March 2021 ESRFnews16
None of this would have been possible without the EBS
ANATOMICAL IMAGING
human torso in three dimensions, non-destructively, at hundreds of times better resolution than has previously been achieved. Not bad for a project that only came into existence last
spring. Lee, a materials scientist at University College Lon- don in the UK, had been approached by Danny Jonigk, the head of the lung research group at the Institute of Pathol- ogy at Hanover Medical School, and Max Ackermann, a physician at Johannes Gutenberg University Mainz, in Germany. Their request: to reconstruct a small sample of tissue from the lung of a COVID-19 victim in three dimen- sions via synchrotron microtomography, to better under- stand why the organ failed. As a long-standing ESRF user, Lee approached ESRF scientist Paul Tafforeau, a pioneer in the use of phase-contrast microtomography for palae- ontology. Though he had spent his entire career looking at fossils, Tafforeau immediately saw the potential of local phase-propagation microtomography techniques and in particular their newly boosted EBS incarnations in bio- logical imaging, for the COVID-19 pandemic and beyond. Swiftly, Lee brought together an international, multidisci- plinary team, including synchrotron imaging scientists at UCL and the ESRF, mathematicians and computer scien- tists at UCL, and medical scientists at Hanover Biobank, the universities of Mainz and Heidelberg in Germany, and the French Alps Anatomy Laboratory University of Grenoble Alps (LADAF) among others. The COVID-19 pandemic changed a lot of things
for many people, says Tafforeau. I realised that several imaging techniques we originally developed for
palaeontology could open access to a new level of imaging precision on complete human organs. Then, while devel- oping the techniques further, we realised that it may be a game-changer for biological imaging in general.
Game changer To understand why it could be a game-changer, one first has to understand how histology currently works in prac- tice. According to Jonigk, whose lab analyses more human lungs than anywhere else in Europe, an organ typically arrives in his lab within minutes of being taken from a patient. First, radiologists usually conduct an overview scan via clinical computed tomography (CT), the poor res- olution (about 500 μm) of which is they hope just about enough to identify regions of interest by their abnormal appearance. In the case of a lung, for instance, this could be a fuzzy texture, like ground glass. Next, pathologists dissect the organ, harvesting dozens of millimetre-sized samples via an array of different imaging modalities, depending on the type of tissue and damage they expect to find. The process is fraught, inefficient and perhaps worst of all patchy. A cubic centimetre would be a lot for a biopsy, then perhaps you image one-hundredth of its volume, Jonigk explains. But lungs are litres and litres of tissue. Hierarchical phase-contrast tomography (HiP-CT), as
the emerging ESRF EBS imaging technique is becoming known, allows an entire organ to be imaged at 20 μm, more than 10 times better than clinical CT imaging; it also allows biopsies to be taken locally anywhere in the organ
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(Left) In c.1510, the anatomical drawings of Leonardo da Vinci provided unprecedented insights into the workings of the human body, especially biomechanics. (Right) Five centuries later, ESRF EBS images of the human lung and other organs showcase the latest in medical-imaging technology. Here, a lung lobe of a 54-year-old male COVID-19 victim can be viewed in its entirety at (a) 25 μm voxel resolution, or zoomed in at (b) 2 μm 100 times better than the resolution of clinical CT imagery. The detail is such that even individual red blood cells can be resolved.
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