Synopsis
UK Biobank is a prospective epidemiological
study of 500,000 participants consisting of extensive questionnaires, physical
measures and biological samples, linking to long-term health outcomes. The
imaging extension for the UK Biobank ultimately aims to image 100,000 subjects
from this cohort, including brain, cardiac and body MRI, bone scans and carotid
ultrasound. We overview the brain imaging component, which includes structural,
functional and diffusion MRI. The value of this open resource arises not only
from multi-modal/multi-organ imaging, but also from the depth of other demographic,
phenotypic and exposure data, and will increase over time as clinical outcomes
are realized in the population.Purpose
To present the brain imaging protocols
included in UK Biobank, a large prospective epidemiological study, and provide an
initial overview of data quality.
Background
UK Biobank is a prospective epidemiological
study of 500,000 participants consisting of extensive questionnaires, physical
measures and biological samples, including genetics1. The study will link
against UK National Health Service records to relate these measures to long-term
health outcomes. All data from UK Biobank are available to researchers
world-wide upon application for access.
An imaging extension for the UK Biobank has
recently been launched that, if fully funded, ultimately aims to image 100,000 subjects
from the original cohort (currently aged 45-78)2. Imaging includes brain,
cardiac and body MRI, DEXA bone scans and carotid ultrasound. The pilot phase
has scanned 6500 participants3 in 18 months, and produced a data release of 5000 subjects,
recently made available to researchers3. Here, we overview the brain imaging
component of UK Biobank.
Protocol Overview
Imaging of 100,000 subjects requires three
dedicated imaging centres operating 7 days/week with throughput of 18
subjects/day over 5 years. This daily throughput places tight timing
constraints, corresponding to one subject completed every 36 minutes. As a
prospective study, the UK Biobank does not target any particular disease or
hypothesis, and hence the imaging protocol must be as broadly useful as
possible.
Following optimization of acquisition
protocols, streamlining of subject preparation and minimization of scanner dead
time, Biobank is now achieving its target participant throughput. The brain
imaging protocol (Table 1) includes T1-weighted MPRAGE (T1) and T2-weighted
FLAIR (T2FLAIR), diffusion MRI (dMRI), task-based fMRI (tfMRI), resting-state
fMRI (rfMRI) and susceptibility-weighted gradient echo (SWI).
Protocol
Considerations
Many considerations went into protocol
design. Here, we highlight decisions relating to the high throughput nature of
Biobank.
° Tight FOVs minimize scan time,
but in large studies these restrictions exclude subjects (e.g. 99% population
compatibility loses 1000 participants). We conducted a study of population
brain size4 that enables our FOVs to target ≥99.9%.
° Calibration scan times
accumulate. By minimizing this “dead time” (e.g. altered shim defaults) we
re-gained several minutes scan time.
° While T1 scan times could have
been reduced, the central role of the T1 to cross-subject and cross-modal
alignment for most processing pipelines made this an unacceptable risk.
° Simultaneous multi-slice
(multiband, MB) acquisition enabled short fMRI5 and dMRI6 runs without
sacrificing statistical robustness or directions/b-values, respectively.
° Field map acquisitions were replaced
with blip-reversed spin echo acquisition as part of dMRI.
° We are piloting a potential protocol
change, reducing task fMRI to 2 minutes with the goal of including a short ASL
perfusion scan.
Image Processing and Associated Phenotypes:
Automated processing pipelines were developed,
primarily based on tools from FSL, with future pipelines expanding the range of
toolkits (e.g. FreeSurfer-based cortical and subcortical/cerebellar modeling).
A streamlined set of image outputs is available for each modality. Example
images for several modalities from the initial 5000 participant data release are shown in Figs 1-4.
Imaging-derived phenotypes (IDPs) were
estimated from the processed outputs. IDPs are single values that would be appropriate
for use by non-imaging experts. Examples of the extracted IDPs currently
include (listed by modality, number of IDPs in parentheses):
° T1: volumetric estimates of tissue types and grey
matter structures (33)
° dMRI: tensor- and NODDI-derived estimates in major
white matter tracts (675)
° rfMRI: network-edge
connectivity estimates for two network decompositions (3,390)
° tfMRI: summary statistics on
BOLD effect size and significance values (18)
° SWI: median T2* values in major
deep grey structures (14)
The set of available IDPs is expected to
expand with improved and novel functionality of processing pipelines.
Discussion
If funding is awarded for the full study,
the UK Biobank will comprise the largest cohort of subjects ever
imaged comprehensively. The value of the resource arises not only from
multi-modal/multi-organ imaging, but also from the depth of other demographic,
phenotypic and exposure data. Discovery
of disease risk factors will increase over time as clinical outcomes are
realized in the population. For example, 5000 cohort participants are expected
to develop Alzheimer’s disease by 2020, rising to 10,000 by 2030.
Acknowledgements
The UK Biobank Imaging Enhancement is funded by the Medical Research Council UK. The work presented here was also supported by the Wellcome Trust (KLM and SMS). We would like to acknowledge the valuable contributions of members of the UK Biobank Imaging Working Group and the UK Biobank coordinating centre. Finally, we are extremely grateful to all UK Biobank study participants, who have made this study possible.
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