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PubMed2005

Fast image acquisition and processing on a TV camera-based portal imaging system.

The present paper describes the fast acquisition and processing of portal images directly from a TV camera-based portal imaging device (Siemens Beamview Plus). This approach employs not only hard- and software included in the standard package installed by the manufacturer (in particular the frame grabber card and the Matrox Intellicam interpreter software), but also a software tool developed in-house for further processing and analysis of the images. The technical details are presented, including the source code for the Matrox interpreter script that enables the image capturing process. With this method it is possible to obtain raw images directly from the frame grabber card at an acquisition rate of 15 images per second. The original configuration by the manufacturer allows the acquisition of only a few images over the course of a treatment session. The approach has a wide range of applications, such as quality assurance (QA) of the radiation beam, real-time imaging, real-time verification of intensity-modulated radiation therapy (IMRT) fields, and generation of movies of the radiation field (fluoroscopy mode).

Humans↗

PubMed2003

Evaluation and interpretation of results for three cross-over designs.

In cross-over designs, individual sequences of treatments are applied to the animals. Within such designs it is possible that every treatment could modify the effect of the subsequent treatment applied to the same animal. We compared three cross-over designs each with three treatments, three periods, and two blocks. This comparison was done with respect to the variance of the estimations of the effects and its biases caused by the interactions between the treatment and the carry over effect of the foregoing treatment. Moreover, different methods of estimating variance components and calculating the degrees of freedom were compared by means of simulation. If the animal variance component is small, then the bias of the REML estimator of the variance components is greater than one of the widespread ANOVA-estimator called 'TYPE3'. But nevertheless, the mean squared error of this estimation is smaller in the case of REML in comparison to ANOVA. Therefore, the REML method should be preferred. For calculating the degrees of freedom, the Kenward-Roger method should be used. After applying this method, the true significance level is almost equal to its required value, but if the Satterthwaite method is used, the true significance level will be too high. If the interaction (treatment x carry over) is ignored in the model although it exists, the standard error of the treatment effect estimation is too great, and, therefore, the true significance level is too small. The methods which have been evaluated are available in the SAS-procedure MIXED (SAS Institute, 1999a). To assist the investigation of cross-over designs by using this software, we developed programs for data management and data analysis. These programs are available from the first author.

Analysis of Variance↗

PubMedDate not supplied

Ultrastructural telepathology--remote EM-diagnostic via Internet.

New collaboratory opportunities in ultrastructural research and diagnostics are now available on the Internet through the combination of digital image acquisition, remote operation of modern digitally controlled and automated electron microscopes, and the development of software specifically tailored for collaboratory needs. Remote experts can examine samples directly, and unique instruments can be utilized from anywhere. In the case of diagnostic dilemmas, the second-opinion expert is no longer constrained by problems inherent in the interpretation of preselected images. The remote examiner can independently choose the area of interest on the sample as well as select the appropriate magnification for an accurate diagnosis. With these capabilities and together with teleconferencing tools and securely accessible databases on-line, telepathology can provide increased effectiveness and support for diagnostics, research, and teaching in many areas. The authors report their experience with remote electron microscope diagnoses of pathological samples using two different dynamic imaging systems and discuss the main technical issues encountered. It appears that only minor technical issues need to be resolved before ultrastructural telepathology can be promoted for routine use in areas with high-speed Internet access.

Dementia, Multi-Infarct↗

PubMed2004

Radiological progression of joint damage in a longitudinal cohort of early DMARD-treated rheumatoid arthritis patients followed for 10 years.

OBJECTIVE: The efficacy of DMARD therapy in rheumatoid arthritis (RA) can be judged by radiological analysis. This study aimed to determine the time-dependent progression of joint damage, acute-phase response, and rates of radiologic progression in early DMARD-treated RA patients over 10 years. PATIENTS AND METHODS: We evaluated outpatient records, and radiographs of hands and feet of 54 early RA patients on DMARDs for 10 years. Radiographs were quantified by the Larsen method using recently developed quantification software. RESULTS: Radiological damage attenuated, with disease progression from baseline to Year 10 [correlation coefficient (r)=0.95, probability (p)<0.001]. Radiographic scores progressed more rapidly during the first 5 years than thereafter. Cumulative erythrocyte sedimentation rate (ESR) was strongly correlated with radiological progression (p<0.001, r=0.88). CONCLUSION: Our findings reveal a higher amount of radiographic RA progression during the first years of DMARD treatment. Thus, our data provide strong evidence for the importance of both early DMARD therapy and continuous radiographic assessments in RA.

Adult↗

PubMed2005

Two-phase computational fluid dynamics assessment of bubble plume in air-diffuser destratification.

Hydrodynamic flow patterns and behavior induced by bubble plumes in a linearly stratified fluid are studied. To optimize an air-diffuser destratification system, we used computational fluid dynamics software to develop a two-phase (air-water) destratification model. The model enables us to simulate complicated stratification conditions with different densities and source strengths. We conducted laboratory experiments to verify the model in thermally stratified fresh water. The computational fluid dynamics model performs well when the plume number ranges from 30 to 600. We successfully explain various phenomena, including the hydrodynamic behavior of bubble plumes and turbulent three dimension flow patterns. Our approach provides a level of detail not possible with other one-dimensional plume models. Contrary to the findings of other researchers, our experiments and computational fluid dynamics simulation indicate that the energy conversion efficiency increases as plume number increases; moreover, the three flow types do not occur in the same plume number regimes defined in other research. The difference is apparently due to the effect of the bubble size.

Air Movements↗

PubMed1998

Arizona hazardous air pollutants monitoring program

In order to evaluate the existing risk to public health in Arizona related to hazardous air pollution, ambient air monitoring for selected hazardous air pollutants (HAPs) was carried out in 1994-1996 in several representative urban and rural areas of Arizona. A wide range of organic HAPs was monitored, requiring a variety of sampling and analysis methods. Stainless steel SUMMA canisters were used for collection of volatile hydrocarbons and halocarbons, which were analyzed by capillary gas chromatography with flame ionization and electron capture detection (GC-FID/ECD). Carbonyl compounds were collected using 2,4-dinitrophenylhydrazine-impregnated cartridges and analyzed by high performance liquid chromatography with ultraviolet detection. Semi-volatile and non-volatile polycyclic aromatic compounds were collected using a sampling train consisting of a filter followed by a PUF/XAD-4/PUF sandwich cartridge. Following extraction, samples were analyzed by capillary GC with mass spectrometric detection (GC-MS). Database software was developed for data processing and reporting functions. This paper describes the sampling strategy and the sampling and analysis methods employed in the monitoring program and presents a summary of all the results obtained during the duration of the sampling program.

Journal Article↗

PubMed2002

Probabilistic assessment of biodegradability based on metabolic pathways: catabol system.

A novel mechanistic modeling approach has been developed that assesses chemical biodegradability in a quantitative manner. It is an expert system predicting biotransformation pathway working together with a probabilistic model that calculates probabilities of the individual transformations. The expert system contains a library of hierarchically ordered individual transformations and matching substructure engine. The hierarchy in the expert system was set according to the descending order of the individual transformation probabilities. The integrated principal catabolic steps are derived from set of metabolic pathways predicted for each chemical from the training set and encompass more than one real biodegradation step to improve the speed of predictions. In the current work, we modeled O2 yield during OECD 302 C (MITI I) test. MITI-I database of 532 chemicals was used as a training set. To make biodegradability predictions, the model only needs structure of a chemical. The output is given as percentage of theoretical biological oxygen demand (BOD). The model allows for identifying potentially persistent catabolic intermediates and their molar amounts. The data in the training set agreed well with the calculated BODs (r2 = 0.90) in the entire range i.e. a good fit was observed for readily, intermediate and difficult to degrade chemicals. After introducing 60% ThOD as a cut off value the model predicted correctly 98% ready biodegradable structures and 96% not ready biodegradable structures. Crossvalidation by four times leaving 25% of data resulted in Q2 = 0.88 between observed and predicted values. Presented approach and obtained results were used to develop computer software for biodegradability prediction CATABOL.

Biodegradation, Environmental↗

PubMed1995

Experiences with the application of QSAR in the routine of the notification procedure.

On behalf of the Umweltbundesamt the Fraunhofer Gesellschaft has developed a software system (SAR-system) comprising more than 90 estimation models for endpoints relevant in environmental risk assessment. These estimation models are based on the approach of quantitative structure-activity relationships (QSAR). All models were checked for their validity and application range. In the last months the Umweltbundesamt started to test the applicability of some models concerning the endpoints fish acute toxicity, daphnia acute toxicity and ready (i.e., ultimate) biodegradability in the daily routine of the notification procedure. For testing these models the corresponding confidential data given in the dossiers of substances notified 1993 in Germany, were used. We were able to make calculations for 36% of the notified substances. For the remaining 64% of the chemicals it was impossible to accomplish SAR estimations due to several reasons, e.g., ionic structure of the compounds. Different results for the applicability of the mentioned endpoints are obtained. The predictions of the fish and Daphnia toxicity are in sufficient agreement with the experimental results, in case of the fish toxicity we receive 58% agreement, for the Daphnia toxicity 56%. The corresponding values which were obtained in the US EPA/E.C. Joint Project on the evaluation of (quantitative) structure activity relationships were 82.3% and 70.9%. About 300 different models were used for the calculations of these endpoints within the framework of the EPA/EC project. The SAR-system presented here contains 8 models for estimating the fish toxicity and 6 models for the Daphnia toxicity. For the prediction of the biodegradability the results obtained with the SAR-system are rather poor and have to be improved. Meanwhile the SAR-system is commercially available and can be ordered at the Fraunhofer Institute for Environmental Chemistry and Ecotoxicology, Schmallenberg (Germany).

Animals↗

PubMed2002

Experimenting with new paradigms for medical education and the emergence of a distance learning degree using the internet: teaching evidence-based medicine.

This paper is focused on designing and developing a teaching environment associated with an introductory course in evidence-based medicine designed for undergraduates. Attempting to break away from the traditional educational model based on acquisition of factual knowledge, we developed a software tool centred on content management, student assessment and feedback. We ran this course on an educational website, using chat rooms and electronic mail for trainer-trainee communication over one academic year. The website served as a repository for knowledge and information and presented freestanding web-based interactive study modules and a non-interactive degree course. Trainers and trainees responded favourably to the computer applications and the Internet. This project demonstrated the feasibility of computer-aided learning and the advantages of distance teaching over the Internet.

Computer-Assisted Instruction↗

PubMed2006

Interactive analysis of Belgian vital statistics on the Internet.

The purpose of the Centre for Operational Research in Public Health (CORPH) is to optimize the accessibility to health information, thus making it possible to measure and follow up the health status of the Belgian population. The Standardized Procedures for Mortality Analysis (SPMA) software was developed in order to facilitate the use of vital statistics for health policy-makers and scientific researchers. Nowadays, SPMA is available on the Internet, because accessibility to health information is crucial. SPMA serves via a system of menus as the interface between databases (population, birth, and mortality) on one hand and statistical procedures on the other hand. Users can choose the parameters such as year, cause of death, geographical level, and statistical indicator, and so dynamic reports are produced 'on demand'. These procedures are available for the following modules: overall mortality, specific cause mortality, and perinatal statistics. Analysis can be carried out for one specific year or for a period over time. Pre-defined procedures accessible through menus make SPMA user-friendly, as it can be used without any preliminary knowledge of the statistical package. Tables, charts, or maps display the results. Users need only an Internet browser to access the application.

Adolescent↗

PubMed2001

Monte Carlo dose verification for intensity-modulated arc therapy.

Intensity-modulated arc therapy (IMAT), a technique which combines beam rotation and dynamic multileaf collimation, has been implemented in our clinic. Dosimetric errors can be created by the inability of the planning system to accurately account for the effects of tissue inhomogeneities and physical characteristics of the multileaf collimator (MLC). The objective of this study is to explore the use of Monte Carlo (MC) simulation for IMAT dose verification. The BEAM/DOSXYZ Monte Carlo system was implemented to perform dose verification for the IMAT treatment. The implementation includes the simulation of the linac head/MLC (Elekta SL20), the conversion of patient CT images and beam arrangement for 3D dose calculation, the calculation of gantry rotation and leaf motion by a series of static beams and the development of software to automate the entire MC process. The MC calculations were verified by measurements for conventional beam settings. The agreement was within 2%. The IMAT dose distributions generated by a commercial forward planning system (RenderPlan. Elekta) were compared with those calculated by the MC package. For the cases studied, discrepancies of over 10% were found between the MC and the RenderPlan dose calculations. These discrepancies were due in part to the inaccurate dose calculation of the RenderPlan system. The computation time for the IMAT MC calculation was in the range of 20-80 min on 15 Pentium-Ill computers. The MC method was also useful in verifying the beam apertures used in the IMAT treatments.

Dose-Response Relationship, Radiation↗

PubMed2003

First images of a digital autoradiography system based on a Medipix2 hybrid silicon pixel detector.

We present the first images of beta autoradiography obtained with the high-resolution hybrid pixel detector consisting of the Medipix2 single photon counting read-out chip bump-bonded to a 300 microm thick silicon pixel detector. This room temperature system has 256 x 256 square pixels of 55 microm pitch (total sensitive area of 14 x 14 mm2), with a double threshold discriminator and a 13-bit counter in each pixel. It is read out via a dedicated electronic interface and control software, also developed in the framework of the European Medipix2 Collaboration. Digital beta autoradiograms of 14C microscale standard strips (containing separate bands of increasing specific activity in the range 0.0038-32.9 kBq g(-1)) indicate system linearity down to a total background noise of 1.8 x 10(-3) counts mm(-2) s(-1). The minimum detectable activity is estimated to be 0.012 Bq for 36,000 s exposure and 0.023 Bq for 10,800 s exposure. The measured minimum detection threshold is less than 1600 electrons (equivalent to about 6 keV Si). This real-time system for beta autoradiography offers lower pixel pitch and higher sensitive area than the previous Medipix1-based system. It has a 14C sensitivity better than that of micro channel plate based systems, which, however, shows higher spatial resolution and sensitive area.

Autoradiography↗

PubMed2004

A new ultrasonic transducer for improved contrast nonlinear imaging.

Second harmonic imaging has provided significant improvement in contrast detection over fundamental imaging. This improvement is a result of a higher contrast-to-tissue ratio (CTR) achievable at the second harmonic frequency. Nevertheless, the differentiation between contrast and tissue at the second harmonic frequency is still in many situations cumbersome and contrast detection remains nowadays as one of the main challenges, especially in the capillaries. The reduced CTR is mainly caused by the generation of second harmonic energy from nonlinear propagation effects in tissue, which hence obscures the echoes from contrast bubbles. In a previous study, we demonstrated theoretically that the CTR increases with the harmonic number. Therefore the purpose of our study was to increase the CTR by selectively looking to the higher harmonic frequencies. In order to be able to receive these high frequency components (third up to the fifth harmonic), a new ultrasonic phased array transducer has been constructed. The main advantage of the new design is its wide frequency bandwidth. The new array transducer contains two different types of elements arranged in an interleaved pattern (odd and even elements). This design enables separate transmission and reception modes. The odd elements operate at 2.8 MHz and 80% bandwidth, whereas the even elements have a centre frequency of 900 kHz with a bandwidth of 50%. The probe is connected to a Vivid 5 system (GE-Vingmed) and proper software is developed for driving. The total bandwidth of such a transducer is estimated to be more than 150% which enables higher harmonic imaging at an adequate sensitivity and signal to noise ratio compared to standard medical array transducers. We describe in this paper the design and fabrication of the array transducer. Moreover its acoustic properties are measured and its performances for nonlinear contrast imaging are evaluated in vitro and in vivo. The preliminary results demonstrate the advantages of such a transducer design for improved contrast detection.

Acoustics↗

PubMed2005

Interpretation and evaluation of the gamma index and the gamma index angle for the verification of IMRT hybrid plans.

In IMRT, the method for a quantitative comparison of two-dimensional dose distributions is still under development. The gamma evaluation method proposed by Low et al is the most accepted approach and has been adapted by many groups. Based on the concept of Low et al we developed a software tool with an intelligent search algorithm to minimize the calculation time. For the interpretation of deviations a y angle distribution and other tools (dose difference map, profiles, y area histograms, etc) are integrated in the software package. Ten hybrid plans are included in the verification study containing 6 IMRT head and neck cases, 2 IMRT prostate cases and one IMRT paravertebral case as well as a standard uniform intensity conformal 4 field box treatment for comparison. IMRT plans are realized with a segmental MLC delivery technique. The fields of a hybrid plan are applied at once and dose distributions are measured with films in three planes of a verification phantom. All y vector calculations are based on a 3% dose criterion and a 3 mm DTA acceptance criterion. The mean value gamma(mean) (mean value in the y distribution) of the various IMRT plans is 0.45+/-0.10 (1 SD). On average, the percentage of points exceeding the acceptance criteria of gamma < or = 1 (gamma > 1) is 5.8+/-5.4% (1 SD). The mean value of gamma 1% (1% of points have an equal or higher gamma value) is 1.47+/-0.59 (1 SD) for IMRT plans. In 5 out of 27 planes, gamma > 1 is substantially larger than the average. This is also indicated in gamma area histograms. Planes with large areas outside the tolerance criteria were further evaluated using gamma angle distributions. This additional information indicates that the large areas with high gamma values are dominated by the dose difference. It is shown that the deviations are influenced by tongue and groove effects. From the statistical evaluation of gamma values (e.g. gamma area histogram), acceptance criteria for IMRT hybrid plans can be defined. For the interpretation of the gamma maps, distributions of the gamma angle and traditional evaluation methods, such as dose profiles, are still very useful.

Algorithms↗

PubMed2003

Time course of cortical hemorrhages after closed traumatic brain injury: statistical analysis of posttraumatic histomorphological alterations.

We examined 305 autopsied brains for histomorphological alterations to determine the time course of reactions in cortical hemorrhages following traumatic closed brain injury. Eighteen morphological criteria were considered: red blood cells (RBCs), polymorphonuclear leukocytes (PMNs), macrophages (Ms), RBC-containing Ms, hemosiderin, hematoidin, lipid-containing Ms, fibroblasts, endothelial cells, collagenous fibres, gemistocytic astrocytes, fibrillary gliosis, hemosiderin-containing astrocytes, neuronal damage, neuronophagy, axonal swelling (beta-amyloid precursor protein: beta-APP), axonal bulbs (van Gieson stain), and mineralisation of neurons. The interval between the time of brain injury and death ranged from 1 min to 58 years. Following routine staining and immunohistochemical staining of microglia (CD68), astrocytes (GFAP) and injured axons (beta-APP), paraffin sections were examined by light microscopy for the presence of the selected histomorphological features. For each cytomorphological phenomenon, the time at which it could be demonstrated for the first time and for the last time (observation period) was determined. The relative frequency of each criterion was established for each observation period. The limits of confidence for the respective relative frequencies were estimated with a reliability of 95% according to Clopper and Pearson. An apparent correlation was found between the frequency of a given histomorphological phenomenon and the length of the posttraumatic interval. To check for accuracy of prediction, half of the cases (group 1; n = 153) were used to develop a multistage evaluation model; half (group 2; n = 152) were used to evaluate the validity of the data of group 1. Applying this model, 117 of the 152 control group cases (76.97%) could be correctly classified and further 26 cases (17.11%) being assigned to an interval close to the correct interval. Thus, this model allows classification of the correct posttraumatic interval or an interval close to the correct posttraumatic interval in about 95% of cases. We developed a software program that allows the estimation of survival time of TBI based on the relative frequency of the 18 morphological features. Applying this software will help to estimate the posttraumatic interval of cortical hemorrhages following TBI of unknown survival time.

Adolescent↗

PubMed2003

Prospects for delivery of recombinant angiostatin by cell-encapsulation therapy.

Implantation of encapsulated nonautologous cells that have been genetically modified to secrete proteins with tumor suppressor properties represents an alternative nonviral strategy to cancer gene therapy. We report an approach to raise the yield of recombinant proteins from encapsulated cells substantially. We hypothesized that by optimizing the encapsulation procedure, the production efficacy from the encapsulated cells could be increased. HEK 293 EBNA cells were genetically engineered to produce angiostatin. Encapsulation was performed by varying bead size, cellular density, homogeneity, and ion composition of the gel. The morphology and viability of the cells and the release of angiostatin were studied. Computer software was developed for three-dimensional imaging and quantification of cell viability. Angiostatin production was assessed at 3, 6, and 11 weeks using enzyme-linked immunosorbent assay (ELISA). Inhomogeneous gels facilitated cell growth and viability. The most efficient inhomogeneous microcapsules were generated by reducing the size and cellular density of the beads. The viability and the production of angiostatin were 3 to 5 times higher than in the homogeneous capsules. Significant amounts of viable cells were present in both homogeneous and inhomogeneous beads after 6 months of culture. The stability of the alginate matrix was greatly enhanced by gelling in the presence of barium. In conclusion, the viability and production efficacy of recombinant angiostatin from alginate-encapsulated cells can be increased considerably by optimizing the encapsulation procedure. The development of such optimized microcapsules brings cell-encapsulation therapy further towards clinical use in cancer therapy.

Alginates↗

PubMedDate not supplied

In vitro, in vivo, in silico: computational systems in tissue engineering and regenerative medicine.

The emergence of computational systems in tissue engineering and regenerative medicine is paralleling the rapid rise of new technology. Developments in software and hardware have allowed access to the huge data streams that are now available. The Human Genome Project led the way and opened many avenues for other branches of science and biology with extensive but contained databanks. The availability of vast amounts of data means nothing without the ability to integrate the information into a useful form. Tissue engineering has always been a practical science in which function and utility are key objectives. This review delineates key areas of this rapidly ascending branch of science and illustrates examples central to the successful integration of computational methods.

Animals↗

PubMed2004

High throughput SNP genotyping with two mini-sequencing assays.

Two mini-sequencing methods, FP-TDI (template-directed dye-terminator incorporation with fluorescence-polarization) and MassArray (matrix assisted laser desorption ionization time of flight detection mass spectrometry), were optimized. A numeric standard was introduced to evaluate the SNP scoring quality of FP-TDI assay, thus made the optimization work easier. At the same time, using multi-PCR technology, 8-plex genotyping of MassArray assay was successfully carried out, some softwares were developed and the data process of MassArray was highly automated. Then these two methods were applied to high throughput SNP genotyping, the accuracy, efficiency and robustness were compared. The result shows FP-TDI is more sensitive to the concentration of SNPprimer and PCR product, as well as extension cycles, the SNPprimer length of FP-TDI should be 24 to 30 bp long, whereas MassArray assay prefers to be as short as only 16 bp. Altogether 6440 SNP sites of human chromosome 3 were genotyped in a sample of 90 individuals, 4792 sites by FP-TDI assay and 1648 sites by MassArray assay, the success rates of FP-TDI and MassArray were 67.7% and 93.6% respectively. The throughput of MassArray was higher than FP-TDI, and the cost of MassArray was lower, MassArray was more suitable for high throughput SNP genotyping.

DNA↗