Consider this scene: a young woman comes to the emergency room having seizures. She undergoes magnetic resonance imaging (MRI) to identify any structural abnormalities in the brain that may be triggering her seizures. A reading of the images suggests no abnormalities because, sometimes, disruptions in the brain’s electrical system are subtle.
Fast-forward to 2015. A young woman enters an emergency room with seizures. Magnetic resonance images of her brain are sent to a sophisticated brain database at a remote site. Word comes back that several areas of her brain do not match the composite brain for similar individuals, based on age, gender, and ethnicity. Specific tests on the affected brain areas are scheduled.
While such diagnostic precision is still years away, the sophisticated brain database that will drive it is fast becoming a reality. So far, researchers have completed brain images of 7,000 demographically diverse individuals ranging in age from 18 to 90 years old. Scientists have also collected geographic, developmental, psychological, educational, and behavioral information for each of the study participants. The type of MRI used in the study produces quantitative maps of tissue features, such as fat and water content, that can be compared over time. Scientists are also collecting DNA samples of the participating volunteers, which may eventually provide valuable information about how genetic factors affect the brain.
More than a decade in the making, the database has still yielded few clues to how the brain works. “Only at the very end will we get results that answer some of the most fundamental questions about the organization of the brain,” says Dr. John C. Mazziotta, principal investigator of the International Consortium for Brain Mapping (ICBM). The consortium is developing the database.
Borrowing from the Movies
What distinguishes this brain database and atlas from previous brain maps is its ability to capture the variability in a population of brains. To do this, the database uses image-warping techniques, some of which were first developed in the movie industry. Image warping allows researchers to transform the geometry of an image in order to superimpose one image on another. Special mathematical formulas created for the database can compare the three-dimensional digital brain atlas with a scan of any given person, while respecting the intricate patterns of variation in an individual’s anatomy. The method enables scientists to compare individual brains with populations of healthy or diseased brains. For example, doctors could see if an individual’s brain is similar to those of people known to have Alzheimer’s disease or schizophrenia.
Before mapping techniques were developed, researchers who wanted to explore the brain relied on postmortem studies in which brains were sliced and put under a microscope to examine cellular and physical features. “This was the ultimate gold standard,” says Dr. Mazziotta, head of the department of neurology at the University of California, Los Angeles.
The ICBM project, which involves eight laboratories in seven countries on four continents, initially gathered information only about brain anatomy, but has expanded to include other information as well. “The richness of this atlas continues to grow,” says Dr. Mazziotta. To chart the roles of specific brain areas, study participants undergo a battery of repetitive tasks. “This is unbelievably boring, but when we complete it, we’ll have a better understanding of the relationship between the structure and function of the brain,” he says.
Tracking the Brain Over Time
The warping techniques also allow researchers to model changes that occur over time. Scientists can chart normal development, aging, disease progression, or changes that occur more rapidly, such as tumor growth or recovery from injuries. The resulting four-dimensional brain map accounts for the spatial and temporal complexity found in the human brain. When comparing multiple brain images, warping shows the changes in every anatomic point in the brain across the disease or developmental stage spanned by the images.
“One hope is that these strategies will provide sensitive surrogate biomarkers for diseases,” says Dr. Mazziotta. The tools used to build the atlas of the healthy human brain can also be applied to study diseased brains. Researchers can watch disease progression and compare affected individuals with healthy, age-matched individuals. For example, scientists can measure the brain changes associated with Alzheimer’s disease. Researchers can also compare the progress of patients who are undergoing conventional therapies for a certain disease or condition with those undergoing experimental therapies.
Improved Prognosis for Brain Trauma
Head injuries are another area in which the brain atlas may be useful. The prognosis for individuals experiencing severe head injuries varies widely depending on age and treatment. Initially, doctors have no way to tell if an individual will fully recover, remain in a vegetative state, or die.
“Head trauma is an extraordinarily difficult situation,” says Dr. Mazziotta. Using the brain atlas and related tools, researchers could identify the trends and challenges connected with head injuries. A study of individuals with brain injury followed over time might enable researchers to discover if they can provide a prognosis more quickly.
Additional work on the continually evolving database includes studies of the brain’s white matter, blood vessel network, and neural connectivity. The researchers will also collaborate with groups developing a pediatric atlas based on magnetic resonance images. When researchers combine the pediatric atlas with the ICBM atlas, they will have information about the brain for the entire human life span.
“There is no end to this project because there are an infinite number of attributes that we can look at,” says Dr. Mazziotta.
Several National Institutes of Health agencies are funding the ICBM. These include the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Mental Health, the National Institute on Drug Abuse, the National Cancer Institute, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke.