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Add-in macros for rapid and versatile calculation of non-compartmental pharmacokinetic parameters on Microsoft Excel spreadsheets.

We developed a package of macro programs (named PK_MOMENT) to automatically calculate non-compartmental pharmacokinetic parameters on Microsoft Excel spreadsheets. These macros include rigorous algorithms to execute moment calculations in a comprehensive manner. An optimum number of terminal data points for infinite-time extrapolation can be calculated with one of these macros so that automatic calculation of infinite moment parameters is possible. The moment calculation with PK_MOMENT provided satisfactory results using the hybrid (mixed linear-logarithmic) trapezoidal method rather than the conventional linear trapezoidal method. The macro-aided pharmacokinetic analyses turned out to be useful in that the macro-containing cells can be easily copied and pasted to analyze other data sets and that powerful tools of Excel can be utilized. The use of our macros will be significantly time-saving for routine pharmacokinetic analyses, considering that pharmacokinetic data are usually stored in a spreadsheet format, typically with Excel.

Administration, Oral↗

Implementation of a reference management system, MacRefer, under HyperCard.

We have developed a reference management system, MacRefer, using HyperTalk on Macintosh personal computers. Using this program, one can automatically acquire data from databases created by EndNote Plus and from OVID- or Medlar-formatted records downloaded via an online use of Medline. The MacRefer's capability of formatting bibliographic database in user-defined formats is comparable with the exemplified bibliography maker, EndNote Plus. Moreover, MacRefer has several competitive features, which are insufficiently equipped with EndNote Plus. For example, MacRefer is capable of (1) maintaining subsets within a database, (2) executing complex, structured searches combining up to nine keywords for any data field with the results and search conditions preserved, and (3) easily browsing (a portion of) reference database. Although MacRefer cannot be recognized as an absolute alternative of EndNote Plus because of several limitations inherent to HyperCard, the compensatory use of these two programs will expand the personal utilization of bibliographic databases.

Computers↗

A computer program for comprehensive ST-segment depression/heart rate analysis of the exercise ECG test.

The ST-segment depression/heart rate (ST/HR) analysis has been found to improve the diagnostic accuracy of the exercise ECG test in detecting myocardial ischemia. Recently, three different continuous diagnostic variables based on the ST/HR analysis have been introduced; the ST/HR slope, the ST/HR index and the ST/HR hysteresis. The latter utilises both the exercise and recovery phases of the exercise ECG test, whereas the two former are based on the exercise phase only. This present article presents a computer program which not only calculates the above three diagnostic variables but also plots the full diagrams of ST-segment depression against heart rate during both exercise and recovery phases for each ECG lead from given ST/HR data. The program can be used in the exercise ECG diagnosis of daily clinical practice provided that the ST/HR data from the ECG measurement system can be linked to the program. At present, the main purpose of the program is to provide clinical and medical researchers with a practical tool for comprehensive clinical evaluation and development of the ST/HR analysis.

Exercise Test↗

Mathematical model for chemically induced lipid peroxidation in precision-cut liver slices: computer simulation and experimental calibration.

A biologically based pharmacodynamic (BBPD) model was developed in order to describe and simulate chemically induced lipid peroxidation in precision cut mouse liver slices. The model was written in Advanced Continuous Simulation Language (ACSL) and simulations were performed using SIMUSOLV software on a VAX/VMS mainframe computer. The BBPD model simulated formation of lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS) over time as a function of the amounts of cytochrome P450 (CYP)-activated chemical inducer and active antioxidants. The rate of peroxidation was controlled by lipid peroxidizability, destruction of CYP, autooxidation, and activity of glutathione peroxidase. The BBPD model was initially parameterized with the literature data for TBARS formation during lipid peroxidation, reported for rat liver slices induced with bromotrichloromethane and tert-butyl hydroperoxide (TBOOH). Then, the biochemical parameters were adjusted to reflect the physiology of the mouse liver, and the BBPD model was used to simulate TBARS formation during lipid peroxidation in precision cut mouse liver slices induced with TBOOH. The BBPD model predictions were in agreement with the experimental data.

Animals↗

A dual approach to structural texture analysis in microscopic cell images.

The computer-based quantitative analysis of microscopic cell images provides important diagnostic information in clinical and experimental pathology. The arrangement of various cell structures can be described as texture. We developed a new approach to structural texture analysis. It assumes that texture consists of homogeneous regions (texture primitives). Texture can be regarded in a dual way--as a composition of regions or as a pattern composed of the regions' boundaries (lines). We implemented methods for the segmentation of regions and lines in grayscale images. The detection of regions is followed by a region-growing process to avoid an oversegmentation. The segmented regions and lines are stored in a uniform data structure which reflects their arrangement in the image. The presented methods were applied to study the chromatin distribution in cell nuclei and the development and differentiation of intermediate filaments in fetal liver cells.

Algorithms↗

Testing a 3-D radiation therapy planning program.

This report describes a systematic effort to test all functions of a large 3-D radiation therapy planning program, including graphics and user interaction. Previous studies in quality assurance for radiation therapy programs do not adequately address the problem of programming errors. They compare dose estimates calculated by planning programs to actual doses measured in phantoms, so they cannot distinguish programming errors from measurement errors or physical unsoundness of the beam model. Moreover, they fail to exercise graphics and user interaction functions. This report describes a different methodology: test cases are derived from the program specification, results are calculated by an independent technique, and compared to program output. Derivation of test cases is described in detail. Effectiveness of testing is assessed by reporting the number of errors revealed by testing and comparing to the number of errors discovered during routine use in five successive program versions. The size of the test set is related to the total program size, and the effort devoted to deriving and performing tests is compared to the total program development effort. We conclude that systematic testing can reveal errors that are not found by informal testing, routine program use, or comparison with measurements. However, additional errors remain that are only discovered during use. This study suggests that a typical large planning system may include more than 100 errors when it is released for clinical use. Methods for increasing testing effectiveness are recommended.

Radiotherapy, Computer-Assisted↗

Portal dose images. I: Quantitative treatment plan verification.

The comparison of a predicted portal dose image, calculated during treatment planning, with the measured image obtained during treatment is proposed as an approach to verify the correct implementation of a patient treatment plan. The comparison inherently verifies both the geometric alignment and the dose delivered. Feasibility studies were conducted with 60Co irradiation of a modular plastic phantom, an anthropomorphic phantom and a patient with lung cancer. Calculations were made with the 3-dimensional scatter ray-trace Delta Volume method. Calculated distributions and/or selected points of transmitted dose correction factors were compared with measurements made with TLD, scanning ionization chamber and film. For the two phantom studies, excellent agreement, usually to within 3%, was achieved when positioning of the phantoms were accurate. The patient study showed that selected point comparisons were inadequate in identifying the cause of errors when disagreement occurred. Simple subtraction of the calculated and measured images showed a 4 mm translational misalignment. The results are encouraging and demonstrate that portal dose images can be used to detect large geometric and dosimetric discrepancies between treatment plan calculations and measurements. The results also show that perfect verification is virtually impossible in the clinical situation. More work is required to use the verification information for improving the estimation of dose to the patient.

Cobalt Radioisotopes↗

Portal dose images. II: Patient dose estimation.

Due to the many sources of uncertainties in radiotherapy, conventional treatment planning can only provide a nominal presentation of the dose delivered to the patient. Provided that large setup errors can be detected and corrected, we propose that measured and calculated portal dose images can be used to improve estimation of patient dose. The iterative approach described in this paper requires an accurate method of dose calculations, 3-dimensional CT data that closely represents the patient and the measured portal dose image. From the CT data, a portal dose image is calculated for comparison with the measured one. The differences are then used to modify the original CT data so that a new image can be calculated. The process is repeated until the calculated and measured images agree to satisfaction. At that point, the internal dose is calculated using the modified CT data. If the method is successful, daily portal dose images could be used to cumulatively estimate patient dose throughout the course of treatment. This manuscript describes 60Co simulation results to demonstrate the feasibility of the approach.

Cobalt Radioisotopes↗

On-line radiotherapy imaging with an array of fiber-optic image reducers.

In the optical approach for on-line radiotherapy imaging, a large metal sheet-fluorescent screen combination is used to convert the radiation intensity distribution into a visible light image. Data are then captured via a mirror with a camera located out of the beam. Although usable portal images can be acquired, presence of the large mirror renders the system impractical in many treatment geometries. We have overcome this limitation by replacing the mirror with an array of 16 by 16 bundles of plastic fiber-optic image reducers. Each bundle, in turn, is made up of 16 by 16 individual optical fibers. The total of 256 by 256 fibers spans an input area of 40 cm by 40 cm with each individual fiber viewing an area of 1.6 mm by 1.6 mm. Within a height of 12 cm, each fiber is reduced to an area of 0.1 mm by 0.1 mm. The reduced portal image is then turned and "piped" to a final 3.0 cm by 3.0 cm output area. For data acquisition and digitization, the fiber output is directly coupled to the sensor of a TV camera interfaced to a small computer via a 512 by 512 frame grabber. In this initial evaluation, the imaging system has been characterized in terms of its line spread function, noise and resistance to radiation damage. Adequate phantom and patient images are presented.

Fiber Optic Technology↗

Full integration of the beam's eye view concept into computerized treatment planning.

A complete set of beam's eye view (BEV) and beam portal design features have been integrated into a computerized 3-dimensional radiotherapy treatment planning system. Among the features implemented is the ability to mix BEV graphics with gray-scale images such as simulator and verification radiographs, and digital reconstructed radiographs. Image processing techniques have been developed to both enhance verification images and to detect radiation field boundaries. These portal simulation and presentation techniques are being used clinically to design and verify radiation fields with manual or automatically-designed field shaping blocks. The ability to perform computer dose calculations for planes which are parallel or perpendicular to a specified beam's central axis is available and this feature has also proven useful for treatment plan evaluation and optimization. Finally, direct comparison of computer-generated portal images with actual simulation and verification radiographs is also possible. These techniques allow the direct integration of "CT-directed treatment planning" with block design, simulator films and port films, and other Beam's Eye View-type displays.

Computer Simulation↗

3D base: a geometrical data base system for the analysis and visualisation of 3D-shapes obtained from parallel serial sections including three different geometrical representations.

In this paper we discuss a geometrical data base that includes three different geometrical representations of one and the same reconstructed 3D shape: the contour-pile, the voxel enumeration, and the triangulation of a surface. The data base is tailored for 3D shapes obtained from plan-parallel serial sections. It is explained how this geometrical data base is useful with the different processing approaches of a 3D shape, such as analysis and visualisation. Methods of conversion between the geometrical representations are discussed. Examples of the operation of the data base as it is embedded in a data base management system are given by illustrations of retrieval of geometrical information.

Algorithms↗

A gray-level thinning method for delineation and representation of arteries.

The quantification of three dimensional (3D) properties of coronary arteries is of significant importance. The performance of the 3D analysis is critically based on low-level representation of the arterial tree for different projections. A skeletal representation of arteries can provide appropriate data structure for registration of multiple angiographic projections and it can be further utilized for 3D reconstruction of the arterial tree. This paper presents an automated method for extracting the skeletal points of an arterial tree directly from the gray-level information without determining the edges a priori. It offers the advantage of improved reliability compared to methods based on detecting dual edges of the arteries. Novel application of filtering techniques provide accurate estimates of the statistics of the background. A recursive search scheme is used to aggregate the skeletal representation at multiple resolutions. Results on a set of Digitally Subtracted Angiograms (DSA) have been presented.

Algorithms↗

Software control procedures for treatment planning systems.

In radiotherapy treatment planning systems, the software programs as well as the beam data have to be updated frequently, when new software versions are released or as beam data change. This update procedure has to be carried out carefully, to ensure the integrity of the system software and data. Moreover, the version of software used for a particular patient treatment plan is important, not only as a record to be retrieved when necessary, but also when there are multiple terminals connected to the same computer. This process of version control is not always carried out in a systematic and standardized fashion. Most clinics often have their own systems to implement this procedure, but while some systems are comprehensive, others may not necessarily incorporate enough safeguards for errors. In addition, treatment planning system manufacturers often do not offer well-designed and fail-safe facilities for this important issue. This report describes the software update control procedures we have implemented on our treatment planning system as well as suggests some general principles that could be applied to other planning systems.

Computer Systems↗

Software tools for interactive instruction in radiologic anatomy.

RATIONALE AND OBJECTIVES: To promote active learning in an introductory Radiologic Anatomy course through the use of computer-based exercises. MATERIALS AND METHODS: DICOM datasets from our hospital PACS system were transferred to a networked cluster of desktop computers in a medical school classroom. Medical students in the Radiologic Anatomy course were divided into four small groups and assigned to work on a clinical case for 45 minutes. The groups used iPACS viewer software, a free DICOM viewer, to view images and annotate anatomic structures. The classroom instructor monitored and displayed each group's work sequentially on the master screen by running SynchronEyes, a software tool for controlling PC desktops remotely. RESULTS: Students were able to execute the assigned tasks using the iPACS software with minimal oversight or instruction. Course instructors displayed each group's work on the main display screen of the classroom as the students presented the rationale for their decisions. The interactive component of the course received high ratings from the students and overall course ratings were higher than in prior years when the course was given solely in lecture format. CONCLUSIONS: DICOM viewing software is an excellent tool for enabling students to learn radiologic anatomy from real-life clinical datasets. Interactive exercises performed in groups can be powerful tools for stimulating students to learn radiologic anatomy.

Anatomy↗

Evaluation of the accuracy of digital model analysis for the American Board of Orthodontics objective grading system for dental casts.

INTRODUCTION: In 1999, after 3 years of field testing, the American Board of Orthodontics (ABO) implemented a grading system for posttreatment orthodontic models and panoramic radiographs, to make the phase III examination both fair and objective. In the ABO's objective grading system, 7 occlusal criteria (tooth alignment, vertical positioning of marginal ridges, buccolingual inclination of posterior teeth, occlusal relationship, occlusal contacts, overjet, and interproximal contacts) are measured on plaster models to assess a patient's final occlusion. To date, no study has evaluated the ABO grading system for use on digital models. The purpose of this study was to determine whether digital models can be used with reasonable accuracy and reliability for assessing patients' final occlusions. METHODS: Plaster and digital (OrthoCAD, Cadent Inc, Carlstadt, NJ) posttreatment models of 24 patients were gathered from the postgraduate orthodontic clinic at Columbia University School of Dental and Oral Surgery. The plaster models were scored by using the ABO measuring gauge and the 7 criteria of the ABO grading system. A second analysis was done on the digital models. To determine interexaminer error, a fourth-year dental student at Columbia University served as a second examiner and repeated all the analyses. RESULTS: The means of the total score and those for marginal ridges, occlusal contacts, occlusal relationships, overjet, and interproximal contacts were not significantly different between plaster and digital models. However, the means for alignment and buccolingual inclination were significantly different. In addition, the scorings of 2 examiners differed for the 2 methods. CONCLUSIONS: This finding suggests that alignment and buccolingual inclination should be reevaluated with both methods, and adequate calibration of the examiners is essential to achieve repeatability in both methods. Digital models might be acceptable for use in the ABO model examination.

Analysis of Variance↗

Application of pulse mixing method in software coincidence counting.

In recent years the software coincidence counting system, designed for absolute activity measurement, has been developed in the Czech Metrology Institute. In this system a true coincidence count rate is calculated from the records of time and amplitude data of individual pulses and may be determined by two different methods. The first one uses a coincidence resolving time, in a manner similar to a classical coincidence measurement. The second method applies the pulse mixing method formulae, so that it does not use the resolving time and the correction for accidental coincidences. Both methods have been tested on the same data from a 4pibeta (PC)-gamma coincidence measurement of 60Co sources. The difference between the results obtained from both calculation methods applied on the data from the same measurement did not exceed 0.015%. The details of both methods and the results of their comparison are presented.

Algorithms↗

Application of PENELOPE code to the efficiency calibration of coaxial germanium detectors.

The code PENELOPE is applied here to the efficiency calibration exercise described in the EUROMET project 428 [Lépy et al., 2001. Appl. Radiat. Isot. 55, 493]. We evaluated the peak efficiencies for a coaxial HPGe detector in the range 60-2000 keV, for point sources located at various distances from the detector and for a cylindrical box containing two different matrixes: a low-density silica and a hydrochloric acid solution. After an optimization of several detector parameters, the results were in good agreement with the experimental values.

Algorithms↗

Software studies for germanium detectors data analysis.

Efficiency calibrations of multiple high-purity germanium (HPGe) detectors are being maintained at the National Institute of Standards and Technology (NIST). Four generally available software packages for HPGe detector gamma-ray spectrum analysis, including the one currently used at NIST, were tested on spectra collected from two HPGe detectors at different source-to-detector distances and using point sources and ampoules as calibration geometries. The resulting efficiency curves were inter-compared.

Algorithms↗