In the 1966 science-fiction movie “Fantastic Voyage,” Raquel Welch was shrunk down to microscopic size and injected into a patient’s bloodstream to perform on-the-spot surgery. Researchers at the Wellman Center for Photomedicine at Massachusetts General Hospital haven’t quite achieved that level of miniaturization, but they have developed a tiny endoscopic device that may transform how screening for Barrett’s esophagus is performed.

Barrett’s esophagus, a precursor of esophageal cancer that affects approximately 3 million Americans, often goes undetected because it may cause no or only minor symptoms and can be diagnosed only by endoscopy. Performing an endoscopy requires a trained physician, can take about 90 minutes to complete, and requires that the patient be sedated. The complexity of this procedure makes large-scale screening programs impractical.

The experimental endomicroscope is an imaging system enclosed in a transparent capsule about the size of a multivitamin pill. This capsule is attached to a tether, which is swallowed by the patient and allowed to descend as far as the gastroesophageal junction. It is then retrieved via the tether, and the process is repeated. During both the downward and upward transits it scans the esophageal lining and generates images, the researchers report in a recent study published online in Nature Medicine.


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The device relies on optical frequency domain imaging technology (OFDI), a technique similar to ultrasound but using infrared light. The operator generates a beam of light, which is then split into two beams using mirror reflection. One beam serves as a reference, while the other is sent through the tether and into the device, where it is directed onto the tissue. The light beam is focused on an area about the diameter of a human hair and is spun around 20 times per second. When the light is sent back to the detector, it is compared with the reference beam and the differences between the two are used to generate an image of the esophagus in microscopic detail. By stacking the cross-sections together, the operator can create a three-dimensional image of the esophagus.

Using the new device, researchers were able to screen nonsedated patients in about 6 minutes, and no training in endoscopy is required.

“The images produced have been some of the best we have seen of the esophagus,” said Gary Tearney, MD, PhD, a professor of pathology at Harvard Medical School and one of the study authors. “By showing the three-dimensional, microscopic structure of the esophageal lining, it reveals much more detail than can be seen with even high-resolution endoscopy.”

The device was tested in 13 subjects, six who were known to have Barrett’s esophagus and seven healthy volunteers. The detailed microscopic images produced by the OFDI system revealed subsurface structures that could not be seen with endoscopy and clearly distinguished the cellular changes that signify Barrett’s esophagus.

“We originally were concerned that we might miss a lot of data because of the small size of the capsule,” Tearney said, “but we were surprised to find that, once the bill has been swallowed, it is firmly grasped by the esophagus, allowing complete microscopic imaging of the entire wall. The capsule device makes it possible to see the surface structure in great detail.”

Currently, screening for Barrett’s esophagus is recommended only for men with symptoms of gastroesophageal reflux disease. An inexpensive, easily tolerated screening system such as this one might allow physicians to screen more patients, identify those at risk for esophageal cancer, and detect it early during a curable stage.