In vivo absorption spectroscopy of tumor sensitizers with femtosecond white light

A system based on a femtosecond white-light continuum and a streak camera was used for recordings of the in vivo absorption spectra of the tumor-seeking agent disulphonated aluminum phthalocyanine. Measurements for different drug doses were performed on tumor tissue (muscle-implanted adenocarcinoma) and normal muscle tissue in rats. It was found that the shape of the spectrum is tissue dependent. The peak of the absorption spectrum is blueshifted in tumor tissue as compared with the muscle. Thus the contrast in the drug-related absorption can be altered by up to a factor of 2 from the primary drug molecular-concentration contrast between normal muscle and tumor by the proper selection of the illumination wavelength

Compact medical fluorosensor for minimally invasive tissue characterization

A compact fiber-optic point-measuring fluorosensor fully adapted to clinical studies is described. The system can use two excitation wavelengths, 337 and 405 nm, obtained from a nitrogen laser directly, or after dye laser conversion, respectively. The image intensifier used in the spectrometer can be gated with a variable time delay, allowing also time-resolved spectra to be extracted, with a time resolution of about 4 ns. Moreover, diffusely scattered white light can be spectrally recorded. The system is fully computer controlled enabling short recording times in clinical application, which are illustrated

Concentration measurement of gas embedded in scattering media by employing absorption and time-resolved laser spectroscopy

Diode-laser-based absorption spectroscopy for the evaluation of embedded gas concentrations in porous materials is demonstrated in measurements of molecular oxygen dispersed throughout scattering polystyrene foam, used here as a generic test material. The mean path length of light scattered in the material is determined with the temporal characteristics of the radiation transmitted through the sample. This combined with sensitive gas-absorption measurements employing wavelength-modulation spectroscopy yields an oxygen concentration in polystyrene foam of 20.4% corresponding to a foam porosity of 98%, which is consistent with manufacturing specifications. This feasibility study opens many possibilities for quantitative measurements by using the method of gas-in-scattering-media absorption spectroscopy. (C) 2002 Optical Society of America

Interstitial photodynamic therapy - diagnostic measurements and treatment in rat malignant experimental tumours

A recently developed multiple fibre system for treating malignant tumours with interstitial photodynamic therapy was used in studies on rats with colon adenocarcinoma inoculated into the muscles of the hind legs. The animals were intraperitonially administrated delta -aminolevulinic acid (ALA), which is metabolised to protoporphyrin IX (PpIX) in the tissue. The treatment system consists of a laser light source, a beam-splitting system dividing the light into three or six output fibres and a dosimetry programme calculating the optimal fibre position within the tumour as well as the treatment time needed to obtain a given threshold value of the light dose. One aim of the study was to compare the treatment outcome with the modelled dosimetry predictions. Tumour reduction was examined three days post treatment. A volume decrease was found in 85\% of the treated tumours. The mean volume reduction was 44\%, with one tumour completely disappearing. Histopathological examination three days post treatment showed substantial necrotic parts which, however, to a smaller extent were present also for non-treated tumours. These results indicated that the tumours have been under treated and the light dose has to be increased. Measurements of the build-up and photo-induced bleaching of PpIX using laser-induced fluorescence were also performed during the experiments

Generation, characterization, and medical utilization of laser-produced emission continua

Intense continua of electromagnetic radiation of very brief duration are formed in the interaction of focused ultra-short terawatt laser pulses with matter. Two different kinds of experiments, which have been performed utilizing the Lund 10 Hz titanium-doped sapphire terawatt laser system are being described, where visible radiation and X-rays, respectively, have been generated. Focusing into water leads to the generation of a light continuum through self-phase modulation. The propagation of the light through tissue was studied addressing questions related to optical mammography and specific chromophore absorption. When terawatt laser pulses are focused onto a solid target with high nuclear charge Z, intense X-ray radiation of few ps duration and with energies exceeding hundreds of keV is emitted. Biomedical applications of this radiation are described, including differential absorption and gated-viewing imaging

Early neoplastic and metastatic mammary tumours of transgenic mice detected by 5-aminolevulinic acid-stimulated protoporphyrin IX accumulation

A photodynamic technique for human breast cancer detection founded upon the ability of tumour cells to rapidly accumulate the fluorescent product protoporphyrin IX (PpIX) has been applied to transgenic mouse models of mammary tumorigenesis. A major goal of this investigation was to determine whether mouse mammary tumours are reliable models of human disease in terms of PpIX accumulation, for future mechanistic and therapeutic studies. The haeme substrate 5-aminolevulinic acid (5-ALA) (200 mg kg−1) was administered to mouse strains that develop mammary tumours of various histological subtypes upon expression of the transgenic oncogenes HRAS, Polyoma Virus middle T antigen, or Simian Virus 40 large T antigen in the mammary gland. Early neoplastic lesions, primary tumours and metastases showed consistent and rapid PpIX accumulation compared to the normal surrounding tissues, as evidenced by red fluorescence (635 nm) when the tumours were directly illuminated with blue light (380–440 nm). Detection of mouse mammary tumours at the stage of ductal carcinoma in situ by red fluorescence emissions suggests that enhanced PpIX synthesis is a good marker for early tumorigenic processes in the mammary gland. We propose the mouse models provide an ideal experimental system for further investigation of the early diagnostic and therapeutic potential of 5-ALA-stimulated PpIX accumulation in human breast cancer patients