Pathak spent the next year vetting the new brain images with Juan Fernandez-Miranda, a Pittsburgh neurosurgeon and neuroanatomist. He wanted to confirm that the virtual tracts he created on his computer screen matched those that the doctor saw during surgery. Fernandez-Miranda edited the images, pointing out when they were correct and when they took a wrong turn. The collaboration created a tenacious feedback cycle in which Pathak tuned the mathematics to create a tract, then Fernandez-Miranda identified what was anatomically correct. Finally, Pathak’s non-invasive virtual dissection rivaled Fernandez-Miranda’s own bloodier one.
Okonkwo immediately saw the implications and began collaborating with Schneider to test the technology in a research trial by recruiting patients with brain injuries.
Pathak and other members in Schneider’s lab then worked with Okonkwo and Fernandez-Miranda on an iPad app to create a tool that was clinically relevant and useful to neurosurgeons as they performed brain surgery or searched for damage in an injured patient.
Visualizing the Damage
Two weeks after the scan, Tom and Karen sat with Okonkwo in an office at the University of Pittsburgh Medical Center Presbyterian. It was September 2012, more than three years since his fall. Tom hoped to hear a conclusive diagnosis, an anatomical explanation for his troubles and the rehabilitation strategy. He had been haunted by memories of the man he was before the accident, and he longed to be himself again.
Using his iPad, Okonkwo pulled up an image of Tom’s brain. Each of the tracts was brightly colored, and looping, twisting and crisscrossing like a whorl of spaghetti.
On the screen, the left side of Tom’s brain was green and the right side, red. There tends to be a natural symmetry between the two halves of the brain, and asymmetry makes us suspicious, Okonkwo explained. Although it could be due to a natural difference between the left and right hemispheres, it might indicate an injury where circuits have been disrupted. In some regions of Tom’s brain, Okonkwo added, the circuits were asymmetrical.
He clicked on a drop-down menu and selected Tom’s Papez circuit, which is key to the control of emotions and memory. “The right side of the brain doesn’t have as much connectivity within the Papez circuit as the left side.” The right side is the one that smacked the ground.
Okonkwo explained that networked connections can be lost. If, for example, the links from the eye to the back of the brain are reduced or severed, it may diminish vision. “That concept is true for the motor system, for the sensory system, and it’s true in a slightly different way for memory, emotion, mood control,” he said. Some of Tom’s Papez circuit connections had been interrupted.
“The part of your brain responsible for encoding new memories isn’t what it once was,” said Okonkwo. He paused to let Tom digest. “And it can also be related to emotional stability and things like that.”
Karen covered her face and started to cry. For the first time, after years of doubt, anxiety and frustration, they saw the broken cables in Tom’s head. Okonkwo showed Tom another damaged brain circuit, the supplemental motor area, which is vital for integrating individual movements to make them smooth. The right side was dramatically different from the left, like someone arbitrarily hacked off huge branches of a tree. “It’s very difficult to be graceful when you have trouble with the supplemental motor area. Does that sound like you?” Tom nodded.
Okonkwo stressed that the implications of the damage were unclear; this research was in its infancy. He told them that thousands of damaged brains must be scanned before doctors understand how various injuries affect brain function.
There’s no obvious cure or therapy for Tom. But for Tom and Karen, just seeing proof that validates his symptoms felt like a step forward. “[It’s] satisfying. Sad. Scary. Heartbreaking,” said Karen. “It’s given us a confirmation that I’m not crazy,” Tom added. “For a long time, I thought I was losing my mind. Now I can finally move on.”
Seeing a detailed scan of the brain is clinically important, both in a diagnostic sense as well as a therapeutic one, says Okonkwo. “There’s actually someone who believes them.”
For the past four years, Schneider and Okonkwo have been tweaking the technology. While they are enthusiastic and hopeful about their approach, others are more cautious. Arthur Toga, director of the Laboratory of Neuro Imaging at the University of Southern California, says there are still many unknowns when it comes to the brain, questions that he and others are trying to answer as part of the national brain mapping initiative called the Human Connectome Project. Many brain circuits are not symmetrical, and simply comparing the right and left halves to detect brain damage may not be reliable. He is also concerned that telling someone the degree of damage may not be helpful. “We don’t know whether it is possible to recover those connections with the right treatments and rehabilitation strategies,” says Toga.
“Walt’s work is really promising, but it’s definitely controversial,” says Peter Bandettini, who specializes in fMRI as director of the fMRI facility at the National Institute of Mental Health. Others in the field doubt whether Schneider’s methods can truly quantify damage to specific fiber tracts, he says. For example, can his approach really determine that 78 percent of the fibers in a particular tract have been destroyed? “The jury’s still out on that.”
But Bandettini supports Schneider’s approach. “It’s important for Walt to thrash this out, push the technology and see what it can do . . . [and] he’s one of the few in brain imaging who is collaborating with the military and TBI doctors on clinical applications.”
Part of that process is building the technical infrastructure that will allow Okonkwo and Schneider to better acquire MRI data, analyze and interpret it, and present brain images to clinicians and patients in a way that’s intuitive. The scan now takes 22 minutes, the analysis just four hours.
Currently the only way to get a high-definition scan of brain fibers is to participate in a research trial. That will remain true for the next three to five years until the FDA approves the technology. But already, Okonkwo and Schneider are glimpsing the fruits of their efforts: They’re helping patients understand the consequences of their brain injuries.
Treatment has been a national priority after military service in Afghanistan and Iraq resulted in a vast number of TBI and PTSD cases. Since 2007, the Department of Defense Combat Casualty Care Program has spent more than $700 million on 500-plus TBI projects, including $10 million from the U.S. Army Medical Research and Material Command for Schneider’s technology. For Col. Dallas Hack, a physician and the brain health/fitness research coordinator at Fort Detrick, Md., the advantage of Schneider’s HDFT technology is the ability to see and quantify the damaged circuits. He can use that to guide rehabilitation for the thousands of soldiers who’ve been through brain-rattling explosions.
For one 46-year-old soldier (who asked that his name not be used because of the nature of his work), participating in Schneider’s research trial has changed his life. He’s spent more than 20 years in the U.S. Army Special Forces infantry division and has served in both Afghanistan and Iraq. After surviving some 400 explosions, he had memory lapses and attention deficits that he knew compromised his ability to lead high-altitude parachute missions into enemy territory — his specialty.
An exam confirmed short-term memory loss, but the problem ran deeper. He used to be a voracious reader and was fluent in several languages. Now he could barely get through an email, written words lost their meaning, and the languages blended unintelligibly in his head.
After the scan, Okonkwo showed him the source of his problems. “My visual tracts that connect the brain to my eyes have taken a beating, which explained to me why I can’t read,” he says. “I’m not an idiot, I’m not completely broken. I just have these cables that aren’t working as well because a lot of them have been destroyed.”
Although a rehabilitation strategy wasn’t clear, in a moment of medical inspiration, one of Schneider’s team members recommended that he read to a beat — specifically using music, rhythm and doing something physical, such as tapping the words. They thought it might possibly retrain his brain to use other intact pathways.
He had nothing to lose. So he plugged in his headphones, set a beat and read his emails or had the computer read them as he looked at the words. It worked. When he’s reading, he says, “I look like I’m cutting a rap record. I’m in the studio, it’s me and Jay-Z, and we’re getting it done!” That said, it takes longer, requires technology, and it’s still not easy. “[But] I can read articles, emails, and I can read a book.” This is all possible, he says, because he had an anatomically accurate scan that revealed which brain pathways were still viable.
With this new technology, the damage is now visible, and that’s “actionable intelligence,” says Schneider, who’s fond of military jargon. “In a decade, we may know how to repair the damage much more effectively.”
Scans done during and after rehabilitation and the use of various medications will prove whether damaged nerves can be repaired — and might begin to reveal how that happens.