Lawrence L. Wald
Professor of Radiology, Harvard Medical School
Biophysicist, Massachusetts General Hospital
Director, MGH NMR Core, Martinos Center
Functional brain imaging has played an important role in recent advances in human neuroscience, allowing traditional psychology experiments to be carried out during non-invasive imaging sensitive to the metabolic or hemodynamic effects of brain activation. This has allowed human neuroscience to move from indirect measurements such as subject responses and reaction times to direct interrogation of the brain regions and circuits used in a task. The application of functional brain imaging has become so central to human neuroscience that most major psychology/neuroscience departments at US universities now operate an fMRI facility.
While fMRI is valued for its ability to noninvasively map the hemodynamic response to brain activation, its sensitivity is relatively low. Studies typically require repeated trials and are averaged across multiple subjects to achieve statistical significance. The consequence of low CNR extends beyond the inconvenience of averaging and missing subtle effects. It prevents fMRI from impacting clinical medicine where decisions must be made for an individual, not a group average. The ability to make statements about a brain circuit’s function or dysfunction in individuals could provide means of phenotyping spectrum diseases such as the major mental illnesses; a potential breakthrough for diagnosis and treatment.
MPI offers an attractive and potentially very sensitive compliment to fMRI. We propose using a similar hemodynamic contrast mechanism; the local Cerebral Blood Volume changes during activation. Since injected SPIONs do not cross the blood-brain barrier, the direct measure of SPION concentration provided by MPI is a measure of local CBV and CBV changes (~20% during brain activation) will be directly effected in a time-series of MPI images.
Lawrence L. Wald, Ph.D., is currently a Professor of Radiology at Harvard Medical School, Affiliated Faculty of the Harvard-MIT Division Health Sciences Technology and Sara & Charles Fabrikant Research Scholar at the Massachusetts General Hospital. He received a BA in Physics at Rice University, and a Ph.D. in Physics from the University of California at Berkeley in 1992 under the direction of Prof. E.L. Hahn with a thesis related to optical detection of NMR. He obtained further (postdoctoral) training in Physics at Berkeley and then in Radiology and MRI at the University of California at San Francisco (UCSF). He began his academic career as an Instructor at the Harvard Medical School and since 1998 has been at the Massachusetts General Hospital Dept. of Radiology A.A. Martinos Center for Biomedical Imaging.
His recent work focuses on improving methods for functional brain imaging. He has worked on the benefits and challenges of highly parallel MRI and its application to faster image encoding and parallel excitation and ultra-high field MRI (7 Tesla) methodology, and also improved method for studying the Human Connectome and portable MRI technology. Recent work has included studying the feasibility of functional brain imaging with Magnetic Particle Imaging (MPI) using Cerebral Blood Volume (CBV) contrast and analysis of the instrumentation needed for fMPI of humans. This has also led to extending understanding of Peripheral Nerve Stimulation (PNS) in human MPI and MRI using electromagnetic body models with full nerve atlases and a detailed neuro-dynamic model to predict magneto-stimulation thresholds. Dr. Wald is a Fellow of the International Society of Magnetic Resonance (ISMRM) and the College of Fellows of the American Institute for Medical and Biologial Engineering (AIMBE). He will serve as President of the ISMRM in 2019.
