The Story of Brain Mapping
Courtney L’Esperance remembers the day in March 2015 a neurologist told them that her husband Jonah had a brain tumor.
“He said, ‘You have a tumor the size of a small apple.’ And I’m thinking it’s like one of those little kid crabapples.”
Then they saw the MRI. It looked more like a baseball.
“It was like someone punching me in the stomach,” Courtney recalls.
They had been married only three weeks. They had just bought a house in Henrietta — a humongous fixer-upper. They were just 25, and a grade 2 astrocytoma was taking over the left side of Jonah’s brain. The tumor had to be removed, but getting to it could disrupt the areas of his brain that control speech, memory and dexterity — functions essential to Jonah’s work as a carpenter and his passion for playing guitar. Not removing it could mean that Jonah could lose the use of his tongue and his right arm and leg.
With so much at stake, a local surgeon referred the couple to UR Medicine, where collaboration between cognitive scientists and neurosurgeons is bringing advances from the laboratory directly into the operating room to help patients with brain tumors. This team — featuring members of Wilmot Cancer Institute and the Del Monte Institute for Neuroscience — maps each patient’s brain in exquisite detail before, during and after surgery. They find a route to the tumor that will least disrupt critical functions, preserving the humanity and abilities of their patients.
This work has immediate implications for individual patients, but the data it generates could also help those far into the future. Cognitive scientist Brad Mahon, Ph.D., and his team are aggregating the results of the pre- and post-operative tests to design a system that would allow neurosurgeons anywhere to plan their strategies better and to predict more accurately the impact of their operations.
“We want to develop the next generation of algorithms, so that surgeons could eventually model surgery on the computer and then generate predictions about cognitive abilities,” Mahon explains. “They could test different surgical approaches and figure out if there is a difference if the incision is here or there.”
Not relying on the average
As with other types of cancer surgery, the goal of brain tumor resection is to remove as much of the tumor as possible. The challenge is that the brain is a complex network of billions of brain cells, and any incision can sever important connections in that network, potentially leaving patients without essential abilities.
While the average brain is organized in roughly the same way, the control centers for different functions can vary by crucial millimeters from person to person. If a tumor is present, then the variation can be even more significant.
“The brain is highly plastic,” explains John Foxe, Ph.D., director of the Del Monte Neuroscience Institute. “If there’s a tumor or lesion, those functions will move as the tumor grows, so you can’t rely on the averages at all.” Before surgery, Mahon’s team pinpoints these functions using functional magnetic resonance imaging, or fMRI. With a magnetic field and radio waves, fMRI detects changes in oxygen concentration in the brain, highlighting areas engaged by different activities. Typically, when fMRI is used in surgery planning, the imaging is limited to about an hour. With Mahon, patients undergo an exhaustive battery of cognitive and behavioral tests over the course of nine hours. They also undergo diffuse tensor imaging, which maps the white matter that connects different parts of the brain.
These images reveal in significantly greater detail what is likely to be affected by an operation. “With tumor surgery, we have to make an incision to remove the tumor, but to get margins around the tumor, you also have to remove small areas of functioning brain,” says Web Pilcher, M.D., Ph.D., who leads UR Medicine’s Neurosurgery department.
“What we want to do is not allow that to impact the human being that you have lying on the table.”
Mapping, testing, verifying
For Jonah L’Esperance, that included preserving his ability to speak, walk, and use tools to craft furniture and remodel kitchens.
In the three weeks before his surgery, Jonah met Mahon and learned of the opportunity to participate in the study. He decided to go forward with the tests. In the fMRI, Jonah lay on his back and looked at a mirror placed above him at a 45-degree angle, reflecting images from a computer screen. “I would watch a slide show in there and I would have to think about everything I’m seeing,” Jonah says. He had to repeat sentences and melodies, read words and do basic math.
“There were other tests where I would have to — with my hand at my side — act out using tools, like pretending to use a hammer, screwdriver, scissors, stuff like that,” Jonah says. “Then someone else would come in and tap my toes or my fingers, and I would just concentrate on where they were tapping to light up that part of the brain. It was cool.”
He completed other tests outside the fMRI on a computer and on paper.
From all of this came a picture of exactly where Jonah’s tumor had grown among the parts of his brain that control sensory and motor function and his ability to use tools and understand three-dimensional space. It also showed the tumor enveloping a crucial neural fiber pathway connecting his speech comprehension and speech production centers.
This picture helped come up with a plan to remove the tumor with the least disruption to Jonah’s abilities. But the surgery would be complicated, and severing that neural pathway would be unavoidable. Jonah’s team expected he would come out of the operation with conduction aphasia, a condition that could cause Jonah to have trouble repeating phrases and finding words.
In the operating room, Pilcher opened Jonah’s cranium, and live images of his brain were projected on a large screen. The video of his brain was overlaid with the fMRI results using a system developed by Mahon and his team. Before making an incision in the brain, Pilcher needed to verify the location of Jonah’s language skills and find the best way in.
To do this, though, Jonah needed to be awake, and anesthesiologist Jeffrey Kolano, M.D., brought him out of sedation. Lying on his side, looking at the screen of a tablet, Jonah began naming the images he’d see. At the same time, Pilcher used a probe to stimulate different places on his brain, looking for the best entry to remove the tumor.
“There would be drawings of stuff and I’d have to say what it was,” Jonah says. “I’d have to say, ‘This is an umbrella,’ ‘This is a sailboat.’ That way if the sentence started getting weird, they would stay away from that part of the brain.”
Pilcher marked each location he stimulated with a number to help identify an area safe for him to make an incision. Each of those spots was assigned coordinates that corresponded to the pre-op fMRI for the scientists to study later. Jonah remained awake as Pilcher made the incision and began removing the tumor. He continued to do tests and talk with the OR team, who also helped him FaceTime with Courtney and his family — a crew of more than 30 crammed in the waiting room. Jonah was groggy from the sedation, but also thirsty.
“At one point, they were like, ‘How are you doing?’ and I was like, ‘I want coffee,’” he recalls, laughing.
Life after surgery
About 40 to 50 patients a year at UR Medicine undergo this kind of extensive brain mapping and awake surgery as part of this collaborative research study, which is funded by the National Institutes of Health. While many of these patients have brain tumors, this procedure is also used with patients who have epilepsy, venous malformations called cavernomas, and other conditions that require surgery in parts of the brain that control critical functions.
“This gives us more feedback and allows us to be more aggressive,” says Wilmot neurosurgeon Kevin A. Walter, M.D. “It also allows us to work on better rehab. The earlier you can identify the problem, the better the results.” Jonah underwent weeks of rehabilitation with speech, physical and occupational therapy every day for hours. He couldn’t hold a spoon. He was nervous to try playing his guitar and shy about singing. He struggled to say words that he recognized on paper and the names of the people who came to visit.
“One of the days, every time I’d try to say something, all I could say was ‘Tony Pepperoni,’” Jonah says, the name of the pizza shop where he’s worked since high school. “I knew I was saying it wrong, but I couldn’t get anything out.”
He learned tricks to help him along — like trying to sing or imagine the words so that another part of his brain would engage and bring it out. Family and friends would quiz him, too. “Courtney’s dad would hold up an acorn and be like, ‘What’s this?’ He’d point to an airplane and he’s like, ‘What’s that?’” Jonah says.
About two months after his surgery, with his head healing and his words returning, Jonah went back to see Mahon and his team to repeat the cognitive tests. He also underwent six weeks of low-dose chemotherapy and radiation, followed by more chemo. Several months later, he returned Mahon’s lab for another round of cognitive testing.
Each time, his abilities improved, and Mahon could see that Jonah’s brain was remapping itself to compensate for the tissue that had been removed during surgery. The connection between his language comprehension and language production centers was changing, and, Mahon suspects, rerouting to the right hemisphere of his brain.
Jonah, who had gone into the operation just wanting to be the same as before, was playing his guitar again and back to crafting coffee tables and countertops.
“I still remembered how to use all the tools,” Jonah says. “It was like riding a bike.”
Space to innovate
For Mahon and his team, watching Jonah’s progress prompted a series of new hypotheses to explore with future patients. They began to wonder whether there is something unique about the brains of patients like Jonah that allows them to recover from conduction aphasia that isn’t present in patients who don’t recover. If so, they wondered, would it be possible to encourage that feature among patients who may be less likely to recover?
Each case reveals new details about the brain’s structure, functions and resilience — adding to the understanding of how the brain works. And with every case come new questions: When functional centers are activated, why do less critical regions light up on the fMRI too? How does interrupting white matter pathways affect brain function? How can the information about the way the brain re-maps itself as tumors grow and are removed be applied to other situations such as stroke?
“We want to develop a better tool to winnow the future fMRI maps to make better predictions about what’s going to be affected,” Mahon says. “We want to improve the quality of the fMRI data and the quality of analysis and interpretation of data.”
Although technology in the field of brain and cognitive science has advanced rapidly over the past two decades, its translation into health care has been slower.
“fMRI still only has a marginal role in neurosurgery, even though it’s been around for about 20 years,” Mahon says. “There’s space to innovate here.” His collaboration with the Neuro-surgery team is making that possible.
“Translational research is the last step in taking a scientific discovery into clinical practice,” Walter says. “It’s a process like this, building on what we know.”
For families like Jonah and Courtney, it’s also an opportunity to make a difference.
“I immediately thought, let’s do it because it’s only going to benefit you and other people who have tumors,” Courtney remembers.
Since then, they’ve finished the renovations on their fixer-upper and are looking for a new home with more space for Jonah’s workshop.
“As with any part in life, you just need patience,” Jonah says, thinking back on his experience and what it has meant. “I was glad to help with that. It was cool.”