Novel MRI dopamine sensor provides new tool for functional
imaging of brain
21 April 2010
Neuroscientists at the Massachusetts Institute of Technology
(MIT) have designed a new MRI sensor that responds to the
neurotransmitter dopamine, an achievement that may significantly improve
the specificity and resolution of future brain imaging procedures.
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 haemoglobin mediates a magnetic change that is detected by
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.
A model of the protein Jasanoff's team
engineered into a dopamine sensor for MRI.
“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
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
“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.
1. 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: