Laser light from Free-Electron Laser used for first time in human surgery

The free electron laser works much differently from other lasers. An electronic accelerator accelerates a beam of electrons, denoted by the yellow line, to relativistic speeds. The electron beam is channelled through a device, called a wiggler, that consists of a series of magnets arranged with alternating north and south poles. This produces a magnetic field that causes the electrons passing through it to "wiggle" back and forth. This stimulates them to produce laser light, denoted in red.

NASHVILLE, Tenn.—Laser light with a precise wavelength of 6.45 microns has an invisible kind of magic. It can slice through soft tissue coolly and cleanly, with less collateral damage than the sharpest steel scalpel.

Its special qualities were discovered five years ago by researchers at Vanderbilt University's free-electron laser center. The scientists still don't know exactly why infrared light of this specific wavelength works so well, but it got its first clinical test Friday, Dec. 17.

Under the expert guidance of Michael Copeland—a former Vanderbilt neurosurgeon now in private practice in Kansas City, Mo.—a beam of infrared light tuned precisely at 6.45 microns (6.45 thousandths of a millimeter) successfully removed a sugar-cube-sized amount of tissue from the center of a golf-ball-sized tumor in the brain of Virginia Whitaker, 78, from Kansas City, Mo. The operation took place on Dec. 17, at Vanderbilt's W. M. Keck Foundation Free-Electron Laser Center.

It is the first time that a free-electron laser (FEL), a powerful type of laser adopted by the Defense Department as part of the "Star Wars" missile defense program, has been used in a clinical operation. (FEL technology was first developed at Stanford University by John Madey, who now heads an FEL program at the University of Hawaii.)

"The operation shows that the FEL is an exceptional tool for exploring never-before-examined territories in surgery," said David Ernst, professor of physics and interim director of the Vanderbilt center, one of five FEL centers in the country supported by the Office of Naval Research. It is the only facility in the world that produces beams of infrared laser light powerful enough to use for surgery and is equipped to perform human operations.

Conventional lasers have been used in some forms of surgery for nearly three decades, but their use in neurosurgery has been limited due to the likelihood that they will damage areas surrounding the diseased tissue. But an FEL creates laser light in a much different fashion, giving an FEL beam special characteristics that allow it to cut a variety of tissues with exceptional cleanliness.

When the cleanness of the FEL cut is combined with computer control of the beam, exceptional precision is the result, as shown by the comparison cuts made in temporal bone.

Ordinary lasers generate light in either a solid (as in ruby lasers) or a gas (carbon dioxide lasers). The FEL, however, works by passing a stream of electrons traveling at nearly the speed of light through a wiggler, a device that produces alternating magnetic fields. These fields cause the electrons to "vibrate" at a specific frequency, which stimulates them to emit a beam of laser light. By varying the energy in the electron beam, an FEL can be tuned to a wide range of frequencies. The design is also capable of generating extremely powerful beams of coherent infrared light.

From the beginning, many scientists realized that FEL technology was an important new tool for a wide range of basic research, including biomedical applications. Among these pioneers were a group of Vanderbilt physicists and medical researchers. In 1986, they submitted an application to the Office of Naval Research's Medical FEL Program for the development of Vanderbilt as an FEL research site. Their bid was successful, giving the university the first FEL facility in the country designed specifically for applications research in the biological and biomedical sciences, as well as physics.

Initial efforts to use the FEL beam as a surgical scalpel centered on a shorter wavelength near 3 microns, but they were a failure. The researchers picked the wavelength because it was one that is absorbed readily by water molecules. But it worked too well, creating microscopic steam explosions and excessive heat that damaged surrounding tissue.

In 1993 Vanderbilt biophysicist Glenn Edwards—now director of Duke's FEL program—got the idea of trying wavelengths around 6.4 microns, a wavelength absorbed both by water and many protein molecules. Many colleagues didn't think the idea had much merit, but Edwards persisted. "It seemed more relevant to focus on the absorption of laser light by the proteins in soft tissue rather than water," he said.

After making some basic measurements and doing some back-of-the-envelope calculations, Edwards and Vanderbilt ophthalmologist Regan Logan tried the beam on some corneal tissue. It drilled a perfect hole. "We looked at it in disbelief. I have never had an experiment work the first time," he said.

Edwards and Logan invited a number of other scientists to test the technique, including Michael Copeland. They conducted a number of experiments on a variety of tissues and found that wavelengths near 6.45 microns were optimal for cutting all soft tissues. They published these results in the journal Nature in 1994.

A comparison of FEL cuts made at a wavelength of 3 microns (left) and 6.45 microns (right) shows the dramatic difference that tuning the laser to the correct wavelength makes. The darkened edges around the 3 micron are formed by damaged tissue. At 6.45 microns such collateral damage is all but eliminated.

Since then other researchers have found two wavelengths—7.5 and 7.7 microns—that cut through bone particularly cleanly. Despite the studies that have been done, however, "we still don't understand why these particular wavelengths work so effectively," Ernst said.

With a peak power of more than 10 megawatts and an average power level exceeding 10 watts, the FEL is more powerful and brighter than conventional lasers. It also produces light in pulses less than a billionth of a second long. Conventional infrared lasers also generate light in the same frequency range (2 to 10 microns), but their average power level is too low and they cannot produce the necessary pulse structure to cut tissue and bone cleanly, according to Edwards.

Researchers in FEL centers at Vanderbilt, Duke, Stanford and the University of California at Santa Barbara—as well those in France, Germany and Japanócontinue studying the basic physics of the interaction between powerful laser beams and living tissue.

At the same time they are beginning to put their findings to work. Copeland led a research effort to define the characteristics of the beam that do the best job of cutting the tissue found in brain tumors. His goal is to vaporize the tumor while minimizing the heat damage to healthy tissue. At the same time biomedical engineer E. Duco Jansen has been working with Copeland to develop a beam delivery system that is safe, efficient and comfortable enough to use in such delicate operations. Jansen found that fiberoptic cables are not suitable for this use—they would melt if exposed to the peak power levels of the FEL beam. So he took advantage of hollow glass tubes called waveguides, developed by James Harrington of Rutgers University, to do the job. The waveguides are small, lightweight and flexible. A highly reflective coating on the interior bends the light, allowing the surgeon to reach most of the areas of the surgical field. The hand piece that Jansen designed has a lens that focuses the beam down to a 0.2 millimeter spot, the size required to concentrate the beam for effective tissue removal.

In 1995, an award from the W.M. Keck Foundation allowed the FEL center to add two human operating suites. Before they could perform surgery on human patients, however, the physicists had to improve the reliability of the FEL beam. William Gabella, associate director of operations, led this effort.

"In order to do surgery we have to guarantee that the beam will stay on for the next four hours," Ernst said. In the last year the Vanderbilt FEL delivered more than 2,000 hours of beam time to facility users. Gabella and his team have demonstrated a reliability approaching that of conventional lasers. For the four days preceding the operation, they put the beam through an intensive series of tests and calibrations designed to ensure that it ran correctly.

The initial operation was designed to be the safest possible test of the FEL's capabilities. Whitaker had a tumor of a type that can be removed using traditional methods with a high success rate. Copeland opened the skull using traditional techniques. He only used the FEL to cut away a small amount of material from the center of the tumor. The rest he cut out using a scalpel.

Ultimately, Vanderbilt neurosurgeons hope to use the University's free-electron laser with a computer-assisted guidance system to remove tiny brain tumors near vital nerves and arteries that are too risky to pursue with conventional medical lasers or by traditional brain surgery.

The role of the Vanderbilt FEL center is to explore and refine medical uses for infrared laser light. Some of these applications will be based on the clean cutting of soft tissue. Other uses may include welding tissue to assist in wound healing, repairing nerves, reattaching retinas, or monitoring neurological activityówhatever applications that are found where infrared light proves superior to other wavelengths.

Contact: David F. Salisbury (615) 343-6803
David.F.Salisbury@vanderbilt.edu

Matt Scanlan (615) 322-4747
Matt.Scanlan@mcmail.vanderbilt.edu