Reconstructing deep-tissue images in real time using spectrophotometric data from optically diffusing thick tissues has been problematic. Continuous wave applications (e.g., pulse oximetry, regional cerebral saturation) ignore both the multiple paths traveled by the photons through the tissue and the effects of scattering, allowing scalar measurements but only under limited conditions; interferometry works poorly in thick, highly-scattering media; frequency- modulated approaches may not allow full deconvolution of scattering and absorbance; and pulsed-light techniques allow for preservation of information regarding the multiple paths taken by light through the tissue, but reconstruction is both computation intensive and limited by the relative surface area available for detection of photons. We have developed a picosecond times-of-flight and absorbance (TOFA) optical system, time-constrained to measure only photons with a narrow range of path lengths and arriving within a narrow angel of the emitter-detector axis. The delay until arrival of the earliest arriving photons is a function of both the scattering and absorbance of the tissues in a direct line between the emitter and detector, reducing the influence of surrounding tissues. Measurement using a variety of emitter and detector locations produces spatial information which can be analyzed in a standard 2-D grid, or subject to computer reconstruction to produce tomographic images representing 3-D structure. Using such a technique, we have been able to demonstrate the principles of tc-TOFA, detect and localize diffusive and/or absorptive objects suspended in highly scattering media (such as blood admixed with yeast), and perform simple 3-D reconstructions using phantom objects. We are now attempting to obtain images in vivo. Potential future applications include use as a research tool, and as a continuous, noninvasive, nondestructive monitor in diagnostic imaging, fetal monitoring, neurologic and cardiac assessment. The technique may lead to real-time optical imaging and quantitation of tissues oxygen delivery.