Mass General researchers have created a new generation of brain mapping images that promises to open the door to understanding and treating brain disorders.
Van Wedeen, MD on brain mapping
Van Wedeen, MD

Using a little creativity and a lot of new technology, Mass General researchers have created a new generation of brain mapping images that promises to open the door to understanding and treating brain disorders.

The dazzling, rainbow-colored images, created in Mass General’s Martinos Center for Biomedical Imaging, reveal, for the first time, the living human brain’s pathways and connections. Sometimes referred to as “Connectome,” the brain mapping pictures are appearing on magazine covers and web pages from National Geographic (February, 2014) to Wikipedia. The breakthrough technology behind the brain mapping images is what Mass General’s Director of Connectomics Van Wedeen, MD, describes as “like an MRI scanner only four times more powerful.”

That modest description of the brain mapping technique, however, fails to capture the mind-bending engineering, radiology and computer science that Dr. Wedeen and his colleagues have combined to turn the wiggling water molecules in brain cells into highly-rendered images of the brain’s intricate communications network—a technique called diffusion tractography. Even more startling, Dr. Wedeen says, is that the brain’s circuits appear to be arranged in a grid-like structure, almost like a 3-D city map of crisscrossing streets. The layout is remarkably “similar to the rectangular modules on a computer chip,” Dr. Wedeen explains.

Opening the Black Box

“We don’t yet know the anatomy of the brain. Connectomics—the mapping of the connections in the brain—will help to get us where we need to be.”

“We think the key to making progress in a variety of neurological and psychiatric disorders is understanding these connections,” says Bruce Rosen, MD, PhD, director of the Martinos Center. “All of medicine is fundamentally built on anatomy,” he adds.  “If you’re going to treat heart disease, for example, you need to know the anatomy of the heart. But we don’t yet know the anatomy of the brain. Connectomics—the mapping of the connections in the brain—will help to get us where we need to be.”

It wasn’t long ago that the living human brain was regarded as a “black box” which could not be observed without opening the skull. But in the 1980s, Dr. Rosen and his colleagues pioneered what came to be known as functional MRI (fMRI), creating the now familiar, colorful images of the functional areas of the brain. Those fMRI pictures helped scientists assemble a type of brain map by identifying which part of the brain activates when someone speaks, laughs, feels pain, recognizes a face or does any of hundreds of activities a person can do while lying in an fMRI scanner. But while fMRI can identify areas of the brain and their functions, it cannot reveal the connections by which one part of the brain communicates with another.

Enter Dr. Wedeen and diffusion tractography. Working on a parallel track to fMRI imaging, Dr. Wedeen, and what he calls “the diffusion community,” were quietly tracking water molecules as they wiggle inside brain tissues—a phenomenon called diffusion. They were trying to map the structure of the brain’s white matter—the long nerve fibers sheathed in a whitish myelin coating that make up the brain’s communications system.

Circuits Visible in Brain Mapping Images

Working with Dr. Wedeen, Mass General physicist Lawrence Wald, PhD, reengineered an MRI scanner in partnership with the manufacturer, Siemens, to push diffusion technology forward. It took decades of work—first in animals and now in humans—to produce the grid-like images of connecting circuits now gaining so much attention. The Connectome diffusion tractography scanner is a one-of a kind device existing only at Mass General. The circuits that are visible in the brain mapping images are not individual nerve cells fibers but represent bundles of fibers, known as axons. They conduct the electrical signals by which the brain communicates.

The wiggling motion of water molecules in the brain's nerve cells is captured by diffusion technology, revealing the pathways by which one part of the brain communicates with another.
The wiggling motion of water molecules in the brain’s nerve cells is captured by diffusion technology, revealing the pathways by which one part of the brain communicates with another.

“Van has changed the whole field,” Dr. Rosen says. “He was the first guy to use the diffusion information to make images of how the fibers are directly organized in the brain, and technical innovations in the years since have enabled him to make ever more precise and beautiful pictures of this wiring.” Dr. Rosen foresees using the brain mapping images as a guide for a surgical procedure, known as deep brain stimulation, now being tested to treat psychiatric diseases ranging from depression to obsessive compulsive disorder. Another possibility is using brain mapping to locate and treat traumatic brain injury. Doctors need to have a clear map of the brain to know how to address the injury, he says, adding: “You can’t treat something if you don’t know where it is.”

Revealing Brain Disorders Early

The brain mapping technology may also reveal the underpinnings of early onset brain disorders such as autism and schizophrenia as well as late-life conditions such as Parkinson’s disease and Alzheimer’s disease. Bradley Hyman, MD, PhD, director of the Massachusetts Alzheimer’s Disease Research Center at Mass General, envisions scanning people’s brains over a period of years to detect very early signs of Alzheimer’s disease. “It will allow us to track degeneration from the earliest point,” Dr. Hyman says.

While clinicians ponder new uses for the Connectome brain mapping images, Dr. Wedeen is fine tuning the process to offer an ever more accurate view of the brain. “The more clearly we can see into the brain,” he says,” the better our options to detect disease earlier, to help develop more effective treatments and to better understand each individual.”