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Near-real-time radiotherapy dosimetry using optically stimulated luminescence of Al2O3:C: mathematical models and preliminary results.

In this paper we report investigations aimed toward applying optically stimulated luminescence (OSL) of Al2O3:C for near-real-time medical dosimetry, especially in radiotherapy. The classical mathematical model normally used for the description of OSL phenomena was expanded to predict the behavior of the luminescence signal in the case when the OSL sample is simultaneously irradiated and optically stimulated. The predictions obtained were used to develop different measurement approaches and correction algorithms for the luminescence signals, thus enabling dose estimation from OSL during rather then after the irradiation procedure. Radiation probes with diameters of less than 1 mm, suitable for the envisioned in-vivo measurements were constructed by attaching small Al2O3:C crystals to optical fiber cables. The OSL fiber probes and a purpose-built, portable OSL stimulation and readout system were used to measure doses at speeds up to 1 data point every 3s, under irradiation at dose rates of the same order of magnitude as those found in conventional radiotherapy techniques. The corrected OSL signal was found to be proportional to the absorbed dose, and accurately followed sudden transitions in the irradiation dose rate.

Algorithms↗

Comparison of different stomatal conductance algorithms for ozone flux modelling.

A multiplicative and a semi-mechanistic, BWB-type [Ball, J.T., Woodrow, I.E., Berry, J.A., 1987. A model predicting stomatal conductance and its contribution to the control of photosynthesis under different environmental conditions. In: Biggens, J. (Ed.), Progress in Photosynthesis Research, vol. IV. Martinus Nijhoff, Dordrecht, pp. 221-224.] algorithm for calculating stomatal conductance (g(s)) at the leaf level have been parameterised for two crop and two tree species to test their use in regional scale ozone deposition modelling. The algorithms were tested against measured, site-specific data for durum wheat, grapevine, beech and birch of different European provenances. A direct comparison of both algorithms showed a similar performance in predicting hourly means and daily time-courses of g(s), whereas the multiplicative algorithm outperformed the BWB-type algorithm in modelling seasonal time-courses due to the inclusion of a phenology function. The re-parameterisation of the algorithms for local conditions in order to validate ozone deposition modelling on a European scale reveals the higher input requirements of the BWB-type algorithm as compared to the multiplicative algorithm because of the need of the former to model net photosynthesis (A(n)).

Algorithms↗

Automatic layout and visualization of biclusters.

BACKGROUND: Biclustering has emerged as a powerful algorithmic tool for analyzing measurements of gene expression. A number of different methods have emerged for computing biclusters in gene expression data. Many of these algorithms may output a very large number of biclusters with varying degrees of overlap. There are no systematic methods that create a two-dimensional layout of the computed biclusters and display overlaps between them. RESULTS: We develop a novel algorithm for laying out biclusters in a two-dimensional matrix whose rows (respectively, columns) are rows (respectively, columns) of the original dataset. We display each bicluster as a contiguous submatrix in the layout. We allow the layout to have repeated rows and/or columns from the original matrix as required, but we seek a layout of the smallest size. We also develop a web-based search interface for the user to query the genes and samples of interest and visualise the layout of biclusters matching the queries. CONCLUSION: We demonstrate the usefulness of our approach on gene expression data for two types of leukaemia and on protein-DNA binding data for two growth conditions in Saccharomyces cerevisiae. The software implementing the layout algorithm is available at http://bioinformatics.cs.vt.edu/~murali/papers/bivoc.

Journal Article↗

Signal-processing algorithm for white-light optical fiber extrinsic Fabry-Perot interferometric sensors.

We present a novel signal-processing algorithm for single-mode optical fiber extrinsic Fabry-Perot interferometric sensors that can achieve both high-resolution, absolute measurement of the cavity length and a large dynamic measurement range simultaneously. The algorithm is based on an accurate model of the characteristics of a fiber-optic sensor that takes into account the phase shift that is due to the coupling of light reflected at the second surface to the lead-in fiber end.

Journal Article↗

Development and testing of an algorithm to detect implantable cardioverter-defibrillator lead failure.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) lead failures often present as inappropriate shock therapy. An algorithm that can reliably discriminate between ventricular tachyarrhythmias and noise due to lead failure may prevent patient discomfort and anxiety and avoid device-induced proarrhythmia by preventing inappropriate ICD shocks. OBJECTIVES: The goal of this analysis was to test an ICD tachycardia detection algorithm that differentiates noise due to lead failure from ventricular tachyarrhythmias. METHODS: We tested an algorithm that uses a measure of the ventricular intracardiac electrogram baseline to discriminate the sinus rhythm isoelectric line from the right ventricular coil-can (i.e., far-field) electrogram during oversensing of noise caused by a lead failure. The baseline measure was defined as the product of the sum (mV) and standard deviation (mV) of the voltage samples for a 188-ms window centered on each sensed electrogram. If the minimum baseline measure of the last 12 beats was <0.35 mV-mV, then the detected rhythm was considered noise due to a lead failure. The first ICD-detected episode of lead failure and inappropriate detection from 24 ICD patients with a pace/sense lead failure and all ventricular arrhythmias from 56 ICD patients without a lead failure were selected. The stored data were analyzed to determine the sensitivity and specificity of the algorithm to detect lead failures. RESULTS: The minimum baseline measure for the 24 lead failure episodes (0.28 +/- 0.34 mV-mV) was smaller than the 135 ventricular tachycardia (40.8 +/- 43.0 mV-mV, P <.0001) and 55 ventricular fibrillation episodes (19.1 +/- 22.8 mV-mV, P <.05). A minimum baseline <0.35 mV-mV threshold had a sensitivity of 83% (20/24) with a 100% (190/190) specificity. CONCLUSION: A baseline measure of the far-field electrogram had a high sensitivity and specificity to detect lead failure noise compared with ventricular tachycardia or fibrillation.

Aged↗

Semiparametric maximum likelihood for measurement error model regression.

This paper presents an EM algorithm for semiparametric likelihood analysis of linear, generalized linear, and nonlinear regression models with measurement errors in explanatory variables. A structural model is used in which probability distributions are specified for (a) the response and (b) the measurement error. A distribution is also assumed for the true explanatory variable but is left unspecified and is estimated by nonparametric maximum likelihood. For various types of extra information about the measurement error distribution, the proposed algorithm makes use of available routines that would be appropriate for likelihood analysis of (a) and (b) if the true x were available. Simulations suggest that the semiparametric maximum likelihood estimator retains a high degree of efficiency relative to the structural maximum likelihood estimator based on correct distributional assumptions and can outperform maximum likelihood based on an incorrect distributional assumption. The approach is illustrated on three examples with a variety of structures and types of extra information about the measurement error distribution.

Algorithms↗

Detecting potential labeling errors in microarrays by data perturbation.

MOTIVATION: Classification is widely used in medical applications. However, the quality of the classifier depends critically on the accurate labeling of the training data. But for many medical applications, labeling a sample or grading a biopsy can be subjective. Existing studies confirm this phenomenon and show that even a very small number of mislabeled samples could deeply degrade the performance of the obtained classifier, particularly when the sample size is small. The problem we address in this paper is to develop a method for automatically detecting samples that are possibly mislabeled. RESULTS: We propose two algorithms, a classification-stability algorithm and a leave-one-out-error-sensitivity algorithm for detecting possibly mislabeled samples. For both algorithms, the key structure is the computation of the leave-one-out perturbation matrix. The classification-stability algorithm is based on measuring the stability of the label of a sample with respect to label changes of other samples and the version of this algorithm based on the support vector machine appears to be quite accurate for three real datasets. The suspect list produced by the version is of high quality. Furthermore, when human intervention is not available, the correction heuristic appears to be beneficial.

Artifacts↗

Characterization of pinhole SPECT acquisition geometry.

A method is presented to estimate the acquisition geometry of a pinhole single photon emission computed tomography (SPECT) camera with a circular detector orbit. This information is needed for the reconstruction of tomographic images. The calibration uses the point source projection locations of a tomographic acquisition of three point sources located at known distances from each other. It is shown that this simple phantom provides the necessary and sufficient information for the proposed calibration method. The knowledge of two of the distances between the point sources proves to be essential. The geometry is estimated by fitting analytically calculated projections to the measured ones, using a simple least squares Powell algorithm. Some mild a priori knowledge is used to constrain the solutions of the fit. Several of the geometrical parameters are however highly correlated. The effect of these correlations on the reconstructed images is evaluated in simulation studies and related to the estimation accuracy. The highly correlated detector tilt and electrical shift are shown to be the critical parameters for accurate image reconstruction. The performance of the algorithm is finally demonstrated by phantom measurements. The method is based on a single SPECT scan of a simple calibration phantom, executed immediately after the actual SPECT acquisition. The method is also applicable to cone-beam SPECT and X-ray CT.

Algorithms↗

Height measurement of astigmatic test surfaces by a keratoscope that uses plane geometry surface reconstruction.

PURPOSE: To assess the accuracy with which the Keratron keratoscope (Optikon 2000, Rome, Italy) measured astigmatic test surfaces by a profile reconstruction algorithm within a plane geometry model and to discriminate between error caused by the model and error caused by other factors. METHODS: Height was reported by the Keratron for eight surfaces with central astigmatism ranging from 4 to 16 diopters. A three-dimensional ray tracing simulation produced theoretic reflected ring patterns on which the Keratron's reconstruction algorithm was performed. The Keratron's measurements were compared with the surfaces' formulas and the ray-traced simulations. RESULTS: With a new mathematical filter for smoothing ring data, now part of the Keratron's software, maximum error was 0.47% of the total height and was usually less than 1% of local power for surfaces with 4 diopters of astigmatism. For surfaces with 16 diopters of astigmatism, maximum error was as high as 2.9% of total height and was usually less than 2.5% of local power. The reconstruction algorithm accounted for 40% and 70% of height error, respectively. CONCLUSIONS: The efficacy of keratoscopes cannot be assumed from their design theories but must be tested. Although plane geometry surface reconstruction contributed greatly to total height error, total error was so small that it is unlikely to affect clinical use.

Algorithms↗

Reconstruction of experimental hyperthermia temperature distributions: application of state and parameter estimation.

Subsets of data from spatially sampled temperatures measured in each of nine experimental heatings of normal canine thighs were used to test the feasibility of using a state and parameter estimation (SPE) technique to predict the complete measured data set in each heating. Temperature measurements were made at between seventy-two and ninety-six stationary thermocouple locations within the thigh, and measurements from as few as thirteen of these locations were used as inputs to the estimation algorithm. The remaining (non "input") measurements were compared to the predicted temperatures for the corresponding "unmeasured" locations to judge the ability of the estimation algorithm to accurately reconstruct the complete experimental data set. The results show that the predictions of the "unmeasured" steady-state temperatures are quite accurate in general (average errors usually < 0.5 degrees C; and small variances about those averages) and that this reconstruction procedure can yield improved descriptors of the steady-state temperature distribution. The accuracy of the reconstructed temperature distribution was not strongly affected by either the number of perfusion zones or by the number of input sensors used by the algorithm. One situation extensively considered in this study modeled the thigh with twenty-seven independent regions of perfusion. For this situation, measurements from ninety-six to thirteen sensors were used as input to the estimation algorithm. The average error for all of these cases ranged from -0.55 degrees C to +0.75 degrees C, respectively, and was not strongly related to the number of sensors used as input to the estimation algorithm.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Noninvasive measurements of regional cerebral blood flow using technetium-99m hexamethylpropylene amine oxime.

The previously reported method for quantitative measurements of whole-brain or hemispheric-brain perfusion using technetium-99m hexamethylpropylene amine oxime (HMPAO) radionuclide angiography is now further developed so that regional cerebral blood flow (rCBF) can be measured. Lassen's correction algorithm is used for the linearization of a curve-linear relationship between the radioactivity in the brain and blood flow as seen with single-photon emission tomography (SPET) images. In this algorithm, the cerebral hemisphere was chosen as the reference region and the correction factor alpha was adapted to rCBF in the reference region. This new method of measuring CBF from SPET has been validated in 33 normal subjects and 22 patients with cerebrovascular disease. Regional CBF values in 20 brain regions of the normal subjects were in good agreement with reported values measured by other methods. Regional CBF in the frontal cortex was greater than that in the temporal, parietal or occipital cortex for the entire age range. This hyperfrontal perfusion tended to be less pronounced with advancing age. Seventeen patients with unilateral brain infarction showed significantly lower rCBF than normal subjects. The infarct core showed a low rCBF value of 11.1 ml/100 g/min on average. An increase in rCBF after acetazolamide administration was observed and measured with this method in five patients with unilateral occlusive vascular pathology. These results suggest that this non-invasive method (without any blood sampling) permits the routine measurement of rCBF from HMPAO SPET tomograms of blood flow.

Acetazolamide↗

A suitable method for identifying cell aggregates in laser scanning cytometry listmode data for analyzing disaggregated cell suspensions obtained from human cancers.

BACKGROUND: The presence of cell aggregates in cell suspensions obtained from human solid tumors can interfere with the measurement of cell DNA content of cell singlets, and can confound multiparameter analysis of other measurements on the same cells. Flow cytometric corrections for cell aggregates based on signal pulse shape have not proven to be reliable. Mathematical models have been developed to correct for cell aggregates in binned DNA histogram data, but they are not suitable for the correction of correlated non-DNA measurements obtained on the same cells. METHODS: A total of 21 samples representing a variety of normal and malignant human cell types, including normal lymphocytes, normal sputum, human breast cancer cell lines, and mechanically disaggregated cell suspensions from primary breast cancers and nonsmall cell lung cancers, were studied by laser scanning cytometry (LSC) using the CompuCyte laser scanning cytometer (Cambridge, MA). Nuclear area, nuclear perimeter, and an LSC-based cell texture parameter were measured on approximately 400 cells in each sample, using an air-cooled, violet laser emitting at a wavelength of 405 nm for DAPI excitation, and each cell was classified as a singlet or aggregate by its appearance under direct observation. A "saddle function" provided by CompuCyte was used, together with an algorithm based on the measurements of nuclear area, perimeter, and cell texture (the APT algorithm), to identify cell aggregates and exclude them from the listmode data file. RESULTS: Proportions of cell aggregates in the uncorrected samples ranging from 6 to 56% (mean, 20%) were reduced to proportions ranging from 0 to 7% (mean, 2.4%) after correction. The discriminant function was "tuned" to maintain both average cell singlet purity and average cell singlet yield at >70% over a broad range of cell DNA contents. CONCLUSIONS: A combined approach to cell aggregate detection, which utilizes both the saddle function and the APT algorithm, produces list mode data files that exclude >80% of cell aggregates from samples of disaggregated cell suspensions of human tumors and other sources of clinical material. Such data files are suitable for multiparameter analysis.

Algorithms↗

Evaluation of two inversion techniques for retrieving health-related aerosol fractions from personal cascade impactor measurements.

Personal cascade impactors are widely used in occupational aerosol exposure assessment. Appropriate algorithms must be used to determine the total particle size distribution from masses collected on the stages of the cascade impactor. Such algorithms should be regarded as integral components of the measurement system. When evaluating algorithms for reconstruction of size distributions from cascade impactor data, the eventual use of the size distribution must be considered. So, from an industrial hygiene perspective, an appropriate basis for comparison of given measurement systems is the accurate retrieval of the inhalable, thoracic, and respirable aerosol fractions as described by the new, internationally accepted, particle size-selective sampling conventions (which are expected to form the basis of future aerosol standards). This article compares two inversion routines in terms of their abilities to retrieve these aerosol mass fractions relative to the masses that would have been obtained using an ideal sampler that perfectly followed the sampling convention. The routines were used to invert measurements made with the Institute of Occupational Medicine personal inhalable dust spectrometer, a miniature cascade impactor that aspirates the inhalable aerosol fraction, and the results are presented graphically as contours of equal mass bias. The simplest algorithm, based on the a priori assumption of lognormality, appears to provide the best results.

Aerosols↗

Characterization of airborne transducers by optical tomography

This paper describes the application of an acousto-optic method to the measurement of airborne ultrasound. The method consists of a heterodyne interferometric probing of the pressure emitted by the transducer combined with a tomographic algorithm. The heterodyne interferometer measures the optical phase shift of the probe laser beam, proportional to the acoustic pressure integrated along the light path. A number of projections of the sound field, e.g. a set of ray integrals obtained along parallel paths, are made in moving the transducer to be tested. The main advantage of the method is its very high sensitivity in air (2 x 10(-4) Pa Hz-1/2), combined with a large bandwidth. Using the same principle as X-ray tomography the ultrasonic pressure in a plane perpendicular to the transducer axis can be reconstructed. Several ultrasonic fields emitted by wide-band home made electrostatic transducers, with operating frequencies between 200 and 700 kHz, have been measured. The sensitivities compared favorably with those of commercial airborne transducers.

Journal Article↗

Modified SIMPSON O(n3) algorithm for the full sibship reconstruction problem.

MOTIVATION: The problem of reconstructing full sibling groups from DNA marker data remains a significant challenge for computational biology. A recently published heuristic algorithm based on Mendelian exclusion rules and the Simpson index was successfully applied to the full sibship reconstruction (FSR) problem. However, the so-called SIMPSON algorithm has an unknown complexity measure, questioning its applicability range. RESULTS: We present a modified version of the SIMPSON (MS) algorithm that behaves as O(n(3)) and achieves the same or better accuracy when compared with the original algorithm. Performance of the MS algorithm was tested on a variety of simulated diploid population samples to verify its complexity measure and the significant improvement in efficiency (e.g. 100 times faster than SIMPSON in some cases). It has been shown that, in theory, the SIMPSON algorithm runs in non-polynomial time, significantly limiting its usefulness. It has been also verified via simulation experiments that SIMPSON could run in O(n(a)), where a > 3. AVAILABILITY: Computer code written in Java is available upon request from the first author. CONTACT: Dmitry.Konovalov@jcu.edu.au.

Algorithms↗

Effect of bio-optical parameter variability and uncertainties in reflectance measurements on the remote estimation of chlorophyll-a concentration in turbid productive waters: modeling results.

Most algorithms for retrieving chlorophyll-a concentration (Chla) from reflectance spectra assume that bio-optical parameters such as the phytoplankton specific absorption coefficient (aPhi*) or the chlorophyll-a fluorescence quantum yield (eta) are constant. Yet there exist experimental data showing large ranges of variability for these quantities. The main objective of this study was to analyze the sensitivity of two Chla algorithms to variations in bio-optical parameters and to uncertainties in reflectance measurements. These algorithms are specifically designed for turbid productive waters and are based on red and near-infrared reflectances. By means of simulated data, it is shown that the spectral regions where the algorithms are maximally sensitive to Chla overlap those of maximal sensitivity to variations in the above bio-optical parameters. Thus, to increase the accuracy of Chla retrieval, we suggest using spectral regions where the algorithms are less sensitive to Chla, but also less sensitive to these interferences. aPhi* appeared to be one of the most important sources of error for retrieving Chla. However, when the phytoplankton backscattering coefficient (bb,Phi) dominates the total backscattering, as is likely during algal blooms, variations in the specific bb,Phi may introduce large systematic uncertainties in Chla estimation. Also, uncertainties in reflectance measurements, which are due to incomplete atmospheric correction or reflected skylight removal, seem to affect considerably the accuracy of Chla estimation. Instead, variations in other bio-optical parameters, such as eta or the specific backscattering coefficient of total suspended particles, appear to have minor importance. Suggestions regarding the optimal band locations to be used in the above algorithms are finally provided.

Algorithms↗

Extraction of local hydrogen exchange data from HDX CAD MS measurements by deconvolution of isotopic distributions of fragment ions.

Hydrogen/deuterium exchange (HDX) coupled to protein fragmentation either in solution (by means of proteolysis) or in the gas phase (using collisional activation of protein ions) and followed by mass spectral measurements of deuterium content of individual fragments has become one of the major experimental tools to probe protein structure and dynamics. One difficulty, which often arises in the course of interpretation of HDX MS data, is a need to separate deuterium contribution to the observed isotopic patterns from that of naturally occurring isotopes. Another frequently encountered problem, especially when HDX in solution is followed by protein ion fragmentation in the gas phase, is a need to determine the deuterium content of an internal protein segment based on the measured isotopic distributions of overlapping fragments. While several algorithms were developed in the past several years to address the first problem, the second one did not enjoy as much attention. Here we report a new algorithm based on a maximum entropy principle, which is capable of extracting local exchange data form the isotope distribution of overlapping fragments, as well as subtracting the background due to the presence of natural isotopes and residual deuterium in exchange buffers. The new method is tested with several proteins and appears to generate stable solutions even under unfavorable circumstances, e.g., when the resolving power of a mass analyzer is not sufficient to avoid signal interference or when the isotopic distributions of individual fragments are complex and cannot be approximated with simple binomial distributions. The latter feature makes the algorithm particularly useful when the exchange in solution is correlated or semicorrelated, paving the way to precise structural characterization of non-native protein states in solution.

Algorithms↗

Perceptual tests of an algorithm for musical key-finding.

Perceiving the tonality of a musical passage is a fundamental aspect of the experience of hearing music. Models for determining tonality have thus occupied a central place in music cognition research. Three experiments investigated 1 well-known model of tonal determination: the Krumhansl-Schmuckler key-finding algorithm. In Experiment 1, listeners' percepts of tonality following short musical fragments derived from preludes by Bach and Chopin were compared with predictions of tonality produced by the algorithm; these predictions were very accurate for the Bach preludes but considerably less so for the Chopin preludes. Experiment 2 explored a subset of the Chopin preludes, finding that the algorithm could predict tonal percepts on a measure-by-measure basis. In Experiment 3, the algorithm predicted listeners' percepts of tonal movement throughout a complete Chopin prelude. These studies support the viability of the Krumhansl-Schmuckler key-finding algorithm as well as a model of listeners' tonal perceptions of musical passages.

Adult↗