Your cells, now in 3D

18 June 2020:

There’s been an explosion in the use of endoscopes in medical procedures over the past 30 years, from examining the liver and stomach (known as laparoscopy) to minimally invasive surgery. The use of these instruments is firmly established as an imaging technique that allows surgeons to ‘see’ inside the body, allowing them to recognise lymph nodes they need to avoid, or assess the health of lung tissue, for example.

One of the most advanced types of endoscopes relies on bundles of minuscule optical fibres — usually thousands of them — to give doctors a picture of the area of concern, and they have saved countless lives.

While optical fibres are perfect for the role — being thin, flexible, chemically inert and non-toxic, as well as immune to electromagnetic interference from other medical instruments — they have one disadvantage: doctors can only see in 2 dimensions, and this flatness of image is a limitation when diagnosing conditions. But that’s all about to change.

Researchers at the Centre for Nanoscale BioPhotonics (CNBP) have developed a clever technique to make the tiny, sometimes blurry, images of cellular regions not only sharper but 3-dimensional. The research has the potential to improve endoscopy by providing a higher quality and more detailed image.

‘We went back over the physics of how the optical fibre bundles work and realised that they actually transmit 3D images as well,’ said Dr Antony Orth, a former research fellow at CNBP’s RMIT University node in Melbourne under Prof Brant Gibson, CNBP chief investigator for nanomaterials and multimodal imaging.

‘People generally assume that each fibre in the bundle only reports the brightness at the other end. But there’s more to it. If you send light at different angles into the fibre, it exits in these beautiful patterns called modes,’ he added. ‘That’s where the magic happens.’

Dr Antony Orth holding an ultra-thin microendoscope used in the study, which revealed the 3D imaging potential of the existing technology. Credit RMIT University.

Dr Orth had been reviewing the basic physics to look for new uses and exchanging ideas around imaging with CNBP colleague Dr Martin Plöschner of the University of Queensland.

‘After playing around with these fibres for a few months, it became apparent that if you shine a light at one end at a really high angle, at the other end you see all these crazy patterns, just seemingly randomly oriented,’ said Dr Orth. ‘It’s a really striking visual effect and totally different to what you get when using the fibre under normal circumstances.

‘I realised that we weren’t just seeing spatial distribution of light, we were also seeing the angular distribution — and if you can measure both of those at the same time, you have a ‘light field’,’ he added.

As it turned out, Dr Orth’s doctorate had centred on light fields, and he could immediately see how the spatial and angular information could be combined to create a 3D image. ‘You can reorganise the light rays to change focus, or send one group of angles to one sensor and another group to another, and have a stereoscopic image,’ he said. ‘It’s like having a tiny multifocal lens in the fibre.’

But making it a reality was anything but straightforward. ‘I knew we should be able to do this, but it took another couple of years to be able to fully realise it,’ he said. ‘We had to flesh out the math to be able to quantitatively turn the modal information into depth information, which was the most challenging part. The intuition was there, you just have to keep slaving away at the math.’

The size of microendoscopes makes them perfect for accessing hard-to-reach areas of the human body. But until now, they’ve been too small to contain the elements needed for complex focusing optics. But ‘light field imaging’, as the technique is known, allows focusing, stereo visualisation and depth mapping at the fibre’s tip, relying on optical fibre bundles already in clinical use. The bundles are just three-quarters of a millimetre wide and contain 30,000 fibres.

‘It gives you the 3D structure of whatever tissue you’re looking at, which may allow you to tell whether a tissue is benign or malignant or somewhere in between,’ said Dr Orth. ‘We’ve experimentally demonstrated you can get 3D information this way. The next step is doing it in animals and then humans.’

In fact, the team’s approach to microendoscopic light field fluorescence imaging — for which a patent is pending — may establish optical fibre bundles as a new class of light field sensor, able to see surface features and map their depth with a rate of accuracy previously unobtainable. And there’s an added advantage that the technique uses off-the-shelf fibres, which will hopefully translate to faster adoption in medicine. ‘The idea is to try to get the same sort of information you get from a biopsy, but do it right at the site. That’s what we want to work towards. This is the first step toward that.’

Dr Orth, now a research officer at National Research Council Canada in Ottawa, continues to collaborate with CNBP, and was delighted with the result: ‘It worked out really well, better than I could’ve hoped.’