ESRF and UCL scientists awarded Chan Zuckerberg Initiative grant for human organ imaging project

02-12-2020

The Chan Zuckerberg Initiative (CZI) has awarded $1 million to an imaging research project led by three researchers, among them ESRF scientist Paul Tafforeau, and Peter Lee and Rebecca Shipley from UCL (University College London), as part of a world-wide call to advance deep tissue imaging.

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The project, named “Anatomical to cellular synchrotron imaging of the whole human body”, promises to develop a transformational X-ray tomography technology that will enable the scanning of a whole human body with resolution of 25 microns, thinner than a human hair – tens of times the resolution of a CT scanner. Further, it can then zoom into local areas with cellular-level imaging, or one micron – over 100x better resolution than a CT scanner. This imaging project is based on the recent Extremely Brilliant Source (EBS) upgrade to the ESRF that has created the world’s first high-energy fourth-generation synchrotron, which is currently the brightest X-ray source in the world. Feasibility studies have already demonstrated it can resolve unprecedented detail revealing the damage caused by COVID-19 on human lungs, linking from the major airways all the way down to the finest micro-vasculature in an intact lung.

The project is led by an international multidisciplinary team of synchrotron imaging scientists (at UCL and ESRF), mathematicians and computer scientists (at UCL) and medics (at Hannover-biobank, Mainz and Heidelberg), brought together to image deep-tissue in COVID-19-injured organs.

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HiP-CT synchrotron technique is being used to image whole human lungs to help understand the injury caused by COVID-19. This 54 year old male victim’s whole lung lobe is first scanned at 25 micron voxel resolution (green cylinder, rendered to show the two vascular systems and occluded vessels). Scientists can then zoom in at 6 (red circle) then 2 micron voxels (blue circle), giving 100X more resolution than clinical CT. Cellular structure is resolved, including individual red blood cells (red arrows). (Credit: P.Tafforeau/ESRF). 

Founded by Dr. Priscilla Chan and Mark Zuckerberg in 2015, the Chan Zuckerberg Initiative (CZI) is a new kind of philanthropy that leverages technology to help solve some of the world’s toughest challenges — from eradicating disease to improving education, to reforming the criminal justice system. Across three core Initiative focus areas of Science, Education, and Justice & Opportunity, engineering is being paired with grant-making, impact investing, and policy and advocacy work to help build an inclusive, just and healthy future for everyone. On 2 December 2020, CZI announced nearly $32 million in funding to support biomedical imaging researchers and technology development to drive breakthroughs in curing, preventing, or managing disease by advancing the imaging field.

From anatomy to 3D histology: new perspectives for medical imaging

As mentioned by CZI, “although there have been significant advances in biomedical imaging, we are far from the ultimate goal: to observe cells and subcellular processes in living organisms and in a minimally invasive manner”.

Using this CZI funding, the international multidisciplinary team of X-ray imaging researchers, mathematicians, biologists and medics from across Europe aim to develop new X-ray tomography techniques called Hierarchical Phase-Contrast Tomography, or HiP-CT, enabling unparalleled local sub-micron cellular imaging in hard- and soft-tissue in a whole human body (using high X-ray energies) with outstanding tissue contrast sensitivity (via phase-propagation). This innovative method will allow scientists to perform virtual 3D histology, non-destructively, anywhere within the intact organ or body and thus to hence understanding of complex living organisms.

To achieve this transformation in X-ray tomography technology, this project will make significant breakthroughs in critical areas, including X-ray optics, detectors and hierarchical correlative image-reconstruction algorithms. This work will be scaled to clinical imaging, using AI to correlate the project’s cellular mapping to clinical diagnostic techniques.

First data from the ESRF’s upgrade to the world’s brightest X-ray source, ESRF-EBS

Performing the first user experiment after ESRF’s Extremely Bright Source (EBS) 150€M upgrade, the scientists demonstrated the technique’s feasibility, scanning entire human organs at 25 microns, or ½ the width of a human hair, then zooming with local phase-propagation tomography to reveal 3D cellular structures with high sensitivity reaching 1.4 microns voxel resolution through 200 mm tissue.

They imaged organs from COVID-19 patients. As shown by the YouTube video of preliminary results (https://youtu.be/zhPWCR7bBeI), the scientists were able to assess the complex vascular system of the lung in 3D, down to the smallest capillaries involved in the alveolar gas exchange, non-destructively. It allowed to show that there is growing evidence that alterations to the vascular system play an important role in the pathophysiology of COVID-19 pneumonia.

These results demonstrate the potentially transformational benefits of the technique to help understand the injury COVID-19, and other diseases, when fully realised.

As ESRF scientist Paul Tafforeau explains, “the COVID-19 pandemic changed a lot of things for many people. I realized that several imaging techniques we originally developed for palaeontology could open access to a new level of imaging precision on complete human organs. While developing the techniques further, we realised that it may be a game changer for biological imaging in general. Our team then decided to apply for the CZI grant in order to turn these promising preliminary results into a real breakthrough that should have a major impact in the coming years in the biomedical community.”

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Paul Tafforeau, ESRF scientist imaging the complete brain and lung of a COVID-19 victim using HiP-CT at the ESRF-EBS, the world’s brightest X-ray source. By resolving cellular features (ca. one-micron resolution) in local areas we hope to help determine if COVID-19 affects the vasculature in the organs. (Credit: ESRF) 

As an X-ray imaging scientist, Peter Lee at UCL adds, “early in the pandemic a group of German medics at Mainz contacted me to see if we could image the damage COVID-19 causes in the lung. We quickly brought together scientists at ESRF and Diamond Light Source, and started imaging biopsy (tiny) samples. Paul Tafforeau realised that using the new synchrotron ESRF-EBS, we could get the same resolution on whole organs as we do in biopsies, which would be transformational as we could link cellular damage at an organ scale. Forming a UK-French-German team, we developed HiP-CT during lockdown, and we are continuing to develop it, while using the results to help clinicians understand the injury COVID-19 has on our organs.”

Harald Reichert, Director of Research, ESRF, concludes that “the award of this grant is a clear sign of trust into the potential of the ESRF-EBS for breakthrough research of the highest impact enabled by the provision of synchrotron X-rays beams with unprecedented brilliance and coherence”.

 

References:

Find out more about the Chan Zuckerberg Initiative here:

Frontiers of Imaging Technology - Chan Zuckerberg Initiative: https://chanzuckerberg.com/science/programs-resources/imaging/frontiers/

Top image: Using the world’s brightest X-ray source, the ESRF-EBS, an ESRF-UCL team of scientists together with German medics are using a synchrotron technique called Hierarchical Phase-Contrast Tomography (HiP-CT) to image with cellular resolution anywhere in a human body. The image shows feasibility results using HiP-CT to assess the complex vascular system of the whole lung lobe of a 54 year old male COVID-19 victim, in 3D, non destructively, to help understand the injury caused by COVID-19. (Credit P.Tafforeau/ESRF).