Alan Jasanoff
Associate Professor, Departments of Biological Engineering, Brain & Cognitive Sciences and Nuclear Science & Engineering
Associate, McGovern Institute for Brain Research; Whitehead/MIT Bioimaging Center
Raymond and Beverly Sackler Foundation Scholar

AB '92 (biochemical sciences) Harvard College
MPhil (chemistry) Cambridge University
PhD '98 (biophysics) Harvard University

My laboratory is developing noninvasive functional imaging methods to study systems-level neural plasticity involved in low-level learning and perceptual behavior in small animals. We are seriously involved in the design of new imaging agents that may help define spatiotemporal patterns of neural activity with far better precision and resolution than current techniques allow. We have produced prototype imaging agents for “molecular fMRI,” and are adapting them for application in vivo. Current imaging experiments in rodents focus on neural mechanisms involved in reward-related learning. In the past year we have developed an awake rat preparation which will allow us to image hemodynamic correlates (and eventually more direct measures) of brain activity while the animal performs tasks in an MRI scanner.

Functional imaging of behavioral correlates. Functional connectivity among brain structures changes on both developmental and behavioral timescales. Among neurophysiological techniques, noninvasive imaging with fMRI offers the unique ability to follow plasticity of activation patterns at the whole-brain level with relatively high spatial resolution and modest temporal resolution. When combined with targeted electrophysiology studies, or with contrast agents that report neuronal activity directly, fMRI studies in awake animals will be an increasingly important tool for studying mechanisms of brain plasticity as a function of behavior.

Contrast agents for functional imaging. Conventional fMRI methods (based on hemodynamics) detect neural population activity indirectly with a temporal resolution of several seconds and spatial resolution up to 50 microns. More precise readouts are required for mechanistic studies of neural networks in the brain. MRI could achieve cellular-level detection of neural activity if used in conjunction with contrast-enhancing chemicals (contrast agents) that are sensitive to aspects of microscopic physiology. Contrast agents are paramagnetic chemicals that influence MRI signal due to their influence on the NMR relaxation rates of water; the extent of this influence is termed relaxivity. A contrast agent can report physiological variables (e.g. metabolite concentrations or ion fluxes) via changes in their relaxivity. We are developing calcium-sensitive contrast agents that could be used for fMRI studies in vivo. In the past year we have synthesized a combinatorial library of potential calcium imaging agents that can eventually be expressed in cells. These agents have been screened by MRI to determine elements of the library that show the greatest relaxivity change in the presence of calcium. We have also developed a calcium-sensitive agent based on superparamagnetic nanoparticles, which have particularly potent effects on MRI signal intensities. Such experimental tools will find broad applicability in brain research; our specific goals are to apply them to several problems in the context of rodent behavior and instrumental learning in particular.