Optical Technique Improves 'Virtual Biopsies'

A new optical imaging technique, optical frequency-domain imaging (OFDI), can provide three-dimensional microscopic views of the inner surfaces of blood vessels and gastrointestinal organs and could be useful for identifying precancerous lesions and dangerous deposits of plaque in the coronary arteries.

The method, developed at the Wellman Center for Photomedicine at Massachusetts General Hospital (MGH), is an advance over optical coherence tomography (OCT), another noninvasive MGH-developed technology that details much smaller areas.

The MGH-Wellman team reports that OFDI successfully captured images of the inner esophageal surfaces of living pigs, revealing the structural details and vascular networks of 4.5-centimeter-long segments with less than six minutes scanning time. Scans of coronary artery surfaces were similarly successful, producing 3-D microscopic images of the surfaces of segments 24 to 63 millimeters long. An experiment designed to evaluate OFDI's ability to detect damage to arterial surfaces confirmed that the technique could differentiate between healthy and damaged tissue.

"For diagnosing early-stage disease, the clinician has been basically looking for a needle in a haystack; so sampling only a few microscopic points of an organ, as we could with OCT, is clearly not sufficient," said Brett Bouma, PhD, of the MGH-Wellman Center, senior author of a report on the method in the journal Nature Medicine. "With OFDI, we can now perform microscopy throughout very large volumes of tissue without missing any locations."

While OCT can examine surfaces one point at a time, OFDI is able to look at over 1000 points simultaneously by using a new type of laser developed at MGH-Wellman. Inside the fiberoptic catheter probe, a constantly rotating laser tip emits a light beam with an ever-changing wavelength. Measuring how each wavelength is reflected back, as the probe moves through the structure to be imaged, allows rapid acquisition of the data required to create the detailed microscopic images.

Among potential applications of OFDI could be diagnosis of Barrett's esophagus, a precursor to esophageal cancer that can be identified with OCT, provided the affected tissue is scanned. The researchers estimate that the esophageal scan conducted in this study could be reduced from six minutes to less than one with more powerful computer processing. Another major application would be examining coronary arteries for the vulnerable plaques believed most likely to rupture and produce heart attacks. A 2005 study from the MGH cardiology division found that OCT could identify vulnerable plaques in symptomatic patients, and the OCT-developed scanning criteria could be used with OFDI to further study the vulnerable plaque hypothesis and potentially to diagnose dangerous plaques and guide their treatment.

The MGH-Wellman researchers also anticipate extending the technology's capabilities into other fields.

"One of the most exciting concepts would be to directly link OFDI with the delivery of therapy, such as laser treatment for early cancer," said Bouma, an associate professor of dermatology at Harvard Medical School. "Our hope is that, thorough one minimally invasive probe, clinicians will be able to diagnose and precisely treat diseased tissue while sparing adjacent healthy tissue."

A National Institutes of Health-funded clinical trial of OFDI to monitor patients with Barrett's esophagus is currently underway at MGH, and a trial of potential cardiovascular applications should start up within the coming weeks. The current study was supported by grants from the National Institutes of Health and from the Terumo Corp., which has licensed cardiovascular applications of OFDI. MGH said it is seeking an industrial partner to develop the gastrointestinal applications. Several of the study's authors hold patents related to aspects of OFDI technology.

For more information, visti: www.mgh.harvard.edu