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Engineering and algorithm design for an image processing Api: a technical report on ITK--the Insight Toolkit.

We present the detailed planning and execution of the Insight Toolkit (ITK), an application programmers interface (API) for the segmentation and registration of medical image data. This public resource has been developed through the NLM Visible Human Project, and is in beta test as an open-source software offering under cost-free licensing. The toolkit concentrates on 3D medical data segmentation and registration algorithms, multimodal and multiresolution capabilities, and portable platform independent support for Windows, Linux/Unix systems. This toolkit was built using current practices in software engineering. Specifically, we embraced the concept of generic programming during the development of these tools, working extensively with C++ templates and the freedom and flexibility they allow. Software development tools for distributed consortium-based code development have been created and are also publicly available. We discuss our assumptions, design decisions, and some lessons learned.

Algorithms↗

MABDOSE. II: Validation of a general purpose dose estimation code.

UNLABELLED: The MABDOSE software represents a general tool to assess internal radiation dose. A suite of tests are described that validate the dosimetry system's implementation. METHODS: The validation suite is divided among tests that verify target digitalization, tumor digitalization and organ replacement, cumulated activity calculation, random number generation, radiation transport, and dose calculation. RESULTS: A comparison between Reference Man organ volumes and MABDOSE organ volumes at (5 mm)3 resolution demonstrates volume correspondence within 10% save for ten organs having dimensions smaller than the target lattice resolution. An accounting of normal organ volume replaced by an arbitrary tumor volume indicates mass is conserved. A comparison between cumulated activities generated by MABDOSE and solutions obtained analytically demonstrates exact correspondence for curve-fitting algorithms. For mathematical modeling algorithms, cumulated activity solutions converge to their correct values provided sufficient data of high precision are input, accompanied by reasonable initial estimates of rate constants. A comparison of MABDOSE results with the MIRD 3 report demonstrates good agreement (<8% difference) in absorbed fractions for spheres at energies from 20 keV to 2.75 MeV. A comparison of MABDOSE results with the Cristy-Eckerman report demonstrates marginal agreement (specific absorbed fractions within a factor of 2 for all Reference Man organs) at simulation energies of 20, 50, and 100 keV. Lack of exact correspondence is attributed to volume digitalization errors, and to differences in cross-section libraries, interpolation schemes between cross-section data points, and random number generators. Finally, the doses reported by MABDOSE correspond to the correct algebraic combination of paired cumulated activities and "S" values. CONCLUSIONS: The MABDOSE program has been validated as a general purpose computation tool for use in internal radionuclide dosimetry.

Humans↗

The art and science of chart review.

BACKGROUND: Explicit chart review was an integral part of an ongoing national cooperative project, "Using Achievable Benchmarks of Care to Improve Quality of Care for Outpatients with Depression," conducted by a large managed care organization (MCO) and an academic medical center. Many investigators overlook the complexities involved in obtaining high-quality data. Given a scarcity of advice in the quality improvement (QI) literature on how to conduct chart review, the process of chart review was examined and specific techniques for improving data quality were proposed. METHODS: The abstraction tool was developed and tested in a prepilot phase; perhaps the greatest problem detected was abstractor assumption and interpretation. The need for a clear distinction between symptoms of depression or anxiety and physician diagnosis of major depression or anxiety disorder also became apparent. In designing the variables for the chart review module, four key aspects were considered: classification, format, definition, and presentation. For example, issues in format include use of free-text versus numeric variables, categoric variables, and medication variables (which can be especially challenging for abstraction projects). Quantitative measures of reliability and validity were used to improve and maintain the quality of chart review data. Measuring reliability and validity offers assistance with development of the chart review tool, continuous maintenance of data quality throughout the production phase of chart review, and final documentation of data quality. For projects that require ongoing abstraction of large numbers of clinical records, data quality may be monitored with control charts and the principles of statistical process control. RESULTS: The chart review module, which contained 140 variables, was built using MedQuest software, a suite of tools designed for customized data collection. The overall interrater reliability increased from 80% in the prepilot phase to greater than 96% in the final phase (which included three abstractors and 465 unique charts). The mean time per chart was calculated for each abstractor, and the maximum value was 13.7 +/- 13 minutes. CONCLUSIONS: In general, chart review is more difficult than it appears on the surface. It is also project specific, making a "cookbook" approach difficult. Many factors, such as imprecisely worded research questions, vague specification of variables, poorly designed abstraction tools, inappropriate interpretation by abstractors, and poor or missing recording of data in the chart, may compromise data quality.

Data Collection↗

Tinkerbell--a tool for interactive segmentation of 3D data.

A software system for interactive manipulation of three-dimensional data has been developed, based on the Open Inventor tool kit. The primary use of this software system is in the segmentation of tomographic reconstructions of subcellular structures. To this end, the reconstruction is represented by volume rendering and displayed in stereo. A three-dimensional cursor with adjustable shape and size is used to define and isolate regions of interest inside the volume, based on the user's expert knowledge. Once isolated, the region of interest can be conveniently analyzed and displayed.

Animals↗

"Plasmo2D": an ancillary proteomic tool to aid identification of proteins from Plasmodium falciparum.

Bioinformatics tools to aid gene and protein sequence analysis have become an integral part of biology in the post-genomic era. Release of the Plasmodium falciparum genome sequence has allowed biologists to define the gene and the predicted protein content as well as their sequences in the parasite. Using pI and molecular weight as characteristics unique to each protein, we have developed a bioinformatics tool to aid identification of proteins from Plasmodium falciparum. The tool makes use of a Virtual 2-DE generated by plotting all of the proteins from the Plasmodium database on a pI versus molecular weight scale. Proteins are identified by comparing the position of migration of desired protein spots from an experimental 2-DE and that on a virtual 2-DE. The procedure has been automated in the form of user-friendly software called "Plasmo2D". The tool can be downloaded from http://144.16.89.25/Plasmo2D.zip.

Animals↗

Automatic segmentation as a tool for examining the handwriting process of children with dysgraphic and proficient handwriting.

The purpose of this study was to use an x-y digitizer to collect handwriting samples typical of those written by the child in his or her natural environment, to analyze these samples with novel segmentation algorithms, and to present them visually in ways that illuminate spatial and temporal dynamic features amongst children with dysgraphic and proficient handwriting. While using the POET software (Penmanship Objective Evaluation Tool), a paragraph was copied onto paper affixed to an x-y digitizer by third-grade students, 14 with proficient and 14 with poor handwriting. A segmentation algorithm was developed to automatically isolate writing segments. Results yielded significant differences between the groups in various measures, including the number of the raw segments (i.e., the number of segments before combined with letters), the number of reverse segments (i.e., when the participant returned to correct or complete a previously written segment), the number of letters per minute, and the mean "In-Air" time between letters. Variability in both the spatial and temporal domains of instances of the same letter throughout the text was greater among the dysgraphic handwriters in comparison to the variability among the proficient. These results demonstrated the potential of using automated analytic techniques and visual display to achieve a more comprehensive understanding of handwriting difficulties.

Agraphia↗

A model-based approach for automated in vitro cell tracking and chemotaxis analyses.

BACKGROUND: Chemotaxis may be studied in two main ways: 1) counting cells passing through an insert (e.g., using Boyden chambers), and 2) directly observing cell cultures (e.g., using Dunn chambers), both in response to stationary concentration gradients. This article promotes the use of Dunn chambers and in vitro cell-tracking, achieved by video microscopy coupled with automatic image analysis software, in order to extract quantitative and qualitative measurements characterizing the response of cells to a diffusible chemical agent. METHODS: Previously, we set up a videomicroscopy system coupled with image analysis software that was able to compute cell trajectories from in vitro cell cultures. In the present study, we are introducing a new software increasing the application field of this system to chemotaxis studies. This software is based on an adapted version of the active contour methodology, enabling each cell to be efficiently tracked for hours and resulting in detailed descriptions of individual cell trajectories. The major advantages of this method come from an improved robustness with respect to variability in cell morphologies between different cell lines and dynamical changes in cell shape during cell migration. Moreover, the software includes a very small number of parameters which do not require overly sensitive tuning. Finally, the running time of the software is very short, allowing improved possibilities in acquisition frequency and, consequently, improved descriptions of complex cell trajectories, i.e. trajectories including cell division and cell crossing. RESULTS: We validated this software on several artificial and real cell culture experiments in Dunn chambers also including comparisons with manual (human-controlled) analyses. CONCLUSIONS: We developed new software and data analysis tools for automated cell tracking which enable cell chemotaxis to be efficiently analyzed.

Cell Culture Techniques↗

Application of the RLGS image analysis tool (RAT) to the construction of a genetic linkage map of recombinant inbred strain SMXA.

The construction of a genetic linkage map is the first, fundamental step to analyze the genetic properties of any organism. For this purpose, the restriction landmark genome scanning method (RLGS) can be used and has been shown to have high productivity in various genetic analyses. However, construction of a genetic linkage map by the RLGS method is laborious, because hundreds of spots must be scored, usually by visual observation. In order to reduce human involvement in the data processing, we developed an image analysis software, RAT (RLGS Analysis Tool). We evaluated its accuracy and feasibility by comparing the parental distribution patterns of RLGS spots obtained by RAT and by human observation, using Syrian hamster strain backcross progeny. We then used RAT to construct a genetic linkage map of the recombinant inbred strain SMXA. We were able to obtain 121 progenitor strain-specific spots that were assigned to a specific chromosome.

Animals↗

An open medical imaging workstation architecture for platform-independent 3-D medical image processing and visualization.

A need for an entirely new medical workstation design was identified to increase the deployment of 3-D medical imaging and multimedia communication. Recent wide acceptance of the Word Wide Web (WWW) as a general communication service within the global network has shown how big the impact of standards and open systems can be. Information is shared among heterogeneous systems and diverse applications on various hardware platforms only by agreeing on a common format for information distribution. For medical image communications, the Digital Imaging and Communication in Medicine (DICOM) standard is possibly anticipating such a role. Logically, the next step is open software: platform-independent tools, which can as easily be transferred and used on multiple platforms. Application of the platform-independent programming language Java enables creation of plug-in tools, which can easily extend the basic system. Performance problems inherent to all interpreter systems can be circumvented by using a hybrid approach. Computationally intensive functions like image processing functions can be integrated into a natively implemented optimized image processing kernel. Plug-in tools implemented in Java can utilize the kernel functions via a Java-wrapper library. This approach is comparable to the implementation of computationally intensive operations in hardware.

Computer Communication Networks↗

Animal disease outbreak control: the use of crisis management tools.

In this era of globalisation the effective control of animal disease outbreaks requires powerful crisis management tools. In the 1990s software packages for different sectors of the government and agricultural industry began to be developed. In 2004, as a special application for tracking the movement of animals and animal products, the European Union developed the Trade Control and Expert System (TRACES) on the basis of its predecessor, the ANImal MOvement (ANIMO) project. The nationwide use of the ANIMO system by the veterinary authorities in Germany marked the beginning of the development in 1993 of a computerised national animal disease reporting system--the TierSeuchenNachrichten (TSN)--using the ANIMO hardware and software components. In addition to TRACES and TSN the third pillar for the management of animal disease outbreaks and crises in Germany is the national cattle and swine database--called Herkunftssicherungs- und Informationssystem für Tiere. A high degree of standardisation is necessary when integrating the different solutions at all levels of government and with the private sector. In this paper, the authors describe the use of these tools on the basis of their experience and in relation to what we can do now and what we should opt for in the future.

Animal Diseases↗

Multianalytical system (MAS): software for enzyme-linked immunosorbent assay (ELISA) data processing with applications to screening and diagnostic tests.

A microcomputer software package for determining the concentration of either the antibody or antigen from ELISA data for IBM PC compatible is presented. In the program optical densities (OD) and fluorescence obtained from 96-well ELISA plate can be input either directly, by interfacing with different brands of microplate reader such as Multiskan II Plus and Organon Teknika to the computer or manually. This software utilizes some mathematical and statistical models to fit the standard curve of each assay and interpolate analyte concentration using data from OD or fluorescence measurements. Cubic spline (Guardabasso et al., 1988), bezier and polynomial (Rodbard, 1979; Baud et al., 1991) interpolation formulas can be used to fit the data over the entire range for estimating the antibody or antigen concentration of the unknown samples whose OD or fluorescence is beyond the entire range. This software package, based on the concentration values of the analyte determined in different fluids (Núnez et al., 1994; Morales et al., 1994) and with some rules and algorithms, is used to calculate the parameters of screening and diagnostic tests such as sensitivity, specificity and predictive values (Coughlin et al., 1992). With the construction of the Receiver Operating Characteristic (ROC) curve it is possible to analyse different values of the sensitivity and specificity of the screening and diagnostic tests. A comparative statistical test for two populations that are non-normally distributed using a non-parametric Mann-Whitney test is provided. This software is an expandable tool designed for general use in clinical and experimental applications, including diagnostic and screening tests.

Antibodies↗

Rapid recognition of aberrant dHPLC elution profiles using the Transgenomic Navigator software.

Despite the availability of numerous technologies for detecting mutations, only a few have been formatted for automated mutation calling. Here, we evaluate the utility of the Transgenomic Navigator software to facilitate automated detection of aberrant denaturing high performance liquid chromatography (dHPLC) elution profiles. We used dHPLC to identify germline variants in MSH6, NEIL2, NEIL3, and OGG1 in 172 patients with multiple colorectal adenomas. 3,747 dHPLC profiles were analysed with the Navigator software using three levels of analysis, each differing in the degree of operator input. 43.5% (60/138) and 98.3% (59/60) of products with profiles distinct from wild type ('outliers') harboured novel variants under Level 1 and Levels 2/3 analysis conditions, respectively. We also assessed the utility of the software to rapidly detect samples carrying common polymorphisms by analysing regions of the genes that harbour polymorphisms with minor allele frequencies between 8 and 40%, therein analysing 2,784 profiles. We showed that 1573/1612 (97.6%) and 1137/1172 (97.0%) of PCR products were correctly classified as wild-type and variant, respectively (Level 3 analysis conditions). Finally, we assessed the utility of the software to detect novel variants in fragments that also harboured common polymorphisms and showed that 59/61 (96.7%) of products with profiles outlying both the wild type and polymorphism groups harboured novel variants. We conclude that the Navigator software provides an excellent tool for rapid discrimination of aberrant dHPLC elution profiles that harbour sequence variants.

Chromatography, High Pressure Liquid↗

[The general practitioner and clinical records: a survey of the knowledge of users of a software package].

The FATMA project--subproject 6, Line of Research 2--aims at implementing a new computerized information network for general practitioners using the same kind of software and homogeneously located throughout Italy. Thus, patients' case form data can be collected for public health purposes. After a study of literature in order to check whether other countries had implemented similar projects and what they consisted of, a survey based on a computerized questionnaire was carried out on a group of g.p.s. who had already received a software for the management of their clinical and professional activities from Janssen Informedica. This survey aimed at judging some aspects of users in order to select potential monitors of the information network who would test a new software. The analysis regards both g.p.s' social and professional data and the use of a computer package with reference to the quality and quantity of the clinical data they input. 2,010 questionnaires were filled in all their parts and mailed back to Informedica. It came out that g.p.s. believe more and more they can improve the organization and management of their work by using a software equipped with routines and easy access procedures so that clinical data, diagnostic reports and treatment can be collected, placed on files and updated. Thus, a new software should be developed. While meeting g.p.s' needs, it must overcome the limits of packages now available concerning the possibility of carrying out epidemiological studies. The software can become a tool to collect clinical data of patients, diseases and diagnostic procedures through standard protocols directly from g.p.s records.

Adult↗

Clinical, information and business process modeling to promote development of safe and flexible software.

Using a factorial vignette survey and modeling methodology, we developed clinical and information models - incorporating evidence base, key concepts, relevant terms, decision-making and workflow needed to practice safely and effectively - to guide the development of an integrated rule-based knowledge module to support prescribing decisions in asthma. We identified workflows, decision-making factors, factor use, and clinician information requirements. The Unified Modeling Language (UML) and public domain software and knowledge engineering tools (e.g. Protégé) were used, with the Australian GP Data Model as the starting point for expressing information needs. A Web Services service-oriented architecture approach was adopted within which to express functional needs, and clinical processes and workflows were expressed in the Business Process Execution Language (BPEL). This formal analysis and modeling methodology to define and capture the process and logic of prescribing best practice in a reference implementation is fundamental to tackling deficiencies in prescribing decision support software.

Asthma↗

[The effect of specialist supervision on the quality of medical documentation in occupational health services].

The effect if different factors on the quality of documentation on medical prophylactic examinations in occupational health services is presented. Following the binding legal regulations, the tools (forms and application software) for evaluating the quality of documentation by regional specialists has been developed. The medical documentation has been kept by authorized doctors using old and new forms. The results of three successive controls carried out in three voivodships during the third term of 1996 showed improved quality parameters (transparency and input of appropriate data) due to new pattern of medical documentation. Nevertheless, the key role in quality assurance of medical documentation is played by a regional specialists, equipped with suitable tools facilitating assessment of documentation kept by individual doctors.

Documentation↗

Processing of gene expression data generated by quantitative real-time RT-PCR.

Quantitative real-time PCR represents a highly sensitive and powerful technique for the quantitation of nucleic acids. It has a tremendous potential for the high-throughput analysis of gene expression in research and routine diagnostics. However, the major hurdle is not the practical performance of the experiments themselves but rather the efficient evaluation and the mathematical and statistical analysis of the enormous amount of data gained by this technology, as these functions are not included in the software provided by the manufacturers of the detection systems. In this work, we focus on the mathematical evaluation and analysis of the data generated by quantitative real-time PCR, the calculation of the final results, the propagation of experimental variation of the measured values to the final results, and the statistical analysis. We developed a Microsoft Excel-based software application coded in Visual Basic for Applications, called Q-Gene, which addresses these points. Q-Gene manages and expedites the planning, performance, and evaluation of quantitative real-time PCR experiments, as well as the mathematical and statistical analysis, storage, and graphical presentation of the data. The Q-Gene software application is a tool to cope with complex quantitative real-time PCR experiments at a high-throughput scale and considerably expedites and rationalizes the experimental setup, data analysis, and data management while ensuring highest reproducibility.

Computational Biology↗

MABDOSE. I: Characterization of a general purpose dose estimation code.

The MABDOSE software represents a general tool to perform internal radiation dosimetry. It uses a three-dimensional lattice in which to conduct radiation transport, scoring energy deposition in discrete voxels. The dosimetry system currently relies on the same algorithm used by the MIRD committee for photon transport, and assumes local deposition of particulate energy. A mathematical description of the dosimetry system's implementation is given. Additionally, a characterization of the system with respect to memory requirements, data libraries used, and simulation timing benchmarks, is presented. Validation of the software is presented in a companion manuscript.

Antibodies, Monoclonal↗

A simple method for hardware and software evaluation.

Subjective data are often the only data available for making decisions and choices in both hardware and software development. These data are therefore both important and valuable. Their importance is such that it is necessary to elicit subjective data from a variety of sources and in a manner that is relatively unbiased. A method which requires participants to compare all criteria and all proposed concepts by pairs provides a non-statistical mechanism for collecting data from a broad base of expertise, for giving appropriate weight to all input, and for reducing personal bias. These characteristics make a comparison of all pairs a useful tool for hardware and software evaluation when decisions and choices must be made. The efficacy of the method was recently demonstrated in the selection of a restraint-attachment device for Space Station Freedom.

Journal Article↗