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Biomedical subjects

Johannes Swartling

Publications and source records attributed to Johannes Swartling.

12 recordsLinked to original sources

Dynamic time-resolved diffuse spectroscopy based on supercontinuum light pulses.

We present a detailed characterization of a system for fast time-resolved spectroscopy of turbid media based on supercontinuum generation in a photonic crystal fiber. The light source provides subpicosecond pulses in the 550-1000-nm spectral range, at 85 MHz, at an average power of up to 50 mW. Wavelength-resolved detection is accomplished by means of a spectrometer coupled to a 16-channel, multianode photomultiplier tube, giving a resolution of 4.5-35 nm/channel, depending on the grating. Time-dispersion curves are acquired with time-correlated single-photon counting, and absorption and reduced scattering coefficients are determined by fitting the data to the diffusion equation. We characterized the system by measuring the time-resolved diffuse reflectance of epoxy phantoms and by assessing the performance in terms of accuracy, linearity, noise sensitivity, stability, and reproducibility. The results were similar to those from previous systems, whereas the full-spectrum (610-810 nm) acquisition time was as short as 1 s owing to the parallel acquisition. We also present the first in vivo real-time dynamic spectral measurements showing tissue oxygenation changes in the arm of a human subject.

Algorithms↗

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↗

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↗

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↗

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↗

Time-resolved spectrophotometer for turbid media based on supercontinuum generation in a photonic crystal fiber.

We describe an instrument for the time-resolved spectroscopy of turbid media that is based on supercontinuum generation in a photonic crystal fiber. The light injected into the sample consists of subpicosecond pulses that cover 550-1000 nm at 85 MHz at an average power of as much as 40 mW. A spectrometer coupled to a multianode photomultiplier tube is used to detect the light simultaneously in 16 wavelength channels, with a resolution of 5-20 nm/channel, depending on the grating. Time-correlated single-photon counting is used to produce time-dispersion curves, which one fits to the diffusion equation to determine absorption and reduced scattering coefficients. We tested the instrument by measuring the time-resolved diffuse reflectance of epoxy phantoms and by performing in vivo measurements on volunteers. The results were similar to those obtained with previous discrete wavelength systems, whereas the full spectrum (610-810 nm) acquisition time was as short as 1 s owing to the parallel acquisition.

Abdomen↗

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↗

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↗

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↗

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↗

Spectroscopic time-resolved diffuse reflectance and transmittance measurements of the female breast at different interfiber distances.

The first, to our knowledge, in-vivo broadband spectroscopic characterization of breast tissue using different interfiber distances as well as transmittance measurements is presented. Absorption and scattering properties are measured on six healthy subjects, using time-resolved diffuse spectroscopy and an inverse model based on the diffusion equation. Wavelength-tunable picosecond-pulse lasers and time-correlated single-photon counting detection are employed, enabling fully spectroscopic measurements in the range 610 to 1040 nm. Characterization of the absorption and reduced scattering coefficients of breast tissue is made with the aim of investigating individual variations, as well as variations due to different measurement geometries. Diffuse reflectance measurements at different interfiber distances (2, 3, and 4 cm) are performed, as well as measurements in transmittance mode, meaning that different sampling volumes are involved. The results show a large variation in the absorption and scattering properties depending on the subject, correlating mainly with the water versus lipid content of the breast. Intrasubject variations, due to different interfiber distances or transmittance modes, correlate with the known structures of the breast, but these variations are small compared to the subject-to-subject variation. The intrasubject variations are larger for the scattering data than the absorption data; this is consistent with different spatial localization of the measurements of these parameters, which is explained by the photon migration theory.

Adult↗

Feasibility of white-light time-resolved optical mammography.

We demonstrate the feasibility of white-light time-resolved optical mammography. The instrumentation is based on supercontinuum light generated in photonic crystal fiber and 32-channel parallel time-correlated single-photon-counting detection. Total measurement time is of the order of 10 min for typical clinical applications. Preliminary measurements performed on volunteers show the ability of the system to determine tissue constituent concentrations and structure over the entire breast area. Furthermore, measurements on a tissue-like sample demonstrate detection and characterization of inclusions.

Adult↗