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.

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.

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.

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.

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.

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.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Performance of outpatient transvaginal hydrolaparoscopy.

STUDY QUESTION: What is the feasibility of performing transvaginal hydrolaparoscopy (THL) in an outpatient setting? SUMMARY ANSWER: It is feasible to perform THL in an outpatient setting, reflected by a low complication and failure rate and a high patients' satisfaction. WHAT IS KNOWN ALREADY: THL is a safe method to investigate tubal patency and exploring the pelvis in subfertile women. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of 1127 subfertile women who underwent THL as primary diagnostic method for testing tubal patency in an outpatient setting. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied all THL procedures performed as a primary diagnostic tubal patency test in an outpatient setting in subfertile women starting from the initial THL in four large hospitals. Baseline characteristics were obtained, as well as the outcome of the procedures in terms of success, complications and findings by examining medical records. We used a uniform visual analogue scale (VAS) score document to collect data on pain and acceptability prospectively and compared two methods of pain relief. MAIN RESULTS AND THE ROLE OF CHANCE: We studied a total of 1103 women who underwent THL. Successful access to the pouch of Douglas was achieved in 1028 women (93.2%), and 1017 women had a complete evaluation (92.2%). Double-sided tubal patency was found in 844 women (83%), unilateral tubal patency in 127 women (12.5%), while in 46 women (4.5%) bilateral occluded tubes were diagnosed. Endometriosis alone was seen in 64 women (6.3%), adhesions alone in 87 women (8.6%) and both endometriosis and adhesions in 42 women (4.1%).Complications occurred in 29 (2.6%) women, including 10 perforations of the rectum (0.9%), 8 perforations of the posterior uterine wall (0.7%) and 5 infections/pelvic inflammatory diseases (PIDs) (0.5%). Bleeding of the vaginal wall requiring intervention and hospital admissions due to pain was seen in 4 (0.4%) and 2 women, respectively (0.2%). The average pain score was rated 4.0 (±2.4 SD) on a VAS from 0 to 10 with 0 meaning no pain at all with no difference in different types of pain relief. Acceptability was rated 1.5 (±2.1 SD). LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study is its retrospective character and the fact that only a fourth of the women were asked for pain and acceptability scores. WIDER IMPLICATIONS OF THE FINDINGS: THL can be used as a primary method for tubal assessment in an outpatient setting. Further randomized studies are needed to assess whether THL is superior to other methods and strategies for tubal assessment in terms of prognostic capacity and cost-effectiveness. STUDY FUNDING/COMPETING INTEREST: No external funding was either sought or obtained for this study. The authors have no competing interests to declare.

Cognition, structural brain changes and complicated grief. A population-based study.

BACKGROUND: Several psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study. METHOD: The present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter-Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test - immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms. RESULTS: Compared with no-grief participants, participants with complicated grief had lower scores for the Letter-Digit Substitution Test [Z-score -0.16 v. 0.04, 95% confidence interval (CI) -0.36 to -0.04, p = 0.01] and Word Fluency Task (Z-score -0.15 v. 0.03, 95% CI -0.35 to -0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI -37.6 to -0.10, p = 0.04). CONCLUSIONS: Participants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population.

Cerebral small vessel disease is related to disturbed 24-h activity rhythms: a population-based study.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep-wake rhythm. It is unknown whether cerebral small vessel disease is related to disturbances in sleep and 24-h activity rhythms. METHODS: This study was conducted in the Rotterdam Study. A total of 970 community-dwelling persons (mean age 59.2 years) underwent brain magnetic resonance imaging and actigraphy. Cerebral small vessel disease was defined as white matter lesions (total volume in millilitres) and the presence of cerebral microbleeds and lacunar infarcts. Twenty-four hour activity rhythms and sleep were measured with actigraphy by estimating the instability and fragmentation of the activity rhythm and total sleep time. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. White matter lesions, instability, fragmentation and sleep quality were standardized for analyses. RESULTS: Higher white matter lesion volume (B = 0.09 per SD, 95% confidence interval 0.02; 0.15) and cerebral microbleeds (B = 0.19 per SD, 95% confidence interval 0.02; 0.37) were significantly related to more fragmented 24-h activity rhythms. None of the small vessel disease markers was related to total sleep time or sleep quality. CONCLUSIONS: White matter lesion volume and the presence of cerebral microbleeds are related to disturbed activity rhythms. This suggests that subclinical brain damage affects the 24-h activity rhythm.

Structural and diffusion MRI measures of the hippocampus and memory performance.

Hippocampal atrophy on MRI and changes in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in patients with Alzheimer's disease. We examined the association between hippocampal volumes, DTI measures of the hippocampus and memory performance in 892 non-demented persons (age ≥ 55 years) across different age groups. Hippocampal volume was segmented on 3D volumetric MRI scans. The segmentations were co-registered to mean diffusivity (MD) and fractional anisotropy (FA) maps to yield mean hippocampal MD and FA measurements. Higher MD of the hippocampus was associated with impaired verbal memory performance. In all persons ≥ 55 years, a higher MD of the hippocampus was associated with a worse memory performance. Hippocampal volumes were very weakly positively associated with delayed recall and only in persons > 65 years. FA of the hippocampus was not associated with memory performance. Follow-up studies will be needed to determine whether higher MD of hippocampus at younger ages could be an earlier marker of incident Alzheimer's disease than hippocampal volume.

Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population.

BACKGROUND: Asymptomatic cerebral lesions on MRI such as white matter lesions (WML), lacunes and microbleeds are commonly seen in older people. We examined the role of a series of candidate genes involved in blood pressure regulation and amyloid metabolism. MATERIALS AND METHODS: The study was embedded in a family-based cohort sampled from a Dutch genetically isolated population. We selected individuals between 55 and 75 years of age with hypertension (N=129). Volumes of WML and presence of lacunes and microbleeds were assessed with MRI. We studied three genes involved in blood pressure regulation (angiotensin, angiotensin II type 1 receptor, α-adducin) and two genes involved in the amyloid pathway (apolipoprotein E (APOE) and sortilin-related receptor gene (SORL1)). RESULTS: All participants had WML (median volume, 3.1 ml; interquartile range, 1.5-6.5 ml); lacunar infarcts were present in 15.5% and microbleeds in 23.3%. Homozygosity for the APOE ε4 allele was associated with lacunes (OR, 4.8; 95% CI, 1.2 to 19.3). Individuals carrying two copies of the variant allele of four single nucleotide polymorphism (SNPs) located at the 3'-end of SORL1 (rs1699102, rs3824968, rs2282649, rs1010159) had significantly more often microbleeds (highest OR, 6.87; 95% CI, 1.78 to 26.44). CONCLUSION: The association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.

Comparing clean intermittent catheterisation and transurethral indwelling catheterisation for incomplete voiding after vaginal prolapse surgery: a multicentre randomised trial.

OBJECTIVE: To compare clean intermittent catheterisation with transurethral indwelling catheterisation for the treatment of abnormal post-void residual bladder volume (PVR) following vaginal prolapse surgery. DESIGN: Multicentre randomised controlled trial. SETTING: Five teaching hospitals and one non-teaching hospital in the Netherlands. POPULATION: All patients older than 18 years experiencing abnormal PVR following vaginal prolapse surgery, with or without the use of mesh. Exclusion criteria were: any neurological or anxiety disorder, or the need for combined anti-incontinence surgery. METHODS: All patients were given an indwelling catheter directly after surgery, which was removed on the first postoperative day. Patients with a PVR of more than 150 ml after their first void were randomised for clean intermittent catheterisation (CIC), performed by nursing staff, or for transurethral indwelling catheterisation (TIC) for 3 days. MAIN OUTCOME MEASURE: Bacteriuria rate at end of treatment. RESULTS: A total of 87 patients were included in the study. Compared with the TIC group (n = 42), there was a lower risk of developing bacteriuria (14 versus 38%; P = 0.02) or urinary tract infection (UTI; 12 versus 33%; P = 0.03) in the CIC group (n = 45); moreover, a shorter period of catheterisation was required (18 hours CIC versus 72 hours TIC; P < 0.001). Patient satisfaction was similar in the two groups, and no adverse events occurred. CONCLUSION: Clean intermittent catheterisation is preferable over indwelling catheterisation for 3 days in the treatment of abnormal PVR following vaginal prolapse surgery.

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.

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.