Neuroscientists from the Massachusetts Institute of Technology (MIT) have designed a new MRI sensor that responds to the neurotransmitter dopamine, an achievement that could improve the specificity and resolution of future brain imaging procedures.
According to the MIT, functional magnetic resonance imaging (fMRI) 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 MRI.
MRI sensors that quickly and directly respond to chemicals involved in the brain’s information processing would provide a much more precise measurement of brain activity.
‘We have designed an artificial molecular probe that changes its magnetic properties in response to the neurotransmitter dopamine,’ said Alan Jasanoff, an associate professor of biological engineering at the 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.’
Measuring dopamine in the living brain is of particular interest to neuroscientists because this neurotransmitter plays a role in motivation, reward and 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 Prof Robert Langer and the laboratory of Frances Arnold at Caltech, borrowed an evolutionary trick.
Starting with a magnetically active protein similar to haemoglobin, the researchers showed that it could be visualised 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 the more precise non-invasive imaging of the brain,’ said 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,’ said Gil Westmeyer, joint first author of the study. ‘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.’
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.
The team hopes to develop a related suite of tools to detect different molecular events across the whole brain and it expects to see additional gains in sensitivity through improved experimental paradigms and further molecular engineering.