scholarly journals Adapting the UK Biobank Brain Imaging Protocol and Analysis Pipeline for the C-MORE Multi-Organ Study of COVID-19 Survivors

2021 ◽  
Vol 12 ◽  
Author(s):  
Ludovica Griffanti ◽  
Betty Raman ◽  
Fidel Alfaro-Almagro ◽  
Nicola Filippini ◽  
Mark Philip Cassar ◽  
...  
Keyword(s):  
Large Scale ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Brain Anatomy ◽  
Uk Biobank ◽  
Analysis Pipeline ◽  
Imaging Protocol ◽  
Diffusion Weighted Images ◽  
Radiology Reports ◽  
The Uk

SARS-CoV-2 infection has been shown to damage multiple organs, including the brain. Multiorgan MRI can provide further insight on the repercussions of COVID-19 on organ health but requires a balance between richness and quality of data acquisition and total scan duration. We adapted the UK Biobank brain MRI protocol to produce high-quality images while being suitable as part of a post-COVID-19 multiorgan MRI exam. The analysis pipeline, also adapted from UK Biobank, includes new imaging-derived phenotypes (IDPs) designed to assess the possible effects of COVID-19. A first application of the protocol and pipeline was performed in 51 COVID-19 patients post-hospital discharge and 25 controls participating in the Oxford C-MORE study. The protocol acquires high resolution T1, T2-FLAIR, diffusion weighted images, susceptibility weighted images, and arterial spin labelling data in 17 min. The automated imaging pipeline derives 1,575 IDPs, assessing brain anatomy (including olfactory bulb volume and intensity) and tissue perfusion, hyperintensities, diffusivity, and susceptibility. In the C-MORE data, IDPs related to atrophy, small vessel disease and olfactory bulbs were consistent with clinical radiology reports. Our exploratory analysis tentatively revealed some group differences between recovered COVID-19 patients and controls, across severity groups, but not across anosmia groups. Follow-up imaging in the C-MORE study is currently ongoing, and this protocol is now being used in other large-scale studies. The protocol, pipeline code and data are openly available and will further contribute to the understanding of the medium to long-term effects of COVID-19.

scholarly journals Adapting the UK Biobank brain imaging protocol and analysis pipeline for the C-MORE multi-organ study of COVID-19 survivors

2021 ◽  
Author(s):  
Ludovica Griffanti ◽  
Betty Raman ◽  
Fidel Alfaro-Almagro ◽  
Nicola Filippini ◽  
Mark Philip Cassar ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Brain Anatomy ◽  
Uk Biobank ◽  
Analysis Pipeline ◽  
Imaging Protocol ◽  
Diffusion Weighted Images ◽  
Radiology Reports ◽  
The Uk

SARS-CoV-2 infection has been shown to damage multiple organs, including the brain. Multiorgan MRI can provide further insight on the repercussions of COVID-19 on organ health but requires a balance between richness and quality of data acquisition and total scan duration. We adapted the UK Biobank brain MRI protocol to produce high-quality images while being suitable as part of a post-COVID-19 multiorgan MRI exam. The analysis pipeline, also adapted from UK Biobank, includes new imaging-derived phenotypes (IDPs) designed to assess the effects of COVID-19. A first application of the protocol and pipeline was performed in 51 COVID-19 patients post-hospital discharge and 25 controls participating in the Oxford C-MORE study. The protocol acquires high resolution T1, T2-FLAIR, diffusion weighted images, susceptibility weighted images, and arterial spin labelling data in 17 minutes. The automated imaging pipeline derives 1575 IDPs, assessing brain anatomy (including olfactory bulb volume and intensity) and tissue perfusion, hyperintensities, diffusivity, and susceptibility. In the C-MORE data, these quantitative measures were consistent with clinical radiology reports. Our exploratory analysis tentatively revealed that recovered COVID-19 patients had a decrease in frontal grey matter volumes, an increased burden of white matter hyperintensities, and reduced mean diffusivity in the total and normal appearing white matter in the posterior thalamic radiation and sagittal stratum, relative to controls. These differences were generally more prominent in patients who received organ support. Increased T2* in the thalamus was also observed in recovered COVID-19 patients, with a more prominent increase for non-critical patients. This initial evidence of brain changes in COVID-19 survivors prompts the need for further investigations. Follow-up imaging in the C-MORE study is currently ongoing, and this protocol is now being used in large-scale studies. The pipeline is widely applicable and will contribute to new analyses to hopefully clarify the medium to long-term effects of COVID-19.

scholarly journals Content-Based Estimation of Brain MRI Tilt in Three Orthogonal Directions

2021 ◽  
Author(s):  
Pooja Prabhu ◽  
A. K. Karunakar ◽  
Sanjib Sinha ◽  
N. Mariyappa ◽  
G. K. Bhargava ◽  
...  
Keyword(s):  
Large Scale ◽  
Brain Mri ◽  
Similarity Measures ◽  
Principal Component ◽  
Brain Anatomy ◽  
Morphological Operations ◽  
Mr Images ◽  
Tilt Correction ◽  
Brain Mr Images ◽  
The Brain

AbstractIn a general scenario, the brain images acquired from magnetic resonance imaging (MRI) may experience tilt, distorting brain MR images. The tilt experienced by the brain MR images may result in misalignment during image registration for medical applications. Manually correcting (or estimating) the tilt on a large scale is time-consuming, expensive, and needs brain anatomy expertise. Thus, there is a need for an automatic way of performing tilt correction in three orthogonal directions (X, Y, Z). The proposed work aims to correct the tilt automatically by measuring the pitch angle, yaw angle, and roll angle in X-axis, Z-axis, and Y-axis, respectively. For correction of the tilt around the Z-axis (pointing to the superior direction), image processing techniques, principal component analysis, and similarity measures are used. Also, for correction of the tilt around the X-axis (pointing to the right direction), morphological operations, and tilt correction around the Y-axis (pointing to the anterior direction), orthogonal regression is used. The proposed approach was applied to adjust the tilt observed in the T1- and T2-weighted MR images. The simulation study with the proposed algorithm yielded an error of 0.40 ± 0.09°, and it outperformed the other existing studies. The tilt angle (in degrees) obtained is ranged from 6.2 ± 3.94, 2.35 ± 2.61, and 5 ± 4.36 in X-, Z-, and Y-directions, respectively, by using the proposed algorithm. The proposed work corrects the tilt more accurately and robustly when compared with existing studies.

scholarly journals Hemochromatosis Mutations, Brain Iron Imaging, and Dementia in the UK Biobank Cohort

2021 ◽  
pp. 1-9
Author(s):  
Janice L. Atkins ◽  
Luke C. Pilling ◽  
Christine J. Heales ◽  
Sharon Savage ◽  
Chia-Ling Kuo ◽  
...  
Keyword(s):  
Iron Reduction ◽  
Brain Mri ◽  
European Ancestry ◽  
Uk Biobank ◽  
Brain Iron ◽  
Mri Features ◽  
Incident Dementia ◽  
Hfe Mutations ◽  
The Uk

Background: Brain iron deposition occurs in dementia. In European ancestry populations, the HFE p.C282Y variant can cause iron overload and hemochromatosis, mostly in homozygous males. Objective: To estimated p.C282Y associations with brain MRI features plus incident dementia diagnoses during follow-up in a large community cohort. Methods: UK Biobank participants with follow-up hospitalization records (mean 10.5 years). MRI in 206 p.C282Y homozygotes versus 23,349 without variants, including T2 * measures (lower values indicating more iron). Results: European ancestry participants included 2,890 p.C282Y homozygotes. Male p.C282Y homozygotes had lower T2 * measures in areas including the putamen, thalamus, and hippocampus, compared to no HFE mutations. Incident dementia was more common in p.C282Y homozygous men (Hazard Ratio HR = 1.83; 95% CI 1.23 to 2.72, p = 0.003), as was delirium. There were no associations in homozygote women or in heterozygotes. Conclusion: Studies are needed of whether early iron reduction prevents or slows related brain pathologies in male HFE p.C282Y homozygotes.

scholarly journals Genetic overlap between Alzheimer’s disease and depression mapped onto the brain

2021 ◽  
Author(s):  
Jennifer Monereo Sánchez ◽  
Miranda T. Schram ◽  
Oleksandr Frei ◽  
Kevin O’Connell ◽  
Alexey A. Shadrin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genome Wide Association Study ◽  
Brain Mri ◽  
Genetic Correlations ◽  
Gaussian Mixture ◽  
Brain Morphology ◽  
Uk Biobank ◽  
Genetic Overlap ◽  
The Uk

ABSTRACTBackgroundAlzheimer’s disease (AD) and depression are debilitating brain disorders that are often comorbid. Shared brain mechanisms have been implicated, yet findings are inconsistent, reflecting the complexity of the underlying pathophysiology. As both disorders are (partly) heritable, characterizing their genetic overlap may provide etiological clues. While previous studies have indicated negligible genetic correlations, this study aims to expose the genetic overlap that may remain hidden due to mixed directions of effects.MethodsWe applied Gaussian mixture modelling, through MiXeR, and conjunctional false discovery rate (cFDR) analysis, through pleioFDR, to genome-wide association study (GWAS) summary statistics of AD (n=79,145) and depression (n=450,619). The effects of identified overlapping loci on AD and depression were tested in 403,029 participants of the UK Biobank (mean age 57.21 52.0% female), and mapped onto brain morphology in 30,699 individuals with brain MRI data.ResultsMiXer estimated 98 causal genetic variants overlapping between the two disorders, with 0.44 concordant directions of effects. Through pleioFDR, we identified a SNP in the TMEM106B gene, which was significantly associated with AD (B=-0.002, p=9.1×10−4) and depression (B=0.007, p=3.2×10−9) in the UK Biobank. This SNP was also associated with several regions of the corpus callosum volume anterior (B>0.024, p<8.6×10−4), third ventricle volume ventricle (B=-0.025, p=5.0×10−6), and inferior temporal gyrus surface area (B=0.017, p=5.3×10−4).DiscussionOur results indicate there is substantial genetic overlap, with mixed directions of effects, between AD and depression. These findings illustrate the value of biostatistical tools that capture such overlap, providing insight into the genetic architectures of these disorders.

S23MACHINE LEARNING METHODS TO PREDICT UNMEASURED PHENOTYPES IN LARGE-SCALE BIOBANK STUDIES: PROOF OF PRINCIPLE USING AUDIT IN THE UK BIOBANK

2019 ◽  
Vol 29 ◽  
pp. S125-S126
Author(s):  
Amanda Gentry ◽  
Roseann Peterson ◽  
Alexis Edwards ◽  
Brien Riley ◽  
B. Todd Webb
Keyword(s):  
Large Scale ◽  
Uk Biobank ◽  
Learning Methods ◽  
The Uk ◽  
Proof Of Principle

scholarly journals Genetic variation in the SIM1 locus is associated with erectile dysfunction

2018 ◽  
Vol 115 (43) ◽  
pp. 11018-11023 ◽  
Author(s):  
Eric Jorgenson ◽  
Navneet Matharu ◽  
Melody R. Palmer ◽  
Jie Yin ◽  
Jun Shan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Erectile Dysfunction ◽  
Sexual Function ◽  
Odds Ratio ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Adult Health ◽  
Uk Biobank ◽  
Melanocortin System ◽  
The Uk

Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 × 10−25). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 × 10−14), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin–melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function.

scholarly journals Altered Cortical Brain Structure and Increased Risk for Disease Seen Decades After Perinatal Exposure to Maternal Smoking: A Study of 9000 Adults in the UK Biobank

2019 ◽  
Vol 29 (12) ◽  
pp. 5217-5233 ◽  
Author(s):  
Lauren E Salminen ◽  
Rand R Wilcox ◽  
Alyssa H Zhu ◽  
Brandalyn C Riedel ◽  
Christopher R K Ching ◽  
...  
Keyword(s):  
Brain Structure ◽  
Brain Mri ◽  
Population Based ◽  
Smoke Exposure ◽  
Sensitivity Analyses ◽  
Uk Biobank ◽  
Increased Risk ◽  
Increase Risk ◽  
Sensory Cortices ◽  
The Uk

Abstract Secondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44–80) who were exposed (n = 2510) or unexposed (n = 6079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volumes. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE−) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+ adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n = 109, unexposed, n = 315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life.

scholarly journals Large-scale analysis of iliopsoas muscle volumes in the UK Biobank

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Julie A. Fitzpatrick ◽  
Nicolas Basty ◽  
Madeleine Cule ◽  
Yi Liu ◽  
Jimmy D. Bell ◽  
...  
Keyword(s):  
Large Scale ◽  
Large Population ◽  
Psoas Muscle ◽  
Magnetic Resonance Images ◽  
Muscle Volume ◽  
Iliopsoas Muscle ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Automated Method ◽  
The Uk

AbstractPsoas muscle measurements are frequently used as markers of sarcopenia and predictors of health. Manually measured cross-sectional areas are most commonly used, but there is a lack of consistency regarding the position of the measurement and manual annotations are not practical for large population studies. We have developed a fully automated method to measure iliopsoas muscle volume (comprised of the psoas and iliacus muscles) using a convolutional neural network. Magnetic resonance images were obtained from the UK Biobank for 5000 participants, balanced for age, gender and BMI. Ninety manual annotations were available for model training and validation. The model showed excellent performance against out-of-sample data (average dice score coefficient of 0.9046 ± 0.0058 for six-fold cross-validation). Iliopsoas muscle volumes were successfully measured in all 5000 participants. Iliopsoas volume was greater in male compared with female subjects. There was a small but significant asymmetry between left and right iliopsoas muscle volumes. We also found that iliopsoas volume was significantly related to height, BMI and age, and that there was an acceleration in muscle volume decrease in men with age. Our method provides a robust technique for measuring iliopsoas muscle volume that can be applied to large cohorts.

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