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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. [ABSTRACT FROM AUTHOR]

Atrophy of corpus callosum (CC) related to axonal loss has previously been observed in patients at the early stage of clinically definite multiple sclerosis (CDMS). Atrophy increases with the progression of the disease. Nevertheless, no data concerning the onset of atrophy of CC are currently available. The purpose of this study is to determine if damage in callosal tissue was present at the earliest stage of MS, in a subgroup of patients presenting with a clinically isolated syndrome suggestive of MS (CISSMS), fulfilling the dissemination in space criteria according to McDonald. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) techniques were applied to measure CC volume, magnetization transfer ratio (MTR), mean diffusivity (MD), N-acetyl aspartate/choline-containing compounds (NAA/Cho) ratio, N-acetyl aspartate/total creatine (NAA/Cr) ratio and Cho/Cr ratio inside the CC of 46 CISSMS patients and 24 sex- and age-matched controls. No atrophy of CC was observed in the CISSMS group. CC of patients was characterized by decreased MTR and increased MD. No change in the NAA/Cr ratio was observed while the NAA/Cho ratio decreased and Cho/Cr ratio increased in the splenium and the central anterior part of CC. These abnormalities were present in patients with, but also without, macroscopic lesions inside the CC. Our results indicate that diffuse structural and metabolic changes, which may be interpreted as representing predominantly myelin pathology, occur in the CC at the earliest stage of MS before any atrophy is detected. [ABSTRACT FROM AUTHOR]

Magnetic resonance spectroscopy (MRS) is proposed in addition to magnetic resonance imaging (MRI) to help in the characterization of brain tumours by detecting metabolic alterations that may be indicative of the tumour class. MRS can be routinely performed on clinical magnets, within a reasonable acquisition time and if performed under adequate conditions, MRS is reproducible and thus can be used for longitudinal follow-up of treatment. MRS can also be performed in clinical practice to guide the neurosurgeon into the most aggressive part of the lesions or to avoid unnecessary surgery, which may furthermore decrease the risk of surgical morbidity. [ABSTRACT FROM AUTHOR]

Objectives: Compelling evidence indicates a significant involvement of cortical lesions in the progressive phase of multiple sclerosis (MS), significantly contributing to late-stage disability. Despite the promise of ultra-high-field magnetic resonance imaging (MRI) in detecting cortical lesions, current evidence falls short in providing insights into the existence of such lesions during the early stages of MS or their underlying cause. This study delineated, at the early stage of MS, (1) the prevalence and spatial distribution of cortical lesions identified by 7 T MRI, (2) their relationship with white matter lesions, and (3) their clinical implications., Materials and Methods: Twenty individuals with early-stage relapsing-remitting MS (disease duration <1 year) underwent a 7 T MRI session involving T1-weighted MP2RAGE, T2*-weighted multiGRE, and T2-weighted FLAIR sequences for cortical and white matter segmentation. Disability assessments included the Expanded Disability Status Scale, the Multiple Sclerosis Functional Composite, and an extensive evaluation of cognitive function., Results: Cortical lesions were detected in 15 of 20 patients (75%). MP2RAGE revealed a total of 190 intracortical lesions (median, 4 lesions/case [range, 0-44]) and 216 leukocortical lesions (median, 2 lesions/case [range, 0-75]). Although the number of white matter lesions correlated with the total number of leukocortical lesions ( r = 0.91, P < 0.001), no correlation was observed between the number of white matter or leukocortical lesions and the number of intracortical lesions. Furthermore, the number of leukocortical lesions but not intracortical or white-matter lesions was significantly correlated with cognitive impairment ( r = 0.63, P = 0.04, corrected for multiple comparisons)., Conclusions: This study highlights the notable prevalence of cortical lesions at the early stage of MS identified by 7 T MRI. There may be a potential divergence in the underlying pathophysiological mechanisms driving distinct lesion types, notably between intracortical lesions and white matter/leukocortical lesions. Moreover, during the early disease phase, leukocortical lesions more effectively accounted for cognitive deficits., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Patients presenting with drug-resistant epilepsy are eligible for surgery aiming to remove the regions involved in the production of seizure activities, the so-called epileptogenic zone network (EZN). Thus the accurate estimation of the EZN is crucial. Data-driven, personalized virtual brain models derived from patient-specific anatomical and functional data are used in Virtual Epileptic Patient (VEP) to estimate the EZN via optimization methods from Bayesian inference. The Bayesian inference approach used in previous VEP integrates priors, based on the features of stereotactic-electroencephalography (SEEG) seizures' recordings. Here, we propose new priors, based on quantitative 23 Na-MRI. The 23 Na-MRI data were acquired at 7T and provided several features characterizing the sodium signal decay. The hypothesis is that the sodium features are biomarkers of neuronal excitability related to the EZN and will add additional information to VEP estimation. In this paper, we first proposed the mapping from 23 Na-MRI features to predict the EZN via a machine learning approach. Then, we exploited these predictions as priors in the VEP pipeline. The statistical results demonstrated that compared with the results from current VEP, the result from VEP based on 23 Na-MRI prior has better balanced accuracy, and the similar weighted harmonic mean of the precision and recall., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2024 Massachusetts Institute of Technology.)

Background: Progression independent of relapse activity (PIRA) has been described since the early stage of relapsing multiple sclerosis (RMS). However, little is known about the relation between PIRA and inflammatory activity that is particularly important at this stage of the disease., Method: We included 110 patients in a prospective study within 18 months of RMS onset. MRI examinations and clinical visits were scheduled on the same day for months 0, 6, 12, 24, 36, 60, 84, 120, 180 and 240., Results: The mean (SD) age of patients was 30 (6.7) years at inclusion and median (range) follow-up 15 (9-20) years. Analysis of 1118 between-visit intervals revealed 93 confirmed disability accumulation events in 68 (62%) patients: 50 (54%) events related to relapse activity worsening and 43 (46%) PIRA events, including 17 (18%) with MRI activity. The risk of PIRA between two visits (stable event as the reference category) was associated with Expanded Disability Status Scale (EDSS) score (HR: 1.41; 95% CI: 1.18 to 1.69; p<0.001), disease duration (HR: 0.75; 95% CI: 0.62 to 0.90; p<0.005) and new lesions between the visits (HR: 1.09 per lesion; 95% CI: 1.01 to 1.17; p<0.05). As compared with PIRA events with MRI activity, PIRA events without such activity occurred in patients with more disability (mean EDSS score 3, p<0.05), longer disease duration (mean 11 years, p<0.001) and greater number of T2-weighted lesions (p<0.05)., Conclusion: This study evidenced that inflammatory activity increases the risk of PIRA in early RMS, arguing that a significant part of PIRA is accessible to treatment targeting inflammation in these patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Whole-brain functional connectivity networks (connectomes) have been characterized at different scales in humans using EEG and fMRI. Multimodal epileptic networks have also been investigated, but the relationship between EEG and fMRI defined networks on a whole-brain scale is unclear. A unified multimodal connectome description, mapping healthy and pathological networks would close this knowledge gap. Here, we characterize the spatial correlation between the EEG and fMRI connectomes in right and left temporal lobe epilepsy (rTLE/lTLE). From two centers, we acquired resting-state concurrent EEG-fMRI of 35 healthy controls and 34 TLE patients. EEG-fMRI data was projected into the Desikan brain atlas, and functional connectomes from both modalities were correlated. EEG and fMRI connectomes were moderately correlated. This correlation was increased in rTLE when compared to controls for EEG-delta/theta/alpha/beta. Conversely, multimodal correlation in lTLE was decreased in respect to controls for EEG-beta. While the alteration was global in rTLE, in lTLE it was locally linked to the default mode network. The increased multimodal correlation in rTLE and decreased correlation in lTLE suggests a modality-specific lateralized differential reorganization in TLE, which needs to be considered when comparing results from different modalities. Each modality provides distinct information, highlighting the benefit of multimodal assessment in epilepsy., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2024 Massachusetts Institute of Technology.)

Introduction: Identifying biomarkers reflecting cellular dysfunctions in early Parkinson's disease patients (ePD) is needed to develop targeted therapeutic strategies. We aimed to determine if cellular energetic dysfunction related to increased brain sodium concentration would be co-located to microstructural alterations and iron deposition in ePD., Methods: We prospectively included 12 ePD (mean disease duration 20.0 ± 10.2 months) and 13 healthy controls (HC), scanned with a 7 T 1 H and 23 Na MRI. Complementary voxel-based and region-based assessments were performed, the latter utilizing a high-resolution multimodal template we created (combining quantitative T 1 maps (qT1), transverse relaxation rate (R2*), quantitative magnetic susceptibility mapping (QSM) images) from 200 subjects. This template allowed a precise multiparametric assessment of sodium concentration, QSM, R 2 *, qT 1 , mean diffusivity, and fractional anisotropy values. A two-sided p-value<0.05 was considered statistically significant after the Bonferroni correction., Results: Relative to HC, ePD showed significantly higher sodium concentration in left Substantia nigra (SN) pars reticulata (46.13 mM ± 3.52 vs 38.60 mM ± 6.10, p = 0.038), a subpart of the SN pars compacta (SNc) and ventral tegmental area, Putamen, Globus Pallidum external, accumbens nucleus and claustrum. Significantly increased QSM and R2* values, and decreased T 1 values, were limited to the Nigrosomes 1 (Nig) and right SNc (all p < 0.05). QSM values in the Nig were significantly correlated to UPDRS-III scores (r = 0.91,p < 0.001)., Conclusion: In ePD, brain sodium accumulation was broad and dissociated from iron accumulation. As with iron accumulation, a sodium-related pathophysiological approach could lead to identifying potential new therapeutic agents and deserves further investigation., Competing Interests: Declaration of competing interest No COI., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To study the relative contributions of brain and upper cervical spinal cord compartmental atrophy to disease aggressiveness in amyotrophic lateral sclerosis (ALS)., Methods: Twenty-nine ALS patients and 24 age- and gender-matched healthy controls (HC) were recruited. Disease duration and the Revised-ALS Functional Rating Scale (ALSFRS-R) at baseline, 3- and 6-months follow-up were assessed. Patients were clinically differentiated into fast (n=13) and slow (n=16) progressors according to their ALSFRS-R progression rate. Brain grey (GM) and white matter, brainstem sub-structures volumes and spinal cord cross-sectional area (SC-CSA) at C1-C2 vertebral levels were measured from a 3D-T1-weighted MRI., Results: Fast progressors showed significant GM, medulla oblongata and SC atrophy compared to HC (p<0.001, p=0.013 and p=0.008) and significant GM atrophy compared to slow progressors (p=0.008). GM volume correlated with the ALSFRS-R progression rate (Rho/p=-0.487/0.007), the ALSFRS-R at 3-months (Rho/p=0.622/0.002), and ALSFRS-R at 6-months (Rho/p=0.407/0.039). Medulla oblongata volume and SC-CSA correlated with the ALSFRS-R at 3-months (Rho/p=0.510/0.015 and Rho/p=0.479/0.024). MRI measures showed high performance to discriminate between fast and slow progressors., Conclusion: Our study suggests an association between compartmental atrophy and disease aggressiveness. This result is consistent with the combination of upper and lower motor neuron degeneration as the main driver of disease worsening and severity in ALS. Our study highlights the potential of brain and spinal cord atrophy measured by MRI as biomarker of disease aggressiveness signature., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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 (T 1D ) 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], T 2,f , T 2,b , R, and free pool T 1 ). 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 T 1 ., 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 T 1 (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 ΔT 1  = -19.0 ms). The single-point methodology yielded consistent MPF and T 1 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., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

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 T 1 data to provide an unprecedented description of subcortical morphological (volume, tissue deformation, and shape) and longitudinal relaxation (T 1 ) 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 T 1 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 T 1 measures looked promising to further differentiate patients based on EZN localization. In particular, the observed differences in T 1 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., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Whole brain ionic and metabolic imaging has potential as a powerful tool for the characterization of brain diseases. We combined sodium MRI ( 23 Na MRI) and 1 H-MR Spectroscopic Imaging ( 1 H-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 ( 23 Na-MRI) and a 3D echo-planar spectroscopic imaging sequence at 3 T ( 1 H-MRSI) in 19 patients suffering from drug-resistant focal epilepsy who underwent presurgical SEEG. We investigated 23 Na MRI parameters including total sodium concentration (TSC) and the sodium signal fraction associated with the short component of T 2 * 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., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: To investigate the association of ihMT (inhom signals with the demyelination and remyelination phases of the acute cuprizone mouse model in comparison with histology, and to assess the extent of tissue damage and repair from MRI data., Methods: Acute demyelination by feeding 0.2% cuprizone for five weeks, followed by a four-week remyelination period was applied on genetically modified plp-GFP mice. Animals were scanned at different time points of the demyelination and remyelination phases of the cuprizone model using a multimodal MRI protocol, including ihMT T 1D -filters, MPF (Macromolecular Proton Fraction) and R 1 (longitudinal relaxation rate). For histology, plp-GFP (proteolipid protein - Green Fluorescent Protein) microscopy and LFB (Luxol Fast Blue) staining were employed as references for the myelin content. Comparison of MRI with histology was performed in the medial corpus callosum (mCC) and cerebral cortex (CTX) at two brain levels whereas ROI-wise and voxel-based analyses of the MRI metrics allowed investigating in vivo the spatial extent of myelin alterations., Results: IhMT high-pass T 1D -filters, targeted toward long T 1D components, showed significant temporal variations in the mCC consistent with the effects induced by the cuprizone toxin. In addition, the corresponding signals correlated strongly and significantly with the myelin content assessed by GFP fluorescence and LFB staining over the demyelination and the remyelination phases. The signal of the band-pass T 1D -filter, which isolates short T 1D components, showed changes over time that were poorly correlated with histology, hence suggesting a sensitivity to pathological processes possibly not related to myelin. Although MPF was also highly correlated to histology, ihMT high-pass T 1D -filters showed better capability to characterize the spatial-temporal patterns during the demyelination and remyelination phases of the acute cuprizone model (e.g., rostro-caudal gradient of demyelination in the mCC previously described in the literature)., Conclusions: IhMT sequences selective for long T 1D components are specific and sensitive in vivo markers of demyelination and remyelination and have successfully captured the spatially heterogeneous pattern of the demyelination and remyelination mechanisms in the cuprizone model. Interestingly, differences in signal variations between the ihMT high-pass and band-pass T 1D -filter, suggest a sensitivity of the ihMT sequences targeted to short T 1D s to alterations other than those of myelin. Future studies will need to further address these differences by examining more closely the origin of the short T 1D components and the variation of each T 1D component in pathology., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Quantification of brain injury in patients with variable disability despite similar disease duration may be relevant to identify the mechanisms underlying disability in multiple sclerosis (MS). We aimed to compare grey-matter sodium abnormalities (GMSAs), a parameter reflecting neuronal and astrocyte dysfunction, in MS patients with benign multiple sclerosis (BMS) and non-benign multiple sclerosis (NBMS)., Methods: We identified never-treated BMS patients in our local MS database of 1352 patients. A group with NBMS was identified with same disease duration. All participants underwent 23 Na magnetic resonance imaging (MRI). The existence of GMSA was detected by statistical analysis., Results: In total, 102 individuals were included (21 BMS, 25 NBMS and 56 controls). GMSA was detected in 10 BMS and 19 NBMS (11/16 relapsing-remitting multiple sclerosis (RRMS) and 8/9 secondary progressive multiple sclerosis (SPMS) patients) ( p  = 0.05). On logistic regression including the presence or absence of GMSA, thalamic volume, cortical grey-matter volume and T2-weighted lesion load, thalamic volume was independently associated with BMS status (odds ratio (OR) = 0.64 for each unit). Nonetheless, the absence of GMSA was independently associated when excluding patients with significant cognitive alteration ( n  = 7) from the BMS group (OR = 4.6)., Conclusion: Detection of GMSA in individuals and thalamic volume are promising to differentiate BMS from NBMS as compared with cortical or whole grey-matter atrophy and T2-weighted lesions.

Background and Purpose: While conventional MR imaging has limited value in amyotrophic lateral sclerosis, nonconventional MR imaging has shown alterations of microstructure using diffusion MR imaging and recently sodium homeostasis with sodium MR imaging. We aimed to investigate the topography of brain regions showing combined microstructural and sodium homeostasis alterations in amyotrophic lateral sclerosis subgroups according to their disease-progression rates., Materials and Methods: Twenty-nine patients with amyotrophic lateral sclerosis and 24 age-matched healthy controls were recruited. Clinical assessments included disease duration and the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. Patients were clinically differentiated into fast ( n = 13) and slow ( n = 16) progressors according to the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale progression rate. 3T MR imaging brain protocol included 1 H T1-weighted and diffusion sequences and a 23 Na density-adapted radial sequence. Quantitative maps of diffusion with fractional anisotropy, mean diffusivity, and total sodium concentration were measured. The topography of diffusion and sodium abnormalities was assessed by voxelwise analyses., Results: Patients with amyotrophic lateral sclerosis showed significantly higher sodium concentrations and lower fractional anisotropy, along with higher sodium concentrations and higher mean diffusivity compared with healthy controls, primarily within the corticospinal tracts, corona radiata, and body and genu of the corpus callosum. Fast progressors showed wider-spread abnormalities mainly in the frontal areas. In slow progressors, only fractional anisotropy measures showed abnormalities compared with healthy controls, localized in focal regions of the corticospinal tracts, the body of corpus callosum, corona radiata, and thalamic radiation., Conclusions: The present study evidenced widespread combined microstructural and sodium homeostasis brain alterations in fast amyotrophic lateral sclerosis progressors., (© 2022 by American Journal of Neuroradiology.)

Purpose: Ultra-high field 1 H 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 B 0 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., (© 2022 International Society for Magnetic Resonance in Medicine.)

Purpose: To minimize the sensitivity of inhomogeneous magnetization transfer gradient-echo (ihMT-GRE) imaging to radiofrequency (RF) transmit field ( B 1 + ) 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 B 1 + variations was investigated by comparing measurements obtained at nominal transmitter adjustments and following a 20% global B 1 + drop. The resulting relative variations (δ ihMTR ) were evaluated voxelwise as a function of the local B 1 + distribution. The reproducibility of the protocol providing minimal B 1 + 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 B 1 + 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 δ ihMTR 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 B 1 + variations and allows for clinical-ready ihMT imaging at 3 T. This feature is of particular interest for high and ultra-high field applications., (© 2021 International Society for Magnetic Resonance in Medicine.)

Hypothalamus (HT), this small structure often perceived through the prism of neuroimaging as morphologically and functionally homogeneous, plays a key role in the primitive act of feeding. The current paper aims at reviewing the contribution of magnetic resonance imaging (MRI) in the study of the role of the HT in food intake regulation. It focuses on the different MRI techniques that have been used to describe structurally and functionally the Human HT. The latest advances in HT parcellation as well as perspectives in this field are presented. The value of MRI in the study of eating disorders such as anorexia nervosa (AN) and obesity are also highlighted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Roger, Lasbleiz, Guye, Dutour, Gaborit and Ranjeva.)

Rugby players are subject to multiple impacts to their head and neck that could have adverse neurological effects and put them at increased risk of neurodegeneration. Previous studies demonstrated altered default mode network and diffusion metrics on brain, as well as more foraminal stenosis, disc protrusion and neck pain among players of contact sports as compared to healthy controls. However, the long-term effects of practice and repetitive impacts on brain and cervical spinal cord (cSC) of the rugby players have never been systematically investigated. In this study, 15 retired professional and amateur rugby players (R) and 15 age-matched healthy controls (HC) (all males; mean age R: 46.8 ± 7.6; and HC: 48.6 ± 9.5) were recruited both to investigate cord impairments and further characterize brain structure damage. Medical questionnaires including modified Japanese Orthopedic Association scale (mJOA) and Neck Disability Index (NDI) were filled by all participants. A 3 T multi-parametric MR protocol including conventional qualitative techniques such as T 1 -, T 2 -, and T 2 *-weighted sequences, as well as state-of-the art quantitative techniques including MP2RAGE T 1 mapping and 3D ihMTRAGE, was used on both brain and cSC. Normalized brain WM and GM volumes, spine Overall Stenosis Score, cord cross-sectional area and regional T 1 and ihMT metrics were derived from these acquisitions. Rugby players showed significantly higher NDI scores, as well as a faster decline of normalized brain GM volume with age as compared to HC. Moreover, higher T 1 values on cSC suggestive of structural degeneration, together with higher T 1 and lower ihMTsat on brain WM suggestive of demyelination, were observed in retired rugby players as compared to age-matched controls, which may suggest cumulative effects of long-term impacts on the tissues. Metrics also suggest early aging and different aging processes on brain tissue in the players. These preliminary observations provide new insights in the domain, which should now be further investigated on larger cohorts and multicentric longitudinal studies, and further correlated to the likelihood of neurodegenerative diseases and risk factors., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 T 1 -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 T 1 values derived from the 3D-MP2RAGE volumes, after correction for residual B 1 + 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 T 1 values was highlighted. This represents a fully automated segmentation process permitting the extraction of unbiased normative T 1 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., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objective: Amygdala enlargement is increasingly described in association with temporal lobe epilepsies. Its significance, however, remains uncertain both in terms of etiology and its link with psychiatric disorders and of its involvement in the epileptogenic zone. We assessed the epileptogenic networks underlying drug-resistant epilepsy with amygdala enlargement and investigated correlations between clinical features, epileptogenicity and morphovolumetric amygdala characteristics., Methods: We identified 12 consecutive patients suffering from drug-resistant epilepsy with visually suspected amygdala enlargement and available stereoelectroencephalographic recording. The epileptogenic zone was defined using the Connectivity Epileptogenicity Index. Morphovolumetric measurements were performed using automatic segmentation and co-registration on the 7TAMIbrain Amygdala atlas., Results: The epileptogenic zone involved the enlarged amygdala in all but three cases and corresponded to distributed, temporal-insular, temporal-insular-prefrontal or prefrontal-temporal networks in ten cases, while only two were temporo-mesial networks. Morphovolumetrically, amygdala enlargement was bilateral in 75% of patients. Most patients presented psychiatric comorbidities (anxiety, depression, posttraumatic stress disorder). The level of depression defined by screening questionnaire was positively correlated with the extent of amygdala enlargement., Conclusions: Drug-resistant epilepsy with amygdala enlargement is heterogeneous; most cases implied "temporal plus" networks., Significance: The enlarged amygdala could reflect an interaction of stress-mediated limbic network alterations and mechanisms of epileptogenesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Rationale: Donepezil is a potent, noncompetitive, reversible, clinically effective acetylcholinesterase inhibitor. The effects of this drug on healthy brains have seldom been investigated., Objectives: The primary objective of the present study was to identify possible functional connectivity markers of the effect of donepezil in healthy young adult volunteers., Methods: The study had a double-blind, randomized, crossover design. 30 healthy adult volunteers underwent resting-state MRI scans during 15 days of donepezil or placebo treatment, in accordance with the design., Results: Results showed significant differences in intrinsic functional connectivity between donepezil and placebo, mainly in the right executive control network (RECN). More specifically, we found a decrease in the connectivity of the right inferior parietal node with other RECN nodes. Analysis using the cingulate cortex and parahippocampal regions as seeds also revealed complex modulation of functional connectivity in the donepezil condition., Conclusions: In conclusion, donepezil treatment for 15 days may result in reorganization of resting-state networks, compared with placebo., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pathophysiology of idiopathic Parkinson's disease (iPD) is complex and still misunderstood. At a time when treatments with disease-modifying potential are being developed, identification of early markers of neurodegeneration is essential. Intracerebral sodium accumulation could be one of them. Indeed, it may be in relation to the mitochondrial dysfunction that early exists in iPD. For the first time, we used brain sodium ( 23 Na) MRI to explore sodium concentration changes that have already been reported to be related to neurodegeneration in other diseases. We prospectively included 10 iPD patients (mean age 52.2 ± 5.9 years-old) with motor symptoms that started <36 months before inclusion and 12 healthy subjects (mean age 53 ± 6.4 years-old). Patients were scanned in OFF medication state by using proton ( 1 H) and 23 Na MRI at 7T. We then extracted quantitative Total Sodium Concentration (TSC) from five regions of interest known to be early impaired in iPD [substantia nigra (SN), putamen, caudate nucleus, pallidum, thalamus] and in one region supposed to be relatively spared in the first stages of the disease [cortical gray matter (neocortex)]. Potential atrophy in these structures was also investigated with 1 H MRI. Relative to healthy subjects, iPD patients showed higher TSC in the SN (43.73 ± 4.64 vs. 37.72 ± 5.62, p = 0.006 after Bonferroni correction). A trend of increase in sodium concentrations was found within the pallidum (45.80 ± 4.19 vs. 41.07 ± 4.94, p = 0.017), putamen (48.65 ± 4.58 vs. 43.66 ± 5.04, p = 0.041) and the cortical gray matter (56.34 ± 3.92 vs. 50.81 ± 5.50, p = 0.021). No significant brain atrophy was found in patients compared to controls. Thus, alteration of sodium homeostasis in the SN in the absence of atrophy could be considered as a potential early marker of cellular dysfunction in iPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Grimaldi, El Mendili, Zaaraoui, Ranjeva, Azulay, Eusebio and Guye.)

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., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Single-voxel proton cardiovascular magnetic resonance spectroscopy ( 1 H-CMRS) benefits from 3 T to detect metabolic abnormalities with the quantification of intramyocardial fatty acids (FA) and creatine (Cr). Conventional point resolved spectroscopy (PRESS) sequence remains the preferred choice for CMRS, despite its chemical shift displacement error (CSDE) at high field (≥ 3 T). Alternative candidate sequences are the semi-adiabatic Localization by Adiabatic SElective Refocusing (sLASER) recommended for brain and musculoskeletal applications and the localized stimulated echo acquisition mode (STEAM). In this study, we aim to compare these three single-voxel 1 H-CMRS techniques: PRESS, sLASER and STEAM for reproducible quantification of myocardial FA and Cr at 3 T. Sequences are compared both using breath-hold (BH) and free-breathing (FB) acquisitions., Methods: CMRS accuracy and theoretical CSDE were verified on a purposely-designed fat-water phantom. FA and Cr CMRS data quality and reliability were evaluated in the interventricular septum of 10 healthy subjects, comparing repeated BH and free-breathing with retrospective gating., Results: Measured FA/W ratio deviated from expected phantom ratio due to CSDE with all sequences. sLASER supplied the lowest bias (10%, vs -28% and 27% for PRESS and STEAM). In vivo, PRESS provided the highest signal-to-noise ratio (SNR) in FB scans (27.5 for Cr and 103.2 for FA). Nevertheless, a linear regression analysis between the two BH showed a better correlation between myocardial Cr content measured with sLASER compared to PRESS (r = 0.46; p = 0.03 vs. r = 0.35; p = 0.07) and similar slopes of regression lines for FA measurements (r = 0.94; p < 0.001 vs. r = 0.87; p < 0.001). STEAM was unable to perform Cr measurement and was the method with the lowest correlation (r = 0.59; p = 0.07) for FA. No difference was found between measurements done either during BH or FB for Cr, FA and triglycerides using PRESS, sLASER and STEAM., Conclusion: When quantifying myocardial lipids and creatine with CMR proton spectroscopy at 3 T, PRESS provided higher SNR, while sLASER was more reproducible both with single BH and FB scans.

This manuscript reviews the contributions of the neuroimaging methods including PET, conventional and advanced MRI methods to monitor the effect of new disease modifying drugs in neurodegenerative diseases. It now seems obvious that in many pathologies these two techniques are more and more complementary., (Copyright © 2020. Published by Elsevier Masson SAS.)

Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation., (© 2020 American Academy of Neurology.)

Objectives: Ultra-high field magnetic resonance imaging (MRI) (≥7 T) is a unique opportunity to improve the clinical diagnosis of brain pathologies, such as multiple sclerosis or focal epilepsy. However, several shortcomings of 7 T MRI, such as radiofrequency field inhomogeneities, could degrade image quality and hinder radiological interpretation. To address these challenges, an original synthetic MRI method based on T1 mapping achieved with the magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) sequence was developed. The radiological quality of on-demand T1-based contrasts generated by this technique was evaluated in multiple sclerosis and focal epilepsy imaging at 7 T., Materials and Methods: This retrospective study was carried out from October 2017 to September 2019 and included 21 patients with different phenotypes of multiple sclerosis and 35 patients with focal epilepsy who underwent MRI brain examinations using a whole-body investigative 7 T magnetic resonance system. The quality of 2 proposed synthetic contrast images were assessed and compared with conventional images acquired at 7 T using the MP2RAGE sequence by 4 radiologists, evaluating 3 qualitative criteria: signal homogeneity, contrast intensity, and lesion visualization. Statistical analyses were performed on reported quality scores using Wilcoxon rank tests and further multiple comparisons tests. Intraobserver and interobserver reliabilities were calculated as well., Results: Radiological quality scores were reported higher for synthetic images when compared with original images, regardless of contrast, pathologies, or raters considered, with significant differences found for all 3 criteria (P < 0.0001, Wilcoxon rank test). None of the 4 radiologists ever rated a synthetic image "markedly worse" than an original image. Synthetic images were rated slightly less satisfying for only 3 epileptic patients, without precluding lesion identification., Conclusion: T1-based synthetic MRI with the MP2RAGE sequence provided on-demand contrasts and high-quality images to the radiologist, facilitating lesion visualization in multiple sclerosis and focal epilepsy, while reducing the magnetic resonance examination total duration by removing an additional sequence., Competing Interests: Conflicts of interest and sources of funding: This study was supported by the following funding sources: 7T-AMI ANR-11-EQPX-0001, A*MIDEX-EI-13-07-130115-08.38-7T-AMISTART, Fondation ARSEP (Fondation pour l'Aide à la recherche sur la Sclérose en Plaques), and CNRS (Centre National de la Recherche Scientifique). Dr Massire is an employee of Siemens Healthcare SAS since September 2019. Dr Troalen is currently an employee of Siemens Healthcare SAS. Dr Kober is a current employee and shareholder of Siemens Healthcare AG and holds patents filed by Siemens Healthcare. For the remaining authors, no relevant relationships are declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms. A harmonized MRI protocol was implemented in 3T-scanners across 13 European sites, each scanning five volunteers twice (test-retest) using 2D-FLAIR. Automated segmentation was performed using Lesion segmentation tool algorithms (LST): the Lesion growth algorithm (LGA) in SPM8 and 12 and the Lesion prediction algorithm (LPA). To assess reproducibility, we applied the LST longitudinal pipeline to the LGA and LPA outputs for both the test and retest scans. We evaluated volumetric and spatial accuracy comparing LGA and LPA with manual tracing, and for reproducibility the test versus retest. Median volume difference between automated WMH and manual segmentations (mL) was -0.22[IQR = 0.50] for LGA-SPM8, -0.12[0.57] for LGA-SPM12, -0.09[0.53] for LPA, while the spatial accuracy (Dice Coefficient) was 0.29[0.31], 0.33[0.26] and 0.41[0.23], respectively. The reproducibility analysis showed a median reproducibility error of 20%[IQR = 41] for LGA-SPM8, 14% [31] for LGA-SPM12 and 10% [27] with the LPA cross-sectional pipeline. Applying the LST longitudinal pipeline, the reproducibility errors were considerably reduced (LGA: 0%[IQR = 0], p < 0.001; LPA: 0% [3], p < 0.001) compared to those derived using the cross-sectional algorithms. The DC using the longitudinal pipeline was excellent (median = 1) for LGA [IQR = 0] and LPA [0.02]. LST algorithms showed moderate accuracy and good reproducibility. Therefore, it can be used as a reliable cross-sectional and longitudinal tool in multi-site studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dynamic Functional Connectivity (dFC) in the resting state (rs) is considered as a correlate of cognitive processing. Describing dFC as a flow across morphing connectivity configurations, our notion of dFC speed quantifies the rate at which FC networks evolve in time. Here we probe the hypothesis that variations of rs dFC speed and cognitive performance are selectively interrelated within specific functional subnetworks. In particular, we focus on Sleep Deprivation (SD) as a reversible model of cognitive dysfunction. We found that whole-brain level (global) dFC speed significantly slows down after 24h of SD. However, the reduction in global dFC speed does not correlate with variations of cognitive performance in individual tasks, which are subtle and highly heterogeneous. On the contrary, we found strong correlations between performance variations in individual tasks -including Rapid Visual Processing (RVP, assessing sustained visual attention)- and dFC speed quantified at the level of functional sub-networks of interest. Providing a compromise between classic static FC (no time) and global dFC (no space), modular dFC speed analyses allow quantifying a different speed of dFC reconfiguration independently for sub-networks overseeing different tasks. Importantly, we found that RVP performance robustly correlates with the modular dFC speed of a characteristic frontoparietal module., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults., Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session., Results: Significant MRI site and vendor effects (p ​< ​.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman's r correlations >0.43, p ​< ​1.39E-36). In particular, volumes larger than 200 ​mm 3 (for amygdalar nuclei) and 300 ​mm 3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε ​< ​5% and DICE ​> ​0.80)., Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives : Evidence from animal studies suggests that aerobic exercise may promote neuroplasticity and could, therefore, provide therapeutic benefits for neurological diseases such as multiple sclerosis (MS). However, the effects of exercise in human CNS disorders on the topology of brain networks, which might serve as an outcome at the interface between biology and clinical performance, remain poorly understood. Methods : We investigated functional and structural networks in patients with relapsing-remitting MS in a clinical trial of standardized aerobic exercise. Fifty-seven patients were randomly assigned to moderate-intensity exercise for 3 months or a non-exercise control group. We reconstructed functional networks based on resting-state functional magnetic resonance imaging (MRI) and used probabilistic tractography on diffusion-weighted imaging data for structural networks. Results : At baseline, compared to 30 healthy controls, patients exhibited decreased structural connectivity that was most pronounced in hub regions of the brain. Vice versa, functional connectivity was increased in hubs. After 3 months, we observed hub independent increased functional connectivity in the exercise group while the control group presented a loss of functional hub connectivity. On a structural level, the control group remained unchanged, while the exercise group had also increased connectivity. Increased clustering of hubs indicates a better structural integration and internal connectivity at the top of the network hierarchy. Conclusion : Increased functional connectivity of hubs contrasts a loss of structural connectivity in relapsing-remitting MS. Under an exercise condition, a further hub independent increase of functional connectivity seems to translate in higher structural connectivity of the whole brain., (Copyright © 2020 Stellmann, Maarouf, Schulz, Baquet, Pöttgen, Patra, Penner, Gellißen, Ketels, Besson, Ranjeva, Guye, Nolte, Engel, Audoin, Heesen and Gold.)

Purpose/background: Alzheimer disease (AD) is a public health issue because of the low number of symptomatic drugs and the difficulty to diagnose it at the prodromal stage. The need to develop new treatments and to validate sensitive tests for early diagnosis could be met by developing a challenge model reproducing cognitive impairments of AD. Therefore, we implemented a 24-hour sleep deprivation (SD) design on healthy volunteers in a randomized, double-blind, placebo-controlled, crossover study on 36 healthy volunteers., Methods/procedure: To validate the SD model, cognitive tests were chosen to assess a transient worsening of cognitive functions after SD and a restoration under modafinil as positive control (one dose of 200 mg). Then, the same evaluations were replicated after 15 days of donepezil (5 mg/d) or memantine (10 mg/d). The working memory (WM) function was assessed by the N-back task and the rapid visual processing (RVP) task., Findings/results: The accuracy of the N-back task and the reaction time of the RVP revealed the alteration of the WM with SD and its restoration with modafinil (changes in score after SD compared with baseline before SD), respectively, in the placebo group and in the modafinil group (-0.2% and +1.0% of satisfactory answers, P = 0.022; +21.3 and +1.9 milliseconds of reaction time, P = 0.025). Alzheimer disease drugs also tended to reverse this deterioration: the accuracy of the N-back task was more stable through SD (compared with -3.0% in the placebo group, respectively, in the memantine group and in the donepezil group: -1.4% and -1.6%, P = 0.027 and P = 0.092) and RVP reaction time was less impacted (compared with +41.3 milliseconds in the placebo group, respectively, in the memantine group and in the donepezil group: +16.1 and +29.3 milliseconds, P = 0.034 and P = 0.459)., Implications/conclusions: Our SD challenge model actually led to a worsening of WM that was moderated by both modafinil and AD drugs. To use this approach, the cognitive battery, the vulnerability of the subjects to SD, and the expected drug effect should be carefully considered.

Amyloid and tau pathological accumulation should be considered for Alzheimer's disease (AD) definition and before subjects' enrollment in disease-modifying trials. Although age, APOEε4, and sex influence cerebrospinal fluid (CSF) biomarker levels, none of these variables are considered by current normality/abnormality cutoffs. Using baseline CSF data from 2 independent cohorts (PharmaCOG/European Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Neuroimaging Initiative), we investigated the effect of age, APOEε4 status, and sex on CSF Aβ42/P-tau distribution and cutoff extraction by applying mixture models with covariates. The Aβ42/P-tau distribution revealed the presence of 3 subgroups (AD-like, intermediate, control-like) and 2 cutoffs. The identification of the intermediate subgroup and of the higher cutoff was APOEε4 dependent in both cohorts. APOE-specific classification (higher cutoff for APOEε4+, lower cutoff for APOEε4-) showed higher diagnostic accuracy in identifying MCI due to AD compared to single Aβ42 and Aβ42/P-tau cutoffs. APOEε4 influences amyloid and tau CSF markers and AD progression in MCI patients supporting i) the use of APOE-specific cutoffs to identify MCI due to AD and ii) the utility of considering APOE genotype for early AD diagnosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: The inhomogeneous magnetization transfer technique has demonstrated high specificity for myelin, and has shown sensitivity to multiple sclerosis-related impairment in brain tissue. Our aim was to investigate its sensitivity to spinal cord impairment in MS relative to more established MR imaging techniques (volumetry, magnetization transfer, DTI)., Materials and Methods: Anatomic images covering the cervical spinal cord from the C1 to C6 levels and DTI, magnetization transfer/inhomogeneous magnetization transfer images at the C2/C5 levels were acquired in 19 patients with MS and 19 paired healthy controls. Anatomic images were segmented in spinal cord GM and WM, both manually and using the AMU 40 atlases. MS lesions were manually delineated. MR metrics were analyzed within normal-appearing and lesion regions in anterolateral and posterolateral WM and compared using Wilcoxon rank tests and z scores. Correlations between MR metrics and clinical scores in patients with MS were evaluated using the Spearman rank correlation., Results: AMU 40 -based C1-to-C6 GM/WM automatic segmentations in patients with MS were evaluated relative to manual delineation. Mean Dice coefficients were 0.75/0.89, respectively. All MR metrics (WM/GM cross-sectional areas, normal-appearing and lesion diffusivities, and magnetization transfer/inhomogeneous magnetization transfer ratios) were observed altered in patients compared with controls ( P < .05). Additionally, the absolute inhomogeneous magnetization transfer ratio z scores were significantly higher than those of the other MR metrics ( P < .0001), suggesting a higher inhomogeneous magnetization transfer sensitivity toward spinal cord impairment in MS. Significant correlations with the Expanded Disability Status Scale (ρ = -0.73/ P = .02, ρ = -0.81/ P = .004) and the total Medical Research Council scale (ρ = 0.80/ P = .009, ρ = -0.74/ P = .02) were observed for inhomogeneous magnetization transfer and magnetization transfer ratio z scores, respectively, in normal-appearing WM regions, while weaker and nonsignificant correlations were obtained for DTI metrics., Conclusions: With inhomogeneous magnetization transfer being highly sensitive to spinal cord damage in MS compared with conventional magnetization transfer and DTI, it could generate great clinical interest for longitudinal follow-up and potential remyelinating clinical trials. In line with other advanced myelin techniques with which it could be compared, it opens perspectives for multicentric investigations., (© 2020 by American Journal of Neuroradiology.)

Background: There is a lack of longitudinal studies exploring the topological organization of functional brain networks at the early stages of multiple sclerosis (MS)., Objective: This study aims to assess potential brain functional reorganization at rest in patients with CIS (PwCIS) after 1 year of evolution and to characterize the dynamics of functional brain networks at the early stage of the disease., Methods: We prospectively included 41 PwCIS and 19 matched healthy controls (HCs). They were scanned at baseline and after 1 year. Using graph theory, topological metrics were calculated for each region. Hub disruption index was computed for each metric., Results: Hub disruption indexes of degree and betweenness centrality were negative at baseline in patients ( p  < 0.05), suggesting brain reorganization. After 1 year, hub disruption indexes for degree and betweenness centrality were still negative ( p  < 0.00001), but such reorganization appeared more pronounced than at baseline. Different brain regions were driving these alterations. No global efficiency differences were observed between PwCIS and HCs either at baseline or at 1 year., Conclusion: Dynamic changes in functional brain networks appear at the early stages of MS and are associated with the maintenance of normal global efficiency in the brain, suggesting a compensatory effect.

The recently-proposed MP2RAGE sequence was purposely optimized for cervical spinal cord imaging at 3T. Sequence parameters were chosen to optimize gray/white matter T 1 contrast with sub-millimetric resolution and scan-time < 10 min while preserving reliable T 1 determination with minimal B 1 + variation effects within a range of values compatible with pathologies and surrounding structures. Results showed good agreements with IR-based measurements, high MP2RAGE-based T 1 reproducibility and preliminary evidences of age- and tract-related T 1 variations in the healthy spinal cord., (© 2019 John Wiley & Sons, Ltd.)

Background: Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disorder. Diffusion magnetic resonance imagining (MRI) studies have consistently showed widespread alterations in both motor and non-motor brain regions. However, connectomics and graph theory based approaches have shown inconsistent results. Hub-centered lesion patterns and their impact on local and large-scale brain networks remain to be established. The objective of this work is to characterize topological properties of structural brain connectivity in ALS using an array of local, global and hub-based network metrics., Materials and Methods: Magnetic resonance imagining data were acquired from 25 patients with ALS and 26 age-matched healthy controls. Structural network graphs were constructed from diffusion tensor MRI. Network-based statistics (NBS) and graph theory metrics were used to compare structural networks without a priori regions of interest., Results: Patients with ALS exhibited global network alterations with decreased global efficiency (Eglob) ( p = 0.03) and a trend of reduced whole brain mean degree ( p = 0.05) compared to controls. Six nodes showed significantly decreased mean degree in ALS: left postcentral gyrus, left interparietal and transverse parietal sulcus, left calcarine sulcus, left occipital temporal medial and lingual sulcus, right precentral gyrus and right frontal inferior sulcus ( p < 0.01). Hub distribution was comparable between the two groups. There was no selective hub vulnerability or topological reorganization centered on these regions as the hub disruption index (κ) was not significant for the relevant metrics (degree, local efficiency and betweenness centrality). Using NBS, we identified an impaired motor subnetwork of 11 nodes and 10 edges centered on the precentral and the paracentral nodes ( p < 0.01). Significant clinical correlations were identified between degree in the frontal area and the disease progression rate of ALS patients ( p < 0.01)., Conclusion: Our study provides evidence that alterations of structural connectivity in ALS are primarily driven by node degree and white matter tract degeneration within an extended network around the precentral and the paracentral areas without hub-centered reorganization., (Copyright © 2019 Fortanier, Grapperon, Le Troter, Verschueren, Ridley, Guye, Attarian, Ranjeva and Zaaraoui.)

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that mainly affects the upper and lower motor neurons. Recent sodium ( 23 Na) MRI studies have shown that abnormal sodium concentration is related to neuronal suffering in neurodegenerative conditions. Purpose To use 23 Na MRI to investigate abnormal sodium concentrations and map their distribution in the brains of study participants with ALS as compared with healthy control subjects. Materials and Methods Twenty-seven participants with ALS (mean age, 54 years ± 10 [standard deviation], eight women) and 30 healthy control subjects (mean age, 50 years ± 10; 16 women) were prospectively recruited between September 2015 and October 2017 and were examined by using conventional proton MRI and sodium MRI at 3 T. Voxel-based statistical mapping was used to compare quantitative whole-brain total sodium concentration (TSC) maps in participants with ALS with those in control subjects and to localize regions of abnormal elevated TSC. Potential overlap of abnormal elevated TSC with regions of atrophy as detected with 1 H MRI also was investigated. Results Voxel-based statistical mapping analyses revealed higher sodium concentration in motor regions (bilateral precentral gyri, corticospinal tracts, and the corpus callosum) of participants with ALS (two-sample t test, P < .005; age and sex as covariates). In these regions, mean TSC was higher in participants with ALS (mean, 45.6 mmol/L wet tissue ± 3.2) than in control subjects (mean, 41.8 mmol/L wet tissue ± 2.7; P < .001; Cohen d = 1.28). Brain regions showing higher TSC represented a volume of 15.4 cm 3 that did not overlap with gray matter atrophy occupying a volume of 16.9 cm 3 . Elevated TSC correlated moderately with corticospinal conduction failure assessed with transcranial magnetic stimulation in the right upper limb (Spearman ρ = -0.57; 95% confidence interval: -0.78, -0.16; P = .005; n = 23). Conclusion Quantitative 23 Na MRI is sensitive to alterations of brain sodium homeostasis within disease-relevant regions in patients with amyotrophic lateral sclerosis (ALS). This supports further investigation of abnormal sodium concentration as a potential marker of neurodegenerative processes in patients with ALS that could be used as a secondary endpoint in clinical trials. © RSNA, 2019 Online supplemental material is available for this article.

Comparison studies between 7T and 1.5 or 3T magnetic resonance imaging (MRI) have demonstrated the added value of ultra-high field (UHF) MRI to better identify, delineate and characterize malformations of cortical development (MCD), and to disambiguate doubtful findings observed at lower field strengths. High resolution structural sequences such as magnetization prepared two rapid acquisition gradient echoes (MP2RAGE), fluid and white matter suppression MP2RAGE (FLAWS), and susceptibility-weighted imaging (SWI) appear to be key to the improvement of MCD diagnosis in clinical practice. 7T MRI offers not only images of high resolution and contrast but also provides many quantitative approaches capable of acting as more efficient probes of microstructure and ameliorating the categorization of MCDs. Post-processing of multiparametric ultra-high resolution and quantitative data may also be used to improve automated detection of MCD via machine learning. Therefore, 7T MRI can be considered as a useful tool in the presurgical evaluation of drug-resistant partial epilepsies, particularly, but not exclusively, in cases of normal appearing conventional MRI. It also opens many perspectives in the fields of in vivo histology and computational anatomy., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Inflammation and demyelination are the main processes in multiple sclerosis. Nevertheless, to date, blood biomarkers of inflammation are lacking. TWEAK, a transmembrane protein that belongs to the TNF ligand family, has been previously identified as a potential candidate., Methods: Twenty-eight patients (9 males, 19 females) were prospectively included after a first clinical episode suggestive of multiple sclerosis and clinically followed during 3 years. Fifty-seven healthy controls were also included. TWEAK serum levels and MRI exams including magnetization transfer imaging were performed at baseline, 6- and 12-month follow-up., Results: TWEAK serum levels were significantly increased in the patient group (mean baseline = 1086 ± 493 pg/mL, mean M6 = 624 ± 302 pg/mL and mean M12 = 578 ± 245 pg/mL) compared to healthy controls (mean = 467 ± 177 pg/mL; respectively p < 0.0001, 0.01 and 0.06). Serum levels of soluble TWEAK were significantly increased during relapses, compared to time periods without any relapse (respectively 935 ± 489 pg/mL and 611 ± 292 pg/mL, p = 0.0005). Moreover, patients presenting at least one gadolinium-enhanced CNS lesion at baseline (n = 7) displayed significantly increased serum TWEAK levels in comparison with patients without any gadolinium-enhanced lesion at baseline (n = 21) (respectively 1421 ± 657 pg/mL vs 975 ± 382 pg/mL; p = 0.02). Finally, no correlation was evidenced between TWEAK serum levels and the extent of brain tissue damage assessed by magnetization transfer ratio., Conclusions: The present study showed that TWEAK serum levels are increased in MS patients, in relation to the disease activity. This simple and reproducible serum test could be used as a marker of ongoing inflammation, contributing in the follow-up and the care of MS patients. Thus, TWEAK is a promising serum marker of the best window to perform brain MRI, optimizing the disease control in patients.

A novel magnetic resonance imaging (MRI) acquisition and reconstruction method for obtaining a series of dynamic sodium 23 Na-MRI acquisitions was designed to non-invasively assess the signal variations of brain sodium during a hand motor task in 14 healthy human volunteers on an ultra high field (7T) MR scanner. Regions undergoing activation and deactivation were identified with reference to conventional task-related BOLD functional MRI (fMRI). Activation observed in the left central regions, the supplementary motor areas and the left cerebellum induced an increase in the sodium signal observed at ultra short echo time and a decrease in the 23 Na signal observed at long echo time. Based on a simple model of two distinct sodium pools (namely, restricted and mobile sodium), the ultra short echo time measures the totality of sodium whereas the long echo time is mainly sensitive to mobile sodium. This activation pattern is consistent with previously described processes related to an influx of Na + into the intracellular compartments and a moderate increase in the cerebral blood volume (CBV). In contrast, deactivation observed in the right central regions ipsilateral to the movement, the precuneus and the left cerebellum induced a slight decrease in sodium signal at ultra short echo time and an increase of sodium signal at longer echo times. This inhibitory pattern is compatible with a slight decrease in CBV and an efflux of intracellular Na + to the extracellular compartments that may reflect neural dendritic spine and astrocytic shrinkage, and an increase of sodium in the extracellular fraction. In conclusion, cerebral dynamic 23 Na MRI experiments can provide access to the ionic transients following a functional task occurring within the neuro-glial-vascular ensemble. This has the potential to open up a novel non-invasive window on the mechanisms underlying brain function., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Increase of brain total sodium concentrations (TSC) is present in multiple sclerosis (MS), but its pathological involvement has not been assessed yet., Objective: To determine in vivo the metabolic counterpart of brain sodium accumulation., Materials/methods: Whole brain 23 Na-MR imaging and 3D- 1 H-EPSI data were collected in 21 relapsing-remitting multiple sclerosis (RRMS) patients and 20 volunteers. Metabolites and sodium levels were extracted from several regions of grey matter (GM), normal-appearing white matter (NAWM) and white matter (WM) T 2 lesions. Metabolic and ionic levels expressed as Z-scores have been averaged over the different compartments and used to explain sodium accumulations through stepwise regression models., Results: MS patients showed significant 23 Na accumulations with lower choline and glutamate-glutamine (Glx) levels in GM; 23 Na accumulations with lower N-acetyl aspartate (NAA), Glx levels and higher Myo-Inositol (m-Ins) in NAWM; and higher 23 Na, m-Ins levels with lower NAA in WM T 2 lesions. Regression models showed associations of TSC increase with reduced NAA in GM, NAWM and T 2 lesions, as well as higher total-creatine, and smaller decrease of m-Ins in T 2 lesions. GM Glx levels were associated with clinical scores., Conclusion: Increase of TSC in RRMS is mainly related to neuronal mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM is linked to clinical scores.