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A. AIMS Though widely used for functional neuroimaging, BOLD fMRI measures a relative change in blood oxygenation and is subject to confounds due to variations in baseline physiology and the competing effects of changes in blood flow and oxygen metabolism. These uncertainties currently limit BOLD imaging and have stymied applications that depend on repeatability. An attractive strategy for working around these BOLD limitations is to pursue a quantitative measure of the relative change in the cerebral metabolic rate of oxygen (rCMRO2) synthesized from a complete set of hemodynamic parameters. fMRI, by itself, is currently unable to provide this complete set of hemodynamic parameters in humans during brain activation without relying on untested assumptions relating flow and volume changes. The goal of this grant is to develop and validate a multi-modality methodology for metabolic neuroimaging of the cortex through the integration of Diffuse Optical Tomography (DOT) and MRI. Diffuse optical imaging has been demonstrated to be an effective tool for monitoring local changes in total hemoglobin concentration and oxygenation during functional brain activation. In this project, we will advance the non-invasive optical neuroimaging technology to increase the quantitative accuracy of estimated baseline and dynamic hemoglobin concentrations. A novel hybrid time domain and continuous wave brain imaging system will be combined with MRI guided reconstruction methods. The quantitative baseline and functional optical measures of total hemoglobin, and deoxyhemoglobin will be combined with fMRI arterial spin labeling measures of the relative change in cerebral blood flow (rCBF) to calculate images of rCMRO2. Validation will be pursued through a combination of graded global and focal modulations and through comparison with analogous fMRI measures. The project will consummate in characterizing the rCMRO2 response to graded levels of somatosensory stimulation and variances in baseli