Using a donated brain, custom technology and one of the most powerful magnetic resonance imaging (MRI) instruments available, scientists at Massachusetts General Hospital have generated the most detailed three-dimensional images of a human brain ever produced. The new images, which are 1,000 times more detailed than a standard clinical MRI, enable researchers to identify features as small as 100 microns — about the size of a grain of table salt. This level of detail is expected to lead to a deeper understanding of the architecture of the brain and provide insight on the structural changes that occur with neurological disease and traumatic brain injury.
“The precision and resolution of these scans will help answer some of the most important questions in clinical neurology.”
“With the amount of technology available, you’d expect the brain would be fully mapped — but we still have a great deal to learn,” says Brian Edlow, MD, a neuroscientist at Mass General’s Center for Neurotechnology and Neurorecovery, who contributed to the project. “The precision and resolution of these scans will help answer some of the most important questions in clinical neurology.”
MRI and the Resolution Gap
Historically, neuroanatomy — the study of the brain and its structures — has relied on thin, slide-mounted slices of post-mortem tissue. Using special chemicals, researchers stain these brain slices to highlight the location of specific cell types, processes or components. When viewed under a microscope, these slides provide exceptional detail. But the process is expensive and time consuming. Sectioning the brain also inevitably introduces distortions in the tissue.
“The other problem is that when you cut the brain into slices, you’re only seeing it in two dimensions,” says Bruce Fischl, PhD, a neuroscientist in the Athinoula A. Martinos Center for Biomedical Imaging at Mass General. Dr. Fischl and his colleague, physicist Andre van der Kouwe, PhD, oversaw the MRI project. “The human brain is so complex, so folded, you need to be able to view it in three dimensions to truly understand it.”
First introduced in the 1970s, MRI technology employs a strong magnetic field and radio waves to capture three dimensional images of internal organs and tissues without the use of dangerous radiation. Despite their utility, MRI scans can’t match the high-resolution detail available in slide-mounted slices.
Putting the Pieces Together
The process behind the new images, published recently in the journal Nature Scientific Data, was the result of more than a decade of work by a team of Mass General neuroscientists, neurologists, engineers, computer scientists and anatomists. “It’s hard to overestimate the amount of expertise that went into this single scan,” Dr. Edlow says.
To produce the scan, the team used a state-of-the-art MRI machine with one of the strongest magnets available. They also built a customized radio coil, designed to fit snugly around the specimen — in this case, the brain of 58-year-old woman who died of viral pneumonia. In an MRI scan, the radio coil functions as the antenna, sending and receiving signals between the subject and the MRI machine.
They also designed custom software to manage the eight terabytes of data — nearly as much as the Hubble Space Telescope generates in a year —produced during the 100-hour scan.
A New World of Opportunities
This new ability to identify features and lesions that might otherwise be missed by traditional means could give researchers and clinicians an advantage when it comes to screening for neurological disorders like Alzheimer’s.
“It’s allowing us to see structures that may help us predict disease onset earlier in the process,” Dr. Fischl says.
Images and data from the scan were made available earlier this year, and the response has been overwhelming. Researchers at the University of Pittsburgh are using the information to map connectivity in the brain. A team in Brazil has used it to expand a leading neuroanatomy atlas. One contributor to the study has incorporated the data into a software platform to help neurosurgeons improve therapeutic outcomes of deep brain stimulation used to treat conditions like Parkinson’s disease.
Seated at his desk, Dr. Edlow watches the image on his screen bloom and recede. The video, compiled from still images from the scan, represents a kind of highlight reel for the team. Despite admitting he’s watched the video “probably a thousand times already,” his sense of wonder is still evident.
“We’re just beginning to realize how much this single data set could impact neuroscience,” he says.
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