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Diagnostics Technology and innovation, Microscopy and imaging

What Lies Beneath

Optical coherence tomography (OCT) – best known as an ophthalmology tool – is an effective way of examining basic tissue structure. The technique illuminates a tissue sample with laser beams and collects the light that bounces back, generating an image of what lies beneath. Why, then, is it not more commonly used in tissue diagnostics? Speckle noise, which results from interference between laser light waves, is an unavoidable side effect that limits OCT’s diagnostic capabilities by hiding fine tissue structures. Until now, there has been no effective solution – but an optical diffuser setup may have overcome the problem (1). The study’s lead author, Orly Liba, tells us more.

How can OCT help with virtual tissue biopsy?

OCT is ideal because of its ability to image tissue structure noninvasively at a very high resolution. The technique can see up to 2 mm deep inside tissue and scan in real-time, making it useful for monitoring tumor progression or response to treatment. It’s also very interesting for intraoperative imaging, because it allows users to look at tissue structure without slicing and preparation. The downside to using OCT is speckle noise. Our method significantly reduces speckle noise – and, unlike other methods, doesn’t degrade the effective resolution of the images.

Why is speckle noise so difficult to remove?

Speckle noise is hard to tackle because it’s an inherent part of the OCT image, rather than an artifact of the imaging system. The noise can be reduced if different speckle patterns are averaged – but in static tissue, speckle doesn’t change time, so there’s nothing to average. Our method, speckle-modulating OCT (SM-OCT), applies local phase changes to alter the interference of light coming from different scatters within a single voxel. These changes vary speckle noise so that it can be averaged out without compromising resolution. SM-OCT was inspired by the speckle variations observed in and below blood vessels; like the diffuser in our setup, cells flowing in blood vessels introduce phase changes.

A mouse ear pinna visualized using a) traditional and b) speckle-modulated OCT, showing the decrease in speckle noise with the latter technique.

What can SM-OCT do for pathologists and laboratory medicine professionals?

OCT and SM-OCT can help by visualizing the areas of interest in large tissue samples – or even intraoperatively. The technique lets pathologists work more efficiently by identifying the abnormal or interesting areas of a given sample via SM-OCT and then obtaining tissue sections from only those regions. That allows them to slice and prepare fewer total sections, while still ensuring that no areas of interest are missed. In some diseases, a diagnosis could even be rendered entirely by SM-OCT, thereby sidestepping the need for biopsy; however, confirming that potential will require clinical trials on a use-case by use-case basis.

Is it ready for the clinic?

The move to the clinic is our next step. We can apply our method to existing commercial OCT systems with off-the-shelf components, meaning that existing OCT systems can be “upgraded” to include SM-OCT speckle reduction without significant cost. We are interested in implementing the technique for retinal imaging, skin imaging (for improved cancer diagnosis), and intraoperative imaging (for better tumor margin detection and selecting the best regions for biopsy collection).

SM-OCT can already reveal fine structures we’ve never previously seen via OCT – for instance, Meisner’s corpuscle (the nerve bundle in human fingertip skin). Ultimately, we believe that clinical SM-OCT will combine the best qualities of our current methods: the resolution and clarity of a microscope with the efficiency and tissue preservation of OCT.

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  1. O Liba et al., “Speckle-modulating optical coherence tomography in living mice and humans”, Nat Commun, 8, 15845 (2017). PMID: 28632205.
About the Author
Michael Schubert

While obtaining degrees in biology from the University of Alberta and biochemistry from Penn State College of Medicine, I worked as a freelance science and medical writer. I was able to hone my skills in research, presentation and scientific writing by assembling grants and journal articles, speaking at international conferences, and consulting on topics ranging from medical education to comic book science. As much as I’ve enjoyed designing new bacteria and plausible superheroes, though, I’m more pleased than ever to be at Texere, using my writing and editing skills to create great content for a professional audience.

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