Doctors thread the catheter through about three feet of a patient's body. They begin at the femoral artery in the groin, go through the aorta, past the heart, up the internal carotid artery in a patient's neck, and into the middle cerebral artery, where 85-90% of clots get stuck.
Portland, OR -By any measure, the five patients were in bad shape.
It was November, 1999, and suffering from severe stroke, each was paralyzed on one side of the body, and had lost the ability to speak. With mortality chances for this condition as high as 70%, their families decided to try a new technique called Laser Thrombolysis (LT) in which doctors thread a catheter through the body, then fire a laser beam at the clot that's blocking blood flow to the brain.
For one patient, the treatment came too late, and he died from effects of the stroke. For two more, the young technology wasn't a match for their advanced conditions; doctors couldn't fit the catheter through the twisting pathways of brain arteries, so they never fired the laser.
But the other two patients had successful operations. And today they have returned to lead nearly normal lives, including walking, talking, and feeding themselves, says Dr. Kenton Gregory, a cardiologist at the Oregon Medical Laser Center (OMLC) at Providence St. Vincent Hospital, and a former engineer. It's not enough that the catheter carry fluid and laser light gently through the body-it also must withstand the torque that doctors apply to steer it. This pioneering medical technique is the fruit of ten years of engineering work in materials, lasers, photonics, and fluid flow dynamics.
Blood lets the body breathe. A stroke is a heart attack of the brain, explains Lisa Buckley, research lab manager at the OMLC. In both cases, a clot stops the blood supply. "It blocks the oxygen and nutrients blood would bring, and over time, cells start to die when they're deprived of oxygen," she says. "A stroke is a brain attack."
Anyone who's held his breath too long in a swimming pool knows that sometimes, time means everything. In fact, the doctors in Buckley's lab have an expression for this: "Time is brain." Indeed, most stroke or heart attack patients must reach a hospital within a scant few hours to have hope of full recovery.
Faced with this challenge of clearing arteries as fast as possible, Gregory was stationed at Massachusetts General Hospital (Boston, MA) in 1988 when he invented a technique to vaporize a clot with 577-nm wavelength laser light, thus avoiding major surgery and incurring less time and lower cost. In 1991 he opened the lab in Oregon, and soon used the method to help heal more than 30 heart attack patients. But the medical market had other heart attack cures, such as balloon catheters and scraping catheters (to reduce clot formation), stents to hold weak arteries open, and drugs to grow whole new arteries. So he started adapting the technique for stroke.
Medical engineering. He had to tackle two major engineering problems first: the catheters were too stiff to navigate the brain's twisted arteries, and they forced doctors to work slowly, since there was no real-time feedback. Fortunately, he had the perfect background for tackling technical puzzles. Gregory started out as a chemical engineer in the oil business. "I was only going into biomedical training for a year, but I got hooked," he says. "Chemical engineering also has a lot of pumps and pipelines, so medicine was something where I had success."
In his original version of LT, doctors threaded a catheter through a patient's arteries to his heart, then beamed a laser along an optical fiber inside, vaporizing the clot. They sporadically tracked the operation with an angiogram, an x-ray technique that photographs the radio-opaque dye injected into a patient's veins. When the dye stops flowing, you have found the clot.
"The unique thing that Dr. Gregory discovered at Mass General was that this standard fluid acted as a wave guide, so it could carry and propagate the light out the end of the catheter," Buckley says. He could shine a laser beam through a 120-cm long catheter, and it would project 1-2 cm beyond the tip, as long as the fluid maintained a smooth laminar flow.
"It turned out serendipitously that radio-opaque fluid has the identical qualities of quartz and fused silica," says Gregory. As long as there is a "refractive index mismatch" between the fluid and the catheter material, laser light will follow the liquid.
This new liquid-core laser had three immediate advantages:
more flexibility than the stiff fiber optic cable
doctors could instantly track their progress with x-ray fluoroscopy (or angiogram), since they were flowing the dye directly through the catheter
it was much cheaper, since it used less fiber optic material and had no expensive lens at the tip
Laser science. But there was still a fatal problem in animal tests; the laser often blasted holes right through the 1 mm thick blood vessel walls. So Gregory studied the clots, and noticed that their hemoglobin gave them a red color that contrasted with the white vessels around them. For laser energy between 400-600 nm wavelength, this red color will absorb 100-300 times more light than white color will. He adjusted the laser to this precise level, using a 1 micro-sec. pulsed dye laser, emitting at 577 nm, at an average power of 100 mW.
"Most high energy medical lasers not only vaporize clots, but also the vessel," Gregory says. "If you push a laser beam 200 microns too far, it can be fatal. So we needed a safer one." The laser he uses heats the clot in a millionth of a second to 500-600C, creating vapor bubbles that expand and collapse so fast they create shock waves that break up the clot.
The whole process takes about 30 minutes, including the painstaking job of snaking a catheter through three feet of arteries, says Dr. Wayne Clark, a neurologist who is director of the Oregon Stroke Center, at Oregon Health Sciences University. Once the catheter is in place, the job takes only 90-100 sec (the team's record is just 49 sec).
"So it's minutes rather than hours," Clark says. By comparison, the only current FDA-approved standard for stroke treatment is an injected enzyme treatment called tissue plasmogen activator (TPA), which takes 90-120 min to take effect, and has the danger of thinning the blood too much, causing excess bleeding, he says.
But there is still room for improvement. The team learned a tough lesson with the two early patients they couldn't help. "With the first couple patients, we couldn't get up through the tight bends and curves in the skull there, so we never even turned on the laser," Clark says. "But then we modified the catheter, so we could steer it up the internal carotid artery, along those snakes and curves, to the middle cerebral artery."
Materials are the future of LT. So the next step is a search for the perfect material, to ensure the catheter is flexible enough to fit through any patient. Potential new materials must satisfy four demands, says Chuck Hadley, CEO of LaTIS (Coon Rapids, MN), which designs and manufactures catheters:
the material must preserve the "refractive index mismatch" with the fluid inside
it must be strong at a very small size, since doctors first thread a catheter with 2.3-mm ID into the body, then snake the 1-mm OD LT catheter inside that
it must stay flexible, so it can negotiate the "loop-de-loop" path of the internal carotid artery inside the brain
and of course, it must satisfy the FDA
There are very few solutions to these materials demands, Hadley says. The company has used teflon in the past, but is now using a proprietary type of extruded plastic.
Based on this early success, the FDA has given the Oregon doctors permission to attempt cures with the method on a dozen patients (including the first five), as the team continues to use engineering to fine-tune LT and shave a few more precious minutes off their response time.
When "time is brain," that's all the difference in the world.
material must refract the laser light from the fluid
material must remain strong in a 1-mm OD catheter
material must stay flexible
material must satisfy FDA regulations for medical usage
laser light must remain at precise strength and wavelength
Other applications for fluid core light technology
A similar technology is used in the "flexible, liquid core light guide," a much larger tube "as big as your pinky finger" which carries non-laser light by using the same principle of a refractive mismatch, says Linda Ware, a spokesperson for the Thomas Jefferson National Accelerator Facility (Newport News, VA).
Researchers at that laboratory recently won a patent for their innovative uses of the technology, such as transmitting ultraviolet light to a remote location to cure glues. And since the technique is so efficient, it can also be used to provide basic or decorative illumination of a room, like shining a flashlight through a hose to wherever the light's most needed. Medically, it can also be used "backwards." When a certain radioactive fluid contacts cancer cells, it emits gamma rays, and the flexible, liquid core light guide can carry these rays back to a detector outside the body. Used as a medical probe this way, it allows a surgeon to confirm that he's removed all the cancer cells after an operation, Ware says.