Photoacoustic tomography imaging, or PAT technology, uses laser-generated ultrasound waves to visualise subtle changes in human veins and arteries.
With the ability to identify these changes in less-than-millimetre-scale veins and arteries up to 15mm deep in human tissues, the technology is crucial in identifying early markers of disease in patients.
Since its early development in 2000, PAT has long been heralded as having the potential to revolutionise medical understanding of biological processes and improve the clinical assessment of cancer and other major diseases. It works using the photoacoustic effect, which occurs when materials absorb light and produce sound waves.
PAT scanners work by firing very short laser bursts at biological tissue. Some of this energy is absorbed, depending on the colour of the target, causing a slight increase in heat and pressure that in turn generates a faint ultrasound wave containing information about the tissue.
Despite developing crucial imaging, though, existing PAT technology has been limited by processing capacity. Existing scanners are often too slow to produce high-enough quality 3D images for use by clinicians, particularly as during a PAT scan, patients must be completely motionless. Any slight movement from the patients could cause the images to blur, rendering them clinically useless – until now.
Researchers from University College London (UCL) have developed a new technology that they claim could overcome these limitations: a hand-held scanner that can generate highly detailed 3D photoacoustic images in just seconds.
While older PAT scanners could take over five minutes to capture an image, the UCL team said that their technology is between 100 and 1,000 times faster, reducing that time to a few seconds or less.
“We’ve come a long way with photoacoustic imaging in recent years, but there were still barriers to using it in the clinic. The breakthrough in this study is the acceleration in the time it takes to acquire images,” said Professor Paul Beard, UCL Medical Physics and Biomedical Engineering and the Wellcome/EPSRC Centre for Interventional and Surgical Sciences.
“This speed avoids motion-induced blurring, providing highly-detailed images of a quality that no other scanner can provide. It also means that rather than taking five minutes or longer, images can be acquired in real time, making it possible to visualise dynamic physiological events. These technical advances make the system suitable for clinical use for the first time, allowing us to look at aspects of human biology and disease that we haven’t been able to before.”
Aiming to overcome the issue of speed, then, the UCL research team sought to reduce the time needed to acquire images, by updating both the scanner design and the mathematical principles used to generate the images.
Unlike earlier PAT scanners, which measured the ultrasound waves at more than 10,000 different points over the tissue surface one at a time, this new scanner detects them at multiple points simultaneously, reducing image acquisition time considerably.
The research team also employed similar mathematical principles to those used in digital image compression. This enabled high-quality images to be reconstructed from a few thousand – rather than tens of thousands – of measurements of the ultrasound wave, again speeding up image acquisition.
“The majority of existing scanner technology is based on piezoelectric sensor technology,” devices that can convert various physical forces, including pressure, vibration and temperature, into electrical charges that can be measured, “But its not the most convenient to use in general clinical practice,” said Dr Nam Trung Huynh, Senior Research Fellow from UCL’s Department of Medical Physics and Biomedical Engineering, and who developed the scanner with his colleague Dr Edward Zhang.
“Some of these scanners just have an excitation laser on the side of the ultrasound probe, so it doesn’t give much more information than normal ultrasound imaging can produce. With our technology, we can see microvasculature very clearly.
“It’s a full 3D imaging capability, so it has removed operator dependence. So, for example, ultrasound is a 2D imaging system, and clinicians may look at the image produced differently; with a 3D image you can actually see the true volume, more objectively.”
During the study, the hand-held scanner was used in pre-clinical tests, on ten patients living with type-2 diabetes, rheumatoid arthritis or breast cancer, along with seven healthy volunteers.
In three patients with type-2 diabetes, the research team said, the scanner was able to produce detailed 3D images of the microvasculature in the feet, highlighting deformities and structural changes in the vessels. The scanner was also used to visualise the skin inflammation linked to breast cancer.
For some conditions, like peripheral vascular disease (PVD), a complication of diabetes, early signs of changes in tiny blood vessels indicative of the disease can’t be seen using conventional imaging techniques such as MRI scans.
But with PAT images they can – offering the potential for treatment before the tissue is damaged and to avoid poor wound healing and amputation, the research team said. Similarly, with cancer, tumours often have a high density of small blood vessels that are too small to see with other imaging techniques.
“One of the complications often suffered by people with diabetes is low blood flow in the extremities, such as the feet and lower legs, due to damage to the tiny blood vessels in these areas. But until now we haven’t been able to see exactly what is happening to cause this damage or characterise how it develops,” said Andrew Plumb, Associate Professor of Medical Imaging at UCL, consultant radiologist at UCLH and a senior author of the study.
“In one of our patients, we could see smooth, uniform vessels in the left foot and deformed, squiggly vessels in the same region of the right foot, indicative of problems that may lead to tissue damage in future. Photoacoustic imaging could give us much more detailed information to facilitate early diagnosis, as well as better understand disease progression more generally.”
While the results of the pilot study were undoubtedly positive, and indicate that this technology could be a potential gamechanger for medical practise and understanding, the researchers said that much more extensive testing is needed.
“We need to make sure our findings are valid, test the technology on a bigger patient cohort and design a more comprehensive clinical study. Even further, we need to develop the scanner so it can be used by untrained engineers – doctors and hospital personnel – and ensure that we are extracting the useful information to help aid them,” added Dr Huynh.
“The collaboration between engineers and the medical industry is crucial. We have been collaborating with clinicians since the very early stages, when we were working on animal models – its key to knowing what we should look at, what kind of diseases we should target.”
Currently, the researchers said that their focus is on peripheral vascular disease, oncology, head and neck cancer, arthritis, diabetes and skin inflammation – guided by collaboration with clinicians from University College Hospital and the Royal Free Hospital.
Looking ahead, the research team is of course setting its sights on approval by the Food and Drug Administration (FDA), which Dr Huynh said could take between three to five years.
“For now, we’re pushing to get more funding to work on further applications, and we’re trying to get industry engagement to develop the perfect technology for their use.
“In the future, photoacoustic imaging could be used to detect a cancerous tumour and monitor it relatively easily. It could also be used to help cancer surgeons better distinguish tumour tissue from normal tissue by visualising the blood vessels in the tumour, helping to ensure all of the tumour is removed during surgery and minimising the risk of recurrence. I can envisage lots of ways it will be useful.”
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