title: In vivodetermination of the absorption and scattering spectra of the human prostate during photodynamic therapy.
abstract: A continuing challenge in photodynamic therapy is the accuratein vivodetermination of the optical properties of the tissue being treated. We have developed a method for characterizing the absorption and scattering spectra of prostate tissue undergoing PDT treatment. Our current prostate treatment protocol involves interstitial illumination of the organviacylindrical diffusing optical fibers (CDFs) inserted into the prostate through clear catheters. We employ one of these catheters to insert an isotropic white light point source into the prostate. An isotropic detection fiber connected to a spectrograph is inserted into a second catheter a known distance away. The detector is moved along the catheter by a computer-controlled step motor, acquiring diffuse light spectra at 2 mm intervals along its path. We model the fluence rate as a function of wavelength and distance along the detector's path using an infinite medium diffusion theory model whose free parameters are the absorption coefficient µaat each wavelength and two variables A and b which characterize the reduced scattering spectrum of the form µ's= Aλ-b. We analyze our spectroscopic data using a nonlinear fitting algorithm to determine A, b, and µaat each wavelength independently; no prior knowledge of the absorption spectrum or of the sample's constituent absorbers is required. We have tested this method in tissue simulating phantoms composed of intralipid and the photosensitizer motexafin lutetium (MLu). The MLu absorption spectrum recovered from the phantoms agrees with that measured in clear solution, and µaat the MLu absorption peak varies linearly with concentration. The µ'sspectrum reported by the fit is in agreement with the known scattering coefficient of intralipid. We have applied this algorithm to spectroscopic data from human patients sensitized with MLu (2 mg kg-1) acquired before and after PDT. Before PDT, the absorption spectra we measure include the characteristic MLu absorption peak. Using our phantom data as a calibration, we have determined the pre-treatment MLu concentration to be approximately 2 to 8 mg kg-1. After PDT, the concentration is reduced to 1 to 2.5 mg kg-1, an indication of photobleaching induced by irradiation. In addition, absorption features corresponding to the oxygenated and deoxygenated forms of hemoglobin indicate a reduction in tissue oxygenation during treatment.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce St., 2 Donner Building, Philadelphia, PA USA 19104.
authors.forename: Jarod C
authors.initials: JC
authors.lastname: Finlay
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce St., 2 Donner Building, Philadelphia, PA USA 19104.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce St., 2 Donner Building, Philadelphia, PA USA 19104.
authors.forename: Andreea
authors.initials: A
authors.lastname: Dimofte
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce St., 2 Donner Building, Philadelphia, PA USA 19104.
authors.forename: Diana
authors.initials: D
authors.lastname: Stripp
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce St., 2 Donner Building, Philadelphia, PA USA 19104.
authors.forename: S Bruce
authors.initials: SB
authors.lastname: Malkowicz
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce St., 2 Donner Building, Philadelphia, PA USA 19104.
authors.forename: Richard
authors.initials: R
authors.lastname: Whittington
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce St., 2 Donner Building, Philadelphia, PA USA 19104.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Miles
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce St., 2 Donner Building, Philadelphia, PA USA 19104.
authors.forename: Eli
authors.initials: E
authors.lastname: Glatstein
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce St., 2 Donner Building, Philadelphia, PA USA 19104.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hahn
keywords: diffuse reflectance; diffusion theory; in-vivo light dosimetry; motexafin lutetium; photodynamic therapy; tissue optical properties