Optical techniques are used extensively in medicine to address a broad variety of disorders. Their impact has expanded from the traditional areas of dermatology and ophthalmology to include gynecology, oncology and cardiology, and, more recently dentistry, radiology, and anesthesiology. Consequently, the relationship between tissue optical properties and photo-medicine is tantamount to the importance of pharmacokinetics in clinical management. More specifically, rapid, accurate determination of tissue optical properties is essential to predicting photon dosimetry during therapeutic procedures, and interpreting the information content of back-scattered or transmitted light during diagnostic studies. Accordingly, we propose the development of frequency-domain photon migration (FDPM), a new optical method for non-invasive, quantitative assessment of tissue absorption and scattering. Since the underlying principle behind FDPM involves the propagation of diffuse photon density waves, this proposal addresses fundamental aspects of density-wave behavior in biological tissues. Our approach incorporates a balanced, interactive mix of theory and experiment. The conceptual framework is based on application of the diffusion approximation to light transport in turbid media. Relatively simple analytical solutions to the photon diffusion equation will be developed for a variety of tissue-like sample geometries. The validity of these equations will be tested in real and simulated tissues, and our experimental results will be used to highlight model limitations. The conceptual framework will be applied in a similar manner to fully describe experimental constraints. Modifications to the instrumentation, conceptual framework, and mathematical structure will, by design, occur in rapid fashion. For example, current photon density wave theory suggests that typical tissue measurements require bandwidths higher than the 250 MHz available with our existing instrument. We therefore propose expanding our system to approximately 500 MHz during the first grant year. High-bandwidth FDPM results will be compared to optical property values derived from conventional methods. Ultra-structural analyses will be performed on tissues in order to identify biological determinants of tissue optical properties. In this manner, a general model for the influence of instrumental parameters, optical properties, and geometrical boundaries on photon density waves will be developed. We expect this fundamental information will have a vital impact on nearly all aspects of photomedicine, including: 1) defining the utility, future applications and design considerations for optical diagnostic devices, 2) characterizing the limitations of current tissue light- transport models and 3) accounting for the numerous disparities between literature-reported tissue optical property values.
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