An international research team led by DZL scientists Professor Dr. Danny Jonigk and Willi Wagner was able to demonstrate changes in blood vessels caused by infection with SARS-CoV-2. Using a highly innovative X-ray technique, they were able to show that massive remodeling of the finest blood vessels occurs in severe COVID-19.
If the SARS-Cov-2 coronavirus enters the lungs, it causes massive tissue damage. A characteristic consequence of the infection is, among other things, the blockage of the pulmonary vessels due to a locally excessive blood clotting. Now, for the first time, an international research team led by DZL scientists Professor Dr. Danny Jonigk from the Institute of Pathology at Hannover Medical School (MHH) and Willi Wagner from Heidelberg University Hospital (TLRC) has been able to demonstrate non-destructively, using a highly innovative X-ray technique, that severe COVID-19 causes massive remodeling of the finest blood vessels by causing normally separate blood systems to join together with unusual frequency.
To do this, the researchers studied the lungs of a COVID-19 victim in cooperation with the European Synchrotron Research Facility (ESRF), the world's third largest particle accelerator, in Grenoble, France. Thanks to the latest technology, a three-dimensional image of the complete organ was generated for the first time using high-resolution X-rays. The work has resulted in two publications in renowned journals: The technical procedure is published in Nature Methods, and the clinical application in the American Journal of Respiratory and Critical Care Medicine (Blue Journal).
HiP-CT shows an entire organ in three dimensions without damaging it
The new X-ray technology works much like a computed tomography (CT) scan in a hospital. However, the resolution is hundreds of times higher. "In the CT scan, we can visualize blood vessels in the millimeter range," Professor Jonigk explains. The new technology called Hierarchical Phase Contrast Tomography (HiP-CT) is able to image the finest vessels with a diameter of five micrometers - about one-tenth the thickness of a hair. HiP-CT makes it possible to penetrate the depths of the lungs and image even the smallest structures, down to individual cells. "This resolution was previously only possible with a microscope, but only in two dimensions and for small tissue samples," says the lung specialist. HiP-CT can do significantly more. The new technique makes it possible for the first time to image an entire organ in three dimensions and at a high magnification without damaging it." This has allowed us to examine structures that are at the limits of resolution and to gain an overview of changes throughout the lung tissue," the pathologist emphasizes.
COVID-19 leads to "short circuits" in the blood vessels of the lung
In this way, the scientists discover what seems to go wrong within the course of COVID-19. Two separate blood systems exist in the lungs - one belongs to the pulmonary circulation and is responsible for supplying oxygen to the entire body, the other supplies the lung tissue itself with the vital gas. In a healthy lung, there are sometimes a few connections between small vessels of the two systems. In the damaged COVID-19 lung, on the other hand, the two blood systems formed numerous such cross-links in many areas. "This large number of irreversible shunts acts like a wide-open floodgate and ensures that the oxygen supply throughout the body no longer functions" explains Professor Jonigk. He suspects that the cause is a dysregulation of the lungs themselves, which thus attempt to compensate for the lack of oxygen caused by the SARS-CoV2 infection in the short term in a kind of short-circuit reaction.
The brilliant, high-resolution technology will revolutionize medical imaging and our understanding of how our bodies are built, Professor Jonigk says. "Now we have the ability to visualize tiny structures three-dimensionally in their proper spatial context on a large scale," he explains. The research team has already begun to create a more advanced organ atlas. In addition to the COVID-19-damaged lung, it already includes images of several healthy human organs such as the brain, lungs, heart, kidneys and spleen from body donations of deceased individuals. In addition, the pathologist is convinced that the HiP-CT X-ray technology will provide new insights into numerous diseases, including cancer and Alzheimer's disease.
The work was done in cooperation between the MHH Institute of Pathology and, among others, the German Center for Lung Research at the Hannover site (DZL Breath), University College London and the University Medical Center Mainz.
The Bronchial Circulation in COVID-19 Pneumonia
Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography