Publications by authors named "Frederik Barkhof"

Objective: To assess the pathological mechanisms contributing to white matter (WM) lesion expansion or contraction and remyelination in multiple sclerosis (MS).

Methods: We assessed 1,613 lesions in 49 people with relapsing-remitting MS in the CCMR-One bexarotene trial (EudraCT 2014-003145-99). We measured lesion orientation relative to WM tracts, surface-in gradients and veins.

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Introduction: Artificial intelligence and neuroimaging enable accurate dementia prediction, but 'black box' models can be difficult to trust. Explainable artificial intelligence (XAI) describes techniques to understand model behaviour and the influence of features, however deciding which method is most appropriate is non-trivial. Vision transformers (ViT) have also gained popularity, providing a self-explainable, alternative to traditional convolutional neural networks (CNN).

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Background And Objectives: Although multiple sclerosis (MS) can be conceptualized as a network disorder, brain network analyses typically require advanced MRI sequences not commonly acquired in clinical practice. Using conventional MRI, we assessed cross-sectional and longitudinal structural disconnection and morphometric similarity networks in people with MS (pwMS), along with their relationship with clinical disability.

Methods: In this longitudinal monocentric study, 3T structural MRI of pwMS and healthy controls (HC) was retrospectively analyzed.

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Background: Biomarkers are needed to track progression in MS trials. Neurofilament heavy chain (NfH) has been underutilized due to assay limitations.

Objective: To investigate the added value of cerebrospinal fluid (CSF) NfH in secondary progressive multiple sclerosis (SPMS) using contemporary immunoassays.

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Importance: Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels.

Objective: To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, APOE ε4 copy number, and age.

Design, Setting, And Participants: This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]).

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Objective: The extent of resection (EOR) and postoperative residual tumor (RT) volume are prognostic factors in glioblastoma. Calculations of EOR and RT rely on accurate tumor segmentations. Raidionics is an open-access software that enables automatic segmentation of preoperative and early postoperative glioblastoma using pretrained deep learning models.

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An emerging biomarker of blood-brain barrier (BBB) permeability is the time of exchange (Tex) of water from the blood to tissue, as measured by multi-echo arterial spin labeling (ASL) MRI. This new non-invasive sequence, already tested in mice, has recently been adapted to humans and optimized for clinical scanning time. In this study, we studied the normal variability of Tex over age and sex, which needs to be established as a reference for studying changes in neurological disease.

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This scientific commentary refers to 'A data-driven model of disability progression in progressive multiple sclerosis', by Garbarino . (https://doi.org/10.

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Background: White matter hyperintensities (WMH) have been implicated in the pathogenesis of neuropsychiatric symptoms of dementia but the functional significance of WMH in specific white matter (WM) tracts is unclear. We investigate whether WMH burden within major WM fibre classes and individual WM tracts are differentially associated with different neuropsychiatric syndromes in a large multicentre study.

Method: Neuroimaging and neuropsychiatric data of seven memory clinic cohorts through the Meta VCI Map consortium were harmonised.

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Disruptions to brain networks, measured using structural (sMRI), diffusion (dMRI), or functional (fMRI) MRI, have been shown in people with multiple sclerosis (PwMS), highlighting the relevance of regions in the core of the connectome but yielding mixed results depending on the studied connectivity domain. Using a multilayer network approach, we integrated these three modalities to portray an enriched representation of the brain's core-periphery organization and explore its alterations in PwMS. In this retrospective cross-sectional study, we selected PwMS and healthy controls with complete multimodal brain MRI acquisitions from 13 European centers within the MAGNIMS network.

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Objectives: Distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) dementia, particularly in patients with DLB and concomitant AD pathology (DLB/AD+), can be challenging and there is no specific MRI signature for DLB. The aim of this study is to examine the additional value of MRI-based brain volumetry in separating patients with DLB (AD+/-) from patients with AD and controls.

Methods: We included 1518 participants from four cohorts (ADC, ADNI, PDBP and PredictND); 147 were patients with DLB (n = 76, DLB/AD+; n = 71, DLB/AD-), 668 patients with AD dementia, and 703 controls.

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Objective: To assess the interrelationship between cortical lesions and cortical thinning and volume loss in people with multiple sclerosis within cortical networks, and how this relates to future cognition.

Methods: In this longitudinal study, 230 people with multiple sclerosis and 60 healthy controls underwent 3 Tesla MRI at baseline and neuropsychological assessment at baseline and 5-year follow-up. Cortical regions (N = 212) were divided into seven functional networks.

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Background: Optical coherence tomography (OCT) inner retinal metrics reflect neurodegeneration in multiple sclerosis (MS). We explored OCT measures as biomarkers of disease severity in secondary progressive MS (SPMS).

Methods: We investigated people with SPMS from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial OCT substudy, analysing brain MRIs, clinical assessments and OCT at baseline and 96 weeks.

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Purpose To extend a previously developed machine learning algorithm for harmonizing brain volumetric data of individuals undergoing neuroradiologic assessment of Alzheimer disease not encountered during model training. Materials and Methods Neuroharmony is a recently developed method that uses image quality metrics as predictors to remove scanner-related effects in brain-volumetric data using random forest regression. To account for the interactions between Alzheimer disease pathology and image quality metrics during harmonization, the authors developed a multiclass extension of Neuroharmony for individuals with and without cognitive impairment.

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Background: Comorbidities including vascular risk factors can be associated with whole and regional brain atrophy in multiple sclerosis (MS). This has been examined in mixed MS cohorts in prospective or observational studies; however, the association between vascular comorbidities (VCM) in secondary progressive MS (SPMS) and brain atrophy has been less well studied. The aim was to investigate the cross-sectional and longitudinal association between VCM, comorbidity burden and brain atrophy in SPMS.

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Human musicality might have co-evolved with social cognition abilities, but common neuroanatomical substrates remain largely unclear. In behavioural variant frontotemporal dementia, social cognitive abilities are profoundly impaired, whereas these are typically spared in Alzheimer's disease. If musicality indeed shares a neuroanatomical basis with social cognition, it could be hypothesized that clinical and neuroanatomical associations of musicality and social cognition should differ between these causes of dementia.

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The first genome-wide significant multiple sclerosis severity locus, rs10191329, has been pathologically linked to cortical lesion load and brain atrophy. However, observational cohorts such as MSBase have not replicated associations with disability outcomes, instead finding other loci. We evaluated rs10191329 and MSBase loci in a unique cohort of 53 people followed for 30 years after a clinically isolated syndrome, with deep clinical phenotyping and MRI measures of inflammation and neurodegeneration.

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Background And Objectives: In multiple sclerosis (MS), brain reserve serves as a protective factor against cognitive impairment. Previous research has suggested a structural counterpart in the spine-spinal cord reserve-seemed to be associated with physical disability. This study aimed to investigate the potential of the cervical canal area (CCaA) as a proxy for spinal cord reserve in a multicentric cohort of people with MS (PwMS).

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Importance: Increasing numbers of people with multiple sclerosis (MS) use disease-modifying therapy (DMT). Long-term stable disease while taking such medications provides a rationale for considering DMT discontinuation given patient burden, costs, and potential adverse effects of immunomodulating therapy.

Objective: To investigate whether first-line DMT can be safely discontinued in patients with long-term stable MS.

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Background: Alexander disease is an autosomal dominant leukodystrophy caused by heterozygous pathogenic variants in the glial fibrillar acidic protein (GFAP) gene. Although increasingly recognised, there is evidence that Alexander disease, particularly later-onset disease, is significantly underdiagnosed and its true prevalence is unknown (the only population-based prevalence was estimated at one in 2.7 million).

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Objective: The 2017 McDonald criteria continued the separation of diagnostic criteria for relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS) for historical, rather than biological, reasons. We aimed to explore the feasibility of a single, unified set of diagnostic criteria when applied to patients with suspected PPMS.

Methods: We retrospectively identified patients evaluated for suspected PPMS at 5 European centers.

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Article Synopsis
  • - The study investigates how brain aging differs between healthy controls and patients with various neurological disorders, focusing on its clinical implications and using a retrospective analysis of MRI data.
  • - A total of 2,913 healthy individuals and 1,600 patients with conditions like multiple sclerosis and Alzheimer's were assessed by comparing their estimated brain age using advanced imaging techniques.
  • - Results showed that individuals with "accelerated" brain age tended to have higher white matter hyperintensities and lower brain volumes, with notable correlations between increased brain age gap and cognitive decline across all disorders examined.
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Background: The increasing prevalence of dementia and the introduction of disease-modifying therapies (DMTs) highlight the need for efficient diagnostic pathways in memory clinics. We present a data-driven approach to efficiently guide stepwise diagnostic testing for three clinical scenarios: 1) syndrome diagnosis, 2) etiological diagnosis, and 3) eligibility for DMT.

Methods: We used data from two memory clinic cohorts (ADC, PredictND), including 504 patients with dementia (302 Alzheimer's disease, 107 frontotemporal dementia, 35 vascular dementia, 60 dementia with Lewy bodies), 191 patients with mild cognitive impairment, and 188 cognitively normal controls (CN).

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Article Synopsis
  • - The study investigates how cognitive impairment, fatigue, and mood disorders interact in individuals with multiple sclerosis (MS) by examining brain atrophy patterns across different patient profiles.
  • - Researchers categorized MS patients into four clusters based on their cognitive performance, fatigue, anxiety, and depression, using k-means clustering to identify distinct patterns among them.
  • - The findings revealed that cognitive tests and mental health factors significantly impact disability scores, with specific clusters showing correlations between cognitive impairment and levels of fatigue, anxiety, and depression.
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Amyloid-PET quantification through the tracer-independent Centiloid (CL) scale has emerged as an essential tool for the accurate measurement of amyloid-β (Aβ) pathology in Alzheimer's disease (AD) patients. The AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations for the CL scale. Compared to histopathology, visual reads, and cerebrospinal fluid, CL quantification accurately reflects the amount of AD pathology.

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