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In 1880, fresh from his invention of the telephone, Alexander Bell was experimenting with using light to carry sound (the resulting “photophone” was a precursor to modern day fibre optic communication). He noticed that shining a beam of sunlight on a rubber sheet produced an audible sound — the first demonstration of the photoacoustic effect.
Interest in this phenomenon, which occurs when materials absorb light and produce sound waves, was further pursued by Lord Rayleigh and Wilhelm Röntgen (of X-ray fame) but then lay dormant for over a century. During the last 25 years, physicists and engineers have revisited this effect and harnessed it to develop an imaging technique set to revolutionise how we detect and develop treatments for cancer.
Photoacoustic imaging delivers exquisitely detailed images of biological tissue purely by listening to the sound that light makes. Ultrashort pulses of laser light of a few billionths of a second are directed at the tissue and selectively absorbed, depending on the colour of different constituents of the tissue.
A very slight heating effect (less than one-tenth of a degree) produces an instantaneous but tiny increase in pressure which generates a low-level ultrasound wave which travels to the surface, carrying with it information about the structures within the tissue. The whole process takes place in just a fraction of a second.
And in a particular twist of ingenuity, the ultrasound wave can be detected using light.
Physicists and engineers at University College London, led by Professor Paul Beard, have pioneered a system where a sound wave causes minute changes in thickness of a thin plastic film which can be measured using a highly-tuned laser beam.
The results reveal tissue structures which have never been seen before.
Prof Beard recalls the first time he realised the capabilities of photoacoustic imaging: “Although we had been developing the technique in the laboratory for several years, I was astonished at the incredible level of detail we could see. It seemed quite extraordinary that such a complex cascade of physical interactions could conspire to give such amazing images; it was as if we could listen directly to the colour of the molecules that make up the tissue.”
The images were not only aesthetically pleasing. It was soon discovered they revealed anatomical structures that would be invisible using conventional medical imaging methods and it became clear that the process could have a major potential as a diagnostic tool.
The technology is exciting clinical teams and researchers alike.
Dr Andrew Plumb, consultant radiologist at University College Hospitals is leading the first clinical trials, funded by Cancer Research UK, in head and neck tumours.
“Photoacoustic imaging is providing a level of detail not previously possible in tumour imaging. It will help surgeons identify where the boundaries of a tumour are and lead to less invasive surgery,” he explained. “If conventional CT imaging is the ‘sat nav’ to show where the tumour is, photoacoustic imaging will be the ‘parking’ sensors to provide the fine detail of its margins.”
This detail is also proving to be an important tool in developing therapies to destroy tumours.
A key target for cancer therapies are the blood vessels which supply tumours with the nutrients they need to survive and proliferate. The 3D visualisation of tumour blood vessels made possible by photoacoustic imaging is transforming research into so-called vascular disrupting agents. These drugs selectively attack the rapid growth of blood vessels, effectively putting the tumour under siege by cutting off vital supply lines.
Barbara Pedley, emeritus professor of cancer biology at UCL Cancer Institute, has spent three decades investigating tumour microvasculature. “Photoacoustic imaging is the most exciting technique I’ve seen in my career” she said.
“High resolution images of individual blood vessels are transforming how we track the impact of drug therapies and understand their efficacy in destroying tumours. Being able to image the same tumour at multiple time-points increases accuracy, efficiency and speed of the drug development process.”
Genetic encoding of cell lines to express a form of melanin which makes them visible to photoacoustic imaging is also being used to see cell behaviour and understand how disease evolves and how it can be attacked.
Prof Beard is optimistic about future developments but is also realistic about the need for targeted research funding and commercial partnerships to realise its full potential.
“Translating the technology from the laboratory to the hospital typically requires interdisciplinary teams of engineers, physicists and clinicians to move from the R&D phase into clinical trials and commercial exploitation,” he says.
UCL’s recently established Wellcome/EPSRC Centre for Interventional and Surgical Sciences is providing an ideal environment for the development of photoacoustic imaging and the translation of engineering research to clinical practice, says Prof Beard.
“The time is ripe for commercial investment to bring the technology into routine clinical use.”