Dual-wavelength fluorescence monitoring of photodynamic therapy: from analytical models to in vivo studies
M. Kirillin1, D. Kurakina1, A. Khilov1, A. Orlova1, M. Shakhova1,2, V. Perekatova1,
N. Shishkova1,3, A. Mironycheva1,2, A. Malygina2, I. Shlivko2, N. Orlinskaya2, S. Gamayuov1,4,
I. Turchin1, and E. Sergeeva1
1Institute of Applied Physics RAS, Nizhny Novgorod, Russia
2Privolzhsky Research Medical University, Nizhny Novgorod, Russia
3N.I. Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia
4Nizhny Novgorod Regional Clinical Oncology Center, Nizhny Novgorod, Russia
Abstract
Photodynamic therapy (PDT) is a treatment modality based on photoactivation of a photosensitizer (PS) delivered to the treated area prior to the procedure resulting in local production of reactive oxygen species. Strong fluorescence of traditionally employed PSs excited in visible range provide wide opportunities for fluorescence imaging use in monitoring of PDT procedures, while high dispersion of biotissues optical properties in this range allow for complementary registration of fluorescence signals from different probing depths. This effect is especially pronounced in chlorin-based PSs exhibiting two absorption peaks in red and blue bands of visible spectra, where significant difference in biotissue optical properties is governed by absorption of blood and melanin. The ratio of the fluorescence signals excited at corresponding wavelengths was previously demonstrated to serve as a measure of fluorophore localization depth.
In this paper we consider a theoretical basis of employing dual-wavelength fluorescence imaging for characterizing PSs localization for both topical administration and intravenous injection. The developed models are based on diffusive approximation of radiative transfer equation and include separate consideration of propagation of probing radiation and fluorescence emission in a biotissue. The developed analytical models of dual-wavelength fluorescence monitoring are in good agreement with corresponding Monte Carlo simulations and experiments with custom-designed phantoms mimicking optical properties of biotissues with embedded PS. For both options of PS administration way, monotonic dependencies of fluorescence signal ratio of PS localization depth are demonstrated revealing the opportunity for its evaluation given that optical properties of biotissue are known. Analysis of the effect of optical properties on the fluorescence signal ratio is also reported.
The developed approach is employed for interpretation of the in vivo measured dynamics of fluorescence signal ration acquired both in laboratory animals and in patients in course of PDT monitoring. The monitoring was performed in PDT procedures with both topical administration and intravenous injection of chlorin-based PS. Owing to specific optical properties, the use of the chlorin-based PS implies the use of both red and blue light for the procedure allowing to choose between superficial or deeper action. The action depth of the PDT procedure can also be monitored through the fluorescence signal ratio, since it is affected by redistribuition of PS concentration in biotissue owing to photobleaching. The interpretations to in vivo observations are given in the frames of this paradigm.
The study is supported by Russian Science Foundation (project 17-15-01264).
Speaker
Mikhail Kirillin
Institute of Applied Physics RAS
Russian
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