The Infinite to the Finite
A professor from the Vanderbilt School of Engineering talks with a neurosurgeon in a hallway at Vanderbilt University Medical Center. Their discussion fine-tunes ideas that the engineer takes forward in implementation. An education researcher at the Kennedy Center meets with a biomedical engineering professor and they brainstorm ways imaging can be used to benefit children. A cancer researcher works with one of the world’s leading imaging experts to characterize tumors and assess the tumors’ response to chemotherapy.
These collaborations occur on a regular basis as Vanderbilt engineers, physicists, chemists, biologists, physicians and students undertake research in advanced methods of imaging and use it in creative and innovative ways to improve patient outcomes, guide surgery, test treatments and advance basic science, along with a myriad of other potential applications.
Technology is Here Now
Imaging — the ability to see inside the body through various technological advances such as computed tomography (CT), magnetic resonance imaging (MRI), spectroscopy, positron emission tomography (PET), ultrasound and even the basic X-ray — has improved dramatically in recent decades, and so have innovations that allow researchers to use multiple imaging techniques in concert. Advances also have helped meld together images taken at different times, such as before and during surgery.
“Ideas that were around 20 or 30 years ago can now be made to work because the technology is here now,” says John Gore, the internationally known director of the Vanderbilt University Institute of Imaging Science. VUIIS is a university-wide research center that brings together engineers and scientists with interests spanning the spectrum of imaging research — from the engineering of imaging techniques to the application of imaging tools to study the brain’s inner workings.
Gore, recently named the Hertha Ramsey Cress University Professor of Radiology and Radiological Sciences and Biomedical Engineering, also holds appointments as professor of physics and professor of molecular physiology and biophysics. Those joint appointments in the schools of Engineering, Arts and Science, and Medicine reflect the imaging institute’s transinstitutional scope.
Thomas Yankeelov, director of cancer imaging research for VUIIS, has a secondary appointment as assistant professor of biomedical engineering. He says Vanderbilt’s university-wide collaborative culture is critical to new discovery. “In order to make progress on the basic science of imaging, we need a lot of expertise,” he says. “To apply and translate those developments requires collaborating with those who are interested in using imaging to advance their own research. That research frequently informs what basic imaging science problems we should be tackling. So being inside a university that actually enables and values collaboration not only makes our jobs easier, it also makes it more fun.”
What Goes on Inside the Brain
At VUIIS, Associate Professor of Biomedical Engineering Adam Anderson and other colleagues are working on imaging projects designed to map brain function. They ask questions about how the brain changes when someone thinks about a certain topic or performs a certain function, such as learning to read or do math. How does brain function change, they want to know, in someone with a psychiatric disorder, learning disability, epilepsy, dementia or Alzheimer’s disease?
The white matter of the brain has bundles of many, many axons that connect the neurons together, Anderson explains. These bundles hold the key to understanding many disease processes. “We use MRI to study the state of these connecting bundles and relate any injury to the bundles to symptoms,” he says.
In patients with schizophrenia, the researchers have found particular pathways where the integrity of the bundles is strongly correlated with disease symptoms, such as hallucinations.
In one study using imaging, the researchers created a model for language function that can aid not only in patients with trauma injuries but in understanding how children learn language. Preliminary data on a small number of subjects in a different study helped make predictions about how well a child might do when exposed to certain tutoring methods. Anderson, who also has appointments in radiology and radiological sciences, has also conducted studies to better understand brain function in children who struggle with math.
Quantifying and Measurement
Associate Professor of Biomedical Engineering Mark Does pursues projects regarding the nervous system. His brain imaging studies seek to find ways to quantify the amount of myelin around certain axons. Since myelin, which forms a sheath around many nerve fibers, becomes damaged from disease, the researchers are seeking quantitative data so more can be understood about disease processes.
Similarly, Does is working in muscle imaging to find ways to measure inflammation as muscles heal. A bone-density tracing project using MRIs seeks to predict which bones might be susceptible to fracture and why. “There are a number of different disease conditions that are known to relate to broken bones. We are trying to find methods to diagnose fracture probability,” Does explains.
Hope for Parkinson’s
Imaging plays a key role in the School of Engineering’s focus on health care, one of its four strategic research areas. Faculty from several departments within the school work on research that involves imaging.
Bennett Landman, assistant professor of electrical engineering and computer science, joined the faculty in January and hit the ground running in developing technologies to study the human brain. Landman extends computer-automated techniques to analyze brain characteristics for large-scale imaging studies. This research targets development of new biomarkers to assist imaging staging, prognosis and treatment guidance in neurological disease. In addition, Landman is working on developing statistical approaches to allow Internet-based collaboration for better medical imaging approaches. Within VUIIS, Landman heads up the new Center for Computational Imaging, which improves the analysis resources available to basic science and medical researchers.
Professor of Electrical Engineering Benoit Dawant uses imaging in his research into innovative deep brain stimulation surgery techniques for patients with Parkinson’s disease and other tremor disorders. An electrode is implanted deep in the brain and connected to a wire on the outside of the body, functioning much like a cardiac pacemaker. The electrode creates an electric field that modifies the way neurons in the brain talk to each other.
Dawant, Research Assistant Professor in Electrical Engineering Pierre-Francois D’Haese and colleagues work with Vanderbilt neurosurgeons Dr. Peter Konrad and Dr. Joseph Neimat as well as neurologists, electrophysiologists and physical therapists in a complex process of patient selection, procedure planning, implantation and monitoring of the device.
In this procedure, the target area, called the subthalamic nucleus, is very small. Implanted in the correct spot, the electrodes suppress the symptoms of Parkinson’s. Incorrectly done, the procedure can create side effects for the patient, so precision is critical. The engineering aspect of the procedure involves using images to calculate precise coordinates for the targets, like creating a map or a GPS system for the brain. The implant is then placed using a stereotactic frame contraption, which is attached to the skull.
During the procedure, the patient is awake and immediate feedback can determine whether the probe is stimulating the correct area of the brain in the right way. The small probe is then removed, and the permanent one is inserted and affixed.
Although, in the long term, brain stimulation may be shown to slow the progression of the disease, it is currently used to minimize the symptoms of Parkinson’s. “So far the probe is not a cure, it’s palliative,” Dawant says. The team has been capturing data about the procedure to create statistical models so that surgeons outside Vanderbilt might one day utilize the same methods. “We’d like to create a big central repository for deep brain stimulation cases,” he says.
Innovations for Image-guided Surgery
J. Michael Fitzpatrick, professor of computer science and computer engineering, has partnered with Dawant to translate some of the same ideas to patients with severe hearing loss. Implanting a cochlear device currently requires removing a piece of bone behind the ear. It can sometimes take a month for the area to heal sufficiently for the surgeon to know whether the procedure was effective. Fitzpatrick, Dawant and colleagues, including Assistant Professor of Mechanical Engineering Robert Webster, have been working with ear surgeon Dr. Robert Labadie, associate professor of otolaryngology, on a concept to make the implantation procedure minimally invasive.
To provide the accuracy required for this delicate surgery, they devised a frame, or platform, similar to that used for deep brain surgery. A three-legged stand somewhat like a tiny table, it mounts behind the ear on bone-implanted anchors and is used with the aid of imaging to guide the surgical instrument in making a very small surgical entryway. There are critical areas to avoid during this procedure, especially the facial nerve and the chorda tympani, which regulates taste.
“Benoit finds where the cochlea is. I find out where the anchors are,” Fitzpatrick says.
The instrumentation still is in the testing phase but preliminary data is encouraging. “We have developed algorithms to localize the sensitive structures. We can automatically find the trajectory, the cochlea and the structures to avoid,” Dawant says, explaining that the rest of the team then designs a platform to guide the drill along that trajectory so that it makes a hole into the cochlea through which an electrode can be inserted. Other team members include Ramya Balachandran, MS’03, PhD’08, research assistant professor of otolaryngology, and research engineer and doctoral student Jason Mitchell, MS’02. Taking the research a step even further, the team is collaborating with colleagues at Leibniz University in Germany to develop a robotic arm that one day may perform parts of the ear surgery autonomously.
Fitzpatrick has been involved in implementing engineering innovations for image-guided surgery at Vanderbilt for decades. “Image-guided surgery was significantly advanced here. The systems people use day-to-day are based on what we developed,” he says. “I see my role not so much as a visionary guy but as an engineer who makes the visionary person’s idea work.”
The Bridge to Health Care
Other VUSE professors are also heavily involved in using imaging in their research. Michael Miga, associate professor of biomedical engineering, is a leading researcher in using imaging to develop compensation strategies for soft tissue deformation during image-guided surgery. Miga and Robert Galloway, professor of biomedical engineering, have conducted research to help align preoperative images with images taken during surgery. The task is difficult in organs such as the brain and liver, which tend to shift and change shape due to varying surgical presentations such as draining of cerebrospinal fluid in the case of the brain, or separation from the surrounding ligamenture with the liver. The result is a presentation of the organ that differs considerably from its anatomical orientation during preoperative scanning.
“Each organ has its own unique challenges based on the organ’s anatomy, physiological nature, and that impacts the approach that a surgeon takes,” Miga says. His research employs computational modeling techniques that mimic the behaviors of the organ and then modify the presurgical images to reflect deformations that occur during surgery. That allows a surgeon to accurately track the location and behavior of the organ despite soft tissue deformation. (See fall 2009 Vanderbilt Engineering.)
Galloway also works on research that involves finding ways to use imaging to help guide surgeons behind the eyeball while avoiding muscles and other important structures.
“What we are doing started out as image-guided surgery. Now it’s much bigger than that,” Galloway says. He sees surgeons as evolutionary, he explains, following a pathway and seeking to constantly improve their craft and patient outcomes. Engineers working with doctors are the revolutionaries, taking basic ideas and applying them to different problems in an attempt to transform and revolutionize the process.
“Vanderbilt is extraordinarily good as an institution with all kinds of imaging,” Galloway says. “It’s very difficult to find a place that does it as well, and yet we’ve been sort of under the radar. Coupled with the imaging institute, we’re the bridge that takes these therapeutic findings into health care.”