Aetiology of acute gastroenteritis in adults requiring hospitalization in The Netherlands.

SUMMARY Infectious gastroenteritis causes a considerable burden of disease worldwide. Effective control should be targeted at diseases with the highest burden and costs. Therefore, an accurate understanding of the relative importance of the different microorganisms is needed. The objective of this study was to determine the incidence and aetiology of gastroenteritis in adults requiring hospital admission in The Netherlands. Five hospitals enrolled patients admitted with gastroenteritis for about 1 year during the period May 2008 to November 2009. Participants completed questionnaires and provided a faecal sample. The hospital completed a clinical questionnaire. In total, 44 adults hospitalized for gastroenteritis were included in the study. The cases had serious symptoms, with 31% subsequently developing kidney failure. One or more pathogens were found in 59% of cases. Overall, rotavirus (22%) was the most common infection. Co-infections were observed relatively often (22%). This study emphasizes that rotavirus can also cause serious illness in adults.

Texture analysis of cervical cell nuclei by segmentation of chromatin patterns.

Texture parameters of the nuclear chromatin pattern can contribute to the automated classification of specimens on the basis of single cell analysis in cervical cytology. Current texture parameters are abstract and therefore hamper understanding. In this paper texture parameters are described that can be derived from the chromatin pattern after segmentation of the nuclear image. These texture parameters are more directly related to the visual properties of the chromatin pattern. The image segmentation procedure is based on a region grow algorithm which specifically isolates high chromatin density. The texture analysis method has been tested on a data set of images of 112 cervical nuclei on photographic negatives digitized with a step size of 0.125 micron. The preliminary results of a classification trial indicate that these visually interpretable parameters have promising discriminatory power for the distinction between negative and positive specimens.

Analysis of measuring system parameters that influence reproducibility of morphometric assessments with a graphic tablet.

The morphometric analysis of nuclear characteristics by means of a graphic tablet is, in principle, objective and highly reproducible. However, a recent study found considerable variation in the morphometric assessments, which was in contrast to the findings of others. The way in which measurements were performed differed in these studies. Therefore, measuring system factors that can potentially influence the quantitative results were analyzed systematically. One observer, experienced in microscopic analysis and working with a commercially available graphic tablet, conducted all the measurements, thus excluding interobserver variation. The tracing speed, localization (on the graphic tablet), magnification, pen and cursor usage, shape, and orientation on the graphic tablet were analyzed. A nomogram was developed for cursor application that indicates the relation between "projected" particle size, tracing speed, and required coefficient of variation (CV). When the influence of these factors is taken into account, a measuring system can be tuned optimally. With such a regimen, the CV can be kept below 1.5%. Our results show that in the assessment of morphometric features with the use of a graphic tablet, errors due to the measuring system can be virtually eliminated.

Evaluation of a Diagnostic Encyclopedia Workstation for ovarian pathology.

The Diagnostic Encyclopedia Workstation (DEW) is a computer system that provides completely integrated pictorial and textual information as reference knowledge in the field of ovarian pathology. The textual component comprises information per diagnosis such as descriptions of macroscopic and microscopic images, clinical signs, and prognosis. In addition, the system offers lists of differential diagnoses and criteria to differentiate among lists of differential diagnoses and criteria to differentiate among them. The present study evaluates to what extent the system influences the diagnostic process in efficiency and outcome. Therefore, two groups of six pathologists each, covering a wide spectrum of experience in ovarian pathology, participated in the evaluation of the DEW. The quality of the resulting diagnoses was statistically analyzed with the Wilcoxon rank sum test with respect to five different viewpoints: classification, morphology, clinical consequences, duration of diagnostic process, and consensus among the participants. The results are discussed and it is concluded that classification and morphology showed better results when books were used. The evaluation experiment was, however, very rigid and negatively biased with respect to the DEW system. Positive aspects of the encyclopedia are the easy access to diagnostic and differential diagnostic information and the large set of illustrations. Insight is acquired with respect to existing bottlenecks and how they may be overcome.

Quantification of epithelial area by image processing applied to endometrial carcinomas: a comparison with ovarian tumors.

In endometrial carcinomas, the epithelial area measured by interactive morphometry is an important feature in the classification of tumors of varying histologic grades. This report describes an image analysis technique for the fully automated estimation of the area percentages of epithelium and stroma in tissue sections of the endometrium obtained from hysterectomy specimens. The method is evaluated using endometrial carcinomas with varying degrees of malignancy. From standard paraffin sections stained with pararosanilin Feulgen and naphthol yellow, a blue-yellow image pair was recorded. The blue image was used to determine the total tissue area and the yellow image was used to determine the epithelial area. Image processing of the blue image was comprised of correction for shading, segmentation of the tissue area, and restoration of the segmented image by removing small artefacts and closing small tears in the tissue. Image processing of the yellow image was based on the fact that epithelial nuclei are generally more tightly packed than stromal nuclei and consists of the following steps: correction for shading, gaussian blurring, segmentation of nuclei, and editing the segmented image by removing small objects and closing small spaces between the epithelial nuclei. These image processing steps are compared with those used for quantification of the epithelial area in ovarian tumors. The performance of the method was evaluated using 120 image pairs from 30 endometrial carcinomas of varying histologic grades. The epithelial area percentages, as assessed by digital image processing, strongly correlate to control percentages that were established by interactive morphometry (r = .987).

A bending energy model for measurement of cardiac shape deformity.

An approach to analyzing and quantifying the shape characteristics of the endocardial contour of the left ventricle of the heart is described. The computation begins by finding the local curvature differences between the contour under consideration and the mean normal contour at each of 100 equidistant points. The weighted square of these differences, summed over a set of points, is shown to be the regional or, global bending energy required to deform the mean normal contour to the characteristic shape of the analyzed contour. Resampling, smoothing and curvature computation issues are considered for the image-derived digital contours that are used in the analysis. Experiments were performed on artificial contour data and data derived from contrast ventriculographic (CV) studies of humans. It is also shown that the method has been adapted to measure endocardial shape form equilibrium radionuclide angiocardiography.

Interaction in the segmentation of medical images: a survey.

Segmentation of the object of interest is a difficult step in the analysis of digital images. Fully automatic methods sometimes fail, producing incorrect results and requiring the intervention of a human operator. This is often true in medical applications, where image segmentation is particularly difficult due to restrictions imposed by image acquisition, pathology and biological variation. In this paper we present an early review of the largely unknown territory of human-computer interaction in image segmentation. The purpose is to identify patterns in the use of interaction and to develop qualitative criteria to evaluate interactive segmentation methods. We discuss existing interactive methods with respect to the following aspects: the type of information provided by the user, how this information affects the computational part, and the purpose of interaction in the segmentation process. The discussion is based on the potential impact of each strategy on the accuracy, repeatability and interaction efficiency. Among others, these are important aspects to characterise and understand the implications of interaction to the results generated by an interactive segmentation method. This survey is focused on medical imaging, however similar patterns are expected to hold for other applications as well.

Age incidence of senile brain amyloidosis.

Neuropathological examination of 1400 successive autopsies in general and mental hospitals revealed that senile plaques and congophilic angiopathy are age related phenomena. There is, however, a remarkable difference between the two types of manifestation of senile amyloidosis. There was a significantly higher incidence of senile plaques in females. Moreover the increase of the incidence with age was also significantly higher in females. Congophilic angiopathy showed no predominance in females. In total 59% of males and 55% of females with senile plaques suffered from Senile Dementia of the Alzheimer Type (SDAT). SDAT appeared to be also an age related phenomenon characterized by a linear increase with age and a predominance in females.

Automated estimation of epithelial volume in breast cancer sections. A comparison with the image processing steps applied to gynecologic tumors.

The paper describes an image analysis technique for automated estimation of the epithelial percentage in standard paraffin tissue sections of invasive ductal breast cancers. Two staining procedures are evaluated: Feulgen (pararosanilin) and CAM 5.2-demonstrating the presence of cytokeratin 8 and 18-, both counterstained with naphthol yellow. In the technique, one image is recorded with a filter to visualize where the epithelium lies. This filter is chosen corresponding to the type of staining: it is yellow for Feulgen and blue for anti-cytokeratin CAM 5.2. To visualize where the stroma lies, the same image can be used for anti-cytokeratin CAM 5.2, whereas for Feulgen, a second image has to be recorded from the same microscope field with a blue filter. The image processing steps to determine the total tissue area comprise correction for shading, segmentation of the tissue area, and restoration of the segmented image by removal of small artefacts and closure of small tears in the tissue. The method for determination of the epithelial area consists of the following steps: correction for shading, gaussian blurring, segmentation of nuclei or epithelial cells, and editing of the segmented image by removal of small objects and closure of small spaces between the epithelial nuclei or cells. These image processing steps are compared to those for quantification of the epithelial percentage in gynecologic tumors of epithelial origin. For the Feulgen stain, the method is evaluated on 30 breast cancers of the ductal type (4 grade I, 12 grade II, and 14 grade III).(ABSTRACT TRUNCATED AT 250 WORDS)

Morphometry of breast cancer. I. Comparison of the primary tumours and the axillary lymph node metastases.

In 234 patients with primary breast cancer, morphometry was performed of three groups of tumour cells: 1. in the primary tumours without lymph node metastases (PRN); 2. in primary tumours with lymph node metastases (PRP) and; 3. in the axillary lymph node metastatic deposits (LMD). The morphometrical analysis included the cellularity index, the mitotic activity index and seven nuclear features. The highest mitotic activity indices (mean: 14.1) were found in the metastatic deposits (LMD), the lowest (mean: 12.5) in the lymph node negative primary tumours (PRN), whereas the lymph node positive primary tumours (PRP) fell in between (mean: 13.2). The cellularity index shows a similar, though reciprocal, trend. The largest standard deviations of the nuclear features were found in primary tumours with lymph node metastases (PRP). In contrast, the metastatic (LMD) nuclei had the smallest standard deviations. The nuclei of the latter are therefore more regular in size and shape. The differences found are not sufficiently large to distinguish PRN and PRP with an acceptable accuracy (the efficiency, sensitivity or specificity did not exceed 67% irrespective of the decision threshold used). Comparison of primary tumours with lymph node metastases and the metastatic deposits, from the same patients, revealed significant correlations of all morphometric features with the exception of the nuclear shape factor and the nuclear axes ratio. Thus, the nuclei of the metastatic cells in general are identical to the nuclei in the primary tumour from which they arise, but in a subset of patients the metastatic tumour cells have much more monomorphous ellipsoid nuclei. Further investigations are needed to see whether this phenomenon indicates a different malignant course.

A computer based handbook and atlas of pathology.

The Diagnostic Encyclopaedia Workstation (DEW) is a computerized handbook of pathology intended for use in diagnostic practice. It consists of a combination of a personal computer (PC), a video disc player (VDP), for which a specially developed disc is used, two monitors, a mouse and software. The hard disc of the computer contains textual information on diagnoses in categories such as macroscopy, common histology, immunopathology, clinical observations and prognosis and case histories. This information is frequently illustrated by pictures on a video disc which is automatically addressed by the computer software. All pictures, at present some 3000, pertain to case histories which are included in the system. Also integrated are classification aids in two categories: diagnostic criteria and differential diagnosis. Advantages of DEW over the use of conventional manuals are 1) the extensive volume of text, 2) the large number of high quality illustrations, 3) the immediate access to cross references and 4) the potential for continuous revision.

Discrete representation of straight lines.

If a continuous straight line segment is digitized on a regular grid, obviously a loss of information occurs. As a result, the discrete representation obtained (e.g., a chaincode string) can be coded more conveniently than the continuous line segment, but measurements of properties (such as line length) performed on the representation have an intrinsic inaccuracy due to the digitization process. In this paper, two fundamental properties of the quantization of straight line segments are treated. 1) It is proved that every ``straight'' chaincode string can be represented by a set of four unique integer parameters. Definitions of these parameters are given. 2) A mathematical expression is derived for the set of all continuous line segments which could have generated a given chaincode string. The relation with the chord property is briefly discussed.

Best linear unbiased estimators for properties of digitized straight lines.

This paper considers the problem of measuring properties of digitized straight lines from the viewpoint of measurement methodology. The measurement and estimation process is described in detail, revealing the importance of a step called ``characterization'' which was not recognized explicitly before. Using this new concept, BLUE (Best Linear Unbiased) estimators are found. These are calculated for various properties of digitized straight lines, and are briefly compared to previous work.

PicToSeek: combining color and shape invariant features for image retrieval.

We aim at combining color and shape invariants for indexing and retrieving images. To this end, color models are proposed independent of the object geometry, object pose, and illumination. From these color models, color invariant edges are derived from which shape invariant features are computed. Computational methods are described to combine the color and shape invariants into a unified high-dimensional invariant feature set for discriminatory object retrieval. Experiments have been conducted on a database consisting of 500 images taken from multicolored man-made objects in real world scenes. From the theoretical and experimental results it is concluded that object retrieval based on composite color and shape invariant features provides excellent retrieval accuracy. Object retrieval based on color invariants provides very high retrieval accuracy whereas object retrieval based entirely on shape invariants yields poor discriminative power. Furthermore, the image retrieval scheme is highly robust to partial occlusion, object clutter and a change in the object's pose. Finally, the image retrieval scheme is integrated into the PicToSeek system on-line at http://www.wins.uva.nl/research/isis/PicToSeek/ for searching images on the World Wide Web.

A method for the acquisition of formalized knowledge in pathology.

A tool is introduced for the acquisition of pathology knowledge in a formalized form, directly by the expert. Formalization of the knowledge is intended to make descriptive pathology knowledge more suitable for computerized diagnostic support since a formal representation of knowledge allows more extensive indexing, hence more flexible access. The knowledge acquisition (KA) tool also provides a useful research instrument to investigate to what extent pathology knowledge can be made explicit, to what degree ambiguity is present, in what way experts differ when formalizing knowledge, and whether it is feasible to incrementally acquire decision criteria on the basis of the formalized descriptive knowledge. Crucial in the design of the KA tool is the incorporated meta-knowledge, which is reflected by the knowledge-base structure and is used to elicit knowledge from the expert. Knowledge is acquired from the expert via a menu-driven user interface, which follows the general steps of the pathologist when describing a case. The paper discusses the considerations underlying the design, the implementation of the KA tool, and the research goals.

Design of a diagnostic encyclopaedia using AIDA.

Diagnostic Encyclopaedia Workstation (DEW) is the name of a digital encyclopaedia constructed to contain reference knowledge with respect to the pathology of the ovary. Comparing DEW with the common sources of reference knowledge (i.e. books) leads to the following advantages of DEW: it contains more verbal knowledge, pictures and case histories, and it offers information adjusted to the needs of the user. Based on an analysis of the structure of this reference knowledge we have chosen AIDA to develop a relational database and we use a video-disc player to contain the pictorial part of the database. The system consists of a database input version and a read-only run version. The design of the database input version is discussed. Reference knowledge for ovary pathology requires 1-3 Mbytes of memory. At present 15% of this amount is available. The design of the run version is based on an analysis of which information must necessarily be specified to the system by the user to access a desired item of information. Finally, the use of AIDA in constructing DEW is evaluated.

Application of the method of multiple thresholding to white blood cell classification.

A new method of image segmentation based on the principle of multiple grey level thresholding has been applied to a data set consisting of 1149 white blood cells of 13 different, clinically important types, randomly chosen on 20 blood smears from leukemia patients. Classification of these cells on the basis of quantitative measurements in the segmented images yields an accuracy of 82.6%. Some of the erroneous classifications must be attributed to intrinsic problems in the assignment of a priori labels. Correcting for such cases, the performance of the method, as measured on the present data set, increases to 89.8%. This illustrates the practical applicability of the segmentation method in automated white blood cell and possibly other cytological and histological analysis systems.

Design of the diagnostic encyclopedia workstation (DEW).

The Diagnostic Encyclopedia Workstation (DEW) contains reference knowledge for diagnostic support in pathology. Illustrations are accessible via a video disc device. DEW can hold more knowledge, pictures and case histories than books, and its information is accessible via several entries. Software for data entry has been written in MUMPS with use of the relational database toolkit AIDA, which is particularly suited for manipulation of free text. The graphical mouse-driven user interface is written in C using MetaWindows. The DEW contains 85 diagnoses in ovarian pathology, covering all frequent cases and many rarities, illustrated by approximately 3000 pictures, divided among 158 cases.

Accuracy of optical density measurement of cells. 1: Low resolution.

In this paper we analyze factors influencing the accuracy and precision of optical density measurement of light microscopical objects. The study is applied to the DNA content of Feulgen-stained cells using a lowresolution, TV-equipped microscope connected to a digital image processing system. Factors influencing the accuracy of density measurement include staining (not considered here), image formation (glare, focus, diffraction), image sampling (distribution, sampling density, noise), and computational accuracy. These factors are reviewed with respect to potential remedies. Evaluation of the measurement error contribution is performed on the level of the individual cell and on the specimen level. It is concluded that a coefficient of variation of 5% (in contrast to 3.5% using flow cytometry of the same specimen) in the measured values of normal cells of one specimen is attainable using adequate shading correction. With relatively simple computational methods, image cytometry may be well suited for pathology practice.