Swinburne University of Technology - Melbourne Australia

Small-scale technology with large-scale benefits

Story by Dr Whitney Macdonald

Early detection has become a key to survival for cancer patients, but one of the most promising technologies for this is unfortunately a massive microscope that takes up two square metres of floor space and costs $1 million, making it impractical for use in routine diagnostics.

To make this important medical tool more accessible, a team under Professor Min Gu at the Centre for Micro-Photonics at Swinburne University of Technology has found a way to, in effect, ‘shrink’ the two-photon fluorescence microscope.

The team is working to refine the technology and turn the tool into a portable unit, taking it from a technology confined mostly to biological research laboratories and turning it into a powerful diagnostic tool compatible with day surgery.

Developed in 1990, the two-photon fluorescence microscope creates high-resolution, three-dimensional images from deep within a tissue sample by using ultra-short, pulsed near-infrared laser to induce what is called two-photon excitation. This is a laser light that enables deep penetration of the tissue and three-dimensional imaging without damaging the cells.

There are high hopes this tool will greatly improve doctors’ ability to detect early stage cancer. It is a technological development that researchers say could improve survival rates for stomach cancer patients from 20 per cent to 95 per cent.

The development by Professor Gu’s team to refine the portability of two-photon microscopy makes the technology more accessible in clinical medicine, and opens the door to more effective disease diagnostics, including access to gastrointestinal cancers. These types of cancers are currently diagnosed using endoscopy – that is, insertion of a small illuminated camera into the organ – to assist in taking biopsies of the affected area.

Professor Gu says the most important advantage of two-photon microscopy is the deep penetration through tissue. "So there could be a very attractive opportunity for medical applications if we can make the system smaller and more portable and combine it with an endoscope to achieve in vivo imaging," he says.

Subtle changes that occur early when healthy cells transform into cancerous cells are often not visible without a microscope, making it difficult for physicians to accurately target a biopsy to a precancerous region.

Scientists all over the world have been part of the race to develop a small, portable, endoscopic two-photon microscope, and Professor Gu’s team has reached the finish line. The team’s results, showcased in the ‘hot topics’ section of the premier international optics conference in 2007, show that it is possible to miniaturise the unit without losing resolution or signal strength.

"The main challenges in making a portable, two-photon endoscope are the efficient delivery of both the excitation beam and the nonlinear optical signals, achieving flexibility and compactness of the probe, and the miniaturisation of its laser-scanning mechanisms," Professor Gu says.

The team’s novel device uses a special kind of fibre optics, called a double-clad photonic crystal fibre coupler, as well as a microelectromechanical mirror to retain the properties of traditional two-photon microscopy, yet with the compactness and flexibility required for a diagnostic endoscope.

To further develop this portable technology and take it to the clinical level, Professor Gu’s research team has been awarded a three-year Australian Research Council Discovery Grant. This grant, which provides more than half a million dollars in funding, is in collaboration with Dr Alex Boussioutas, a senior lecturer at the University of Melbourne and gastroenterologist affiliated with the Peter MacCallum Cancer Centre and the Western Hospital.

Dr Boussioutas, who is testing the ability of the portable endoscopic two-photon microscope to detect precancerous changes in the gastrointestinal tract of mice, says the power of this technology lies in its ability to specifically target biopsies to tissue regions containing early precancerous lesions.

The sheer size of the gastrointestinal tract further decreases the chance of targeting cancerous cells through random biopsy employed during screening. By combining endoscopy with the three-dimensional imaging ability of two-photon microscopy, doctors may be able to see mucosal changes at the cellular level and specifically target these areas for biopsy, providing a chance for early detection of gastric cancer, when treatment provides better long-term survival.

"We are currently working to detect individuals at risk of developing cancer before they get their cancer," Dr Boussioutas says. "The idea is that if patients do progress, then we watch them very closely. Unfortunately, there is currently no good way to watch very closely unless you can target your biopsies accurately. This technology basically adds that missing link by allowing targeted biopsies."

For cancers of the gastrointestinal tract, there are certain conditions that are known to be precancerous stages in many cases. For instance, Barrett’s oesophagus is a precancerous condition that requires diagnosis through microscopic examination of biopsies.

People with Barrett’s oesophagus have a 30 to 40 times greater risk of developing cancer of the oesophagus compared with the healthy population. This risk may be decreased by regularly monitoring the precancerous cells with biopsies. Dr Boussioutas says that the two-photon endoscopy would be particularly useful in monitoring these patients.

"Once we’ve identified people who may progress to cancer, the question is what are we going to do about it? The aim would be to offer a prevention strategy incorporating treatment of precancerous lesions to halt progression to cancer, as well as offering a test enabling identification of these cancers at an early stage. We know that in the stomach, doing standard white-light endoscopy is not good for diagnosing early or premalignant lesions. So that’s why this sort of technology is just ideal for diagnosing these conditions."

Portable two-photon endoscopy applications are not limited to gastrointestinal cancers, but are also expected to include skin cancer, surgical endoscopy, and stem cell therapy.

One in three Australians will be affected by cancer at some point in their lifetime. With the prototype of the portable unit expected to be completed before the end of 2008, and plans for the clinical studies of this technology expected to progress to humans before 2010, it is hoped that the cancer toll on society will be reduced.