Dual-Wavelength Fluorescence Monitoring of Photodynamic Therapy: From Analytical Models to Clinical Studies

Abstract

Fluorescence imaging modalities are currently a routine tool for the assessment of marker distribution within biological tissues, including monitoring of fluorescent photosensitizers (PSs) in photodynamic therapy (PDT). Conventional fluorescence imaging techniques provide en-face two-dimensional images, while depth-resolved techniques require complicated tomographic modalities. In this paper, we report on a cost-effective approach for the estimation of fluorophore localization depth based on dual-wavelength probing. Owing to significant difference in optical properties of superficial biotissues for red and blue ranges of optical spectra, simultaneous detection of fluorescence excited at different wavelengths provides complementary information from different measurement volumes. Here, we report analytical and numerical models of the dual-wavelength fluorescence imaging of PS-containing biotissues considering topical and intravenous PS administration, and demonstrate the feasibility of this approach for evaluation of the PS localization depth based on the fluorescence signal ratio. The results of analytical and numerical simulations, as well as phantom experiments, were translated to the in vivo imaging to interpret experimental observations in animal experiments, human volunteers, and clinical studies. The proposed approach allowed us to estimate typical accumulation depths of PS localization which are consistent with the morphologically expected values for both topical PS administration and intravenous injection.

Devices and Methods for Dosimetry of Personalized Photodynamic Therapy of Tumors: A Review on Recent Trends

“…The authors in [48] demonstrated the effectiveness of dual-wavelength ALA-PDT dosimetry of patients with actinic keratosis (n = 15) using PpIX photobleaching with fluorescence excitation at 405 and 639 nm, which makes it possible to take into account the PS distribution in the superficial and deeper layers of biological tissues. Previously, the effectiveness of two-wave Ce6-PDT monitoring for changes in the PS fluorescence intensity at different depths of biological tissue was also demonstrated and the results were shown to correspond to the results of Monte Carlo simulation [124]. Currently, preliminary numerical modeling methods are also being introduced into clinical practice to predict optimal PDT energy doses.…”

Post-Operational Photodynamic Therapy of the Tumor Bed: Comparative Analysis for Cold Knife and Laser Scalpel Resection

“…Another factor that may affect the performance of PDT in deeper tissue layers is the penetration depth of irradiation, which is used to activate the accumulated PS. In this study, with the chlorin-based PS, we compare the effect of PDT performance at the wavelengths of 660 and 405 nm, both of which correspond to chlorin e6 absorption peaks [ 24 ] and were proposed for PDT performance [ 26 ]. Since the absorbed light dose distribution within tissue cannot be measured directly, we performed Monte Carlo simulations of the absorbed dose distribution for the values of optical properties typical for tumors and muscular tissues summarized in Table 2 .…”

“…Topically applied PSs do not require intravenous injection, and they benefit from a simple application procedure [ 23 ]. Chlorin-based photosensitizers feature two peaks in their absorption spectrum in the red and blue bands, thus providing different penetration depths owing to significant differences in the biotissue optical properties of these bands [ 24 , 25 ]. Previously, PDT with topically applied PS has demonstrated limited efficiency in tumor treatment, owing to the limited penetration of PS into the tumor [ 26 ]; however, its application to the tumor bed after the procedure seems to be promising.…”

Combined Monte Carlo and k-Wave Simulations for Reconstruction of Blood Oxygen Saturation in Optoacoustics: A Pilot Study

“…Traditional Monte Carlo (MC) technique for light transport studies is based on modeling of a large number of random photon trajectories in turbid media with following statistical analysis of the collected data [32]. In this work previously developed platform for threedimensional MC modeling of light propagation in biological tissues [22,33,34] was customized by implementing elongated absorbers mimicking different vessels filled with blood within biotissue. It was employed for the generation of the maps of the absorbed light dose distribution at probing wavelength λex 𝐻(𝑥, 𝑦, 𝑧, λ 𝑒𝑥 ) in a flat tissue-like homogenous medium containing cylinders mimicking blood vessels of different diameters, embedding depths and orientations corresponding to typical morphological parameters.…”