Jun 4th 2009 The Economist (print edition)
Biomedical technology: A novel scanning technique that combines optics with ultrasound could provide detailed images at greater depths
IF LIGHT passed through objects, rather than bouncing off them, people might now talk to each other on “photophones”. Alexander Graham Bell demonstrated such a device in 1880, transmitting a conversation on a beam of light. Bell’s invention stemmed from his discovery that exposing certain materials to focused, flickering beams of light caused them to emit sound—a phenomenon now known as the photoacoustic effect.
It was the world’s first wireless audio transmission, and Bell regarded the photophone as his most important invention. Sadly its use was impractical before the development of optical fibres, so Bell concentrated instead on his more successful idea, the telephone. But more than a century later the photoacoustic effect is making a comeback, this time transforming the field of biomedical imaging.
A new technique called photoacoustic (or optoacoustic) tomography, which marries optics with ultrasonic imaging, should in theory be able to provide detailed scans comparable to those produced by magnetic-resonance imaging (MRI) or X-ray computerised tomography (CT), but with the cost and convenience of a hand-held scanner. Since the technology can operate at depths of several centimetres, its champions hope that within a few years it will be able to help guide biopsy needles deep within tissue, assist with gastrointestinal endoscopies and measure oxygen levels in vascular and lymph nodes, thereby helping to determine whether tumours are malignant or not. There is even scope to use photoacoustic imaging to monitor brain activity and gene expression within cells.
To create a photoacoustic image, pulses of laser light are shone onto the tissue being scanned. This heats the tissue by a tiny amount—just a few thousandths of a degree—that is perfectly safe, but is enough to cause the cells to expand and contract in response. As they do so, they emit sound waves in the ultrasonic range. An array of sensors placed on the skin picks up these waves, and a computer then uses a process of triangulation to turn the ultrasonic signals into a two- or three-dimensional image of what lies beneath.
The technique works at far greater depths (up to seven centimetres) than other optical-imaging techniques such as confocal microscopy or optical-coherence tomography, which penetrate to depths of only about a millimetre. And because the degree to which a particular wavelength of light is absorbed depends on the type of tissue and, in the case of blood, on whether it is oxygenated or deoxygenated, there is, in effect, a natural contrast agent. This makes the technique superior to ultrasound alone when it comes to picking out detailed features such as veins.
MRI and CT scans are also capable of delivering this kind of detail. But they usually require contrast dyes to be injected into the bloodstream, says Lihong Wang, a photoacoustic researcher at Washington University in St Louis, Missouri. CT scans also involve potentially harmful ionising radiation. And MRI and CT scans are very expensive, using machines that cost millions of dollars and require dedicated staff to operate them. Photoacoustic tomography, by contrast, could eventually be performed using portable hand-held devices, similar to those used for ultrasound scanning. This would allow doctors to diagnose and monitor patients in clinics, and reduce the need to refer them to consultants. “Photoacoustics provides greater access at a much lower cost than these other technologies,” claims Michael Thornton of Endra, a medical-imaging company based in Ann Arbor, Michigan.
Shining a light
A pioneer of the technique in the late 1980s was Alexander Oraevsky, who was based at the Soviet Academy of Sciences in Moscow at the time. He had been evaluating lasers as a means of removing tissue, but in the course of his experiments he realised that his samples were producing ultrasound, and began exploring the potential of this effect for imaging. Since then the technology has come a long way, not least because of the development of nanosecond pulsing lasers. Being able to deliver such brief pulses of energy to the sample being imaged—a nanosecond is a thousand-millionth of a second—has helped improve the resolution of the resulting images. Dr Oraevsky and other researchers have shown that it is possible to image the entire blood-supply system of a mouse, for example, down to a resolution of about half a millimetre.
One of the most promising applications for photoacoustics is in the treatment of cancer. Since blood cells are natural absorbers of light, photoacoustics is particularly good at providing high-contrast images of the formation of blood vessels (angiogenesis) and detecting increased metabolic activity (hypermetabolism), both of which are hallmarks of cancer, notes Dr Wang. Preliminary clinical research is now under way to look at how the technology can be used to monitor the development of breast cancer and identify how far it has progressed.
Even with mammography and ultrasound, the current gold standards for breast-cancer screening, doctors cannot tell if a tumour is malignant or benign without performing an invasive and expensive biopsy. “About eight out of ten patients who undergo a biopsy come back negative,” says Dr Oraevsky, who now works for Fairway Medical Technologies, a company based in Houston, Texas. Photoacoustic tomography could potentially be used to diagnose women in the doctor’s surgery.
One approach being explored by Michael Pashley, head of ultrasound imaging and therapy at Philips Research in Briarcliff Manor, New York, is to develop a hybrid ultrasound scanner that can produce ordinary ultrasound scans as well as photoacoustic images. In theory the two images could even be superimposed, he says. At the moment the work, which is being carried out in collaboration with Dr Wang, is geared towards monitoring the development of breast cancers that have already been diagnosed, says Dr Pashley. But if the technology proves successful, he hopes to move on to using it for the initial diagnosis.
Getting the picture
Although the different absorption characteristics of oxygenated and deoxygenated blood provide an extremely good natural contrast agent, this approach has its limits. So some companies are exploring the use of photoacoustics in conjunction with artificial contrast-agents introduced to the bloodstream. VisualSonics, an ultrasound-imaging company based in Toronto, has been evaluating contrast agents made up of gold nanorods attached to antibodies that bind to specific targets found in cancer cells. Ultrasound is already used to detect such agents but its resolution is sufficient to show only the structure of blood vessels. Dr Wang reckons that if contrast agents that are too small to be picked up by ordinary ultrasound were introduced into a patient’s bloodstream, they could be detected using photoacoustic imaging. Furthermore, it would be possible to see where the contrast agents built up, and hence determine the extent of a tumour. And by creating contrast agents that bind to specific genetic targets, the same technique could be used to monitor gene expression, he suggests.
Room for improvement
Despite its potential and its many advantages over other methods, there are some difficulties with photoacoustic imaging that have not yet been resolved. As light penetrates deeper into tissue, the resulting ultrasonic signal diminishes. This is partly because some of the light has been absorbed by the preceding tissue, but it is also because the laser light is dispersed, diffused and back-scattered. This places limits on just how deeply photoacoustic imaging can delve. In the future it might be possible to go a little deeper, says Dr Wang, but probably not by much. “If light is delivered from both sides of the tissue, ten-centimetre-thick tissue can potentially be imaged,” he says.
Bone tissue represents another obstacle to the technology, but not for the reason you might think. Laser light usually passes easily through bone, but sound does not. The speed at which sound travels through bone is different from the speed at which it travels through soft tissue, and as the ultrasound passes from one medium to the next it is distorted. Air cavities, many of which are found inside the human body, pose a similar problem, says Dr Wang.
Even so, VisualSonics and other companies are keen to explore the use of photoacoustics for neuroimaging. It is not an insurmountable problem, says Dr Wang, who is working on a technique to model the skull so that its effects on the ultrasonic waves can be predicted and eliminated in software, restoring clarity to the signals. If he can get this approach to work, it would further extend the revolutionary potential of photoacoustic imaging in the coming years. Doctors would not merely be able to diagnose cancer in the comfort of their own surgeries—they would be able to perform brain scans, too. A technology that traces its roots to a stillborn 19th-century communications device would have taken another step towards the futuristic dream of the all-purpose hand-held medical tricorder seen in “Star Trek”.
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