We all know what human lungs look like, but few people have seen the lungs after being infected with the new crown virus.
The picture below shows the lungs of a 54-year-old covid-19 patient.
Among them, the alveoli and respiratory bronchiole are blue, the open blood vessels are red, and the occluded and damaged blood vessels are yellow.
This picture can see the damage caused by the new crown virus to the blood vessels in the lungs, and we have seen many similar pictures on the Internet.
But interestingly, this picture is not a computer drawing, nor a simulated lung model, but a real lung. It was an X-ray.
This was unimaginable not so long ago...
Human beings have studied organs and human tissues for thousands of years, ancient medical books have structural diagrams of organs, and modern technology can also let us clearly see cells and microorganisms.
But here's a counterintuitive fact:
We humans don't know exactly what organs look like.
"Probably most people will be surprised." Andrew Cook, a cardiac anatomist at the University of London, said, "Although we have been studying the structure of the heart hundreds of years ago, it has not yet been conclusive what the normal structure of the heart should look like. The muscle cells of the heart in particular, and how it changes as the heart beats. ”
Humans certainly have a lot of beautiful, detailed heart maps, but claire Walsh, a postdoctoral researcher, says those are just artistic creations.
"In anatomy textbooks, we can see a lot of large-scale and small-scale diagrams. There's a reason these are hand-drawn drawings: because we don't have real pictures, we can only interpret them in art. ”
This is due to the limited human technology to map out the complete organs at the cellular level.
Medical X-rays such as CT and MRI can take pictures of entire organs, but their resolution is not high.
Biopsies allow scientists to look at tissue samples under a microscope, and their resolution is high, but the image shows only a small part of the organ and cannot know what the whole thing looks like.
Figuratively speaking, humans study organs, just like nature lovers exploring forests,
Either by flying over the forest in a large jet or hiking along a forest path, the whole and detail cannot be combined.
But now, a new technology has emerged that can make people soar through the forest like birds, waving their wings, overlooking the forest, and gazing at the dew.
(Left kidney of a 94-year-old woman scanned with Hip-CT technology, resolution of 25.08 microns)
"For the first time, we were finally able to make real pictures." Walsh said excitedly, "We bridge the gap between medical CT photos and biopsy photos. ”
(Claire Walsh)
This technology is called Hip-CT, something that ushered in a new era of histology.
And its birth is that scientists want to study the harm of the new crown virus to the human body.
In 2020, shortly after the start of the COVID-19 pandemic, Danny Jonigk, a thoracic scientist at the Hannover Medical School in Germany, and Maximilian Ackermann, a pathologist at the University of Mainz, felt that the virus was unusual.
(Danny Jonny)
Both of them had expertise in lung disease and soon noticed that the patient was reported to have an "invisible hypoxia" phenomenon.
"Invisible hypoxia" means that the patient does not have symptoms of breathing difficulties and does not have obvious discomfort, but the blood oxygen concentration in the body drops sharply. Because it is difficult to detect, the patient's condition will be delayed for a long time, and he is often in a critical state when entering the hospital.
Jonick and Ackerman suspect that the coronavirus is somehow attacking the blood vessels in the lungs.
(Maximilian Ackerman)
In March 2020, after the virus spread in Germany, the two conducted an autopsy on the covid-19 deaths, comparing their lung tissue with the lungs of ordinary deceased people.
The two soon discovered that the smallest blood vessels in the lungs of the covid-19 victims were twisted and took on different forms. There is a large number of fine vascular systems in the human body, and even if only 1% of the blood vessels are attacked by the virus, the ability of blood flow and absorption of oxygen will be impaired.
(Site of vascular distortion)
In May 2020, they published their results in an academic journal saying that COVID-19 is not strictly a respiratory disease, but a vascular disease that may affect organs throughout the body.
(Research published by two)
After knowing that the virus affects blood vessels, the two want to understand what the damage is like, which requires the picture to be clear enough to zoom in to the cell scale.
"Although the lungs do very simple, oxygen in, carbon dioxide out, but the blood vessels inside tens of thousands of miles long, very finely arranged, is simply a miracle." 」 "So, what are we going to do to study something as complex as COVID-19 without damaging the organs," Jonick said. ”
Thinking about it, Jonny and Ackerman thought of using X-rays.
(The vascular system in the kidneys of a 94-year-old woman scanned by HiP-CT technology)
They contacted materials scientist Peter Lee, who excelled at studying biomaterials with X-rays, and soon introduced them to the European Temple of Scientists, the European Institute for Synchrotron Radiation.
The European Institute of Synchrotron Radiation, or ESRF for short, is a large joint research institute located in Grenoble,d'Org, France.
(European Institute of Synchrotron Radiation)
More than 8,000 scientists visit and conduct more than 2,000 experiments every year, and what attracts them here is the particle accelerator.
ESRF's particle accelerators allow electrons to travel along a half-mile circular orbit at speeds close to light.
As electrons run in circles, powerful magnets in orbit bend the flow of particles, causing the electrons to emit extremely bright X-rays.
(Accelerator track in ESRF)
This powerful X-ray allows ESRF to observe objects at micron, or even nanometer, resolution.
It is commonly used to study alloys and composites, to observe the molecular structure of proteins, and to study fossil bones inside without breaking stones.
Jonick and Ackerman want to use it to perform the world's most sophisticated X-ray scans of human organs, which Paul Tafforeau, who oversees accelerator technology, said should be possible.
(Paul Taverno)
Not long ago, ESRF completed the upgrade of the "ExtremeLy Bright X-ray Source" (EBS for short), which can shoot the world's brightest X-rays, which are 10 trillion times more powerful than ordinary medical X-rays and 100 times that of the previous generation of X-ray sources.
EBS can image complex objects at the atomic level, generate a three-dimensional model after scanning, and the internal structure is clear.
(Particle Accelerator for ESRF)
The reason why ordinary medical X-rays are difficult to present clear human organs is because X-rays rely on the absorption of different substances to map, and heavy elements absorb more than light elements.
Human tissue is mainly composed of light elements (such as carbon, hydrogen, oxygen), so it is difficult to distinguish.
But EBS doesn't have this problem because its rays are very synchronized, advancing at the same frequency and alignment.
When X-rays pass through an object, subtle differences in density cause the ray's route to shift slightly, and the farther away from the object, the easier it is to detect this difference.
So, even with light elements, EBS can still clearly depict the internal image of soft tissue.
(Using HiP-CT technology, the heart of a 94-year-old woman scanned under an EBS radiation source)
The only problem is that human tissue is difficult to fix, and if it moves more than one thousandth of a millimeter during the scan, the final image may be wrong because the rays cannot be aligned.
After thinking about these things, Tafro began to study how to fix the organs in containers.
He extracted a gel from seaweed with a lot of ethanol in it, then found pig offal from the slaughterhouse and wrapped it up.
Then, on top of a variety of techniques for studying fossils, he developed a scanning technique called HipP-CT, which can scan entire organs and enlarge any part of interest up to the cellular level.
(The brain scanned with HiP-CT can be continuously enlarged.)
In May last year, Tafro scanned pig lungs with HiP-CT and appeared to be fine.
He then scanned the left lung of a 54-year-old man who had just died of COVID-19 and sent the photos to Jonick and Ackerman.
In fact, Tafro was quite nervous, and after seeing the first picture of human lung, he thought he had failed, and sent an email to the members of the entire project to apologize, saying that he did not make a high-quality scan.
"Those few pictures were terrible for me, but they were great for them!" Tafolo said.
Li, who saw the photo, was amazed that Tafolo gave a three-dimensional image of the lungs, which could be magnified at will where he wanted to see, "the amount of information is a million times that of medical CT."
HiP-CT technology enables the resolution of human body scanning to reach 25 microns, which is thinner than human hair,
After selecting the area to enlarge, it can also reach a single micron resolution, which is 100 times the resolution of medical CT!
(Lung scans that can be zoomed in to cell structures)
"When we first saw the picture, everyone fell silent." Walsh said, "No one has seen such a detailed picture of human organs before. ”
Jonik and Ackerman were delighted because the three-dimensional images showed the blood vessels in the lungs expanding and swelling, and also forming abnormal miniature vascular bundles, which is a step closer to understanding the new crown virus.
This scary-looking graph also managed to convince their relatives and friends to get vaccinated.
(Researchers analyzing images swept out by HiP-CT)
HiP-CT's work hasn't stopped, and Tafro's team has set up a human organ atlas program that wants to scan all the organs and put three-dimensional images in the cloud for all medical researchers to see. These diagrams are equivalent to Google Maps of the human body.
So far, the team has released three-dimensional maps of the heart, brain, kidneys, lungs and spleen, completed scans of another 30 organs, and 80 organs are waiting in line.
(5 organs from HiP-CT scan)
The technology is invaluable in understanding the disease, and more than 40 research groups have contacted them in the hope that they will help sweep it.
The HiP-CT team is also testing ESRF's latest beam device, called the BM18, which produces a larger X-ray beam, meaning it takes less time to scan.
BM18 is also working well, and they plan to scan the entire human body by the end of 2023.
Originally, humans also needed to rely on painting to make organ structure diagrams, but now it only takes half a day to get a real organ map.
Human beings are one step closer to understanding themselves, thanks to the development of science and technology...