Infinite Feature Selection on Shore-Based Biomarkers Reveals Connectivity Modulation after Stroke

Connectomics is gaining increasing interest in the scientific and clinical communities. It consists in deriving models of structural or functional brain connections based on some local measures. Here we focus on structural connectivity as detected by diffusion MRI. Connectivity matrices are derived from microstructural indices obtained by the 3D-SHORE. Typically, graphs are derived from connectivity matrices and used for inferring node properties that allow identifying those nodes that play a prominent role in the network. This information can then be used to detect network modulations induced by diseases. In this paper we take a complementary approach and focus on link as opposed to node properties. We hypothesize that network modulation can be better described by measuring the connectivity alteration directly in the form of modulation of the properties of white matter fiber bundles constituting the network communication backbone. The goal of this paper is to detect the paths that are most altered by the pathology by exploiting a feature selection paradigm. Temporal changes on connection weights are treated as features and those playing a leading role in a patient versus healthy controls classification task are detected by the Infinite Feature Selection (Inf-FS) method. Results show that connection paths with high discriminative power can be identified that are shared by the considered microstructural descriptors allowing a classification accuracy ranging between 83% and 89%

A two dimensional, two fluid model for sodium boiling in LMFBR fuel assemblies

A two dimensional numerical model for the simulation of sodium boiling transient was developed using the two fluid set of conservation equations. A semiimplicit numerical differencing scheme capable of handling the problems associated with the ill-posedness implied by the complex characteristic roots of the two fluid problems was used, which took advantage of the dumping effect of the exchange terms. Of particular interest in the development of the model was the identi- fication of the numerical problems caused by the strong disparity between the axial and radial dimensions of fuel assemblies. A solution to this problem was found which uses the particular geometry of fuel assemblies to accelerate the convergence of the iterative technique used in the model. The most important feature of the model was its ability to simulate severe conditions of sodium boiling, in particular flow reversal, which was shown in the tests performed with the model. Three sodium boiling experiments were simulated with the model, with good agreement between the experimental results and the model predictions."Sponsored by U.S Department of Energy, General Electric Co. and Hanford Engineering Development Laboratory.

Nanotecnologia na agricultura: prospecção dos indicadores de impactos ambientais e sociais.

Resumo: A Nanotecnologia está baseada na crescente capacidade da tecnologia moderna de manipular átomos e partículas em nanoescala, com aplicações em diversas áreas de atuação, desde a medicina, meio ambiente e agricultura. Apesar das nanotecnologias apresentarem propriedades físicas específicas, a avaliação dos impactos associados ao seu emprego e liberação no meio ambiente ainda não é uma prática corrente. Neste cenário, o presente trabalho propõe um estudo de caso sobre as nanopartículas na agricultura, através da formulação de indicadores de impacto a partir de levantamento da literatura científica

Método 'Impactos-Nanotec' para avaliação dos impactos ambientais: estudo de caso das nanotecnologias na agricultura.

Resumo: A Nanotecnologia está baseada na crescente capacidade da tecnologia moderna de manipular átomos e partículas em nanoescala, com aplicações em diversas áreas de atuação desde a medicina, meio ambiente e agricultura. Apesar das nanotecnologias apresentarem propriedades físicas específicas, a avaliação dos impactos associados ao seu emprego e liberação no meio ambiente ainda não é uma prática corrente. Neste cenário, o presente trabalho propõe o estudo de caso de nanopartículas na agricultura, através do levantamento de indicadores, utilizando uma metodologia empregada para estudo de transgênicos, adaptada para um novo software de avaliação de risco de nanoproduto

The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients.

Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients. Thirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue. In patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005) and a decrease of T1 relaxation times in the pallidum (p < 0.05), which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value < 2.2e-16) and a significant increase in MTR (p-value < 1e-6), suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics-and not changes in lesions or brain volume-were correlated to motor and cognitive tests scores evolution (Adj-R(2) > 0.4, p < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies

MP2RAGE provides new clinically-compatible correlates of mild cognitive deficits in relapsing-remitting multiple sclerosis.

Despite that cognitive impairment is a known early feature present in multiple sclerosis (MS) patients, the biological substrate of cognitive deficits in MS remains elusive. In this study, we assessed whether T1 relaxometry, as obtained in clinically acceptable scan times by the recent Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) sequence, may help identifying the structural correlate of cognitive deficits in relapsing-remitting MS patients (RRMS). Twenty-nine healthy controls (HC) and forty-nine RRMS patients underwent high-resolution 3T magnetic resonance imaging to obtain optimal cortical lesion (CL) and white matter lesion (WML) count/volume and T1 relaxation times. T1 z scores were then obtained between T1 relaxation times in lesion and the corresponding HC tissue. Patient cognitive performance was tested using the Brief Repeatable Battery of Neuro-psychological Tests. Multivariate analysis was applied to assess the contribution of MRI variables (T1 z scores, lesion count/volume) to cognition in patients and Bonferroni correction was applied for multiple comparison. T1 z scores were higher in WML (p < 0.001) and CL-I (p < 0.01) than in the corresponding normal-appearing tissue in patients, indicating relative microstructural loss. (1) T1 z scores in CL-I (p = 0.01) and the number of CL-II (p = 0.04) were predictors of long-term memory; (2) T1 z scores in CL-I (β = 0.3; p = 0.03) were independent determinants of long-term memory storage, and (3) lesion volume did not significantly influenced cognitive performances in patients. Our study supports evidence that T1 relaxometry from MP2RAGE provides information about microstructural properties in CL and WML and improves correlation with cognition in RRMS patients, compared to conventional measures of disease burden

A multi-contrast MRI study of microstructural brain damage in patients with mild cognitive impairment.

OBJECTIVES: The aim of this study was to investigate pathological mechanisms underlying brain tissue alterations in mild cognitive impairment (MCI) using multi-contrast 3 T magnetic resonance imaging (MRI). METHODS: Forty-two MCI patients and 77 healthy controls (HC) underwent T1/T2* relaxometry as well as Magnetization Transfer (MT) MRI. Between-groups comparisons in MRI metrics were performed using permutation-based tests. Using MRI data, a generalized linear model (GLM) was computed to predict clinical performance and a support-vector machine (SVM) classification was used to classify MCI and HC subjects. RESULTS: Multi-parametric MRI data showed microstructural brain alterations in MCI patients vs HC that might be interpreted as: (i) a broad loss of myelin/cellular proteins and tissue microstructure in the hippocampus (p ≤ 0.01) and global white matter (p < 0.05); and (ii) iron accumulation in the pallidus nucleus (p ≤ 0.05). MRI metrics accurately predicted memory and executive performances in patients (p ≤ 0.005). SVM classification reached an accuracy of 75% to separate MCI and HC, and performed best using both volumes and T1/T2*/MT metrics. CONCLUSION: Multi-contrast MRI appears to be a promising approach to infer pathophysiological mechanisms leading to brain tissue alterations in MCI. Likewise, parametric MRI data provide powerful correlates of cognitive deficits and improve automatic disease classification based on morphometric features

Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis

Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) specific damage to CNS tissue components. This review summarizes recent technical advances in quantitative MRI, existing pathological validation of quantitative MRI techniques, and emerging applications of quantitative MRI to patients with multiple sclerosis in both research and clinical settings. The current level of clinical maturity of each quantitative MRI technique, especially regarding its integration into clinical routine, is discussed. We aim to provide a better understanding of how quantitative MRI may help clinical practice by improving stratification of patients with multiple sclerosis, and assessment of disease progression, and evaluation of treatment response

Cell-binding IgM in CSF is distinctive of multiple sclerosis and targets the iron transporter SCARA5

Intrathecal IgM production in multiple sclerosis (MS) is associated with a worse disease course. To investigate pathogenic relevance of autoreactive IgM in MS, CSF from two independent cohorts, including MS patients and controls, were screened for antibody binding to induced pluripotent stem cell-derived neurons and astrocytes, and a panel of CNS- related cell lines. IgM binding to a primitive neuro-ectodermal tumour cell line discriminated 10% of MS donors from controls. Transcriptomes of single IgM producing CSF B cells from patients with cell-binding IgM were sequenced and used to produce recombinant monoclonal antibodies for characterisation and antigen identification. We produced 5 cell-binding recombinant IgM antibodies, of which one, cloned from an HLA-DR + plasma-like B cell, mediated antigen-dependent complement activation. Immunoprecipitation and mass spectrometry, and biochemical and transcriptome analysis of the target cells identified the iron transport scavenger protein SCARA5 as the antigen target of this antibody. Intrathecal injection of a SCARA5 antibody led to an increased T cell infiltration in an EAE model. CSF IgM might contribute to CNS inflammation in MS by binding to cell surface antigens like SCARA5 and activating complement, or by facilitating immune cell migration into the brain