Pushing the resolution limit of Phase Contrast CT Imaging

Christian Dullin, an expert in preclinical studies at the University Medical Center Göttingen, and Giuliana Tromba, in charge of Euro-BioImaging’s Phase Contrast Imaging Node, have been collaborating for many years. Their collaboration began in 2010 and  when Euro-BioImaging became operational in 2019, Christian was one of the first Euro-BioImaging users. For over 5 years, Christian and Giuliana and their teams have been working to push the resolution limit in phase contrast imaging on phantom lung models. Their newest setup, which results in high-resolution tomographic images with 7x better details and 2-3 times less exposure than traditional CT, has been published in a recent paper “Pulmonary phase contrast CT imaging – A novel setup at the Italian synchrotron for the study of fresh lungs at human scale” the European Respiratory Journal of ESR. We spoke to Giuliana and Christian to find out more about this novel phase-contrast technique and its potential for patient studies. 

Christian Dullin is an expert in x-ray and optical imaging as well as in image processing and software development.  His research focuses on lung morphology and pathology. His first experiments at the Phase Contrast Imaging Node were on quantification of morphological changes in lungs of an asthma mouse model in-situ, as part of a European project named "Public Private Partnership for Asthma Genomics and Imaging (P3AGI)."  But his long-term vision has always been to use the Synchrotron for patient studies.

“Synchrotron radiation-based phase contrast imaging (SRCT) is capable of very high spatial and temporal resolutions. It is therefore extremely useful for studying lesions, cancer nodules or fibrosis,” explains Giuliana Tromba. “Conventional systems are not accurate enough.”

“While SRCT provides superior image quality, its use is currently limited to small animal models, such as mice and rats because of high radiation doses. It is difficult to translate to the clinic,” continues Giuliana. “That is why, in collaboration with Christian, we wanted to develop a setup that allows for ex vivo imaging of intact human organs, such as the lung, at clinical relevant x-ray dose levels that would allow to further translate the technology to patients.”

“The first experiment was performed in 2018, using the existing setup of the beamline. But the phantom was quite tricky to use. Our new set-up is based on a novel custom-made human-size chest based on a pig lung phantom from MiMEDA GmbH, Germany that is relatively easy to handle and relatively light. Furthermore, it includes a system to simulate breathing…” says Christian.

“Our dedicated sample stage is based on a rotating disc with a modern photon-counting detector mounted more than 10 meters downstream of the phantom. This long sample-to-detector distance is the key to our ability to increase the resolution,” explains Christian. (For full description of the setup, see article: Dullin et al., European Respiratory Journal 2024; DOI: 10.1183/13993003.01604-2023)

Christian, Giuliana and their teams tested the set-up on several pig lungs, which are very close to the human lungs, to evaluate the perspective of using this set-up in humans. 

“While the experiments have become more realistic with the new phantom, we cannot apply the technology at the human scale for the moment because of the energy needed,” regrets Giuliana. “But a new beamline is under construction (Elettra 2.0) – and this new beamline will make imaging of any kind of lungs (including in humans) possible at low dose.” 

“So, what we have published is a realistic feasibility study that we are confident to apply to humans once we have the new machine,” concludes Giuliana. 

But there are still a few drawbacks, one of which is leaving the hospital environment to come to the Synchrotron. Furthermore, patients must be able to sit on the rotating stage while images are acquired. Supported by radiologists and pulmonologists, Giuliana and Christian think the effort is reasonable for patients with specific pathologies, such as interstitial lung disease or suspicious cancer lesions  when conventional lung CT is not conclusive, where the benefits of 7x higher resolution would be enormous. 

What will be the impact of the increased resolution? 

A specific example of where this setup could be a game-changer is in detecting the early formation of lung fibrosis, not visible in conventional CT. Images from the synchrotron would be important because there aren’t many alternatives (biopsies are invasive, and not recommended for cases of fibrosis). In addition, suspect cancer nodules are not clearly understood with conventional CT or MRI, and could be elucidated with higher resolution. This setup could also be used as an interpretation key for doubtful images obtained with conventional CT and contribute to solving many questions. The possibilities are endless, but one thing is sure: such unprecedented image detail will be a game-changer in the clinical diagnosis of lung disease. 

Giuliana and Christian have already begun preparing the protocol that would make it possible to offer this setup to patients one day. Then they would need to obtain authorizations from several ministries and work with a wide-range of stakeholders to implement a test phase.  

In the meantime, the experimental set-up developed at the SYRMEP beamline of the Italian

synchrotron ELETTRA to investigate lungs of human scale is available in open-access to all pulmonary scientists via Euro-BioImaging (www.eurobioimaging.eu).