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Experimental validation of dose calculation algorithms for the GliaSite RTS, a novel 125I liquid-filled balloon brachytherapy applicator.

This paper compares experimentally measured and calculated dose-rate distributions for a novel 125I liquid-filled brachytherapy balloon applicator (the GliaSite RTS), designed for the treatment of malignant brain-tumor resection-cavity margins. This work is intended to comply with the American Association of Physicists in Medicine (AAPM) Radiation Therapy Committee's recommendations [Med. Phys. 25, 2269-2270 (1998)] for dosimetric characterization of low-energy photon interstitial brachytherapy sources. Absolute low dose-rate radiochromic film (RCF) dosimetry measurements were performed in coronal planes about the applicator. The applicator was placed in a solid water phantom, machined to conform to the inflated applicator's surface. The results were used to validate the accuracy of Monte Carlo photon transport (MCPT) simulations and a point-source dose-kernel algorithm in predicting dose to water. The absolute activity of the 125I solution was determined by intercomparing a National Institute of Standards and Technology (NIST) 125I standard with a known mass of radiotherapy solution (Iotrex) in an identical vial and geometry. For the two films not in contact with applicator, the average agreement between RCF and MCPT (specified as the mean absolute deviation in successive 4 mm rings) was found to be within +/-5% at distances 0.2-25 mm from the film centers. For the two films touching the catheter, the mean agreement was +/-14.5% and 7.5% near the balloon surface but improving to 7.5% and 6% by 3.5 mm from the surface. These errors, as large as 20% in isolated pixels, are likely due to trim damage, 125I contamination, and poor conformance with the balloon. At larger distances where the radiation doses were very low, the observed discrepancies were significantly larger than expected. We hypothesize that they are due to a dose-rate dependence of the RCF response. A 1%-10% average difference between a simple one-dimensional path-length semiempirical dose-kernel model and the MCPT calculations was observed over clinically relevant distances.

Algorithms↗

G-protein-coupled receptor affinity prediction based on the use of a profiling dataset: QSAR design, synthesis, and experimental validation.

A QSAR model accounting for "average" G-protein-coupled receptor (GPCR) binding was built from a large set of experimental standardized binding data (1939 compounds systematically tested over 40 different GPCRs) and applied to the design of a library of "GPCR-predicted" compounds. Three hundred and sixty of these compounds were randomly selected and tested in 21 GPCR binding assays. Positives were defined by their ability to inhibit by more than 70% the binding of reference compounds at 10 microM. A 5.5-fold enrichment in positives was observed when comparing the "GPCR-predicted" compounds with 600 randomly selected compounds predicted as "non-GPCR" from a general collection. The model was efficient in predicting strongest binders, since enrichment was greater for higher cutoffs. Significant enrichment was also observed for peptidic GPCRs and receptors not included to develop the QSAR model, suggesting the usefulness of the model to design ligands binding with newly identified GPCRs, including orphan ones.

Combinatorial Chemistry Techniques↗

Experimental validation of sino-atrial conduction time using sinus node potential recording, right and left atrial continuous pacing method.

In an experimental study indirect sino-atrial conduction time (SACT) was measured, using continuous pacing method from right and left atrial sites, and compared with direct SACT obtained from sinus node potential recording, all the determination being done before and after autonomic blockade. The distance between the two sites of stimulation may be taken into account as a correction factor for SACT determination. The SACT obtained with sinus node potential technique is the same as the indirect SACT after autonomic blockade. These findings are valuable for SACT determination with transesophageal pacing method. Left atrial pacing, thus transesophageal pacing, is a valuable method in estimating the SACT, but a time correction and autonomic blockade is required in order to obtain a real value, eliminating the extrinsic influences.

Animals↗

Automatic treatment of radioimmunoassay data: an experimental validation of the results.

A computational method for the automatic treatment of radioimmunoassay data has been developed and a computer program has been written in accordance. The main features of the approach used are the following: (a) a constant ratio between the bound fraction and its variance is assumed and estimated in each assay; (b) the points of the dose-response curve are fitted using the three-parameter function y' equals b1/(1 plus b2x(-b)3) where y' equals bound - nonspecific counts and x is the amount of hormone; the fitting is performed using the nonlinear, least-squares technique; (c) the values of the unknown samples are evaluated from the fitted standard curve; their confidence limits are computed taking into account both the variance of the bound replicates and the variance of the parameters of the dose-response curve. Experimental data that support the validity of the assumption on the variance of bound measurement and the suitability of the chosen function to fit the points of the standard curve are presented. A comparison between the confidence limits of the unknowns experimentally obtained and those computed by the program is reported and discussed.

Analysis of Variance↗

[Experimental validation of using ozonized physiological solutions in intraocular infection].

The study was aimed at assessing the efficacy of ozonized normal salines in experimental endophthalmitis. Experiments demonstrated that, as the control group developed grave endophthalmitis and the clinical picture deteriorated by the end of experiment, eventuating in melting of tissues both in the anterior and posterior segments of the eye, in experimental animals, to which ozonized normal saline was administered directly after infection, endophthalmitis either did not develop at all or was less severe. The anterior segment of the eyeball was not involved in the infectious process, and the changes in the vitreous body were not so grave as in the controls, and by the end of experiment the inflammation ceased completely. By the end of the infectious process in the experimental group the majority of tissue structures of the posterior pole of the eyeball, including the retina, were retained. After administration of ozonized normal saline to animals with full-blood endophthalmitis the symptoms of the inflammatory process abated and the disease took a more favorable course than in control. Hence, experiments demonstrated that even a single intravitreal instillation of ozonized solution during an infectious process brings about a high prophylactic and therapeutic effect.

Animals↗

Transit time flow measurement: experimental validation and comparison of three different systems.

BACKGROUND: Bloodflow measurements are of major clinical importance for quality control in vascular surgery. They allow detection of low-flow situations which may influence outcome adversely. The purpose of the present study was to validate three different flow systems for measuring absolute blood flow. METHODS: Measurements were performed in an experimental flow model using arteries and veins and blood or saline at two different temperatures. As a reference method true flow was measured by volume sampling. RESULTS: Correlation coefficients between transit time flow and true flow measurements ranged between 0.71 and 0.92. Systematic overestimation and underestimation of transit time flow were observed, but after second-order correction all correlations were excellent, ranging from 0.93 to 0.95 irrespective of flow medium and temperature. CONCLUSIONS: Transit time flow measurements are exact and reproducible. Second-order correction yields good accuracy and high precision, with minimal differences among the three systems evaluated.

Blood Flow Velocity↗

An adiabatic approximation to the tissue homogeneity model for water exchange in the brain: II. Experimental validation.

A frequently reported limitation to using water as a tracer for measuring CBF has been the dependence of the CBF estimate on the experimental time (referred to as the falling flow phenomenon, FFP). To eliminate the FFP, we have developed the adiabatic solution of the tissue homogeneity model to replace the solution of the single-compartment Kety model. In Part I, the derivation of the adiabatic solution was presented. In this second part, the adiabatic solution was applied to measure CBF in rabbits using nuclear magnetic resonance spectroscopy and the tracer deuterium oxide. It was shown that the FFP, observable when the 2H clearance data were analyzed with the Kety equation, was significantly reduced when the same data were analyzed with the adiabatic solution of the tissue homogeneity model. By concurrently measuring CBF with radioactive microspheres, it was determined that the CBF estimates from the adiabatic solution were accurate for true blood flow values less than 60 mL x 100 g(-1) x min(-1). Above this value the CBF estimate was progressively underestimated, which was attributed to the diffusion limitation of water in the brain.

Animals↗

Technetium-99m-tetrofosmin to assess myocardial blood flow: experimental validation in an intact canine model of ischemia.

UNLABELLED: Technetium-99m-tetrofosmin is a 99mTc-labeled perfusion tracer demonstrating promise for myocardial perfusion imaging. To determine if 99mTc-tetrofosmin tracks myocardial flow over a pathophysiologic range, the initial myocardial uptake and clearance of 99mTc-tetrofosmin relative to microsphere flow were evaluated in a canine model of ischemia during pharmacological vasodilatation. METHODS: Six open-chest dogs were subjected to complete left anterior descending coronary artery occlusion. Dogs were injected with 99mTc-tetrofosmin and radiolabeled microspheres during pharmacological stress. Coincident with radiotracer injection, dynamic planar imaging and arterial sampling were performed to assess 99mTc-tetrofosmin clearance from blood, myocardium, lung and liver. Fifteen minutes after injection, hearts were excised for well counting of myocardial 99mTc-tetrofosmin activity and flow. RESULTS: Myocardial 99mTc-tetrofosmin activity correlated linearly with microsphere flow (r = 0.84). Relative 99mTc-tetrofosmin activity underestimated flow at higher flow ranges (> 2.0 ml/min/g) and overestimated flow in low flow ranges (< 0.2 ml/min/g). Technetium-99m-tetrofosmin cleared rapidly from the blood and was retained in the myocardium. Resting target-to-background activity ratios (heart:lung = 3.57 +/- 1.01; heart:liver = 0.58 +/- 0.04) were acceptable 10 min after injection. CONCLUSION: Our experimental data support both the validity of 99mTc-tetrofosmin as a myocardial perfusion tracer and the use of early poststress 99mTc-tetrofosmin imaging for the assessment of myocardial perfusion in man.

Adenosine↗

[Mechanisms disordering wound healing on the lip after bilateral crossing of the inferior alveolar nerve and experimental validation of correction methods].

The mechanisms of lip wound healing after bilateral crossing of the inferior alveolar nerve (IAN) were studied on Chinchilla rabbits in 3 experimental series, 6 animals per series. In group 1 bilateral crossing of IAN was carried out, in group 2 bilateral crossing of IAN was paralleled by removal of a mucous flap in the middle of the lower lip, and in group 3 the same wound as in group 2 was created, after which the wounds in this group were daily treated with a special ointment and a single injection of lidocaine (1% solution) under the wound. The nerve crossing led to development of ulcer on the lip with degenerative changes in the vascular walls, destruction of nerve fibers, and fragmentation of some axial cylinders. Crossing of IAN simultaneously with removal of the lower lip flap led to more severe degenerative changes in the tissue. Daily treatment of the lip with the ointment and lidocaine blocking normalized wound healing. A possible mechanism of the changes observed is discussed.

Anesthetics, Local↗

Sparse 2-d arrays for 3-D phased array imaging--experimental validation.

To be able to describe more precisely the behavior of a real-time 3-D ultrasound system with either a dense array or various sparse designs, experimental data from a 2-D fully connected array prototype with 50 x 50 elements have been collected. The data have been processed off line to form synthetic aperture 3-D volume images. Simulated and experimental results are compared and show good correlation. The performance of the best sparse designs, all thinned to more than 50%, offer performances comparable to a dense array.

Imaging, Three-Dimensional↗

Experimental validation of coincidence summing corrections computed by the ETNA software.

The ETNA software has been developed to compute efficiency transfer and coincidence summing corrections. Different experiments are combined to test the validity of this last facility. Point sources with multi-gamma emitters are measured at several source-to-detector distances. Experimental correction factors are determined from the variation in the peaks' relative intensities versus the geometrical conditions. The ETNA code is used to compute the corrections due to coincidence summing for the same geometries. The calculated values are compared to the experimental ones.

Algorithms↗

Isotachophoresis at pH extremes: theory and experimental validation.

The evolution of an isotachophoresis (ITP) system in acidic or basic pH ranges can be quite different from that predicted by the existing theory. It was found theoretically and proved experimentally that the contribution of hydrogen or hydroxyl ion to conductivity of solution and/or its net charge changes the behavior of the ITP system, creating in the terminating electrolyte an additional zone close to the initial interfaces between electrolytes (leader and terminator). One boundary of the zone, being either sharp or dispersed, moves toward the leader; the other is always sharp and stationary and coincides with initial electrolytes' discontinuity. The latter can be registered in the presence of electroosmotic flow which delivers it to the detection point. In order to describe the dynamics of the ITP system at pH extremes an algorithm of analytical solution was developed, based on the revised Kohlrausch theory. Its predictions coincide well with computer simulations and experimental data. The results presented can help in a correct analysis of ITP data and explain some confusing phenomena which were considered to be artifacts.

Algorithms↗

[An experimental validation of the combined use of dimephosphon with nonsteroidal anti-inflammatory preparations].

The effects of dimephosphon combined with nonsteroidal anti-inflammatory drugs were studied in rats and mice with experimental inflammation. The influence of dimephosphon on ulcerogenic activity of these drugs was also investigated. The dependence of the combinations efficiency on the scheme of dimephosphon administration was established. Synergism in anti-inflammatory activity between dimephosphon and ortophen (sodium diclofenac), indomethacin, and acetylsalicylic acid was shown. The possibility of decreasing the ulcerogenic effects of the drugs by dimephosphon was established. The effects of dimephosphon combinations are discussed as the basis for their use in clinical practice.

Animals↗

A three-dimensional finite element model of radiofrequency ablation with blood flow and its experimental validation.

A novel three-dimensional finite element model for the study of radiofrequency ablation is presented. The model was used to perform an analysis of the temperature distribution in a tissue block heated by RF energy and cooled by blood (fluid) flow. This work extends earlier models by including true flow in place of a convective boundary condition to simulate realistic experimental conditions and to improve the prediction of blood temperatures. The effect of fluid flow on the temperature distribution, the lesion dimensions, and the ablation efficiency was studied. Three flow velocities were simulated: (i) 30, (ii) 55, and (iii) 85 mm/s. The modeling results were validated qualitatively and quantitatively with in vitro data. The correlation coefficients between the modeling and the experimental temperature measurements were 0.98, 0.97, and 0.95 for flows (i)-(iii), respectively. The slopes were 0.89, 0.95, and 1.06, and the mean root mean square differences between modeling and experimental temperature measurements were 17.3% +/- 11.6%, 15.8% +/- 13.4%, and 18.8% +/- 14.9% for flows (i)-(iii), respectively. A comparison of temperature distribution obtained with a convective boundary versus inclusion of fluid motion showed that the convective boundary resulted in a similar tissue temperature distribution, but overestimated fluid temperatures and lacked the flow asymmetry seen in the true flow model.

Arrhythmias, Cardiac↗

[Experimental validation of calcium phosphate precipitation modeling in a pellet reactor].

Calcium phosphate precipitation is studied in this article. The P-recovery process is carried out in a fluidized sand bed, the so-called pellet reactor which presents major advantages from the hydrodynamical viewpoint. The associated chemistry is yet relatively complex, due to pH gradient along the column and to the residence time of the various precipitates. The experimental observations showed three different phenomena: first, an agglomeration of fines around the sand grains is observed, second, a stagnation of fines in the bed occurs while a significant amount of fines also leaves the bed with the liquid effluent. The purpose of this work is to validate the thermodynamical model developed in our previous works on a semi-industrial sized pilot. Additional experimental runs carried out for various operating conditions showed the robustness of the model. These results open some interesting perspectives for the determination of optimized operating conditions at industrial scale.

Calcium Phosphates↗

Experimental validation of a finite element model of light-activated polymerization shrinkage.

An important consideration in improving the longevity of dental resin composite restorations is how to minimize the stresses that develop between resin composites and the wall of the preparation as the resin shrinks during polymerization. If the stress is too great, failure of the bonded interface occurs and microleakage results, with possible margin failure, staining, and secondary caries. This present project was performed to validate a previously developed FEM approach for investigating polymerization shrinkage. Light-cured resin composite was condensed into a cylindrical cavity preparation, which contained a centrally located wire. A profilometer stylus was positioned on the end of the wire to detect the initial surface displacement as the wire moved with the superficial layer of composite resin. The plots of the experimentally derived data were compared to the data plot from the FEM. The initial segments of the experimental plots matched the calculated plot very closely in shape, thus validating the FEM approach.

Dental Materials↗

Modelling of neutron survey instrument performance and experimental validation of those calculated response data.

Three moderator-type neutron survey instruments have been modelled for energy and angle dependence of the response, in greater detail than before. These response data have been verified by comparison with published experimental measurements and measurements made specifically for this project. Influences on the instrument response have also been investigated. These have included its mode-of-use and perturbations caused by variations in the instrument manufacture. The implications of these new response data have been assessed by an extensive programme of folding the responses with workplace energy distributions.

Computer Simulation↗