Biomedical subjects

Stefan Andersson-Engels

Publications and source records attributed to Stefan Andersson-Engels.

At least 19 recordsLinked to original sources

PubMed2006

Methods for detailed histopathological investigation and localization of biopsies from cervix uteri to improve the interpretation of autofluorescence data.

Fluorescence spectroscopy is one of many optical methods that are potentially clinically useful for noninvasive detection and characterization of disorders on the cervical part of uterus, including precancerous lesions. The cervix uteri exhibits a biologically complex tissue and the morphology of a biopsy is generally not homogenous. The standard histopathological protocol accounts only for the most severe condition found within the biopsy and no information is given on other constituents potentially influencing the recorded fluorescence spectra. Spectra are usually correlated, using multivariate techniques, to the histopathological diagnosis of the biopsies. Since the probe volume of fluorescence spectroscopy is considerably smaller than the extension of the biopsy, this can cause problems in the search for correlation between the fluorescence signals and the pathological structures. In addition, the orientation and location of the biopsies are normally not recorded. We now report on the first detailed histopathological protocol where numerous tissue parameters, such as thickness and type of the epithelium and the number of blood vessels, glands, and inflammatory cells, are tabulated and the orientation and location of the biopsy are recorded as precisely as possible. Hopefully, the use of this protocol together with sophisticated mathematical methods will increase the probability to classify cervical disorders of the uterus, including precancerous lesions, with high sensitivity and specificity.

Adult↗

PubMed2006

Photodynamic therapy of nodular basal cell carcinoma with multifiber contact light delivery.

To overcome the limited treatment depth of superficial photodynamic therapy we investigate interstitial light delivery. In the present work the treatment light was delivered using a system in which three or six clear-cut fibers were placed in direct contact with the tumor area. This placement was thought to represent a step toward general purpose interstitial PDT. Twelve nodular basal cell carcinomas were treated employing delta-aminolevulinic acid and 635 nm laser irradiation. Fluorescence measurements were performed monitoring the buildup and subsequent bleaching of the produced sensitizer protoporphyrin IX. The treatment efficacy, judged at a 28-month follow-up, showed a 100% complete response. Two punch excisions at 7 months converted two partial responses to complete responses. One patient failed to appear at all follow-up sessions. The outcome of the treatments was comparable to superficial photodynamic therapy in terms of histological, clinical, and cosmetic results.

Adult↗

PubMed2005

Least-squares support vector machines modelization for time-resolved spectroscopy.

By use of time-resolved spectroscopy it is possible to separate light scattering effects from chemical absorption effects in samples. In the study of propagation of short light pulses in turbid samples the reduced scattering coefficient and the absorption coefficient are usually obtained by fitting diffusion or Monte Carlo models to the measured data by use of numerical optimization techniques. In this study we propose a prediction model obtained with a semiparametric modeling technique: the least-squares support vector machines. The main advantage of this technique is that it uses theoretical time dispersion curves during the calibration step. Predictions can then be performed by use of data measured on different kinds of sample, such as apples.

Algorithms↗

PubMed2005

Real-time absorption and scattering characterization of slab-shaped turbid samples obtained by a combination of angular and spatially resolved measurements.

We present a fast and accurate method for real-time determination of the absorption coefficient, the scattering coefficient, and the anisotropy factor of thin turbid samples by using simple continuous-wave noncoherent light sources. The three optical properties are extracted from recordings of angularly resolved transmittance in addition to spatially resolved diffuse reflectance and transmittance. The applied multivariate calibration and prediction techniques are based on multiple polynomial regression in combination with a Newton--Raphson algorithm. The numerical test results based on Monte Carlo simulations showed mean prediction errors of approximately 0.5% for all three optical properties within ranges typical for biological media. Preliminary experimental results are also presented yielding errors of approximately 5%. Thus the presented methods show a substantial potential for simultaneous absorption and scattering characterization of turbid media.

Absorption↗

PubMed2005

Clinical system for interstitial photodynamic therapy with combined on-line dosimetry measurements.

A system for interstitial photodynamic therapy with delta-aminolaevulinic acid and multiple optical fibers has been developed. The system enables photodynamic treatment of large embedded tumor volumes and utilizes real-time measurements to allow on-line dosimetry. Important parameters such as light fluence rate, sensitizer fluorescence intensity, and changes in local blood oxygen saturation are measured with the same fibers that deliver the therapeutic light. Data from the first clinical treatments on nodular basal cell carcinomas indicate a major treatment-induced light absorption increase, rapid sensitizer photobleaching, and a relatively constant global tissue oxygen saturation level during the treatment.

Aminolevulinic Acid↗

PubMed2005

Characterization of normal breast tissue heterogeneity using time-resolved near-infrared spectroscopy.

In recent years, extensive efforts have been made in developing near-infrared optical techniques to be used in detection and diagnosis of breast cancer. Variations in optical properties of normal breast tissue set limits to the performance of such techniques and must therefore be thoroughly examined. In this paper, we present intra- and intersubject as well as contralateral variations of optical and physiological properties in breast tissue as measured by using four-wavelength time-resolved spectroscopy (at 660, 786, 916 and 974 nm). In total, 36 volunteers were examined at five regions at each breast. Optical properties (absorption, mu(a), and reduced scattering, mu'(s)) are derived by employing diffusion theory. The use of four wavelengths enables determination of main tissue chromophores (haemoglobin, water and lipids) as well as haemoglobin oxygenation. Variations in all evaluated properties seen over the entire breast are approximately twice those for small-scale heterogeneity (millimetre scale). Intrasubject variations in optical properties are almost in all cases below 20% for mu'(s), and 40% for mu(a). Overall variations in water, lipid and haemoglobin concentrations are all in the order of 20%. Oxygenation is the least variable of the quantities evaluated, overall intrasubject variations being 6% on average. Extracted physiological properties confirm differences between pre- and post-menopausal breast tissue. Results do not indicate systematic differences between left and right breasts.

Adult↗

PubMed2005

Performance assessment of photon migration instruments: the MEDPHOT protocol.

We propose a comprehensive protocol for the performance assessment of photon migration instruments. The protocol has been developed within the European Thematic Network MEDPHOT (optical methods for medical diagnosis and monitoring of diseases) and is based on five criteria: accuracy, linearity, noise, stability, and reproducibility. This protocol was applied to a total of 8 instruments with a set of 32 phantoms, covering a wide range of optical properties.

Benchmarking↗

PubMed2005

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.

Absorption↗

PubMed2005

Fluorescence spectra provide information on the depth of fluorescent lesions in tissue.

The fluorescence spectrum measured from a fluorophore in tissue is affected by the absorption and scattering properties of the tissue, as well as by the measurement geometry. We analyze this effect with Monte Carlo simulations and by measurements on phantoms. The spectral changes can be used to estimate the depth of a fluorescent lesion embedded in the tissue by measurement of the fluorescence signal in different wavelength bands. By taking the ratio between the signals at two wavelengths, we show that it is possible to determine the depth of the lesion. Simulations were performed and validated by measurements on a phantom in the wavelength range 815-930 nm. The depth of a fluorescing layer could be determined with 0.6-mm accuracy down to at least a depth of 10 mm. Monte Carlo simulations were also performed for different tissue types of various composition. The results indicate that depth estimation of a lesion should be possible with 2-3-mm accuracy, with no assumptions made about the optical properties, for a wide range of tissues.

Algorithms↗

PubMed2005

Time-resolved NIR spectroscopy for quantitative analysis of intact pharmaceutical tablets.

Near-infrared (NIR) spectroscopy is a useful technique for quantitative measurements of intact tablets, but it suffers from limitations due to the fact that changes in the physical properties of a sample strongly affect the recorded spectrum. In this work, time-resolved transmission NIR spectroscopy was utilized to conduct quantitative measurements of intact tablets. The technique enables separation of the absorption properties of the sample from the scattering properties and can therefore handle changes of the physical parameters of the samples in a better way than conventional NIR transmission spectroscopy. The experiments were conducted using a pulsed Ti:sapphire laser coupled into a nonlinear photonic crystal fiber as light source. The light transmitted through the sample was measured by a time-resolving streak camera. A comparison of the results from the time-resolved technique with the results from conventional transmission NIR spectroscopy was made using tablets containing different concentrations of iron oxide and manufactured with different thicknesses. A PLS model made with data from the time-resolved technique predicted samples 5 times better than a PLS model made data from the conventional NIR transmission technique. Furthermore, an improvement to predict samples with physical properties outside those included in the calibration set was demonstrated.

Calibration↗

PubMed2005

Numerical simulations of light scattering by red blood cells.

Scattering of electromagnetic waves from a red blood cell is simulated using the finite-difference time-domain method (FDTD), the Rytov approximation and the discrete dipole approximation (DDA). Both FDTD and DDA are full wave methods that give accurate results in a wide range of wavelengths. The Rytov approximation is a much simpler method that is limited to scattering angles within 30 degrees from the forward direction. The investigation comprehends different wavelengths and different orientations of the cell. It shows that the shape, volume, and orientation of the cell have a large influence on the forward scattering.

Algorithms↗

PubMed2005

Scatter correction of transmission near-infrared spectra by photon migration data: quantitative analysis of solids.

The scope of this work is a new methodology to correct conventional near-infrared (NIR) data for scattering effects. The technique aims at measuring the absorption coefficient of the samples rather than the total attenuation measured in conventional NIR spectroscopy. The main advantage of this is that the absorption coefficient is independent of the path length of the light inside the sample and therefore independent of the scattering effects. The method is based on time-resolved spectroscopy and modeling of light transport by diffusion theory. This provides an independent measure of the scattering properties of the samples and therefore of the path length of light. This yields a clear advantage over other preprocessing techniques, where scattering effects are estimated and corrected for by using the shape of the measured spectrum only. Partial least squares (PLS) calibration models show that, by using the proposed evaluation scheme, the predictive ability is improved by 50% as compared to a model based on conventional NIR data alone. The method also makes it possible to predict the concentration of active substance in samples with other physical properties than the samples included in the calibration model.

Algorithms↗

PubMed2004

Determination of urea, glucose, and phosphate in dialysate with Fourier transform infrared spectroscopy.

Individual control and quantification of phosphate removal is desirable in dialysis treatment. Currently, no on-line method exists to quantify phosphate removal. We demonstrate that a multivariate calibration model based on infrared transmission spectra is capable of predicting phosphate, urea, and glucose concentrations at clinically relevant levels. The on-line monitoring of these components by infrared spectroscopy is therefore feasible.

Aged↗

PubMed2004

Light scattering by multiple red blood cells.

The interaction of light with multiple red blood cells was systematically investigated by the finite-difference time-domain method (FDTD). The simulations showed that the lateral multiple scattering between red blood cells is very weak and that the polarization has an almost insignificant influence on the distribution of the scattered light. The numerical results of the FDTD method were compared with the results from the Rytov approximation and the discrete dipole approximation (DDA). The agreement with the DDA was excellent.

Algorithms↗

PubMed2003

Comparison of spatially and temporally resolved diffuse-reflectance measurement systems for determination of biomedical optical properties.

Time-resolved and spatially resolved measurements of the diffuse reflectance from biological tissue are two well-established techniques for extracting the reduced scattering and absorption coefficients. We have performed a comparison study of the performance of a spatially resolved and a time-resolved instrument at wavelengths 660 and 786 nm and also of an integrating-sphere setup at 550-800 nm. The first system records the diffuse reflectance from a diode laser by means of a fiber bundle probe in contact with the sample. The time-resolved system utilizes picosecond laser pulses and a single-photon-counting detection scheme. We extracted the optical properties by calibration using known standards for the spatially resolved system, by fitting to the diffusion equation for the time-resolved system, and by using an inverse Monte Carlo model for the integrating sphere. The measurements were performed on a set of solid epoxy tissue phantoms. The results showed less than 10% difference in the evaluation of the reduced scattering coefficient among the systems for the phantoms in the range 9-20 cm(-1), and absolute differences of less than 0.05 cm(-1) for the absorption coefficient in the interval 0.05-0.30 cm(-1).

Animals↗

PubMed2003

Influence of cell shape and aggregate formation on the optical properties of flowing whole blood.

We studied the influence of shape and secondary, or intercellular, organization on the absorption and scattering properties of red blood cells to determine whether these properties are of any practical significance for optical evaluation of whole blood and its constituents. A series of measurements of transmittance and reflectance of light from bovine blood in a flow cuvette was conducted with a 650-900-nm integrating sphere at shear rates of 0-1600 s(-1), from which the influence of cell orientation, elongation, and aggregate formation on the absorption (mu(a)) and the reduced scattering (mu(s)') coefficients could be quantified. Aggregation was accompanied by a decrease of 4% in mu(s)' compared with the value in randomly oriented single cells. Increasing the degree of cell alignment and elongation as a result of increasing shear rate reduced mu(s)' by 6% and mu(a) by 3%, evaluated at a shear rate of 1600 s(-1). Comparison with T-matrix computations for oblate- and prolate-shaped cells with corresponding elongation and orientation indicates that the optical properties of whole blood are determined by those of its individual cells, though influenced by a collective scattering factor that depends on the cell-to-cell organization. We demonstrate that cell morphological changes must be taken into consideration when one is conducting whole blood spectroscopy.

Animals↗

PubMed2003

Accelerated Monte Carlo models to simulate fluorescence spectra from layered tissues.

Two efficient Monte Carlo models are described, facilitating predictions of complete time-resolved fluorescence spectra from a light-scattering and light-absorbing medium. These are compared with a third, conventional fluorescence Monte Carlo model in terms of accuracy, signal-to-noise statistics, and simulation time. The improved computation efficiency is achieved by means of a convolution technique, justified by the symmetry of the problem. Furthermore, the reciprocity principle for photon paths, employed in one of the accelerated models, is shown to simplify the computations of the distribution of the emitted fluorescence drastically. A so-called white Monte Carlo approach is finally suggested for efficient simulations of one excitation wavelength combined with a wide range of emission wavelengths. The fluorescence is simulated in a purely scattering medium, and the absorption properties are instead taken into account analytically afterward. This approach is applicable to the conventional model as well as to the two accelerated models. Essentially the same absolute values for the fluorescence integrated over the emitting surface and time are obtained for the three models within the accuracy of the simulations. The time-resolved and spatially resolved fluorescence exhibits a slight overestimation at short delay times close to the source corresponding to approximately two grid elements for the accelerated models, as a result of the discretization and the convolution. The improved efficiency is most prominent for the reverse-emission accelerated model, for which the simulation time can be reduced by up to two orders of magnitude.

Computer Simulation↗

PubMed2003

Influence of temperature on water and aqueous glucose absorption spectra in the near- and mid-infrared regions at physiologically relevant temperatures.

Near- and mid-infrared absorption spectra of pure water and aqueous 1.0 g/dL glucose solutions in the wavenumber range 8000-950 cm-1 were measured in the temperature range 30-42 degrees C in steps of 2 degrees C. Measurements were carried out with an FT-IR spectrometer and a variable pathlength transmission cell controlled within 0.02 degree C. Pathlengths of 50 microns and 0.4 mm were used in the mid- and near-infrared spectral region, respectively. Difference spectra were used to determine the effect of temperature on the water spectra quantitatively. These spectra were obtained by subtracting the 37 degrees C water spectrum from the spectra measured at other temperatures. The difference spectra reveal that the effect of temperature is highest in the vicinity of the strong absorption bands, with a number of isosbestic points with no temperature dependence and relatively flat plateaus in between. On the basis of these spectra, prospects for and limitations on data analysis for infrared diagnostic methods are discussed. As an example, the absorptive properties of glucose were studied in the same temperature range in order to determine the effect of temperature on the spectral shape of glucose. The change in water absorption associated with the addition of glucose has also been studied. An estimate of these effects is given and is related to the expected level of infrared signals from glucose in humans.

Artifacts↗