Creating a 3D atlas of human organs

Using transformational X-ray tomography technology to scan the whole human body with a resolution thinner than a human hair.

The different biomedical imaging techniques available until now have not been able to show organs and other body parts in detailed resolution. For example, computed tomography (CT) uses X-rays to create 3D images in slices, in millimetre resolution. Magnetic resonance imaging (MRI) uses magnetic fields and radio waves to create images, also with millimetre resolution. Even when a biopsy is taken and microscopy used to examine it, this is only a tiny part of a whole organ. Imaging entire human organs with micron resolution has been impossible until now. This means for diseases such as Covid-19, you cannot see how the disease progresses through the lungs, how variable the damage is, or the patterns of injury across the organ as a whole.

In response to this, Professor Peter Lee and Dr Claire Walsh from UCL Mechanical Engineering led an imaging research project – the Human Organ Atlas – to advance capabilities in biomedical imaging. They partnered with Dr Paul Tafforeau from the European Synchrotron Radiation Facility (ESRF), and were awarded $2.75m of funding from the Chan Zuckerberg Initiative (CZI), for this project to enable cellular-level imaging anywhere in whole human organs.

Technology used by biologists and palaeontologists

The idea for a solution to organ images with more detail began with an imaging technique used to reconstruct large paleontological specimens. Synchrotrons produce X-rays that are in-phase or coherent . This allows researchers to see when the phase of the X-rays changes due to tiny density differences inside the sample. These changes are used to create tomographic 3D images in very high detail. In the past, this technology has been used to scan ancient human skulls, dinosaur fossils and mummified animals.

The idea to use X-ray tomography technology for biomedical imaging was helped along by the development of the ESRF’s Extremely Brilliant Source (EBS) in 2020. This created the brightest X-ray source in the world, 100 times brighter than before, and made the coherence even better. This technology enabled the larger soft samples such as human organs to be scanned in more detail.

It was the onset of the Covid-19 pandemic that created the urgency to see if this technology could indeed be applied to human biomedical imaging. Early in the pandemic, scientists and doctors did not understand how Covid-19 was damaging the lungs, and how this was contributing to deaths. There was a need to scan damaged lungs post-mortem to begin to investigate this, but existing technology did not offer the detail needed to make accurate conclusions.

On video: HiP-CT imaging of a Covid-19 injured human lung using the ESRF-EBS.

YouTube Widget Placeholderhttps://www.youtube.com/watch?v=c79SkNXbKds

Making the Human Organ Atlas a reality

The project has so far created 3D images of lungs, brains, hearts, kidneys, spleens and livers. The Human Organ Atlas team aims to have the entire human body scanned by 2025. The aim is for this to become a reference database of organ images that everyone can access.

The group of scientists working on the project – now an international team of 80 – have called this scanning technique Hierarchical Phase-Contrast Tomography (HiP-CT). This is because the technology has been created using 3D reconstructions of whole intact organs, that can be interrogated down to the cellular level. These scans can be done with a resolution of 25 microns, thinner than a human hair and twenty times the resolution of a CT scanner. It also allows localised scanning with micron resolution, at five hundred times the resolution of a CT scanner. Professor Lee describes the organ view scans as having “one million times the information” of standard CT scans.

Already the imagery has changed some previously held beliefs about organs that have been scanned. For example, the alveoli in the lungs are depicted and thought of as spherical, but for the most part they are actually often more like shallow bowls. “In many anatomy textbooks, you see beautiful hand-drawn images because we do not have any real 3D images of these structures. Now, for the first time, we can make the real thing,” says Dr Walsh.

In terms of the effect of Covid-19 on the lungs, HiP-CT scans of several lungs from victims have shown more detail about the exact damage that has occurred, which includes changes in the connections of the blood vessels in the lungs. On CT scans, this damage appears as merely an indistinct texture. Researchers are using the images to understand what role these vessel connections play in the course of Covid-19 and the other types of damage seen in the lung.

Dozens of different research groups have contacted the team to find out more about the technique. The ability to see the impact of disease on the whole body from HiP-CT scanning – and not just individual organs – will also be crucial to feed into the next steps of biomedical research. Professor Lee explains: “Being able to see within our intact bodies to capture dynamic processes with cellular resolution will also help us to overcome a wide range of challenges, such as understanding how osteoarthritis affects our joints or understanding patterns in diseases that affect multiple organs in the body."