A New Way to Treat Cerebral Aneurisms
December 2008 / January 2009
Volume 6 Number 6
Each year, about 30,000 people in the U.S. die or suffer neurological damage from cerebral aneurysms, which form when a weak or thin region on a blood vessel in the brain bulges and fills with blood. An aneurysm can put pressure on a nerve or the surrounding brain tissue. If left untreated, an aneurysm can grow until it leaks or ruptures, spilling blood into the surrounding tissue and causing a hemorrhagic stroke.
Stroke is the leading cause of disability in the U.S. and the third most common cause of death, after heart disease and cancer. Although strokes are most common in the elderly, they can occur in people of all ages, including children and infants. Significant strides have been made during the past few decades to lessen the stroke occurrence rate. According to the Centers for Disease Control and Prevention, the number of strokes has decreased steadily since the 1950s, primarily because more people are controlling their blood pressure and taking steps to prevent diseases that can lead to stroke. The decreased number can also be traced to better treatment options for people who have aneurysms.
Lawrence Livermore researchers are collaborating with colleagues from the University of California (UC) at Davis's Center for Biophotonics, Science, and Technology and from UC Berkeley to develop safer, faster, and more cost-effective treatments for patients with cerebral aneurysms. The team's effort is funded primarily through Livermore's Laboratory Directed Research and Development (LDRD) Program, the National Institutes of Health (NIH), and the National Science Foundation.
Livermore scientist Duncan Maitland, who leads the team of 30, stresses the need for individualized approaches to the problem. "Cerebral aneurysms are not life-threatening until they begin pressing on the brain or burst," he states. "The problem is that few technical solutions currently exist for treating these aneurysms. Each aneurysm is unique and therefore requires customized treatment. We are widening the range of treatment options."
Today, two treatment categories are available for aneurysms: surgical and nonsurgical. The goal of each is to prevent blood from entering the bulged-out section of the vessel, called the sac. Blood flow in this region increases pressure on the weakened vessel wall and heightens the risk of rupture.
Microvascular clipping, introduced in 1937, is the most common surgical treatment for cerebral aneurysms. For this treatment, a section of the skull is removed to expose the aneurysm under a microscope. The aneurysm is then completely closed off with a tiny (1- to 2-centimeter-long) metal clip to prevent bleeding or rupture and thereby protect nearby brain tissue from damage.
If the aneurysm has grown enough to severely damage the blood vessel, the surgeon may elect to reroute the blood flow around the damaged area by grafting a piece of blood vessel from another part of the body.
The second procedure, called embolic coiling, is a nonsurgical treatment that was approved in the early 1990s for patients with inoperable aneurysms. For this treatment, a small plastic catheter is inserted in either the femoral (leg) or carotid (neck) artery. A contrast dye injected in the bloodstream through the catheter highlights the normal blood vessels and delineates the aneurysm.
Continuous X-rays of the patient's vascular system, provided by an imaging technique called fluoroscopy, help the surgeon maneuver a microcatheter into the aneurysm through the original catheter. Then tiny platinum wires—€”only slightly larger in diameter than a human hair—€”are deposited into the aneurysm. Finally, the wires take on a coil shape and induce blood clotting, which reduces or blocks blood flow in the sac.
Aneurysms with small entrance points, called narrow-neck aneurysms, are generally treated with the wire coils. A wide-neck aneurysm can also be treated with coils, but a stent or balloon must be used with the coils to prevent them from migrating to the parent vein or artery.
Doctors consider several factors when deciding which treatment option is best for a patient. These factors include the type, size, and location of the aneurysm; risk of rupture; patient's age, health, and medical history; and risk of treatment. Both surgical and nonsurgical methods have some drawbacks. "Using detachable coils to treat an aneurysm avoids many of the risks associated with surgery, but the treatment is a time-consuming process," says Maitland. "Because the coils can compact over time in the sac, 40 percent of the patients must have more coils implanted at a later date. In addition, each implanted coil has a 2-percent risk of bursting the aneurysm."
"Smart" Foams
To address these shortcomings, Maitland's team developed an alternative treatment that isolates an aneurysm from the rest of the vascular system with one implanted device—€”a "plug" made from shape-memory-polymer (SMP) foam. SMPs are a class of polymeric materials that remember their primary (original) shape after being molded into a secondary (temporary) shape. Depending on the type of SMP, it can be altered from one shape to the next using heat, moisture, pH, or electric or magnetic fields. The Livermore-developed SMP foam plug is altered with heat.
Researchers first cut a plug out of the foam material to match the contours of an aneurysm. Then a crimping machine with heated blades compresses the foam plug into a stable secondary shape that can be fed through catheters via a fiber-optic cable to the aneurysm sac. Once the plug reaches the sac, it is heated with diode-laser light through the fiber-optic cable. Heating time could range from as little as 10 seconds to several tens of seconds, depending on the temperature at which the foam plug is designed to fully expand to its primary shape. As the plug expands, it absorbs blood, which congeals and forms clots to stop blood flow inside the aneurysm.
Although foam plugs have not been directly compared with platinum coils in statistically significant trials, studies with an in vitro aneurysm model demonstrated that the technology is efficient in filling the aneurysm sac. Livermore chemical engineer Thomas Wilson, a polymer materials expert, says, "A key feature of Livermore's SMP foam formulas is an open-cell structure, which makes the foam very porous and absorbent. We can make a foam plug that expands 80 to 90 times its compressed secondary shape."
Foam Versus Platinum
If Livermore's foam-plug procedure is approved for clinical trials, it could lead to a new, nonsurgical treatment option for patients. Wilson is optimistic because the foam plugs offer several advantages over platinum coils, including faster and more complete occlusion of the aneurysm and lower and more uniform stresses to the aneurysm wall, thereby decreasing the risk of hemorrhage.
"A doctor may have to add 20 platinum coils, one at a time, to fill the volume of an aneurysm that would require only one or two foam plugs to fill," says Maitland. "If the coils become compacted, the already vulnerable aneurysm wall may be reexposed to blood flow. We want to eliminate the need to treat an aneurysm more than once during a patient's lifetime."
The foam plugs may also prove safer than platinum coils, which can unravel and migrate into the blood vessel, potentially increasing the risk for aneurysm regrowth and rupture. "The foams are softer and have more tissuelike mechanical properties, so they are less likely to injure surrounding arterial tissue," says Wilson. What's more, each plug device can be customized to fit the distinct contours of the aneurysm being treated and is therefore more likely to stay in place.
In addition, unlike platinum coils, Livermore's foam plugs could be made from bio-absorbable material, which could help to heal the aneurysm. "We hope to develop a foam plug that can biodegrade into small molecules and be safely absorbed," says Wilson. "Over time, the device would essentially disappear and be replaced by human tissue."
Chemistry and Dynamics
The Livermore SMP foam plugs are composed of four materials: hexamethylene diisocyanate; 2,2,4-trimethyl hexamethylene diisocyanate; 2-hydroxypropyl ethylenediamine; and triethanolamine. By adjusting the relative amounts of these materials, Wilson has developed three foam "recipes," which respond to various ranges of temperatures.
The temperature at which a compressed foam plug resumes its primary shape is called the glass transition temperature (Tg). Foams with a low Tg expand to their primary shape when heated from a cooler temperature to below normal body temperature (37°C); foams with a mid-range Tg expand when heated to 45°C; and foams with a high-range Tg expand when heated to 60°C and above. Wilson can alter each recipe to allow for greater heating and cooling margins as necessary. When the Tg of a foam plug is above normal body temperature, a laser or other heating mechanism is required to restore the foam’s primary shape.
The Livermore group is working with UC Berkeley to develop a measurement system that records aneurysm-wall temperatures during laser delivery of the implanted plug devices. The system will help researchers assess the effects on arteries from heating the foam plugs internally. "Foams with a transition temperature just above normal body temperature are optimal because they won't require much additional heat to expand," explains Wilson. "The goal is to reduce the foam's transition temperature to minimize internal damage to tissue."
Shape-Changing Team Dynamics
In 2008, the team received five years of NIH funding to test Livermore's plug devices on animals at Texas A&M University. As a result, Wilson will continue leading the team's research efforts at Livermore, while Maitland is in Texas working with a team of veterinary surgeons to test the plug devices on animals.
In addition, Maitland will continue to focus on the advancement of SMP foams originally developed at Livermore. He notes that SMPs are receiving a great deal of scientific interest for applications that range far beyond medicine. "Our SMP foams could be used to deploy large structures in space such as solar panels," says Maitland. "They could also be used to make expandable packing materials to protect a delicate instrument during shipping." Another application could be self-expanding insulation in clothing.
The team is now in discussions with companies to license the SMP foams for treating aneurysms, although it may be some years before Livermore's foam technology materializes into medical devices. Wilson is optimistic that Livermore's SMP foam technology holds the potential to radically improve the prognosis for those with aneurysms. Livermore biomedical engineer Jane Bearinger says, "Our technology can leverage existing delivery systems to transport a foam plug to an affected vessel. The foam plug will fill more of the aneurysm than present therapies and encourage clotting, thereby blocking off the defective vessel region." Maitland adds, "Cerebral aneurysms are an undertreated medical problem. Our new foam technology has the potential to make dramatic gains in survivability and quality of life."
Kristen Light is a writer at the Lawrence Livermore National Laboratory.
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