Sharper focus

Equipment that displays sharp-focus, high-resolution images during endoscopies has been shown to provide diagnostics so accurate it reduces the need for biopsies.

The Confocal Endomicroscope was jointly developed by Pentax and Australia-based Optiscan Imaging for use in gastrointestinal tract examinations. Typical uses include surveillance for neoplastic change, where normal cells change into tumour cells, and diagnosis of conditions difficult to confirm by regular endoscopic examination and random biopsy technique.

In confocal microscopy, a point of illumination is projected over a specimen and the reflected light is screened to eliminate out-of-focus information. It has a controllable depth of field, giving the ability to collect serial optical sections from thick specimens.

The technique shows individual cells up to 250 micrometres below the surface of the gut wall mucosa at detail equivalent to examination under a microscope. This allows in vivo cellular analysis to guide accurately targeted biopsies.

Optiscan imaging created a partnership with Pentax in 2002 to develop the miniaturisation required for flexible endoscopy. Optiscan designs and manufactures the confocal components, including the scanner, control electronics, laser illumination and the software. Pentax manufactures the scanner lens and integrates the scanner in to the endomicroscope.

Peter Delaney, director of technology and founder of Optiscan, said a number of technologies were converged. ‘The original innovation was the use of a specialised optical fibre element acting as both the illumination and detection pinhole in a confocal microscope. Previously, bench-top confocal microscopes were large and used physical pinholes to achieve optical sectioning of thick tissue.

‘To take advantage of the fibre, miniaturised scan mechanisms had to be invented and a means of controlling the depth of imaging in the tissue had to be highly miniaturised. We solved this using shape memory alloy materials to achieve a tiny form factor with precise control. These came with a multi-element, tiny objective lens designed jointly by Pentax and Optiscan.’

Because of the rigorous safety standards demanded for medical devices, even prototypes were designed like a final product. Pentax brought the full functionality of a conventional endoscope to prototypes to produce versions for use in clinical environments.

The first UK users were Dr Paul Hurlstone at the Royal Hallamshire Hospital and Dr Mike Thompson at the Sheffield Children’s Hospital.

Thompson, a leader in UK paediatric endoscopy, started testing the equipment in parallel with regular techniques six months ago and says it has already proven a great success. ‘For the first time we’ve been able to do colonoscopies on children and not have to take biopsies,’ he said. ‘Although we currently still have to take samples as it’s a comparative study, potentially you’ll be able to do an examination and not have to take pieces of tissue away from the lining of the patient’s bowel.’

The main adult application will be in diagnosing cancer but the technique can be used for all gastrointestinal indications in paediatrics.

In addition to increased accuracy, the technique could make identification of a condition significantly faster. ‘You can identify a condition without having to take a bit of tissue, wait for the lab to analyse it and then have a look at it under the microscope, which takes around five days,’ said Thompson. ‘It helps to make an immediate diagnosis and if you do need to take a biopsy, it also helps you identify where would be the most potentially useful area to take it from.’

Although Pentax’s endomicroscope is more expensive to buy than current equipment, it could save money in use. ‘Aside from the safety issue, the biopsies that we take are quite expensive,’ said Thompson. ‘If you can avoid taking them, that’s an additional financial saving advantage. We spend upwards of £400,000 a year on biopsies on children just at this one centre, so the potential cost saving is enormous.’

He believes the technology will continue to evolve. ‘I think we’re likely to see smaller scopes which are easier to use by mouth. Current scope size prevents us using it in really small children under the age of about a year.’

Delaney sees the Confocal Endomicroscope going where ultra-high resolution imaging has never been before, and making it more automated for applications that are now established and well understood. ‘Molecular targeted imaging also looms large as a major application area,’ he said.