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
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Materials Sciences
23.03.2018 | Agricultural and Forestry Science
23.03.2018 | Physics and Astronomy