Monitoring tissue response to photodynamic therapy: the potential of minimally invasive electrical impedance spectroscopy and high-frequency ultrasound

Electrical impedance spectroscopy (EIS) and high-frequency ultrasound (HFU) have been evaluated in various in vivo and in vitro models as potential methods to monitor biological changes induced by photodynamic therapy (PDT). EIS was assessed in tumor-bearing rat leg in vivo, in multicell tumor spheroids in vitro, and in normal rat liver tissue in vivo. HFU measurements, both imaging and backscatter frequency scanning, were tested in normal rat brain and skin treated in vivo. Marked changes in the EIS spectra were seen in all 3 models following PDT, depending on the photosensitizer and treatment parameters. With HFU, significant increases in echogenicity of the PDT-treated tissues were observed, with evidence of dose dependency and correlation with apoptotic cell death in vivo. While the results are encouraging for both modalities, a number of technical problems remain, particularly in the case of EIS, before these methods can be used reliably in mechanistic and clinical PDT applications.

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