Neuronavigator
By pioneering a 3D-guidance technique called stereotaxy, Michael L.J. Apuzzo takes his place among neurosurgeons who have made seminal contributions to their field.
by Christopher Tedeschi
Neurosurgeon Michael Apuzzo shuffles a visitor into his office where they squint at a sheet of slides pressed against the window.
Instead of the brain surgery images he expects to see, the visitor looks at a stone tunnel from the ruins of the Ancient Greek kingdom of Pergamum-Apuzzo's favorite example of a medical technology 2,600 years old. The Greeks used the tunnel, with its gently running water and natural skylights, to ease the suffering of madness.
For Michael L. J. Apuzzo, M.D.(pictured at right), neurosurgery is about exploring the limits of the technological future, creating concepts and bringing them to practical application. It is about how technology-whether a stone tunnel or focused beams of radiation-can improve the practice of medicine. In his quarter-century at USC, he has played a role in expanding the technological frontier, specifically by developing and helping to introduce advanced cerebral "navigation" and focused beam stereotactic radiation treatment to neurosurgery. In those years, his work has offered expanding hope for patients who receive the daunting diagnosis of brain tumor.
Since 1989, Apuzzo has been the Edwin M. Todd/Trent H. Wells, Jr. Professor of Neurological Surgery at the USC School of Medicine. Having published more than 350 scientific works, in 1992, he became editor of the influential surgical journal Neurosurgery, further establishing his role as a key player in the international advancement of his field. For his contributions to neurosurgery, Apuzzo was recently honored by the World Health Organization and the World Federation of Neurosurgical Societies in Madrid, where he was presented with the Sixto Obrador medal by Queen Sophia of Spain.
Apuzzo used the Greek tunnel slides last summer while delivering the concluding address at the 11th International Congress of Neurological Surgery in Amsterdam, a meeting attended by more than 6,000 neurosurgeons from around the world. The title of his lecture: "Advanced Neurosurgery: Key Elements in the Emerging Technical and Intellectual Metamorphosis." The pie-in-the-sky flavor of Apuzzo's lectures has roots in his desire to treat greater numbers of patients with increased success.
Patients from the tiny portion of the population that will ever need the services of a brain surgeon come to USC to find a uniquely strong and experienced team with diverse expertise. They come to Apuzzo, to department chair and professor Martin Weiss, M.D., and to the nine other faculty members of the Department of Neurological Surgery who practice at USC University Hospital, USC/Norris Comprehensive Cancer Center and Hospital, LAC+USC Medical Center and Childrens Hospital Los Angeles.
USC's strong neurosurgery tradition for innovation and the development of concepts and instrumentation that changed the field world-wide reaches back to the 1950s and '60s, when emeritus professors engineer Trent Wells, Jr. and neurosurgeon Edwin Todd, M.D., devised and applied utilized instrumentation for the treatments of movement disorders and pain. In addition, former surgery professor and neurosurgery pioneer Theodore Kurze, M.D., helped to introduce the operating microscope universally to the neurosurgery operating room. Since then, USC's leadership role has not faltered.
"The productivity of the department has been a testimony to the climate and the environment here, which is fertile for the expression of creativity and innovative thought," says Apuzzo.
Apuzzo has taken his place in the long line of USC neurosurgeons who have made seminal contributions to their field. Since he came to the School of Medicine from Yale Medical School in 1973, Apuzzo has pioneered a subspecialty called image-directed stereotaxis, or stereotaxy, and the concept of minimally invasive surgery.
The Apuzzo family has a long maritime tradition of family members sailing on 19th century clipper ships. With hereditary links and as a former member of the U.S. Navy's nuclear submarine service, Apuzzo has taken some of his cues from the world of naval navigation, applying similar concepts to the navigational challenges of the brain. Submarines employ a variety of techniques, such as inertial guidance, bottom contour mapping, and satellite, star and radio beacon fixation for orientation, he says, and surgeons can similarly use different kinds of imaging information in concert to create brain images of ultra-sharp resolution as a database for subsequent navigation.
Based principally on research and innovations developed at USC in the 1970s and '80s, neurosurgeons now regularly use stereotaxy to pinpoint locations in the central nervous system, often deep within the brain. Stereotaxy starts with the premise that every physical location in the brain can be described as part of a three-dimensional coordinate system, and that each unique location in the brain has a unique set of coordinates- just like points on a globe can be precisely identified with a latitude and longitude.
Before brain surgery, those points in the brain must be described as specifically as possible, along with the path that will lead surgeons to their destination. They can then plan the safest possible surgical approach, usually to remove a range of unwanted things-from a tumor, to a section of brain responsible for epileptic seizures, to a bullet. Stereotactic technology used during the course of an operation helps to guide instruments to their target's location, or to focus beams of radiation on tumors without making an incision.
Information about brain structure only benefits the neurosurgeon because it gives clues about brain function. Yet in each individual, the worlds of speech, vision, memory and just about every other brain function exist in slightly different physical areas. Now functional correlates are obtainable. In the best cases, surgeons have information about structure and function before operating on a patient, heightening their chances that an operation to remove a deep-seated tumor, for example, would not damage brain areas vital to speech or memory.
In some instances, patients remain awake throughout an operation so that surgeons can assess functions like speech and memory as the surgery takes place. Since the brain itself feels no pain, a local anesthetic and a sedative usually suffice to keep a patient relaxed while surgeons observe the connection between structure and function.
Advances in imaging and biomedical engineering, Apuzzo explains, lets surgeons "take stereotaxy to another level," with structural and functional imaging and navigation, allowing Apuzzo's team to perform brain surgeries with little damage to healthy tissue, while localizing their efforts to smaller and smaller areas.
With the unique assistance of USC Schools of Cinema and Engineering and the California Institute of Technology Jet Propulsion Laboratory, part of the technological future has already arrived on the Health Sciences Campus. A peek into the neurosurgery operating room at USC University Hospital reveals an assortment of medical technology assembled by Apuzzo and his colleagues. A rack of video monitors lines the wall, a nearby bank of computers allows surgeons to rehearse delicate procedures before undertaking the real thing.
For patients, the physician expertise, intellectual resources and the innovative set up at USC means that surgeons can do more-and that they can do it with less invasive procedures. The Gamma Knife, a nuclear medicine device that uses gamma rays to attack cancer, can successfully kill or shrink brain tumors without invasive procedures. More than a decade ago, this concept of "stereotactic radiosurgery" was introduced first at the USC/Norris Hospital by Apuzzo and his colleagues Zbigniew Petrovich, M.D., the Albert Soiland Professor and chair of the Department of Radiation Oncology, and Gary Luxton, Ph.D., associate professor and vice chair of the Department of Radiation Oncology and head of the division of radiation physics, giving them the longest experience with the method of any western regional group.
Most adults diagnosed with brain tumors, Apuzzo explains, have gliomas-malignant growths arising from the cells that accompany neurons in the brain and spinal cord. A combination of experience, judgment, stereotactic navigation, radiosurgery, and dexterity allows neurosurgeons to manage such lesions, without harming healthy surrounding brain tissue.
In 1976, Apuzzo established one of the original molecular biology laboratories for the study of brain neoplasms and their relation to the body's immune system. Along with research in this area, he pioneered concepts related to cellular and molecular methods for the treatment of Parkinson's disease and created the term "cellular and molecular neurosurgery," a current area of intensive global investigation in neurological science.
USC faculty, including Apuzzo and gene therapy researcher W. French Anderson, M.D., director of the USC Gene Therapy Laboratories and professor of biochemistry and pediatrics, have already begun clinical trials of a gene therapy approach that could help patients with gliomas. This method uses a gene mounted on a viral delivery system which can be inserted into the cancer cell-that could work to eliminate the remaining cancer cells. Even more sophisticated "molecular neurosurgery" is being researched, Apuzzo says, along with advanced techniques for getting genetically engineered cells to precisely the right location in the brain.
The quest to expand his world seems to drive Apuzzo's constant motion. In the coming years, Apuzzo will train his sights on the development of molecular neurosurgery, endeavoring to use gene therapy to treat central nervous system disorders like stroke, cancer, Alzheimer's and Parkinson's diseases. Molecular neurosurgery will acquaint brain surgeons with the prospect of introducing new tissue or molecular fragments into their patients, most likely engineered cells with the ability to kill cancer cells, for instance, or to replace the vital neurotransmitters that patients with Parkinson's can no longer produce on their own.
There is no endpoint, Apuzzo says, no stage at which he and his colleagues will lean back in their chairs with a sigh and finally acknowledge that they have accomplished their elusive goal. Instead, the search for better technologies and safer treatments will continue indefinitely. With staggering advances being reported regularly by neuroscientists and molecular biologists, Apuzzo and his colleagues will be busy for decades to come. In particular, Apuzzo is hopeful that an important transfer of technology can be established with the resident space scientists at the Jet Propulsion Laboratory in Pasadena, Calif.-an alliance that has already borne considerable fruit.
The surgeon's challenge, Apuzzo says, is first to properly serve his patients, and second, to fulfill a moral obligation to acquire knowledge and properly apply technology in the service of a community. Not a far cry from the healers of ancient Greece, using their most advanced technology to contribute to society.n
For more information about Michael L. J. Apuzzo, M.D., and the USC Department of Neurological Surgery or any of The Doctors of USC and their specialties, please call 1-800-USC-CARE (1-800-872-2273).