Scientist Develops Chemical Sensors Detectable by MRI Machines

CAMBRIDGE, MA /BUSINESS WIRE/ -- Neuroscientists eagerly anticipate the day when they can use noninvasive brain imaging to see precisely what the 10 billion neurons are doing throughout a person's brain. But a trio of limitations facing current fMRI technology stands in a way of that goal: time, space, and specificity. At the McGovern Institute for Brain Research at MIT, Alan Jasanoff is developing new chemical sensors, detectable by MRI machines, that will overcome these limitations. The first of these tools, a nano-sized calcium contrast agent, is reported in the October 3, 2006, issue of the Proceedings of the National Academy of Sciences.

"Using conventional fMRI to study the brain is like trying to understand how a computer works by feeling which parts of it are hot because of energy dissipation in different components of the machine," explained Jasanoff. "But chemical sensors for MRI could show what each individual element in each integrated circuit is doing and how it performs the computations and processes information."

The analogy is apt because fMRI indirectly measures neural activity by detecting changes in blood flow to brain regions with increased energy requirements. However, these hemodynamic changes occur several seconds after the neurons have actually fired, too slow to study precise neural activity. The spacing of the capillaries limits the spatial resolution of the technique to volumes containing at least 1000 neurons, too coarse for discrimination of highly specialized functional areas within a brain region.

Calcium, however, provides a direct measure of neural activity because calcium almost instantly flows into neurons when they fire, and the faster the rate of firing, the higher the calcium level. Thus, tracking calcium levels in the brain actually tracks information flow through the brain's circuitry.

MRI detects changes in magnetic properties, so to be visible to MRI, a calcium contrast agent must include a magnetically active "paramagnetic" component. Jasanoff designed the sensor to incorporate so-called "superparamagnetic nanoparticles"—extra strength molecular-size magnets previously designed for ultrasensitive tumor imaging—that produce large MRI contrast changes capable of producing very high-resolution images.

Jasanoff's sensor is actually made from two similar types of superparamagnetic nanoparticles that stick to each like Velcro-coated balls when calcium levels rise. This aggregation is reversible, which allows the sensor to indicate the temporal dynamics of calcium-related neural activity, such as the sequence in which populations of cells become active, or the synchronization of neurons during certain behaviors. Graduate student Tatjana Atanasijevic, who is the lead author on the PNAS paper, is working on noninvasive methods to deliver the calcium sensor to brain cells in vivo, while others in his group are modifying the nanaparticles so that they can target specific genetic characteristics or different populations of neurons, such as inhibitor neurons or those that produce neurotransmitters like dopamine or serotonin.

"These will be tools for making the shift from imaging gross functional properties of the brain through its hemodynamic changes to a fine-tuned analysis based on information flow involving cells and circuits," Jasanoff said. "There are many potential applications for studying learning, memory, and behavior, and we need the new tools to get to the applications."

In addition to his appointment as an associate member of the McGovern Institute, Jasanoff is assistant professor in the departments of nuclear science & engineering, brain & cognitive sciences, and biological engineering division. This research is supported by grants from the Raymond & Beverley Sackler Foundation and the NIH/NIBIB, and a McKnight Foundation Technological Innovations in Neuroscience award.

About the McGovern Institute at MIT
The McGovern Institute at MIT is a neuroscience research institute committed to improving human welfare and advancing communications. Led by a team of world-renowned, multidisciplinary neuroscientists, the McGovern Institute was established in February 2000 by Lore Harp McGovern and Patrick J. McGovern to meet one of the great challenges of modern science—the development of a deep understanding of thought and emotion in terms of their realization in the human brain. Additional information is available on the institute's Web site.

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