Pushing the frontiers of MRI
Functional magnetic resonance imaging (fMRI) has revolutionized our understanding of the human brain, but the method is now approaching the limit of its capabilities. Alan Jasanoff hopes to break through this limit and to develop new technologies for imaging the molecular and cellular phenomena that underlie brain function.
Beyond blood flow
Functional MRI takes advantage of the fact that when a particular brain region becomes more active it consumes more oxygen, and blood flow increases to that region increases to compensate. These changes can be detected during a brain scan because the blood protein hemoglobin changes its magnetic properties when it is depleted of oxygen.
Although fMRI has yielded much valuable information, it suffers from two fundamental limitations. First, changes in the blood are slow relative to the speed of neural activity, making it impossible to measure rapid brain events. Second, the source of the activity can only be localized to the nearest blood vessel. It is not precise enough to provide detailed information about activity in specific neurons and circuits.
Jasanoff is working to overcome these limitations. He is devising new contrast agents whose magnetic properties are altered by events in the neurons themselves, rather than their surrounding blood vessels. If successful, such an approach could reveal an unprecedented level of information about brain activity as it unfolds in real time.
The next generation of contrast agents
When neurons become active, they rapidly take up calcium from their environment. Jasanoff hopes to visualize these rapid changes using magnetic nanoparticles that are coupled to a calcium-binding protein. In collaboration with colleagues at the MIT chemistry department, he is also developing a new class of molecules that can be engineered to accumulate inside cells and to reveal changes in the intracellular chemical environment.
Another one of Jasanoff's approaches is to develop indicator molecules that can be genetically encoded and targeted to specific cell types. Jasanoff is developing an indicator for dopamine. Dopamine is a neurotransmitter that is depleted in Parkinson's disease. Many psychiatric drugs and substances of abuse target dopamine receptors in the brain. So the ability to detect changes in dopamine in living animals would have many applications for the study of brain disorders. Eventually, Jasanoff hopes it may be possible to adapt the approach for use in human subjects, thereby providing a powerful new tool for clinical research and drug development.
Alan Jasanoff is an associate member of the McGovern Institute and Associate Professor of Biological Engineering, with appointments in Brain and Cognitive Sciences and Nuclear Science and Engineering. He was awarded tenure in 2011. Prior to joining the MIT faculty, he was a Whitehead Fellow at the Whitehead Institute for Biomedical Research at MIT. He was named a Raymond and Beverly Sackler Foundation Scholar in 2004 and received the McKnight Technological Innovations in Neuroscience Award in 2006. Jasanoff was also a 2007 recipient of the Director's New Innovator Award from the National Institutes of Health.
Image: Kent Dayton