Improving explanation of motor disability with diffusion-based graph metrics at onset of the first demyelinating event.

Background: Conventional magnetic resonance imaging (MRI) does not account for all disability in multiple sclerosis.

Objective: The objective was to assess the ability of graph metrics from diffusion-based structural connectomes to explain motor function beyond conventional MRI in early demyelinating clinically isolated syndrome (CIS).

Methods: A total of 73 people with CIS underwent conventional MRI, diffusion-weighted imaging and clinical assessment within 3 months from onset.

Quantifying neurodegeneration of the cervical cord and brain in degenerative cervical myelopathy: A multicentre study using quantitative magnetic resonance imaging.

Background And Purpose: Simultaneous assessment of neurodegeneration in both the cervical cord and brain across multiple centres can enhance the effectiveness of clinical trials. Thus, this study aims to simultaneously assess microstructural changes in the cervical cord and brain above the stenosis in degenerative cervical myelopathy (DCM) using quantitative magnetic resonance imaging (MRI) in a multicentre study.

Methods: We applied voxelwise analysis with a probabilistic brain/spinal cord template embedded in statistical parametric mappin (SPM-BSC) to process multi parametric mapping (MPM) including effective transverse relaxation rate (R2*), longitudinal relaxation rate (R1), and magnetization transfer (MT), which are indirectly sensitive to iron and myelin content.

What contributes to disability in progressive MS? A brain and cervical cord-matched quantitative MRI study.

Background: We assessed the ability of a brain-and-cord-matched quantitative magnetic resonance imaging (qMRI) protocol to differentiate patients with progressive multiple sclerosis (PMS) from controls, in terms of normal-appearing (NA) tissue abnormalities, and explain disability.

Methods: A total of 27 patients and 16 controls were assessed on the Expanded Disability Status Scale (EDSS), 25-foot timed walk (TWT), 9-hole peg (9HPT) and symbol digit modalities (SDMT) tests. All underwent 3T brain and (C2-C3) cord structural imaging and qMRI (relaxometry, quantitative magnetisation transfer, multi-shell diffusion-weighted imaging), using a fast brain-and-cord-matched protocol with brain-and-cord-unified imaging readouts.

Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis.

Background And Purpose: Newly appearing lesions in multiple sclerosis (MS) may evolve into chronically active, slowly expanding lesions (SELs), leading to sustained disability progression. The aim of this study was to evaluate the incidence of newly appearing lesions developing into SELs, and their correlation to clinical evolution and treatment.

Methods: A retrospective analysis of a fingolimod trial in primary progressive MS (PPMS; INFORMS, NCT00731692) was undertaken.

Networks of microstructural damage predict disability in multiple sclerosis.

Background: Network-based measures are emerging MRI markers in multiple sclerosis (MS). We aimed to identify networks of white (WM) and grey matter (GM) damage that predict disability progression and cognitive worsening using data-driven methods.

Methods: We analysed data from 1836 participants with different MS phenotypes (843 in a discovery cohort and 842 in a replication cohort).

influences long-term disability progression and tissue damage on MRI in relapse-onset multiple sclerosis.

Background: Whether genetic factors influence the long-term course of multiple sclerosis (MS) is unresolved.

Objective: To determine the influence of on long-term disease course in a homogeneous cohort of clinically isolated syndrome (CIS) patients.

Methods: One hundred seven patients underwent clinical and MRI assessment at the time of CIS and after 1, 3, 5 and 15 years.

Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

Objective: In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis.

SENSE EPI reconstruction with 2D phase error correction and channel-wise noise removal.

Purpose: To develop a robust reconstruction pipeline for EPI data that enables 2D Nyquist phase error correction using sensitivity encoding without incurring major noise artifacts in low SNR data.

Methods: SENSE with 2D phase error correction (PEC-SENSE) was combined with channel-wise noise removal using Marcenko-Pastur principal component analysis (MPPCA) to simultaneously eliminate Nyquist ghost artifacts in EPI data and mitigate the noise amplification associated with phase correction using parallel imaging. The proposed pipeline (coined SPECTRE) was validated in phantom DW-EPI data using the accuracy and precision of diffusion metrics; ground truth values were obtained from data acquired with a spin echo readout.

Acute corticospinal tract diffusion tensor imaging predicts 6-month functional outcome after intracerebral haemorrhage.

Introduction: Diffusion tensor imaging (DTI) can assess the structural integrity of the corticospinal tract (CST) in vivo. We aimed to investigate whether CST DTI metrics after intracerebral haemorrhage (ICH) are associated with 6-month functional outcome and can improve the predictive performance of the existing ICH score.

Methods: We retrospectively included 42 patients with DTI performed within 5 days after deep supratentorial spontaneous ICH.

B Cells in the CNS at Postmortem Are Associated With Worse Outcome and Cell Types in Multiple Sclerosis.

Background And Objectives: To define the clinical and pathologic correlations of compartmentalized perivascular B cells in postmortem progressive multiple sclerosis (MS) brains.

Methods: Brain slices were acquired from 11 people with secondary progressive (SP) MS, 5 people with primary progressive (PP) MS, and 4 controls. Brain slices were immunostained for B lymphocytes (CD20), T lymphocytes (CD3), cytotoxic T lymphocytes (CD8), neuronal neurofilaments (NF200), myelin (SMI94), macrophages/microglia (CD68 and IBA1), astrocytes (glial fibrillary acidic protein [GFAP]), and mitochondria (voltage-dependent anion channel and cytochrome c oxidase subunit 4).

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation.

Tracking White and Gray Matter Degeneration along the Spinal Cord Axis in Degenerative Cervical Myelopathy.

This study aims to determine tissue-specific neurodegeneration across the spinal cord in patients with mild-moderate degenerative cervical myelopathy (DCM). Twenty-four mild-moderate DCM and 24 healthy subjects were recruited. In patients, a T2-weighted scan was acquired at the compression site, whereas in all participants a T2*-weighted and diffusion-weighted scan was acquired at the cervical level (C2-C3) and in the lumbar enlargement (i.

Brain microstructural and metabolic alterations detected in vivo at onset of the first demyelinating event.

In early multiple sclerosis, a clearer understanding of normal-brain tissue microstructural and metabolic abnormalities will provide valuable insights into its pathophysiology. We used multi-parametric quantitative MRI to detect alterations in brain tissues of patients with their first demyelinating episode. We acquired neurite orientation dispersion and density imaging [to investigate morphology of neurites (dendrites and axons)] and 23Na MRI (to estimate total sodium concentration, a reflection of underlying changes in metabolic function).

White matter integrity correlates with cognition and disease severity in Fabry disease.

Cerebral white matter pathology is a common CNS manifestation of Fabry disease, visualized as white matter hyperintensities on MRI in 42-81% of patients. Diffusion tensor imaging (DTI) MRI is a sensitive technique to quantify microstructural damage within the white matter with potential value as a disease biomarker. We evaluated the pattern of DTI abnormalities in Fabry disease, and their correlations with cognitive impairment, mood, anxiety, disease severity and plasma lyso-Gb3 levels in 31 patients with genetically proven Fabry disease and 19 age-matched healthy control subjects.

MRI-visible perivascular spaces as an imaging biomarker in Fabry disease.

Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting in vascular glycosphingolipid accumulation and increased stroke risk. MRI findings associated with FD include white matter hyperintensities (WMH) and cerebral microbleeds (CMBs), suggesting the presence of cerebral small vessel disease. MRI-visible perivascular spaces (PVS) are another promising marker of small vessel disease associated with impaired interstitial fluid drainage.

Pathologic correlates of the magnetization transfer ratio in multiple sclerosis.

Objective: To identify pathologic correlates of magnetization transfer ratio (MTR) in multiple sclerosis (MS) in an MRI-pathology study.

Methods: We acquired MTR maps at 3T from 16 fixed MS brains and 4 controls, and immunostained 100 tissue blocks for neuronal neurofilaments, myelin (SMI94), tissue macrophages (CD68), microglia (IBA1), B-lymphocytes, T-lymphocytes, cytotoxic T-lymphocytes, astrocytes (glial fibrillary acidic protein), and mitochondrial damage (COX4, VDAC). We defined regions of interest in lesions, normal-appearing white matter (NAWM), and cortical normal-appearing gray matter (NAGM).

Magnetisation transfer ratio combined with magnetic resonance neurography is feasible in the proximal lumbar plexus using healthy volunteers at 3T.

Magnetic resonance neurography (MRN) has been used extensively to study pathological conditions affecting the peripheral nervous system (PNS). However, tissue damage is assessed qualitatively with little information regarding the underlying pathophysiological processes involved. Magnetisation transfer ratio (MTR) is a quantitative magnetic resonance imaging method which is sensitive to tissue macromolecular content and may therefore have an important role in the study of pathologies affecting the PNS.

Disrupted principal network organisation in multiple sclerosis relates to disability.

Structural network-based approaches can assess white matter connections revealing topological alterations in multiple sclerosis (MS). However, principal network (PN) organisation and its clinical relevance in MS has not been explored yet. Here, structural networks were reconstructed from diffusion data in 58 relapsing-remitting MS (RRMS), 28 primary progressive MS (PPMS), 36 secondary progressive (SPMS) and 51 healthy controls (HCs).

Ongoing microstructural changes in the cervical cord underpin disability progression in early primary progressive multiple sclerosis.

Background: Pathology in the spinal cord of patients with primary progressive multiple sclerosis (PPMS) contributes to disability progression. We previously reported abnormal Q-space imaging (QSI)-derived indices in the spinal cord at baseline in patients with early PPMS, suggesting early neurodegeneration.

Objective: The aim was to investigate whether changes in spinal cord QSI over 3 years in the same cohort are associated with disability progression and if baseline QSI metrics predict clinical outcome.

Generalised boundary shift integral for longitudinal assessment of spinal cord atrophy.

Spinal cord atrophy measurements obtained from structural magnetic resonance imaging (MRI) are associated with disability in many neurological diseases and serve as in vivo biomarkers of neurodegeneration. Longitudinal spinal cord atrophy rate is commonly determined from the numerical difference between two volumes (based on 3D surface fitting) or two cross-sectional areas (CSA, based on 2D edge detection) obtained at different time-points. Being an indirect measure, atrophy rates are susceptible to variable segmentation errors at the edge of the spinal cord.

Reduced neurite density in the brain and cervical spinal cord in relapsing-remitting multiple sclerosis: A NODDI study.

Background: Multiple sclerosis (MS) affects both brain and spinal cord. However, studies of the neuraxis with advanced magnetic resonance imaging (MRI) are rare because of long acquisition times. We investigated neurodegeneration in MS brain and cervical spinal cord using neurite orientation dispersion and density imaging (NODDI).

Lifespan normative data on rates of brain volume changes.

We provide here normative values of yearly percentage brain volume change (PBVC/y) as obtained with Structural Imaging Evaluation, using Normalization, of Atrophy, a widely used open-source software, developing a PBVC/y calculator for assessing the deviation from the expected PBVC/y in patients with neurological disorders. We assessed multicenter (34 centers, 11 acquisition protocols) magnetic resonance imaging data of 720 healthy participants covering the whole adult lifespan (16-90 years). Data of 421 participants with a follow-up > 6 months were used to obtain the normative values for PBVC/y and data of 392 participants with a follow-up <1 month were selected to assess the intrasubject variability of the brain volume measurement.

Periventricular magnetisation transfer ratio abnormalities in multiple sclerosis improve after alemtuzumab.

Background: In multiple sclerosis (MS), disease effects on magnetisation transfer ratio (MTR) increase towards the ventricles. This periventricular gradient is evident shortly after first symptoms and is independent of white matter lesions.

Objective: To explore if alemtuzumab, a peripherally acting disease-modifying treatment, modifies the gradient's evolution, and whether baseline gradients predict on-treatment relapses.