Modulation-frequency dependency of optical measurements in turbid media: Phantom and simulation studies E L Maclin1, J Kimnach1, K A Low1 , M Fabiani1, G Gratton1 & A Y Hsu2 1University of Illinois, Urbana-Champaign, 2Sandia National Laboratory Conclusions: The data suggest that, for semi-infinite media, the effects of changes in transparency (absorption) on phase are critically dependent on the relative position of the absorbing object with respect to the average photon path. Objects located closer to the surface than the average path may produce an effect opposite to that determined by objects at locations deeper than the average path. This principle is critical to understanding phase effects. Phase is particularly sensitive to deep effects compared to intensity measures. Finally, the sensitivity to deep effects depends on the modulation frequency, suggesting a mechanism (in addition to source-detector distance) for separating superficial from deep events. Acknowledgments: Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy’s National Nuclear Security Administration under contract DE-AC04-94AL85000. This project was supported by NIBIB grant #R01 EB002011 to Gabriele Gratton and NIA grant #AG21887 to Monica Fabiani. Introduction: Functional brain imaging using the event- related optical signal (EROS, based on modulated near-infrared light) has been demonstrated to possess both good spatial (<10 mm) and temporal resolution (<50 ms) in numerous sensory and cognitive studies. Low signal-to-noise ratio (SNR) in EROS and limited penetration (<4 cm) are known limitations of the technique. Previous efforts have experimentally investigated the effects of modulation frequency and laser wavelength on SNR. Changes in EROS parameters such as AC amplitude and phase have been observed by varying modulation frequency. This phenomenon is investigated here in phantom and simulated conditions as a possible way to improve EROS SNR. Methods : For the phantom study, three 400- micron source fibers emitting light at 690nm, and three 3mm-detector fiber bundles coupled to PMTs were arranged in a line on the surface of skim milk in an aquarium (Figure 1). A 1.4 cm diameter black disk was lowered along the midline of the source/detector line DC and AC amplitude and phase (delay) data were collected between each source/detector pair using an ISS Imagent® oxymeter at three modulation frequencies: 100, 200 and 300 MHz. A three-dimensional finite-element time- dependent Monte-Carlo model was developed to theoretically simulate and understand photon transport in the human brain as related to EROS measurements. Results - Phantom study : The phase shows a biphasic effect as a function of the depth. The phase is sensitive to deeper phenomena than is intensity data. The phase sensitivity to deeper phenomena is amplified at low (100 MHz) compared to high (300 MHz ) modulation frequencies. Greater src-det distance probes deeper Results - Monte Carlo Simulation : The Monte Carlo results are qualitatively similar to the milk tank results; Phase is biphasic Phase probes deeper than AC Lower modulation frequency has greater depth sensitivity Increasing the scattering coefficient increases the sensitivity to deep sources