New research from a team at our Cambridge Research Institute, led by Dr Sarah Bohndiek, could open up a new way of detecting precancerous changes that could develop into oesophageal cancer. Here, one of the scientists behind the discovery, Dale Waterhouse, shares the team’s findings.
Early detection: two words that can give a crucial advantage to doctors in their fight against cancer.
An earlier diagnosis can mean more treatment options are available, and that these treatments are more likely to be successful. And for cancers that develop through cellular changes linked to other conditions, early detection could even mean the chance to prevent a cancer developing.
But spotting the earliest signs of a disease isn’t easy.
In hospitals, more advanced surveillance takes place through the use of specialised tests and technology, in the hope that the signs of precancerous changes or early stage tumours will trigger alarm bells.
By combining our expertise in imaging, engineering and biochemistry, we’ve developed a new way of taking pictures of cells using a specialised camera and fluorescent light given off by a dye.
And it offers a glimpse at what happens when good cells go bad.
Our research into the early detection of oesophageal cancer is focused on the presence of a different condition, called Barrett’s oesophagus.
The condition causes changes to the cells that line the oesophagus, meaning that patients with Barrett’s have an increased risk of developing oesophageal cancer. And because of this, they are often closely monitored using endoscopy, a technique that captures videos of the inside of the oesophagus.
This method uses a normal white light camera – like the one found inside your smartphone – to carefully scrutinise the surface of the oesophagus, searching for the early changes that could become cancer, known as dysplasia. Accurately spotting these changes is important, as it could offer a chance to remove the cells before they become cancerous.
But this is challenging. Unlike many cancers, which form lumps that we can see and feel, the precancerous changes caused by Barrett’s appear as flat patches, sometimes with very little change in the colour of the tissue.
These changes are difficult to spot with simple white light imaging, and therefore often evade early detection in spite of regular patient monitoring.
So, to improve the visibility of the precancerous changes, we first tested using a fluorescent dye that sticks to specific molecules on oesophageal cells. When we shine a specific colour of light on the cells in the lab, the targeted dye gives off a different colour of light back to the camera so we can see if the dye has stuck or not.
The molecule the dye sticks to is only found on healthy oesophageal cells, but not the precancerous regions. These precancerous changes should then be clearly revealed as dark patches surrounded by brighter light from the normal, healthy tissue.
But there’s a problem – it turns out the cells lining the oesophagus are also fluorescent.
People who are at a high risk of developing oesophageal cancer, such as those with Barrett’s oesophagus, could be closely monitored with this technique. But we need to do some further testing before clinical trials with patients can be set up to see how effective the approach could be at saving lives
– Dr Sarah Bohndiek
The healthy cells lining the oesophagus naturally give off fluorescent light that is similar to the dye and is picked up by the camera. And in our lab tests, even the precancerous areas that we were expecting to be dark also gave off this glow.
So, the difference in brightness between the different cells was very low, and the precancerous regions evaded us once more.
To overcome this challenge, we selected a new targeted dye that gives off a different fluorescent colour to that of the oesophagus.
This way, if we look at the particular colour of our targeted dye using the camera, we no longer see the fluorescence of the oesophagus, and the precancerous areas will appear dark again.
The colour we chose for our dye is not one visible to the human eye – it’s ‘near-infrared’. This is the range of light between familiar red light, such as that from a traffic light, and invisible infrared light, similar to that sent from our remote controls to the television.
To capture images of this dye, we require a specialised camera that can be turned into an endoscope to ‘see’ the near-infrared light.
And our new study outlines the design, development and testing of this device.
We’ve carefully tested the device in the lab to see if it might be able to spot the unhealthy cells.
This includes pinpointing the smallest object the endoscope can detect (its resolution), the smallest amount of dye it can detect (its sensitivity) and the largest object that can be seen in a single image.
And so far these lab tests are showing promise.
To check that our endoscope accurately picks up the dye, we took images of the dye sprayed onto human oesophageal tissue samples in the lab, and compared these to images captured with a standard near-infrared camera. The images closely matched, indicating that our dye approach works on real cells.
This study marks an important next step in the development of our new surveillance technique. But there’s still more work to be done to keep honing the approach.
We hope that further development and safety testing of the device will lead to a clinical trial of this technique in people with Barrett’s oesophagus.
And if successful, it could help detect those precancerous changes earlier, potentially preventing more cases of oesophageal cancer in the future.
Waterhouse, D., et al. (2016). Design and validation of a near-infrared fluorescence endoscope for detection of early esophageal malignancy. Journal of Biomedical Optics, 21 (8). DOI: 10.1117/1.JBO.21.8.084001