Photodynamic therapy with porfimer sodium (PS) is a treatment option for high grade dysplasia associated with Barrett's
esophagus. This study sought to investigate the optical properties of Barrett's dysplasia that may be useful in light
dosimetry planning and to determine the effect of PS on tissue absorption and scattering. Fiber optic reflectance spectra
were collected before and 48 hours after administration of 2 mg/kg PS. Mucosal biopsies were collected at the same
locations. According to Monte Carlo analysis, the fiber optic probe sampled only the mucosal layer. A mathematical fit
of the reflectance spectra was performed as a function of blood volume fraction, oxygen saturation and scattering. The
average calculated blood volume was 100% higher in Barrett's tissue than normal esophageal tissue. The average
scattering slope from 620 to 750 nm was 26% higher for Barrett's dysplasia than normal esophageal tissue, indicating an
increase in the size of scattering particles. The difference in the scattering amplitude was not statistically significant,
suggesting no significant increase in the number of scattering particles. PS tissue content was determined with extraction
methods. Changes in the scattering slope due to PS sensitization were observed; however they were not proportional to
the extracted PS concentration.
Background: Photodynamic therapy using porfimer sodium (Ps-PDT) is approved for use in patients with Barrett's highgrade dysplasia and esophageal carcinoma. Ps-PDT light dosimetry, however, is critically important to treatment outcomes since insufficient ablation results in residual dysplasia and carcinoma while excessive treatment results in stricture formation. Aim: The aim of this study was to model esophageal PDT with optical absorption and scattering coefficients derived from an ex-vivo porcine multilayer esophagus model. Methods: Optical coefficients were derived for the mucosal and muscle layers of normal pig esophagus. The mucosal layer (mucosa, muscularis mucosa and submucosa) was separated from the muscle layer. Diffuse reflectance and transmittance were measured with an integrating sphere spectrophotometer. Absorption and reduced scattering coefficients were determined with the inverse adding doubling method.
(Table not available in abstract, see pdf of paper) Multilayer Monte Carlo simulation and single-layer mathematical dosimetry equations were employed to model esophageal PDT with the derived coefficients. Porfimer sodium addition was modeled with an increase in both absorption and scattering. Depth of injury, assumed to require a threshold light dose, was estimated for various light doses commonly used in clinical practice. Depth of injury was then compared to clinical outcomes reported in the literature for various light doses.
The design of fiber-optic probes plays an important role in optical spectroscopic studies, including fluorescence spectroscopy of biological tissues. It can affect the light delivery and propagation into the tissue, the collection efficiency (total number of photons collected vs. total number of photons launched) and the origin of collected light. This in turn affects the signal to noise ratio (SNR) and the extend of tissue interrogation, thus influencing the diagnostic value of such techniques. Three specific fiber-optic probe designs were tested both experimentally and computationally
via Monte Carlo simulations. In particular, the effects of probe architecture (single-fiber vs. two bifurcated multifiber probes), probe-to-target distance (PTD), and source-to-detector separation (SDS) were investigated on the collected diffuse reflectance of a Lambertian target and an agar-based tissue phantom. This study demonstrated that probe architecture, PTD, and SDS are closely intertwined and considerably affect the light collection efficiency, the extend of target illumination, and the origin of the collected reflected light. Our findings can be applied towards optimization of
fiber-optic probe designs for quantitative fluorescence spectroscopy of diseased tissues.
Skin reflection spectra were measured before and 24 hours after administration of Photofrin (Reg. TM) to basal cell nevus syndrome (BCNS) patients. The drug reduced the reflectivity of uninvolved BCNS skin and increased the reflectivity of basal cell cancers. Photofrin (Reg. TM) absorption in normal rat skin and uninvolved BCNS skin was resolved by the diffusion approximation. Optical constants calculated with a two-layer skin model indicate that the drug increased light scattering in tumor tissues. The possible use of reflection spectra for PDT light dosimetry is discussed.
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