Shining light on early cancer

First up, oesophageal cancer. Thousands of people are diagnosed each year with this disease. It’s the 14th most common cancer in adults; it mostly affects older people and tends to present late in the disease course, which can limit options for treatment. But if it could be detected earlier, outcomes are likely to be much better. That’s the approach that Cambridge University researcher Sarah Bohndiek is taking, and she spoke to Chris Smith...

Sarah - What we’re thinking about is trying to augment the vision of the endoscopist. What we mean by that is providing contrast for really early signs of cancer which are currently very, very difficult for the endoscopist to see.

Chris - What’s an endoscopist?

Sarah - An endoscopist is someone who uses a very long, thin flexible tube to look inside the body, and they typically do this in a way that replicates what your eye can see if you were able to peer inside.

Chris - You’ve got one on the table in front of you?

Sarah - I have.

Chris - I presume that’s the thing in front of us. So this is a long tube; you’re threading it down something. In this case you’re threading it down someone’s throat and you’d be looking at the lining of the intestines or the oesophagus but, critically, you’d be looking with what the human eye can see?

Sarah - That’s exactly right. Normally we’re looking with a white light camera that has red, green, and blue colour channels just like we have red, green, and blue cones in our eye. And that has strengths because we are able to signs of cancer, macroscopic signs as the disease is developing, but it also has weaknesses. When the disease is at a very early stage it’s usually flat so it’s quite close to the lining and also it’s often just a slightly different shade of pink from the normal tissue, so it makes it very difficult to spot with only three colour channels.

Chris - What’s your solution then?

Sarah - Our solution is to try to create what we call a multi-dimensional endoscope. So instead of just looking at three channels of colour, we look at a broad spectrum of colour beyond what the human eye can see. In addition to looking at a wider range of colours of light, we also introduce other properties of light. For example, light has a property of angle which is the angle at which it travels through the medium and what we can do with our new technology is also measure the angle of the light. All of these different properties interact with cancer in a different way than they interact with normal tissue. So by picking all of them up we hope to be able to enhance the contrast and augment the vision of the endoscopist.

Chris - Will this be a sort of laser source then so when the gastroenterologist does the endoscopy, they’ll thread the tube down into the person, they can see what they’re doing but, at the same time, you’re able to inject say laser light, or some other light source down the endoscope so it reflects all the way down, comes out the end, and they’re then inspecting the lining of the oesophagus with this extra light added?

Sarah - We can do more clever things with the existing light that they send down. They normally send broadband light down and they bin it into these different channels, so we can already use the existing light source and collect more interesting properties from it. But, as you say, we can also introduce additional light sources, such as laser light, which have nice properties in terms of how they travel into the oesophagus. By using that and pulling out additional information, and combining those two things together, the endoscopist will have their normal white light image which is easy for the eye to interpret. And what we’d really like to do is have an overlay which has a colour channel which essentially has a big arrow saying - “biopsy here, this is a suspicious area”.

Chris - I was going to say, are you going to sort of feed back onto the image that they’re seeing, what your system is interpreting, so it comes out of the endoscope, goes to a computer, that crunches through all the other information coming in and then represents that over the top of what the surgeon can see, or the gastroenterologist can see in plane light, and then you can highlight the bits that you want?

Sarah - That’s exactly right. It’s really important for adopting new technology into healthcare that you think about how it’s going to fit into the existing standard of care. If we’re able to use that existing standard of the white light and feed in all of our information into one really useful image to the endoscopist, it just makes their workflow really, really easy and adds information and adds value.

Chris - What is it about the cancer cells that means they’re different in a way that you can see with these additional light investigations?

Sarah - There’s actually a number of different things. The simplest one is just that the microstructure changes. If you imagine a normal tissue, it has a very ordered structure of cells, as the cells become abnormal and turn towards cancer they proliferate more which means they divide very rapidly. That means they tend to push out and dislodge the normal tissue around and that disorder will interact, for example, with laser light, to depolarise the light which means that it changes and removes the property of angle, and if we measure that angular property we can see that change.

But there are also other properties that change, for example, metabolism. Imagine if cells are dividing really rapidly, they need more energy to be able to do that. There are certain molecules in the body that are related to their energy which you can actually visualise using optics, and we can also probe those if we look at more colour channels.

Chris - We had Gareth Corbett on the programme a month or two back; he’s a gastroenterologist; he’s working on a camera you can swallow. The idea is that rather than people having to have tubes like the one you’ve got in front of you shoved where the sun don’t shine, which isn’t everyone's cup of tea, you can just swallow this thing and it makes it’s own way through your gastrointestinal tract taking photos on it’s way through. Then it beams the pictures wirelessly to a belt that you carry and then you bring that back to the hospital and the doctor can see all of the images as it made it’s way through you, and you don’t even have to retrieve the camera - that’s the other added bonus! Could you take your technology and engineer it into something like that so that you’re not tied to a endoscope because, obviously, the benefit of your approach is that you can perhaps pick up cancer earlier, but that’s only as good as someone regularly getting investigated with an endoscopy, which isn’t ideal, is it?

Sarah - The small device architecture of having a capsule is exactly compatible with our technology. In fact, the projects that’s just been funded develops a new set of optical filters which could be miniaturised and placed into a capsule format if we wanted to. For the oesophagus that’s a bit of a challenge because when you swallow something it travels really fast.

Chris - It doesn’t hang around no.

Sarah - So you do have to think about how you can do that and one approach is to put it on a tether. Other people have shown that if you put the pill on a string and don’t allow it to go too quickly, that allows you to get better quality images.

Chris - But you could use the same approach, albeit perhaps with different filters or a different sort of interrogation of the tissue, for anywhere that you could stick an endoscope. So would this work, for instance, for lung cancer?

Sarah - You could, yes. You could look in the lung, you could look in the colon. It’s very flexible and, in principle, we imagine that we would see similar sorts of contrasts for very early cancers, and there are similar challenges in those diseases as well.

Chris - Cervical cancer as well? That’s a big problem we’re trying to do a lot of screening for that. Could it work in the same way?

Sarah - Yeah, very much so.