Light microscope (Credit: Jan Chlebik for the ICR 2011)
Take 1: photoacoustic imaging!
Physics is cool, as everyone knows, but it becomes really exciting when we apply it to biological problems in biology.
The photoacoustic (aka optoacoustic) effect has been known in physics since 1880 and was discovered by Alexander Graham Bell, the famous telecommunication scientist and polymath, while exploring techniques that could be used for remote communication.
If you shine a pulse of light into an object, for example using a laser, the object absorbs the optical energy, is transiently heated, and tries to expand because of the corresponding transient increase in pressure. The transient increase in pressure then acts as an internal source of sound – the light-absorbing object produces its own ultrasound acoustic signal.
By measuring the amplitude of this acoustic signal and its time of arrival after pulsing the light, it is possible to reconstruct an image of the object’s optical absorption properties – using ultrasound!
If we illuminate biological tissue – for example, in a tumour – with a pulsed laser, using wavelengths in the near infra-red range that can penetrate a few centimetres, we can learn a lot about the tissue’s molecular composition, in a completely non-invasive manner, simply because different molecules absorb light differently.
We can measure, for example, the proportions of molecules of oxy- and deoxy-haemoglobin, melanin, water and lipids. All of this is possible without any need to inject contrast agents (radioactive or not). Once again, physics is at its best while interacting with biology!
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Take 2: What photoacoustic imaging has done for me
Researchers in the ICR’s Ultrasound and Optical Imaging Team have been studying and developing photoacoustic imaging for more than a decade. I used the technology in my PhD to help me image blood oxygenation – calculating the proportion of oxygenated and deoxygenated haemoglobin – deep within tissue.
Why did I need to measure this? I desperately needed a technique that allowed me to infer where hypoxia, or areas with low oxygen concentration, were in tumours.
Hypoxia is a common tumoural microenvironmental phenomenon, with low oxygen concentration linked strongly with greater tumour aggressiveness, and worse outcome for patients.
In the course of my PhD, I wanted to investigate how to overcome the problem that hypoxia causes for treating tumours with radiotherapy. Hypoxic cells tend to be more resistant to radiation, either not shrinking in response to the treatment or returning a few months later.
Combining photoacoustic imaging with another emerging technology of which the ICR is a global pioneer – high intensity focused ultrasound (HIFU) – I aimed to kill cells in hypoxic regions of tumours in mice.
My project was possible thanks to an EPSRC grant that allowed us to purchase a commercial whole-body mouse photoacoustic imaging system and a small animal radiation research platform.
In combination these systems provided me with the anatomical and functional information I needed to relate the tumour properties to the radiation treatments given.
Take 3: So where is photoacoustic imaging heading?
Photoacoustic imaging is still not yet used in routine clinical practice, but in the future could prove to be a faster and cheaper modality, with higher spatial resolution, than other alternatives like Positron Emission Tomography and Magnetic Resonance Imaging.
Dr Anant Shah, from the Ultrasound and Optical Imaging Team at the ICR, is developing photoacoustic imaging for use in cancer treatment, and recently played a leading role in an important study that established its ability to track the response of melanoma cells to treatment. Dr Shah explains:
“In the last decade, photoacoustic imaging has witnessed unprecedented growth in its preclinical usage and has also advanced towards first-in-human clinical trials. With increasing adoption of the imaging technique, medical companies like Canon, iThera, Fuji-Film VisualSonics and many more, are prudently exploring the market by manufacturing optoacoustic-ultrasound imaging scanners.
“Photoacoustic imaging holds great promise in medical imaging in the years to come, with a potential for incorporating functional and molecular imaging within a conventional ultrasound examination.
“It has potential advantages over other imaging methods of examination convenience, reduced cost, rapid examination, repeatability, high imaging frame rate, high resolution and the ability to easily integrate the result in a multivariate approach with other ultrasound modalities”.
It was a great experience to learn and help to develop this cutting-edge imaging modality, here at the ICR. Hopefully, the Institute will lead this technique into clinical practice and implement it in order to improve radiotherapy outcome.
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