Methods, Instrumentation and Mechanisms for Optical Characterization of Tissue and Treatment of Malignant Tumours

Abstract: In this thesis, different optical methods utilising visible light for characterization of tissue have been developed and evaluated. The feasibility of many of these methods has been demonstrated in the laboratory or in animal experiments. However, the goal is naturally to develop methods useful in the clinic, and thus the emphasis in this thesis has been put on in vivo examinations. Raman spectroscopy is an optical method that can provide information regarding vibrational modes in molecules and concentrations of tissue constituents. The Raman spectra contain sharp peaks and are suited for multivariate evaluation since one specific peak represents a vibrational mode that can be present in many different molecules. The Raman signal is weak and is often hidden in the strong fluorescence emission from tissue. The main challenge lies in the development of clinical Raman spectroscopy systems that are capable of recording Raman spectra with high resolution and low noise in a short accumulation time. This problem is discussed together with applications of Raman spectroscopy in cardiology and dermatology. Fluorescence spectroscopy is another technique used for tissue characterization and detection of lesions. The application of fluorescence spectroscopy for the delineation of borders between normal and malignant tissue in oncological dermatology and neurosurgery is discussed as well as the potential of classification of myocardial biopsies from patients with transplanted hearts. The construction and usefulness of a small clinical system is also discussed. In the development of models capable of correlating fluorescence spectra with clinical diagnosis, the problem of biopsy location and biological variability within the biopsies has been addressed in a study of protocols for histopathological evaluation in the field of gynaecology. The use of light for treatment of malignant tumours is often associated with the thermal impact of laser ‘knifes’ employed during excisions. However, light can also be a constituent in non-thermal photochemical reactions where light, together with a tumour-seeking photosensitizer and tissue oxygen, react and lead to critical cell death, which kills tumours. This treatment modality is called photodynamic therapy and some of the involved mechanisms have been explored in the thesis. Due to the limited penetration of visible light, a system for interstitial delivery of treatment light has been developed to be able to treat thicker and deeply located tumours. The dosimetry is important and the photodynamic threshold dose has been estimated.