On the use of light for the characterization and treatment of malignant tumours

Claes af Klinteberg

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Some aspects on the use of light for tissue characterization and treatment of malignant tumours are discussed within this thesis. The work presented aims at improving optical techniques for tissue characterization, especially to detect malignant and pre-malignant lesions. A knowledge on the interaction between light and tissue is of utmost importance to understand and improve the various techniques. A relatively thorough discussion on the light propagation in scattering media is given. A commonly used mathematical model, the diffusion approximation of the transport equation, is derived. Moreover, knowledge of the optical properties of tissue, <i>i.e.</i>, the absorption and scattering coefficients, the scattering anisotropy, and the refractive index, is needed to use the mathematical models. Various techniques for <i>in vivo</i> measurements of the tissue optical properties are presented. Furthermore, some of these techniques have been developed into prototype equipment to be used for breast cancer detection, as an alternative to the ordinary mammography based on ionizing X-rays.

A therapeutic modality, photodynamic therapy (PDT), presently being introduced into clinical practice has also been investigated. This technique relies on the selective uptake of a photosensitizing agent, and the subsequent irradiation using light. The light absorbed by the photosensitizer triggers a photochemical reaction, leading to local cell death. In the work presented here, d-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) has been used as a photosensitizer. A randomized Phase III clinical trial has been conducted to compare PDT with cryosurgery for the treatment of basal cell carcinomas of the skin. The influence on the treatment of various parameters have been investigated and are discussed.

Laser-induced fluorescence studies were performed to detect and demarcate superficial malignant and pre-malignant lesions. Both the tissue autofluorescence and the characteristic emission of fluorescent tumour markers were employed. Fluorescence was also used to monitor the selective buildup and the photodegradation of the photosensitizer in connection to PDT, using a point-monitoring technique. Two fluorescence imaging systems have also been used to outline skin lesions.

Laser-Doppler perfusion imaging is a non-contact optical technique used to monitor the superficial blood perfusion, and was here used to evaluate the healing time following cryosurgery and PDT.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Atomic Physics
Supervisors/Advisors
  • Andersson-Engels, Stefan, Supervisor
Award date1999 May 7
Publisher
ISBN (Print)91-628-3511-4
Publication statusPublished - 1999

Bibliographical note

Defence details

Date: 1999-05-07
Time: 10:15
Place: Lecture Hall B, Department of Physics, Sölvegatan 14, Lund, Sweden

External reviewer(s)

Name: Tromberg, Bruce J
Title: Assoc. Prof
Affiliation: Beckman Laser Institute, University of California, Irvine, CA, USA

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Article: I. R. Berg, S. Andersson-Engels, C. af Klinteberg, S. Svanberg and O. Jarlman,Optical imaging for medical diagnostics using femtosecond white light,in Advances in Optical Imaging and Photon Migration, ed. R.R. Alfano, Proc. OSA vol. 21, 126-128 (1994).

Article: II. C. af Klinteberg, R. Berg, S. Andersson-Engels and S. Svanberg,Diffusely scattered femtosecond white light examination of breast tissue in vitro and in vivo,in Photon Propagation in Tissues, eds. B. Chance, D.T. Delpy and G.J. Müller, Proc. SPIE vol. 2626, 149-157 (1995).

Article: III. C. af Klinteberg, C. Lindquist, A. Pifferi, R. Berg, S. Andersson-Engels and S. Svanberg,Diffusely scattered femtosecond white light examination of breast tissue,in Medical and Biological Applications, ed. R. Cubeddu, OSA Trends in Optics and Photonics vol. 6, 30-35 (1996).

Article: IV. C. af Klinteberg, A. Pifferi, S. Andersson-Engels, R. Cubeddu and S. Svanberg,In vivo absorption spectrum of disulphonated aluminium phthalocyanine (AlS2Pc) using femtosecond white light,Manuscript for Photochem. Photobiol. (1999).

Article: V. C. af Klinteberg, C. Lindquist, I. Wang-Nordman, A. Vaitkuviene and K. Svanberg,Laser-induced fluorescence studies of premalignant and benign lesions in the female genital tract,in Optical Biopsies and Microscopic Techniques II, eds. I.J. Bigio, K. Svanberg, H. Schneckenburger, J. Slavik and P.M. Viallet, Proc. SPIE 3197, 34-40 (1997).

Article: VI. C. af Klinteberg, M. Andreasson, O. Sandström, S. Andersson-Engels and S. Svanberg,Compact medical fluorosensor for minimally invasive tissue characterisation,Manuscript (1999).

Article: VII. C. af Klinteberg, I. Wang, I. Karu, T. Johansson, N. Bendsoe, K. Svanberg, S. Andersson-Engels, S. Svanberg, G. Canti, R. Cubeddu, A. Pifferi, P. Taroni and G. Valentini,Diode laser-mediated ALA-PDT guided by laser-induced fluorescence imaging,Submitted to Lasers Med. Sci. (1999).

Article: VIII. S. Andersson-Engels, G. Canti, R. Cubeddu, C. Eker, C. af Klinteberg, A. Pifferi, K. Svanberg, S. Svanberg, P. Taroni, G. Valentini and I. Wang,Spectroscopic characterisation of basal cell carcinomas of the skin with multi-colour and lifetime fluorescence imaging,Submitted to Lasers Surg. Med. (1999).

Article: IX. I. Karu, S. Pålsson, I. Wang, C. af Klinteberg, N. Bendsoe, S. Andersson-Engels, S. Svanberg and K. Svanberg,Photodynamic therapy using d-amino levulinic acid and intensity modulated diode laser light,Submitted to Lasers Med. Sci. (1999).

Article: X. I. Karu, I. Wang, C. af Klinteberg, S. Andersson-Engels, S. Svanberg and K. Svanberg,Evaluation of pain and dysesthesia in connection with diode laser mediated ALA-PDT,Submitted to Br. J. Dermatol. (1999).

Article: XI. I. Wang, N. Bendsoe, C. af Klinteberg, A.M.K. Enejder, S. Andersson-Engels, S. Svanberg and K. Svanberg,Photodynamic therapy versus cryosurgery of basal cell carcinomas; results of a Phase III clinical trial,Manuscript for Cancer (1999).

Article: XII. C. af Klinteberg, A.M.K. Enejder, I. Wang, S. Andersson-Engels, S. Svanberg and K. Svanberg,Kinetic fluorescence studies of 5-aminolaevulinic acid-induced protoporphyrin IX in basal cell carcinomas,J. Photochem. Photobiol. B, In press (1999).

Article: XIII. C. af Klinteberg, I. Wang, A.M.K. Enejder, S. Andersson-Engels, S. Svanberg and K. Svanberg,5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in basal cell carcinomas of the skin,Manuscript for Photochem. Photobiol. (1999).

Article: XIV. A.M.K. Enejder, C. af Klinteberg, I. Wang, S. Andersson-Engels, N. Bendsoe, S. Svanberg and K. Svanberg,Blood perfusion studies on basal cell carcinomas in conjunction with photodynamic- and cryotherapy employing laser-Doppler imaging,Submitted to Acta Derm. Venereol. (1999).

Subject classification (UKÄ)

  • Atom and Molecular Physics and Optics

Keywords

  • Diffusion equation
  • Aminolevulinic acid
  • Protoporphyrin IX
  • Photodynamic therapy
  • Fluorescence spectroscopy
  • Fluorescence imaging
  • Laser-Doppler perfusion imaging
  • Atom- och molekylärfysik
  • Atomic and molecular physics
  • Multiple scattering
  • Tissue optics
  • Tissue optical properties
  • Fysicumarkivet A:1999:Klinteberg

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