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Geometric parameter analysis to predetermine optimal radiosurgery technique for the treatment of arteriovenous malformation.

PURPOSE: To develop a method of predicting the values of dose distribution parameters of different radiosurgery techniques for treatment of arteriovenous malformation (AVM) based on internal geometric parameters. METHODS AND MATERIALS: For each of 18 previously treated AVM patients, four treatment plans were created: circular collimator arcs, dynamic conformal arcs, fixed conformal fields, and intensity-modulated radiosurgery. An algorithm was developed to characterize the target and critical structure shape complexity and the position of the critical structures with respect to the target. Multiple regression was employed to establish the correlation between the internal geometric parameters and the dose distribution for different treatment techniques. The results from the model were applied to predict the dosimetric outcomes of different radiosurgery techniques and select the optimal radiosurgery technique for a number of AVM patients. RESULTS: Several internal geometric parameters showing statistically significant correlation (p < 0.05) with the treatment planning results for each technique were identified. The target volume and the average minimum distance between the target and the critical structures were the most effective predictors for normal tissue dose distribution. The structure overlap volume with the target and the mean distance between the target and the critical structure were the most effective predictors for critical structure dose distribution. The predicted values of dose distribution parameters of different radiosurgery techniques were in close agreement with the original data. CONCLUSIONS: A statistical model has been described that successfully predicts the values of dose distribution parameters of different radiosurgery techniques and may be used to predetermine the optimal technique on a patient-to-patient basis.

Algorithms↗

Evolutionary optimization of enzyme kinetic parameters; effect of constraints.

The distribution of the kinetic parameters of enzymic reactions is theoretically studied, on the assumption that, during evolution, the increase of reaction rates was an important target of natural selection. In extension of previous work on the optimization of enzyme kinetic parameters, the influence of constraints concerning upper limits of the individual rate constants is analyzed. The concept of "evolutionary effort" is applied to derive an expression for the cost function, leading to an overall upper limit for the values of the rate constants. The resulting optimization problem is solved for ordered mechanisms involving different numbers of elementary steps. It is shown that the optimum for the enzyme kinetic parameters strongly depends on the concentrations of the reactants. Low reactant concentrations lead generally to a tight binding of the reactants, while high concentrations result in a weak binding, favouring the rate constants of the other steps. In particular, states of maximum activity are not always characterized by maximal values of second-order rate constants. The results support the hypothesis that there is a mutual adaptation of Michaelis constants and reactant concentrations in an evolutionary timescale. In the limit of infinite values of the exponent of the cost function the results of the present "overall limit model" turn into the results of a model which takes into account individual upper limits for rate constants ("separate limit model"). The distributions of optimal rate constants are discussed in terms of free-energy profiles. The model is applied to the interpretation of the kinetic data of triosephosphate isomerase and inorganic pyrophosphatase.

Animals↗

RT-PCR amplification of CK19 mRNA in the blood of breast cancer patients: correlation with established prognostic parameters.

We optimized the assay for detection of cytokeratin 19 (CK19) mRNA by the reverse transcriptase-polymerase chain reaction (RT-PCR) in blood as an index of circulating tumor cells in breast cancer patients. The limit of detection of < 1 MCF7 tumor cells per 10(6) peripheral blood leukocytes (PBL) was achieved in mixing experiments. We did not detect CK19 mRNA in control bloods (0/30) or in the blood of patients with benign breast disease (0/15). In blood samples from 109 patients with invasive breast cancer, CK19 mRNA was detected in 7/23 patients with node-negative disease, in 21/58 with node-positive disease, and in 20/28 with distant metastases. There was a significant association (P < 0.01) of CK19 positivity with distant metastatic versus both node-negative and node-positive disease, but not with any other histopathological parameter examined. In a small number of patients with distant metastases, increased intensity of the CK19 RT-PCR signal was associated with a reduced survival.

Biomarkers, Tumor↗

Finding optimal radial-function parameters for S atoms in the Hansen-Coppens multipole model through refinement of theoretical densities.

The multipolar model of the valence-electron-density distribution for S atoms has been optimized based on theoretical structure factors for six organic molecules. The evaluation of different sets of radial function parameters shows that: (a) the ratio of the n(l) values for different l is more important than their absolute values, as parallel changes in all n(l) for a given atom are compensated for by a change in the refined value of the kappa' parameter, and (b) the (2,4,6,8) set of n(l) with kappa' refined as a single value is an optimal choice of radial function parameters for S atoms.

Journal Article↗

The impact of healthy start peritoneal dialysis on the evolution of residual renal function and nutrition parameters.

The optimal time to start renal replacement therapy remains controversial. Residual renal function (RRF) and nutrition status being important prognostic factors, the present study evaluates the impact of timely start of peritoneal dialysis (PD) on their evolution. Our study used a prospective database on pre-end-stage renal disease patients at a tertiary care center. We included 18 patients who were planned to start PD at a GFR > 8 mL/min between 1 January and 31 December 1999. At the start of PD (month 0), creatinine clearance (CCr) was 11.3 +/- 3.9 mL/min, actual glomerular filtration rate (GFR) was 8.6 +/- 3.3 mL/min, and Kt/V was 1.56 +/- 0.65. The monthly declines of GFR and CCr before and after the start of PD were -0.47 +/- 0.64 mL/min (GFR) and -0.59 +/- 0.46 mL/min (CCr), and -0.06 +/- 0.30 mL/min (GFR) and -0.05 +/- 0.39 mL/min (CCr) respectively (p = 0.034 and 0.001, respectively). Before the start of PD, CCr was 21.9 +/- 4.6 mL/min (month -12) and 18.1 +/- 4.8 mL/min (month -6, p < 0.001). After the start of PD, CCr was 12.0 +/- 4.3 mL/min (month 3), 11.5 +/- 4.9 mL/min (month 6), and 13.1 +/- 5.4 mL/min (month 12, p = 0.9). Serum albumin dropped until just before the start of PD: 3.89 +/- 0.59 g/dL (month -6) and 3.78 +/- 0.51 g/dL (month -3) versus 2.56 +/- 1.60 g/dL (month 0, p = 0.04). Serum albumin then increased to 3.42 +/- 0.95 mg/dL (month 3 after the start of PD) and 3.35 +/- 0.86 mg/dL (month 6 after the start of PD, p = 0.04). In the months preceding the start of PD, the normalized protein catabolic rate (nPCR) dropped from 1.41 +/- 0.36 g/kg daily (month -6) and 1.34 +/- 0.46 g/kg daily (month -3) to 1.12 +/- 0.25 g/kg daily (month 0). It then stabilized at 1.17 +/- 0.25 g/kg daily (month 3) and 1.18 +/- 0.17 g/kg daily (months 6). One patient died owing to a cerebrovascular accident after 18 months of PD, and one was transferred to hemodialysis because of ultrafiltration failure after 19 months of PD. During 264 patient-months, 14 peritonitis episodes occurred. Of the 14 episodes, 12 resolved without complication, and the catheter was replaced in 2 episodes. After timely start of PD, the rate of RRF decline decreases. Already, at a GFR > 8 mL/min, uremia has a negative impact on nutrition parameters. Timely initiation of PD could reverse the negative evolution of albumin and stop the decline of nPCR. No severe complications related to PD were seen. In view of the important impact of RRF and nutrition on patient outcome, our data may favor an early start of PD.

Creatinine↗

Modeling of auditory spatial receptive fields with spherical approximation functions.

A spherical approximation technique is presented that affords a mathematical characterization of a virtual space receptive field (VSRF) based on first-spike latency in the auditory cortex of cat. Parameterizing directional sensitivity in this fashion is much akin to the use of difference-of-Gaussian (DOG) functions for modeling neural responses in visual cortex. Artificial neural networks and approximation techniques typically have been applied to problems conforming to a multidimensional Cartesian input space. The problem with using classical planar Gaussians is that radial symmetry and consistency on the plane actually translate into directionally dependent distortion on spherical surfaces. An alternative set of spherical basis functions, the von Mises basis function (VMBF), is used to eliminate spherical approximation distortion. Unlike the Fourier transform or spherical harmonic expansions, the VMBFs are nonorthogonal, and hence require some form of gradient-descent search for optimal estimation of parameters in the modeling of the VSRF. The optimization equations required to solve this problem are presented. Three descriptive classes of VSRF (contralateral, frontal, and ipsilateral) approximations are investigated, together with an examination of the residual error after parameter optimization. The use of the analytic receptive field model in computational models of population coding of sound direction is discussed, together with the importance of quantifying receptive field gradients. Because spatial hearing is by its very nature three dimensional or, more precisely, two dimensional (directional) on the sphere, we find that spatial receptive field models are best developed on the sphere.

Acoustic Stimulation↗

Optimization of the physiochemical parameters for the culture of Bombyx mori insect cells used in recombinant protein production.

Silkworm (Bombyx mori, Bm5) cell growth at different environmental conditions was systematically studied in controlled bioreactors. The physiochemical parameters, which affect the growth of Bm5 cells, were defined and optimized. The growth rate was maximal at a medium osmolality of about 370 mosm kg-1; and more than 90% of the maximum growth rate was achieved with osmolality between 350 and 385 mosm kg-1. The optimum pH for Bm5 cell growth was from 6.10 to 6.30. Moreover, the effect of dissolved oxygen concentrations (higher than 20% air saturation) on growth was minimal. However, the maximum cell density decreased markedly with dissolved oxygen tensions less than 20%. The shear protection additive Pluronic F-68 had a very important effect on the growth of Bm5 cells in bioreactors with an optimum concentration of 0.2% (w/v). Compared to the original culture condition, the optimized conditions resulted in a twofold increase in cell yield and a reduced population doubling time from 48 to 36 h. Furthermore, the yield of a recombinant protein (CAT) was increased substantially in the optimized cultures.

Animals↗

Quantitation of indirect sandwich enzyme-linked immunosorbent assay parameters.

The optimization of data from the indirect sandwich enzyme-linked immunosorbent assay has been commonly accomplished by linear regression analysis, even though the data are often essentially sigmoid. A new microcomputer software program (LISACRV) that uses a nonlinear regression statistical model to analyze the data from enzyme-linked immunosorbent assay titration experiments was developed.

Enzyme-Linked Immunosorbent Assay↗

Particulated growth media for optimal liquid and gaseous fluxes to plant roots in microgravity.

An important and yet relatively under researched area of plant growth in microgravity, deals with the rooting environment of plants. A comprehensive approach for selecting the physical characteristics of root growth media which optimizes the dynamic availability of water and dissolved nutrients, and gases to plant roots was developed and tested. Physically-based and parametric models describing the relationship between content and fluxes of liquids and gases were used to cast a multi-objective optimization problem. This methodology reveals that a medium's ability to supply liquid and gas fluxes optimally is dependent upon physiological target values, system operation limits and root module design which dictate the medium's range of soil water characteristic and particle size distribution. Optimized media parameters designate a particle size distribution from which a particulated growth media was constructed and matched to the optimized media parameters. This methodology should improve the selection of optimal media properties for plant growth in microgravity as well as other porous media applications.

Culture Media↗

The parameterization and validation of generalized born models using the pairwise descreening approximation.

Generalized Born Surface Area (GBSA) models for water using the Pairwise Descreening Approximation (PDA) have been parameterized by two different methods. The first method, similar to that used in previously reported parameterizations, optimizes all parameters against the experimental free energies of hydration of organic molecules. The second method optimizes the PDA parameters to compensate only for systematic errors of the PDA. The best models are compared to Poisson-Boltzmann calculations and applied to the computation of potentials of mean force (PMFs) for the association of various molecules. PMFs present a more rigorous test of the ability of a solvation model to correctly reproduce the screening of intermolecular interactions by the solvent, than its accuracy at predicting free energies of hydration of small molecules. Models derived with the first method are sometimes shown to fail to compute accurate potentials of mean force because of large errors in the computation of Born radii, while no such difficulties are observed with the second method. Furthermore, accurate computation of the Born radii appears to be more important than good agreement with experimental free energies of solvation. We discuss the source of errors in the potentials of mean force and suggest means to reduce them. Our findings suggest that Generalized Born models that use the Pairwise Descreening Approximation and that are derived solely by unconstrained optimization of parameters against free energies of hydration should be applied to the modeling of intermolecular interactions with caution.

Journal Article↗

Modeling DNA structure, elasticity, and deformations at the base-pair level.

We present a generic model for DNA at the base-pair level. We use a variant of the Gay-Berne potential to represent the stacking energy between the neighboring base pairs. The sugar-phosphate backbones are taken into account by semirigid harmonic springs with a nonzero spring length. The competition between these two interactions and the introduction of a simple geometrical constraint lead to a stacked right-handed B-DNA-like conformation. The mapping of the presented model to the Marko-Siggia and the stack-of-plates model enables us to optimize the free model parameters so as to reproduce the experimentally known observables such as persistence lengths, mean and mean-squared base-pair step parameters. For the optimized model parameters, we measured the critical force where the transition from B- to S-DNA occurs to be approximately 140 pN. We observe an overstretched S-DNA conformation with highly inclined bases which partially preserves the stacking of successive base pairs.

Base Composition↗

Efficiency of an elliptically shaped x-ray mirror.

Curved reflecting mirrors are widely used as x-ray optical elements for both laboratory and synchrotron radiation sources. In general, the mirror parameters are optimized by numerical simulation. We discuss an analytical approach that is useful for deriving the mirror parameters, including eccentricity, length, angular acceptance, and magnification. We have examined in particular an elliptical surface from which we learned that, given the distance between the foci of the ellipse, the magnification, and the critical angle of total external reflection, it is possible to find analytically the optimal eccentricity that maximizes the angular acceptance and the optimal mirror length. We found that the last-named parameter, in a first approximation, depends only on the distance between the foci of the ellipse and on the magnification factor. We present as well a comparison of optimal parameters obtained with analytical calculation and with ray-tracing simulation that yielded good agreement.

Journal Article↗

Evolutionary algorithms and flow cytometry to examine the parameters influencing transconjugant formation.

An evolutionary algorithm was used to determine the optimal combination of parameters for transconjugant formation. As a model system, a gfp tagged TOL plasmid pWW0 was chosen to examine transfer from Pseudomonas putida to Escherichia coli. A comparison of flow cytometry results with plating and microscopy showed that the majority of transconjugants were not culturable. The transconjugant ratio therefore was determined by flow cytometry. The evolutionary algorithm showed that the optimal conditions were obtained at 28 degrees C and at the highest nutrient concentrations. This work demonstrates that evolutionary algorithms can be used to find optimal parameter interactions in environmental microbiology.

Algorithms↗

Long-term variations in optimal programming of cardiac resynchronization therapy devices.

The optimal follow-up and long-term programming of cardiac resynchronization therapy (CRT) devices are uncertain. The aim of this study was to quantify the temporal variations in programming parameters to optimize the follow-up of these devices. Before, during, and at specified intervals over 9 months after implant, 40 recipients of CRT devices were studied. At each visit, the patients were tested with a fixed sequence of stimulation parameters during echocardiographic and electrocardiographic (ECG) recordings. The optimal AV delay and inter-ventricular delays (V-V) were determined according to echocardiographic criteria. The echocardiographic data were, in turn, compared with the ECG recordings. Among the 40 patients, the optimal stimulation parameters remained unchanged throughout the follow-up in only three patients. In 18 patients, adjustments were required at each follow-up sessions. There was a trend toward reduction in the left ventricular (LV) predominance of the optimal V-V delay and an increase in the AV delay during follow-up. The mean optimal V-V delay at implant was 22 ms (-12 to +32 ms) with the LV activated first, versus 12 ms (-16 to +32 ms) at 9 months. The mean AV delay at implant was 115 ms versus 137 ms at 9 months. Individual changes could not be accurately predicted. The optimal stimulation parameters for CRT vary over time. Detailed, regular reevaluations, and reprogramming of optimal parameters may be appropriate.

Cardiac Pacing, Artificial↗

[Optimization of numerical measurement parameters for ECG-triggered MRI snapshot-FLASH myocardial perfusion studies].

BACKGROUND AND AIMS: In MR examinations of myocardial perfusion by the use of Snapshot-FLASH sequences it is of major importance that the achievable signal difference between pre- and normal postcontrast myocardium be maximized. METHODS: In ECG-triggered Snapshot-FLASH sequences the signal intensity of the myocardium depends on the flip angle alpha, the inversion time TI and the trigger delay TD (both depending on the cardiac frequency f) for unchanged slice thickness (SL), matrix size (MA), repetition time (TR) and echo time (TE). Therefore a simulation of the signal behavior of pre- and postcontrast myocardium based on Bloch's equations was performed by varying the flip angle alpha, TI and TD for different cardiac frequencies in order to determine an optimized combination of the measurement parameters. RESULTS: In normal heart rates (50-70 beats/min) maximal signal differences between pre- and normal postcontrast myocardium can be reached for inversion times TI = 170-200 ms and a flip angle alpha = 11 degrees. For higher heart rates again alpha = 11 degrees and TI = 200-220 ms with shortened TD (TD = 0 for f > 90 beats/min) were found to be optimal. The calculated values were semiquantitatively confirmed in phantom and volunteer measurements. CONCLUSIONS: The described method allows cardiac frequency dependent optimization of the Snapshot-FLASH measurement parameters alpha, TI and TD in order to reach a maximum in signal contrast between normal and malperfused myocardium.

Computer Graphics↗

Nonlinear parameter estimation applied to a model of smooth pursuit eye movements.

We present a procedure that optimally adjusts specified parameters of a mathematical model to describe a set of measured data. The technique integrates a dynamic systems-simulation language with a robust algorithm for nonlinear parameter estimation, and it can be implemented on a microcomputer. Sensitivity functions are generated that indicate how the operation of the model is affected by each updated parameter. This procedure offers a greater resolution of optimal parameter values than other, less rigorous methods. To illustrate this technique we have applied it to the model of human smooth pursuit eye movements proposed by D.A. Robinson and colleagues (1986).

Eye Movements↗

Estimating degradation model parameters using neighborhood pattern distributions: an optimization approach.

Noise models are crucial for designing image restoration algorithms, generating synthetic training data, and predicting algorithm performance. There are two related but distinct estimation scenarios. The first is model calibration, where it is assumed that the input ideal bitmap and the output of the degradation process are both known. The second is the general estimation problem, where only the image from the output of the degradation process is given. While researchers have addressed the problem of calibration of models, issues with the general estimation problems have not been addressed in the literature. In this paper, we describe a parameter estimation algorithm for a morphological, binary, page-level image degradation model. The inputs to the estimation algorithm are 1) the degraded image and 2) information regarding the font type (italic, bold, serif, sans serif). We simulate degraded images using our model and search for the optimal parameter by looking for a parameter value for which the local neighborhood pattern distributions in the simulated image and the given degraded image are most similar. The parameter space is searched using a direct search optimization algorithm. We use the p-value of the Kolmogorov-Smirnov test as the measure of similarity between the two neighborhood pattern distributions. We show results of our algorithm on degraded document images.

Algorithms↗

Hybrid cardiac imaging with MR-CAT scan: a feasibility study.

We demonstrate the feasibility of a new versatile hybrid imaging concept, the combined acquisition technique (CAT), for cardiac imaging. The cardiac CAT approach, which combines new methodology with existing technology, essentially integrates fast low-angle shot (FLASH) and echoplanar imaging (EPI) modules in a sequential fashion, whereby each acquisition module is employed with independently optimized imaging parameters. One important CAT sequence optimization feature is the ability to use different bandwidths for different acquisition modules. Twelve healthy subjects were imaged using three cardiac CAT acquisition strategies: a) CAT was used to reduce breath-hold duration times while maintaining constant spatial resolution; b) CAT was used to increase spatial resolution in a given breath-hold time; and c) single-heart beat CAT imaging was performed. The results obtained demonstrate the feasibility of cardiac imaging using the CAT approach and the potential of this technique to accelerate the imaging process with almost conserved image quality.

Coronary Vessels↗