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Modelling of light propagation in diffusive media with applications to tissue spectroscopy, tomography and photodynamic therapy

Šušnjar, Stefan LU orcid (2026) In Lund Reports on Atomic Physics, LRAP
Abstract
This thesis introduces the field of biomedical or diffuse optics and covers basic principles of light propagation in highly scattering media. Physics is well supported by mathematical derivations and equations, which is essential for the development of analytical models. These models are applied to three main fields.

First, in photodynamic therapy (PDT) — a promising approach, based on a dynamic interaction between light, photosensitiser (PS) and oxygen — for the treatment of prostate cancer. Real-time feedback based on three key components can be beneficial for better outcomes. The first component is tissue absorption, and measurements of tissue absorption have already been applied in clinical trials. The second is the spatial... (More)
This thesis introduces the field of biomedical or diffuse optics and covers basic principles of light propagation in highly scattering media. Physics is well supported by mathematical derivations and equations, which is essential for the development of analytical models. These models are applied to three main fields.

First, in photodynamic therapy (PDT) — a promising approach, based on a dynamic interaction between light, photosensitiser (PS) and oxygen — for the treatment of prostate cancer. Real-time feedback based on three key components can be beneficial for better outcomes. The first component is tissue absorption, and measurements of tissue absorption have already been applied in clinical trials. The second is the spatial distribution of PS concentration. In this work, we develop models and methods to monitor PS distribution during treatment. The models are based on diffuse fluorescence tomography (DFT). Developed methods include numerical simulations, inverse problem solving in two stages, preparation of tissue-mimicking phantoms with PS, and experimental validation. The third parameter is oxygen concentration, which could be a subject of future work.

After the basics of inverse problem solving in diffuse optical tomography (DOT), the fundamental principles of ultrasound optical tomography (UOT) are introduced. Mechanisms that cause the frequency of light to shift in the presence of ultrasound are discussed, and simplified modelling, based on the diffusion equation and perturbation approach, is presented. The developed model enables rapid simulation of UOT images of media with inhomogeneous absorption, which is essential for inverse problem solving and clinical translation of the technique.

Finally, within the field of diffuse optics, where mainly elastic scattering of light is discussed, inelastic Raman scattering is introduced for the purpose of spectroscopic applications with excellent chemical specificity. Diffuse Raman spectroscopy (DRS) for two-layered media is supported with thorough mathematical derivation and suggestions for further refinement.

In conclusion, this thesis connects three seemingly different fields of application (DFT in PDT, UOT, and DRS) by one common thread –– analogy in mathematical modelling. Raman scattered light, PS fluorescence, and ultrasound-modulated light are all kinds of “tagged’’ light that “carries information’’ about where this “tagging” has occurred. This is beneficial for spatial resolution in DFT and UOT, and is also used to separate Raman spectra of layered media. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof. Lilge, Lothar, University of Toronto, Canada.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
diffuse optics, photodynamic therapy (PDT), photosensitiser (PS) fluorescence, diffuse optical tomography (DOT), inverse problems, ultrasound optical tomography (UOT), tissue-mimicking phantoms, Raman spectroscopy
in
Lund Reports on Atomic Physics, LRAP
issue
622
publisher
Department of Physics, Lund University
defense location
Lecture Hall Rydbergsalen, Department of Physics, Professorsgatan 1, Faculty of Engineering LTH, Lund University, Lund.
defense date
2026-04-24 13:15:00
ISSN
0281-2762
ISBN
978-91-8104-923-7
978-91-8104-924-4
language
English
LU publication?
yes
id
f4e74501-aed6-476a-958c-3052f0091bfa
date added to LUP
2026-03-28 16:00:32
date last changed
2026-04-01 03:20:07
@phdthesis{f4e74501-aed6-476a-958c-3052f0091bfa,
  abstract     = {{This thesis introduces the field of biomedical or diffuse optics and covers basic principles of light propagation in highly scattering media. Physics is well supported by mathematical derivations and equations, which is essential for the development of analytical models. These models are applied to three main fields.<br/><br/>First, in photodynamic therapy (PDT) — a promising approach, based on a dynamic interaction between light, photosensitiser (PS) and oxygen — for the treatment of prostate cancer. Real-time feedback based on three key components can be beneficial for better outcomes. The first component is tissue absorption, and measurements of tissue absorption have already been applied in clinical trials. The second is the spatial distribution of PS concentration. In this work, we develop models and methods to monitor PS distribution during treatment. The models are based on diffuse fluorescence tomography (DFT). Developed methods include numerical simulations, inverse problem solving in two stages, preparation of tissue-mimicking phantoms with PS, and experimental validation. The third parameter is oxygen concentration, which could be a subject of future work.<br/><br/>After the basics of inverse problem solving in diffuse optical tomography (DOT), the fundamental principles of ultrasound optical tomography (UOT) are introduced. Mechanisms that cause the frequency of light to shift in the presence of ultrasound are discussed, and simplified modelling, based on the diffusion equation and perturbation approach, is presented. The developed model enables rapid simulation of UOT images of media with inhomogeneous absorption, which is essential for inverse problem solving and clinical translation of the technique.<br/><br/>Finally, within the field of diffuse optics, where mainly elastic scattering of light is discussed, inelastic Raman scattering is introduced for the purpose of spectroscopic applications with excellent chemical specificity. Diffuse Raman spectroscopy (DRS) for two-layered media is supported with thorough mathematical derivation and suggestions for further refinement.<br/><br/>In conclusion, this thesis connects three seemingly different fields of application (DFT in PDT, UOT, and DRS) by one common thread –– analogy in mathematical modelling. Raman scattered light, PS fluorescence, and ultrasound-modulated light are all kinds of “tagged’’ light that “carries information’’ about where this “tagging” has occurred. This is beneficial for spatial resolution in DFT and UOT, and is also used to separate Raman spectra of layered media.}},
  author       = {{Šušnjar, Stefan}},
  isbn         = {{978-91-8104-923-7}},
  issn         = {{0281-2762}},
  keywords     = {{diffuse optics; photodynamic therapy (PDT); photosensitiser (PS) fluorescence; diffuse optical tomography (DOT); inverse problems; ultrasound optical tomography (UOT); tissue-mimicking phantoms; Raman spectroscopy}},
  language     = {{eng}},
  number       = {{622}},
  publisher    = {{Department of Physics, Lund University}},
  school       = {{Lund University}},
  series       = {{Lund Reports on Atomic Physics, LRAP}},
  title        = {{Modelling of light propagation in diffusive media with applications to tissue spectroscopy, tomography and photodynamic therapy}},
  url          = {{https://lup.lub.lu.se/search/files/246068187/Thesis_Stefan_Susnjar_LUCRIS.pdf}},
  year         = {{2026}},
}