The history of endoscopy is the history of advances in technology leading doctors deeper into the gastrointestinal tract and providing clearer views of what they find there. And the past several years have seen tremendous strides in endoscope design, offering greater access to the GI tract, higher sensitivity and an ability to probe areas that are often inaccessible to conventional systems. Physicians have sought ways to peer inside the gastrointestinal (GI) tract for millennia: Greek, Roman and Egyptian scholars all devised specula with which to see inside the body’s orifices, according to Eric M. Pauli and Jeffrey L. Ponsky in a recent chapter on the history of flexible GI endoscopy. But endoscopy as we know it today did not arrive until the early 19th century. In 1806, Philipp Bozzini, a doctor in Mainz, Germany, described the Lichtleiter (light conductor), which used candlelight and assorted mirrors and specula to inspect the nose, esophagus and bladder, among other orifices. The technique continued to evolve in the following decades, with advances including the use of lens arrays and small electric bulbs at the tips of the instruments. Further advances came in the first half of the 20th century, with the introduction of semiflexible instruments and the delivery of “cold light” to body cavities through endoscopic tubes. Finally, in 1957, Basil Hirschowitz and Larry Curtiss invented the first fiber optic endoscope, thus heralding the modern era of endoscopy. An endoscopy system from EndoChoice Inc. provides 330-degree views during colonoscopies, thanks to three small cameras in the distal tip. At the same time, the LEDs used to illuminate the field offer greater longevity and durability than conventional fiber optic illumination. Courtesy of EndoChoice Inc. Progress hasn’t slowed in the 50-some-odd years since then. At the same time, endoscope design now faces a host of nontechnological challenges as well. These include cost-reduction challenges, material selection and, not least, intellectual property and the question of where smaller companies can compete (see sidebar: The market for endoscopes). “The space is crowded, and all the big camera companies have solid IP portfolios,” said Doug Ladd, chief marketing officer at EndoChoice Inc., a platform GI company based in Alpharetta, Ga. Not surprisingly, the crowded IP space has spurred some companies to find innovative solutions to long-standing problems. EndoChoice did just this in developing its Fuse system, a full-spectrum endoscopy system that gives doctors a 330-degree view during colonoscopies. The system projects images from the cameras on three screens, enabling views of areas that might go undetected with conventional colonoscopies – areas behind colonic and pyloric folds, for example. Courtesy of EndoChoice Inc. “Traditional endoscopes have limited space they can offer to the clinician to get tools and devices down to the problem,” Ladd said. “We wanted to change that, and by revisiting the anatomy of an endoscope from a different vantage point, we found ways to convert space to uses valued more highly by endoscopists. “What they value is the ability to see more anatomy – that rates higher in importance than something like getting to the cecum faster. So we looked for ways to expand their view.” The system includes an arrangement of three small cameras at the tip of a flexible GI endoscope, enabling imaging of almost twice as much surface area as traditional endoscopes, using only a single camera, allow. This greater coverage can translate to greater efficacy. In a recent multicenter trial conducted in the US, Europe and Israel, the system missed fewer adenomas during exams than conventional colonoscopes did: Traditional colonoscopes missed 42 percent of adenomas during the trial, while the EndoChoice system missed only 8 percent, as the researchers reported at Digestive Disease Week in Orlando, Fla., in May. A less-bitter pill to swallow In recent years, the technique known as capsule endoscopy has enabled doctors to move beyond the esophagus and duodenum on the one side, and the colon and distal part of the small intestine on the other, to probe those portions of the small intestine not accessible by traditional endoscopy. The technique takes advantage of a capsule the shape and size of a pill that contains a small camera. A patient swallows the capsule, and it acquires images as it passes through the GI tract. A recent example: A team at Massachusetts General Hospital in Boston described a technique called tethered-capsule endomicroscopy in a Nature Medicine paper published earlier this year. Here, the capsule acquires cross-sectional images as it travels through the digestive tract; light from a rotating laser reflects off the lining of the esophagus and is detected by internal sensors, which transmit the information to an imaging console. Tethered-capsule endoscopy is far less uncomfortable for patients than conventional endoscopies, and because it doesn’t involve sedation, doctors can perform the technique without the specialized equipment and staff that are currently needed for endoscopies. This suggests a number of advantages: not least, say the authors of the study, the potential for population-based screening and diagnosis with organs in the GI tract. The market for endoscopes The endoscope market is large and, although it is dominated by a few large companies, involves a number of players. Dr. Kamran Zamanian, CEO of iData Research Inc., recently provided an overview of the market. Among the highlights of Zamanian’s report: • In 2011, the US market for GI endoscopic devices was valued at nearly $1.97 billion, exhibiting 4.4 percent growth over the previous year. The growth rate decreased somewhat precipitously with the recession, but it has remained in the positive numbers. This stands in contrast to many other markets, which have shrunk in value during the same period. Stanford University professor Joseph Kahn (right), along with graduate students Reza Nasiri Mahalati (left) and Ruo Yu Gu (center), has described a prototype of a multimode fiber-based endoscopy system as small as a human hair. Courtesy of John Todd. • Sales of colonoscopes dominate the market, though procedural demand has led to a considerable increase in unit sales of ultrasound and double-balloon endoscopes. The higher price of the latter devices has contributed to the market’s ability to weather the recession thus far. • Other factors driving growth: the introduction and adoption of high-definition endoscopes, especially among facilities seeking to attract patients with state-of-the-art equipment; the aging population in the US; and increased awareness of colorectal cancer. • The US market for GI endoscopic devices is a crowded field, dominated by Olympus, Boston Scientific and Cook Medical, with a combined market share of 59.6 percent in 2011. Of these, Olympus is the most prominent, with a 31.1 percent share of the overall market and a 76 percent share of the market for endoscopes – the largest segment in the US market. Endoscopes no bigger than a human hair With all the developments in instrument design over the years and decades, one thing hasn’t changed: Endoscopies aren’t much fun. Just the thought of the instrument snaking down their throat can be enough to send patients running for the hills. Now, though, developments in single-fiber endoscopes could help to mitigate these fears. Researchers at Stanford University, for example, have described a prototype of an endoscope that’s no bigger than a human hair and yet offers a resolution four times greater than devices with a comparable design. In an Optics Express paper published early this year, electrical engineering professor Joseph Kahn and colleagues reported resolution of 2.5 µm, noting that a 0.3-µm resolution was in their sights. Conventional high-resolution endoscopes offer resolution of about 10 µm. The researchers achieved this by using a multimode fiber and a combination of a spatial light modulator and an adaptive algorithm to unscramble the information conveyed through the fibers. Currently, the endoscope must remain rigid – bending the multimode fiber would render the image information unusable – but they are working toward a flexible version of the prototype.