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Photodynamic Therapy Light Dosimetry
Photodynamic therapy (PDT) is a cancer treatment that has been used experimentally for various types of malignancies including head and neck, bronchial, gastric, skin, lung, bladder and esophageal carcinoma. PDT with Photofrin(r) has recently received FDA approval in the US for treatment of esophageal and lung cancer.
PDT involves the interaction of a photosensitizing dye and red light, neither of which have any effect alone. Twenty-four hours after intravenous administration, the dye is cleared from normal tissue and localized in tumor tissue. Red laser light (chosen for optimal penetration) is applied to the tumor site. The red light is absorbed by the dye and raises the dye to an excited singlet state. The excited dye transfers energy to molecular oxygen in the tumor, resulting in highly reactive singlet oxygen that oxidizes biological targets such as cell membranes and organelles. The dye has a finite excited lifetime so the oxygen must be available near the excited dye molecule. The singlet oxygen also has a short lifetime and must be created near the desired target. PDT requires dual dosimetry for the drug dose and the light dose to ensure effective treatment of the entire tumor. It has been shown that a threshold light absorption is necessary to cause irreversible tumor necrosis. The light dose applied to the front surface must be sufficient to allow a threshold absorption at the deepest part of the tumor. Light penetration through the skin depends on tissue pigmentation, dye absorption and light scattering.
A material is optically characterized at the wavelengths of interest by microscopic absorption and scattering coefficients,k and s, and the anisotropy, g, or average cosine of the scattering angle. The light flux in a highly scattering medium can be calculated with the photon diffusion equation which is derived from radiative transfer theory. The distribution of light throughout the material as well as the diffuse reflectance and transmittance, R and T, of a material can be determined from k, s and g with mathematical tissue optics theories or with a Monte Carlo computer simulation. In order to determine the microscopic coefficients, the "inverse method" is employed: R and T are measured for an optically thin sample and k and s(1-g) are mathematically fitted to the measurements with optical theory. In this project, anisotropy will be measured directly with a goniometer.
The propagation of light through tissue has been successfully modeled with Monte Carlo simulation. Photon "bundles" are injected into the tissue and allowed to move throughout the specified dimensions with scattering and absorbing events occuring until the bundle is attenuated. Light that emerges from the front or rear surface is counted as reflection or transmission. Absorbed light is counted in a two or three-dimensional array to allow for flux density output.
Recent clinical studies [Jones and Grossweiner 1996] have shown that administration of Photofrin(r) causes increased reflectance of red light in basal cell skin tumors. In contrast, normal skin reflectance decreases, presumably due to light absorption by the dye. We have hypothesized that the increase in reflectance for tumors can be explained by a change in the scattering properties of the tissue. It is not known whether the changes in scattering are due to differences in localization or differences in dye binding or some other factor. It is important to investigate the cause of the scattering differences and to quantify the new scattering coefficient. Accurate light dosimetry must be based on the corrected optical coefficients of sensitized tissue.
College of Charleston Tissue Optics Lab
The tissue optics lab is equipped with an integrating sphere spectrophotometer and a goniometer, allowing determination of optical absorption and scattering coefficients as well as the average cosine of the scattering angle for thin tissue samples. The optical parameters may be used to model light flux through larger tissue samples with a Monte Carlo simulation of light-tissue interaction. We are currently examining photosensitizer-induced changes in the optical properties of cultured cells.
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