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Biomedical subjects

P W Hamilton

Publications and source records attributed to P W Hamilton.

At least 73 records · Page 4Linked to original sources

Machine vision-based histometry of premalignant and malignant prostatic lesions.

The implementation of knowledge-guided control of the processing and segmentation of histopathologic images of prostatic lesions has made automated analysis and interpretation possible. To establish correspondence between histopathologic concepts, terms and diagnostic criteria, and computed histometric entities, "interpretive transforms" are introduced. Scene segmentation is controlled by an expert system following a model-based reasoning process. The expert system is structured as an associative network with frames at each node, which controls a knowledge file and a large library of image processing algorithms.

Expert Systems↗

Diagnostic decision support for prostate lesions.

The diagnostic evaluation of premalignant and malignant lesions of the prostate may benefit from the application of an inference network. Used as a diagnostic decision support system, an inference network provides standardized assessment of diagnostic clues which is supported by computer graphics and comparison imagery, uncertainty management by possibility and probabilistic schemes and the systematic combination of different pieces of diagnostic evidence. This assessment results in a numeric measure of belief in the final diagnosis.

Diagnosis, Computer-Assisted↗

Monoclonal antibodies Ki-67 and MIB1 in the distinction of tuboendometrial metaplasia from endocervical adenocarcinoma and adenocarcinoma in situ in formalin-fixed material.

This study was undertaken to determine whether immunostaining with the monoclonal antibodies Ki-67 and MIB1 is of use in the distinction of tuboendometrial metaplasia from endocervical adenocarcinoma and adenocarcinoma in situ (AIS) on formalin-fixed, paraffin-embedded tissue. Tissue sections from 100 cases (52 normal endocervix, 27 endocervical tuboendometrial metaplasia, eight endocervical AIS, 13 endocervical adenocarcinoma) were stained with Ki-67 and MIB1 after microwave pretreatment in citrate buffer. Ki-67 and MIB1 labelling indices (LIs) were calculated in each case by determining the percentage of positive-staining nuclei. Five hundred nuclei were counted in each case. Significant differences in Ki-67 and MIB1 LIs existed between the adenocarcinoma group and the tuboendometrial metaplasia group and between the AIS group and the tuboendometrial metaplasia group. No significant differences existed between the adenocarcinoma and AIS groups. Over all groups, the Ki-67 LI was consistently lower than the MIB1 LI. The results indicate that immunohistochemical staining with Ki-67 and MIB1 may be of use in the often difficult histological distinction of tuboendometrial metaplasia from malignant endocervical glandular lesions.

Adenocarcinoma↗

Knowledge-guided segmentation and morphometric analysis of colorectal dysplasia.

The histopathologic grading of colorectal adenomatous dysplasia is a subjective process. In this study, automated image analysis using knowledge-guided software was used to quantitatively assess colorectal glandular characteristics. Cases of histologically normal mucosa and of low, moderate and high grade dysplasia were examined using the technique. A total of 19 morphometric and densitometric features were measured on each gland. These included gland shape, epithelial area, nuclear stratification and nuclear optical density. Discriminant analysis of the data revealed those morphometric features which provided the best discrimination between the various histologic groups. The area of epithelium occupied by nuclei was the strongest discriminating variable, and this, in combination with a discriminant function derived from the remaining variables, was used to plot cases in bivariate sample space. The plots revealed that the data for normal glands were consistently well separated from dysplastic gland data. Data sets belonging to the various grades of dysplasia showed varying degrees of separation, depending which two histologic groups the discriminant function was based on. This study showed that automated image analysis of complex histologic scenes is possible using knowledge-guided segmentation and that it can provide useful data for the objective classification of colorectal dysplasia.

Adenoma↗

Clinical applications of Bayesian belief networks in pathology.

Bayesian belief networks (BBNs) are a novel tool for representing knowledge about diagnostic decision making and for obtaining a numerical measure of certainty in the final diagnosis. Belief networks have been applied to the pathological assessment of breast, prostate and skin lesions and have been shown to provide consistency in the grading of microscopic features and improve diagnosis. These applications are reviewed in the current paper. The application of BBNs has been further facilitated through the use of standardised imagery which is stored digitally and used to enter evidence into a BBN. It is predicted that the further development of BBNs with improved logical capabilities represent the key to improved decision making in pathology.

Bayes Theorem↗

Nuclear texture measurements in normal colorectal glands.

OBJECTIVE: To examine differences in epithelial cell nuclear texture along the length of normal, well-oriented colorectal glands. STUDY DESIGN: Histologically normal mucosa was obtained from four patients who had a family history of cancer and no hyperproliferation as assessed by bromodeoxyuridine immunohistochemistry. Serial sections were stained using the Feulgen technique and viewed to identify glands that were sectioned along their entire length. Two glands were sampled from each patient. Each gland was divided into three compartments based on epithelial cell counts along the length of the gland. Within each compartment, 10 nuclei were randomly selected and their nuclear texture features measured using computerized image analysis. RESULTS: Analysis of variance demonstrated that significant differences exist in the nuclear texture of cells in the different compartments of the gland. Discriminant analysis selected three variables that were important and independent in the quantitative discrimination of the gland compartments. These features were related to the elliptical shape, optical density distribution and cooccurrence structure of the chromatin texture within the epithelial nuclei. CONCLUSION: It is clear that these differences are associated with the spatial variation in proliferation and differentiation status found within colorectal mucosal glands. Nuclear measurements from colorectal epithelium with near-normal architecture should therefore be stratified in relation to position within the gland. Nuclear texture and size measurements within defined compartments may provide a sensitive means of detecting early malignant transformation.

Cell Nucleus↗

Light microscopic and three-dimensional morphology of the human muscular sarcocyst.

Established criteria for morphological typing of sarcocysts was applied to a large series of cases of human skeletal muscle sarcocystosis in Malaysia to determine the type of sarcocyst present. We also wanted to test the general usefulness of this classification and to determine if there are any new cyst types. Three-dimensional (3-D) reconstruction was done to see if the sarcocyst has a distinct 3-D morphology. A total of 66 sarcocysts from 21 cases of human muscle sarcocystosis obtained from a previous prevalence study were examined. Tissue sections (5 microns thick) were stained with haematoxylin and eosin and studied under the light microscope. For 3-D reconstruction, an image analyser was used to align and reconstruct the sarcocyst after microscopic images had been captured with a charge-coupled device (CCD) camera. All the cysts best fit into the type 4 category. This classification is generally useful, although cyst wall characteristics and zoite size appear to be the most reliable criteria for classification. The cyst width averaged 77 microns (range, 30-137.5 microns). Cyst walls were smooth, had no cytophaneres and were less than 1 micron thick. No secondary cyst wall or surrounding inflammation was evident. Numerous cyst merozoites with diameters averaging 1 micron filled the cyst lumen. Although septa were not apparent, in many cysts, zoites were arranged in a unique, curvilinear fashion that suggested their presence. 3-D reconstruction showed the sarcocyst to be a long, tortuous "cylinder" with no branching or other distinguishing feature.

Animals↗

Three-dimensional computerised analysis of epithelial cell proliferation in the gastrointestinal tract.

This study describes a new technique for the visualisation and quantitation of glandular epithelial cell proliferation in gastrointestinal mucosa using computerised three-dimensional reconstruction. The tissue used in this study was colorectal biopsy tissue infiltrated in vitro with bromodeoxyuridine (BrdU), although the method could be applied to any gastrointestinal site labelled with any specific marker for cell proliferation. The method is as follows. Five-micron-thick serial sections (> 100) were cut from colorectal biopsies infiltrated in vitro with BrdU. After labelling all the sections for BrdU-positive cells using standard immunohistochemistry, colorectal glands were identified which were completely sectioned within the series. Each microscopic image of the sectioned gland was orientated, digitised and stored using a Kontron image analyser. On each of the stored images, the crypt profile, the positive cells and the negative cells were interactively marked and digitally stored. Using three-dimensional (3-D) reconstruction software, the outer surface of the crypt, the total positive and the total negative fractions could be viewed in three dimensions. The total BrdU-positive cell number could be automatically calculated for the complete crypt or, alternatively, compartmental analysis of the labelling pattern within the crypt could be obtained. This represents a powerful technique: it does not require orientation, it can be carried out on complex glandular structures and is not affected by the biases involved in measuring labelling indices from single tissue sections.

Bromodeoxyuridine↗

Expert system support using Bayesian belief networks in the diagnosis of fine needle aspiration biopsy specimens of the breast.

AIM: To develop an expert system model for the diagnosis of fine needle aspiration cytology (FNAC) of the breast. METHODS: Knowledge and uncertainty were represented in the form of a Bayesian belief network which permitted the combination of diagnostic evidence in a cumulative manner and provided a final probability for the possible diagnostic outcomes. The network comprised 10 cytological features (evidence nodes), each independently linked to the diagnosis (decision node) by a conditional probability matrix. The system was designed to be interactive in that the cytopathologist entered evidence into the network in the form of likelihood ratios for the outcomes at each evidence node. RESULTS: The efficiency of the network was tested on a series of 40 breast FNAC specimens. The highest diagnostic probability provided by the network agreed with the cytopathologists' diagnosis in 100% of cases for the assessment of discrete, benign, and malignant aspirates. Atypical probably benign cases were given probabilities in favour of a benign diagnosis. Suspicious cases tended to have similar probabilities for both diagnostic outcomes and so, correctly, could not be assigned as benign or malignant. A closer examination of cumulative belief graphs for the diagnostic sequence of each case provided insight into the diagnostic process, and quantitative data which improved the identification of suspicious cases. CONCLUSION: The further development of such a system will have three important roles in breast cytodiagnosis: (1) to aid the cytologist in making a more consistent and objective diagnosis; (2) to provide a teaching tool on breast cytological diagnosis for the non-expert; and (3) it is the first stage in the development of a system capable of automated diagnosis through the use of expert system machine vision.

Bayes Theorem↗

Prostatic intraepithelial neoplasia. Development of a Bayesian belief network for diagnosis and grading.

The diagnosis and grading of prostatic intraepithelial neoplasia (PIN) are affected by uncertainties that arise from the fact that almost all our knowledge of PIN histopathology is not expressed in numeric form but rather in descriptive linguistic terms, words and concepts. A Bayesian belief network (BBN) was used to reduce the problem of uncertainty in diagnostic clue assessment while considering the dependencies between elements in the reasoning sequence. A shallow network was developed with an open-tree topology, with a root node containing the diagnostic alternatives and seven first-level descendant nodes for the diagnostic clues. One of these nodes was based on tissue architecture and the others on cell features. The results obtained with prototypes of relative likelihood ratios showed that beliefs for the diagnostic alternatives are very high. The network can grade and differentiate PIN lesions from other prostate lesions with certainty. A number of diagnostic clues greater than seven did not significantly improve network performance, whereas a reduced number of clues resulted in decreased beliefs. A BBN for PIN diagnosis and grading offers a descriptive classifier that is readily implemented and allows the use of linguistic, fuzzy variables. A BBN allows the accumulation of evidence presented by diagnostic clues, each offering only weak evidence.

Bayes Theorem↗

Morphometric analysis of colorectal cancer.

Thirteen nuclear and cellular morphometric variables were measured in 312 cases of colorectal adenocarcinoma. All variables, except nuclear shape factors, differed significantly (P < 0.001) between normal colorectal and tumor tissue. In adenocarcinomas, epithelial nuclei in well-differentiated mucosa tended to be elliptic, while those in poorly differentiated mucosa were more spheric. Increasing values of maximum nuclear and elliptic diameter were associated with progression from none to simple tubule configuration (P < 0.001), none to easily discerned nuclear polarity (P < 0.001), and expanding growth pattern (P < 0.001). Univariate survival analysis revealed that none of the morphometric variables was significantly related to patient survival. Multivariate regression analysis showed that no morphometric variable could add significantly to a model containing the variables of patient age, Dukes stage, and tumor differentiation. Morphometry may be useful in distinguishing malignant from normal tissue and degrees of differentiation, but it is of little prognostic value in colorectal adenocarcinoma.

Adenocarcinoma↗

Aligning histological serial sections for three-dimensional reconstruction using an excimer laser beam.

Accurate alignment of histological sections has always been a fundamental problem in the three-dimensional reconstruction of tissue structures from serial sections. An excimer laser was used to create small holes in paraffin processed colorectal tissue blocks. The laser holes were 200-230 microns in diameter and penetrated the tissue approximately 0.5 mm. No damage was caused to the surrounding tissue. Using a VIDAS image analyser, these microscopic holes could be used as artificial reference points (ARPs) for the accurate alignment of consecutive serial sections and three-dimensional reconstruction of colorectal glandular tissue.

Colon↗

Knowledge-guided segmentation of colorectal histopathologic imagery.

Scene segmentation in images of sections of colorectal glands is guided by a knowledge-based system. The construction of the knowledge file, processing sequences and computation of a crowding index for adenomatous glands are described. The histologic sections were stained by hematoxylin and eosin, and the image segmentation was difficult. The knowledge-based system has to determine, on the basis of context and logic, which detected object groups belong to which histologic components. Image segmentation was followed by a reconstruction process. Acceptable segmentation was attained in approximately 85% of the glands processed.

Adenoma↗

Morphometry of gastric carcinoma: its association with patient survival, tumour stage, and DNA ploidy.

Morphometric image analysis of nuclear features was performed on tissue from 46 patients who had had curative resections for gastric cancer. Clinical, pathological, flow cytometric, and follow-up data were available for these patients, which were drawn from a larger, previously reported series. The morphometric data were compared with patient survival, clinico-pathological status, and DNA ploidy. Univariate survival analysis revealed that morphometric parameters were not significantly related to survival, but examination of clinico-pathological data showed lymph node involvement, involvement of the resection margin, and lymphatic invasion to be significantly associated (P < 0.01) with patient prognosis. Multivariate survival analysis using the Cox model found only lymph node and resection margin involvement to be independently related to survival. Comparison of morphometric results with the clinico-pathological parameters showed various features, relating to nuclear size, and its variation to be significantly associated (P < 0.01) with the presence of lymphatic invasion, resection margin involvement, and tumour pattern (intestinal/diffuse). A comparison of morphometry with flow cytometric analysis in these cases showed that nuclear size was not significantly related to either DNA aneuploidy or the DNA proliferative index.

Aged↗

Grading of superficial antral gastritis: comparison of cell-counting and photographic-based methods.

A cell-counting technique and a photographic-based scoring system for assessing inflammatory cell infiltration were compared for agreement in 275 endoscopic gastric antral biopsies from 55 dyspeptic patients. Each biopsy was independently scored 0-5 for polymorphs and mononuclear cells using both methods, and a mean score was derived for each patient. There was a highly significant correlation between the mean patient scores obtained using each method (P less than 0.001). Agreement statistics showed that the mean score difference (cell-counting minus photographic score) was negative for polymorphonuclear and mononuclear cells, indicating that the photographic method yielded higher mean patient scores. Scatterplots of difference versus mean by the two methods showed that only 3.6 per cent of scores fell outside +/- 2 SD of the mean difference. The use of standard photomicrographs to grade superficial antral gastritis therefore provides accurate results, comparable to those obtained by cell counting, yet is a faster and much cheaper technique.

Biopsy↗

A comparison of symptoms between non-ulcer dyspepsia patients positive and negative for Helicobacter pylori.

The role of Helicobacter pylori infection in the symptom complex associated with non-ulcer dyspepsia is uncertain, despite the presence of the organism in a high proportion of these patients. In order to exclude physician bias in history taking, 18 patients (9 female) diagnosed as non-ulcer dyspepsia, after endoscopy and gallbladder ultrasonography, underwent computer interrogation using the Glasgow Diagnostic System for Dyspepsia (GLADYS). Five antral and 3 fundal endoscopic biopsies from these patients were also histologically examined for the presence of Helicobacter pylori and quantitatively analysed for polymorph and chronic inflammatory cell densities per mm2 of lamina propria using computer-linked image analysis. In the group of 9/18 patients who were positive for Helicobacter pylori, there were significantly higher antral and fundal inflammatory cell counts than in negative patients. However, analysis of the GLADYS interrogation data showed no significant positive relationships between Helicobacter pylori positivity and any gastrointestinal symptoms. These results confirm a significant association between Helicobacter pylori and superficial gastritis but suggest that non-ulcer dyspepsia in patients with Helicobacter pylori colonisation is probably not a clinically identifiable and distinct syndrome.

Biopsy↗