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Registration is a core component of many imaging pipelines. In case of clinical scans, with lower resolution and sometimes substantial motion artifacts, registration can produce poor results. Visual assessment of registration quality in large clinical datasets is inefficient. In this work, we propose to automatically assess the quality of registration to an atlas in clinical FLAIR MRI scans of the brain. The method consists of automatically segmenting the ventricles of a given scan using a neural network, and comparing the segmentation to the atlas ventricles propagated to image space. We used the proposed method to improve clinical image registration to a general atlas by computing multiple registrations - one directly to the general atlas and others via different age-specific atlases - and then selecting the registration that yielded the highest ventricle overlap. Finally, as an example application of the complete pipeline, a voxelwise map of white matter hyperintensity burden was computed using only the scans with registration quality above a predefined threshold. Methods were evaluated in a single-site dataset of more than 1000 scans, as well as a multi-center dataset comprising 142 clinical scans from 12 sites. The automated ventricle segmentation reached a Dice coefficient with manual annotations of 0.89 in the single-site dataset, and 0.83 in the multi-center dataset. Registration via age-specific atlases could improve ventricle overlap compared to a direct registration to the general atlas (Dice similarity coefficient increase up to 0.15). Experiments also showed that selecting scans with the registration quality assessment method could improve the quality of average maps of white matter hyperintensity burden, instead of using all scans for the computation of the white matter hyperintensity map. In this work, we demonstrated the utility of an automated tool for assessing image registration quality in clinical scans. This image quality assessment step could ultimately assist in the translation of automated neuroimaging pipelines to the clinic., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

Enlarged perivascular spaces (EPVS) in the brain are an emerging imaging marker for cerebral small vessel disease, and have been shown to be related to increased risk of various neurological diseases, including stroke and dementia. Automated quantification of EPVS would greatly help to advance research into its etiology and its potential as a risk indicator of disease. We propose a convolutional network regression method to quantify the extent of EPVS in the basal ganglia from 3D brain MRI. We first segment the basal ganglia and subsequently apply a 3D convolutional regression network designed for small object detection within this region of interest. The network takes an image as input, and outputs a quantification score of EPVS. The network has significantly more convolution operations than pooling ones and no final activation, allowing it to span the space of real numbers. We validated our approach using a dataset of 2000 brain MRI scans scored visually. Experiments with varying sizes of training and test sets showed that a good performance can be achieved with a training set of only 200 scans. With a training set of 1000 scans, the intraclass correlation coefficient (ICC) between our scoring method and the expert's visual score was 0.74. Our method outperforms by a large margin - more than 0.10 - four more conventional automated approaches based on intensities, scale-invariant feature transform, and random forest. We show that the network learns the structures of interest and investigate the influence of hyper-parameters on the performance. We also evaluate the reproducibility of our network using a set of 60 subjects scanned twice (scan-rescan reproducibility). On this set our network achieves an ICC of 0.93, while the intrarater agreement reaches 0.80. Furthermore, the automated EPVS scoring correlates similarly to age as visual scoring., (Copyright © 2018. Published by Elsevier B.V.)

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., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

18FDG PET-CT is useful for early and differential diagnosis of dementia. ASL-MRI seems an attractive alternative. Visual agreement was calculated in 21 brain regions bilaterally in 9/11 patients with suspected early-stage dementia, excluding 2 patients due to ASL-MRI motion artefacts. Overall gross agreement was almost perfect and identical between and within modalities (κ=0.85-0.86, p<0.05). Intermodality regional agreement was variable, moderate (κ=0,56 in posterior cingulate) to perfect (including in precuneus), not different from intramodality agreement. Diagnostic accuracy was 5/9 (56%) for ASL-MRI and 7/9 (78%) for FDG PETCT. (p=0.31). Clinical experience and optimisation may further improve ASL-MRI's performance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

Background and Purpose: Determining language dominance with fMRI is challenging in patients with brain tumor, particularly in cases of suspected atypical language representation. Supratentorial activation patterns must be interpreted with great care when the tumor is in or near the presumed language areas, where tumor tissue or mass effect can lead to false-negative fMRI results. In this study, we assessed cerebrocerebellar language fMRI lateralization in healthy participants and in patients with brain tumors with a focus on atypical language representation., Materials and Methods: Twenty healthy participants and 38 patients with a brain tumor underwent fMRI with a verb-generation task. Cerebral and cerebellar language lateralizations were separately classified as left-sided, right-sided, or symmetric. Electrocortical stimulation was performed in 19 patients. With the McNemar test, we evaluated the dependency between language lateralization in the cerebrum and cerebellum, and with Pearson correlation analysis, the relationship between the cerebral and cerebellar lateralization indices., Results: There was a significant dependency between cerebral and cerebellar language activation, with moderate negative correlation (Pearson r = -0.69). Crossed cerebrocerebellar language activation was present in both healthy participants and patients, irrespective of handedness or typical or atypical language representation. There were no discordant findings between fMRI and electrocortical stimulation., Conclusions: Language lateralization in the cerebellum can be considered an additional diagnostic feature to determine language dominance in patients with brain tumor. This is particularly useful in cases of uncertainty, such as the interference of a brain tumor with cerebral language activation on fMRI and atypical language representation., (© 2015 by American Journal of Neuroradiology.)

Intraplaque hemorrhage (IPH) is a characteristic of the vulnerable atherosclerotic plaque that has been associated with ischemic stroke. Not much is known about determinants of IPH. We studied whether blood pressure parameters are associated with presence of IPH. Within the framework of a prospective population-based cohort study, The Rotterdam Study, the carotid arteries of 1006 healthy participants ≥45 years and with intima-media thickening (≥2.5 mm) on ultrasound were imaged with a 1.5-T magnetic resonance imaging scanner. IPH was defined as a hyperintense signal on a 3D-T1w-GRE magnetic resonance sequence. Generalized estimation equation analysis, adjusted for age, sex, carotid wall thickness, and cardiovascular risk factors, was used to assess the association between blood pressure parameters and IPH. Magnetic resonance imaging of the carotid arteries revealed presence of IPH in 444 of 1860 plaques (24%). Systolic blood pressure and pulse pressure (PP) were significantly associated with IPH after adjustment for age and sex. In multivariate analysis, PP yielded the strongest association, with an odds ratio per SD increase in PP of 1.22 (95% CI, 1.07-1.40). The odds ratio per SD for systolic blood pressure was 1.13 (0.99-1.28). Only PP remained significant after additional adjustment for other blood pressure components. The combination of smoking and isolated systolic hypertension was associated with 2.5 times increased risk of IPH (1.2-5.2). In conclusion, PP was the strongest determinant of IPH independent of cardiovascular risk factors and other blood pressure components. The association between pulsatile flow and IPH may provide novel insights in the development of the vulnerable plaque.

Background and Purpose: The clinical relevance of improved detection of cerebral microbleeds by using advanced-versus-conventional MR imaging techniques remains uncertain. As part of the population-based Rotterdam Scan Study, we compared whether participants whose microbleeds were only demonstrated on a high-resolution MR imaging sequence differed with respect to risk profile and risk of new microbleeds from participants whose microbleeds were also depicted on a conventional MR imaging sequence., Materials and Methods: Two hundred participants (mean age, 79.2 years) underwent both conventional 2D T2*-weighted MR imaging and high-resolution 3D T2*-weighted MR imaging at 1.5T. Vascular risk factors, APOE allele status, and markers of small vessel disease and risk of incident microbleeds were compared for microbleed status by using logistic regression models adjusted for age and sex., Results: There were no significant associations between any of the factors and microbleed presence in participants whose microbleeds were only demonstrated on a high-resolution MR imaging sequence. However, the estimates in these participants were more similar to those in participants whose microbleeds were also depicted on a conventional MR imaging sequence than to those in participants without microbleeds. Moreover, significantly more participants whose microbleeds were only demonstrated on high-resolution MR imaging developed new CMBs during follow-up compared with participants without CMBs (25.0% versus 5.9%; OR, 5.98; 95% CI, 1.35-26.49)., Conclusions: Improved detection of microbleeds may contribute to more accurate identification of persons with underlying small-vessel pathology in the general elderly population. Further studies are needed to replicate these findings and firmly establish the role of improved detection of CMBs in the identification of persons with vasculopathy.

Background: Cerebral microbleeds are focal deposits of hemosiderin that can be visualized with MRI. Little is known on their prevalence in the general population and on their etiology. It has been suggested that, in analogy to spontaneous intracranial hemorrhage, the etiology of microbleeds differs according to their location in the brain, with lobar microbleeds being caused by cerebral amyloid angiopathy and deep or infratentorial microbleeds resulting from hypertension and atherosclerosis. We investigated the prevalence of and risk factors for microbleeds in the general population aged 60 years and older., Methods: This study is based on 1,062 persons (mean age 69.6 years) from the population-based Rotterdam Scan Study. MRI was performed at 1.5 T and included a sequence optimized to increase the conspicuity of microbleeds. We assessed the relation of APOE genotype, cardiovascular risk factors, and markers of small vessel disease to the presence and location of microbleeds with multiple logistic regression., Results: Overall prevalence of cerebral microbleeds was high and increased with age from 17.8% in persons aged 60-69 years to 38.3% in those over 80 years. APOE epsilon 4 carriers had significantly more often strictly lobar microbleeds than noncarriers. In contrast, cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location but not in a lobar location., Conclusion: The prevalence of cerebral microbleeds is high. Our data support the hypothesis that strictly lobar microbleeds are related to cerebral amyloid angiopathy, whereas microbleeds in a deep or infratentorial location result from hypertensive or atherosclerotic microangiopathy.

Previously reported leftward asymmetry in language-related gray and white matter areas of the brain has been proposed as a structural correlate of left-sided functional hemispheric language lateralization. However, structural asymmetry in non-left-sided functional language lateralization has as yet not been studied. Furthermore, the neuroanatomical basis of the reported volumetric white matter asymmetry is not fully understood. In 20 healthy volunteers, including 13 left-handers, we performed functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). We studied the relative fiber density (RFD) of the arcuate fasciculus (AF), using DT-tractography, in relation to functional hemispheric language lateralization. Hemispheric language lateralization was right-sided in five left-handed individuals. We demonstrated an overall significant leftward asymmetry in RFD of the AF, irrespective of handedness or functional language lateralization. Furthermore, in right-handers, the degree of structural asymmetry was found to be correlated with the degree of functional lateralization. We conclude that structural asymmetry in the AF does not seem to reflect functional hemispheric language lateralization, as has been proposed previously. Our findings suggest that the previously reported white matter asymmetry may be explained by a structural asymmetry in the arcuate fasciculus. These findings have important implications for the understanding of the functional and structural lateralization of brain regions as well as for the clinical evaluation of language function.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]