1. Wysong, Pippa

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Getting histologic images of the esophagus and other parts of the digestive tract may soon be as easy as getting patients to swallow pill-sized cameras. Called tethered capsule endomicroscopy (TCE), the technology can take multiple microscope images and it shows promise for diagnosing and monitoring Barrett's esophagus.


The cameras allow for getting real-time histological images of tissue without requiring anesthesia or endoscopy in what some researchers are referring to as optical or digital tissue biopsy. TCE cameras were initially developed at The Tearney Lab at Massachusetts General Hospital and prototypes of several versions are under development. TCE is also sometimes referred to as volumetric laser endomicroscopy.


Prototype TCE cameras that use optical coherence tomography (OCT) imaging technology have shown the greatest advancement and are designed for use in Barrett's esophagus. "We have a multi-center clinical study going on at five centers where we're studying the natural history of Barrett's esophagus," said Guillermo Tearney, MD, PhD, Professor of Pathology at Harvard Medical School.


Initial results of that study were presented at the 2019 SPIE BiOS conference in San Francisco (2019; Here, TCE obtained 3D microscopic images of the entire esophageal wall of 59 patients with Barrett's esophagus. The capsule moved down the luminal organ via peristalsis and continued to take images even as the tether was pulled upward during retrieval. The image magnification was 10 [mu]m, which can give a good look at individual cells. Patients were able to go to a primary care screening center where they could swallow the capsule and undergo TCE imaging.


Michael Wallace, MD, a gastroenterologist from the Mayo Clinic, Jacksonville, was part of the study team. "What's unique about this device is it's small, swallowable, does not require sedation, and it gives you both the endoscopic view which has been the basis of screening for early cancers and also gives you the optic biopsy," he told Oncology Times. The OCT technology allows for images to be obtained from depths that are 2-3mm below the tissue surface, something not possible with endoscopy.


Another study from the Tearney Lab investigated how well gastroenterologists reading standardized OCT TCE images agreed in terms of their ability to interpret Barrett's esophagus and associated neoplasia. It found that there was a high level of agreement and accuracy among high-volume users. The study included eight high-volume users defined as gastroenterologists who have read over 50 TCE examinations in Barrett's esophagus from different academic centers. For the study, those reading the images were given 120 digital slides with non-identified histological images. They had to identify them as gastric cardia, esophageal squamous mucosa, nonneoplastic Barrett's esophagus, and neoplastic Barrett's esophagus.


The high level of agreement between the readers shows the technology can be applied in a uniform manner across sites, study authors said, but noted that studies still need to look at diagnostic accuracy.


Wallace noted there is another upcoming non-invasive option for gathering histological samples-a swallowable sponge-capsule. "It's essentially a compressed sponge on a string, you swallow it and it expands in the stomach and it scrapes off some cells as you pull the string out. With that you can get the cells but not the image," he noted.


OCT isn't the only technology being used in TCE cameras. Some that are under development use confocal microscopy. In both types, the cameras are tethered and swallowed, usually with water, to make swallowing easier. The capsules are about the size of a typical calcium supplement pill, or a shelled whole almond.


"When you swallow a capsule with OCT, we're able to grab 3-dimensional images of the entire GI tract," Tearney said.


For the confocal microscopy version of the cameras, researchers at the Tearney Lab invented the spectrally encoded confocal microscopy technology. "It's basically a very, very fast form of confocal microscopy. We put it in a capsule, you swallow it, and we can get microscopic images of the whole esophagus. It has an even higher resolution than what we have with OCT, down to 1 micron. We can see individual cells with this technology," he explained.


So far, prototype OCT microscopy capsules have been tested on about 300 patients, and confocal microscopy has been tested in about 100 patients. Various projects are ongoing for applications in Barrett's esophagus, esophageal cancer, eosinophilic esophagitis, stomach cancer, celiac disease, and environmental enteric dysfunction. In addition, a project on Crohn's disease is about to start. Tearney estimates some TCE devices will start being available on the market in about 2 years.


His team is working on multiple TCE cameras that are different sizes, shapes, and weights because variations are needed for different indications. "Every disease has its own unique characteristics and things you need to be able to see. In different parts of the GI tract, you need to configure the capsules differently so they can most efficiently go to those different parts.


"For example, if you're going further into the GI tract the tether has to be longer so the capsule can go there. If you want to get out of the stomach and into the small intestine, we found you need to make the capsule heavier so it can get through the sphincter," he said. TCE devices for pediatric patients have to be different sizes than those for adults.


Additional types of cameras that should prove useful in diagnosing and monitoring digestive tract cancers are being developed.


A question at this point is who will interpret the images? Tearney said this issue still needs to be worked out. If they are read real-time by gastroenterologists, then extra training is needed for those who use these technologies. Other possibilities include pathologists who might have the option of reading images on site in real-time, or the images could be sent to a lab.


Pippa Wysong is a contributing writer.


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