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PubMed1989

Fully automated measurements by light microscopy of tissue sections using a cellular array computer.

Software was developed for the acquisition, segmentation and analysis of microscopic OD-images on a VICOM digital image processor, extended with a VISIOMORPH morphoprocessor board. The delineation algorithms for peroxisomes, lysosomes, and nuclei in liver, kidney, and adrenal gland sections start by thresholding the difference between the original image and a low pass filtered version. The resulting binary mask is then processed by morphological operations in order to produce an object overlay. The efficiency of the programs is evaluated by comparing delineated objects at different OD-levels, created by varying the stain or by multiplying the original pixel values with constant factors. Manual delineation on some images is also used as a reference. More complex algorithms are used for the delineation of muscle fibres in ATP-ase-stained sections and immunocytochemically labelled cells in monolayer preparations. Muscle images from parallel sections with different stainings are matched with a coordinate transform, enabling the transfer of the object mask from a single delineated image to the unprocessed images and thus obtain all necessary information for fibre classification. After segmentation, the OD-images and their object overlays are fed into a data extraction program, measuring for each delineated object user-selected features. Data are sent to a VAX for statistical interpretation.

Adrenal Cortex↗

PubMed2003

Implementation of a PDA based program to quantify urology resident in-training experience.

INTRODUCTION: There currently is no simple and reliable mechanism for Residency program directors to assess how well their trainees are being exposed to all spheres of their specialty. We report on the use of hand-held personal digital assistants (PDA's) to document all clinical and academic activities of urology residents at one academic institution. MATERIALS AND METHODS: Software was developed to create customized pick lists allowing residents to record all activities on their individual PDA's. Categories included Adult Ambulatory, Pediatric Ambulatory, Adult operative, Pediatric operative, and Academic. Activities were subcategorized into detailed pick lists and time-tracking fields. Residents synchronized with a central database on a standalone hotsync server. RESULTS: In the first 8 months, 21 178 resident-hours and 5333 activities were recorded. Preliminary observations can be made regarding how residents spend the majority of their time: 28% operative, 20% self-study, 19% ward work, 10% Academics, 6% ER consultations, 5% clinic, and 4% inpatient consultations. The most common adult diagnoses encountered while attending to clinic, ward, or ER consultations were lower urinary tract symptoms, urolithiasis and hematuria. Similarly for Pediatrics: neurogenic bladder, antenatal hydronephrosis, infection, and hypospadias were most often reported. Residents reported 5,333 activities, relating to the following spheres of Urology: academics (23%), endourology (18%), oncology (15%), lower urinary tract symptoms (10%), congenital anomalies (5%), urolithiasis (5%), reconstruction (5%), and infection (3%). CONCLUSIONS: This tool provides an objective assessment of resident experience as it relates to selection of rotations, and for addressing curriculum weaknesses. It is applicable at a national level for the study of regional differences in training experience, and trends in graduate Urological education. With minimal effort it could be modified for application to other specialty training programs.

Adult↗

PubMed1997

Validation of a new UNIX-based quantitative coronary angiographic system for the measurement of coronary artery lesions.

We describe a method of validation of computerized quantitative coronary arteriography and report the results of a new UNIX-based quantitative coronary arteriography software program developed for rapid on-line (digital) and off-line (digital or cinefilm) analysis. The UNIX operating system is widely available in computer systems using very fast processors and has excellent graphics capabilities. The system is potentially compatible with any cardiac digital x-ray system for on-line analysis and has been designed to incorporate an integrated database, have on-line and immediate recall capabilities, and provide digital access to all data. The accuracy (mean signed differences of the observed minus the true dimensions) and precision (pooled standard deviations of the measurements) of the program were determined x-ray vessel phantoms. Intra- and interobserver variabilities were assessed from in vivo studies during routine clinical coronary arteriography. Precision from the x-ray phantom studies (6-In. field of view) for digital images was 0.066 mm and for digitized cine images was 0.060 mm. Accuracy was 0.076 mm (overestimation) for digital images compared to 0.008 mm for digitized cine images. Diagnostic coronary catheters were also used for calibration; accuracy.varied according to size of catheter and whether or not they were filled with iodinated contrast. Intra- and interobserver variabilities were excellent and indicated that coronary lesion measurements were relatively user-independent. Thus, this easy to use and very fast UNIX based program appears to be robust with optimal accuracy and precision for clinical and research applications.

Algorithms↗

PubMed2004

CAAT-Box, Contigs-Assembly and Annotation Tool-Box for genome sequencing projects.

MOTIVATION: Contigs-Assembly and Annotation Tool-Box (CAAT-Box) is a software package developed for the computational part of a genome project where the sequence is obtained by a shotgun strategy. CAAT-Box contains new tools to predict links between contigs by using similarity searches with other whole genome sequences. Most importantly, it allows annotation of a genome to commence during the finishing phase using a gene-oriented strategy. For this purpose, CAAT-Box creates an Individual Protein file (IPF) for each ORF of an assembly. The nucleotide sequence reported in an IPF corresponds to the sequence of the ORF with 500 additional bases before the ORF and 200 bases after. For annotation, additional information like Blast results can be added or linked to the IPFs as well as automatic and/or manual annotations. When a new assembly is performed, CAAT-Box creates new IPFs according to the old IPF panel. CAAT-Box recognizes the modified IPFs which are the only ones used for a new automatic analysis after each assembly. Using this strategy, the user works with a group of IPFs independently of the closure phase progression. The IPFs are accessible by a web server and can therefore be modified and commented by different groups. RESULT: CAAT-Box was used to obtain and to annotate several complete genomes like Listeria monocytogenes or Streptococcus agalactiae. AVAILABILITY: The program may be obtained from the authors and is freely available to non-profit organisations.

Algorithms↗

PubMed1996

[A computer software system for dental caries rates: databases and statistical analysis].

A computer software system developed ICADAPLUS, is presented in order to create and tabulate data bases, calculate the DMF rate, perform statistical comparison of two populations, and calculate confidence intervals. The system offers a simplified method for health services in the area of dentistry, using dental records to carry out epidemiological surveys of tooth decay. The system's main feature is that it does not require specialists either in the area of dentistry or computing, demanding of the user only basic data-entry typing skills, since it presents simple menus, and standardized reports, with no possibility of error. The system comprises four steps: Data-entry, Processing, Reports and Utilities. In Data-entry the regions, towns and institutions supplying the data are initially registered, once only. Each record receives a code number, and it is this code which is available to the user through a Function Key, by means of which the code is transferred to the desired data field. Furthermore, there is a choice of type of dental chart: Klein and Palmer's DMF; the DMF proposed by the WHO; Klein, Palmer and Knutson's DMF surfaces; or Gruebbel's def. It is possible to include, alter and exclude records in each option. In Processing, it is necessary, first of all, to organise the indexes, totalize the data, and remit them to the data base, where no further alteration or exclusion occurs. From this stage on, reports can be prepared from the proposed indexes, grouped according to age, or age and gender. The system was validated by comparison with other methods. This comparison justifies the recommendation of its implementation.

Confidence Intervals↗

PubMed1999

Global spatial normalization of human brain using convex hulls.

UNLABELLED: Global spatial normalization transforms a brain image so that its principal global spatial features (position, orientation and dimensions) match those of a standard or atlas brain, supporting consistent analysis and referencing of brain locations. The convex hull (CH), derived from the brain's surface, was selected as the basis for automating and standardizing global spatial normalization. The accuracy and precision of CH global spatial normalization of PET and MR brain images were evaluated in normal human subjects. METHODS: Software was developed to extract CHs of brain surfaces from tomographic brain images. Pelizzari's hat-to-head least-square-error surface-fitting method was modified to fit individual CHs (hats) to a template CH (head) and calculate a nine-parameter coordinate transformation to perform spatial normalization. A template CH was refined using MR images from 12 subjects to optimize global spatial feature conformance to the 1988 Talairach Atlas brain. The template was tested in 12 additional subjects. Three major performance characteristics were evaluated: (a) quality of spatial normalization with anatomical MR images, (b) optimal threshold for PET and (c) quality of spatial normalization for functional PET images. RESULTS: As a surface model of the human brain, the CH was shown to be highly consistent across subjects and imaging modalities. In MR images (n = 24), mean errors for anterior and posterior commissures generally were <1 mm, with SDs < 1.5 mm. Mean brain-dimension errors generally were <1.3 mm, and bounding limits were within 1-2 mm of the Talairach Atlas values. The optimal threshold for defining brain boundaries in both 18F-fluorodeoxyglucose (n = 8) and 15O-water (n = 12) PET images was 40% of the brain maximum value. The accuracy of global spatial normalization of PET images was shown to be similar to that of MR images. CONCLUSION: The global features of CH-spatially normalized brain images (position, orientation and size) were consistently transformed to match the Talairach Atlas in both MR and PET images. The CH method supports intermodality and intersubject global spatial normalization of tomographic brain images.

Adult↗

PubMed1997

Calculation of residence times and radiation doses using the standard PC software Excel.

We developed a program which aims to facilitate the calculation of radiation doses to single organs and the whole body. IMEDOSE uses Excel to include calculations, graphical displays, and interactions with the user in a single general-purpose PC software tool. To start the procedure the input data are copied into a spreadsheet. They must represent percentage uptake values of several organs derived from measurements in animals or humans. To extrapolate these data up to seven half-lives of the radionuclide, fitting to one or two exponentional functions is included and can be checked by the user. By means of the approximate time-activity information the cumulated activity or residence times are calculated. Finally these data are combined with the absorbed fraction doses (S-values) given by MIRD pamphlet No. 11 to yield radiation doses, the effective dose equivalent and the effective dose. These results are presented in a final table. Interactions are realized with push-buttons and drop-down menus. Calculations use the Visual Basic tool of Excel. In order to test our program, biodistribution data of fluorine-18 fluorodeoxyglucose were taken from the literature (Meija et al., J Nucl Med 1991; 32:699-706). For a 70-kg adult the resulting radiation doses of all target organs listed in MIRD 11 were different from the ICRP 53 values by 1%+/-18% on the average. When the residence times were introduced into MIRDOSE3 (Stabin, J Nucl Med 1996; 37:538-546) the mean difference between our results and those of MIRDOSE3 was -3%+/-6%. Both outcomes indicate the validity of the present approach.

Adult↗

PubMed2000

Simulation-based medical planning for cardiovascular disease: visualization system foundations.

A technique for visualizing computational models along with volumetric imaging data in a real-time, interactive, simulation-based medical planning system for cardiovascular disease treatment is described. This technique involves an ordered rendering of faceted geometry and volumetric image data. We have developed a software system based on this image-fusion technique that is capable of capturing and representing the inherent anatomic constraints of an individual patient. Such constraints must be represented accurately in a medical planning system to ensure the validity of a potential procedure. A hypothetical clinical scenario is described for which vascular treatment plans were constructed pre-operatively without reference to the physical anatomic structure. These models were later embedded into patient-specific diagnostic MRA scans to establish the anatomic context for physiologic observations.

Algorithms↗

PubMed2000

RHIZOSCAN: A semiautomatic image processing system for characterization of the morphology and secondary metabolite concentration in hairy root cultures.

We describe the application of the newly developed RHIZOSCAN software for accurate morphological analysis and determination of overall and local secondary metabolite concentrations in two clones of Beta vulgaris throughout the growth period. Local secondary metabolite concentrations may be determined at any point in the root, and pigment gradients in each lateral root can be followed during culture and saved to the computer. Throughout the entire analysis process, an image appears in a graphical result window on the screen, which enables visual evaluation of the numerical output at each stage of the analysis. Biosynthetic data on concentrations obtained by image analysis were validated by spectrophotometric analysis. The importance of determining appropriate scanning and analysis conditions (scanning resolution, background color, threshold value, segmentation plane in the hue-saturation-intensity color system and pruning length) for obtaining accurate morphological measurements is examined and the means of fixing these parameters is described. Our results show that, using RHIZOSCAN, detailed and accurate information on root architecture and secondary metabolite concentrations can be obtained in a short time.

Automation↗

PubMed2006

The multidimensionality of cell behaviors underlying morphogenesis: a case study in ascidians.

Databases where different types of information from different sources can be integrated, cross-referenced and interactively accessed are necessary for building a quantitative understanding of the molecular and cell biology intrinsic to the morphogenesis of an embryo. Tassy and colleagues recently reported the development of software tailor-made to perform such a task, along with the generation and integration of three-dimensional anatomical models of embryos. They convincingly illustrated the utility of their approach by applying it to the early ascidian embryo.

Animals↗

PubMed2004

Continuous glucose monitoring and control in a rotating wall perfused bioreactor.

A glucose control system consisting of a single in-line glucose sensor, concentrated glucose solution, and computer hardware and software were developed. The system was applied to continuously control glucose concentrations of a perfusion medium in a rotating wall perfused vessel (RWPV) bioreactor culturing BHK-21 cells. The custom-made glucose sensor was based on a hydrogen peroxide electrode. The sensor continuously and accurately measured the glucose concentration of GTSF-2 medium in the RWPV bioreactor during cell culture. Three sets of two-point calibrations were applied to the glucose sensor during the 55-day cell culture. The system first controlled the glucose concentration in perfusing medium between 4.2 and 5.6 mM for 36 days and then at different glucose levels for 19 days. A stock solution with a high glucose concentration (266 mM) was used as the glucose injection solution. The standard error of prediction (SEP) for glucose measurement by the sensor, compared to measurement by the Beckman glucose analyzer, was +/-0.4 mM for 55 days.

Animals↗

PubMed2005

Novel approach to quantify immobilized-enzyme distributions.

The quantitative intraparticle enzyme distribution of Assemblase, an industrially employed polydisperse immobilized penicillin-G acylase, was measured. Because of strong autofluorescence of the carrier, the generally applied technique of confocal scanning microscopy could not be used; light microscopy was our method of choice. To do so, Assemblase particles of various sizes were sectioned, labeled with antibodies specifically against the enzyme, and analyzed light microscopically. Image analysis software was developed and used to determine the intraparticle enzyme distribution, which was found to be heterogeneous, with most enzyme located in the outer regions of the particles. Larger particles showed steeper gradients than smaller ones. A mathematical representation of the intraparticle profiles, based on in-stationary enzyme diffusion into the particles, was validated successfully for a broad range of particle sizes using data for volume-averaged particle size and enzyme loading. The enzyme gradients determined in this work will be used as input for a physical model that quantitatively describes the complex behavior of Assemblase. Such a physical model will lead to identification of the current bottlenecks in Assemblase and can serve as a starting point for the design of improved biocatalysts that also may be based on intelligent use of enzyme gradients.

Catalysis↗

PubMed2004

Detailed anatomy of the abdomen and pelvis of the visible human female.

We report on a virtual anatomical preparation of the abdomen and pelvis of the Visible Human Female (VHF) for laparoscopic surgery training. The detailed cross-sectional image data set from the U.S. National Library of Medicine was used as the basis to build an exemplary model of the female abdomen and pelvis. Segmentation software was developed to delineate organ outlines and more than 300 structures of interest, including organs, blood vessels, bones, muscles, and ligaments, have been segmented and three-dimensionally reconstructed. Analyzing the normal anatomy we found several variations and pathologies of the VHF, such as missing muscles (gemellus superior, psoas minor), additional veins as well as spondylophytes (vertebral column, pubic bone), and colon diverticula. The complete data set may be viewed on the home page of the project (http://www.vision.ee.ethz.ch/projects/Lasso/start.html).

Abdomen↗

PubMed2005

Analysis of virtual two-dimensional gels based upon affinity capillary electrophoresis hyphenated to ion trap-mass spectrometry.

Affinity capillary electrophoresis (ACE) is a robust tool for the study of noncovalent biomolecular interactions and to determine the binding constants. It is advantageous due to the speed of analysis, the high and reproducible separation efficiencies, the low consumption of analytes, the ability to study several interactions at the same time, and to cover a wide range of affinity. The use of an ion trap-mass spectrometer as a sensitive and specific detector, coupled on-line with a classical UV detector, permits extracting simultaneously the electropherograms corresponding to each ionic species. The mass spectra, acquired by scanning the results of a first separation due to ACE, were assimilated into a virtual two-dimensional (2-D) gel. We developed a software application, which was designed to create and analyze these virtual 2-D gels. The validity of this new analytical tool for probing biomolecular interactions has been demonstrated on mixtures of antibiotics of the vancomycin group and several dipeptide substrates. Using the dynamic equilibrium affinity electrophoresis approach, we have shown that molecular components interacting with a low affinity are easily located on the virtual 2-D gels, and that binding constants and stoichiometry of the interactions can be assessed. As the binding constants derived from ACE-electrospray ionization-mass spectrometry (ESI-MS) are unreliable, they must only be determined with the UV detector.

Electrophoresis, Capillary↗

PubMed2006

Motivation and synthesis of the FIAC experiment: Reproducibility of fMRI results across expert analyses.

The Functional Imaging Analysis Contest (FIAC) culminated in the FIAC Workshop held at the 11th Annual Meeting of the Organization for Human Brain Mapping in Toronto in 2005. This special issue summarizes various analyses used by contestants with a single functional magnetic resonance imaging (fMRI) study, a cortical-language study using sentence repetition. The results from the cognitive neuroscientists who developed the test-base language study, and report their data analysis, are complemented by expert analyses of the same test-base data by most of the major groups actively developing fMRI software packages. Analyses include many variants of the general linear model (GLM), cutting-edge spatial- and temporal-wavelets, permutation-based, and ICA approaches. A number of authors also include surface-based approaches. Several articles describe the important emerging areas of diagnostics for GLM analysis, multivariate predictive modeling, and functional connectivity analysis. While the FIAC did not achieve all of its goals, it helped identify new activation regions in the test-base data, and more important, through this special issue it illustrates the significant methods-driven variability that potentially exists in the literature. Variable results from different methods reported here should provide a cautionary note and motivate the Human Brain Mapping community to explore more thoroughly the methodologies they use for analyzing fMRI data.

Brain Mapping↗

PubMed2006

SNPSplicer: systematic analysis of SNP-dependent splicing in genotyped cDNAs.

Functional annotation of SNPs (as generated by HapMap (http://www.hapmap.org) for instance) is a major challenge. SNPs that lead to single amino acid substitutions, stop codons, or frameshift mutations can be readily interpreted, but these represent only a fraction of known SNPs. Many SNPs are located in sequences of splicing relevance-the canonical splice site consensus sequences, exonic and intronic splice enhancers or silencers (exonic splice enhancer [ESE], intronic splice enhancer [ISE], exonic splicing silencer [ESS], and intronic splicing silencer [ISS]), and others. We propose using sets of matching DNA and complementary DNA (cDNA) as a screening method to investigate the potential splice effects of SNPs in RT-PCR experiments with tissue material from genotyped sources. We have developed a software solution (SNPSplicer; http://www.ikmb.uni-kiel.de/snpsplicer) that aids in the rapid interpretation of such screening experiments. The utility of the approach is illustrated for SNPs affecting the donor splice sites (rs2076530:A>G, rs3816989:G>A) leading to the use of a cryptic splice site and exon skipping, respectively, and an exonic splice enhancer SNP (rs2274987:C/T), leading to inclusion of a new exon. We anticipate that this methodology may help in the functional annotation of SNPs in a more high-throughput fashion.

Alternative Splicing↗

PubMed2006

Interactive magnetic resonance cholangiography (MRC) with adaptive averaging.

PURPOSE: To implement and evaluate a technique for adaptively averaging 2D magnetic resonance cholangiography (MRC) images obtained using an interactive imaging system with a view to improving image quality at reduced fields of view (FOVs). MATERIALS AND METHODS: Images were obtained using an interactive implementation of a single-shot half-Fourier rapid acquisition with relaxation enhancement (RARE) technique. Software was developed for adaptively averaging images, and an evaluation was performed in a phantom and a cohort of 10 patients referred for standard MRC. Adaptively averaged and standard single-shot MRC images were evaluated with respect to their ability to demonstrate the common bile duct and main left and right intrahepatic duct branches. RESULTS: In all patient studies there was no difference in the ability of either the adaptive technique or the standard single-shot method to demonstrate the common bile duct and the main left and right intrahepatic duct branches. However, in seven of the 10 patient studies the adaptive technique provided better visualization of the peripheral bile duct system (P = 0.035; sign test). There was no difference in the diagnostic confidence of the two techniques (P = 0.32, Wilcoxon signed-rank test). CONCLUSION: Adaptive averaging of MRC images obtained using an interactive imaging paradigm significantly improves visualization of peripheral intrahepatic ducts.

Adolescent↗

PubMed2003

Direct analysis of drug candidates in tissue by matrix-assisted laser desorption/ionization mass spectrometry.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been used to directly analyze and image pharmaceutical compounds in intact tissue. The anti-tumor drug SCH 226374 was unambiguously determined in mouse tumor tissue using MALDI-QqTOFMS (QSTAR) by monitoring the dissociation of the protonated drug at m/z 695.4 to its predominant fragment at m/z 228.1. A second drug, compound A, was detected in slices of rat brain tissue following oral administration with doses ranging from 1-25 mg/kg. Quantitation of compound A from whole brain homogenates using routine high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) procedures revealed that concentrations of the drug in whole brain varied from a low of 24 ng/g to a high of 1790 ng/g. The drug candidate was successfully detected by MALDI-QqTOF in samples from each dose, covering a range of approximately two orders of magnitude. In addition, good correlation was observed between the MALDI-QqTOFMS intensities at each dose with the HPLC/MS/MS results. Thus the MALDI-MS response is proportional to the amount of drug in tissue. Custom software was developed to facilitate the imaging of small molecules in tissue using the MALDI-QqTOF mass spectrometer. Images revealing the spatial localization of SCH 226374 in tumor tissue and compound A in brain tissue were acquired.

Animals↗