Characterization of cortico-meningeal translocator protein expression in multiple sclerosis.

Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. PET targeting the 18 kDa mitochondrial translocator protein (TSPO) is a molecular-specific approach to quantifying immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. This study aimed to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry.

White matter paramagnetic rim and non-rim lesions share a periventricular gradient in multiple sclerosis: A 7-T imaging study.

Background: Paramagnetic rim white matter (WM) lesions (PRL) are thought to be a main driver of non-relapsing multiple sclerosis (MS) progression. It is unknown whether cerebrospinal fluid (CSF)-soluble factors diffusing from the ventricles contribute to PRL formation.

Objective: To investigate the distribution of PRL and non-rim brain WM lesions as a function of distance from ventricular CSF, their relationship with cortical lesions, the contribution of lesion phenotype, and localization to neurological disability.

A translational MRI approach to validate acute axonal damage detection as an early event in multiple sclerosis.

Axonal degeneration is a central pathological feature of multiple sclerosis and is closely associated with irreversible clinical disability. Current noninvasive methods to detect axonal damage in vivo are limited in their specificity and clinical applicability, and by the lack of proper validation. We aimed to validate an MRI framework based on multicompartment modeling of the diffusion signal (AxCaliber) in rats in the presence of axonal pathology, achieved through injection of a neurotoxin damaging the neuronal terminal of axons.

In vivo characterization of microglia and myelin relation in multiple sclerosis by combined C-PBR28 PET and synthetic MRI.

Background: The in vivo relation between microglia activation and demyelination in multiple sclerosis is still unclear.

Objective: We combined C-PBR28 positron emission tomography and rapid estimation of myelin for diagnostic imaging (REMyDI) to characterize the relation between these pathological processes in a heterogeneous MS cohort.

Methods: C-PBR28 standardized uptake values normalized by a pseudo-reference region (SUVR) were used to measure activated microglia.

Cortical and white matter lesion topology influences focal corpus callosum atrophy in multiple sclerosis.

Background And Purpose: Corpus callosum (CC) atrophy is a strong predictor of multiple sclerosis (MS) disability but the contributing pathological mechanisms remain uncertain. We aimed to apply advanced MRI to explore what drives the often nonuniform callosal atrophy.

Methods: Prospective brain 7 Tesla and 3 Tesla Human Connectom Scanner MRI were performed in 92 MS patients.

Cortical and phase rim lesions on 7 T MRI as markers of multiple sclerosis disease progression.

In multiple sclerosis, individual lesion-type patterns on magnetic resonance imaging might be valuable for predicting clinical outcome and monitoring treatment effects. Neuropathological and imaging studies consistently show that cortical lesions contribute to disease progression. The presence of chronic active white matter lesions harbouring a paramagnetic rim on susceptibility-weighted magnetic resonance imaging has also been associated with an aggressive form of multiple sclerosis.

Quantitative 7-Tesla Imaging of Cortical Myelin Changes in Early Multiple Sclerosis.

Cortical demyelination occurs early in multiple sclerosis (MS) and relates to disease outcome. The brain cortex has endogenous propensity for remyelination as proven from histopathology study. In this study, we aimed at characterizing cortical microstructural abnormalities related to myelin content by applying a novel quantitative MRI technique in early MS.

Influence of Mesenchymal Stem Cell Sources on Their Regenerative Capacities on Different Surfaces.

Current gold-standard strategies for bone regeneration do not achieve the optimal recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells-such as mesenchymal stem cells (MSCs)-and bioactive ceramic scaffolds-such as calcium phosphate-based (CaPs) bioceramics-seem promising. The biological properties of MSCs are influenced by the tissue source.

The relevance of multiple sclerosis cortical lesions on cortical thinning and their clinical impact as assessed by 7.0-T MRI.

Objective: This study aimed to investigate at 7.0-T MRI a) the role of multiple sclerosis (MS) cortical lesions in cortical tissue loss b) their relation to neurological disability.

Methods: In 76 relapsing remitting and 26 secondary progressive MS patients (N = 102) and 56 healthy subjects 7.

Publisher Correction: A predominant involvement of the triple seropositive patients and others with rheumatoid factor in the association of smoking with rheumatoid arthritis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

7 T imaging reveals a gradient in spinal cord lesion distribution in multiple sclerosis.

We used 7 T MRI to: (i) characterize the grey and white matter pathology in the cervical spinal cord of patients with early relapsing-remitting and secondary progressive multiple sclerosis; (ii) assess the spinal cord lesion spatial distribution and the hypothesis of an outside-in pathological process possibly driven by CSF-mediated immune cytotoxic factors; and (iii) evaluate the association of spinal cord pathology with brain burden and its contribution to neurological disability. We prospectively recruited 20 relapsing-remitting, 15 secondary progressive multiple sclerosis participants and 11 age-matched healthy control subjects to undergo 7 T imaging of the cervical spinal cord and brain as well as conventional 3 T brain acquisition. Cervical spinal cord imaging at 7 T was used to segment grey and white matter, including lesions therein.

Characterization of thalamic lesions and their correlates in multiple sclerosis by ultra-high-field MRI.

Background: Thalamic pathology is a marker for neurodegeneration and multiple sclerosis (MS) disease progression.

Objective: To characterize (1) the morphology of thalamic lesions, (2) their relation to cortical and white matter (WM) lesions, and (3) clinical measures, and to assess (4) the imaging correlates of thalamic atrophy.

Methods: A total of 90 MS patients and 44 healthy controls underwent acquisition of 7 Tesla images for lesion segmentation and 3 Tesla scans for atrophy evaluation.

A predominant involvement of the triple seropositive patients and others with rheumatoid factor in the association of smoking with rheumatoid arthritis.

The major environmental risk factor for rheumatoid arthritis (RA) is smoking, which according to a widely accepted model induces protein citrullination in the lungs, triggering the production of anti-citrullinated protein antibodies (ACPA) and RA development. Nevertheless, some research findings do not fit this model. Therefore, we obtained six independent cohorts with 2253 RA patients for a detailed analysis of the association between smoking and RA autoantibodies.

Whole brain in vivo axonal diameter mapping in multiple sclerosis.

Traditional techniques based on diffusion MR imaging suffer from extremely low specificity in separating disease-related alterations in white matter microstructure, which can involve multiple phenomena including axonal loss, demyelination and changes in axonal size. Multi-shell diffusion MRI is able to greatly increase specificity by concomitantly exploring multiple diffusion timescales. If multi-shell acquisition is combined with an exploration of different diffusion times, diffusion data allows the estimation of sophisticated compartmental models, which provide greatly enhanced specificity to the presence of different tissue sub-compartments, as well as estimates of intra-voxel axonal diameter distributions.

Profiles of cortical inflammation in multiple sclerosis by C-PBR28 MR-PET and 7 Tesla imaging.

Background: Neuroinflammation with microglia activation is thought to be closely related to cortical multiple sclerosis (MS) lesion pathogenesis.

Objective: Using C-PBR28 and 7 Tesla (7T) imaging, we assessed in 9 relapsing-remitting multiple sclerosis (RRMS) and 10 secondary progressive multiple sclerosis (SPMS) patients the following: (1) microglia activation in lesioned and normal-appearing cortex, (2) cortical lesion inflammatory profiles, and (3) the relationship between neuroinflammation and cortical integrity.

Methods: Mean C-PBR28 uptake was measured in focal cortical lesions, cortical areas with 7T quantitative T* (q-T*) abnormalities, and normal-appearing cortex.

Evidence of diffuse cerebellar neuroinflammation in multiple sclerosis by C-PBR28 MR-PET.

Background: Activated microglia, which can be detected in vivo by C-PBR28 positron emission tomography (PET), represent a main component of MS pathology in the brain. Their role in the cerebellum is still unexplored, although cerebellar involvement in MS is frequent and accounts for disability progression.

Objectives: We aimed at characterizing cerebellar neuroinflammation in MS patients compared to healthy subjects by combining C-PBR28 MRI-Positron Emission Tomography (MR-PET) with 7 Tesla (T) MRI and assessing its relationship with brain neuroinflammation and clinical outcome measures.

Longitudinal Characterization of Cortical Lesion Development and Evolution in Multiple Sclerosis with 7.0-T MRI.

Background Cortical lesions develop early in multiple sclerosis (MS) and play a major role in disease progression. MRI at 7.0 T shows high sensitivity for detection of cortical lesions as well as better spatial resolution and signal-to-noise ratio compared with lower field strengths.

Evidence of early microstructural white matter abnormalities in multiple sclerosis from multi-shell diffusion MRI.

Irreversible white matter (WM) damage, including severe demyelination and axonal loss, is a main determinant of long-term disability in multiple sclerosis (MS). Non-invasive detection of changes in microstructural WM integrity in the disease is challenging since commonly used imaging metrics lack the necessary sensitivity, especially in the early phase of the disease. This study aims at assessing microstructural WM abnormalities in early-stage MS by using ultra-high gradient strength multi-shell diffusion MRI and the restricted signal fraction (FR) from the Composite Hindered and Restricted Model of Diffusion (CHARMED), a metric sensitive to the volume fraction of axons.

Evidence for Progressive Microstructural Damage in Early Multiple Sclerosis by Multi-Shell Diffusion Magnetic Resonance Imaging.

In multiple sclerosis (MS), it would be of clinical value to be able to track the progression of axonal pathology, especially before the manifestation of clinical disability. However, non-invasive evaluation of short-term longitudinal progression of white matter integrity is challenging. This study aims at assessing longitudinal changes in the restricted (i.

Functional implications of single nucleotide polymorphisms rs662 and rs854860 on the antioxidative activity of paraoxonase1 (PON1) in patients with rheumatoid arthritis.

Background: Atherosclerosis leading to cardiovascular disease (CVD) is the main cause of mortality and morbidity in patients with rheumatoid arthritis (RA). Paraoxonase1 (PON1) is the best understood member of plasma paraoxonases with anti-atherogenic properties.

Patients And Methods: Spanish RA (n = 549) consecutively recruited from 1 single center and 477 ethnically matched healthy controls were included in a case-control study.

Differential Expression of Genes in Mesenchymal Stem Cells from Osteoarthritic Patients Is Independent of Their Promoter Methylation.

Skeletogenesis, remodeling, and maintenance in adult tissues are regulated by sequential activation of genes coding for specific transcription factors. The conserved Homeobox genes (, in humans) are involved in several skeletal pathologies. Osteoarthritis (OA) is characterized by homeostatic alterations of cartilage and bone synthesis, resulting in cartilage destruction and increased bone formation.

Specific Association of HLA-DRB1*03 With Anti-Carbamylated Protein Antibodies in Patients With Rheumatoid Arthritis.

Objective: Recognition of a new type of rheumatoid arthritis (RA)-specific autoantibody, the anti-carbamylated protein antibodies (anti-CarP), has provided an opportunity to improve the management and understanding of RA. The current study was undertaken to assess the relationship between anti-CarP antibodies and HLA-DRB1 alleles in RA.

Methods: Serum samples were obtained from 3 different collections, comprising a total of 1,126 RA patients.

Changes in structural network are associated with cortical demyelination in early multiple sclerosis.

The aim of this study was to investigate the interplay between structural connectivity and cortical demyelination in early multiple sclerosis. About 27 multiple sclerosis patients and 18 age-matched controls underwent two MRI scanning sessions. The first was done at 7T and involved acquiring quantitative T and T * high-resolution maps to estimate cortical myelination.

Early axonal damage in normal appearing white matter in multiple sclerosis: Novel insights from multi-shell diffusion MRI.

Conventional diffusion-weighted MR imaging techniques provide limited specificity in disentangling disease-related microstructural alterations involving changes in both axonal density and myelination. By simultaneously probing multiple diffusion regimens, multi-shell diffusion MRI is capable of increasing specificity to different tissue sub-compartments and hence separate different contributions to changes in diffusion-weighted signal attenuation. Advanced multi-shell diffusion models impose significant requirements on the amount of diffusion weighting (i.