Originally Published MDDI April 2003

R&D DIGEST

New research findings at the University of California, Berkeley, could significantly improve the resolution of scans generated by functional magnetic resonance imaging (fMRI) systems. Scientists at UC Berkeley's Group in Vision Science believe that the new findings could one day have significant clinical benefits. Among these are earlier detection of brain disorders and such neurologic diseases as Alzheimer's and Parkinson's.

A noninvasive procedure, fMRI can be used to detect increased levels of blood flow into certain areas of the brain that infer neural activity. But the researchers recently reported results of a study that suggest an initial decrease in blood oxygen levels is an earlier and more spatially precise signal of nerve cell activity. They believe that the findings could lead to fMRI scans with a resolution measured in micrometers. Most current methods have a resolution of a few millimeters. 

Though he did not take part in the study, Mark D'Esposito, MD, head of UC Berkeley's Henry H. Wheeler Jr. Brain Imaging Center, suggests that the study has clear implications for basic neuroscience. “A few millimeters in the brain translate into hundreds of thousands of neurons. There is no doubt that any method that can improve spatial resolution will help scientists better understand brain function,” he says. 

Ralph Freeman, UC Berkeley professor of vision science and optometry and principal investigator of the study, says, “All diseases begin at the cellular level. If we can eventually get a better look at what is occurring at the cellular level, then we can get a better handle on disease processes at an earlier stage in their development.” 

The scientists say the experiments also confirm a long-standing hypothesis that nerve cell activation is directly connected with increased oxygen consumption at a localized level. The experiment involved use of a custom-made sensor that combined two microelectrodes. One electrode measured the electrical activity of a single neuron. The other measured the concentration of oxygen in an area about 60 µm in diameter. The researchers monitored 21 nerve cells in the visual cortex of four cats. Visual stimuli were displayed on a monitor in front of the cats to trigger specific neurons. The group found statistically significant decreases in oxygen levels while these neurons were activated. 

The study revealed that when neurons are triggered, there is an uptake of oxygen to fuel the activity. This leads to a decrease in levels of oxygenated hemoglobin. The body then reacts to this decrease in oxygen level by increasing the flow of oxygen-enriched blood to the area. 

Says Freeman, “A common reaction among neuroscientists when they learn of this study is, ‘Why hasn't this been done before?' Measuring metabolic and neuronal activity at the same time provides direct evidence for the link that had been theorized for so long.” 

Use of fMRI is based on the fact that deoxygenated hemoglobin has slightly different magnetic properties than does oxygenated hemoglobin. The system is able to translate the metabolic changes into an image of brain activity. Says Jeffrey Thompson, a UC Berkeley graduate student in vision science and lead author of the study, “The initial dip in oxygen occurs in a very localized area. The subsequent increase in oxygen, which most functional MRI scans measure, covers a relatively broader area. Zeroing in on the early dip could substantially improve the spatial resolution of fMRI.” 

There are several hurdles to be overcome before the findings can be put to clinical use. Thompson notes, for example, that because the initial dip in oxygen levels is relatively small, the signal is weak and will be difficult to find. Thompson compares the problem with finding a radio station with a weak signal. He believes that it may be possible to detect the signal by increasing the volume, but that would also lead to an increase in static and background noise that would need to be filtered out. 

Nevertheless, the researchers say the study results justify further research on this initial dip in oxygen in the effort to create higher-resolution fMRI scans that can be used to better understand and detect brain disorders. 

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