We propose to explore the feasibility of using frequency-domain methods to obtain near-infrared optical images of thick tissues. The ability to image the interior of the human body arguably constitutes the single major advance in medicine during the last century. In addition to anatomical features, it is desirable to obtain information about metabolism within various tissues. The use of near-infrared radiation has been proposed as an attractive, alternative to obtain information about the oxygenation state of tissues due to the difference in optical spectra of the oxy- and deoxy- form of hemoglobin in this spectral region. Near-infrared radiation penetrates more than 10 cm in various tissues including the brain, breast and muscles. In the optical sense, image formation is impossible because scattering produces incoherent radiation after penetrating a few millimeters into the tissue. In tissues, light undergoes a diffusive process and the transmitted intensity arises from an average of a large number of different optical paths. Different light paths can be sorted by measuring the time of flight of a short light pulse. The idea is that the """"""""early photons"""""""" correspond to the shorter paths. Our approach uses the equivalent process in the frequency-domain, i.e., the propagation of high frequency amplitude modulated light. We realize that, in the frequency- domain, propagation of the amplitude modulated intensity wave in a highly scattering medium is analogous with wave optics. In this respect, an object immersed in the medium produces deformation of the propagating wavefront of the amplitude modulated wave and the result is relatively easy to detect and analyze. This wavefront perturbation results in an easy identification of absorbing and scattering objects such as blood vessels or bone. Furthermore, frequency-domain techniques are particularly suitable for array detectors; the most promising technology for real-time imaging. We are assembling a CCD camera system which, in conjunction with a high frequency modulated laser source and a computer for data processing and display, can produce real-time images of the interior of the body. In particular, we propose to focus on: i) a systematic study of the modalities of light propagation in tissues in the framework of diffusional wave optics; ii) the design and construction of the CCD camera system with particular emphasis on the modulation and synchronization capability of these devices; and iii) the development of ancillary computer algorithms to display in real-time the wavefront of the amplitude modulated wave after traversing the tissue, i.e., display the value of the amplitude and phase at every pixel of the projection image. Instead, the application of the optical imaging technique to specific medical areas is outside the goal of this proposal. After the three year period of this grant we should be able to assess the capabilities of the frequency-domain optical imaging technique in terms of spatial resolution, contrast, penetration, sensitivity and real-time response of the CCD camera apparatus.
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