The field of medical research is enjoying a golden age with cross-disciplinary collaboration at its core. Computer scientists have introduced ideas like data analytics and the internet of things (IoT), which, at its simplest level, allows patients’ vitals to be tracked and analysed remotely by their doctor. The nanoscience branch of physics has shown revolutionary potential, helping to create highly targeted delivery mechanisms and accurate early diagnosis tests. The past couple of years have seen the growing influence of another, perhaps more surprising, discipline: astrophysics.
In September 2016, a team of astrophysicists at the University of Sussex began applying statistical techniques used to catalogue galaxies to the subject of dementia. It embarked on the analysis of 96,000 GP records to try to identify common early indicators of the disease. And November of that year saw the publication of ‘Gamma Cameras for Interventional and Intraoperative Imaging’, which outlines a new technology set to sprinkle some space dust on the world of medical imaging.
Brought down to earth
Professor John Lees works at the University of Leicester’s Department of Physics and Astronomy, where he specialises in the development of imaging systems for spacecraft. He became interested in how his work with advanced astronomical sensors could be applied to life sciences and, in 1999, established the Bioimaging Unit that has since generated five patents, and attracted £3 million in research and commercial funding. Around ten years ago, he and a colleague had a chance encounter with a doctor from London’s famous Royal Marsden Hospital, a specialist cancer treatment facility. They asked what kind of new ideas would make a difference in the clinical environment and a compact gamma camera came top of the list.
“A patient has to get to the medical department then has to get injected and go on the machine, and, for some people, that is quite difficult,” Lees says. “Maybe they’re not well enough to move, or they find some of these big static machines quite intimidating or claustrophobic. The big machines are great because they are whole-body scanners, but they don’t give you the high detail you want for some applications. And, of course, they’re expensive and they’re not portable so you can’t take them to the bedside – you have to take the patient to them every time.”
Lees began looking at gamma imaging instruments his team had designed for satellites, and saw their potential in the operating theatre and at the patient’s bedside. The big challenge was how to go about miniaturising them and adapting them for such a different environment, where usability and safety are paramount. After ten years of research and development, funded by the Science and Technology Facilities Council’s (STFC) Challenge-Led Applied Systems Programme (CLASP), the team now has a safe, compact gamma-ray camera with a notable edge over comparable technologies developed over the same period.
Gamma images are often messy and imprecise – “blobs in space” as Lees calls them – which is a problem when it comes to the smaller parts of the body that a handheld camera would most likely be used for. His team’s compact gamma camera is therefore combined with an optical camera, allowing medical practitioners to photograph in either mode but also produce fused image output in which one overlays the other. This allows the operator to locate the gamma readings with far greater precision than with the gamma reading alone or with other forms of hybrid.
“If you’re looking at a patient’s thyroid, neck or whatever it might be, you can then match the gamma frequencies coming from the inside of the patient to the outside, to their anatomy,” Lees explains. “It’s a nice combination there, and we are quite convinced that our technology from that point of view is fairly unique. A surgeon might want to open up a patient because they know there’s a tumour 2–3cm below the surface, but they obviously can’t see it. If we inject it with a radioisotope and it binds to the tumour, he can image it and operate right above the particular spot, and he knows he can go down the minimum distance before he finds the tumour.”
In September 2014, the results of a test were presented at the tenth International Conference on Positon Detectors at the University of Surrey. The team first tested the camera on a lymphatic vessel phantom then on real-life patients undergoing a nuclear lacrimal drainage scan, a non-invasive study that applies a low dose of radiation to the eye to assess the performance of the tear duct. The paper concluded that “the clinical advantages of fusing the gamma image to the optical image are clear”, and “diagnosis, surgical investigation and the visualisation of drug delivery” are some of the areas where it could prove effective.
In January 2016, the paper investigation of an small-field-of-view (SFOV) hybrid gamma camera for thyroid imaging was published in the Physica Medica journal. It compared the performance of a hybrid compact gamma camera with a traditional large-field-of-view system in imaging a selection of thyroid phantoms of different shapes and configurations. The paper also presented the first clinical case of a patient undergoing thyroid imaging with the new camera.
The studies found that the lower sensitivity of the hybrid camera did have a detrimental effect on image quality, yet the contrast of its images outstripped that of the large-field-of-view (LFOV) camera for certain images, “particularly when a high-resolution pinhole collimator was used”. The paper concluded that “HCGC [hybrid gamma camera] has been shown to be suitable for clinical thyroid imaging and was comparable to LFOV systems in terms of image contrast”, and “future development of the energy response of the HCGC is expected to further improve image detectability.”
Adaptability challenge
The path from the satellite to the hospital bedside has been a long one. In space, the camera operates in a vacuum; the only real considerations are its weight and the quality of image it produces. In the clinical environment, the device has to be light enough for handheld use yet well shielded, in the interests of patient protection. Lead is typically used for shielding, yet hospitals won’t allow it to be used unless it’s cased in plastic, adding to the weight/shielding conundrum. The team eventually settled for 3mm of tungsten shielding around the camera head, sealed in a ‘non-toxic plastic enclosure’ for the sake of thermal and electrical isolation.
Coming up with the final design involved a lot of end-user consultation, another requirement that is somewhat novel for a team of astrophysicists. Surgeons tend to be wary of new technology at the best of times, so it took some time to help them understand the possible benefits of the project. To make this process as easy as possible, Lees would recommend that anyone else making the move into medical device design bring in a medical physicist, someone who understands clinical application and can give a quick ‘thumbs up’ or ‘thumbs down’ to any proposals.
“Surgeons don’t want to spend any time at all manipulating the images or changing the contrast,” Lees says. “They want to see an image that means something to them clinically so they can make a quick decision. That’s another area that we found really interesting. Fortunately, we’ve been working with one of the academics in medical physics from Queen’s Medical Centre, in Nottingham; in particular, Alan Perkins. He’s been working with physicians for a long time. Having someone you can bounce ideas off of is a huge help.”
Now that the technology is in place and the first book has been published outlining this new area of imaging, the goal is gaining European regulatory approval (CE marking) for the SFOV gamma camera and optical imaging system. The researchers from the universities of Leicester and Nottingham have already formed a company, Gamma Technologies, which has raised £250,000 of first-round venture-capital funding, also courtesy of CLASP, which offers grants for projects in the areas of energy storage, nuclear energy, future energy grids, energy materials, and sensing and monitoring.
“Hopefully, we’ll continue to refine the technology and find funding, which is, of course, an ongoing issue,” Lees says. “And if we get CE marking in the UK that opens up the door to all of Europe and the next big jump would be to the US for FDA approval. I’m just looking to the next variation on what we can do. I can see potential applications in a number of areas.”
Gamma science
Gamma cameras map the functions and processes of the human body. A tracer is introduced into the body that emits a molecule marked with a gamma-emitting radioisotope. These, in turn, pass through the skin where they are picked up by the camera. The camera contains a collimator, a series of lead-lined hexagonal tubes that absorb non-parallel rays while funnelling parallel rays through to a scintillator, which re-emits the gamma rays as tiny sparks of light. These sparks then go through a series of photomultiplier tubes to boost the electronic signal, before appearing as a multicoloured image on a computer screen.
