We report on the development of an iterative image reconstruction scheme for optical tomography that is based on the equation of radiative transfer. Unlike the commonly applied diffusion ...approximation, the equation of radiative transfer accurately describes the photon propagation in turbid media without any limiting assumptions regarding the optical properties. The reconstruction scheme consists of three major parts: (1) a forward model that predicts the detector readings based on solutions of the time-independent radiative transfer equation, (2) an objective function that provides a measure of the differences between the detected and the predicted data, and (3) an updating scheme that uses the gradient of the objective function to perform a line minimization to get new guesses of the optical properties. The gradient is obtained by employing an adjoint differentiation scheme, which makes use of the structure of the finite-difference discrete-ordinate formulation of the transport forward model. Based on the new guess of the optical properties a new forward calculation is performed to get new detector predictions. The reconstruction process is completed when the minimum of the objective function is found within a defined error. To illustrate the performance of the code we present initial reconstruction results based on simulated data.
Objective: To identify classifiers in images obtained with sagittal laser optical tomography (SLOT) that can be used to distinguish between joints affected and not affected by synovitis. Methods: 78 ...SLOT images of proximal interphalangeal joints II–IV from 13 patients with rheumatoid arthritis were compared with ultrasound (US) images and clinical examination (CE). SLOT images showing the spatial distribution of scattering and absorption coefficients within the joint cavity were generated. The means and standard errors for seven different classifiers (operator score and six quantitative measurements) were determined from SLOT images using CE and US as diagnostic references. For classifiers showing significant differences between affected and non-affected joints, sensitivities and specificities for various cut off parameters were obtained by receiver operating characteristic (ROC) analysis. Results: For five classifiers used to characterise SLOT images the mean between affected and unaffected joints was statistically significant using US as diagnostic reference, but statistically significant for only one classifier with CE as reference. In general, high absorption and scattering coefficients in and around the joint cavity are indicative of synovitis. ROC analysis showed that the minimal absorption classifier yields the largest area under the curve (0.777; sensitivity and specificity 0.705 each) with US as diagnostic reference. Conclusion: Classifiers in SLOT images have been identified that show statistically significant differences between joints with and without synovitis. It is possible to classify a joint as inflamed with SLOT, without the need for a reference measurement. Furthermore, SLOT based diagnosis of synovitis agrees better with US diagnosis than CE.
The presented study consists of two parts. The overall goal is to introduce and experimentally test a novel optical tomographic imaging algorithm that is based on the equation of radiative transfer. ...Using the equation of radiative transfer rather than the diffusion equation permits the consideration of highly scattering media that contain void-like regions that have very low absorption and scattering coefficients. In part I we concentrate on the detailed description and evaluation of a numerical forward model that accurately describes photon propagation in such media. In part II we focus on the inclusion of this forward model into a model-based iterative image reconstruction (MOBIIR) scheme. Using the MOBIIR scheme one can determine the spatial distribution of optical properties inside highly scattering media from measurements acquired on the surface of the medium. The mathematical and numerical background for the reconstruction algorithm, especially the adjoint differentiation scheme for the gradient calculation, will be presented. The code is tested with experimental data from tissue-phantoms that contain water-filled, void-like regions.
The forward model to be described in part I is based on an upwind-difference discrete-ordinate formulation of the time-independent equation of radiative transfer. The upwind-difference representation has the advantage that it provides a convenient mathematical framework for calculating the derivative of the fluence with respect to the optical parameters using an adjoint differentiation technique, to be described in part II. The performance of the forward model is tested with experimental data obtained from homogeneous tissue-phantoms and from phantoms that contain void-like regions. We find good agreement between experimental measurements and theoretical predictions of the measurements.
The quantification of a nonuniform quantum yield or fluorophore absorption distribution is of major interest in molecular imaging of biological tissue. We introduce what is believed to be the first ...fluorescence image reconstruction algorithm based on the equation of radiative transfer that recovers the spatial distribution of light-emitting fluorophores inside a highly scattering medium from measurements made on the surface of the medium. We obtain images of either the quantum yield or the fluorophore absorption.
Purpose To better understand the importance of the environmental conditions for drug release from biodegradable microparticles allowing for the development of more appropriate in vitro release ...measurement techniques. Methods Propranolol HCl diffusion in various agarose gels was characterized by NMR and UV analysis. Fick's law was used to theoretically predict the mass transport kinetics. Drug release from PLGA-based microparticles in such agarose gels was compared to that measured in agitated bulk fluids (“standard” method). Results NMR analysis revealed that the drug diffusivity was almost independent of the hydrogel concentration, despite of the significant differences in the systems' mechanical properties. This is due to the small size of the drug molecules/ions with respect to the hydrogel mesh size. Interestingly, the theoretically predicted drug concentration-distance-profiles could be confirmed by independent experiments. Most important from a practical point of view, significant differences in the release rates from the same batch of PLGA-based microparticles into a well agitated bulk fluid versus a semi-solid agarose gel were observed. Conclusion Great care must be taken when defining the in vitro conditions for drug release measurements from biodegradable microparticles. The obtained new insight can help facilitating the development of more appropriate in vitro release testing procedures.
Age determination of single plutonium particles was demonstrated using five particles of the standard reference material, NBS 947 (Plutonium Isotopic Standard. National Bureau of Standards, ...Washington, D.C. 20234, August 19, 1982, currently distributed as NBL CRM-137) and the radioactive decay of
241Pu into
241Am. The elemental ratio of Am/Pu in Pu particles found on a carbon planchet was measured by wavelength dispersive X-ray spectrometry (WDX) coupled to a scanning electron microscope (SEM). After the WDX measurement, each plutonium particle, with an average size of a few μm, was picked up and relocated to a silicon wafer inside the SEM chamber using a micromanipulator. The silicon wafer was then transferred to a quartz tube for dissolution in an acid solution prior to chemical separation. After the Pu was chemically separated from Am and U, the isotopic ratios of Pu (
240Pu/
239Pu,
241Pu/
239Pu and
242Pu/
239Pu) were measured with a thermal ionization mass spectrometer (TIMS) for the calculation of Pu age. The age of particles determined in this study was in good agreement with the expected age (35.9 a) of NBS 947 within the measurement uncertainty.
Since 1984, the World Health Organization (WHO) European Region has pursued the goal of eliminating measles. In 2005, it was decided to also stop the endemic transmission of rubellavirus, thereby ...eliminating congenital rubella syndrome. Both infections are to be eliminated by 2015. To document the progress and verify the elimination at country level, national verification committees should be established in WHO EU memberstates.
In December 2012, the German Ministry of Health appointed the German National Verification Committee for Measles and Rubella Elimination. The commission meets at least twice a year to compile and analyze data on the epidemiology of measles and rubella in Germany and on the vaccination coverage/ immunity of the German population against these infections to assess progress in the elimination goals. Furthermore, the commission indicates whether the available data are sufficient or contain inconsistencies, evaluates the success of key strategies implemented, and advises on activities related to the verification of the elimination process in the country. A scientific report on the commission's findings is to be submitted annually to the WHO regional office.
Germany is committed to the aim of eliminating measles and rubella. Thus, every possible effort should be made to reach this goal by the responsible players in the German immunization system. The commission - as an independent group of experts - will critically accompany and evaluate this process.
The isotopic composition of single uranium and plutonium particles was measured with an inductively coupled plasma mass spectrometer (ICP-MS) and a thermal ionization mass spectrometer (TIMS). ...Particles deposited on a carbon planchet were first analyzed with an energy dispersive X-ray spectrometer (EDX) attached to a scanning electron microscope (SEM) and then transferred on to a silicon wafer using a manipulator. The particle on the silicon wafer was dissolved with nitric acid and the isotopic ratios of U and Pu were measured with ICP-MS and TIMS. The results obtained by both methods for particles of certified reference materials showed good agreement with the certified values within the expected uncertainty. The measurement uncertainties obtained in this study were similar for both mass spectrometric methods. This study was performed to establish the method of particle analysis with SEM, EDX, the particle manipulation and chemical preparation technique, and the measurement of isotopic ratios of U and Pu in a single particle by mass spectrometry.
Depending on the type of formulation, the experimental setup might or might not substantially affect the observed release kinetics from parenteral controlled drug delivery systems.
The aim of this ...study was to evaluate the impact of the experimental conditions on drug release measurements from parenteral depot systems. Frequently applied setups were used, including agitated and “non-agitated” flasks and tubes, flow-though cells as well as agarose gels. The bulk fluid volumes and flow rates were varied. Lipid implants (prepared by direct compression or melting & casting) as well as PLGA-based microparticles (prepared by O/W or W/O/W or S/O/W solvent extraction/evaporation methods) were studied. Theophylline, lidocaine, prilocaine, propranolol HCl, dexamethasone and ibuprofen were used as model drugs at different initial loadings. In all cases, the release medium was phosphate buffer pH 7.4, kept constant at 37°C. Particle size analysis, SEM, X-ray diffraction, DSC analysis and mathematical modeling were applied to better understand the observed phenomena. Interestingly, the importance of the impact of the experimental conditions ranged from negligible to significant, depending on the specific type of drug delivery system and setup. Both, lipid implants as well as PLGA-based microparticles can exhibit more or less sensitive/robust drug release patterns. The observed differences in sensitivity could partially be explained in a mechanistic way, but in many cases they are not yet fully understood. A thorough understanding of the underlying drug release mechanisms can be very helpful. If the devices are poorly characterized and treated as “black boxes”, great care must be taken when drawing conclusions from in vitro drug release measurements.
Optical tomography is a novel imaging modality that is employed to reconstruct cross-sectional images of the optical properties of highly scattering media given measurements performed on the surface ...of the medium. Recent advances in this field have mainly been driven by biomedical applications in which near-infrared light is used for transillumination and reflectance measurements of highly scattering biological tissues. Many of the reconstruction algorithms currently utilized for optical tomography make use of model-based iterative image reconstruction (MOBIIR) schemes. The imaging problem is formulated as an optimization problem, in which an objective function is minimized. In the simplest case the objective function is a normalized-squared error between measured and predicted data. The predicted data are obtained by using a forward model that describes light propagation in the scattering medium given a certain distribution of optical properties.
In part I of this two-part study, we presented a forward model that is based on the time-independent equation of radiative transfer. Using experimental data we showed that this transport-theory-based forward model can accurately predict light propagation in highly scattering media that contain void-like inclusions. In part II we focus on the details of our image reconstruction scheme (inverse model). A crucial component of this scheme involves the efficient and accurate determination of the gradient of the objective function with respect to all optical properties. This calculation is performed using an adjoint differentiation algorithm that allows for fast calculation of this gradient. Having calculated this gradient, we minimize the objective function with a gradient-based optimization method, which results in the reconstruction of the spatial distribution of scattering and absorption coefficients inside the medium. In addition to presenting the mathematical and numerical background of our code, we present reconstruction results based on experimentally obtained data from highly scattering media that contain void-like regions. These types of media play an important role in optical tomographic imaging of the human brain and joints.
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