Some patients dread the endoscope more than the potential diagnosis — but a new prototype is less scary: It's as small as a human hair, and it happens to deliver resolution four times better than previous devices of similar design. The instrument could enable new methods in diverse fields ranging from brain studies to early cancer detection. The micro-endoscope, developed under the direction of Stanford University electrical engineering professor Joseph Kahn, can resolve objects about 2.5 µm in size, with a resolution of 0.3 µm within reach. By comparison, today’s high-resolution endoscopes can resolve objects only to about 10 µm. Kahn’s work on endoscopy began two years ago when he and electrical engineering colleague Olav Solgaard were discussing biophotonics. "Olav wanted to know if it would it be possible to send light through a single hair-thin fiber, form a bright spot inside the body and scan it to record images of living tissue," Kahn said. The opportunity and the challenge, they knew, rested in multimode fibers. Light is very good at conveying complex information through such fibers — whether computer data or images — but it gets scrambled potentially beyond recognition along the way. This information could be unscrambled, Kahn and colleagues discovered, by using a spatial light modulator and an adaptive algorithm. Professor Joseph Kahn (right), and graduate students Reza Nasiri Mahalati (left) and Ruo Yu Gu (center) with their prototype single-fiber endoscope. The device improves resolution by four times over previous instruments. Couretsy of John Todd. Research on the micro-endoscope took an unexpected and fortunate turn when graduate student Reza Nasiri Mahalati mentioned seminal work in magnetic resonance imaging (MRI) done by John Pauly, another Stanford electrical engineer. Pauly had used random sampling to dramatically speed up image recording in MRIs. "Nasiri Mahalati said, 'Why not use random patterns of light to speed up imaging through multimode fiber?' and that was it. We were on our way," said Kahn. "The record-setting micro-endoscope was born." In the new micro-endoscope, a spatial light modulator projects random light patterns through the fiber into the body to illuminate the object under observation. The light reflecting off the object returns through the fiber to a computer, which measures the reflected power of the light and uses algorithms developed by Nasiri Mahalati and fellow graduate student Ruo Yu Gu to reconstruct an image. Kahn and his students were stunned by their endoscope’s resolution. "Previous single-fiber endoscopes were limited in resolution to the number of modes in the fiber," Kahn said, "so this is a fourfold improvement. "This meant that, somehow, we were capturing more information than the laws of physics told us could pass through the fiber. It seemed impossible." The investigators wrestled with the scientific conundrum for several weeks before they came up with an explanation: The random intensity patterns mix the modes that propagate through the fiber, increasing the number of modes fourfold and producing four times as much detail in the image. "Previous research had overlooked the mixing,” Kahn said. “The unconventional algorithm we used for image reconstruction was the key to revealing the hidden image detail.” The working prototype they created is limited because the fiber must remain rigid; bending a multimode fiber scrambles the image beyond recognition. Instead, the fiber is placed in a thin needle to hold it rigid for insertion. Rigid endoscopes — those used frequently for surgeries — are common, but they often use relatively thick, rod-shaped lenses to yield good images. Flexible endoscopes, on the other hand — the kind used in colonoscopies and ureteroscopies — usually employ bundles of tens of thousands of individual fibers, each conveying a single pixel of the image. Both types of devices are bulky and have limited resolution. The Stanford single-fiber endoscope would be the ultimate minimally invasive imaging system, and has been the focus of intense research in optical engineering over the past few years. Kahn’s group is not the first to develop such a device, but in boosting the resolution it is possible now to conceive of a fiber endoscope about two-tenths of a millimeter in diameter — just thicker than a human hair — that can resolve about 80,000 pixels at a resolution of about 0.3 µm. Today's best flexible fiber endoscopes, by comparison, are about 0.5 mm in diameter and can resolve roughly 10,000 pixels with a resolution of about 3 µm. "No one knows if a flexible single-fiber endoscope is even possible, but we're going to try," Kahn said. The results appear in Optics Express (doi: 10.1364/OE.21.001656). For more information, visit: www.stanford.edu