The focus of the research of the Laser Biophysics group is the development and application of new therapeutic and diagnostic techniques based on the use of lasers and other optical technologies. In this translational research, a wide range of methodolo- gies are used: theoretical and experimental studies of light transport in tissues, development of light sources/optical-fiber light delivery devices and of optical dosimeters, photobiological studies at the cellular and tissue level, in vivo optical spectroscopy of tissues, development of prototype clinical instruments, and co-operative clinical trials.
Two examples will serve to illustrate the work: the first therapeutic and the second diagnostic. Photodynamic therapy (PDT), the use of light-activated drugs (photosensitizers), is being developed as a new method for selective destruction of solid tumours. We are currently using an animal model to study the relationships between tissue response and the light and photosensitizer 'doses'. A particular focus at present is on malignant brain tumours. This involves induction of intracranial tumours in an animal model, PDT treatment via interstitially-placed optical fibers with simultaneous measurement of light fluences in situ, followed by quantitative histopathology and biochemical analysis of resected tissues. These data are then combined in a model of the photodynamic process to determine the fundamental PDT sensitivity of the tissue-photosensitizer combination. We have recently found that one photosensitizer (5d-aminolevulinic acid, a heme precursor) has an extremely high sensitivity in tumour compared to normal white matter in the brain. This will lead to a Phase I clinical trial of this drug.
Tissue fluorescence, the re-emission of longer wavelength light by a molecule after absorption of a shorter wavelength photon, is being investigated as a possible method for detection of early cancer during endoscopy of the gastrointestinal tract. In the present work, supported by industry, fluorescence spectra of normal, benign and malignant tissues of esophagus, stomach and colon are being made using an optical-fiber based instrument during white-light endoscopy in selected groups of patients. These data then form the basis for developing imaging algorithms to be used in a real-time fluorescence endoscope, a prototype of which is undergoing initial clinical trials here. Human tissue biopsies are being analyzed by confocal fluorescence microscopy and, together with studies of the attenuation of light in gastrointestinal tissues, the measurements are being used to develop a quantitative model of the in vivo fluorescence process. Recently an animal model of chemically-induced cancer has been started to make more controlled and detailed studies of the relationships between tumour progression and changes in tissue fluorescence.