
Many materials are visually opaque because photons traveling within them are predominantly scattered rather than absorbed. Some common examples of these highly scattering media include white paint, foam, mayonnaise, and human tissue. Indeed, anyone who has held a flashlight up to his or her hand will notice some of this light is transmitted, albeit after experiencing many scattering events. Light travels through these materials in a process similar to heat diffusion. Diffuse light imaging and spectroscopy aims to investigate tissue physiology millimeters to centimeters below the tissue surface [1,2]. The cost of this aim is we must abandon traditional optical spectroscopies and traditional microscopy. The traditional methodologies require optically thin samples. In addition, light penetration must be large in order to reach tissue located centimeters below the surface. Fortunately, a spectral window exists within tissues in the near-infrared from 700 nm to 900 nm, wherein photon transport is dominated by scattering rather than absorption. The absorption of hemoglobin and water is small in the near-infrared, but elastic scattering from organelles and other microscopic interfaces is large. These are precisely the conditions required for application of the diffusion model. Using this physical model it is possible to quantitatively separate tissue scattering from tissue absorption, and to accurately incorporate the influence of boundaries, such as the air-tissue interface, into the transport theory. The diffusion approximation also provides a tractable basis for tomographic approaches to image reconstruction using highly scattered light. Even though absorption in the near-infrared is relatively small, the spectra of major tissue chromophores, particularly oxy- and deoxy- hemoglobin and water, differ significantly in the near-infrared. As a result, the diffuse optical methods are sensitive to blood dynamics, blood volume, blood oxygen saturation, and water and lipid content of interrogated tissues. In addition, one can induce optical contrast in tissues with exogenous contrast agents, for example chemical species that occupy vascular and extravascular space and preferentially accumulate in diseased tissue. Together these sensitivities provide experimenters with access to a wide spectrum of biophysical problems. The greater blood supply and metabolism of tumors compared to surrounding tissues provides target heterogeneity for tissue maps based on absorption. Similar maps can be applied for studies of brain bleeding, and cerebral oxygen dynamics associated with activation by mental and physical stimulation. Other applications of the deep tissue methods include the study of mitochondrial diseases, the study of muscle function and disease, and the study of photodynamic therapy.
[1] Yodh AG, Chance B, "Spectroscopy and Imaging with Diffusing
Light", Physics Today, Volume 48, No. 3, 34-40(1995); reprinted in
Japanese by The Maruzen Co., in the Japanese Physics journal "Parity"
pp. 8-17 (Feb. 1996).
[2] Yodh, AG and Boas, DA. "Functional Imaging with Diffusing Light."
Biomedical Photonics. ed. Vo-Dinh, T. Boca Raton: CRC Press,
2003. 21-1 - 21-45.
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These images show three dimenstional reconstruction of dynamic changes in cerebral blood flow (CBF) due to cortical spreading depression (CSD) measured on a rat brain through intact skull. Waves of increased CBF followed by a period of inhibition spreads out radially from a point on the top, middle of each image. The images correspond to top of the skull, the cortex (where the activity is), bottom of the cortex and below the cortex. Two waves of CSD are visible in this animation. |