The past few decades have witnessed extraordinary progress in the development of techniques for noninvasive structural and functional imaging of the human brain.  However, despite this progress, no existing medical imaging modality provides all of the information required for best clinical practice or cutting edge basic research.  MRI is the premier technique for characterizing the soft tissue anatomy of the human brain, but has significant limitations for defining the geometry of the skull.  Functional MRI, and PET  provided detailed pictures of spatial patterns of neural activation based on associated hemodynamic changes, but cannot capture the temporal dynamics of electrophysiological activation on its characteristic timescale.  MEG and EEG provide excellent temporal resolution of neural population dynamics but are limited in spatial resolution by the ambiguity and ill-posed nature of the current reconstruction problem.  Electrical and magnetic stimulation offer the possibility of direct intervention in central or peripheral neural pathways, but depend on knowledge of anatomical and functional organization drawn from other sources.  Other methods, including optical and magnetic resonance spectroscopy, SPECT and nuclear medicine, histology, endoscopy, neurosurgical intervention, etc., each provide important and unique insight into neural function and functional organization.  Although the mix and relative importance of imaging technologies will continue to evolve, the need to integrate information from multiple methods will remain.

The goal of research supported by the Human Brain Project is to develop composite techniques for noninvasive, functional brain imaging that provide spatial and temporal resolution superior to any available imaging technique.  We are developing experimental, theoretical and computational procedures to combine anatomical MRI, functional MRI, and MEG into an integrated structural/functional imaging technique that exploits the strengths and minimizes the weaknesses of each modality alone.
 

The second major effort addresses the development and application of Advanced Optical Methods  for tissue measurements on the macroscopic and microscopic scale.  For macroscopic measurements the principal challenge is the highly scattering nature of biological tissue.  Tissue is relatively translucent, particularly in the near IR, and these wavelengths provide useful spectral data, e.g. allowing measurement of the quantity and oxygenation state of hemoglobin.  However, a photon in the near IR may scatter >10 times per cm , so that light travels through tissue by a process that resembles diffusion.  To address the uncertainty in path and pathlength we are developing time-resolved imaging methods that allow measurement of the time of flight of photons launched into the medium.  The first approach  employs high-speed gated intensifiers (gate time ~200 ps) coupled to cooled CCDs.  A second strategy currently being explored will employ time-resolved photon counting technologies developed at Los Alamos.  This class of methods coupled with sophisticated modeling techniques shows promise for noninvasive quantitative characterization and tomographic reconstruction of the optical properties of highly scattering media such as brain tissue.

A second project is developing a hybrid hardware/software technology for confocal and spectral imaging via microscope or endoscope.  A prototype imager has been employed for in situ imaging of fast intrinsic signals associated with excitation in the brainstem of an experimental animal, and shows promise for characterizing patterns of cellular activity in extended neural networks.  These technologies are presently being developed with support from the DOE Technology Transfer Initiative

Brain Imaging And Modeling
Human Brain Project
Bayesian Inference
MEGAN
NetMEG File
MRIVIEW