Contribution of the MP2RAGE 7T Sequence in MS Lesions of the Cervical Spinal Cord.

BACKGROUND AND PURPOSE: The detection of spinal cord lesions in patients with MS is challenging. Recently, the 3D MP2RAGE sequence demonstrated its usefulness at 3T. Benefiting from the high spatial resolution provided by ultra-high-field MR imaging systems, we aimed to evaluate the contribution of the 3D MP2RAGE sequence acquired at 7T for the detection of MS lesions in the cervical spine. MATERIALS AND METHODS: Seventeen patients with MS participated in this study. They were examined at both 3T and 7T. The MR imaging examination included a Magnetic Imaging in MS (MAGNIMS) protocol with an axial T2*-WI gradient recalled-echo sequence ("optimized MAGNIMS protocol") and a 0.9-mm isotropic 3D MP2RAGE sequence at 3T, as well as a 0.7-mm isotropic and 0.3-mm in-plane-resolution anisotropic 3D MP2RAGE sequences at 7T. Each data set was read by a consensus of radiologists, neurologists, and neuroscientists. The number of lesions and their topography, as well as the visibility of the lesions from one set to another, were carefully analyzed. RESULTS: A total of 55 lesions were detected. The absolute number of visible lesions differed among the 4 sequences (linear mixed effect ANOVA, P = .020). The highest detection was observed for the two 7T sequences with 51 lesions each (92.7% of the total). The optimized 3T MAGNIMS protocol and the 3T MP2RAGE isotropic sequence detected 41 (74.5%) and 35 lesions (63.6%), respectively. CONCLUSIONS: The 7T MP2RAGE sequences detected more lesions than the 3T sets. Isotropic and anisotropic acquisitions performed comparably. Ultra-high-resolution sequences obtained at 7T improve the identification and delineation of lesions of the cervical spinal cord in MS.

Alterations of Microstructure and Sodium Homeostasis in Fast Amyotrophic Lateral Sclerosis Progressors: A Brain DTI and Sodium MRI Study.

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 1H T1-weighted and diffusion sequences and a 23Na 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.

Quantification of diffuse myocardial fibrosis using CMR extracellular volume fraction and serum biomarkers of collagen turnover with histologic quantification as standard of reference.

PURPOSE: To compare the assessment of diffuse interstitial myocardial fibrosis in valvular diseases using cardiac magnetic resonance (CMR) extracellular volume fraction (ECV) quantification and serum biomarkers of collagen turnover using results of myocardial biopsy as standard of reference. MATERIALS AND METHODS: This prospective monocentric study included consecutive patients before aortic valvular replacement. All patients underwent: i), 1.5T CMR with pre and post contrast T1 mapping sequence and ECV computation; ii), serum quantification of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) and iii), myocardial biopsies were collected during surgery to assess collagen volume fraction (CVF). Patients with coronary artery disease were excluded. Correlation between native T1, ECV, CVF and serum biomarkers were assessed using Pearson correlation test. Agreement between basal anteroseptal ECV with global ECV was assessed using Bland-Altman test. RESULTS: Twenty-one patients, 16 with aortic stenosis and 5 with aortic regurgitation were included. There were 12 men and 9 women with a mean age of 74.1±6.8 (SD) years (range: 32-84 years). Mean global ECV value was 26.7±2.7 (SD) % (range: 23.4-32.5%) and mean CVF value was 12.4±9.7% (range: 3.2-25.7%). ECV assessed at the basal anteroseptal segment correlated moderately with CVF (r=0.6; P=0.0026). There was a strong correlation and agreement between basal anteroseptal ECV and global ECV, (r=0.8; P<0.0001; bias 5.4±6.1%) but no correlation between global ECV and CVF (r=0.5; P=0.10). Global ECV poorly correlated with serum TIMP-1 (r=0.4; P=0.037) and MMP-2 (r=0.4; P=0.047). No correlation was found between serum biomarkers and basal anteroseptal- ECV or native T1. CONCLUSION: In patients with severe aortic valvulopathy, diffuse myocardial fibrosis assessed by anterosepto-basal ECV correlates with histological myocardial fibrosis. Anteroseptobasal ECV strongly correlates with global ECV, which poorly correlates with TIMP-1 and MMP-2, serum biomarkers involved in the progression of heart failure.

The circadian dynamics of the hippocampal transcriptome and proteome is altered in experimental temporal lobe epilepsy.

Gene and protein expressions display circadian oscillations, which can be disrupted in diseases in most body organs. Whether these oscillations occur in the healthy hippocampus and whether they are altered in epilepsy are not known. We identified more than 1200 daily oscillating transcripts in the hippocampus of control mice and 1600 in experimental epilepsy, with only one-fourth oscillating in both conditions. Comparison of gene oscillations in control and epilepsy predicted time-dependent alterations in energy metabolism, which were verified experimentally. Although aerobic glycolysis remained constant from morning to afternoon in controls, it increased in epilepsy. In contrast, oxidative phosphorylation increased in control and decreased in epilepsy. Thus, the control hippocampus shows circadian molecular remapping, which is altered in epilepsy. We suggest that the hippocampus operates in a different functioning mode in epilepsy. These alterations need to be considered when studying epilepsy mechanisms, designing drug treatments, and timing their delivery.

Quantitative assessment of sciatic nerve changes in Charcot-Marie-Tooth type 1A patients using magnetic resonance neurography.

BACKGROUND AND PURPOSE: Nerve tissue alterations have rarely been quantified in Charcot-Marie-Tooth type 1A (CMT1A) patients. The aim of the present study was to quantitatively assess the magnetic resonance imaging (MRI) anomalies of the sciatic and tibial nerves in CMT1A disease using quantitative neurography MRI. It was also intended to seek for correlations with clinical variables. METHODS: Quantitative neurography MRI was used in order to assess differences in nerve volume, proton density and magnetization transfer ratio in the lower limbs of CMT1A patients and healthy controls. Disease severity was evaluated using the Charcot-Marie-Tooth Neuropathy Score version 2, Charcot-Marie-Tooth examination scores and Overall Neuropathy Limitations Scale scores. Electrophysiological measurements were performed in order to assess the compound motor action potential and the Motor Unit Number Index. Clinical impairment was evaluated using muscle strength measurements and Charcot-Marie-Tooth examination scores. RESULTS: A total of 32 CMT1A patients were enrolled and compared to 13 healthy subjects. The 3D nerve volume, magnetization transfer ratio and proton density were significantly different in CMT1A patients for the whole sciatic and tibial nerve volume. The sciatic nerve volume was significantly correlated with the whole set of clinical scores whereas no correlation was found between the tibial nerve volume and the clinical scores. CONCLUSION: Nerve injury could be quantified in vivo using quantitative neurography MRI and the corresponding biomarkers were correlated with clinical disability in CMT1A patients. The sensitivity of the selected metrics will have to be assessed through repeated measurements over time during longitudinal studies to evaluate structural nerve changes under treatment.

The Bayesian Virtual Epileptic Patient: A probabilistic framework designed to infer the spatial map of epileptogenicity in a personalized large-scale brain model of epilepsy spread.

Despite the importance and frequent use of Bayesian frameworks in brain network modeling for parameter inference and model prediction, the advanced sampling algorithms implemented in probabilistic programming languages to overcome the inference difficulties have received relatively little attention in this context. In this technical note, we propose a probabilistic framework, namely the Bayesian Virtual Epileptic Patient (BVEP), which relies on the fusion of structural data of individuals to infer the spatial map of epileptogenicity in a personalized large-scale brain model of epilepsy spread. To invert the individualized whole-brain model employed in this study, we use the recently developed algorithms known as No-U-Turn Sampler (NUTS) as well as Automatic Differentiation Variational Inference (ADVI). Our results indicate that NUTS and ADVI accurately estimate the degree of epileptogenicity of brain regions, therefore, the hypothetical brain areas responsible for the seizure initiation and propagation, while the convergence diagnostics and posterior behavior analysis validate the reliability of the estimations. Moreover, we illustrate the efficiency of the transformed non-centered parameters in comparison to centered form of parameterization. The Bayesian framework used in this work proposes an appropriate patient-specific strategy for estimating the epileptogenicity of the brain regions to improve outcome after epilepsy surgery.

Cardiac magnetic resonance assessment of left ventricular dilatation in chronic severe left-sided regurgitations: comparison with standard echocardiography.

PURPOSE: The purpose of this study was to investigate the potential additional value of cardiac magnetic resonance (CMR) in the assessment of left ventricular (LV) dilatation and dysfunction by comparison to standard echocardiography in patients with chronic left-sided valvular regurgitation. MATERIALS AND METHODS: We prospectively enrolled patients with chronic severe mitral regurgitation (MR) or aortic regurgitation (AR). They underwent standard echocardiography and CMR using aortic flow and LV-function sequences. LV dilatation or dysfunction was assessed with each technique, based on thresholds used for surgery indication. Reference regurgitation severity was defined following previously reported CMR-based regurgitant volume thresholds. RESULTS: A total of 71 patients with chronic severe MR (n=44) or severe AR (n=27) were prospectively included. There were 60 men and 11 women with a mean age of 61±14 (SD) years (range: 18-83 years). CMR-based regurgitation severity was significantly greater in the LV dysfunction group when assessed with CMR (MR, P=0.011; AR, P=0.006) whereas it was not different when LV dysfunction was assessed using standard echocardiography. Among standard echocardiography and CMR volumetric indices, CMR-derived end-diastolic volume showed the best ability to predict regurgitation severity (area under the curve [AUC]=0.78 for MR; AUC=0.91 for AR). Diagnostic thresholds identified on receiver operating characteristics-curve analysis were lower than those of current European recommendations and closer to North-American guidelines. CONCLUSION: CMR assessment of LV end-diastolic volume in chronic severe left-sided regurgitations is more reliably associated with CMR-based regurgitant volume by comparison with standard echocardiography diameter. CMR may provide useful evaluation before surgery decision for severe asymptomatic regurgitations.

Sensitivity of the Inhomogeneous Magnetization Transfer Imaging Technique to Spinal Cord Damage in Multiple Sclerosis.

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 AMU40 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: AMU40-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.

Quantification of right ventricular extracellular volume in pulmonary hypertension using cardiac magnetic resonance imaging.

PURPOSE: The purpose of this prospective study was to assess the value of biventricular extracellular volume (ECV) in pre-capillary pulmonary hypertension (PH) obtained using cardiac magnetic resonance imaging (CMR) and to correlate ECV with markers of prognosis such as strain echocardiography and blood biomarkers of fibrosis. MATERIALS AND METHODS: Twelve patients with PH (6 men, 6 women; mean age=50±16 [SD] years; age range: 22-73 years) underwent the same day: (i), transthoracic echocardiography including measurement of right ventricular (RV) fractional shortening (RVfs), tricuspid annular plane systolic excursion (TAPSE), maximal tricuspid annular velocity, RV global and segmental deformation; (ii), right heart catheterization measuring pulmonary arterial pressures (inmmHg) and cardiac output (inL/min); (iii), CMR at 1.5-T measuring RV volumes and ejection fraction; (iv), native and 15min post-contrast T1 mapping using modified look-locker inversion-recovery sequence; and (v), serum quantification of two biomarkers of collagen turnover and hematocrit. Non-parametric Mann-Whitney tests were used to search for differences between categorical variables. Spearman correlation test was used for search for correlation between quantitative values. RESULTS: Global RV ECV was 34%±4.2 (SD) for our entire population. A significant correlation was found between RV ECV and RVfs (r=0.6; P=0.026), S wave velocity (r=0.7; P=0.009), TAPSE (r=0.6; P=0.040) and RV systolic ejection fraction on CMR (r=0.6; P=0.04). There were no correlations between the ECV values in the lateral wall of the RV and in the septum (r=0.4; P=0.206). A significant correlation was found between septal ECV and 2D septal strain (r=0.7; P=0.013). CONCLUSION: ECV in PH as obtained using CMR appears to correlate with known echocardiographic prognostic markers and more specifically with the markers, which assess RV systolic function.

Assessment of proximal femur microarchitecture using ultra-high field MRI at 7 Tesla.

PURPOSE: The purpose of this study was to investigate bone microarchitecture of cadaveric proximal femurs using ultra-high field (UHF) 7-Tesla magnetic resonance imaging (MRI) and to compare the corresponding metrics with failure load assessed during mechanical compression test and areal bone mineral density (ABMD) measured using dual-energy X-ray absorptiometry. MATERIALS AND METHODS: ABMD of ten proximal femurs from five cadavers (5 women; mean age=86.2±3.8 (SD) years; range: 82.5-90 years) were investigated using dual-energy X-ray absorptiometry and the bone volume fraction, trabecular thickness, trabecular spacing, fractal dimension, Euler characteristics, connectivity density and degree of anisotropy of each femur was quantified using UHF MRI. The whole set of specimens underwent mechanical compression tests to failure. The inter-rater reliability of microarchitecture characterization was assessed with the intraclass correlation coefficient (ICC). Associations were searched using correlation tests and multiple regression analysis. RESULTS: The inter-rater reliability for bone microarchitecture parameters measurement was good with ICC ranging from 0.80 and 0.91. ABMD and the whole set of microarchitecture metrics but connectivity density significantly correlated with failure load. Microarchitecture metrics correlated to each other but did not correlate with ABMD. Multiple regression analysis disclosed that the combination of microarchitecture metrics and ABMD improved the association with failure load. CONCLUSION: Femur bone microarchitecture metrics quantified using UHF MRI significantly correlated with biomechanical parameters. The multimodal assessment of ABMD and trabecular bone microarchitecture using UHF MRI provides more information about fracture risk of femoral bone and might be of interest for future investigations of patients with undetected osteoporosis.

Malformations of cortical development: The role of 7-Tesla magnetic resonance imaging in diagnosis.

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.

Distribution of left ventricular trabeculation across age and gender in 140 healthy Caucasian subjects on MR imaging.

PURPOSE: The purpose of this study was to quantify the distribution of trabeculated (T) and compact (C) left ventricular (LV) myocardium masses in a healthy Caucasian population against age, gender and LV parameters, and to provide normal values for T, C and T/C. MATERIALS AND METHODS: One hundred and forty healthy subjects were prospectively recruited and underwent cardiac MRI at 1.5T with a stack of short-axis cine sequences covering the entire LV. End-diastolic volume (EDV), C and T masses were quantified using a semi-automatic method. Ejection fraction (EF) and T/C ratio were computed. RESULTS: We included 70 men and 70 women with a mean age of 44±14 (SD) years (range: 20-69 years). The mean EF was 63.7±6.3 (SD) % (range: 50.7-82.0%), the mean EDV was 75.9±16.2 (SD) mL/m2 (range: 36.4-112.2mL/m2), the mean C mass was 53.9±11.2 (SD) g/m2 (range: 26.5-93.4g/m2) and the mean T mass was 4.9±2.4 (SD) g/m2 (range: 1.1-11.4g/m2). The T/C ratio was 9.2±4.5% (range: 2.0-29.4%). Multivariate ANOVA test showed that the compact mass was influenced by EDV (P<0.0001), EF (P=0.001) and gender (P<0.0001), and the trabeculated mass depended on EDV (P<0.0001), gender (P=0.002) and age (P<0.0001), while the T/C ratio was only influenced by age (P=0.0003). Spearman test showed a correlation between EDV and C (r=0.60; P<0.0001),T (r=0.46; P<0.0001) and T/C ratio (r=0.26; P=0.0023).T and T/C ratio correlated with EF (r=-0.18, P=0.0373; r=-0.18, P=0.0321, respectively). CONCLUSION: While the compact and trabeculated myocardium masses appear to relate separately to the cardiac function, age and gender, their ratio T/C appears to only decrease with age. Furthermore, we propose here normal values for T, C and T/C in a cohort of healthy Caucasians subjects.

Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis.

BACKGROUND AND PURPOSE: Inhomogeneous magnetization transfer is a new endogenous MR imaging contrast mechanism that has demonstrated high specificity for myelin. Here, we tested the hypothesis that inhomogeneous magnetization transfer is sensitive to pathology in a population of patients with relapsing-remitting MS in a way that both differs from and complements conventional magnetization transfer. MATERIALS AND METHODS: Twenty-five patients with relapsing-remitting MS and 20 healthy volunteers were enrolled in a prospective MR imaging research study, whose protocol included anatomic imaging, standard magnetization transfer, and inhomogeneous magnetization transfer imaging. Magnetization transfer and inhomogeneous magnetization transfer ratios measured in normal-appearing brain tissue and in MS lesions of patients were compared with values measured in control subjects. The potential association of inhomogeneous magnetization transfer ratio variations with the clinical scores (Expanded Disability Status Scale) of patients was further evaluated. RESULTS: The magnetization transfer ratio and inhomogeneous magnetization transfer ratio measured in the thalami and frontal, occipital, and temporal WM of patients with MS were lower compared with those of controls (P < .05). The mean inhomogeneous magnetization transfer ratio measured in lesions was lower than that in normal-appearing WM (P < .05). Significant (P < .05) negative correlations were found between the clinical scores and inhomogeneous magnetization transfer ratio measured in normal-appearing WM structures. Weaker nonsignificant correlation trends were found for the magnetization transfer ratio. CONCLUSIONS: The sensitivity of the inhomogeneous magnetization transfer technique for MS was highlighted by the reduction in the inhomogeneous magnetization transfer ratio in MS lesions and in normal-appearing WM of patients compared with controls. Stronger correlations with the Expanded Disability Status Scale score were obtained with the inhomogeneous magnetization transfer ratio compared with the standard magnetization transfer ratio, which may be explained by the higher specificity of inhomogeneous magnetization transfer for myelin.

New brain lesions with no impact on physical disability can impact cognition in early multiple sclerosis: A ten-year longitudinal study.

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

Addition of droperidol to prophylactic ondansetron and dexamethasone in children at high risk for postoperative vomiting. A randomized, controlled, double-blind study.

BACKGROUND: : The combination of dexamethasone (DEX), ondansetron (OND) and droperidol (DRO) is efficacious in preventing postoperative nausea and vomiting in adults, but has not been well assessed in children. METHODS: : Children undergoing elective surgery under general anaesthesia and considered at high risk for postoperative vomiting (POV) were randomly assigned to receive a combination of DEX, OND and placebo (Group A) or a combination of DEX, OND and DRO (Group B). The primary outcome was the incidence of POV during the first 24 hours after surgery. We hypothesized that the addition of DRO to the standard antiemetic prophylaxis would provide a further 15% reduction in the residual risk for POV. The secondary outcome considered was any adverse event occurring during the study. RESULTS: : One hundred and fifty-three children, aged three to 16 years, were randomized to Group A and 162 to Group B. The overall incidence of POV did not differ significantly between the two groups, with 16 patients in Group A (10.5%) and 18 in Group B (11.1%) presenting with one or more episodes of POV, P =0.86. Fewer patients presented with adverse events in Group A (2%) compared with Group B (8%), P =0.01. Drowsiness and headache were the principal adverse events reported. CONCLUSIONS: : The addition of DRO to a combination of OND and DEX did not decrease POV frequency below that obtained with the two-drug combination in children at high risk of POV, but increased the risk of drowsiness. The combination of DEX and OND should be recommended in children with a high risk of POV. CLINICAL TRIAL REGISTRATION.: NCT01739985.

The Virtual Epileptic Patient: Individualized whole-brain models of epilepsy spread.

Individual variability has clear effects upon the outcome of therapies and treatment approaches. The customization of healthcare options to the individual patient should accordingly improve treatment results. We propose a novel approach to brain interventions based on personalized brain network models derived from non-invasive structural data of individual patients. Along the example of a patient with bitemporal epilepsy, we show step by step how to develop a Virtual Epileptic Patient (VEP) brain model and integrate patient-specific information such as brain connectivity, epileptogenic zone and MRI lesions. Using high-performance computing, we systematically carry out parameter space explorations, fit and validate the brain model against the patient's empirical stereotactic EEG (SEEG) data and demonstrate how to develop novel personalized strategies towards therapy and intervention.

[What can we expect from clinical trials in psychiatry?] / Que peut-on attendre des essais cliniques en psychiatrie ?

Clinical trials in psychiatry allow to build the regulatory dossiers for market authorization but also to document the mechanism of action of new drugs, to build pharmacodynamics models, evaluate the treatment effects, propose prognosis, efficacy or tolerability biomarkers and altogether to assess the impact of drugs for patient, caregiver and society. However, clinical trials have shown some limitations. Number of recent dossiers failed to convince the regulators. The clinical and biological heterogeneity of psychiatric disorders, the pharmacokinetic and pharmacodynamics properties of the compounds, the lack of translatable biomarkers possibly explain these difficulties. Several breakthrough options are now available: quantitative system pharmacology analysis of drug effects variability, pharmacometry and pharmacoepidemiology, Big Data analysis, brain modelling. In addition to more classical approaches, these opportunities lead to a paradigm change for clinical trials in psychiatry.

[About laryngeal mask: is the lowest price material the better cost-efficacy choice?]. / Comparaison de quatre masques laryngés à usage unique pour la chirurgie carcinologique du sein: une approche médico-économique.

OBJECTIVE: The main goal of this study was to achieve a medico-economic comparison between four disposable laryngeal masks (LM) (LMA-Unique™, Ambu AuraOnce™, I-Gel™ and LMA-Suprême™). STUDY DESIGN: A prospective, randomized, monocentre study. MATERIAL AND METHODS: In a center, using routinely LMA-Unique masks, scheduled breast surgery patients were allocated into four groups according to the LM model. After the induction, the modalities of use were collected, as well as the intraoperative events that required additional anesthetic equipment. The real cost of each model was calculated (cost of the mask+extra cost related to complications). Using the LMA-Unique as a reference, we performed a cost-efficacy analysis. We realized a cost-efficiency analysis putting in parallel the impact on the cost and the incidence of the events. RESULTS: A total of 178 patients were included. According to the cost-efficacy analysis, the dominant model was the Ambu AuraOnce™ (Δreal cost: -34.2%, Δevents: -30.6%). The LMA-Unique™ was dominated because of a high morbidity rate. The I-Gel™ and LMA-Suprême™ models were more efficient but more expensive (Δreal cost: +16% and +22.5% respectively). To compensate for additional costs, it would be necessary to apply a price reduction of at least 50%. CONCLUSIONS: Despite their better efficiency and safety, the latest generation laryngeal masks are still expensive in spite of a low rate of complication. These results do not take into account very rare and severe complications not met in this study in the limited size; then the economic and medical impact can influence the choice beyond the simple analysis cost-efficiency.

Classification of EEG abnormalities in partial epilepsy with simultaneous EEG-fMRI recordings.

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

Structural and functional reorganization of working memory system during the first decade in schizophrenia. A cross-sectional study.

INTRODUCTION: Progressive atrophy occurs in brain regions involved in the working memory network along the schizophrenia's course, but without parallel evolution of working memory impairment. We investigated the functional organization inside this network at different stages of the disease. METHODS: Twenty-eight patients with schizophrenia (16 with long disease duration (>60 months) and 12 with short disease duration (<60 months)) and eleven healthy controls underwent structural and functional MRI during an n-back task to determine atrophy and activation patterns. RESULTS: At similar n-back performances and relative to short disease duration patients, long disease duration patients activated more frontal temporal parietal and frontal network during 0-back and 1-back tasks respectively. n-back scores were correlated to atrophy in the frontal-temporal areas. DISCUSSION: Functional reorganization in the working memory network may play a compensatory role during the first ten years of schizophrenia.