Linear registration to stereotaxic space is a common first step in many automated image-processing tools for analysis of human brain MRI scans. This step is crucial for the success of the subsequent ...image-processing steps. Several well-established algorithms are commonly used in the field of neuroimaging for this task, but none have a 100% success rate. Manual assessment of the registration is commonly used as part of quality control. To reduce the burden of this time-consuming step, we propose Deep Automated Registration Qc (DARQ), a fully automatic quality control method based on deep learning that can replace the human rater and accurately perform quality control assessment for stereotaxic registration of T1w brain scans.
In a recently published study from our group comparing linear registration methods, we used a database of 9325 MRI scans and 64476 registrations from several publicly available datasets and applied seven linear registration tools to them. In this study, the resulting images that were assessed and labeled by a human rater are used to train a deep neural network to detect cases when registration failed. We further validated the results on an independent dataset of patients with multiple sclerosis, with manual QC labels available (n=1200).
In terms of agreement with a manual rater, our automated QC method was able to achieve 89% accuracy and 85% true negative rate (equivalently 15% false positive rate) in detecting scans that should pass quality control in a balanced cross-validation experiments, and 96.1% accuracy and 95.5% true negative rate (or 4.5% FPR) when evaluated in a balanced independent sample, similar to manual QC rater (test-retest accuracy of 93%).
The results show that DARQ is robust, fast, accurate, and generalizable in detecting failure in linear stereotaxic registrations and can substantially reduce QC time (by a factor of 20 or more) when processing large datasets.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present an improved image analysis pipeline to detect the percent brain volume change (PBVC) using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) in populations with ...Alzheimer's dementia. Our proposed approach uses the improved brain extraction mask from BEaST (Brain Extraction based on nonlocal Segmentation Technique) instead of the conventional BET (Brain Extraction Tool) for SIENA. We compared four varying options of BET as well as BEaST and applied these five methods to analyze scan-rescan MRIs in ADNI from 332 subjects, longitudinal ADNI MRIs from the same 332 subjects, their repeat scans over time, and OASIS longitudinal MRIs from 123 subjects. The results showed that BEaST brain masks were consistent in scan-rescan reproducibility. The cross-sectional scan-rescan error in the absolute percent brain volume difference measured by SIENA was smallest (p≤0.0187) with the proposed BEaST-SIENA. We evaluated the statistical power in terms of effect size, and the best performance was achieved with BEaST-SIENA (1.2789 for ADNI and 1.095 for OASIS). The absolute difference in PBVC between scan-dataset (volume change from baseline to year-1) and rescan-dataset (volume change from baseline repeat scan to year-1 repeat scan) was also the smallest with BEaST-SIENA compared to the BET-based SIENA and had the highest correlation when compared to the BET-based SIENA variants. In conclusion, our study shows that BEaST was robust in terms of reproducibility and consistency and that SIENA's reproducibility and statistical power are improved in multiple datasets when used in combination with BEaST.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a new automatic method for segmentation of multiple sclerosis (MS) lesions in magnetic resonance images. The method performs tissue classification using a model of intensities of the ...normal appearing brain tissues. In order to estimate the model, a trimmed likelihood estimator is initialized with a hierarchical random approach in order to be robust to MS lesions and other outliers present in real images. The algorithm is first evaluated with simulated images to assess the importance of the robust estimator in presence of outliers. The method is then validated using clinical data in which MS lesions were delineated manually by several experts. Our method obtains an average Dice similarity coefficient (DSC) of 0.65, which is close to the average DSC obtained by raters (0.66).
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors that typically emerge by 24 months of age. To develop effective early ...interventions that can potentially ameliorate the defining deficits of ASD and improve long-term outcomes, early detection is essential. Using prospective neuroimaging of 59 6-month-old infants with a high familial risk for ASD, we show that functional connectivity magnetic resonance imaging correctly identified which individual children would receive a research clinical best-estimate diagnosis of ASD at 24 months of age. Functional brain connections were defined in 6-month-old infants that correlated with 24-month scores on measures of social behavior, language, motor development, and repetitive behavior, which are all features common to the diagnosis of ASD. A fully cross-validated machine learning algorithm applied at age 6 months had a positive predictive value of 100% 95% confidence interval (CI), 62.9 to 100, correctly predicting 9 of 11 infants who received a diagnosis of ASD at 24 months (sensitivity, 81.8%; 95% CI, 47.8 to 96.8). All 48 6-month-old infants who were not diagnosed with ASD were correctly classified specificity, 100% (95% CI, 90.8 to 100); negative predictive value, 96.0% (95% CI, 85.1 to 99.3). These findings have clinical implications for early risk assessment and the feasibility of developing early preventative interventions for ASD.
Increased age and cognitive impairment is associated with an increase in cerebrovascular pathology often measured as white matter hyperintensities (WMHs) on MRI. Whether WMH burden differs between ...cognitively unimpaired older adults with subjective cognitive decline (SCD +) and without subjective cognitive decline (SCD −) remains conflicting, and could be related to the methods used to identify SCD. Our goal was to examine if four common SCD classification methods are associated with different WMH accumulation patterns between SCD + and SCD − . A total of 535 cognitively unimpaired older adults with 1353 time points from the Alzheimer’s Disease Neuroimaging Initiative were included in this study. SCD was operationalized using four different methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry. Linear mixed-effects models were used to investigate the associations between SCD and overall and regional WMH burden. Overall temporal WMH burden differences were only observed with the Worry questionnaire. Higher WMH burden change over time was observed in SCD + compared to SCD − in the temporal and parietal regions using the CCI (temporal,
p
= .01; parietal
p
= .02) and ECog (temporal,
p
= .02; parietal
p
= .01). For both the ECog + Worry and Worry questionnaire, change in WMH burden over time was increased in SCD + compared to SCD − for overall, frontal, temporal, and parietal WMH burden (
p
< .05). These results show that WMH burden differs between SCD + and SCD − depending on the questionnaire and the approach (regional/global) used to measure WMHs. The various methods used to define SCD may reflect different types of underlying pathologies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Autism Spectrum Disorder (ASD) is a developmental disorder defined by behavioural features that emerge during the first years of life. Research indicates that abnormalities in ...brain connectivity are associated with these behavioural features. However, inclusion of individuals past the age of onset of the defining behaviours complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioural abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified as ASD. The current study maps the emergence of these inefficiencies in the first year of life. Methods The study utilizes data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions in order to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. Results Inefficiencies in high-risk infants later classified as ASD were detected from 6 months onward in regions involved in low-level sensory processing. Additionally, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. Conclusion These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization, and eventually higher-level cognitive processes and social behaviour.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•The expected atrophy was shown in the frontal lobes and anterior temporal regions.•Subcortical structures were notably affected in our bvFTD cohort.•Ventricles and sulci within frontotemporal ...regions were larger in the bvFTD cohort.•Ventricles and sulci showed significant enlargement and over a one-year period.•Ventricular expansion was the most prominent differentiator of bvFTD from controls.
To objectively quantify how cerebral volume loss could assist with clinical diagnosis and clinical trial design in the behavioural variant of frontotemporal dementia (bvFTD).
We applied deformation-based morphometric analyses with robust registration to precisely quantify the magnitude and pattern of atrophy in patients with bvFTD as compared to cognitively normal controls (CNCs), to assess the progression of atrophy over one year follow up and to generate clinical trial sample size estimates to detect differences for the structures most sensitive to change. This study included 203 subjects - 70 bvFTD and 133 CNCs - with a total of 482 timepoints from the Frontotemporal Lobar Degeneration Neuroimaging Initiative.
Deformation based morphometry (DBM) revealed significant atrophy in the frontal lobes, insula, medial and anterior temporal regions bilaterally in bvFTD subjects compared to controls with outstanding subcortical involvement. We provide detailed information on regional changes per year. In both cross-sectional analysis and over a one-year follow-up period, ventricle expansion was the most prominent differentiator of bvFTD from controls and a sensitive marker of disease progression.
Automated measurement of ventricular expansion is a sensitive and reliable marker of disease progression in bvFTD to be used in clinical trials for potential disease modifying drugs, as well as possibly to implement in clinical practice. Ventricular expansion measured with DBM provides the lowest published estimated sample size for clinical trial design to detect significant differences over one and two years.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cerebral vascular images obtained through angiography are used by neurosurgeons for diagnosis, surgical planning, and intraoperative guidance. The intricate branching of the vessels and furcations, ...however, make the task of understanding the spatial three-dimensional layout of these images challenging. In this paper, we present empirical studies on the effect of different perceptual cues (fog, pseudo-chromadepth, kinetic depth, and depicting edges) both individually and in combination on the depth perception of cerebral vascular volumes and compare these to the cue of stereopsis. Two experiments with novices and one experiment with experts were performed. The results with novices showed that the pseudo-chromadepth and fog cues were stronger cues than that of stereopsis. Furthermore, the addition of the stereopsis cue to the other cues did not improve relative depth perception in cerebral vascular volumes. In contrast to novices, the experts also performed well with the edge cue. In terms of both novice and expert subjects, pseudo-chromadepth and fog allow for the best relative depth perception. By using such cues to improve depth perception of cerebral vasculature, we may improve diagnosis, surgical planning, and intraoperative guidance.
MRI studies show that obese adults have reduced grey matter (GM) and white matter (WM) tissue density as well as altered WM integrity. Bariatric surgery can lead to substantial weight loss and ...improvements in metabolic parameters, but it remains to be examined if it induces structural brain changes. The aim of this study was to characterize GM and WM density changes measured with MRI in a longitudinal setting following sleeve gastrectomy, and to determine whether any changes are related to inflammation and cardiometabolic blood markers.
29 participants with obesity (age: 45.9 ± 7.8 years) scheduled to undergo sleeve gastrectomy were recruited. High-resolution T1-weighted anatomical images were acquired 1 month prior to as well as 4 and 12 months after surgery. GM and WM densities were quantified using voxel-based morphometry (VBM). Circulating lipid profile, glucose, insulin and inflammatory markers (interleukin-6, C-reactive protein and lipopolysaccharide-binding protein) were measured at each time point. A linear mixed effect model was used to compare brain changes before and after SG, controlling for age, sex, initial BMI and diabetic status. To assess the associations between changes in adiposity, metabolism and inflammation and changes in GM or WM density, the mean GM and WM densities were extracted across all the participants using atlas-derived regions of interest, and linear mixed-effect models were used.
As expected, weight, BMI, waist circumference and neck circumference significantly decreased after SG compared with baseline (p < 0.001 for all). A widespread increase in WM density was observed after surgery, particularly in the cerebellum, brain stem, cerebellar peduncle, cingulum, corpus callosum and corona radiata (p < 0.05, after FDR correction). Significant increases in GM density were observed 4 months after SG compared to baseline in several brain regions such as the bilateral occipital cortex, temporal cortex, postcentral gyrus, cerebellum, hippocampus and insula as well as right fusiform gyrus, right parahippocampal gyrus, right lingual gyrus and right amygdala. These GM and WM increases were more pronounced and widespread after 12 months and were significantly associated with post-operative weight loss and the improvement of metabolic alterations. A linear mixed-effect model also showed associations between post-operative reductions in lipopolysaccharide-binding protein, a marker of inflammation, and increased WM density. To confirm our results, we tested whether the peak of each significant region showed BMI-related differences in an independent dataset (Human Connectome Project). We matched a group of individuals who were severely obese with a group of individuals who were lean for age, sex and ethnicity. Severe obesity was associated with reduced WM density in the brain stem and cerebellar peduncle as well as reduced GM density in cerebellum, regions that significantly changed after surgery (p < 0.01 for all clusters).
Bariatric surgery-induced weight loss and improvement in metabolic alterations is associated with widespread increases in WM and GM densities. These post-operative changes overlapped with baseline brain differences between participants who were severely obese and those who were normal-weight in a separate dataset, which may suggest a recovery of WM and GM alterations after bariatric surgery.
•Bariatric surgery-induced weight loss was associated with increased WM and GM densities.•These WM and GM increases were related to post-operative metabolic improvements.•Post-operative brain changes lie in brain areas that are relevant for severe obesity.•These results may suggest a recovery of WM and GM alterations after SG.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP