Linking immune-mediated damage to neurodegeneration in multiple sclerosis: could network-based MRI help?

Inflammatory demyelination characterizes the initial stages of multiple sclerosis, while progressive axonal and neuronal loss are coexisting and significantly contribute to the long-term physical and cognitive impairment. There is an unmet need for a conceptual shift from a dualistic view of multiple sclerosis pathology, involving either inflammatory demyelination or neurodegeneration, to integrative dynamic models of brain reorganization, where, glia-neuron interactions, synaptic alterations and grey matter pathology are longitudinally envisaged at the whole-brain level. Functional and structural MRI can delineate network hallmarks for relapses, remissions or disease progression, which can be linked to the pathophysiology behind inflammatory attacks, repair and neurodegeneration. Here, we aim to unify recent findings of grey matter circuits dynamics in multiple sclerosis within the framework of molecular and pathophysiological hallmarks combined with disease-related network reorganization, while highlighting advances from animal models (in vivo and ex vivo) and human clinical data (imaging and histological). We propose that MRI-based brain networks characterization is essential for better delineating ongoing pathology and elaboration of particular mechanisms that may serve for accurate modelling and prediction of disease courses throughout disease stages

An X-ray study of the SNR G344.7-0.1 and the central object CXOU J170357.8-414302

Aims. We report results of an X-ray study of the supernova remnant (SNR) G344.7-0.1 and the point-like X-ray source located at the geometrical center of the SNR radio structure. Methods. The morphology and spectral properties of the remnant and the central X-ray point-like source were studied using data from the XMM-Newton and Chandra satellites. Archival radio data and infrared Spitzer observations at 8 and 24 $\mu$m were used to compare and study its multi-band properties at different wavelengths. Results. The XMM-Newton and Chandra observations reveal that the overall X-ray emission of G344.7-0.1 is extended and correlates very well with regions of bright radio and infrared emission. The X-ray spectrum is dominated by prominent atomic emission lines. These characteristics suggest that the X-ray emission originated in a thin thermal plasma, whose radiation is represented well by a plane-parallel shock plasma model (PSHOCK). Our study favors the scenario in which G344.7-0.1 is a 6 x 10^3 year old SNR expanding in a medium with a high density gradient and is most likely encountering a molecular cloud on the western side. In addition, we report the discovery of a soft point-like X-ray source located at the geometrical center of the radio SNR structure. The object presents some characteristics of the so-called compact central objects (CCO). However, its neutral hydrogen absorption column (N_{H}) is inconsistent with that of the SNR. Coincident with the position of the source, we found infrared and optical objects with typical early-K star characteristics. The X-ray source may be a foreground star or the CCO associated with the SNR. If this latter possibility were confirmed, the point-like source would be the farthest CCO detected so far and the eighth member of the new population of isolated and weakly magnetized neutron stars.Comment: 9 pages, 8 figures, accepted for publication in Astronomy and Astrophysics. Higher resolution figures can be seen on A&

Covarying patterns of white matter lesions and cortical atrophy predict progression in early MS

Objective We applied longitudinal 3T MRI and advanced computational models in 2 independent cohorts of patients with early MS to investigate how white matter (WM) lesion distribution and cortical atrophy topographically interrelate and affect functional disability. Methods Clinical disability was measured using the Expanded Disability Status Scale Score at baseline and at 1-year follow-up in a cohort of 119 patients with early relapsing-remitting MS and in a replication cohort of 81 patients. Covarying patterns of cortical atrophy and baseline lesion distribution were extracted by parallel independent component analysis. Predictive power of covarying patterns for disability progression was tested by receiver operating characteristic analysis at the group level and support vector machine for individual patient outcome. Results In the study cohort, we identified 3 distinct distribution types of WM lesions (cerebellar, bihemispheric, and left lateralized) that were associated with characteristic cortical atrophy distributions. The cerebellar and left-lateralized patterns were reproducibly detected in the second cohort. Each of the patterns predicted to different extents, short-term disability progression, whereas the cerebellar pattern was associated with the highest risk of clinical worsening, predicting individual disability progression with an accuracy of 88% (study cohort) and 89% (replication cohort), respectively. Conclusion These findings highlight the role of distinct spatial distribution of cortical atrophy and WM lesions predicting disability. The cerebellar involvement is shown as a key determinant of rapid clinical deterioration

Continuous reorganization of cortical information flow in multiple sclerosis : a longitudinal fMRI effective connectivity study

Effective connectivity (EC) is able to explore causal effects between brain areas and can depict mechanisms that underlie repair and adaptation in chronic brain diseases. Thus, the application of EC techniques in multiple sclerosis (MS) has the potential to determine directionality of neuronal interactions and may provide an imaging biomarker for disease progression. Here, serial longitudinal structural and resting-state fMRI was performed at 12-week intervals over one year in twelve MS patients. Twelve healthy subjects served as controls (HC). Two approaches for EC quantification were used: Causal Bayesian Network (CBN) and Time-resolved Partial Directed Coherence (TPDC). The EC strength was correlated with the Expanded Disability Status Scale (EDSS) and Fatigue Scale for Motor and Cognitive functions (FSMC). Our findings demonstrated a longitudinal increase in EC between specific brain regions, detected in both the CBN and TPDC analysis in MS patients. In particular, EC from the deep grey matter, frontal, prefrontal and temporal regions showed a continuous increase over the study period. No longitudinal changes in EC were attested in HC during the study. Furthermore, we observed an association between clinical performance and EC strength. In particular, the EC increase in fronto-cerebellar connections showed an inverse correlation with the EDSS and FSMC. Our data depict continuous functional reorganization between specific brain regions indicated by increasing EC over time in MS, which is not detectable in HC. In particular, fronto-cerebellar connections, which were closely related to clinical performance, may provide a marker of brain plasticity and functional reserve in MS

Altered grey matter integrity and network vulnerability relate to epilepsy occurrence in patients with multiple sclerosis

Background and purpose: The aim of this study was to investigate the relevance of compartmentalized grey matter (GM) pathology and network reorganization in multiple sclerosis (MS) patients with concomitant epilepsy. Methods: From 3-T magnetic resonance imaging scans of 30 MS patients with epilepsy (MSE group; age 41 ± 15 years, 21 females, disease duration 8 ± 6 years, median Expanded Disability Status Scale [EDSS] score 3), 60 MS patients without epilepsy (MS group; age 41 ± 12 years, 35 females, disease duration 6 ± 4 years, EDSS score 2), and 60 healthy subjects (HS group; age 40 ± 13 years, 27 females) the regional volumes of GM lesions and of cortical, subcortical and hippocampal structures were quantified. Network topology and vulnerability were modelled within the graph theoretical framework. Receiver-operating characteristic (ROC) curve analysis was applied to assess the accuracy of GM pathology measures to discriminate between MSE and MS patients. Results: Higher lesion volumes within the hippocampus, mesiotemporal cortex and amygdala were detected in the MSE compared to the MS group (all p < 0.05). The MSE group had lower cortical volumes mainly in temporal and parietal areas compared to the MS and HS groups (all p < 0.05). Lower hippocampal tail and presubiculum volumes were identified in both the MSE and MS groups compared to the HS group (all p < 0.05). Network topology in the MSE group was characterized by higher transitivity and assortativity, and higher vulnerability compared to the MS and HS groups (all p < 0.05). Hippocampal lesion volume yielded the highest accuracy (area under the ROC curve 0.80 [0.67–0.91]) in discriminating between MSE and MS patients. Conclusions: High lesion load, altered integrity of mesiotemporal GM structures, and network reorganization are associated with a greater propensity for epilepsy occurrence in people with MS

Myelination- and immune-mediated MR-based brain network correlates

Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by inflammatory and neurodegenerative processes. Despite demyelination being a hallmark of the disease, how it relates to neurodegeneration has still not been completely unraveled, and research is still ongoing into how these processes can be tracked non-invasively. Magnetic resonance imaging (MRI) derived brain network characteristics, which closely mirror disease processes and relate to functional impairment, recently became important variables for characterizing immune-mediated neurodegeneration; however, their histopathological basis remains unclear. Methods In order to determine the MRI-derived correlates of myelin dynamics and to test if brain network characteristics derived from diffusion tensor imaging reflect microstructural tissue reorganization, we took advantage of the cuprizone model of general demyelination in mice and performed longitudinal histological and imaging analyses with behavioral tests. By introducing cuprizone into the diet, we induced targeted and consistent demyelination of oligodendrocytes, over a period of 5 weeks. Subsequent myelin synthesis was enabled by reintroduction of normal food. Results Using specific immune-histological markers, we demonstrated that 2 weeks of cuprizone diet induced a 52% reduction of myelin content in the corpus callosum (CC) and a 35% reduction in the neocortex. An extended cuprizone diet increased myelin loss in the CC, while remyelination commenced in the neocortex. These histologically determined dynamics were reflected by MRI measurements from diffusion tensor imaging. Demyelination was associated with decreased fractional anisotropy (FA) values and increased modularity and clustering at the network level. MRI-derived modularization of the brain network and FA reduction in key anatomical regions, including the hippocampus, thalamus, and analyzed cortical areas, were closely related to impaired memory function and anxiety-like behavior. Conclusion Network-specific remyelination, shown by histology and MRI metrics, determined amelioration of functional performance and neuropsychiatric symptoms. Taken together, we illustrate the histological basis for the MRI-driven network responses to demyelination, where increased modularity leads to evolving damage and abnormal behavior in MS. Quantitative information about in vivo myelination processes is mirrored by diffusion-based imaging of microstructural integrity and network characteristics

Bamboo reinforced concrete: a critical review

© 2018, The Author(s). The use of small diameter whole-culm (bars) and/or split bamboo (a.k.a. splints or round strips) has often been proposed as an alternative to relatively expensive reinforcing steel in reinforced concrete. The motivation for such replacement is typically cost—bamboo is readily available in many tropical and sub-tropical locations, whereas steel reinforcement is relatively more expensive—and more recently, the drive to find more sustainable alternatives in the construction industry. This review addresses such ‘bamboo-reinforced concrete’ and assesses its structural and environmental performance as an alternative to steel reinforced concrete. A prototype three bay portal frame, that would not be uncommon in regions of the world where bamboo-reinforced concrete may be considered, is used to illustrate bamboo reinforced concrete design and as a basis for a life cycle assessment of the same. The authors conclude that, although bamboo is a material with extraordinary mechanical properties, its use in bamboo-reinforced concrete is an ill-considered concept, having significant durability, strength and stiffness issues, and does not meet the environmentally friendly credentials often attributed to it

Deposition of Carbon Nanotubes Onto Aramid Fibers Using as-received and Chemically Modified Fibers

Multiwall carbon nanotubes (MWCNTs) oxidized by an acid treatment were deposited on the surface of as-received commercial aramid fibers containing a surface coating (“sizing”), and fibers modified by either a chlorosulfonic treatment or a mixture of nitric and sulfuric acids. The surface of the aramid fiber activated by the chemical treatments presents increasing density of CO, COOH and OH functional groups. However, these chemical treatments reduced the tensile mechanical properties of the fibers, especially when the nitric and sulfuric acid mixture was used. Characterization of the MWCNTs deposited on the fiber surface was conducted by scanning electron microscopy, Raman spectroscopy mapping and X-ray photoelectron spectroscopy. These characterizations showed higher areal concentration and more homogeneous distribution of MWCNTs over the aramid fibers for as-received fibers and for those modified with chlorosulfonic acid, suggesting the existence of interaction between the oxidized MWCNTs and the fiber coating. The electrical resistance of the MWCNT-modified aramid yarns comprising ∼1000 individual fibers was in the order of MΩ/cm, which renders multifunctional properties

Prognostic value of single-subject grey matter networks in early multiple sclerosis

The identification of prognostic markers in early multiple sclerosis (MS) is challenging and requires reliable measures that robustly predict future disease trajectories. Ideally, such measures should make inferences at the individual level to inform clinical decisions. This study investigated the prognostic value of longitudinal structural networks to predict five-year EDSS progression in patients with relapsing-remitting MS (RRMS). We hypothesized that network measures, derived from magnetic resonance imaging (MRI), outperform conventional MRI measurements at identifying patients at risk of developing disability progression. This longitudinal, multicentre study within the Magnetic Resonance Imaging in MS (MAGNIMS) network included 406 patients with RRMS (mean age = 35.7 ± 9.1 years) followed up for five years (mean follow-up = 5.0 ± 0.6 years). Expanded Disability Status Scale (EDSS) was determined to track disability accumulation. A group of 153 healthy subjects (mean age = 35.0 ± 10.1 years) with longitudinal MRI served as controls. All subjects underwent MRI at baseline and again one year after baseline. Grey matter (GM) atrophy over one year and white matter (WM) lesion load were determined. A single-subject brain network was reconstructed from T1-weighted scans based on GM atrophy measures derived from a statistical parameter mapping (SPM)-based segmentation pipeline. Key topological measures, including network degree, global efficiency and transitivity, were calculated at single-subject level to quantify network properties related to EDSS progression. Areas under receiver operator characteristic (ROC) curves were constructed for GM atrophy, WM lesion load and the network measures, and comparisons between ROC curves were conducted. The applied network analyses differentiated patients with RRMS who experience EDSS progression over five years through lower values for network degree [H(2)=30.0, p<0.001] and global efficiency [H(2)=31.3, p<0.001] from healthy controls but also from patients without progression. For transitivity, the comparisons showed no difference between the groups (H(2)= 1.5, p=0.474). Most notably, changes in network degree and global efficiency were detected independent of disease activity in the first year. The described network reorganization in patients experiencing EDSS progression was evident in the absence of GM atrophy. Network degree and global efficiency measurements demonstrated superiority of network measures in the ROC analyses over GM atrophy and WM lesion load in predicting EDSS worsening (all p-values < 0.05). Our findings provide evidence that GM network reorganization over one year discloses relevant information about subsequent clinical worsening in RRMS. Early GM restructuring towards lower network efficiency predicts disability accumulation and outperforms conventional MRI predictors