<title>Feasibility studies of electrical impedance spectroscopy for monitoring tissue response to photodynamic therapy</title>

Abstract

Electrical impedance spectroscopy (EIS) has been evaluated as a non- or minimally-invasive technique to monitor the acute tissue response to photodynamic therapy (PDT). In this study the EIS spectra of normal muscle tissue in the rat hind leg were monitored immediately before and at time intervals up to 96 hours post-PDT treatment with different photosensitizers (Photofrin, ALA-induced PpIX, BenzoPorphyrin Derivative), at varying photosensitizer and light doses. EIS measurements were made using a pair of solid matrix Ag-AgCl electrodes placed parallel to one another on either side of the muscle mass and interfaced to a precision LCR impedance meter scanning the frequency range 1 - 1000 KHz. Independent histological grading of tissue injury was performed on tissue sections from treated and untreated legs at the 96 hour end point. Significant and PDT dose-dependent changes in the EIS spectra following treatment were observed, including increases in conductivity which correlated with the immediate post-PDT edematous response with Photofrin and ALA and which resolved or partially-resolved over the measurement time course. Photofrin treatments exhibited a clear drug dose response at 96 hours that was evident in both the EIS spectra and the histological sections. These changes included significant tissue necrosis as well as edema, inflammation and early fibroplasia. The BPD data were less clear, but potentially quite interesting. Most striking were below unity ratios of treated-to-untreated muscle spectra components at 24 hours which reversed to above unity by 96 hours in the through skin measurements. This phenomenon is indicative of a tissue response distinctly different than that observed with Photofrin or ALA. These data also suggest that EIS measured changes are sensitive enough to detect differences in PDT-initiated tissue damage that may be photosensitize-specific. While the data are derived from a small number of animals, the findings are quite encouraging in terms of the potential for EIS to track PDT-induced changes in tissue.