Researchers used the world’s brightest X-rays to image intact organs in unprecedented detail and created an open access portal for exploring the intricate images.
In 2021, as the COVID-19 pandemic rampaged across the world, researchers sought to understand how SARS-CoV-2 infection triggered structural damage in lungs. Since there was no imaging platform to map intact lungs at a high resolution, scientists at University College London (UCL) and the European Synchrotron Radiation Facility (ESRF) joined forces to create one.
Among other organs, researchers imaged and mapped the intact human heart from entire organ level scale to two micrometer scale.
They developed a technique called hierarchical phase-contrast tomography (HiP-CT), leveraging the world’s brightest X-rays—nearly 100 billion times brighter than conventional hospital X-rays—to image postmortem intact human lungs at scales ranging from the entire organ to individual cells.1 The scientists soon realized the widespread applications of this technique beyond just the lungs.
“It quickly became apparent that this technique…could be rolled out across other organs,” said Claire Walsh, an imaging scientist at UCL. “And all the data…could really provide some fundamental changes for how we understand human anatomy and physiology.”
Building on this, Walsh and her colleagues recently launched the Human Organ Atlas, an online portal which allows users to zoom into intact human organs.2 The open repository, described in Science Advances, offers unprecedented insights into intricate structures within organs, providing a valuable resource to understand human anatomy.
The Human Organ Atlas Offers a Never-Seen-Before Look into Organs
After Walsh and her colleagues released their prototype and the early data in 2021, “We spent a lot of time working with the community to understand how would they use this data,” said Walsh. “And we've been really building functionality into the portal ever since then. And it’s really built into something much more powerful.”
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Obtaining deep insights into ex vivo organs was a monumental effort on part of a multidisciplinary team, said Walsh. Clinicians, data engineers, image analysts, and scientists from nine institutes across Europe and the US formed a consortium to make the data accessible in a meaningful manner.
At the moment, the Human Organ Atlas portal contains more than 300 images from 32 donors across 13 organs: brain, colon, eye, female genitalia, heart, kidney, liver, lung, placenta, prostate, spleen, testis, and uterus.
Users can choose the organ they want to explore, and access images of the whole organ zooming in to near-cellular resolution, down to less than one micrometer, or 50 times thinner than a human hair. According to the team, the Human Organ Atlas currently offers the highest resolution open access 3D dataset of human organs.
Peter Lee, from UCL, Paul Tafforeau, from the European Synchrotron Radiation Facility (ESRF) and Claire Walsh, from UCL preparing to scan a human heart and a human brain at the ESRF.
ESRF/vuedici.org
Imaging Organs in 3D at a Cellular Level
To build the atlas, the researchers used organs surgically removed during autopsies. They then fixed the organs in order to scan them using X-rays. To zoom into the organs at a micrometer scale, the HiP-CT setup requires a synchrotron, or particle accelerator “sort of the size of a football stadium,” explained Walsh. “It accelerates electrons very, very fast. And as these electrons are bent with magnets, they give off X-rays. And it's these X-rays that we're using for imaging.”
At the particle accelerator at ESRF, this X-ray beam is large and of high energy such that it can penetrate through big samples and scan intact whole organs and resolve cellular detail in practically feasible time frames. Other imaging methods either cannot resolve at such small sizes or take months to complete. In contrast, HiP-CT works in under a day to provide intricate near-cellular maps of organs.1
Seeing the first images at such a zoomed in level was “exciting,” according to Walsh. She recalled Zoom meetings where the first datasets left many experts speechless and confused. “I was opening some datasets and being like…‘I saw this really weird thing here,’ and show the clinicians and they'd be like, ‘Wow, oh yeah, that is weird,’” recalled Walsh. After getting a similar response from histopathologists in the group, she had an epiphany.
“You realize you're looking at a scale that no one ever sees before. Because you're not down at the very small cells that the histopathologists look at [in] 2D slices. And you're not at the scale of clinical imaging. You're at this middle [scale],” she said. “And I think the thing that really struck me is how much unknown there is in the middle with human biology.”
Applications of the Human Organ Atlas
Since Walsh and her team first developed the technique in 2021, the researchers and others have already leveraged it to obtain insights into healthy and diseased states of the heart and uterus.3,4 According to her, the team is now using data from the atlas to map the connections within the brain.
Scientists from the Human Organ Atlas Hub are now using data from the atlas to map the connections within the brain.
Despite the immense applications, Walsh noted that all the samples come from older donors, skewing the data toward aging-related diseases. “It is a bit challenging that we don't have healthy controls, but I think that's also normal in most work with human individuals,” she said. She also noted that one of the biggest economic healthcare burdens today is diseases of aging, “and that's what's incredibly well represented in our set.”
Going forward, Walsh said the team plans to expand the collection to add more organs as well as develop tools to obtain insights from the data. “We have scratched the surface of what there is to look at and analyze with these data,” she said. “I'm excited to see what people do with it. That’s kind of the most exciting thing, to actually see what the rest of the world wants to do with this.”
Sneha Khedkar is an Assistant Editor at The Scientist. She has a Master’s degree in biochemistry, after which she studied the molecular mechanisms of skin stem cell migration during wound healing as a research fellow at the Institute for Stem Cell Science and Regenerative Medicine in Bangalore, India. She has previously written for Scientific American, New Scientist, and Knowable Magazine, among others.
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