04 Apr 2007
Optical coherence tomography (OCT) - a non-invasive interferometric optical imaging technique - currently generates sales in excess of £30 million a year in the ophthalmology market. Most likely that's just for starters, as the technology also offers a vast, and as yet mostly untapped, range of potential applications in areas such as cancer diagnostics, orthopaedics and vascular disease.
A recent meeting organized by the UK's Photonics Knowledge Transfer Network, the British Medical Laser Association and Michelson Diagnostics (an OCT start-up) brought together manufacturers, researchers and users of OCT systems to examine the commercial opportunities in OCT. The brief: to determine how this new medical imaging modality can take a bigger slice of the $100 bn global medical imaging market.
Yet this was not simply a case of vendors looking to push their products into opportune new markets. There's a strong pull from the end-users, notably clinicians gunning to get their hands on an in-vivo OCT system that will deliver minimally invasive, micron-resolution optical imaging.
Feel the need
Hugh Barr, consultant general and gastrointestinal surgeon at the Gloucestershire Royal Hospital in the UK, sees a real need for such a system. He cited the example of the diagnosis and management of oesophageal cancer, explaining that in order to treat this disease in the most effective way, it's important to detect any pre-cancerous (dysplastic) changes as early as possible.
Unfortunately, standard visual endoscopy does not always detect early dysplasia. Screening for degeneration by taking random biopsies every couple of years is not a viable option either. Another obstacle is that inter-observer agreement on the diagnosis is often poor. "The diagnosis of precancer is an opinion. It's very challenging both for us and for the patients," Barr explained.
What's needed, he suggested, is a reliable method of in-vivo diagnosis. "We want in-vivo pathology, where you don't need to take out the tissue to find out what it is," he explained. Such information can be provided by a range of optical techniques, including fluorescence imaging and spectroscopy, elastic scattering, Raman spectroscopy and – of course – OCT.
With this in mind, Barr and his colleagues at Gloucestershire Royal Hospital have recently embarked upon a research programme investigating the use of OCT to examine excised tissue. They will compare scans taken using Michelson Diagnostics' OCT equipment with histology results from the same samples.
The samples being examined include oesophageal tumour tissue removed from the body by surgeons. This procedure requires a delicate balance between removing all of the cancerous tissue and sparing normal tissue. As a result, inadequate local removal of early invasive cancer can sometimes be a problem. OCT imaging should help the clinicians visualize the margins of the excised tumour.
"We use OCT to assess whether we've got all of the tumour out - it's real-time histopathology," Barr explained. Another benefit of OCT is that it provides depth-related information, enabling him to assess whether the cancer is invasive. Of course, the ideal situation – and Barr's ultimate aspiration – would be to use OCT to perform real-time, in-vivo diagnosis, and then to guide the removal of any cancerous or precancerous tissue during the same procedure.
The big goal
If the end-game is non-invasive optical biopsy, is OCT technology ready to deliver? According to Wolfgang Drexler, head of the biomedical imaging group at Cardiff University's school of optometry and vision sciences, OCT doesn't quite match up to conventional histopathology yet. Nevertheless, "it is becoming an extremely important potential adjunct," he said.
To accomplish its ultimate goal, said Drexler, OCT needs to meet a few key criteria. First and foremost, the technology needs to offer as high as possible a resolution, a target that has been sped towards of late with the emergence of low-cost, broad-bandwidth light sources. OCT now offers a resolution of 1-10 μm, which is approximately 100 times better than that of conventional ultrasound.
Another prerequisite for efficient optical biopsy is real-time operation. "With increased resolution, the more you see the better the diagnosis, but the next issue is really speed," said Drexler. This challenge is now being realized with the development of frequency-domain OCT, which emerged in a flurry of publications in 2003.
The first-generation technology, time-domain OCT, used a moving-mirror-based interferometer that was limited by the speed at which the mirror can move. Frequency-domain OCT, on the other hand, has no moving parts in the interferometer. "Instead of moving the mirror, you use interference in frequency or wavelength," Drexler explained.
The use of frequency-domain OCT can ramp the image acquisition speed by up to two orders of magnitude compared with the time-domain technique, without reducing the signal-to-noise ratio. "The efficiency is much higher, which leads to either higher speed or higher signal-to-noise ratio. This is really like CT or MR imaging with microscopic resolution but limited to superficial organ regions," he said.
In vivo OCT imaging requires the development of hand-held probes for surface imaging or fibre-optic-based probes that can fit into the biopsy port of an endoscope. "A lot of endoscope probes have been developed in the last years," said Drexler, noting that research has already been published demonstrating the feasibility of endoscopic OCT in humans.
Drexler also discussed a number of emerging OCT variants that have stemmed from frequency-domain OCT. Combining ultrahigh-resolution OCT with fast data acquisition techniques, for example, enables 3D depth scanning. Other promising areas include polarization-sensitive OCT, which detects changes on a molecular or subcellular basis, and OCT using (exogenous or endogenous) agents to enhance the image contrast.
Finally, Drexler presented the idea of spectroscopic OCT, a technique that can provide depth-resolved functional (metabolic) information while also enhancing the image contrast. By analysing spectral information to determine the wavelength of maximum absorption in different regions of an OCT scan, clinicians could create a map of haemoglobin and oxyhaemoglobin distribution, for example.
With so many OCT variants under development, how near are the manufacturers to releasing advanced clinical instruments onto the market? According to Jon Holmes, chief executive officer of UK-based start-up Michelson Diagnostics, OCT is currently transitioning from a technology looking for applications to one that's looking for where best to do business. "OCT is well-established for use in retinal applications, but commercial applications are now starting to happen in many other areas too."
Holmes cited the exponential rise in the number of papers published on OCT – more than 800 in 2006. While over half of these publications discussed ophthalmic applications, other key areas of interest include the use of OCT to study cancer and heart disease, as well as dental and neural applications.
"Areas where the research is being done give some indication of which areas are approaching commercial interest," said Holmes. He also pointed out the large number of patents being filed in OCT – around 90 last year. "Clearly there's a lot of activity. This area is taking off."
As for vendors that are already active in the OCT arena, Holmes says that there are now 19 companies offering OCT-related products (11 in North America, seven in Europe and one in Japan). What's more, only one third of these are focusing on ophthalmics, with other target areas including vascular, cancer and dental applications.
"Six companies are selling OCT systems for clinical retinal applications, one is making OCT systems for clinical cancer applications and five have OCT products that are not cleared for clinical use, but could be used for clinical research," Holmes explained. "The other companies have not yet announced a product or made clear their intentions, beyond that they are developing or licensing OCT technology."
Holmes reckons that the development of frequency-domain OCT boosted the number of companies in the field. "The number has shot up in the last couple of years. Last year, another seven companies came out of the woodwork and I'm told there are a large number of others under the radar."
But its not just the systems vendors that stand to benefit from the increasing uptake of OCT. Holmes predicts some big market opportunities out there for suppliers of components such as fibre-optic couplers, light sources and detectors, software, PACS interfaces, PCs and line cards. In-vivo applications open up an additional area of opportunity for manufacturers of endoscopes, optical probes, scanning devices and disposable covers.
In particular, Holmes cited the need for advanced light sources. "It's the light source that drives the capabilities of OCT equipment, so there's a tremendous opportunity for suppliers of lasers and superluminescent LEDs to push products into the supply chain," he noted. "We've hit the commercial tipping point now. We need to get onto that tidal wave of activity that's started."