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[Response analysis for an approximate 3-D image reconstruction in cone-beam SPECT].

Cone-beam Single Photon Emission Computed Tomography (SPECT) offers the potential for a large increase in sensitivity as compared with parallel hole or fan-beam collimation. Three-dimensional image reconstruction was approximately accomplished by backprojecting filtered projections using a two-dimensional fan-beam algorithm. The cone-beam projection data were formed from mathematical phantoms as analytically derived line integrals of the density. In order to reduce the processing time, the filtered projections were backprojected into each planes parallel to the circle on which the focal point moved. Discrepancy of source position and degradation of resolution were investigated by computer simulation in three-dimensional image space. The obtained results suggest that, the nearer to the central plane or the axis of rotation, the less image degradation is performed. By introducing a parameter of angular difference between the focal point and fixed point in the image space during rotation, degradation of the reconstructed image can be estimated for any cone-beam SPECT system.

Algorithms

Optimization by stimulating molecular evolution.

Based on the analogy between mathematical optimization and molecular evolution and on Eigen's quasi-species model of molecular evolution, an evolutionary algorithm for combinatorial optimization has been developed. This algorithm consists of a versatile variation scheme and an innovative decision rule, the essence of which lies in a radical revision of the conventional philosophy of optimization: A number of configurations of variables with better values, instead of only a single best configuration, are selected as starting points for the next iteration. As a result the search proceeds in parallel along a number of routes and is unlikely to get trapped in local optima. An important innovation of the algorithm is introduction of a constraint to let the starting points always keep a certain distance from each other so that the search is able to cover a larger region of space effectively. The main advantage of the algorithm is that it has more chances to find the global optimum and as many local optima as possible in a single run. This has been demonstrated in preliminary computational experiments.

Algorithms

Automated particle classification based on digital acquisition and analysis of flow cytometric pulse waveforms.

In flow cytometry, the typical use of front-end analog processing limits the pulse waveform features that can be measured to pulse integral, height, and width. Direct digitizing of the waveforms provides a means for the extraction of additional features, for example, pulse skewness and kurtosis, and Fourier properties. In this work, we have first demonstrated that the Fourier properties of the pulse can be employed usefully for discrimination between different types of cells that otherwise cannot be classified by using only time-domain features of the pulse. We then implemented and evaluated automatic procedures for cell classification based on neural networks. We established that neural networks could provide an efficient means of classification of cell types without the need for user interaction. The neural networks were also employed in an innovative manner for analysis of the digital flow cytometric data without feature extraction. The performance of the neural networks was compared with that of a more conventional means of classification, the K-means clustering algorithm. Neural networks can be realized in hardware, and this, in addition to their highly parallel architecture, makes them an important potential part of real-time analysis systems. These results are discussed in terms of the design of a real-time digital data acquisition system for flow cytometry.

Animals

Quantitative analysis of gel electrophoretograms by image analysis and least squares modeling.

A computer-aided quantitative method for a complex analysis of gel electrophoretograms is presented. The analysis consists of several steps: (i) determination of the background image by methods of mathematical morphology and its subtraction from the gel image, (ii) selection of an appropriate part of the gel lane including curved lanes and lanes with a nonuniform width, (iii) computation of the lane densitogram by averaging several lane-parallel scans, (iv) decomposition of the lane densitogram into component bands using a data selecting algorithm and Marquardt's minimizer. Several different functions for component bands are utilized. It is shown that the densitogram can be decomposed into component bands with reasonable accuracy only if an appropriate model function is chosen. The algorithms are tested on several different gel electrophoretograms which show typical features as a nonuniform background, curved lanes, an asymmetrical band shape and a superposition of small bands on the shoulders of big ones. It is shown that overlapped bands are best approximated by an asymmetrical Gausian curve and an asymmetrical Gauss-Cauchy function. Linear response to the serial dilution of the protein sample is tested.

DNA, Bacterial

The clinical utility of renal concentrating capacity in polycystic kidney disease.

We studied 177 adult nonazotemic subjects with autosomal dominant polycystic kidney disease (ADPKD) and 123 unaffected family members (NADPKD). In order to assess the factors influencing renal concentrating capacity maximal urinary osmolality (UOsm) after overnight water deprivation and vasopressin was measured. UOsm was reduced in ADPKD (680 +/- 14) compared to NADPKD subjects (812 +/- 13 mOsm/kg). A greater severity of the architectural abnormality as assessed by cyst number and size and remaining volume of normal parenchyma was associated with a greater impairment of renal concentrating capacity. The concentrating defect was present in the youngest ADPKD subjects and the rate of decline of concentrating capacity with age in ADPKD paralleled that in NADPKD subjects. Based on the initial 135 subjects studied, we developed an algorithm for diagnostic screening for ADPKD utilizing blood pressure, serum creatinine and UOsm designed to maximize sensitivity. When applied to a subsequent population of 165 adults, 121 with ADPKD and 44 unaffected relatives, this algorithm would have spared 20% of unaffected subjects from the cost of ultrasound while failing to detect less than 2% of affected subjects. This simple protocol thus offers a rapid and inexpensive way to screen for ADPKD.

Adult

Neural networks and physical systems with emergent collective computational abilities.

Computational properties of use of biological organisms or to the construction of computers can emerge as collective properties of systems having a large number of simple equivalent components (or neurons). The physical meaning of content-addressable memory is described by an appropriate phase space flow of the state of a system. A model of such a system is given, based on aspects of neurobiology but readily adapted to integrated circuits. The collective properties of this model produce a content-addressable memory which correctly yields an entire memory from any subpart of sufficient size. The algorithm for the time evolution of the state of the system is based on asynchronous parallel processing. Additional emergent collective properties include some capacity for generalization, familiarity recognition, categorization, error correction, and time sequence retention. The collective properties are only weakly sensitive to details of the modeling or the failure of individual devices.

Animals

A comparison of three electron planning algorithms for a 16 MeV electron beam.

PURPOSE: We report results of a comparison of three electron planning algorithms, an Age-Diffusion Pencil beam algorithm and two (2-D) and three dimensional (3-D) Hogstrom pencil beam algorithms, using simple 2 x 2 cm air and hard bone inhomogeneities and a complex anthropomorphic head and neck phantom. METHODS AND MATERIALS: The simple inhomogeneities have variable dimensions outside the plane of calculation to test the effects of out of plane scattering on 2-D algorithms, compared with dose measured by film below the inhomogeneity in the dose fall-off range. Comparisons are also made of a parotid treatment field for 16 MeV electrons, and the dose measured by high sensitivity thermoluminescent dosimeters in the head and neck phantom. RESULTS: Behind the simple inhomogeneities, the electron algorithms are found to underestimate the dose behind the air cavity by up to 40% and overestimated the dose behind bone by up to 30%. In the head phantom, the presence of inhomogeneities also presents problems for the algorithms, with overestimations of dose of up to 20% found behind bone-tissue interfaces, apparently due to shielding by high density bone. Overestimations of up to 17% are also found beside interfaces parallel to the beam. Underestimations of dose of up to 10% are found on the beam-side of interfaces, due to under-prediction of backscattered electrons. All three investigated algorithms underestimate the dose by up to 20% behind extreme surface curvature. One algorithm is found to underestimate the dose in the falloff region while another overestimates the dose around the 90% isodose. CONCLUSION: Clinicians should be aware of the limitations of their planning systems.

Algorithms

Design and fitting of neural network transfer functions.

An algorithm is presented which (a) allows construction of mathematical models involving arbitrary combinations of linear cascades, parallel pathways, and feedback loops, (b) computes a total transfer function of the system, (c) performs a least-squares optimization of model parameters to best fit the model to experimental data, and (d) provides a measure of goodness-of-fit to the data. The technique has been employed to construct and test models of neural networks which mimic a class of responses observed in the cat vestibular nuclei in response to tilt, namely responses which show both a gain increase and progressive phase lag as the stimulation frequency goes from 0.01 to 2 Hz. A network consisting of a simple gain element in parallel with an inhibitory high-pass filtered version of the input provided a satisfactory fit to these data.

Animals

Evoked potential techniques in the evaluation of visual function.

Visual evoked potentials (VEPs) can be used in a multitude of ways to assess the various levels of visual processing. The human visual system consists of multiple, parallel channels which process different information, and each channel constitutes a set of sequential processes. An algorithm of sequential steps that can be used to assess visual function is reviewed. The pathophysiology of retinal, anterior visual pathways and retrochiasmal pathways can be objectively evaluated by VEPs.

Adolescent

Parallel hardware for sequence comparison and alignment.

Sequence comparison, a vital research tool in computational biology, is based on a simple O(n2) algorithm that easily maps to a linear array of processors. This paper reviews and compares high-performance sequence analysis on general-purpose supercomputers and single-purpose reconfigurable, and programmable co-processors. The difficulty of comparing hardware from published performance figures is also noted.

Algorithms

Comparison of non parallel immunoassay curves resulting from mixtures of competing antigens.

Relative potency is a measure that has been used for many years to summarize the comparison of dose-response curves in parallel line bioassays. When response curves for two preparations are not parallel the traditional definition of relative potency no longer applies. We review the concept of relative potency and show that, in some situations, it can be given meaning for non-parallel curves as the ratio of biological activity in full strength assay preparations. Under an assumption that non-parallel curves result from the competition of mixtures of antigens for receptor binding sites, estimation of relative potency for non-parallel curves can be accomplished. We show that estimation of models for both parallel curve and response attenuation situations may be accomplished within the framework of generalized linear models. This estimation depends on the ability to deal with non-linear parameters appearing in the link function, and an iterative algorithm depending on direct parameter updates is outlined. The topics discussed are illustrated with the analysis of data from two immunoassays conducted with veterinary vaccines. The models developed here depend in an essential way on the assumption of response attenuation by competing antigens. Our methods may not be appropriate for non-parallel curves caused by other phenomena.

Algorithms

Sample size estimation for comparing two or more treatment groups in clinical trials.

Methods for estimating required sample size for comparing two population means have been published. Most involve the use of complicated formulae and tables. These methods are limited to comparing two groups. Although techniques exist to determine sample sizes for comparing more than two groups, they are intrinsically far more complicated. A simple linear nomogram is proposed as a solution to these problems, and its use is illustrated with examples of parallel group, ordered parallel group and factorial designs.

Algorithms

Asymmetric Boltzmann machines.

We study asymmetric stochastic networks from two points of view: combinatorial optimization and learning algorithms based on relative entropy minimization. We show that there are non trivial classes of asymmetric networks which admit a Lyapunov function L under deterministic parallel evolution and prove that the stochastic augmentation of such networks amounts to a stochastic search for global minima of L. The problem of minimizing L for a totally antisymmetric parallel network is shown to be associated to an NP-complete decision problem. The study of entropic learning for general asymmetric networks, performed in the non equilibrium, time dependent formalism, leads to a Hebbian rule based on time averages over the past history of the system. The general algorithm for asymmetric networks is tested on a feed-forward architecture.

Algorithms

A two-dimensional pencil-beam algorithm for calculation of arc electron dose distributions.

A two-dimensional pencil-beam algorithm is presented for the calculation of arc electron dose distributions in any plane that is perpendicular to the axis of rotation. The dose distributions are calculated by modelling the arced beam as a single broad beam defined by the irradiated surface of the patient. The algorithm is two-dimensional in that the anatomical cross section of the patient and the skin collimators are assumed identical in parallel planes outside the plane of calculation. The broad beam is modelled as a collection of strip beams, each strip beam being characterised by its planar fluence, mean projected angular direction and a root-mean-square spread about the mean direction. Using these parameters, the dose distribution is calculated using pencil-beam theory. Examples of strip-beam parameters and resulting dose distributions for patient geometries are presented. Features of the algorithm, which include (1) incorporation of pencil-beam theory for the calculation of dose in heterogeneous tissue, (2) run times of only about twice that of comparable-sized fixed electron fields and (3) the input requirement of only a single depth dose and four off-axis dose profiles of measured data, make the algorithm practical for clinical use.

Algorithms

Graded changes in the response of individual human basophils to stimulation: distributional behavior of early activation events.

These studies examine the distribution of single-cell responses in basophil preparations in the context of four events that may be associated with early activation by anti-immunoglobulin E (IgE) antibody and the bacterial peptide fMet-Leu-Phe (fMLP). In general, we measured the single-cell response distributions after challenge with a concentration of stimulus that resulted in an optimal response and compared this with the distribution that occurred after challenge with suboptimal concentrations of the same stimulus. The elevation in cytosolic calcium, as detected in Fura-2-labeled basophils, after challenge with anti-IgE or fMLP showed graded characteristics in that the distributions were unimodal under conditions of optimal or suboptimal challenge with little skewing from a normal distribution. Similarly, the up-regulation of the cell surface adhesion molecule CD11b, as determined by flow cytometry, showed graded unimodal increases after challenge with anti-IgE antibody at optimal and suboptimal concentrations. In addition, stimulation of basophils led to increased F-actin polymerization. After challenge with an optimal concentration of anti-IgE antibody, the F-actin content of basophils increased to a maximum between 10 and 15 min and returned to near prechallenge levels by 60 min. There was a close correlation between the maximum increase in F-actin content and histamine release regardless of the stimulus; anti-IgE antibody, fMLP, and phorbol ester (PMA) responses lay on the same regression line. The single-cell F-actin polymerization distributions were also unimodal and graded according to the magnitude of the histamine release response. During measurements of the calcium response under the microscope we noted that basophils underwent significant changes in morphology after challenge with any stimulus. These changes were related to both degranulation and nondegranulation events and could be quantitated by a series of image-processing algorithms, which are presented. The kinetics of the morphological change, measured as a change in cell perimeter, paralleled degranulation. Single-cell distributions of the morphologic changes were also unimodal under conditions of both optimal and suboptimal stimulation. Therefore, no evidence of all-or-nothing responses could be observed in the context of these four early activation events. In general, the response distributions resembled normal distributions at both optimal and suboptimal levels of stimulation, which indicated that single basophils responded in a graded manner.

Basophils

Infrared spectroscopy of dystrophic mdx mouse muscle tissue distinguishes among treatment groups.

Four groups of mdx mice (deflazacort, high dose of 1.5 mg/kg and low dose of 0.75 mg/kg; prednisone, 1.0 mg/kg; and a placebo) were examined in a double-blind protocol. The experiments tested the hypothesis that infrared spectroscopy can distinguish among gastrocnemius muscle tissues derived from dystrophic animals (n = 22) from different treatment groups and from control muscle tissue (n = 23). Results showed that muscle, inflamed muscle, and tendon can be distinguished on the basis of their infrared absorption patterns. Distinctions among the spectra of the four treatment groups were sought with automated pattern-recognition methods. These classification methods, based either on spectral regions (900-1,500 cm-1) or on principal-component analysis, were in close agreement, assigning 15 or 16, respectively, of 22 mdx spectra to the correct treatment group. Both trials cleanly separated the high-dose deflazacort from the placebo group of muscles, whereas the prednisone and low-dose deflazacort groups were persistently confused in these classifications. Changes in the histology of muscle inflammation paralleled the spectral-classification results. Thus the proposed method, combining infrared spectroscopy with pattern-recognition algorithms, can distinguish treatment effects on muscle tissue. Specific spectral features characteristic of tissue type, disease progression, and treatment effects are not yet elucidated.

Algorithms