Researchers at MIT have developed an imaging system that enables high-speed, 3-D imaging of microscopic precancerous changes in the esophagus or colon. The new system is based on optical coherence tomography (OCT) techniques, which offer a way to see below the surface with detail that traditional screening methods can’t provide. Endoscopy currently is the method of choice for cancer screening of the colon or esophagus, which are diagnosed in more than 1.5 million people worldwide each year, according to the American Cancer Society. In the procedure, a tiny camera attached to a long thin tube is snaked into the colon or down the throat, giving doctors a relatively noninvasive way to look for abnormalities. But standard endoscopy can examine only the surface of tissues and thus may miss important changes occurring below the surface that indicate cancer development. OCT, on the other hand, can examine layers of tissue below the surface and can visualize structures just a few microns in size. Over the past two decades, OCT has become commonplace in ophthalmology, where it is being used to generate images of the retina and to help diagnose and monitor diseases such as glaucoma. It also has emerging applications in cardiology, where it is used to examine unstable plaques in blood vessels that can trigger heart attacks. The new endoscopic OCT imaging system reported by OCT pioneer James G. Fujimoto of MIT and his colleagues, works at record speeds, capturing data at a rate of 980 frames (equivalent to 480,000 axial scans) per second — nearly 10 times faster than previous devices — while imaging microscopic features less than 8 μm in size. The group describes its work in the July issue of Biomedical Optics Express. This is a 3-D OCT volumetric data set from an excised human colon specimen. (A) En face view shows the regular organization of normal colon. (B and C) Cross-sectional views along two different directions show subsurface features. Two cross sections are shown as examples; however, multiple cross-sectional views can be extracted from the data. Scale bar = 500 μm. (Image: MIT) At such high speeds and resolution, the novel system promises to enable 3-D microscopic imaging of precancerous changes in the esophagus or colon and the guidance of endoscopic therapies. “Ultrahigh-speed imaging is important because it enables the acquisition of large three-dimensional volumetric data sets with micron-scale resolution,” Fujimoto said. “This new system represents a significant advance in real-time, 3-D endoscopic OCT imaging in that it offers the highest volumetric imaging speed in an endoscopic setting, while maintaining a small probe size and a low, safe drive voltage,” said Xingde Li of Johns Hopkins University, who is not affiliated with the research team. In OCT imaging, microscopic-scale structural and pathological features are examined by directing a beam of light on a tissue and measuring the magnitude and echo time-delay of backscattered light. Because the amount of light that can be recaptured and analyzed decreases quickly with depth in tissue resulting from scattering, the technique generally can be used only to visualize subsurface features to a depth of 1 to 2 mm. “However, these depths are comparable to those sampled by pinch biopsies and, unlike biopsy, information is available in real time,” Fujimoto said. By using miniature fiber optic scanning catheters or probes, either on their own or in combination with standard endoscopes, colonoscopes or laparoscopes, OCT imaging can be performed inside the body. In collaboration with clinicians at the VA Boston Healthcare System and Harvard Medical School, the team is investigating endoscopic OCT as a method for guiding excisional biopsy — the removal of tissue for histological examination — to reduce false-negative rates and improve diagnostic sensitivity. “Excisional biopsy is one of the gold standards for the diagnosis of cancer, but is a sampling procedure. If the biopsy is taken in a normal region of tissue and misses the cancer, the biopsy result is negative, although the patient still has cancer,” Fujimoto said. Endoscopic OCT requires miniature optical catheters or probes that can scan an optical beam in two dimensions to generate high-resolution 3-D data sets. Scanning the beam in one transverse direction generates an image in a cross-sectional plane, whereas scanning the beam in two directions generates a stack of cross-sectional images — that is, a 3-D (or volumetric) image. “This device development is one of the major technical challenges in endoscopic OCT because probes must be small enough so that they can be introduced into the body but still be able to scan an optical beam at high speeds,” Fujimoto said. “Increasing imaging speeds has also been an important research objective because high-resolution volumetric imaging requires very large amounts of data in order to cover appreciable regions of tissue. So rapid image acquisition rates are a powerful advantage." For more information, visit: www.mit.edu