What is the first indication of skin cancer? An odd-looking mole on the skin. How about cervical cancer? We search for cells that look abnormal. The eyeball, whether aided by microscopes or not, has a critical role to play in medicine, since it feeds information to a brain that is very good at picking out subtle differences.

This is why endoscopes are so useful: they allow doctors to see what would otherwise be hidden. But even then, most endoscopes only show the surface features of organs, while a good diagnosis requires looking at cells that are hidden beneath the surface. This is exactly the problem that a large group of scientists, doctors, and engineers has addressed. The researchers have developed an endoscope that is much better at revealing hidden features.

Water is transparent

In some ways, we should be surprised that we cannot see beneath the surface of our skin. If you’ve ever looked at cells under a microscope, it is really hard to make anything out. You see a couple of thin, barely visible membranes and a few mostly transparent lumps. A cell is mostly water, and most of the light simply passes through it.

Unfortunately, those barely visible parts are enough to change the direction of any light that does pass through, making the next layer blurry. If there were only two layers, you might overcome the blurriness. But there are thousands of layers, each contributing its own distortion, leaving you with a white haze.

At the level of physics, each photon has its direction changed slightly every time it passes through a membrane or bounces off a vesicle. As a result, a reflected photon travels by a random path into the tissue and back out. The randomness of the path is a blessing and a curse: the photon carries some of the path information with it, but interpreting the information is very difficult, and this prevents an image from being reconstructed.

You can see this effect yourself by putting your hand over a bright light. Your fingers will start to glow from the light that passes through the tissue, but the image of the filament is lost by the random path the light takes through your hand.

Labeling photons

But imagine that you could put a tag on each photon—we won’t go into how you do this, because you can’t, though there is a way to label groups of photons. Photons Anna, Bill, and Celine are sent into the tissue, and we time how long they are away for. Bill might return first, followed by Anna, while Celine drags in last having spent her time on a photonic pub crawl.

Now, given the travel time and an idea of the average properties of the material the light traveled through (water, in our case), we can compute the distance that Bill, Anna, and Celine traveled.

An image can be reconstructed by doing that for billions more photons. You carefully keep the illumination conditions the same and measure photons exiting from different locations of tissue.

Once these measurements are combined, an image can be created in various ways. Essentially, image reconstruction requires that all photons have scattered through the same volume, and, therefore, all photon trajectories can be explained by the properties of that volume. A sort of reverse-search of possible volumes reveals the most-likely 3D structure of the volume.

This imaging technique is called optical coherence tomography.

Old new and new news

Optical coherence tomography is old, and it has even been used in endoscopes. But the images tend to be quite blurry. The problem is basically how to squeeze everything into a tube that’s small enough to send inside a human, all while keeping the quality of the optics high.

The issue is that all lenses have imperfections, called aberrations, even if the fabrication is absolutely perfect. Typically, the smaller the lens, the larger the effect of the aberration. In terms of optical coherence tomography, this means that we blur the point where we sample photons. As a result, the quality of the image goes down.

To overcome this problem, the researchers turned to metamaterials. A metamaterial is an ordinary material that has been structured at the scale of the wavelength of light. In doing so, the structure changes the optical properties of the material. That means, effectively, that we can engineer fake materials that do some very strange things.

The researchers created a 2D metamaterial that basically consists of rings of pillars. The diameter and spacing of the pillars modifies the optical properties of the surface locally. Effectively, the light emitted from each ring mixes with the light from all the other rings. The mixing can result in constructive interference (a bright spot) or destructive interference (a dark spot). The rings are structured such that at a distance of about 0.5mm, there is a single very tiny spot, just like you would get from a lens. However, this metamaterial lens is flat (like a Fresnel lens) and has been engineered to minimize many of the aberrations.

Searching for alveoli

The metamaterial-lens-equipped endoscope outperformed two other endoscopes that used more traditional optical components (a normal lens and a fiber that focuses light).

After characterizing performance, the researchers imaged a number of tissue samples, including human lung tissue (ex vivo, in this study). They showed that they could obtain relatively clear images of the epidermis, alveoli, cartilage, and blood vessels; they also picked up an abnormality that had been highlighted in the histological images. The key point being that some of these features could not even be seen in images taken with traditional endoscopes.

Some of you may be waiting for a bigger reveal—it’s science and there must be some big discovery. But there isn’t one. I know we like to talk about big breakthroughs and fundamental insights. Science and medicine don’t just advance in big jumps, though. Lots of little steps are more common. And, when you look closely, many of the big jumps involve a run up of lots of little steps.

This endoscope may be one of those little steps. The imaging improvement is not going to revolutionize anything, but it will save lives if it ends up in clinics. And it should allow research scientists to spot tissue abnormalities earlier and understand their development better. All of that makes a difference.

Nature Photonics, 2018, DOI: 10.1038/s41566-018-0224-2. (About DOIs).