Optical coherence tomography (OCT) is a scanning technology commonly used by ophthalmologists to check for eye diseases. A team of scientists has figured out how to retrofit these high-performance machines with off-the-shelf components, increasing OCT's resolution by several-fold, promising earlier detection of retinal and corneal damage, incipient tumors, and more.

The upper image, showing a section of a mouse's outer ear, is considerably enhanced by the team's refinements compared with one obtained by conventional technology (lower image). (Courtesy of the de la Zerda lab.)

The relatively simple, low-cost fix — entailing a pair of lenses, a piece of ground glass and some software tweaks — erases blemishes that have bedeviled images obtained via OCT since its invention in 1991. This improvement, combined with the technology's ability to optically penetrate up to 2 millimeters into tissue, could enable physicians to perform “virtual biopsies,” visualizing tissue in three dimensions at microscope-quality resolution without excising any tissue from patients.

The researchers tested the enhancement in two different commercially available OCT devices. They were able to view cell-scale features in intact tissues, including in a living mouse's ear and a human fingertip.

Every year, more than 10 million OCT scans are performed to diagnose or monitor conditions from age-related macular degeneration to melanoma. The technology has also been adapted for endoscopic use in pulmonary, gastrointestinal, and cardiovascular medicine.

Somewhat analogous to ultrasound, OCT penetrates tissues optically instead of with sound waves. The device aims beams of laser light at an object — say, a tissue sample, or a patient's eye — and records what comes back when light bounces off reflective elements within the sample or eyeball. Adjusting the depth of penetration, a user can scan layer upon layer of a tissue and, piling virtual slices of tissue atop one another, assemble them to generate a volumetric image.

But to this day, OCT continues to be plagued by a form of noise that, unlike the random noise generated by any sensing system, can't be washed away simply by repeatedly imaging the object of interest and averaging the results.

The noise generated by OCT, called “speckle,” is an inherent feature of the architecture of the object being viewed and the unique properties of laser light.

A photon isn't a mere particle. It's also a wave whose power waxes and wanes as it travels. When two waves collide, their combined height at the moment of their collision depends on whether each was at its peak, its trough, or somewhere in between.

The photons comprising a beam of laser light are in phase; they share the same wavelength, with their peaks and troughs occurring in sync. But when these photons bounce off of two separate surfaces — say, two closely situated components of a cell — the lengths of their return routes differ slightly, so they're no longer in phase. In that case, they may cancel each other out, creating a false-black speckle on the resulting image. Or they may reinforce one another, creating a false-white speckle. If the speckle-generating components’ positions are fixed, as is the case in most tissues (circulating blood being one exception), those same speckles will pop up in the same places on every successive OCT scan.

In principle, if you could reach in with a molecular tweezers and move one of those two interfering components just a tiny bit, you would change the speckle pattern. The scientists have found a way to do essentially the same thing, optically speaking.

By positioning a couple of additional lenses in the OCT device's line of sight, they were able to create a second image — a holograph-like exact lookalike of the viewed sample that appeared elsewhere along the line of sight, between the added lenses and the sample. By inserting what they call a “diffuser” — a plate of glass they'd roughened by randomly etching tiny grooves into it — at just the right point in the line of sight and methodically moving it between each round of repeated scans, they achieved the optical equivalent of shifting the geographical relationship of the sample's components just a tiny bit each time they scanned it.

Now, averaging the successive images removed the speckles. The team was able to acquire detailed, essentially noise-free images of a living, anesthetized mouse's ear, its retina and cornea. They were also able to see sebaceous glands, hair follicles, blood vessels, and lymph vessels.

In a scan of a human finger, they saw an anatomical feature never before glimpsed with OCT: Meissner's corpuscle, a nerve bundle responsible for tactile sensations.

For more information, contact Bruce Goldman, This email address is being protected from spambots. You need JavaScript enabled to view it..

Photonics & Imaging Technology Magazine

This article first appeared in the November, 2017 issue of Photonics & Imaging Technology Magazine.

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