A research team at Massachusetts General Hospital (MGH; Boston, MA) has developed a laser-based technique that, because it can visualize deposits of plaque, macrophages, and other dangerous components inside coronary arteries quickly, accurately, and in three dimensions, holds the promise of helping to diagnose the early stages of heart disease in real time. The technique—optical frequency-domain imaging (OFDI)—has proved successful in initial tests on live pigs. Now, its developers have started the first clinical trials of the method on human patients. These include a project in collaboration with doctors at the Lahey Clinic in Burlington, MA.
If the trials and subsequent research prove successful, the technology would give cardiologists a fresh, noninvasive diagnostic tool. “This is a fundamentally new way of looking at coronary disease,” Gary Tearney, associate professor in the Wellman Center for Photomedicine at MGH, told a seminar in Boston University’s Photonics Center.
The method also has potential for detecting early signs of certain cancers, such as that of the esophagus. Ultimately, the developers suggest, it might be possible to link OFDI with the delivery of laser treatment for cancers detected in their early stages. “Our hope is that, through one minimally invasive probe, clinicians will be able to diagnose and precisely treat diseased tissue while sparing adjacent healthy tissue,” explains Tearney’s colleague Brett Bouma.
The technique relies on a unique laser source that uses a semiconductor optical amplifier and a custom-made filter based on a polygonal scanner, says Tearney. The system emits pulses across a wavelength range of 111 nm with a repetition rate of 64 kHz, and average power of 10 mW. In action, the laser tip rotates inside a fiber-optic catheter probe inserted in the appropriate blood vessel. As it rotates, the laser tip emits an infrared beam with a wavelength that changes continuously and rapidly between 1264 and 1376 nm. Moving along the blood vessel, the probe captures light reflected by the interior walls of the vessel. The system determines the echo time delay and the amplitude of the reflected light by detecting spectrally resolved interference between the walls and a reference. Images from the interference pattern are produced by applying a Fourier-transform procedure.
Scanning long stretches
Optical-frequency-domain imaging resembles optical-coherence tomography (OCT), another imaging technique developed at MGH, in that both processes use interferometry to measure the electric field amplitude of light reflected from inside a particular organ or blood vessel. However, OFDI has one key advantage over OCT: speed. “From a practical standpoint it’s a couple of orders of magnitude faster,” Tearney explains.
That is important because of the basic roadblock that faces any clinician who tries to visualize the interiors of blood vessels. The blood itself obscures plaque deposits, macrophages and other features in images captured by OCT and similar techniques. To obtain clear images, therefore, technicians must first flush the artery under study with saline solution. That preparatory process temporarily clears out the blood and gives investigators several seconds to capture images before the blood returns. Plainly, the faster and more efficient the imaging method, the more information it can obtain during that period.
Even with the speed limitation, OCT can successfully identify plaque in coronary arteries. However, it works too slowly to permit continuous scanning of the interior walls of arteries. Instead, clinicians use the procedure to sample specific points along those walls. By contrast, OFDI can scan entire long stretches of an artery’s interior, to reveal both vascular networks that contain the arteries and the structural details inside individual blood vessels. In one preliminary study on live pigs, for instance, OFDI scans provides detailed images of the surfaces of artery segments 24 to 63 mm long. Close examination of the images confirmed that the method could differentiate between healthy and diseased tissue.
The technology also has potential for use in postoperative monitoring. In one demonstration, the MGH team intentionally overinflated a balloon catheter in a pig’s artery to damage the arterial wall and implanted a stent that partly overlapped the damaged region. An OFDI image of the entire region shows the stent’s metallic mesh and clearly differentiates between the disrupted and undamaged region of the artery (see figure).
The team’s experiments also included successful imaging of live pigs’ esophagi, which suggests the possible use of OFDI to diagnose Barrett’s esophagus, a precursor to cancer of the esophagus in humans. What is clear, Tearney says, is that “OFDI is now a clinically viable technology.”