Although functional magnetic resonance imaging (fMRI) has enhanced our understanding of brain function since it was first introduced about 20 years ago, the technology actually measures blood flow, which is a slow and indirect readout of neural activity.
When a brain region becomes active, blood vessels in that region dilate, causing increased blood flow to the site. Iron found in the blood’s hemoglobin mediates a magnetic change that is detected by MRI.
But MRI sensors that directly and rapidly respond to chemicals involved in the brain’s information processing would provide a much more precise measurement of brain activity. This technology has not been available until now.
“We have designed an artificial molecular probe that changes its magnetic properties in response to the neurotransmitter dopamine,” explains Alan Jasanoff, an associate professor of biological engineering at MIT and senior author of the Nature Biotechnology paper describing the work. “This new tool connects molecular phenomena in the nervous system with whole-brain imaging techniques, allowing us to probe very precise processes and relate them to the overall function of the brain and of the organism. With molecular fMRI, we can say something much more specific about the brain’s activity and circuitry than we could using conventional blood-related fMRI.” Jasanoff holds appointments in the McGovern Institute for Brain Research and in the departments of Brain and Cognitive Sciences and Nuclear Science and Engineering.
Measuring dopamine in the living brain is of particular interest to neuroscientists because this neurotransmitter plays a role in motivation, reward, addiction, and several neurodegenerative conditions including Parkinson’s disease.
To design a molecular probe that binds to dopamine, Jasanoff’’s group, in collaboration with MIT Institute Professor Robert Langer and the laboratory of Frances Arnold at Caltech, borrowed an evolutionary trick. Starting with a magnetically active protein similar to hemoglobin, the researchers showed that it could be visualized by MRI, and then ‘evolved’ the protein – through rounds of artificial mutation and selection – to bind specifically to dopamine.
“By harnessing the power of protein engineering we now have the ability to advance neuroscience through more precise non-invasive imaging of the brain,” says Mikhail Shapiro, joint first author of the study and a former graduate student supervised by Jasanoff and Langer. Shapiro devised the directed evolution approach used to make MRI sensors in the study.
After confirming that the protein responded to dopamine produced by cells in test tubes, the researchers tested whether it could detect dopamine in the living brain. They found a change in the MRI intensity precisely when they artificially triggered dopamine release in the presence of the sensor.
“This means that we can see signal changes in the brain due to the modulation of dopamine,” explained Gil Westmeyer, joint first author of the study and a postdoctoral fellow in Jasanoff’s lab who directed the in vivo work. “This novel MRI sensor will enable us to study the spatial and temporal patterns of dopamine transmission over the vast and heterogeneous dopamine network in the brain.”
Next Steps: Jasanoff’s team will use the new MRI sensor to study how the spatial and temporal patterns of dopamine release relate to an animal’s experience of reward, learning, and reinforcement. They hope to develop a related suite of new tools to detect different molecular events across the whole brain, and they expect to see additional gains in sensitivity through improved experimental paradigms and further molecular engineering.
While synthetic molecules are typically introduced into the brain with external devices, Jasanoff’s new sensor is based on a protein, which means that researchers may also have the ability to genetically encode the sensor to express on its own. The new dopamine sensor is an important tool for animal research, but the researchers also hope one day to develop agents that can measure neural activity in the human brain.
Source: Shapiro MG, Westmeyer GG, Romero PA, Szablowski JO, Küster B, Shah A, Otey CR, Langer R, Arnold FH, & Jasanoff A. Directed evolution of an MRI contrast agent for noninvasive imaging of dopamine. Nature Biotechnology. 28 February 2010. DOI: 10.1038/nbt.1609
Funding: Fannie and John Hertz Foundation, Paul and Daisy Soros Fellowship, Dana Foundation Brain & Immuno-Imaging Grant, Raymond & Beverley Sackler Fellowship, NIH, Caltech Jacobs Institute for Molecular Medicine, McGovern Institute for Brain Research.
Jen Hirsch | Newswise Science News
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences