Just over 15 years ago, using technology that would revolutionize the telecommunications industry, researchers at the Massachusetts Institute of Technology developed an elegant optical imaging technique—optical coherence tomography (OCT). The technique, analogous to ultrasound, uses near-infrared light rather than sound waves to create images. Light reflects off of tissue and is captured by a detector. Image analysis software combines the signals from the reflected light to form an image.
Initially, researchers used OCT to examine the fine structures of the eye’s retina. Ophthalmologists embraced OCT because it gave them a noninvasive way to view the retina and at a relatively low cost compared with other techniques such as magnetic resonance imaging. Because every layer of the retina could be viewed by OCT, the technique could assist in tracking conditions such as glaucoma, macular holes (retinal tears), and nonvascular macular edema (swelling of the retina’s center). The technique could also monitor how well retinal drug therapies were working. OCT is now considered the “gold standard” for retinal imaging.
Although OCT’s image quality and image acquisition rates were adequate for ophthalmology studies, they were not good enough for use in other clinical fields. Since its introduction, researchers and engineers around the world have worked to improve OCT’s image resolution and speed. The technique now can provide clear three-dimensional images taken in real time.
With these advances, OCT is now poised to make a contribution in a number of fields including surgical oncology, cardiology, gastroenterology, and tissue engineering. OCT’s ability to give immediate quantitative information may also make it an integral component of point-of-care diagnostics.
Needle biopsies remove cells from a suspect area in the body, and those cells are then examined under a microscope to determine the extent of disease present. The procedure can have a high rate of nondiagnosis, which means captured tissue contains only normal cells even though another screening technique has shown an abnormal mass exists. In these cases, patients must undergo surgical biopsy. For breast cancer, roughly 10-15% of needle biopsies are nondiagnostic. For lung nodules, the nondiagnostic biopsy rate can be as high as 50% for nodules less than 1cm. Often this nondiagnosis comes after hours of imaging to guide needle placement.
Image-guided needle biopsy and surgical tumor removal can benefit from imaging technologies capable of producing high-resolution images that show structural and, with the use of contrast agents or imaging dyes, molecular information about surrounding tissue. “[Conventional] pathology grossly under-samples tissue, and it can’t look at all the tissue [in its native state] microscopically,” says Stephen Boppart, professor of electrical and computer engineering, bioengineering, and medicine and head of the Biophotonics Imaging Laboratory at the Beckman Institute at the University of Illinois, Urbana-Champaign. “Our contention is that things are being missed.”
To extend OCT’s reach within the body, Boppart’s group has developed special needles that contain all the imaging components within the needle’s tip. These can also be adapted for use in a flexible catheter when the biopsy location is in blood vessels or the gastrointestinal tract. “We need to hire craftsmen to assemble these microscopic components, but this is all feasible,” he says.
Boppart and his group have developed an OCT surgical system that allows surgeons to examine tumor beds, tissue margins, and lymph nodes during surgery and get a comprehensive picture of the patient’s situation. When surgeons remove tumors, they take as much of the tumor as possible as well as additional tissue to see how far the cancer has spread. Currently, no tool in clinical practice can give a surgeon quantitative information on how much tissue to remove. “[An OCT system] won’t supplant pathology as the gold standard, but it will offer data, up front, to help make decisions about the locations for additional tissue removal,” he says.
Improved Stent Placement
OCT offers cardiologists a nimble tool for examining the body’s extensive network of blood vessels. In two areas, for instance, OCT comes out ahead of intravascular ultrasound (IVUS), a technology commonly used for imaging blood vessels. OCT can image the inner lining of a vessel well enough to pick up early stages of plaque development, and the OCT catheters are about five times smaller than the IVUS probes.
When it comes to placing stents (mesh tubes that expand to keep the vessel open), cardiologists would like to see what the stent looks like and how the stent has affected surrounding tissue. With OCT, clinicians can now see whether the stent is overexpanded and whether the blood vessel has been injured through placement.
Assessing the Esophagus
Barrett’s esophagus, a precancerous condition, arises when the cells lining the lower part of the esophagus become abnormal as a result of continued drenching by stomach acid. To monitor the condition, patients undergo regular biopsies. The standard of care for Barrett’s is random quadrant biopsies, an approach that may miss areas that may be undergoing potentially harmful changes. In the future, OCT may offer these patients a less invasive way to monitor their condition. Clinicians would use OCT to survey the esophagus and detect suspicious lesions and then, based on those findings, biopsy dubious areas.
Visualizing Tissue Structure and Function
Engineering tissue for the skin, eyes (in the form of corneas), and other organs is in its infancy. Often the tissue fails because it is a mechanical mismatch in the wound bed. Current imaging systems cannot penetrate deep enough into the cell layers to give clues about the structural and functional properties of the tissue. By applying optical coherence techniques to microscopy, Boppart and his colleagues can noninvasively and nondestructively visualize in three dimensions the structural and functional properties of engineered tissue. This allows them to observe changes in the tissue over time and will help improve the design of engineered tissue.
Promise for Point-of-Care Diagnostics
Few technologies are capable of delivering the structural and molecular data that OCT provides, especially during an operation or when a blood vessel is reopened. When OCT was first introduced in 1991, “it filled a hole,” says Boppart and “enhanced the diagnostic ability of the average ophthalmologist.” Today, OCT has the potential to enhance the diagnostic ability of each surgeon, cardiologist, gastroenterologist, and other medical practitioner.
For outpatient procedures such as skin cancer removal and dental visits, OCT represents a quantum leap forward in point-of-care diagnostics. OCT’s ability to pinpoint suspicious areas and give quantitative information about tissue could dramatically alter how and when clinicians decide on treatment. “OCT changes the process of diagnosis,” says Boppart. “This will allow us to change the standard of care.”
This work is supported in part by the National Institute of Biomedical Imaging and Bioengineering.
Zysk AM, Nguyen FT, Oldenberg AL, Marks DL, Boppart SA. Optical coherence tomography: a review of clinical development for bench to bedside. Journal of Biomedical Optics 2007 12(5):051403.