The impact of the Covid-19 pandemic on adult diagnostic neuroradiology in Europe.

PURPOSE: The purpose of this survey was to understand the impact the Covid-19 pandemic has or has had on the work, training, and wellbeing of professionals in the field of diagnostic neuroradiology. METHODS: A survey was emailed to all ESNR members and associates as well as distributed via professional social media channels. The survey was held in the summer of 2020 when the first wave had subsided in most of Europe, while the second wave was not yet widespread. The questionnaire featured a total of 46 questions on general demographics, the various phases of the healthcare crisis, and the numbers of Covid-19 patients. RESULTS: One hundred sixty-seven responses were received from 48 countries mostly from neuroradiologists (72%). Most commonly taken measures during the crisis phase were reduction of outpatient exams (87%), reduction of number of staff present in the department (83%), reporting from home (62%), and shift work (54%). In the exit phase, these measures were less frequently applied, but reporting from home was still frequent (33%). However, only 22% had access to a fully equipped work station at home. While 81% felt safe at work during the crisis, fewer than 50% had sufficient personal protection equipment for the duration of the entire crisis. Mental wellbeing is an area of concern, with 61% feeling (much) worse than usual. Many followed online courses/congresses and considered these a viable alternative for the future. CONCLUSION: The Covid-19 pandemic substantially affected the professional life as well as personal wellbeing of neuroradiologists.

Differences Between MR Brain Region Segmentation Methods: Impact on Single-Subject Analysis.

For the segmentation of magnetic resonance brain images into anatomical regions, numerous fully automated methods have been proposed and compared to reference segmentations obtained manually. However, systematic differences might exist between the resulting segmentations, depending on the segmentation method and underlying brain atlas. This potentially results in sensitivity differences to disease and can further complicate the comparison of individual patients to normative data. In this study, we aim to answer two research questions: 1) to what extent are methods interchangeable, as long as the same method is being used for computing normative volume distributions and patient-specific volumes? and 2) can different methods be used for computing normative volume distributions and assessing patient-specific volumes? To answer these questions, we compared volumes of six brain regions calculated by five state-of-the-art segmentation methods: Erasmus MC (EMC), FreeSurfer (FS), geodesic information flows (GIF), multi-atlas label propagation with expectation-maximization (MALP-EM), and model-based brain segmentation (MBS). We applied the methods on 988 non-demented (ND) subjects and computed the correlation (PCC-v) and absolute agreement (ICC-v) on the volumes. For most regions, the PCC-v was good ( > 0.75 ), indicating that volume differences between methods in ND subjects are mainly due to systematic differences. The ICC-v was generally lower, especially for the smaller regions, indicating that it is essential that the same method is used to generate normative and patient data. To evaluate the impact on single-subject analysis, we also applied the methods to 42 patients with Alzheimer's disease (AD). In the case where the normative distributions and the patient-specific volumes were calculated by the same method, the patient's distance to the normative distribution was assessed with the z-score. We determined the diagnostic value of this z-score, which showed to be consistent across methods. The absolute agreement on the AD patients' z-scores was high for regions of thalamus and putamen. This is encouraging as it indicates that the studied methods are interchangeable for these regions. For regions such as the hippocampus, amygdala, caudate nucleus and accumbens, and globus pallidus, not all method combinations showed a high ICC-z. Whether two methods are indeed interchangeable should be confirmed for the specific application and dataset of interest.

Clinical practice of language fMRI in epilepsy centers: a European survey and conclusions by the ESNR Epilepsy Working Group.

PURPOSE: To assess current clinical practices throughout Europe with respect to acquisition, implementation, evaluation, and interpretation of language functional MRI (fMRI) in epilepsy patients. METHODS: An online survey was emailed to all European Society of Neuroradiology members (n = 1662), known associates (n = 6400), and 64 members of European Epilepsy network. The questionnaire featured 40 individual items on demographic data, clinical practice and indications, fMRI paradigms, radiological workflow, data post-processing protocol, and reporting. RESULTS: A total of 49 non-duplicate entries from European centers were received from 20 countries. Of these, 73.5% were board-certified neuroradiologists and 69.4% had an in-house epilepsy surgery program. Seventy-one percent of centers performed fewer than five scans per month for epilepsy. The most frequently used paradigms were phonemic verbal fluency (47.7%) and auditory comprehension (55.6%), but variants of 13 paradigms were described. Most centers assessed the fMRI task performance (75.5%), ensured cognitive-task adjustment (77.6%), trained the patient before scanning (85.7%), and assessed handedness (77.6%), but only 28.6% had special paradigms for patients with cognitive impairments. fMRI was post-processed mainly by neuroradiologists (42.1%), using open-source software (55.0%). Reporting was done primarily by neuroradiologists (74.2%). Interpretation was done mainly by visual inspection (65.3%). Most specialists (81.6%) were able to determine the hemisphere dominance for language in more than 75% of exams, attributing failure to the patient not performing the task correctly. CONCLUSION: This survey shows that language fMRI is firmly embedded in the preoperative management of epilepsy patients. The wide variety of paradigms and the use of non-CE-marked software underline the need for establishing reference standards.

Orientation Prior and Consistent Model Selection Increase Sensitivity of Tract-Based Spatial Statistics in Crossing-Fiber Regions.

The goal of this paper is to increase the statistical power of crossing-fiber statistics in voxelwise analyses of diffusion-weighted magnetic resonance imaging (DW-MRI) data. In the proposed framework, a fiber orientation atlas and a model complexity atlas were used to fit the ball-and-sticks model to diffusion-weighted images of subjects in a prospective population-based cohort study. Reproducibility and sensitivity of the partial volume fractions in the ball-and-sticks model were analyzed using TBSS (tract-based spatial statistics) and compared to a reference framework. The reproducibility was investigated on two scans of 30 subjects acquired with an interval of approximately three weeks by studying the intraclass correlation coefficient (ICC). The sensitivity to true biological effects was evaluated by studying the regression with age on 500 subjects from 65 to 90 years old. Compared to the reference framework, the ICC improved significantly when using the proposed framework. Higher t-statistics indicated that regression coefficients with age could be determined more precisely with the proposed framework and more voxels correlated significantly with age. The application of a fiber orientation atlas and a model complexity atlas can significantly improve the reproducibility and sensitivity of crossing-fiber statistics in TBSS.

Stuttering and gray matter morphometry: A population-based neuroimaging study in young children.

Stuttering is a developmental speech disorder originating in early childhood. We aimed to replicate the association of stuttering and structural morphometry using a large, population-based prospective cohort, the Generation R Study, and explore the neurobiological mechanism of stuttering in children. Twenty-six children with a history of stuttering and 489 fluent speaking peers (ages 6-9) were included in the MRI sub-study. Cortical and subcortical regions of interest were analyzed using linear regression models. Compared to fluent speakers, children with a history of stuttering had less gray matter volume in the left inferior frontal gyrus and supplementary motor area. Exploratory surface-based brain analysis showed thinner cortex in the left inferior frontal gyrus, and in bilateral frontal and parietal areas. These findings corroborate previous studies that reported aberrant brain morphometry in speech motor and auditory regions in children who stutter. Future research is needed to explore the causal nature of this association.

Dementia imaging in clinical practice: a European-wide survey of 193 centres and conclusions by the ESNR working group.

PURPOSE: Through a European-wide survey, we assessed the current clinical practice of imaging in the primary evaluation of dementia, with respect to standardised imaging, evaluation and reporting. METHODS: An online questionnaire was emailed to all European Society of Neuroradiology (ESNR) members (n = 1662) and non-members who had expressed their interest in ESNR activities in the past (n = 6400). The questionnaire featured 42 individual items, divided into multiple choice, single best choice and free text answers. Information was gathered on the context of the practices, available and preferred imaging modalities, applied imaging protocols and standards for interpretation, reporting and communication. RESULTS: A total of 193 unique (non-duplicate) entries from the European academic and non-academic institutions were received from a total of 28 countries. Of these, 75% were neuroradiologists, 12% general radiologists and 11% (neuro) radiologists in training. Of responding centres, 38% performed more than five scans/week for suspected dementia. MRI was primarily used in 72% of centres. Over 90% of centres acquired a combination of T2w, FLAIR, T1w, DWI and T2*w sequences. Visual rating scales were used in 75% of centres, most often the Fazekas and medial temporal atrophy scale; 32% of respondents lacked full confidence in their use. Only 23% of centres performed volumetric analysis. A minority of centres (28%) used structured reports. CONCLUSIONS: Current practice in dementia imaging is fairly homogeneous across Europe, in terms of image acquisition and image interpretation. Hurdles identified include training on the use of visual rating scales, implementation of volumetric assessment and structured reporting.

Cavum Septum Pellucidum in the General Pediatric Population and Its Relation to Surrounding Brain Structure Volumes, Cognitive Function, and Emotional or Behavioral Problems.

BACKGROUND AND PURPOSE: The cavum septum pellucidum, a cavity filled with CSF, is localized between the 2 lateral ventricles of the brain. The cavum is present in all neonates, but it typically closes within 5 months after birth. In some cases, this closure does not occur and a persistent or enlarged cavum septum pellucidum has been linked, in some studies, to psychiatric disorders. However, the clinical relevance in the general population is unknown. In this study, we examined the relationship between the cavum septum pellucidum and volumes of brain structures, cognitive function, and emotional and behavioral problems in children. MATERIALS AND METHODS: This study was embedded in the Generation R Study, a prospective cohort in Rotterdam, the Netherlands. MR imaging studies of 1070 children, 6-10 years of age, were systematically evaluated for the presence and length of a persistent cavum septum pellucidum. An enlarged cavum septum pellucidum was defined as a cavum length of ≥6 mm. Groups without, with persistent, and with enlarged cavum septi pellucidi were compared for brain structure volumes, nonverbal intelligence, and emotional and behavioral problems. RESULTS: The prevalence of cavum septi pellucidi in our sample was 4.6%. Children with an enlarged cavum septum pellucidum had a larger corpus callosum, greater thalamic and total white matter-to-total brain volume ratio, and smaller lateral ventricle volumes. We did not find a relationship between cavum septi pellucidi and cognitive function or emotional and behavioral problems. CONCLUSIONS: The cavum septum pellucidum is a normal structural brain variation without clinical implications in this population-based sample of school-aged children.

Glioma imaging in Europe: A survey of 220 centres and recommendations for best clinical practice.

OBJECTIVES: At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. METHODS: Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists' societies and distributed via social media. RESULTS: Responses were received from 220 institutions (59% academic). Conventional imaging protocols generally include T2w, T2-FLAIR, DWI, and pre- and post-contrast T1w. Perfusion MRI is used widely (85.5%), while spectroscopy seems reserved for specific indications. Reasons for omitting advanced imaging modalities include lack of facility/software, time constraints and no requests. Early postoperative MRI is routinely carried out by 74% within 24-72 h, but only 17% report a percent measure of resection. For follow-up, most sites (60%) issue qualitative reports, while 27% report an assessment according to the RANO criteria. A minority of sites use a reporting template (23%). CONCLUSION: Clinical best practice recommendations for glioma imaging assessment are proposed and the current role of advanced MRI modalities in routine use is addressed. KEY POINTS: • We recommend the EORTC-NBTS protocol as the clinical standard glioma protocol. • Perfusion MRI is recommended for diagnosis and follow-up of glioma. • Use of advanced imaging could be promoted with increased education activities. • Most response assessment is currently performed qualitatively. • Reporting templates are not widely used, and could facilitate standardisation.

[Risk of vitamin K antagonists in cases of cerebral microbleeds]. / Risico's van vitamine K-antagonisten bij cerebrale microbloedingen.

- Cerebral microbleeds are associated with a higher risk of intracerebral hemorrhage.- When microbleeds are detected, the possible underlying pathology should be considered; this includes cerebral amyloid angiopathy and other factors that increase the risk of haemorrhage, particularly hypertension. - No randomised trials have yet been conducted into haemorrhagic complications and cerebral infarctions in patients with microbleeds who take vitamin K antagonists. This means that it is not clear whether the intended prevention of cerebral infarctions outweighs the increased risk of haemorrhage associated with use of vitamin K antagonists by these patients.- When deciding whether or not an older patient should be given anticoagulants the following should be taken into consideration as well: comorbidities, polypharmacy, the risk of falls and the probability that the patient can be optimally titrated to vitamin K antagonists. - If there is an increased risk of intracerebral haemorrhage but anticoagulants are indicated, direct oral anticoagulants (DOACs) might be preferable to vitamin K antagonists in patients with a history of cerebral microbleeds.

A spatio-temporal reference model of the aging brain.

Both normal aging and neurodegenerative disorders such as Alzheimer's disease (AD) cause morphological changes of the brain. It is generally difficult to distinguish these two causes of morphological change by visual inspection of magnetic resonance (MR) images. To facilitate making this distinction and thus aid the diagnosis of neurodegenerative disorders, we propose a method for developing a spatio-temporal model of morphological differences in the brain due to normal aging. The method utilizes groupwise image registration to characterize morphological variation across brain scans of people with different ages. To extract the deformations that are due to normal aging we use partial least squares regression, which yields modes of deformations highly correlated with age, and corresponding scores for each input subject. Subsequently, we determine a distribution of morphologies as a function of age by fitting smooth percentile curves to these scores. This distribution is used as a reference to which a person's morphology score can be compared. We validate our method on two different datasets, using images from both cognitively normal subjects and patients with Alzheimer disease (AD). Results show that the proposed framework extracts the expected atrophy patterns. Moreover, the morphology scores of cognitively normal subjects are on average lower than the scores of AD subjects, indicating that morphology differences between AD subjects and healthy subjects can be partly explained by accelerated aging. With our methods we are able to assess accelerated brain aging on both population and individual level. A spatio-temporal aging brain model derived from 988 T1-weighted MR brain scans from a large population imaging study (age range 45.9-91.7y, mean age 68.3y) is made publicly available at www.agingbrain.nl.

Carotid Plaque Morphology and Ischemic Vascular Brain Disease on MRI.

BACKGROUND AND PURPOSE: Vulnerable carotid plaque components are reported to increase the risk of cerebrovascular events. Yet, the relation between plaque composition and subclinical ischemic brain disease is not known. We studied, in the general population, the association between carotid atherosclerotic plaque characteristics and ischemic brain disease on MR imaging. MATERIALS AND METHODS: From the population-based Rotterdam Study, 951 participants underwent both carotid MR imaging and brain MR imaging. The presence of intraplaque hemorrhage, lipid core, and calcification and measures of plaque size was assessed in both carotid arteries. The presence of plaque characteristics in relation to lacunar and cortical infarcts and white matter lesion volume was investigated and adjusted for cardiovascular risk factors. Stratified analyses were conducted to explore effect modification by sex. Additional analyses were conducted per carotid artery in relation to vascular brain disease in the ipsilateral hemisphere. RESULTS: Carotid intraplaque hemorrhage was significantly associated with the presence of cortical infarcts (OR, 1.9; 95% confidence interval, 1.1-3.3). None of the plaque characteristics were related to the presence of lacunar infarcts. Calcification was the only characteristic that was associated with higher white matter lesion volume. There was no significant interaction by sex. CONCLUSIONS: The presence of carotid intraplaque hemorrhage on MR imaging is independently associated with MR imaging-defined cortical infarcts, but not with lacunar infarcts. Plaque calcification, but not vulnerable plaque components, is related to white matter lesion volume.

[Incidental findings on brain MRIPrevalence, clinical management and natural course]. / Toevalsbevindingen bij MRI-onderzoek van de hersenen.

OBJECTIVE: Diagnostic brain imaging has been performed increasingly since the 1990s. A direct result of this is the rise in the detection of incidental findings. The objective of this study is to provide insight into the prevalence, clinical relevance and natural course of incidental findings on brain magnetic resonance imaging (MRI) scans. DESIGN: Prospective cohort study. METHOD: Within the framework of the Rotterdam study, 5800 participants underwent a brain MRI scan during the period 2005-2014. Their average age was 64.9 years, and 55.1% were female. Trained reviewers and experienced neuroradiologists evaluated all scans for clinically relevant incidental findings. We calculated the prevalence of abnormalities discovered, and investigated which clinical management followed in those participants who were referred. On the basis of subsequent scans within the framework of the Rotterdam study we investigated the natural course of findings found in participants who were not referred. RESULTS: There were incidental findings in 549 of 5800 (9.5%) participants. The most common abnormalities were meningiomas in 143 participants (2.5%) and aneurysms in 134 participants (2.3%). A total of 188 participants (3.2%) were referred to a medical specialist, who chose for a wait-and-see policy or discharge after the initial consultation in 144 participants (76.6%). The majority of meningiomas and aneurysms not referred or untreated, remained stable in size during the average follow-up period of 48-60 months. CONCLUSION: Incidental findings on brain MRI are made relatively frequently in people of middle age or older. In 3% of these people these findings are reason for additional clinical evaluation, mostly without further clinical consequences.

Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms.

Despite a substantial genetic component, efforts to identify common genetic variation underlying depression have largely been unsuccessful. In the current study we aimed to identify rare genetic variants that might have large effects on depression in the general population. Using high-coverage exome-sequencing, we studied the exonic variants in 1265 individuals from the Rotterdam study (RS), who were assessed for depressive symptoms. We identified a missense Asn396Ser mutation (rs77960347) in the endothelial lipase (LIPG) gene, occurring with an allele frequency of 1% in the general population, which was significantly associated with depressive symptoms (P-value=5.2 × 10-08, ß=7.2). Replication in three independent data sets (N=3612) confirmed the association of Asn396Ser (P-value=7.1 × 10-03, ß=2.55) with depressive symptoms. LIPG is predicted to have enzymatic function in steroid biosynthesis, cholesterol biosynthesis and thyroid hormone metabolic processes. The Asn396Ser variant is predicted to have a damaging effect on the function of LIPG. Within the discovery population, carriers also showed an increased burden of white matter lesions (P-value=3.3 × 10-02) and a higher risk of Alzheimer's disease (odds ratio=2.01; P-value=2.8 × 10-02) compared with the non-carriers. Together, these findings implicate the Asn396Ser variant of LIPG in the pathogenesis of depressive symptoms in the general population.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

HASE: Framework for efficient high-dimensional association analyses.

High-throughput technology can now provide rich information on a person's biological makeup and environmental surroundings. Important discoveries have been made by relating these data to various health outcomes in fields such as genomics, proteomics, and medical imaging. However, cross-investigations between several high-throughput technologies remain impractical due to demanding computational requirements (hundreds of years of computing resources) and unsuitability for collaborative settings (terabytes of data to share). Here we introduce the HASE framework that overcomes both of these issues. Our approach dramatically reduces computational time from years to only hours and also requires several gigabytes to be exchanged between collaborators. We implemented a novel meta-analytical method that yields identical power as pooled analyses without the need of sharing individual participant data. The efficiency of the framework is illustrated by associating 9 million genetic variants with 1.5 million brain imaging voxels in three cohorts (total N = 4,034) followed by meta-analysis, on a standard computational infrastructure. These experiments indicate that HASE facilitates high-dimensional association studies enabling large multicenter association studies for future discoveries.

Population imaging in neuroepidemiology.

Neuroepidemiologic studies have traditionally focused on studying associations between determinants and neurologic outcomes, while treating the pathway in between both as a "black box." With the rise of noninvasive, advanced neuroimaging techniques, it has become possible to directly study brain changes occurring in this "black box." This importantly aids to unravel disease pathways, find new markers of disease, or identify subjects at risk of disease. Imaging in neuroepidemiologic studies is also called population neuroimaging. This chapter discusses the rationale of population neuroimaging, the different imaging modalities that can be applied, and the various ways to extract visual or quantitative information from these images. Population neuroimaging is a fast-progressing field, partly due to new techniques and partly due to the growing need for collaboration, harmonization, and standardization among studies. Considerations for future applications of imaging in neuroepidemiology are discussed against this background.

High shear stress relates to intraplaque haemorrhage in asymptomatic carotid plaques.

BACKGROUND AND AIMS: Carotid artery plaques with vulnerable plaque components are related to a higher risk of cerebrovascular accidents. It is unknown which factors drive vulnerable plaque development. Shear stress, the frictional force of blood at the vessel wall, is known to influence plaque formation. We evaluated the association between shear stress and plaque components (intraplaque haemorrhage (IPH), lipid rich necrotic core (LRNC) and/or calcifications) in relatively small carotid artery plaques in asymptomatic persons. METHODS: Participants (n = 74) from the population-based Rotterdam Study, all with carotid atherosclerosis assessed on ultrasound, underwent carotid MRI. Multiple MRI sequences were used to evaluate the presence of IPH, LRNC and/or calcifications in plaques in the carotid arteries. Images were automatically segmented for lumen and outer wall to obtain a 3D reconstruction of the carotid bifurcation. These reconstructions were used to calculate minimum, mean and maximum shear stresses by applying computational fluid dynamics with subject-specific inflow conditions. Associations between shear stress measures and plaque composition were studied using generalized estimating equations analysis, adjusting for age, sex and carotid wall thickness. RESULTS: The study group consisted of 93 atherosclerotic carotid arteries of 74 participants. In plaques with higher maximum shear stresses, IPH was more often present (OR per unit increase in maximum shear stress (log transformed) = 12.14; p = 0.001). Higher maximum shear stress was also significantly associated with the presence of calcifications (OR = 4.28; p = 0.015). CONCLUSIONS: Higher maximum shear stress is associated with intraplaque haemorrhage and calcifications.