Sara Pålsson

Changes in tissue optical properties due to radio-frequency ablation of myocardium

The optical properties of pig heart tissue were measured after in vivo ablation therapy had been performed during open-heart surgery. In vitro samples of normal and ablated tissue were subjected to measurements with an optically integrating sphere set-up in the region 470–900 nm. Three independent measurements were made: total transmittance, total reflectance and collimated transmittance, which made it possible to extract the absorption and scattering coefficients and the scattering anisotropy factor g, using an inverse Monte Carlo model. Between 470 and 700 nm, only the reduced scattering coefficient and absorption could be evaluated. The absorption spectra were fitted to known tissue chromophore spectra, so that the concentrations of haemoglobin and myoglobin could be estimated. The reduced scattering coefficient was compared with Mie computations to provide Mie equivalent average radii. Most of the absorption was from myoglobin, whereas haemoglobin absorption was negligible. Metmyoglobin was formed in the ablated tissue, which could yield a spectral signature to distinguish the ablated tissue with a simple optical probe to monitor the ablation therapy. The reduced scattering coefficient increased by, on average, 50% in the ablated tissue, which corresponded to a slight decrease in the Mie equivalent radius.

Compact fiber-optic fluorosensor using a continuous-wave violet diode laser and an integrated spectrometer

A compact fluorosensor with a fiber-optic measurement probe was developed, employing a continuous-wave violet diode laser as an exciting source and an integrated digital spectrometer for the monitoring of fluorescence signatures. The system has the dimensions 22×13×8 cm3, and features 5 nm spectral resolution and an excellent detectivity. Results from measurements on vegetation and human premalignant skin lesions are reported, illustrating the potential of the instrument.

Kinetics of the superficial perfusion and temperature in connection with photodynamic therapy of basal cell carcinomas using esterified and non-esterified 5-aminolaevulinic acid.

Summary Background Photodynamic therapy (PDT) is a local treatment modality with increasing indications for various malignant and non malignant diseases. The treatment parameters have not yet been optimized as there is a need for a better understanding of the process. The skin is an important target and serves as a good model for monitoring and evaluating the interaction of light with biological tissue.

Interstitial photodynamic therapy for primary prostate cancer incorporating realtime treatment dosimetry

Photodynamic therapy (PDT) for the treatment of prostate cancer has been demonstrated to be a safe treatment option capable of inducing tissue necrosis and decrease in prostate specific antigen (PSA). Research groups report on large variations in treatment response, possibly due to biological variations in tissue composition and short-term response to the therapeutic irradiation. Within our group, an instrument for interstitial PDT on prostate tissue that incorporates realtime treatment feedback is being developed. The treatment protocol consists of two parts. The first part incorporates the pre-treatment plan with ultrasound investigations, providing the geometry for the prostate gland and surrounding risk organs, an iterative random-search algorithm to determine near-optimal fiber positions within the reconstructed geometry and a Block-Cimmino optimization algorithm for predicting individual fiber irradiation times. During the second part, the therapeutic light delivery is combined with measurements of the light transmission signals between the optical fibers, thus monitoring the tissue effective attenuation coefficient by means of spatially resolved spectroscopy. These data are then used as input for repeated runs of the Block-Cimmino optimization algorithm. Thus, the irradiation times for individual fibers are updated throughout the treatment in order to compensate for the influence of changes in tissue composition on the light distribution at the therapeutic wavelength.

Analysis of spatial variability in hyperspectral imagery of the uterine cervix in vivo

The use of fluorescence and reflectance spectroscopy in the analysis of cervical histopathology is a growing field of research. The majority of this research is performed with point-like probes. Typically, clinicians select probe sites visually, collecting a handful of spectral samples. An exception to this methodology is the Hyperspectral Diagnostic Imaging (HSDI) instrument developed by Science and Technology International. This non-invasive device collects contiguous hyperspectral images across the entire cervical portio. The high spatial and spectral resolution of the HSDI instruments make them uniquely well suited for addressing the issues of coupled spatial and spectral variability of tissues in vivo. Analysis of HSDI data indicates that tissue spectra vary from point to point, even within histopathologically homogeneous regions. This spectral variability exhibits both random and patterned components, implying that point monitoring may be susceptible to significant sources of noise and clutter inherent in the tissue. We have analyzed HSDI images from clinical CIN (cervical intraepithelial neoplasia) patients to quantify the spatial variability of fluorescence and reflectance spectra. This analysis shows the spatial structure of images to be fractal in nature, in both intensity and spectrum. These fractal tissue textures will limit the performance of any point-monitoring technology.

In-vivo fluorescence and reflectance imaging of human cervical tissue

A hyperspectral imaging spectrograph has been used to measure the fluorescence and reflectance of cervical tissue in vivo. The instrument was employed in a clinical trial in Vilnius, Lithuania, where 111 patients were examined. The patients were initially screened by Pap smear, examined by colposcopy and a tissue sampling procedure was performed. Detailed histopathological assessments were performed on the biopsies, and these assessments were correlated with spectra and images. The results of the spectroscopic investigations show that different tissue types within one biopsy region exhibit different spectral signatures. A spectral analysis of the entire image localizes dysplastic regions in both fluorescence and reflectance, suggesting that the hyperspectral imaging technique is useful in the management of cervical malignancies.

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

A recently developed multiple fiber system for treating malignant tumors 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 metabolized 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 fibers and a dosimetry program calculating the optimal fiber position within the tumor 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. Tumor reduction was examined three days post treatment. A volume decrease was found in 85% of the treated tumors. The mean volume reduction was 44%, with one tumor completely disappearing. Histopathological examination three days post treatment showed substantial necrotic parts which, however, to a smaller extent were present also for non-treated tumors. These results indicated that the tumors 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.

Integrated system for interstitial photodynamic therapy

To develop PDT beyond treatment of thin superficial tumors, to also be an efficient treatment alternative to deeply located and/or thick tumors, a system based on interstitial illumination using multiple fibers has been developed. Conditions that could benefit from such a treatment modality are for instance malignant brain tumors and tumors in the oral cavity. In interstitial PDT one needs to use multiple fibers for light delivery in order to allow treatments of tumors larger than a few millimeters in diameter. Our sytem consists of a laser light source, a beam-splitting system dividing the light into three or six output fibers and a custom-made dosimetry program. The concept is then to use these fibers not only for delivering the treatment light, but also to measure parameters of interest for the treatment outcome. The fluence rate of the light emitted by each fiber is measured at the positions of the other fiber tips. From these results the light dose at all positions could be recalculated. Changes in optical properties as well as bleaching and concentration of the photosensitizer during the treatment could be monitored and compensated for in the dosimetry. Tumors have been treated both in experimental studies and in patients with thick superficial Basal Cell Carcinomas. Almost all treated skin lesions responded with complete response.

Compact fiber-optic fluorosensor using high-power continuous-wave violet diode laser

In this work a compact fluorosensor has been built for point-monitoring and imaging applications. The instrument has been applied in fluorescence studies on green vegetation and on malignant tissue. The instrument is based on a violet diode laser, an integrated spectrometer and optical fibers for light delivery and collection of the fluorescence signal. This combination makes the system very compact. The high laser output power allows for coupling of the laser light into a hyperspectral diagnostic imaging instrument, developed and built by Science and Technology International. In point-monitoring mode, the instrument has been tested on superficial skin tumors and when using δ-aminolevulinic acid induced protoporphyrin IX as a tumor sensitizer, good contrast between normal and malignant tissue was achieved, clearly demonstrating its feasibility in cancer diagnostics. In imaging mode, the instrument functioned solely as a light source, coupling the excitation light into the hyperspectral imaging instrument. The set-up was tested by studying chlorophyll fluorescence from vegetation. The fluorescence signal showed a low signal-to-noise ratio mainly because of inefficient light coupling into the imaging instrument.