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The evolution of imaging: Seeing deeper and clearer

December 11 2013

Clinicians and scientists on both sides of the Atlantic are collaborating to push imaging technologies forward in order to better detect and diagnose eye diseases. OT’s Ryan O’Hare reports 

"This is the best one in the world.” The confident words of Michel Michaelides, a consultant and senior lecturer, based at Moorfields Eye Hospital and UCL Institute of Ophthalmology in London, describing the culmination of years of collaborative work between UK and US researchers, a new ophthalmic imaging device at the hospital which has vast potential for imaging the microscopic landscape of the inner eye.

“I think few people would argue that this is [not] the best device in the world in terms of image quality and range of capabilities and the only one like it is the one in Alfredo Dubra and Joseph Carroll’s lab,” said Mr Michaelides. Professor Dubra is a world leader in the field and one of the collaborators based at the Medical College of Wisconsin in the US. Along with fellow Wisconsin Professor Joseph Caroll, he built the technology: The Adaptive Optics Scanning Light Ophthalmoscope, or AOSLO for short.

Over 50 patients have already been scanned by the device at Moorfields, which reveals the structure of the back of the eye at a level of detail not previously possible with standard Fluorescein Angiography (FA) or Optical Coherence Tomography (OCT). Not only does it offer unparalleled resolution of the eye’s extensive network of microscopic blood vessels, it can discriminate the separate layers of the retina, and even the cells which make them up.

“It allows us to visualise the individual cells of the retina directly, in vivo, in real time,” explained Mr Michaelides. “It provides a level of resolution that could only previously be obtained post-mortem, from [cadaverised] tissues. The images we get by using this technology are truly fantastic.”

[The figure above shows is a composite of an SD-OCT image of a diseased retina taken (top image), with the images taken using AOSLO showing individual cone cells (bottom). Image courtesy of UCL/Moorfields Hospital London]

A universe within

The technology which is the foundation of the AOSLO, adaptive optics (AO), was originally developed by astronomers looking at objects light years away in space. Although ophthalmologists and astronomers may make strange bedfellows, they faced a similar issue. As light passes from one medium to another, such as from the vacuum of space to the Earth’s atmosphere, the waves can become distorted. The same is true of light passing through different areas of the eye, such as from the lens to the vitreous humour. The result of this wavefront distortion is a lower resolution image.

To cancel out this effect, astronomers used a series of lenses and mirrors to correct for the distortions and to focus the scattered light waves back into a straight wavefront – meaning a much higher resolution of image. Professor Dubra and colleagues combined AO with an ophthalmoscope to increase its imaging capabilities and improve resolution of images of the eye. They have since built a handful of machines in several hospitals and institutions.

Much like corrective eyewear can allow a patient to suddenly discriminate the characters of fine newspaper print, AO brings the minute detail of images into sharp focus, offering clarity of the branching networks of the microvasculature, photoreceptors and other key structures previously seen as a blur.

Implications

In order to bring the AOSLO to London, Mr Michaelides and the team at Moorfields and UCL Institute of Ophthalmology acquired a grant of £250,000 from the Wellcome Trust to build the machine. They then raised an additional £100,000 through the Moorfields Eye Charity to further develop its capacity and capabilities, including the ability to visualise the retinal pigment epithelial layer and microvasculature at the back of the eye.

There is palpable excitement from those involved with the project. “It really does have potential for all retinal disease,” explained Michaelides. “We are in an ideal place in that we have an unparalleled patient resource. The position we are in at Moorfields is unrivalled.”

The hope for the AOSLO is that it will lead to earlier disease detection and provide better insight into disease pathogenesis. Mr Michaelides highlights inherited retinal disease and diabetic retinopathy, and even various neuro-degenerative conditions for which there is no treatment, as areas in which there is potential for impact. He also highlighted the scope for the tool to work within macular degeneration, in order to “help tease out the different sub-types of the disease.”

It will also add to the existing arsenal of diagnostic tools for clinical trials, allowing clinicians to identify novel targets for treatment and to more sensitively and rapidly detect effects of any treatments being trialled. Inherited retinal diseases are high on the list of therapeutic targets for the team. The ability to peer into the eye with greater clarity means more options for gene therapy for those with genetic conditions. Such high resolution imaging could help identify patients most likely to benefit  from gene replacement therapy – a modified virus can be used to deliver functioning replacement copies of the gene to the retina.

Looking to the future

One challenge faced by the scientists and clinicians alike is the vast amount of data produced by this method, so the demands for analytical computing power must be addressed. “In one hour of imaging, you get around 10 hours of data to process, so actually the challenges are to process that data in an efficient way,” Mr Michaelides explained.

This aside, there may even be potential to use this type of technology as a diagnostic tool to detect changes happening at the very heart of the central nervous system. “It allows a window to the brain, so there is potential for looking at early signs of disease for some of these neurological disorders, like Alzheimer’s and Parkinson’s disease,” he said, adding: “Adaptive optics could potentially allow us to do that.”

“We are part of a collaborative network of researchers,” emphasised Michaelides, “so we are working very hard as a team to try and take all of these ambitions forward.”

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