ppm and 11.01, respectively. The group‐average metabolic ratios were in good agreement with previous studies and showed intersession reproducibility variations below 30%. Conclusion: The developed approach allows a rise of the acquired MRS signal quality and of the quantification robustness as compared to previous studies hence offering strengthened possibilities to probe the metabolism of degenerative and traumatic spinal cord pathologies. [ABSTRACT FROM AUTHOR]

Purpose: To minimize the sensitivity of inhomogeneous magnetization transfer gradient‐echo (ihMT‐GRE) imaging to radiofrequency (RF) transmit field (B1+) inhomogeneities at 3 T. Methods: The ihMT‐GRE sequence was optimized by varying the concentration of the RF saturation energy over time, obtained by increasing the saturation pulse power while extending the sequence repetition time (TR). Different protocols were tested using numerical simulations and human in vivo experiments in the brain white matter (WM) of healthy subjects at 3 T. The sensitivity of the ihMT ratio (ihMTR) to B1+ variations was investigated by comparing measurements obtained at nominal transmitter adjustments and following a 20% global B1+ drop. The resulting relative variations (δihMTR) were evaluated voxelwise as a function of the local B1+ distribution. The reproducibility of the protocol providing minimal B1+ bias was assessed in a test‐retest experiment. Results: In line with simulations, ihMT‐GRE experiments conducted at high concentration of the RF energy over time demonstrated strong reduction of the B1+ inhomogeneity effects in the human WM. Under the optimal conditions of 350‐ms TR and 3‐µT root mean square (RMS) saturation power, 73% of all WM voxels presented δihMTR below 10%. Reproducibility analysis yielded a close‐to‐zero systematic bias (ΔihMTR = −0.081%) and a high correlation (ρ² = 0.977) between test and retest experiments. Conclusion: Concentrating RF saturation energy in ihMT‐GRE sequences mitigates the sensitivity of the ihMTR to B1+ variations and allows for clinical‐ready ihMT imaging at 3 T. This feature is of particular interest for high and ultra‐high field applications. [ABSTRACT FROM AUTHOR]

We present a new consensus atlas of deep grey nuclei obtained by shape‐based averaging of manual segmentation of two experienced neuroradiologists and optimized from 7T MP2RAGE images acquired at (.6 mm)3 in 60 healthy subjects. A group‐wise normalization method was used to build a high‐contrast and high‐resolution T1‐weighted brain template (.5 mm)3 using data from 30 out of the 60 controls. Delineation of 24 deep grey nuclei per hemisphere, including the claustrum and 12 thalamic nuclei, was then performed by two expert neuroradiologists and reviewed by a third neuroradiologist according to tissue contrast and external references based on the Morel atlas. Corresponding deep grey matter structures were also extracted from the Morel and CIT168 atlases. The data‐derived, Morel and CIT168 atlases were all applied at the individual level using non‐linear registration to fit the subject reference and to extract absolute mean quantitative T1 values derived from the 3D‐MP2RAGE volumes, after correction for residual B1+ biases. Three metrics (the Dice and the volumetric similarity coefficients and a novel Hausdorff distance) were used to estimate the inter‐rater agreement of manual MRI segmentation and inter‐atlas variability, and these metrics were measured to quantify biases due to image registration, and their impact on the measurements of the quantitative T1 values was highlighted. This represents a fully automated segmentation process permitting the extraction of unbiased normative T1 values in a population of young healthy controls as a reference for characterizing subtle structural alterations of deep grey nuclei relevant to a range of neurological diseases. [ABSTRACT FROM AUTHOR]

Although multiple sclerosis (MS) is frequently accompanied by visuo‐cognitive impairment, especially functional brain mechanisms underlying this impairment are still not well understood. Consequently, we used a functional MRI (fMRI) backward masking task to study visual information processing stratifying unconscious and conscious in MS. Specifically, 30 persons with MS (pwMS) and 34 healthy controls (HC) were shown target stimuli followed by a mask presented 8–150 ms later and had to compare the target to a reference stimulus. Retinal integrity (via optical coherence tomography), optic tract integrity (visual evoked potential; VEP) and whole brain structural connectivity (probabilistic tractography) were assessed as complementary structural brain integrity markers. On a psychophysical level, pwMS reached conscious access later than HC (50 vs. 16 ms, p <.001). The delay increased with disease duration (p <.001, β =.37) and disability (p <.001, β =.24), but did not correlate with conscious information processing speed (Symbol digit modality test, β =.07, p =.817). No association was found for VEP and retinal integrity markers. Moreover, pwMS were characterized by decreased brain activation during unconscious processing compared with HC. No group differences were found during conscious processing. Finally, a complementary structural brain integrity analysis showed that a reduced fractional anisotropy in corpus callosum and an impaired connection between right insula and primary visual areas was related to delayed conscious access in pwMS. Our study revealed slowed conscious access to visual stimulus material in MS and a complex pattern of functional and structural alterations coupled to unconscious processing of/delayed conscious access to visual stimulus material in MS. [ABSTRACT FROM AUTHOR]

Purpose: Diffusion tensor imaging (DTI), which is frequently used to characterize microstructure impairments in many spinal cord diseases at clinical fields, may benefit from 7T investigations. Yet, it presents specific technical challenges, such as increased magnetic susceptibility‐induced image distortions. Methods: Eight healthy volunteers were scanned at 7T using a prototype diffusion multi‐slice multi‐angle (MSMA) single‐shot spin‐echo echo planar imaging (EPI) sequence developed to explore the whole cervical spinal cord while limiting the partial volume effects related to the cord curvature. To mitigate the increased susceptibility‐induced distortions encountered at 7T, a reverse phase‐encoding strategy was also used. Images acquired from C1‐to‐C7 were registered to the AMU40 template to automatically extract DTI metrics in gray matter/white matter regions of interest. Effects of B 1 + inhomogeneities on the DTI metrics and repeatability of the measurements were also investigated. Lastly, a DTI acquisition with a 400‐µm in‐plane resolution was acquired on one volunteer to push forward 7T potentialities. Results: The MSMA sequence allowed accessing to high‐resolution axial diffusion images sampling the whole cord within a single acquisition. DTI metrics were found in agreement with literature at lower field, stable along a 50–120% relative B 1 + variation range, with a mean inter‐scan coefficient of variation of 8%. The two‐‐fold spatial‐resolution increase of the additional DTI acquisition enabled main white matter tracts visualization on a single‐subject basis. Conclusion: Although C7‐level imaging needs some improvement, this preliminary study shows that transverse 7T DTI of the whole cervical spinal cord is feasible, laying the groundwork for improved multi‐parametric MR investigations and microstructure characterization of the spinal cord. Magn Reson Med 80:947–957, 2018. © 2018 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Purpose: To implement, characterize, and optimize an interleaved inhomogeneous magnetization transfer (ihMT) gradient echo sequence allowing for whole‐brain imaging within a clinically compatible scan time. Theory and Methods: A general framework for ihMT modelling was developed based on the Provotorov theory of radiofrequency saturation, which accounts for the dipolar order underpinning the ihMT effect. Experimental studies and numerical simulations were performed to characterize and optimize the ihMT‐gradient echo dependency with sequence timings, saturation power, and offset frequency. The protocol was optimized in terms of maximum signal intensity and the reproducibility assessed for a nominal resolution of 1.5 mm isotropic. All experiments were performed on healthy volunteers at 1.5T. Results: An important mechanism driving signal optimization and leading to strong ihMT signal enhancement that relies on the dynamics of radiofrequency energy deposition has been identified. By taking advantage of the delay allowed for readout between ihMT pulse bursts, it was possible to boost the ihMT signal by almost 2‐fold compared to previous implementation. Reproducibility of the optimal protocol was very good, with an intra‐individual error < 2%. Conclusion: The proposed sensitivity‐boosted and time‐efficient steady‐state ihMT‐gradient echo sequence, implemented and optimized at 1.5T, allowed robust high‐resolution 3D ihMT imaging of the whole brain within a clinically compatible scan time. Magn Reson Med 79:2607–2619, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

In this preliminary study, our objective was to investigate the potential of high-resolution anatomical imaging, diffusion tensor imaging (DTI) and conventional/inhomogeneous magnetization transfer imaging [magnetization transfer (MT)/inhomogeneous magnetization transfer (ihMT)] at 3 T, analyzed with template-extracted regions of interest, to measure the atrophy and structural changes of white (WM) and gray (GM) matter spinal cord (SC) occurring in patients with amyotrophic lateral sclerosis (ALS). Ten patients with ALS and 20 age-matched healthy controls were recruited. SC GM and WM areas were automatically segmented using dedicated templates. Atrophy indices were evaluated from T2*-weighted images at each vertebral level from cervical C1 to C6. DTI and ihMT metrics were quantified within the corticospinal tract (CST), posterior sensory tract (PST) and anterior GM (aGM) horns at the C2 and C5 levels. Clinical disabilities of patients with ALS were evaluated using the Revised ALS Functional Rating Scale, upper motor neuron (UMN) and Medical Research Council scorings, and correlated with MR metrics. Compared with healthy controls, GM and WM atrophy was observed in patients with ALS, especially at lower cervical levels, where a strong correlation was also observed between GM atrophy and the UMN score ( R = −0.75, p = 0.05 at C6). Interestingly, a significant decrease in ihMT ratio was found in all regions of interest ( p < 0.0008), fractional anisotropy (FA) and MT ratios decreased significantly in CST, especially at C5 ( p < 0.005), and λ// (axial diffusivity) decreased significantly in CST ( p = 0.0004) and PST ( p = 0.003) at C2. Strong correlations between MRI metrics and clinical scores were also found (0.47 < | R| < 0.87, p < 0.05). Altogether, these preliminary results suggest that high-resolution anatomical imaging and ihMT imaging, in addition to DTI, are valuable for the characterization of SC tissue impairment in ALS. In this study, in addition to an important SC WM demyelination, we also observed, for the first time in ALS, impairments of cervical aGM. [ABSTRACT FROM AUTHOR]

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. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test-retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z-scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Recently, there has been an increased interest in the use of automatically segmented subfields of the human hippocampal formation derived from magnetic resonance imaging (MRI). However, little is known about the test-retest reproducibility of such measures, particularly in the context of multisite studies. Here, we report the reproducibility of automated Freesurfer hippocampal subfields segmentations in 65 healthy elderly enrolled in a consortium of 13 3T MRI sites (five subjects per site). Participants were scanned in two sessions (test and retest) at least one week apart. Each session included two anatomical 3D T1 MRI acquisitions harmonized in the consortium. We evaluated the test-retest reproducibility of subfields segmentation (i) to assess the effects of averaging two within-session T1 images and (ii) to compare subfields with whole hippocampus volume and spatial reliability. We found that within-session averaging of two T1 images significantly improved the reproducibility of all hippocampal subfields but not that of the whole hippocampus. Volumetric and spatial reproducibility across MRI sites were very good for the whole hippocampus, CA2-3, CA4-dentate gyrus (DG), subiculum (reproducibility error∼2% and DICE > 0.90), good for CA1 and presubiculum (reproducibility error ∼ 5% and DICE ∼ 0.90), and poorer for fimbria and hippocampal fissure (reproducibility error ∼ 15% and DICE < 0.80). Spearman's correlations confirmed that test-retest reproducibility improved with volume size. Despite considerable differences of MRI scanner configurations, we found consistent hippocampal subfields volumes estimation. CA2-3, CA4-DG, and sub-CA1 (subiculum, presubiculum, and CA1 pooled together) gave test-retest reproducibility similar to the whole hippocampus. Our findings suggest that the larger hippocampal subfields volume may be reliable longitudinal markers in multisite studies. Hum Brain Mapp 36:3516-3527, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT 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 [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

In multiple sclerosis (MS), it seems likely that the variability of the long-term disability might be partly due to the variability of the early gray matter (GM) injury. In the present study, we assessed the variability of GM injury in early MS, using a method designed to determine individual pathological GM patterns. Eighteen patients presenting with a clinically isolated syndrome and 24 healthy matched control subjects were included in this study. Patients were explored using a 1.5 Tesla MR scanner (Magnetom Vision Plus; Siemens). Brain MR protocol included magnetization transfer ratio imaging (MTR). Statistical mapping analyses were performed to compare each subject's GM MTR maps with those of the whole group of control subjects (SPM5). The statistical threshold was taken to be the maximum P value showing no significant cluster when any control individual was compared with the whole control population. GM abnormalities were observed in 83% of the patients, ranging in size from 0.3 to 125 cm3. Among the patients with GM abnormalities, 87% had abnormalities located in the temporal cortex, 80% in the frontal cortex, 80% in the limbic cortex, 73% in the posterior fossa, 53% in the deep GM, 47% in the parietal cortex, and 47% in the occipital cortex. Individual statistical mapping of MTR data, which gives a quantitative assessment of individual GM lesions, demonstrates great variability of grey matter injury in the first stage of multiple sclerosis. J. Magn. Reson. Imaging 2010;32:424-428. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A better understanding of interstructure relationship sustaining drug-resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting-state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single-shot GE-EPI acquisitions were acquired in 37 right-handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time-course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC-AntHip link, and a trend of decreased connectivity of the left AntHip-PostHip link. In contrast, a trend of increased connectivity of the right AntHip-PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms. Hum Brain Mapp 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

To determine the potential value of multimodal MRI for the presurgical management of patients with brain tumors, we performed combined magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS) in 164 patients who presented with tumors of various histological subtypes confirmed by surgical biopsy. Univariate statistical analysis of metabolic ratios carried out on the first 121 patients demonstrated significant differences in between-group comparisons, but failed to provide sufficiently robust classification of individual cases. However, a multivariate statistical approach correctly classified the tumors using linear discriminant analysis (LDA) of combined MRI and MRS data. After initial separation of contrast-enhancing and non-contrast-enhancing lesions, 91% of the former and 87% of the latter were correctly classified. The results were stable when this diagnostic strategy was tested on the additional 43 patients included for validation after the initial statistical analysis, with over 90% of correct classification. Combined MRI and MRS had superior diagnostic value compared to MRS alone, especially in the contrast-enhancing group. This study shows the clinical value of a multivariate statistical analysis based on multimodal MRI and MRS for the noninvasive evaluation of intracranial tumors. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal-appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT. Hum. Brain Mapping 24:216-228, 2005. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose To determine whether voxel-based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS). Materials and Methods We acquired GM MTR maps in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex- and age-matched healthy controls. We evaluated the clinical status of the patients using the MS functional composite score and the expanded disability status scale. A two-sample t-test ( P < 0.0001, k = 20, uncorrected for height threshold) was used to compare GM MTR maps from patients and controls on a voxel-by-voxel basis. We then extracted data from regions with t-values above the statistical threshold to verify the significance of differences using a nonparametric Mann-Whitney U-test. Results A between-groups comparison of GM maps revealed large abnormalities in the basal ganglia, including the bilateral thalamus, bilateral lenticular nucleus, bilateral head of caudate, and protuberance, and smaller abnormalities in the right insula, right BA 4, and left BA 40. The MTR measured in the left caudate and right insula was inversely correlated with duration following the first clinical event. Conclusion These results suggest that although MS is a multifocal demyelinating disease that affects white matter (WM), a pattern of tissue damage is present inside the GM involving predominantly basal ganglia at the earliest stage of the disease. J. Magn. Reson. Imaging 2004;20:765-771. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Summary: Purpose: This study compared the metabolic regional alterations, characterized by proton magnetic spectroscopic imaging (1 H-MRSI), with electrophysiological abnormalities recorded by using depth electrodes and with structural lesions, in patients with several subtypes of temporal lobe epilepsy (TLE). Methods: Twenty-five subjects were investigated, including 15 controls and 10 patients with drug-resistant unilateral TLE, nine of whom had structural abnormalities identified by MRI. All patients underwent noninvasive presurgical evaluation and then stereoelectroencephalography (SEEG). We performed an original metabolic exploration combining two 1 H-MRS imaging acquisitions associated with two single-voxel acquisitions (temporal poles) to map the most informative regions of interest (ROIs) including mesial and neocortical localizations. The N -acetyl aspartate/(choline+creatine) ratio was chosen as a metabolic index. SEEG analysis allowed the classification of each ROI as electrically normal or abnormal (i.e., involved in ictal and/or interictal discharges). Groups were compared by using a nonparametric Mann–Whitney U test. Results: N -Acetyl aspartate/(choline+creatine) was significantly lower in all regions involved in SEEG electrophysiological epileptic abnormalities than in controls (p < 0.05). In contrast, the regions without any electrophysiological abnormalities were not metabolically different from those in controls (p > 0.05) except in one ROI. No differences between the metabolic profiles of epileptogenic and irritative zones were found. The metabolic alterations included, but also extended beyond, the lesions. The presence of metabolic abnormalities in mesial structures was not specific for the mesial subtype and generally extended outside the mesial structures. Conclusions: These results indicate that metabolic abnormalities are linked to ictal and interictal epileptiform activities rather than to structural... [ABSTRACT FROM AUTHOR]

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