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 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 Associations of cigarette smoking with gray and white matter in the UK Biobank

2019 ◽  
Author(s):  
Joshua Gray ◽  
Matthew Thompson ◽  
Chelsie Benca-Bachman ◽  
Max Michael Owens ◽  
Mikela Murphy ◽  
...  
Keyword(s):  
White Matter ◽  
Cigarette Smoking ◽  
Gray Matter ◽  
Brain Structure ◽  
Mean Diffusivity ◽  
Medial Lemniscus ◽  
Uk Biobank ◽  
Matter Volume ◽  
Increased Risk ◽  
The Uk

Chronic cigarette smoking is associated with increased risk for myriad health consequences including cognitive decline and dementia, but research on the link between smoking and brain structure is nascent. We assessed the relationship of cigarette smoking (ever smoked, cigarettes per day, and duration) with gray and white matter using the UK Biobank cohort (gray matter N = 19,615; white matter N = 17,760), adjusting for numerous demographic and health confounders. Ever smoked and duration were associated with smaller total gray matter volume. Ever smoked was associated with reduced volume of the right VIIIa cerebellum, as well as elevated white matter hyperintensity volumes. Smoking duration was associated with reduced total white matter volume. With regard to specific tracts, ever smoked was associated with reduced fractional anisotropy in the left cingulate gyrus part of the cingulum, left posterior thalamic radiation, and bilateral superior thalamic radiation and increased mean diffusivity in the middle cerebellar peduncle, right medial lemniscus, bilateral posterior thalamic radiation, and bilateral superior thalamic radiation. Overall, we found significant associations of cigarette exposure with global measures of gray and white matter. Furthermore, we found select associations of ever smoked, but not cigarettes per day or duration, with specific gray and white matter regions. These findings inform our understanding of the connections between smoking and variation in brain structure and clarify potential mechanisms of risk for common neurological sequelae.

scholarly journals The effect of network thresholding and weighting on structural brain networks in the UK Biobank

2019 ◽  
Author(s):  
Colin R. Buchanan ◽  
Mark E. Bastin ◽  
Stuart J. Ritchie ◽  
David C. Liewald ◽  
James Madole ◽  
...  
Keyword(s):  
White Matter ◽  
Mean Diffusivity ◽  
Clustering Coefficient ◽  
Uk Biobank ◽  
Whole Brain ◽  
Threshold Levels ◽  
Network Measures ◽  
Structural Networks ◽  
The Uk ◽  
Structural Brain

AbstractWhole-brain structural networks can be constructed using diffusion MRI and probabilistic tractography. However, measurement noise and the probabilistic nature of the tracking procedure result in an unknown proportion of spurious white matter connections. Faithful disentanglement of spurious and genuine connections is hindered by a lack of comprehensive anatomical information at the network-level. Therefore, network thresholding methods are widely used to remove ostensibly false connections, but it is not yet clear how different thresholding strategies affect basic network properties and their associations with meaningful demographic variables, such as age. In a sample of 3,153 generally healthy volunteers from the UK Biobank Imaging Study (aged 44—77 years), we constructed 85 × 85 node whole-brain structural networks and applied two principled network thresholding approaches (consistency and proportional thresholding). These were applied over a broad range of threshold levels across six alternative network weightings (streamline count, fractional anisotropy, mean diffusivity and three novel weightings from neurite orientation dispersion and density imaging) and for four common network measures (mean edge weight, characteristic path length, network efficiency and network clustering coefficient). We compared network measures against age associations and found that the most commonly-used level of proportional-thresholding from the literature (retaining 68.7% of all possible connections) yielded significantly weaker age-associations (0.070 ≤ |β| ≤ 0.406) than the consistency-based approach which retained only 30% of connections (0.140 ≤ |β| ≤ 0.409). However, we determined that the stringency of the threshold was a stronger determinant of the network-age association than the choice of threshold method and the two thresholding approaches identified a highly overlapping set of connections (ICC = 0.84) when matched at a plausible level of network sparsity (70%). Generally, more stringent thresholding resulted in more age-sensitive network measures in five of the six network weightings, except at the highest levels of sparsity (>90%), where crucial connections were then removed. At two commonly-used threshold levels, the age-associations of the connections that were discarded (mean β ≤ |0.068|) were significantly smaller in magnitude than the corresponding age-associations of the connections that were retained (mean β ≤ |0.219|, p < 0.001, uncorrected). Given histological evidence of widespread degeneration of structural brain connectivity with increasing age, these results indicate that stringent thresholding methods may be most accurate in identifying true white matter connections.

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.

Abstract T P234: Multiparametric Assessment of Longitudinal Changes in Tissue Microstructure in Normal and Abnormal Brain Tissue in Patients with Small Vessel Disease

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Maria D Valdes-Hernandez ◽  
Paul A Armitage ◽  
Eleni Sakka ◽  
Susana Munoz Maniega ◽  
Natalie A Royle ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Tissue ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Tissue Loss ◽  
Minor Stroke ◽  
Normal Brain ◽  
Limited Information ◽  
Time Points

Background: Volume measures of normal brain tissue and white matter hyperintensities (WMH) between two time points gives limited information about the complex dynamics of tissue change. We evaluated two quantitative parameters that characterise the microstructure of normal-appearing white matter (NAWM), deep grey matter (DGM) and WMH on brain images obtained at presentation with minor stroke and at 1 year to investigate the microstructural changes. Methods: From 182 brain MRI datasets of patients with minor stroke obtained at baseline and 1 year, we extracted the WMH, DGM and NAWM, and separated WMH into less-intense and intense WMH, using validated semi-automatic methods and validated criteria. We registered the binary structural masks to diffusion space and performed a voxel-wise subtraction of the combined masks at both time points. Then we measured fractional anisotropy (FA) and mean diffusivity (MD)(valuex10 -9 m 2 /s) in each tissue mask at baseline and 1 year. Results: WMH volume median increase was 1.4ml (IQR 6.98) mainly due to changes in less-intense WMH: 0.94ml (7.13). WMH that were visible at both time points, ie damage that remained after a year, had the lowest FA= 0.21(0.06) and highest MD=1.05(0.12) at baseline, and were mainly intense WMH at baseline (FA=0.12(0.03), MD=1.55(0.27)). WMH seen only at follow-up, ie that were NAWM at baseline, had the highest FA=0.30(0.06) and lowest MD=0.85 (0.06) at baseline. WMH that were observed only at baseline had intermediate FA=0.26(0.08) and MD=0.90(0.10). NAWM FA=0.26(0.03), MD=0.78(0.04) and DGM FA=0.23(0.03), MD=0.79(0.06) did not change between time points. Conclusions: WMH at baseline can partially evolve to normal-appearing tissues, remain or precede tissue loss. Differentiation between severe and subtle damage and spatial analysis are necessary to characterise the dynamic of WMH evolution.

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.

Abstract P366: High Burden of Tract-Specific White Matter Hyperintensities Relates to Impaired Microstructural Integrity of Distal White Matter Tracts in Community-Dwelling Elders

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
YANPENG LIU ◽  
YIWEI XIA ◽  
XIAOXIAO WANG ◽  
YI WANG ◽  
LUMENG YANG ◽  
...  
Keyword(s):  
Executive Function ◽  
White Matter ◽  
Cognitive Dysfunction ◽  
White Matter Hyperintensities ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Community Dwelling ◽  
Superior Longitudinal Fasciculus ◽  
High Burden ◽  
Microstructural Integrity

Background and purpose: White matter hyperintensities (WMH) are common in elderly individuals and contribute to age-related cognitive dysfunction. Converging evidence indicates that WMH affect white matter (WM) microstructural integrity in WMH and their penumbra. We aimed to investigate whether this effect extends to the distal WM tracts, and to examine the association between distal WM microstructural integrity and cognitive dysfunction in community-dwelling elderly people. Methods: Brain MRI data including FLAIR and DTI sequences of 174 participants (74 ± 5 years) of the Shanghai Aging Study (SAS) were collected and analyzed. For each participant, WMH lesions were segmented automatically. Eighteen major WM tracts were reconstructed using automated quantitative tractography, and the mean diffusivity (MD) of distal WM tracts (excluding an area of 12 mm around the WMH) was calculated. Multivariable linear regression was performed. Results: A high burden of tract-specific WMH was related to a high MD of distal WM tracts in the forceps major (FMA), anterior thalamic radiations (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a high MD of distal tracts was linked to worse attention and executive function in the forceps minor (FMI), right CCG, left inferior longitudinal fasciculus (ILF), SLFP, SLFT and UNC. Conclusions: The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions farther than the penumbra and eventually might affect attention and executive function.

scholarly journals Associations of cigarette smoking with gray and white matter in the UK Biobank

2020 ◽  
Vol 45 (7) ◽  
pp. 1215-1222
Author(s):  
Joshua C. Gray ◽  
Matthew Thompson ◽  
Chelsie Bachman ◽  
Max M. Owens ◽  
Mikela Murphy ◽  
...  
Keyword(s):  
White Matter ◽  
Cigarette Smoking ◽  
Uk Biobank ◽  
The Uk

scholarly journals Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity

2019 ◽  
Vol 14 (5) ◽  
pp. 1468-1476 ◽  
Author(s):  
Donald M. Lyall ◽  
Simon R. Cox ◽  
Laura M. Lyall ◽  
Carlos Celis-Morales ◽  
Breda Cullen ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Aging ◽  
Social Deprivation ◽  
Mean Diffusivity ◽  
Brain Magnetic Resonance Imaging ◽  
Smoking History ◽  
White Matter Hyperintensity ◽  
Future Research ◽  
Uk Biobank ◽  
Intermediate Phenotypes

Abstract Apolipoprotein (APOE) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive aging.

Sign in / Sign up

Export Citation Format

Share Document