CiteULike: Tag histopathology

Reactions to Uncertainty and the Accuracy of Diagnostic Mammography

Patricia Carney — 2007-01-23T12:08:50-00:00

Journal of General Internal Medicine

The comparative power of the discriminant methods used in toxicological pathology.

T Holland — 2006-11-09T20:18:46-00:00

Toxicol Pathol, Vol. 33, No. 4. (2005), pp. 490-494.

It is highly desirable to use experimental methodologies in toxicological pathology that combine statistical power, practicality, and objective reviewability to detect small differences. The different ways of gathering data at the microscope can result in clear differences in power to discriminate small, but real, differences between treated and control rodent groups with nonneoplastic lesions. Six alternative methods of gathering and analysing results are compared. They are referred to as the Measuring, Ordering, Scoring (or Grading), Pair-contrast, Outside-control, and Affected methods. Measuring and Ordering methods are uniformly more powerful than other more common and highly esteemed methods, such as Scoring/Grading. From the practical perspective, Measuring and Ordering can be applied objectively, reviewed objectively, and interpreted to standards that are widely accepted as valid throughout experimental science e.g., using confidence limits and intervals. They also are intuitively natural extensions of routine toxicological histopathological examinations. Establishing a small difference between control and treated groups is commonly a problem when reporting no-observed-effect levels. Ordering is the recommended method for assessing if a small difference between treated and control groups is within chance variation or is the result of a true treatment effect, when measurement is impractical.

A survey of discriminant methods used in toxicological histopathology.

T Holland — 2006-11-09T20:17:33-00:00

Toxicol Pathol, Vol. 29, No. 2. (r 2001), pp. 269-273.

A cluster survey of United Kingdom (UK)-based toxicological pathologists has been made of the methods used to discriminate treatment-related from spontaneous variation in histopathological material from toxicity studies. The response rate was 78% of 102 polled. Respondents overwhelmingly preferred methods based on grading or scoring lesions and comparatively avoided methods based on ranking, measuring, counting, pairwise comparisons, or overviewing. This preference was in spite of regarding parametric and ranking methods as both more powerful and specific than some commonly used scoring methods. Respondents were evenly divided on the use of blind examination and tended to avoid using historic material to form an opinion.

Inductive Risk and Values in Science

Heather Douglas — 2006-11-09T18:45:56-00:00

Philosophy of Science, Vol. 67, No. 4. (2000), pp. 559-579.

Although epistemic values have become widely accepted as part of scientific reasoning, non-epistemic values have been largely relegated to the "external" parts of science (the selection of hypotheses, restrictions on methodologies, and the use of scientific technologies). I argue that because of inductive risk, or the risk of error, non-epistemic values are required in science wherever non-epistemic consequences of error should be considered. I use examples from dioxin studies to illustrate how non-epistemic consequences of error can and should be considered in the internal stages of science: choice of methodology, characterization of data, and interpretation of results.

Accuracy of Radiography, Nuclear Scintigraphy, and Histopathology for Determining the Proximal Extent of Distal Radius Osteosarcoma in Dogs

Nicole Leibman — 2007-07-26T22:22:26-00:00

Veterinary Surgery, Vol. 30, No. 3. (2001), pp. 240-245.

Objective- To compare the accuracy of radiography, nuclear scintigraphy, and histopathology for determining the proximal extent of distal radius osteosarcoma in dogs. Study Design- Retrospective clinical study. Sample Population- Twenty client-owned dogs taken to Colorado State University with osteosarcoma of the distal radius. Methods- Medical records of 20 dogs with confirmed osteosarcoma that underwent a limb-salvage procedure were reviewed. Measurements were performed directly from the lateral view of each radius, from both the scintigram and the radiograph, to determine the length of the radius and the distance from the proximal extent of the tumor to the distal radiographic or scintographic extent of the radius. The ratio of distal radial involvement to total radius length was calculated. A similar ratio was also determined using the macroslide, which included the entire portion of bone that was excised during the limb-salvage procedure. All 3 methods of measurement were compared. Results- Nuclear scintigraphy significantly overestimated tumor length when compared with macroslide specimen measurements. Radiography also overestimated tumor length, but these results were not significantly different from macroslide specimen measurements. Conclusions- Both radiography and nuclear scintigraphy overestimate the extent of distal radiaus osteosarcoma in dogs when compared with histopathologic macroslides of the same lesions. Nuclear scintigraphy overestimated tumor extent to a larger degree than did radiography. Clinical Relevance- Although radiography is a more accurate method of measurement of the extent of distal radius osteosarcoma, because nuclear scintigraphy overestimates tumor length to a greater degree, scintigraphy may provide a larger margin of safety for determining the site of proximal osteotomy during a limb-salvage procedure. However, caution should be taken when utilizing scintigraphy, because this method may overestimate length of radius involved to such an extent as to cause the surgeon to believe that a patient is not a suitable limb-salvage candidate. cCopyright 2001 by The American College of Veterinary Surgeons

Canine model of ischemic stroke with permanent middle cerebral artery occlusion: clinical and histopathological findings.

BT Kang — 2007-11-28T13:13:21-00:00

J Vet Sci, Vol. 8, No. 4. (December 2007), pp. 369-376.

The aim of the present study was to assess the clinical and histopathological findings in a canine model of ischemic stroke. Cerebral ischemic stroke was induced by middle cerebral artery occlusion in four healthy beagle dogs using silicone plugs. They showed neurological signs of forebrain dysfunction such as reduced responsiveness, head turning, circling, postural reaction deficits, perceptual deficits, and hemianopsia. These signs gradually regressed within 4 weeks without therapy. On magnetic resonance imaging, T2 hyperintensity and T1 hypointensity were found in the cerebral cortex and basal ganglia. These lesions were well-defined and sharply demarcated from adjacent brain parenchyma with a homogenous appearance. No abnormalities of the cerebrospinal fluid were observed. At necropsy, atrophic and necrotic lesions were observed in the cerebral cortex. The cerebral cortex, basal ganglia, and thalamus were partially unstained with triphenyl- tetrazolium chloride. Histopathologically, typical features of infarction were identified in cortical and thalamic lesions. This study demonstrates that our canine model resembles the conditions of real stroke patients.

Calcification of intervertebral discs in the dachshund: a radiographic and histopathologic study of 20 dogs

Oyvind Stigen — 2007-12-21T22:47:07-00:00

Acta Veterinaria Scandinavica, Vol. 49 (21 December 2007), 39.

Morphometric analysis of experimentally induced periapical lesions: radiographic vs histopathological findings.

A De Rossi — 2007-08-21T16:05:17-00:00

Dentomaxillofac Radiol, Vol. 36, No. 4. (May 2007), pp. 211-217.

OBJECTIVES: To evaluate the accuracy and reliability of conventional (Kodak Ektaspeed Plus film) and digitized radiographic images to detect the presence as well to estimate the size, as measured by an image analysis programme, of periapical radiolucencies induced in dog teeth in comparison with the histomorphometric data obtained from the same lesions by conventional and fluorescence microscopy. METHOD: After the removal of pulp, the root canals of five premolars from the same animal were left exposed for 7 days after which they were sealed for 60 days. At day 53, three more premolars were opened and left exposed to the oral cavity for 7 days. Intact premolars were used as control. Conventional radiographs were taken at day 0, day 7, day 30, day 45 and day 60. Morphometry in digitized radiographic images and histological sections were compared at day 7 and day 60 after setting the experimental series. RESULTS: Radiographically, periapical lesions were only detected 30 days after coronal sealing. A progressively increasing radiolucent lesion area was observed at day 45 and day 60. Histopathologically, 7 days after pulp removal dense inflammatory infiltrate and root resorption in the periapical region was observed. At day 7 and day 60, the lesion sizes were similar when evaluated by both conventional and fluorescence microscopy. Lesion size was about 20% larger in digitized radiographs in comparison with histological measurements. CONCLUSIONS: Although image digitization could not improve the detection of the early stages of periapical lesions, it provides a valuable quantitative assessment of extensive periapical lesions. In addition, fluorescence light microscopy enhances the visualization of the apical and periapical structures and seems to be a highly useful tool for histological evaluation, valuable for both qualitative and quantitative studies of periapical disease.

An assessment of digital image analysis to measure fibrosis in liver biopsy specimens of patients with chronic hepatitis C.

MJ O'Brien — 2008-02-01T16:25:02-00:00

Am J Clin Pathol, Vol. 114, No. 5. (November 2000), pp. 712-718.

The aim was to assess the validity of a digitally computed fibrosis ratio as a measure of fibrosis stage in liver biopsy specimens. We scored 230 liver biopsy specimens from patients with chronic hepatitis C for fibrosis using modified Knodell criteria; fibrosis ratios were computed from digital images that encompassed the complete trichrome-stained section of each case. Although an overall correlation between fibrosis ratio and ordinal score was present, subset analysis showed that this correlation existed only among biopsy specimens with high scores (3-6, early bridging fibrosis to established cirrhosis). There was no correlation or difference between category means found among biopsy specimens with low scores (0-3, normal to early bridging fibrosis). Furthermore, concordance by both estimates in direction of fibrosis change among serial liver biopsy specimens was found in only 11 (30%) of 37 pairs compared. The findings suggest that a qualitative assessment of the computerized fibrosis pattern is necessary for the interpretation of computerized fibrosis ratio measurements, particularly in patients with early stage fibrosis.

Modern imaging technologies in toxicologic pathology: An overview.

X Ying — 2008-02-05T15:22:48-00:00

Toxicol Pathol, Vol. 34, No. 7. (2006), pp. 815-826.

Modern imaging technology, now utilized in most biomedical research areas (bioimaging), enables the detection and visualization of biological processes at various levels of the molecule, organelle, cell, tissue, organ and/or whole body. In toxicologic pathology, the impact of modern imaging technology is becoming apparent from digital histopathology to novel molecular imaging for in vivo studies. This overview summarizes recent progresses in digital microscopy imaging and newly developed digital slide techniques. Applications of virtual microscopy imaging are discussed and compared to traditional optical microscopy reading. New generation digital pathology approaches, including automatic slide inspection, digital slide databases and image management are briefly introduced. Commonly used in vivo preclinical imaging technologies are also summarized. While most of these new imaging techniques are still undergoing rapid development, it is important that toxicologic pathologists embrace and utilize these technologies as advances occur.

An automated machine vision system for the histological grading of cervical intraepithelial neoplasia (CIN)

Stephen Keenan — 2008-03-05T00:00:00-00:00

The Journal of Pathology, Vol. 192, No. 3. (2000), pp. 351-362.

The histological grading of cervical intraepithelial neoplasia (CIN) remains subjective, resulting in inter- and intra-observer variation and poor reproducibility in the grading of cervical lesions. This study has attempted to develop an objective grading system using automated machine vision. The architectural features of cervical squamous epithelium are quantitatively analysed using a combination of computerized digital image processing and Delaunay triangulation analysis; 230 images digitally captured from cases previously classified by a gynaecological pathologist included normal cervical squamous epithelium (n=30), koilocytosis (n=46), CIN 1 (n=52), CIN 2 (n=56), and CIN 3 (n=46). Intra- and inter-observer variation had kappa values of 0.502 and 0.415, respectively. A machine vision system was developed in KS400 macro programming language to segment and mark the centres of all nuclei within the epithelium. By object-oriented analysis of image components, the positional information of nuclei was used to construct a Delaunay triangulation mesh. Each mesh was analysed to compute triangle dimensions including the mean triangle area, the mean triangle edge length, and the number of triangles per unit area, giving an individual quantitative profile of measurements for each case. Discriminant analysis of the geometric data revealed the significant discriminatory variables from which a classification score was derived. The scoring system distinguished between normal and CIN 3 in 98.7% of cases and between koilocytosis and CIN 1 in 76.5% of cases, but only 62.3% of the CIN cases were classified into the correct group, with the CIN 2 group showing the highest rate of misclassification. Graphical plots of triangulation data demonstrated the continuum of morphological change from normal squamous epithelium to the highest grade of CIN, with overlapping of the groups originally defined by the pathologists. This study shows that automated location of nuclei in cervical biopsies using computerized image analysis is possible. Analysis of positional information enables quantitative evaluation of architectural features in CIN using Delaunay triangulation meshes, which is effective in the objective classification of CIN. This demonstrates the future potential of automated machine vision systems in diagnostic histopathology. Copyright © 2000 John Wiley & Sons, Ltd.

Image processing, diagnostic information extraction and quantitative assessment in pathology

Alfredo Santinelli — 2008-01-31T14:16:22-00:00

Journal of Cellular and Molecular Medicine, Vol. 6, No. 1. (2002), pp. 93-106.

Abstract As we enter the information age we hold strong beliefs in the benefits of digital technology applied to pathology: numerical representation offers objectivity. Digital knowledge may indeed lead to significant information discovery, and, processing systems might be designed to allow a true evolution of capabilities. Questions arise whether the methodology underlying quantitative analysis provides the information that we need and whether it is appropriate for some of the problems encountered in diagnostic and prognostic histopathology. While one certainly would not dispute the value of statistical procedures, the clinical needs call for individual patient targeted prognosis.

Combined histomorphometric and gene-expression profiling applied to toxicology

Andres Kriete — 2008-04-15T19:02:38-00:00

Genome Biology, Vol. 4, No. 5. (2003)

We have developed a unique methodology for the combined analysis of histomorphometric and gene-expression profiles amenable to intensive data mining and multisample comparison for a comprehensive approach to toxicology. This hybrid technology, termed extensible morphometric relational gene-expression analysis (EMeRGE), is applied in a toxicological study of time-varied vehicle- and carbon-tetrachloride (CCl4)-treated rats, and demonstrates correlations between specific genes and tissue structures that can augment interpretation of biological observations and diagnosis.

A Framework for the Automated Analysis of Subcellular Patterns in Human Protein Atlas Images

Justin Newberg — 2008-04-26T04:07:50-00:00

J. Proteome Res. (25 April 2008)

Abstract: The systematic study of subcellular location patterns is required to fully characterize the human proteome, as subcellular location provides critical context necessary for understanding a proteins function. The analysis of tens of thousands of expressed proteins for the many cell types and cellular conditions under which they may be found creates a need for automated subcellular pattern analysis. We therefore describe the application of automated methods, previously developed and validated by our laboratory on fluorescence micrographs of cultured cell lines, to analyze subcellular patterns in tissue images from the Human Protein Atlas. The Atlas currently contains images of over 3000 protein patterns in various human tissues obtained using immunohistochemistry. We chose a 16 protein subset from the Atlas that reflects the major classes of subcellular location. We then separated DNA and protein staining in the images, extracted various features from each image, and trained a support vector machine classifier to recognize the protein patterns. Our results show that our system can distinguish the patterns with 83% accuracy in 45 different tissues, and when only the most confident classifications are considered, this rises to 97%. These results are encouraging given that the tissues contain many different cell types organized in different manners, and that the Atlas images are of moderate resolution. The approach described is an important starting point for automatically assigning subcellular locations on a proteome-wide basis for collections of tissue images such as the Atlas.