For many people, the word ‘ultrasound’ conjures up images of nurses and doctors showing grainy footage of foetuses to pregnant women. Although imaging unborn babies is undoubtedly important, the technology has an incredible array of clinical uses outside the obstetrician’s office.
Ultrasound technologies perform vital diagnostic and therapeutic functions in the treatment of cancer, and the equipment is relatively mobile and low-cost. Developing advanced ultrasound techniques is therefore an incredibly attractive prospect. In the treatment of cancer, ultrasound is used to give a clearer picture for surgeons before they operate and can be used to guide radiotherapy. Using ultrasound to pinpoint a tumour’s location and track its movement allows the radiation to be targeted more effectively, decreasing damage to healthy tissue.
There are even experimental techniques where ultrasound is used to actually treat cancers, called high-intensity focused ultrasound (HIFU), although these are still at a very early-stage. We may see exciting treatments coming from the technology in the future, but right now ultrasound imaging is where we’re seeing developments move into the clinic.
Researchers at The Institute of Cancer Research, London have been among the pioneers in this field since the 1960s and continue to make exciting developments. Imaging is a vital weapon in the fight against cancer, and a dedicated Centre for Cancer Imaging is currently being built at The Institute of Cancer Research (ICR). Dr Jeff Bamber has led the ICR ultrasound and optical imaging team since 1986, and is currently developing and investigating uses of a range of ultrasound technologies with great clinical potential.
We can now monitor the blood vessel structures of tumours thanks to rapid advances in photoacoustic imaging, which uses laser light to generate pulses of sound at a target location. The laser causes tissue at the target location to heat and expand, and thus emit sound waves which can be detected by ultrasonic microphones. This builds up an image based on optical absorption, which can clearly show blood vessels since the dark colour of blood causes it to absorb more light than surrounding tissue.
Yet even the latest imaging technologies are always open to improvement, and it can be difficult for light to penetrate many layers of tissue. Sound emitted from strong light absorption near the surface can bounce around in the tissue, to return later and be confused with the weak signals that we need from deeper tissues. These confusing signals are known as clutter, and limit the useful imaging depth. ‘We are currently working on a method to reduce clutter in the imaging process,’ says Dr Bamber. ‘We hope that it will enable us to see clear images much further into the body.’
Photoacoustic techniques can also be used to image and measure aspects of the molecular composition of tissues and fluids, and Bamber’s team have developed both laboratory measurement and clinical imaging devices based on this principle.
‘For use in the clinic, our system employs a modified conventional ultrasound scanner,’ explains Dr Bamber. ‘We illuminate blood with a laser that can be tuned to different colours and measure the resulting ultrasound waves for each colour. This shows us where and when the blood is oxygenated, as well as how much blood there is.
‘This is crucial for planning cancer treatment but is currently only available from multi-million pound MRI or PET scanners. The photoacoustic method could provide this information on a much finer scale and enable, in a research context, the study of changes in local oxygen level which as yet are poorly understood.’
As well as detecting levels of molecules naturally found in blood or tissue, such as the deoxygenated and oxygenated forms of haemoglobin, or melanin (important in skin cancer), photoacoustic imaging can also be used to look for intravenously injected contrast agents that are targeted to specific biomarkers.
‘This whole field is currently in a phase of rapid discovery and development of targeted contrast agents with a trend towards the future that is not dissimilar to the way that PET is used,’ says Bamber. ‘Furthermore, it is being found that many of the labelled injectables already employed for preclinical fluorescence imaging are also useful for photoacoustic imaging, enabling, for example, the images to show whether a drug has killed cancer cells.’
Bamber’s team are also investigating the use of gold ‘nanorods’ to image objects of interest on a molecular level. These tiny cylinders of gold, no more than 50nm in length, can be bound to molecular targets such as those on cancer cells using specific antibodies.
‘Gold particles of this size are perfect for photoacoustic imaging as they absorb the laser light so strongly, are readily synthesised and the chemistry for directing them to specific targets is understood’ says Dr Bamber. ‘The resulting vibrations are easily detected by any ultrasonic receiver. So far it looks as if “nanogold” will eventually be developed into an excellent medical imaging agent.’
Photoacoustic imaging isn’t the only innovative ultrasound technology being pioneered at the ICR. Elastography is an emerging field of ultrasound which can be used to measure the elasticity, or stiffness, of tissue.
‘We are currently undertaking trials to see if the stiffness of a tumour is an indicator for its response to treatment,’ explains Bamber. ‘It takes a long time for a tumour to shrink after successful treatment, and until it does we cannot tell if the treatment is working.’
However, it is possible that a tumour’s stiffness will change before it starts to shrink, which could give an early indication of a treatment’s effectiveness. ‘It is still too early to say whether tumour stiffness is a reliable indicator for response to treatment,’ says Bamber, ‘Nevertheless, the work shows that elastography can be a powerful and unique diagnostic tool.’
By applying pressure to tissue and using ultrasound to observe the resulting motion, it is possible to create two- or three-dimensional images showing elasticity, ‘elastograms’. Bamber is a leading expert in the field, and recently was the primary author of a set of European guidelines on how best to use elastography techniques.
‘ Elastography has the potential to provide images with much greater contrast between different types of tissue than traditional ultrasound and provide additional information not available in any other way,’ says Bamber. ‘Since forces are transmitted by the structural matrix, the “scaffolding” of tissue, elastography can give us a clear picture of what that structure is like. In the context of cancer, this information may be related to how aggressive a tumour is and how it will respond to certain treatments.’