Photoacoustic imaging goes for gold

11 Jun 2007

Photoacoustic imaging is an optical technique that can be used to visualize abnormalities in soft tissue. Now, a Netherlands-based research consortium is investigating the possibility of adding gold nanoparticles into the photoacoustic mix in the hope that the work will one day yield a cost-effective breast-cancer detection system, and perhaps even a new type of therapy.

Most optical-imaging techniques work by sending photons into a sample, with reflected or transmitted photons subsequently used to construct an image of optical absorbers that may be hidden inside. Unfortunately, a conventional approach like this is not ideal for studying thick living tissue (because light is strongly scattered by biological matter, leading to poor resolution).

Photoacoustic imaging is not like other optical techniques, though. "We send in photons, but then we measure ultrasound that is produced by the photons that get absorbed," said Srirang Manohar, from the biophysical engineering group at the University of Twente in the Netherlands.

This unusual situation – photons in, ultrasound out – arises because tissue heats up when it absorbs photons. Illuminating absorbing tissue structures with a pulsed laser causes them to change temperature, and as a result they expand. Pressure waves propagate out from the expanding structures, and these can be picked up by an ultrasound transducer. "The advantage of photoacoustics is that you can get imaging based on optical-absorption contrast, but you have resolutions as good as with ultrasound," explained Manohar.

The trouble is that the intrinsic optical contrast of biological tissue may not always be high, which means that conventional photoacoustic imaging is only capable of picking out strongly absorbing structures. The consortium thinks that it can improve the technique, however, with the help of specially designed gold nanoparticles. "We can overcome the problem of low intrinsic contrast by putting strongly light-absorbing particles in the area of interest," Manohar told medicalphysicsweb.

Heart of gold Manohar and colleagues think that gold nanorods should be ideal for this purpose. Gold nanospheres absorb green light very strongly, but to achieve maximum penetration of the laser light into tissue, the researchers need to use near-infrared wavelengths. Thanks to their geometry, however, the nanorods also have a sharp absorption peak in this region of the spectrum. This means that they heat up much more than surrounding tissue components, and therefore emit a stronger photoacoustic signal.

The optical properties are only half the story, however. To form part of a photoacoustic cancer-detection system, the particles have to be tailored so that when they are injected into a patient's bloodstream they preferentially accumulate in the tumour. This can be done by attaching tumour-specific antibodies that will only bind to, say, breast-cancer cells. In this way, the researchers can be sure that an area of high contrast in their images is a breast tumour.

"The idea of this project is to bring three concepts together: photoacoustic imaging, nanoparticles and targeting," said Manohar. Over the next five years, the multidisciplinary team, which is headed by Ton van Leeuwen of the University of Twente, and also comprises researchers from the Erasmus Medical Centre (Rotterdam, the Netherlands) and several industry partners, will be testing the technique in vitro and in small animals to assess its potential as a new method for diagnosing breast cancer.

The fact that photoacoustic imaging is considerably cheaper compared to MRI, also that it doesn't require patients to be subjected to ionizing radiation, makes it an attractive option for patients and clinicians alike.

The researchers will also be investigating whether the method could be used for treating tumours. If the laser–nanoparticle combination can produce a sufficient local temperature rise to induce apoptosis in the surrounding cells, then this could form the basis of a highly targeted non-invasive cancer therapy. "Once we've got the nanoparticles at the disease site we can use them for imaging, but we hope that we can also turn up the light energy and do photothermal therapy," explained Manohar.

However, these applications are still a long way off. Even if the consortium's results are good, it will take many years to obtain approval for using the nanoparticles in people. On the other hand, because the technique is very cost effective compared to other imaging modalities, there are several areas where it might prove very useful, such as animal research and drug discovery.

"We hope that by the end of this project we will have, if nothing else, increased the knowledge base to a very high level, and have really pushed the state of the art forward," concluded Manohar.

• See also Medical imaging goes for gold on nanotechweb.