It’s a conundrum that every neurosurgeon faces. Remove too little tumor and you decrease a patient’s chance for survival. Damage healthy tissue near a critical brain function and the patient may incur neurological deficits, impacting his or her ability to see, speak and move.
Although existing surgical navigation systems are pre-loaded with an anatomical map of a patient’s brain, they don’t contain the location of language, vision and motor control centers. That information is obtained separately, and requires patient cooperation before or during brain surgery.
Now researchers from Washington University School of Medicine (WUSM), including Mallinckrodt Institute of Radiology (MIR), are collaborating to provide neurosurgeons with a way to make these surgeries easier, more efficient and safer for patients.
Researchers at WUSM and MIR, along with medical device maker Medtronic, are developing a software program that merges images of patient’s brain anatomy with the location of key functional centers of the brain to create personalized 3D brain maps. The goal is to embed the software in a surgical navigation system that can be used by neurosurgeons anywhere.
“In many ways, the traditional way of getting information for the surgeon doesn’t work for every patient,” says Joshua Shimony, MD, PhD, associate professor of radiology at MIR.
“With the new 3D mapping, not only will the surgeon know where they are in the brain but they’ll know what that part of brain does,” says Eric Leuthardt, MD, professor of neurosurgery at WUSM.
Shimony and Leuthardt are co-principal investigators of this research, which is being financed by a $3.6 million grant from the National Cancer Institute of the National Institutes of Health.
Shimony is a member of MIR’s neuroradiology clinical section and Neuroimaging Laboratory (NIL). Leuthardt is director of the Center for Innovation in Neuroscience and Technology for the Department of Neurological Surgery. Together they’ve been working on the software since 2010. “The new grant will allow us to build upon and continue our research,” Shimony says.
Above: Joshua Shimony, MD, PhD (first row, center) and a multi-disciplinary team from MIR and WUSM were involved in developing the software that creates 3D brain maps.
If You Build It, They Will Come
Unlike most grants, where an investigator comes up with an idea and then seeks funding, this was research guided by topic, says Shimony. The need was specific. The NIH put out a request for an application, or RFA. “They wanted to encourage industry-academic collaborations in neuroimaging, and they wanted it in the area of cancer.”
Eric Leuthardt, MD, is co-principal investigator of the NIH-funded grant with Joshua Shimony, MD, PhD.
The timing was perfect. Shimony and Leuthardt previously worked with Medtronic, and had been investigating how to extract “resting state” data from functional MRI (fMRI) scans to localize speech, vision and motor control centers.
The concept was novel, and MIR was one of the first institutions to publish an article about this new paradigm for pre-surgical planning. It appeared in Academic Radiology in 2009 and Shimony was the lead author. Despite his early involvement, Shimony didn’t appreciate the significance of resting state as soon as his NIL peers did. His colleagues at the time, including MIR pioneering radiologist and neurologist Marcus Raichle, MD, were studying resting state after discovering that a previously unknown brain network – called the default mode – could be seen with it. It was their work that piqued Shimony’s interest. “It kind of dawned on me that this might be something big.”
“Resting” Doesn’t Mean Inactive
Resting state doesn’t mean the brain is at rest. It means the patient is resting, daydreaming or not engaged in a task during their scan. The brain remains busy.
Task-based fMRI requires patient cooperation. Patients have to perform a task. They may have to tap their finger, repeat a word, or look at flashing lights. “We look for stimulation changes in the brain associated with the process.”
“But task-based fMRI doesn’t work in about half of the patients who need brain scans,” says Shimony. They include patients who are cognitively impaired, perhaps because of a brain tumor, or have certain physical limitations or are very young or very old. “The thinking then became if you can figure out a way to acquire this information from resting state fMRI, you could solve the problem.”
It turns out you can. “Different systems in the brain carry on internal communication even when at rest,” says Shimony. “By analyzing resting state data for this internal communication, we can obtain information very similar to that acquired with the task fMR.” And it’s faster and more reliable.
“We often have to do multiple attempts for traditional fMRI,” says Michelle Miller-Thomas, MD, assistant professor of radiology. In fact, functional MRI has a failure rate estimated at 30%, which means the results are not useable and the scan has to be repeated.
What’s unique about this resting state technique compared to a more traditional functional MRI is that the patient doesn’t necessarily have to comply with what we want them to do,” says Miller-Thomas, who also runs the advanced imaging service in neuroradiology.
Advantages and Challenges
Resting state fMRI is easy to perform. “All the patient has to do is lie quietly in the MRI scanner,” says Shimony. They can even sleep or be sedated, which is helpful in very young patients and those with anxiety.
In some cases it’s an alternative to cortical stimulation, a process that localizes brain function with an electrical current during surgery while the patient is temporarily awake. This method increases the length and cost of surgery, and has some risks, including seizures.
But resting-state fMRI has its own set of challenges, including, how to process the advanced imaging datasets so that it can be used clinically. To accomplish this and to use resting state fMRI in their navigational system, Shimony and Leuthardt relied on neuroscientists and computer programmers to develop software to process the raw data. Carl Hacker, an MD/PhD student, together with colleagues, developed the software that is a key component of the analysis. The Neuroimaging and Informatics Center at MIR also played a major role in creating an imaging pipeline and interface to transfer patient information to PACS stations and the
operating room. They formed a mechanism to transfer data back and forth.
In a concerted effort that involved a diverse range of talents — from neuroscientists to computer programmers to graduate students — locations of brain functions were laid on top of the anatomic images. “What we’re creating for surgeons are pictures or an idea of where the important parts of the brain are for specific functions,” says Miller-Thomas. “Surgeons can then plan their surgeries before they enter the operating room. They can plan their approach and may see whether one approach may disrupt one of these important centers or the fibers that connect them.”
Supply and Demand
Results were good, and demand for resting state fMRI grew as word got out among neurosurgeons.
“It got to the point where it became very desirable to stop treating this as experimental medicine and treat it as a clinical method,” Shimony says. “We studied it in many patients for a couple of years, and it worked really well.”
In 2015, with the help of a Barnes-Jewish Foundation Grant, resting state fMRI was offered as a routine clinical service for neurosurgeons performing brain surgery at Barnes-Jewish Hospital. Since then, they’ve performed over 1000 cases using resting state fMRI.
“I think this effort characterizes and separates us,” Leuthardt says. “We’re the only institution in the nation that regularly uses resting state fMRI for clinical surgery.”
Above: Michelle Miller-Thomas, MD, runs the advanced imaging service in neuroradiology.
Time Will Tell
While the product works for research and in academic hands at MIR, it still needs some extensive refinement before it’s commercially available.
“Right now, it’s kind of an interim solution to incorporating the data into the navigation system, and we want to come up with an elegant, permanent solution,” Shimony says.
“There are a lot of details that need to get hammered out,” says Leuthardt. “There’s the grand and dramatic vision that we’ve implemented. But getting this to a hard-baked clinical algorithm that anybody can use, that actually requires a lot of work.”