The purpose of these studies was to test clinical devices generating noninvasive bedside measurements and images of brain function using low-power infrared light. A real-time bedside monitor for high-risk patients might allow care to be changed early in the course of injury, possibly preventing such injury from becoming irreversible, as well as permit monitoring of the efficacy of any intervention. Low-level visible and near-infrared light pass through human bone and tissue in small amounts, and the time of photon transit through the tissue can be used to measure tissue oxygenation, as well as to reconstruct images of the tissue (Benaron, Science, 1993). We modified an existing time-of-flight system and algorithms to allow conversion of real optical data into images at the bedside. We demonstrated the device to be 75% effective in detecting hemorrhages detected via ultrasound (Benaron, Peds. Res., 1996). In this study, mean predicted oxygen saturation error in model systems ranged from ± 0.4% at 1 cm estimated depth to ± 1.7% at 6 cm estimated depth. The device was then used in humans to measure 1) oxygenation in an ischemia model, 2) oxygenation in the neonatal brain, and 3) localized oxygenation changes in the brain during motor stimulation. We found that: 1) changes in oxygenation measured optically in the ischemia model corresponded in magnitude and direction to expected changes; 2) absolute optical measures of oxygenation in neonatal brain corresponded to measured jugular or SVC oxygenation as determined by standard invasive methods, and that an optical image of oxygenation in an infant with a stroke showed areas of low oxygenation that corresponded to the location of the stroke in a CT scan; and 3) monitoring of changes in oxygenation over the intact cerebral motor cortex in adults allowed imaging of regional motor stimulation during sequential finger movement. These findings are being correlated with functional MRI studies. In summary, a time-of-flight tomographic system for cerebral capillary estimation has been built which produces noninvasive, tomographic images of brain oxygenation using low-power nonionizing optical radiation. Bedside optical images of neonatal brain oxygenation can be produced continuously, and we have imaged stroke and functional brain activation. Supported by NIH N43-NS-4-2315 & RR-00081, ONR contract N-00014-94-1-1024, and by the Spectros Corporation (equity held except DKS, JVH).