Bouncing light off biological tissue has become a mainstay of modern medical imaging and microscopy. But most existing techniques are limited in their ability to penetrate the body by more than just a few millimetres. However, a technique called photoacoustics, a marriage of optical and ultrasonic technologies, could be about to change the situation.

The idea behind photoacoustics, which is also known as optoacoustics, is simple: use light to stimulate interior tissue so that it gives off acoustic waves in the ultrasonic range. These waves can be then be detected using wide-band ultrasonic transducers and used to build up high-resolution images of subsurface tissue structure (Fig. 1).

“We want to reach what’s called super depth,” says Lihong Wang, at Washington University in St Louis, Missouri, USA, and one of the most active researchers
in the field of photoacoustics. The hope, he says, is that by using photoacoustics clinicians will be able to carry out safe, high resolution three-dimensional imaging and microscopy at depths of centimetres rather than millimetres, and without the use of potentially harmful ionizing radiation, such as X-rays.

In addition, photoacoustics should open up new opportunities for diagnosing, monitoring and treating diseases. For example, it could help to guide biopsy needles deep beneath the skin, assist endoscopic techniques for diagnosing gastrointestinal cancer, measure oxygen saturation levels in haemoglobin and study subsurface vascular and lymph nodes to visualize and quantify malignant tumours. It can even be used to probe the brain and to monitor gene expression.

Although the latest photoacoustic apparatus make use of state-of-the-art laser technology, the first examples of using light to stimulate acoustic waves date back to the nineteenth century. As far back as 1880, Alexander Graham Bell discovered that it was possible to make a thin disk emit sound when exposed to a beam of pulsing sunlight. Initially Bell sought to use the effect as a means of communication, converting sound into the light, sending it through free space and then converting it back into sound again. “He called it the photophone,” says Wang. Needless to say, his other idea, the telephone, proved a more popular invention, not least because it didn’t have issues with line-of-sight.

After that, photoacoustics was largely ignored until the 1970s when the development and availability of lasers triggered an interest in its use for nondestructive testing. But it wasn’t until the late 1980s that its medical applications started to become apparent. Initially interested in the effects of laser absorption on tissue, Alexander Oraevsky, then at the USSR Academy of Sciences, Moscow, started to look at how the interaction could
be used for imaging — a technique he dubbed optoacoustics.

His initial experiments showed that cells produced pulses of ultrasound in response to the pulses of laser light. Oraevsky left Moscow in 1991 to continue his work at the University of Texas, and has since become vice president of research and development with Fairway Medical Technologies, in Houston, Texas.

Fairway, with its commercialization partner, Seno Medical Instruments of San Antonio, Texas, is one of a handful of companies now developing the technology for real-life applications.

Oraevsky explains that as light passes through the tissue certain wavelengths are preferentially absorbed by cells. The absorbed energy causes a very small amount of heating that makes the cell swell. This so-called thermoelastic expansion produces acoustic pressure waves that can then be detected by
placing ultrasonic transducers on the skin.

But to get really useful high-resolution imagery requires lasers capable of emitting nanosecond pulses, says Oraevsky. “You have to use a short enough pulse to ensure that the energy is delivered before it can escape as pressure,” he says. Wang agrees. Nanosecond pulsing, along with lasers capable of high spectral purity, is really necessary if you want to obtain very high spatial resolution, says Wang.

What makes photoacoustics different from other three-dimensional imaging techniques — such as optical coherence tomography (OCT), two-photon microscopy and confocal microscopy (see Table 1) — is that it relies on light being absorbed rather scattered. One of the reasons that these other techniques are so limited in how deep they can delve is that back-scattered light is diffused by the tissue, making it difficult to
detect in any meaningful way.

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