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Radiotherapy using x-rays is a widely used and effective treatment for killing tumours, and half of all cancer patients receive this treatment. Directing an x-ray beam at the tumour causes DNA damage and induces cell death. However, healthy tissue nearby can also be damaged – especially when patients are poorly positioned, or there are inaccuracies in treatment delivery.
Radiotherapy’s full potential is being limited by the lack of a system capable of providing visual feedback on the radiation dosage delivered.
The EU-funded AMPHORA project is developing non-invasive ultrasound technology that measures the amount of radiation delivered to the tumour and the healthy surrounding tissues. This approach, known as in-situ dosimetry, could help improve patient safety during treatment.
At the project’s outset, the AMPHORA team identified prostate cancer – the second most common cancer in men – as the most suitable target application. They have been working with clinical experts to fully understand the challenges associated with ultrasound imaging of the prostate and using that insight to underpin the prototype system’s design.
‘This technology will provide immediate feedback to radiotherapists about the quantity and location of radiation given to the patient, which means there is less room for treatment error and a lower risk of damaging healthy tissue,’ says project coordinator Jan D’hooge of KU Leuven in Belgium. ‘The system aims to increase the accuracy of radiation therapy, which will directly impact on the quality of treatment experienced by the patient.’
Unique nano-droplet technology
AMPHORA’s primary work focused on developing ultrasound contrast agents (UCAs) to accurately sense radiation dosages.
By mid-2019, AMPHORA researchers at Tor Vergata University had developed UCAs that could be injected into the bloodstream in order to reach the tumour and surrounding tissues.
They recently demonstrated that these minute liquid droplets – just half of a thousandth of a millimetre across – evaporate upon exposure to radiation to form microscopic bubbles that light up in an ultrasound image. Thus, the number of bubbles seen in the ultrasound scan relates to the quantity of radiation delivered to the tissue. In this way, an accurate ‘dose map’ is formed.
The ultrasound readout system is being designed to minimise the invasiveness of the procedure and to prevent interference with the radiation beam during treatment. Two bespoke ultrasound probes are being manufactured by project partners at the Fraunhofer Institute for Biomedical Engineering. These new probes will be capable of 3D imaging and therefore dose mapping using state-of-the-art instrumentation to cope with the high data throughput.
From x-rays to proton beams
The system is still at a low-technology readiness level, so it has yet to be commercialised. However, several partners in the consortium are investigating opportunities to adapt it to other applications.
‘Alternative cancer treatments to radiotherapy, such as proton-beam therapy, can deliver a higher concentration of radiation, thereby increasing the potential risk to patients due to imprecision in positional accuracy,’ says D’hooge. ‘We’re now also investigating the application of AMPHORA’s droplet technology to proton-beam therapy, which has been the focus of our second key research output, showing very positive results.’