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H Christen

Publications and source records attributed to H Christen.

At least 19 recordsLinked to original sources

Methods in quantitative image analysis.

The main steps of image analysis are image capturing, image storage (compression), correcting imaging defects (e.g. non-uniform illumination, electronic-noise, glare effect), image enhancement, segmentation of objects in the image and image measurements. Digitisation is made by a camera. The most modern types include a frame-grabber, converting the analog-to-digital signal into digital (numerical) information. The numerical information consists of the grey values describing the brightness of every point within the image, named a pixel. The information is stored in bits. Eight bits are summarised in one byte. Therefore, grey values can have a value between 0 and 256 (2(8)). The human eye seems to be quite content with a display of 5-bit images (corresponding to 64 different grey values). In a digitised image, the pixel grey values can vary within regions that are uniform in the original scene: the image is noisy. The noise is mainly manifested in the background of the image. For an optimal discrimination between different objects or features in an image, uniformity of illumination in the whole image is required. These defects can be minimised by shading correction [subtraction of a background (white) image from the original image, pixel per pixel, or division of the original image by the background image]. The brightness of an image represented by its grey values can be analysed for every single pixel or for a group of pixels. The most frequently used pixel-based image descriptors are optical density, integrated optical density, the histogram of the grey values, mean grey value and entropy. The distribution of the grey values existing within an image is one of the most important characteristics of the image. However, the histogram gives no information about the texture of the image. The simplest way to improve the contrast of an image is to expand the brightness scale by spreading the histogram out to the full available range. Rules for transforming the grey value histogram of an existing image (input image) into a new grey value histogram (output image) are most quickly handled by a look-up table (LUT). The histogram of an image can be influenced by gain, offset and gamma of the camera. Gain defines the voltage range, offset defines the reference voltage and gamma the slope of the regression line between the light intensity and the voltage of the camera. A very important descriptor of neighbourhood relations in an image is the co-occurrence matrix. The distance between the pixels (original pixel and its neighbouring pixel) can influence the various parameters calculated from the co-occurrence matrix. The main goals of image enhancement are elimination of surface roughness in an image (smoothing), correction of defects (e.g. noise), extraction of edges, identification of points, strengthening texture elements and improving contrast. In enhancement, two types of operations can be distinguished: pixel-based (point operations) and neighbourhood-based (matrix operations). The most important pixel-based operations are linear stretching of grey values, application of pre-stored LUTs and histogram equalisation. The neighbourhood-based operations work with so-called filters. These are organising elements with an original or initial point in their centre. Filters can be used to accentuate or to suppress specific structures within the image. Filters can work either in the spatial or in the frequency domain. The method used for analysing alterations of grey value intensities in the frequency domain is the Hartley transform. Filter operations in the spatial domain can be based on averaging or ranking the grey values occurring in the organising element. The most important filters, which are usually applied, are the Gaussian filter and the Laplace filter (both averaging filters), and the median filter, the top hat filter and the range operator (all ranking filters). Segmentation of objects is traditionally based on threshold grey values. (AB

Algorithms

Telepathology: frozen section diagnosis at a distance.

Telepathology may be used to provide a frozen section service to hospitals without a department or institute of pathology. We have developed a telepathology system using the commercially available Integrated Services Digital Network (ISDN). The main software and hardware elements of our system are: Apple Macintosh workstations, a program for simultaneous transfer of image, voice and data, and a data bank for storage of patients' data and microscopic images. A picture instrument manager (PIM) makes remote control of microscopes or other instruments possible. The system connects the Department of Pathology of the University of Basel with the Regional Hospital of Samedan, 250 km away, and the Regional Hospital of Burgdorf, 100 km away. During a period of 20 months, frozen sections with the hospitals in Samedan and Burgdorf were performed in 53 patients. Between 54 and 58 s were required for the transfer of a diagnostic 8-bit grey level image containing 341 +/- 26.1 (standard error) kbytes (n = 13) or a diagnostic 24-bit colour image containing 165 +/- 16.9 kbytes (n = 40). Frozen section diagnosis was completed in 20-40 min. True-positive diagnoses of malignant tumours were achieved in 85.7% of cases (sensitivity = 0.857). No false-positive diagnosis was made. In 3 of the 53 cases telepathological diagnosis was not possible for technical reasons.

Frozen Sections

Diagnostic tools for differentiating pleural mesothelioma from lung adenocarcinoma in paraffin embedded tissue. II. Design of an expert system and its application to the diagnosis of mesothelioma.

A panel of 14 antibodies (panepithelial antibody Lu-5, anti-keratin-18, anti-keratin-7, Ber-EP4, anti-Leu-M1, HEA-125, anti-carcinoembryonic antigen, anti-blood group-related antigens A, B, H, B72.3, anti-placental alkaline phosphatase, anti-vimentin and BMA-120), which have been evaluated for use in differentiating mesothelioma from lung adenocarcinoma, was applied to a group of 24 suspected mesotheliomas. Using the established qualitative, descriptive criteria derived from monovariate statistical analysis of the tumour control groups (definite mesotheliomas, adenocarcinomas), a definitive allocation was possible in only 25% of suspected cases. We therefore constructed two "expert systems", based on multivariate discriminant analysis with either the ALLOC 80 program for ordinal data or a newly developed analysis program for binomial data. With these two systems diagnostic allocation of suspected mesotheliomas was improved to 75% and 79%. The use of binomial data ("positive" versus "negative") in conjunction with the probability-based test system is of particular interest because the primary data are easy to record and the test results have a higher statistical probability.

Adenocarcinoma

Telepathology with an integrated services digital network--a new tool for image transfer in surgical pathology: a preliminary report.

We describe a low-cost telepathology system working via a commercial integrated services digital network (ISDN) and consisting of modular software and hardware elements. The main elements are Apple Macintosh workstations; a software program for the simultaneous transfer of pictures, voice, and data; and procedures for image processing and general administration of all the information generated. Additionally, the system allows remote control of any peripheral instruments by a "picture-instrument manager." The transfer rate is currently 64 kbit/s; it will be extended to 128 kbit/s (ISDN basic rate) in the near future and to 2 Mbit/s (ISDN primary rate) in the next 2 years. The system was tested by the regional hospital in Samedan, Switzerland, and the Department of Pathology, University of Basel, Basel, Switzerland, a distance of 250 km, by offering a remote frozen section service to the regional hospital in 16 cases. Fifty-four to 58 seconds were needed for the transfer of a diagnostic 8-bit grey-level image containing 341 (median value) +/- 26.1 (standard error) kbytes (n = 13) or a diagnostic 24-bit color image containing 165 (median value) +/- 16.9 (standard error) kbytes (n = 3). The time required for a diagnostic session was between 25 and 35 minutes.

Adult

Age-related modification of average volume and anisotropy of vascular smooth muscle cells.

The aim of this study was to determine what changes in the arterial wall are related to age. In two groups of rabbits, one young and one adult, the aorta and carotid were studied using a morphometric approach based on stereological axioms and planimetric morphometry. The problem of anisotropy of smooth muscle cells is discussed in detail. Two forms of anisotropy must be distinguished, that of single cell and that due to the histological pattern of the smooth muscle cells in the arterial wall. Our results show in adult animals, as compared to the young ones, statistically significant decrease in anisotropy of the cell pattern which tends to become more regular. Moreover, in aorta and carotid of young and adult animals there is an increment of 95.39% and 80% of the absolute cell volume, respectively. We suggest that there may be a direct relationship between aging and phenotypical modulation of the smooth muscle cells and that the modification of the architectural cell pattern with age may represent an adaptive event related to the change in forces acting upon the arterial wall.

Aging

Morphological, immunohistochemical, stereological and nuclear shape characteristics of proliferative Leydig cell alterations in rats.

Proliferative Leydig cell (LC) alterations (hyperplasia, adenoma) of laboratory rats often pose diagnostic problems because the progression from normal to hyperplasia to neoplasia is continuous. The LC compartments of 130 Wistar rats (kfm: WIST strain) of approximately 2 years of age were examined. Ten typical cases conventionally classified as being normal or as showing diffuse or focal hyperplasia or small or large adenomata were investigated in more detail. In large adenomata, areas with large and small LC nuclei were identified. Immunohistochemical characterization, EM examination, as well as stereologic and planimetric investigations were performed. Hyperplastic and neoplastic LC essentially retained their normal appearance and immunohistochemical characteristics, but were found to contain more lipid droplets, fibroblast-like cells and patches of collagen than normal LC at the EM level. LC proliferation was accompanied by significant LC hypertrophy. LC nuclei of hyperplastic LC compartments were slightly larger while those of LC adenoma were markedly larger than nuclei of normal LC. The values for circle-related and ellipticity factors indicated that the nuclei of normal and hyperplastic LC were more markedly oval than nuclei of neoplastic LC. Concavity factor and bending energy measurements revealed that the small and oval nuclei of normal and hyperplastic LC had significantly more and deeper indentations than the larger and somewhat rounder nuclei of neoplastic LC. It is concluded that LC proliferations conventionally diagnosed as hyperplasia or adenoma on the basis of their size were composed of cytologically different LC populations.

Adenoma

[Morphology and function of macrophages in AIDS in broncho-alveolar lavages (BAL)].

HIV infects susceptible T-cell and mononuclear phagocyte targets. Unlike the dramatic changes that occur with T-cells during HIV disease, changes in monocyte and macrophage phenotype and function are qualitatively minimal. The aim of the study was to quantitatively analyze the morphology of macrophages in broncho-alveolar lavages in patients without AIDS, with AIDS, with AIDS complicated by Pneumocystis carinii and in carcinoma patients. In patients with AIDS, the nuclei of macrophages demonstrate a higher integrated optical density (2P less than 0.10), are bigger in size (2P less than 0.05) and have less notches (2P less than 0.02).

Acquired Immunodeficiency Syndrome

[What role does informatics play in pathology?].

Informatics can be understood as an element of management, dealing with structures of files, algorithms and hardware. The most important prerequisite to successful use of informatics is an optimal compatibility between these single elements. To realize this compatibility and to ascertain a permanent operability of informatics in pathology, the realization of the following two conditions are advisable: 1) The differentiation between a general administrative system of the whole department of pathology and systems of special units (e.g. laboratories); 2) the modularity of the laboratory systems.

Humans

Some fundamental aspects of morphometry in clinical pathology, demonstrated on a simple, multipurpose analysis system.

The aim of this study was (1) to investigate the value of morphometry, (2) to fix a set of parameters suitable for analyzing diagnostic problems, and (3) to create a general strategy for data storage and for user-friendly data management. The intrinsic value of morphometry lies in the fact that in contrast to other morphologic methods, it permits the presentation of findings in the form of numbers. The following set of morphometric parameters, in the broad sense of the term morphometry, is standard in our laboratory: planimetric parameters (shape descriptors), parameters of the gray value histogram (descriptors of the general gray value distribution), texture parameters (descriptors of the correlation between various image segments), invariant moments (descriptors of the size and localization of textural image segments) and densitometric parameters. The introduction of morphometric procedures into the daily routine is facilitated if data registration and evaluation are performed separately. Original data generated by direct measurement are primary or raw data, which are stored as such. In a separate, second step these raw data are used to compare more or less complex morphometric parameters, which are called "secondary data". A system designed for separate data registration and evaluation can easily be adapted to new methodologic developments. For instance, primary data on objects (gray values, coordinates of the contour) measured one time in the past can be reused at any other time for computing new features from these data. This procedure is comparable to the possibilities in immunohistochemical staining: new immunohistochemical stains can be applied to newly prepared sections of old tissue blocks.

Computer Communication Networks

The significance of morphometric methods in cytologic diagnostics: differentiation between mesothelial cells, mesothelioma cells and metastatic adenocarcinoma cells in pleural effusions with special emphasis on chromatin texture.

Opinions differ widely as to the value of morphometric techniques for differentiating between mesothelial cells, mesothelioma cells and metastatic adenocarcinoma cells in pleural effusions. The significance of the changes in the chromatin structure to differentiate between these three cell types was stressed by various scientific groups only qualitatively, and until now no group has used digital methods to quantify chromatin structures. The controversy about the value of morphometric methods was the reason for conducting the following study. We wanted to investigate (i) the importance of various planimetric and texture parameters as well as invariant moments as morphometric discriminators; and (ii) to set up a data structure to make possible the further diagnostic use of the multivariate morphometric analyses method for other applications. The present findings show that nuclear size and form are not the decisive factors in differentiating between reactive cells and mesothelioma cells, but pixel related texture parameters and invariant moments are. All parameter types used showed differences between reactive cells and cells of adenocarcinoma metastases. Invariant moments and shape descriptors, but not texture parameters are used to discriminate between mesothelioma cells and cells of adenocarcinoma metastases.

Adenocarcinoma

[Prerequisites for the application of statical morphometry in diagnostics].

The aims of the present paper were: 1. to test a set of parameters suitable for quantifying morphological features; 2. to create a generally valuable strategy for data storage and for a user friendly data management; 3. to examine the parameter set and the conception for an optimal data management by the quantification of cytological specimens of pleural effusions. The significance of a distinction between "primary parameters" (data directly captured during the measurement) and "secondary data" (data calculated from the primary data) is explained. In the first step of classification of the cytological specimens 81.8% of the patients with reactive alterations of mesothelial cells (n = 11) and 100% of the patients with tumours (mesotheliomas and metastasis of adenocarcinomas) (n = 19) were correctly classified with the aid of a little "expert system". In the second step (discrimination between mesotheliomas (n = 6) and metastasis of adenocarcinomas (n = 13] all patients were correctly classified.

Cytodiagnosis

A simple "expert system" for morphometric evaluation of cells in pleural effusions.

Quantitation in diagnostic pathology serves to improve both diagnostic reliability and the prognosis of various malignant tumors. Unfortunately, flexible, user-friendly, reasonably priced and compatible morphometric systems are hardly available on the market. A modular Apple II PC-based system was therefore developed in-house. It records stereologic, planimetric and digital image analysis data and calculates secondary parameters. Detailed statistical analyses can be performed, after data transfer, on larger computers. A typical application of diagnostic morphometry is to determine whether, and with which probability a patient with an unclear histopathologic finding can be assigned to one or more groups of patients with known diseases and prognoses. To this end morphometric data of the patient under investigation are compared with other patient data stored in an expert system. This paper describes the concept of an expert system carried out on the Apple II PC system mentioned above and outlines the evaluation procedures. Invariant moments were used to describe nucleus textures. Results obtained from the cytological analysis of pleural effusions demonstrate that with this approach it is possible to differentiate between normal mesothelium, mesothelioma and metastases of adenocarcinomas.

Adenocarcinoma

Digital image analysis in cytological diagnosis: a morphometric analysis on pleural mesotheliomas.

In the course of the last years digital image analysis has become increasingly important in the field of quantitative pathology. This may be due to the technical development of computers which have now reached a high user-friendly standard. In the present paper we present: (1) the development of a simple system for the measurement of digital image analysis; (2) the development of a general data structure applicable to various measurements and classification strategies; and (3) the analysis of the value of invariant moments (IM) as regional descriptors to distinguish mesothelial cells from mesothelioma cells in cytologic smears of pleural fluid. The results show that the invariant moments contain information concerning the geometric distribution of the grey values of the pixels as well as the staining intensity. The invariant moments present combination parameters and are therefore ideal morphometric parameters. With the invariant moments 7 out of 7 patients with mesotheliomas and 8 out of 11 control subjects could be assigned correctly in a nonparametric discriminant analysis procedure.

Cell Nucleus

Prognostic significance (relapse, non-relapse) of nuclear shape parameters in lymph node negative breast cancer.

A series of 15 postmenopausal patients with stage I invasive breast cancer (pT1-2, pNO, cMO) of uniform histologic type (ductal, NOS) was selected from the Basel Cancer Registry for retrospective analysis. A group of seven patients with a minimal disease-free survival of 9 years was compared to a group of eight patients with clinical and/or histopathological relapse within 8 years of mastectomy. Computer-assisted morphometry of cancer nuclei in routine histological material was used to investigate possible correlations of clinical outcome with nuclear size and shape parameters. Significant differences were found for certain shape descriptors by nonparametric statistical analysis. Stepwise discriminant analysis was applied to find the best combination of parameters separating the two prognostic groups. Application of the 'leaving one out method' showed correct classification in 6 of 8 recurrent cases and in all non-recurrent cases. The number of patients is small, therefore the results should be carefully interpreted.

Breast Neoplasms