As the fetal brain develops, new neurons are born and migrate to different parts of the brain, forming the complex and highly ordered structure of the cerebral cortex. But every now and again, that process goes awry. Sometimes tiny architectural glitches in the cortex lead to big problems, such as the uncontrolled electrical storms in the brain that underlie seizures.
Now higher-resolution brain-imaging technologies could help doctors find these hidden flaws, allowing surgeons to remove the damaged area – and giving scientists new insight into the causes of epilepsy.
Epilepsy is characterized by recurring seizures, caused by uncontrolled waves of electrical activity that propagate throughout the brain. About two-thirds of epilepsy patients can control the disease with drugs. The remaining third can sometimes undergo surgery to remove the tiny section of brain tissue that sparks seizures – but only if surgeons can find the offending spot with a brain scan.
Scientists estimate that about 25 percent of these patients have tiny abnormalities – which likely originated during cortical development – that are too subtle to be detected with traditional brain imaging. But new imaging technologies, such as those being developed by researchers at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH) in Boston, are bringing relief to these patients. In a study released last fall, Ellen Grant, chief of pediatric neuroradiology at MGH, and colleagues were able to detect lesions in about two-thirds of epileptic patients whose previous brain scans had been declared normal, making these patients better candidates for neurosurgery. The team is now engineering even higher-resolution devices, which they’ll use to study learning disabilities and other developmental disorders, such as autism.
“This technology is a very good improvement over previous high-resolution technologies,” says Imad Najm, an epilepsy expert at the Cleveland Clinic in Ohio. “It will allow us to see some lesions we did not see before and to see bigger lesions where we could see only smaller ones, lesions which were just the tip of the iceberg.”
With traditional magnetic resonance imaging (MRI), a large magnet is coupled with a radio-frequency detector that picks up characteristic signals from different tissues in the brain, generating a detailed picture of the brain’s structure. Scientists are now developing devices that use arrays of anywhere from 8 to 256 detectors to get higher-resolution images of the brain. “It’s like a compound eye for MRI,” says Bruce Rosen, director of the Martinos Center.
Each detector is positioned over a specific part of the brain, generating a high-resolution image of that tiny piece. (With conventional scanners, a single detector picks up signals from the entire brain, generating a much lower signal-to-noise ratio.) The sections are then put together to form a detailed picture of the whole brain. “You can make individual channels smaller, so they have greater sensitivity to parts of the head that are close to that channel,” says Graham Wiggins, a research fellow in radiology at Harvard Medical School, who helps to engineer the arrays.
These array detectors are fast becoming standard practice – Siemens now offers a commercial 32-channel array system. But Wiggins’ team, in collaboration with Siemens, is engineering much denser arrays with even better resolution, that they say would be useful for understanding a number of neurological diseases. “We might be able to see white matter anomalies connected to multiple sclerosis or early changes related to Alzheimer’s disease,” he says.
Cleveland’s Najm says the higher resolution is key to understanding epilepsy and other diseases. “I think we need to continue to improve imaging ability, until we get to a cellular resolution about 10 to 15 microns, where a cell will be seen as cell. Then we can really see the cellular organization.” He adds that combining MRI with other types of imaging, such as molecular imaging, which allows scientists to examine activity inside a cell, will also help identify abnormalities associated with epilepsy.
Grant and colleagues are now trying to couple these high-resolution structural images with other technologies that measure the electrical activity of a seizure, to determine exactly how structural glitches generate seizures.
Extremely high-resolution imaging has its downside, too, though. It’s possible, for example, that many people have tiny cortical flaws that don’t noticeably affect their health. “The more sensitive the imaging studies get, the more you have to think about how findings are related to the illness,” says William H. Theodore, chief of the Clinical Epilepsy Section at the National Institutes of Health in Bethesda, MD. He adds that the value of new imaging technologies also depends heavily on the person reading the scan. “An expert reader of a somewhat inferior MRI scan may do just as well as a less expert [reader] of a better MRI scan,” he says.