Assessing PDT response with diffuse optical spectroscopies
Rohrbach, Daniel J.
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Photodynamic therapy (PDT) is used to treat a variety of conditions including cancer. Effective PDT requires three components: a photosensitizer (PS), light of a specific wavelength to activate the PS and oxygen. When all three are present in a lesion it leads to cell death and vascular destruction. Optical techniques such as diffuse reflectance spectroscopy (DRS), diffuse fluorescence spectroscopy (DFS) and diffuse correlation spectroscopy (DCS) can be used to quantify vascular parameters and photosensitizer content before and after PDT, providing valuable information for assessing response. For the quantification of vascular parameters, a probe-specific empirical light transport model was developed. A look-up-table was constructed using tissue simulating phantoms made of Intralipid to control the scattering, India Ink to control the absorption and water. The empirical model allowed the quantification of optical properties as well as the vascular parameters blood volume fraction (BVf) and blood oxygen saturation (SO 2 ) with DRS. Blood flow was measured using DCS. For the quantification of PS content two techniques were used. DRS was used to fit the absorption of the PS and DFS measured the fluorescence of the PS. For quantification of PS content from measured fluorescence, a correction factor was developed using Monte Carlo simulations to account for the optical properties at the excitation and emission wavelengths. The three techniques were used to assess PDT response in pre-clinical and clinical studies. For the preclinical study, mice were treated with HPPH-PDT and blood flow was measured continuously with DCS. Blood flow variables were compared to STAT3 crosslinking (a molecular marker for PDT photoreaction) and CD31 staining (to visualize intact endothelial cells after PDT). For the clinical study, patients in a clinical trial for HPPH-PDT were measured with DRS, DFS and DCS before and after treatment. Multiple parameters were compared to the clinical response. No individual parameter was a good predictor of response, but when multiple parameters were combined into a single classifier, the assessment of response improved. This study shows that diffuse optical spectroscopies are a valuable tool for assessing PDT response in clinical settings.