{"id":21127,"date":"2022-01-27T17:32:06","date_gmt":"2022-01-28T00:32:06","guid":{"rendered":"https:\/\/oralcancernews.org\/wp\/?p=21127"},"modified":"2022-01-27T17:32:06","modified_gmt":"2022-01-28T00:32:06","slug":"worlds-brightest-x-rays-reveal-covid-19s-damage-to-the-body","status":"publish","type":"post","link":"https:\/\/oralcancernews.org\/wp\/worlds-brightest-x-rays-reveal-covid-19s-damage-to-the-body\/","title":{"rendered":"World\u2019s brightest x-rays reveal COVID-19\u2019s damage to the body"},"content":{"rendered":"

Source: National Geographic<\/a>
\nDate: January 26th, 2022
\nAuthor: Michael Grashko<\/p>\n

Featured Image by National Geographic:<\/strong>
\nThe Human Organ Atlas project, an international team including ESRF staff scientist Paul Tafforeau, has used HiP-CT to scan the organs of COVID-19 victims, including their brains. HiP-CT scans can zoom in from a whole-organ scan to provide a cellular view of regions of interest.<\/span><\/span><\/strong><\/h5>\n

When Paul Tafforeau saw his first experimental scans of a COVID-19 victim\u2019s lung, he thought he had failed. A paleontologist by training, Tafforeau had been laboring with a team strewn across Europe for months to turn a particle accelerator in the French Alps into a revolutionary medical scanning tool.<\/p>\n

It was the end of May 2020, and scientists were anxious for a better view of the ways human organs were being ravaged by COVID-19. Tafforeau had been tasked with developing a technique that could make use of the powerful x-rays generated at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. He\u2019d pushed boundaries on high-resolution x-rays of rock-hard fossils and desiccated mummies as an ESRF staff scientist. Now, he was dismayed by a lump of soft, squishy tissue.<\/p>\n

But when his colleagues caught their first glimpse of the lung scans, they felt something else: awe.<\/p>\n

The images presented them with richer detail than any medical CT scan they\u2019d seen before, allowing them to bridge a stubborn gap in how scientists and doctors can visualize\u2014and make sense of\u2014human organs. \u201cIn anatomy textbooks, when you see, This is the large scale, and this is the smaller one, they\u2019re all beautiful hand-drawn images for a reason: They\u2019re artistic interpretations, because we have no images for it,\u201d says Claire Walsh, a senior postdoctoral fellow at University College London (UCL). \u201cFor the first time, we can make the real thing.\u201d<\/p>\n

Tafforeau and Walsh are part of an international team of more than 30 researchers that has created a powerful new kind of x-ray scan called hierarchical phase-contrast tomography (HiP-CT). With it, they can finally go from a complete human organ to a zoomed-in view of the body\u2019s tiniest blood vessels and even individual cells.<\/p>\n

The technique is already providing fresh insights into how COVID-19 damages and reshapes the blood vessels of the lungs. And while its long-term promise is hard to define, because nothing quite like HiP-CT has ever existed before, researchers excited by its potential are enthusiastically dreaming up new ways to understand disease and more rigorously chart the terrains of human anatomy.<\/p>\n

\u201cWhat is perhaps a surprise to most people is we\u2019ve been studying the heart anatomically since hundreds of years ago,\u201d says UCL cardiac anatomist Andrew Cook, \u201cbut there isn\u2019t a consensus about the normal structure of the heart, particularly the muscle cells, and how it changes as the heart beats.\u201d<\/p>\n

A technique with HiP-CT\u2019s promise, he says, is something \u201cI\u2019ve been waiting for my whole career.\u201d<\/p>\n

Needing a bigger magnifying glass<\/h2>\n

The HiP-CT technique got its start as two German pathologists raced to track the SARS-CoV-2 virus\u2019s punishing effects across the human body.<\/p>\n

As soon as news of unusual pneumonia cases began trickling out of China, Danny Jonigk\u2014a thoracic diseases pathologist at Hannover Medical School\u2014and Maximilian Ackermann, a pathologist at University Medical Center Mainz, were on high alert. Both had expertise in lung disease, and right away they knew COVID-19 was unusual. The two were especially concerned about reports of a \u201csilent hypoxia\u201d that left COVID-19 patients awake but caused their blood oxygen levels to plummet.<\/p>\n

Ackermann and Jonigk suspected that SARS-CoV-2 was somehow attacking the lungs\u2019 blood vessels. As the disease spread through Germany in March 2020, the duo began conducting autopsies of COVID-19 victims. They soon tested their blood-vessel hypothesis by injecting tissue samples with resin and then dissolving the tissues in acid, which left behind faithful casts of the original vasculature.<\/p>\n

Using this technique, Ackermann and Jonigk compared the tissues of people who hadn\u2019t died of COVID-19 with those who had. They immediately saw that among COVID-19 victims, the smallest blood vessels in the lungs were distorted and reshaped. These landmark results, published online in May 2020<\/a>, showed that COVID-19 wasn\u2019t strictly a respiratory disease but a vascular one\u2014one that could affect organs across the entire body.<\/p>\n

\u201cIf you go through the human body and you take all the blood vessels in one line, you come up with [60,000] to 70,000 miles, double the distance around the Equator,\u201d says Ackermann, who is also a pathologist at Wuppertal, Germany\u2019s HELIO Clinics. If just one percent of these blood vessels gets attacked by a virus, he adds, the blood\u2019s flow and ability to absorb oxygen can be impaired, with potentially devastating consequences across entire organs.<\/p>\n

As soon as they recognized COVID-19\u2019s vascular effects, Jonigk and Ackermann realized that they needed a much better view of the damage.<\/p>\n

Medical x-rays such as CT scans can provide a view of an entire organ, but they weren\u2019t high-resolution enough. Biopsies can let scientists study tissue samples under a microscope, but the resulting images are only small bits of a whole organ and can\u2019t show how COVID-19 progresses across an entire lung. And the team\u2019s resin technique required dissolving tissue, which destroys the sample and limits further study.<\/p>\n

\u201cAt the end of the day, [the] lung is oxygen in, carbon dioxide out\u2014but for that, it has thousands and thousands of miles of blood vessels and capillaries that are so finely and nicely arranged \u2026 it\u2019s almost a miracle,\u201d says Jonigk, the founding principal investigator of the German Center of Lung Research. \u201cSo how could we actually assess something as complex as COVID-19 \u2026 without destroying the organ?\u201d<\/p>\n

Jonigk and Ackermann needed the unprecedented: a series of x-rays, all done on the same organ, that would let researchers zoom into portions of the organ down to the cellular scale. In March 2020, the German duo reached out to a longtime collaborator of theirs, Peter Lee, a materials scientist and chair of emerging technologies at UCL. Lee\u2018s specialty is studying biological materials with powerful x-rays\u2014so his mind immediately went to the French Alps.<\/p>\n

Getting the scans to work<\/h2>\n

The European Synchrotron Radiation Facility sits in the northwestern corner of Grenoble on a triangular plot of land where two rivers meet. The facility is a particle accelerator that makes electrons travel at nearly the speed of light around a half-mile-long circular track<\/a>. As these electrons careen round and round, powerful magnets along the track bend the particle stream, which causes the electrons to emit the world\u2019s brightest x-rays.<\/p>\n

This powerful radiation lets the ESRF peer into objects at the scale of micrometers, even nanometers. It is frequently used to study materials such as alloys and composites, check the molecular structures of proteins, and even reconstruct ancient fossils without having to separate rock from bone. Ackermann, Jonigk, and Lee wanted to use this huge instrument to perform the world\u2019s most detailed x-ray scans of a human organ.<\/p>\n

Enter Tafforeau, whose work at the ESRF has stretched the limits of what synchrotron scans can see. His impressive bag of tricks previously let scientists peer inside dinosaur eggs and virtually unwrap mummies, and almost immediately, Tafforeau confirmed that the synchrotron could, in theory, make a good scan of an entire lung lobe. But actually scanning a whole human organ posed a grand challenge.<\/p>\n

For one, there\u2019s the issue of contrast. Standard x-rays make images based on how much radiation gets absorbed by different materials, with heavier elements absorbing more than lighter ones. Soft tissues are mostly made of light elements\u2014carbon, hydrogen, oxygen, and so on\u2014which is why they don\u2019t show up clearly in a classic medical x-ray.<\/p>\n

One of the ESRF\u2019s great benefits is that its x-ray beams are very coherent: Light moves in waves, and in the ESRF\u2019s case, its x-rays all start out with the same frequency and alignment, undulating in unison like the marks left behind by a zen garden\u2019s rake. But as these x-rays move through an object, subtle differences in density can cause each x-ray\u2019s path to deviate slightly, a difference that gets more detectable the farther the x-rays propagate once they exit the object. These deviations can reveal the slight density differences within an object, even if it is made of light elements.<\/p>\n

But stability is another challenge. To pull off a series of zoomed-in x-rays, a given organ would have to be immobilized in its natural shape so it wouldn\u2019t flex and shift by more than a thousandth of a millimeter. Any more wiggle than that, and successive x-ray scans on the same organ wouldn\u2019t align with each other. Needless to say, though, organs can be quite floppy.<\/p>\n

Lee and his team at UCL rushed to devise containers that could withstand the synchrotron\u2019s x-rays but also let through as many waves as possible. Lee also juggled the project\u2019s overall organization\u2014such as the finer points of shipping human organs between Germany and France\u2014and recruited Walsh, who specializes in huge biomedical datasets, to help work out how to analyze the scans. Back in France, Tafforeau\u2019s jobs included refining the scanning procedure and figuring out how to keep the organs still within the containers that Lee\u2019s team was building.<\/p>\n

To preserve the organs from decay and make the scans as sharp as possible, Tafforeau knew that they would need to be treated with several rounds of ethanol-water solutions. He also knew that he needed to stabilize the organs in something that exactly matched the organs\u2019 density. His working plan was to somehow embed the organs in an ethanol-rich agar, a jelly-like substance derived from seaweed.<\/p>\n

However, the devil would be in the details\u2014and Tafforeau, like much of Europe, was stuck at home in lockdown. So Tafforeau relocated his research to his home laboratory: a former secondary kitchen that he had spent years decking out with 3D printers, basic chemistry equipment, and the tools used to prepare animal skeletons for anatomical study.<\/p>\n

Tafforeau used supplies from a local grocery store to work out how to make his agar. He even collected rainwater runoff from his recently cleaned roof to obtain demineralized water, a standard ingredient in lab-grade agar recipes<\/a>. To practice packing organs in agar, he got pig entrails from a local slaughterhouse.<\/p>\n

Tafforeau got permission to return to the ESRF in mid-May to perform the first test scans of a pig\u2019s lung. As May turned to June, he had prepared and scanned the left lung lobe of a 54-year-old man who had died from COVID-19, which Ackermann and Jonigk had shipped to Grenoble from Germany.<\/p>\n

\u201cWhen I saw the first image, the email I sent to all the people on the project was, I apologize: We failed, I was not able to have high-quality scans,\u201d he says. \u201cI just sent them two pictures that, for me, were bad, but for them were excellent.\u201d<\/p>\n

For UCL\u2019s Lee, the images were awe-inspiring: an organ-wide view like a standard medical CT scan, but \u201cwith one million times the information.\u201d It was as if the researchers had spent their lives studying a forest by either flying over it in a jumbo jet or hiking along one trail. Now they were soaring just above the forest canopy, like birds on the wing.<\/p>\n

\u201cThe first time we saw the middle resolution \u2026 It was just like, silence,\u201d Walsh says.<\/p>\n

Tackling future challenges<\/h2>\n

The team published its first full description of the HiP-CT method<\/a> in November 2021, and the researchers also have published a detailed look at how COVID-19 affects certain kinds of blood circulation in the lungs<\/a>.<\/p>\n

The scans also yielded an unanticipated bonus: helping the researchers convince friends and relatives to get vaccinated. In severe COVID-19 cases, many of the lungs\u2019 blood vessels look dilated and bloated, and at smaller scales, abnormal bundles of tiny blood vessels form.<\/p>\n

\u201cWhen you see the structure of lungs of people who die from COVID, it does not look like lungs\u2014it\u2019s a big mess,\u201d Tafforeau says.<\/p>\n

Even in healthy organs, he adds, the scans were revealing subtle anatomical features that had never been documented because nobody has ever seen a human organ in this level of detail before. With more than a million dollars in funding from the Chan Zuckerberg Initiative\u2014a nonprofit founded by Facebook CEO Mark Zuckerberg and physician Priscilla Chan, Zuckerberg\u2019s wife\u2014the HiP-CT team is now creating what it\u2019s calling the Human Organ Atlas<\/a>.<\/p>\n

So far, the group has released scans of five types of organs\u2014the heart, brain, kidneys, lungs, and spleen\u2014based on donated organs from Ackermann and Jonigk\u2019s COVID-19 autopsies in Germany and healthy \u201ccontrol\u201d organs from LADAF, a Grenoble-based anatomy lab. The team has made the data,\u00a0as well as fly-through movies based on the data<\/a>, freely available online.<\/p>\n

The Human Organ Atlas is rapidly growing: Another 30 organs have already been scanned, and 80 more are in various stages of preparation. Lee says that some 40 different research groups have contacted the team to learn more about the method.<\/p>\n

Cook, the UCL heart specialist, see enormous potential in using HiP-CT to understand basic anatomy. And Joe Jacob, a UCL radiologist who specializes in lung disease, says that HiP-CT will be \u201cinvaluable for understanding diseases,\u201d especially in 3D structures such as blood vessels.<\/p>\n

Even artists are joining the fray. Barney Steel, of the London-based experiential art collective Marshmallow Laser Feast, says that he is actively researching how to explore HiP-CT data in immersive virtual reality. \u201cWe\u2019re basically creating journeys through the human body,\u201d he says.<\/p>\n

But for all HiP-CT\u2019s promise, there are also considerable challenges. First, Walsh says, HiP-CT scans generate a \u201cterrifying amount of data,\u201d easily several terabytes per organ. For clinicians to make real-world use of these scans, the researchers hope to develop a cloud-based interface to navigate them, like Google Maps for the human body.<\/p>\n

They also need to turn the scans into workable 3D models with greater ease. Like all CT scanning techniques, HiP-CT works by making many 2D slices of a given object and stacking them together. Even today, much of this process is manual, especially for scans of abnormal or diseased tissues. Lee and Walsh say that a major priority for the HiP-CT team is to develop machine-learning techniques that can lighten the load.<\/p>\n

These challenges will scale as the Human Organ Atlas expands\u2014and as researchers\u2019 ambitions grow with it. The HiP-CT team is using the ESRF\u2019s newest beam facility, called BM18, to continue scanning the project\u2019s organs. BM18 produces a much bigger x-ray beam, which means scans take less time, and BM18\u2019s x-ray detector can be placed up to 125 feet (38 meters) away from the object being scanned, which makes its scans far sharper. The BM18 results are already so good, Tafforeau says, that he has re-scanned some of the the Human Organ Atlas\u2019s original samples on the new system.<\/p>\n

BM18 also has the space to scan very large objects. Thanks to the new facility, the team\u2019s vision is to scan an entire torso of a human body in one fell swoop by the end of 2023.<\/p>\n

In exploring this technique\u2019s immense potential, Tafforeau says, \u201cwe are really at the very beginning.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

Source: National Geographic Date: January 26th, 2022 Author: Michael Grashko Featured Image by National Geographic: The Human Organ Atlas project, an international team including ESRF staff scientist Paul Tafforeau, has used HiP-CT to scan the organs of COVID-19 victims, including their brains. HiP-CT scans can zoom in from a whole-organ scan to provide a cellular view of regions of interest. When Paul Tafforeau saw his first experimental scans of a COVID-19 victim\u2019s lung, he thought he had failed. A paleontologist by training, Tafforeau had been laboring with a team strewn across Europe for months to turn a particle accelerator in the French Alps into a revolutionary medical scanning tool. It was the end of May 2020, and scientists were anxious for a better view of the ways human organs were being ravaged by COVID-19. Tafforeau had been tasked with developing a technique that could make use of the powerful x-rays generated at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. He\u2019d pushed boundaries on high-resolution x-rays of rock-hard fossils and desiccated mummies as an ESRF staff scientist. Now, he was dismayed by a lump of soft, squishy tissue. But when his colleagues caught their first glimpse of the lung scans, they felt something else: awe. The images presented them with richer detail than any medical CT scan they\u2019d seen before, allowing them to bridge a stubborn gap in how scientists and doctors can visualize\u2014and make sense of\u2014human organs. \u201cIn anatomy textbooks, when you see, This is the large scale, […]<\/p>\n","protected":false},"author":41,"featured_media":21129,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-21127","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-oral_cancer_news"],"_links":{"self":[{"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/posts\/21127","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/users\/41"}],"replies":[{"embeddable":true,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/comments?post=21127"}],"version-history":[{"count":2,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/posts\/21127\/revisions"}],"predecessor-version":[{"id":21130,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/posts\/21127\/revisions\/21130"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/media\/21129"}],"wp:attachment":[{"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/media?parent=21127"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/categories?post=21127"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/tags?post=21127"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}