How the World’s Largest Bioimaging Study Could Change Our Understanding of Disease

What is the connection between genes, lifestyle, and disease? That’s the question driving most biomedical research today.

Until recently, researchers haven’t had sufficient information to answer it. Medical research studies are often too small, too short or too limited to yield much-needed insights into human health and translate those findings into useful information that doctors can use to treat disease.

UK Biobank, the world’s largest biomedical dataset and research resource, was launched in 2006 to change that. Since then, half a million adults in the United Kingdom, aged 40 to 69 at the outset, have provided biological samples and genetic data, answered surveys about their health and activities, and allowed for their health to be followed over many years through electronic medical records. Their participation isn’t one-and-done. Instead, they participate repeatedly, so the dataset grows in detail as they age. By following participants’ health throughout their lives, the researchers aim to unravel the complex relationship between genes, lifestyle factors and the most common chronic diseases.

Imaging also sets UK Biobank apart. A subset of participants have already had detailed brain and body scans taken, creating a trove of biomedical imaging data. These whole-body images provide a view of how the brain, abdominal organs and bones are structured and how they function.

Now UK Biobank is launching the world’s largest longitudinal repeat imaging study. Approximately 60,000 people will have their entire body re-imaged as part of UK Biobank’s Repeat Imaging Project. Jointly funded by the Chan Zuckerberg Initiative (CZI), Calico and the UK Medical Research Council, the Reimaging Project will make it possible for researchers to compare pictures of an individual’s brain and body at two different time points and investigate how it changes with age and disease.

This image shows visceral and subcutaneous fat around the organs in a study investigating T2 diabetes and coronary heart disease risk. Photo courtesy of UK Biobank.

The project’s goal is closely aligned with CZI’s Science mission to cure, prevent or manage all diseases by the end of the century. It also complements CZI’s science programs, which are accelerating progress on brain disorders through the Neurodegeneration Challenge Network and advancing scientific imaging research and technology through the Imaging program.

“The Repeat Imaging Project will enhance UK Biobank’s discovery power,” says Katja Brose, Program Officer for CZI’s Neurodegeneration Challenge Network. “There is currently no comparison for the scale, breadth, depth and quality of what it would offer the research and clinical community.”

Even in the age of big data, the Repeat Imaging Project stands out. Its size and richness — a combination of imaging data and all the other information UK Biobank offers — are unmatched.

It is likely to yield extraordinary insights into the complexity of the human body as it ages and when chronic diseases take hold. Scientists may also come to understand why one person develops Alzheimer’s, cancer or heart disease whereas another does not. They might even be able to predict their risk for future health conditions.

Accelerating Brain Science: From COVID to dementia

The banging and whirring of MRI machines and other imaging technologies are just getting underway for the Repeat Imaging Project. Still, a study spurred by the COVID-19 pandemic has already demonstrated its potential, especially for brain research.

UK Biobank was not designed to help researchers study how infectious diseases like COVID-19 change the body. Yet, it allowed researchers to investigate worrisome neurological symptoms associated with SARS-CoV-2 infection, including muddled thoughts, memory lapses, problems with focus or attention, and loss of taste and smell.

The opportunity to conduct the world’s first longitudinal study of SARS-CoV-2 and the brain came about because when the pandemic hit, tens of thousands of Britons had already had their bodies scanned for science. Some of those healthy volunteers became infected with COVID-19. That provided researchers with the rare opportunity to look at how their brains were affected following SARS-CoV-2 infection — and whether they could detect abnormalities that might explain symptoms like brain fog and loss of smell.

The UK Biobank COVID-19 repeat imaging study created the only study in the world with scans of internal organs taken before and after infection, with just over 2,000 participants taking part — half of whom had previously had COVID-19 while the other half had not. The scans captured information about the shape, size, and metabolic activity of various brain regions. The volunteers also underwent a series of cognitive tests.

The research findings revealed tissue damage and greater shrinkage in brain areas related to smell. Whether those changes persist long-term or increase the risk for cognitive impairment or neurodegenerative diseases like Alzheimer’s is still unknown but may be the focus of future research.

High-resolution brain imaging allows for detailed measurement of brain volume. Photo courtesy of UK Biobank.

UK Biobank’s COVID-19 study is just one example of the power of its imaging component. The Repeat Imaging Project could advance brain research and treatment in several other ways.

As the global population ages, the burden of Alzheimer’s and related dementias is increasing. For instance, in the UK, an estimated 944,000 people live with dementia. That figure is expected to rise to more than 1 million by 2030 and 1.6 million by 2050. Globally, the number of people living with dementia will increase by more than 200 percent, from 50 million in 2018 to 152 million in 2050. Scientists and clinicians are in a race against time to predict who is at the greatest risk for the condition, how to prevent it, how to diagnose it early, and how to intervene.

Re-imaging data, which captures detailed information about how the brain changes with age, could be enormously helpful. By tapping into UK Biobank’s imaging data, researchers may be able to pick up brain signatures of dementia at a time when symptoms are non-existent or too subtle to be detected in the clinic.

Paul Matthews, Director of the UK Dementia Research Institute at Imperial College London and Chair of the Imaging Working Group for UK Biobank, estimates that 6,000 to 8,000 of UK Biobank healthy volunteers will develop dementia over the course of the study. For a subset of those volunteers, researchers will have before-and-after pictures of their brains. “We’ll be able to look at the trajectory of these diseases through time — from their earliest stages — which is something we’ve never been able to do,” he says. “That’s pretty remarkable.”

The Repeat Imaging Project will also make it possible to study how diseases evolve. Getting a grasp on how they progress over time is not possible from imaging data collected only at a single time point.

As a result of the project, “we’ll be able to begin to chart the trajectory across the lifespan for people who are going to have better or less good health outcomes. We’ll be able to do this in multiple organ systems at the same time, including the brain,” says Matthews.

Pushing the Limits of Imaging Science

The Repeat Imaging Project will also show us what is needed to help scientists and clinicians get the most out of existing imaging data and gain an even deeper understanding of human biology.

“The UK Biobank Repeat Imaging Project is using state-of-the-art technologies, and it may deliver predictive biomarkers of disease. It’s also going to show us where the gaps are, helping us understand where we need to push the technology in the future,” says Stephani Otte, CZI Science Program Officer for Imaging.

Radiographers review data from an individual in an MRI machine at a UK Biobank imaging center. Photo courtesy of UK Biobank.

For example, biomedical research is undergoing a transformation, spurred by developments in machine learning and artificial intelligence (AI). AI methods are now routinely used to analyze biomedical images and extract meaning from them. Machine learning has also entered the clinic, where it can diagnose skin cancer, eye disorders and changes to heart function. The sheer scale of the data in UK Biobank could help train machine learning systems and test computational algorithms that can extract features and take precise measurements of the human body.

These new technologies will have a ripple effect in medical research, especially in imaging and computational biology — two fields supported by CZI Science.

As the Repeat Imaging Project progresses, UK Biobank and its partners are also working to ensure that the data are accessible to researchers worldwide. That may sound like an obvious goal, however, as the size and scope of UK Biobank have increased, so too has the challenge of data sharing, especially for imaging data, which are large and specialized in form and content.

“The challenge that UK Biobank has now is to enable greater exploitation of the resource by investigators all over the world. We want to stimulate the most creative science. However, we are very aware of the challenges of using this rich and therefore complex resource. We are engaging with partners like CZI to address this. It’s mission-critical. By doing so, will change the way science is done,” says Matthews.

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Chan Zuckerberg Initiative Science

Supporting the science and technology that will make it possible to cure, prevent, or manage all diseases by the end of the century.