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D J Zahniser

Publications and source records attributed to D J Zahniser.

At least 19 recordsLinked to original sources
PubMed1995

Combined malignancy associated change and contextual analysis for computerized classification of cervical cell monolayers.

Previous efforts to automate cervical cell analysis have focused on algorithms that use measurements of high resolution images of individual cells for 'rare event' detection of abnormal cells, sometimes in combination with cluster analysis of low resolution images. A new methodology was developed in which intermediate cell markers (indicating malignancy associated change) and contextual analysis of slide architecture were performed on the same digital images at 0.33 mu pixel resolution. A total of one hundred and forty-six cases that were either negative or at least high grade squamous intraepithelial lesions (HGSIL) were prepared as monolayers, and about 20 fields per slide were analyzed. Features most important for intermediate cell marker analysis were those that measured the variation in nuclear texture measurements across the slide as well as densitometric features. The most discriminatory contextual features were those that measured the variation of the arrangement of cells within a cluster across the slide. Linear discriminants were calculated using the most important features from both types of analysis; they provided smear classification accuracies of 71-86%.

Carcinoma↗
PubMed1994

Computerized contextual analysis in diagnosis.

Cervical cytology specimens prepared as monolayers were analyzed with a combination of high-resolution single-cell image analysis and lower-resolution contextual image analysis. For the latter, quantitative features of cluster architecture, object distribution and background were used to mimic the pathologists global assessment of a specimen. Contextual analysis correctly classified 81% of the cases for diagnosis, about on a par with the companion single-cell cytometric analysis. Contextual and single cell analysis complemented each other, yielding greater accuracy when the two methods were combined. Additional applications of contextual analysis are discussed.

Discriminant Analysis↗
PubMed1994

Homogeneous sampling accounts for the increased diagnostic accuracy using the ThinPrep Processor.

Recent clinical trials indicated that the ThinPrep method of sample preparation has greater diagnostic sensitivity than the conventional direct Papanicolaou smear. The authors hypothesized that nonhomogeneous cell sampling during transfer from the sampling device to the microscope slide was a contributing factor to the reduced accuracy of the conventional direct Pap smears in these trials. To test this hypothesis, four direct smear methods were compared with the newly developed, fluid-based, filter-transfer method. Counts of epithelial cells on conventional smears showed that only a fraction of the available epithelial cells on the sampling devices (medians, 6.5% to 62.5%) was actually deposited on the slides. In all 27 cases studied with the ThinPrep method, equivalent diagnostic material was obtained on each of the replicate slides prepared per specimen. This identifies a new source of error, preparation error, in conventional smears.

Cell Biology↗
PubMed1992

Measurement of subvisual changes in cervical squamous metaplastic cells for detecting abnormality.

Quantitative measures of visually normal squamous metaplastic cells exfoliated from the uterine cervix were obtained to test the hypothesis that these cells, like intermediate squamous and endocervical columnar cells, show subvisual evidence of atypia in cases of bonafide squamous intraepithelial neoplasia. The cells identified as squamous metaplastic were obtained from 14 abnormal (dysplastic) and 9 diagnostically negative cases. Although the cell populations so grouped showed no statistically significant differences in overall cell size, nuclear area or nuclear/cytoplasmic ratios, there were significant differences in nuclear and cytoplasmic densitometric features and in nuclear texture features. A combination of three features (nuclear density, texture and cytoplasmic density) permitted 76% of the cells to be categorized correctly as originating in normal versus abnormal slides. It is concluded that selected quantitative features of exfoliated metaplastic cell populations may contribute to improved diagnostic accuracy in automated screening for cervical abnormalities.

Cell Nucleus↗
PubMed1991

Contextual analysis and intermediate cell markers enhance high-resolution cell image analysis for automated cervical smear diagnosis.

Until now, efforts to automate cervical smear diagnosis have focused on analyzing features of individual cells. In a complex specimen such as that obtained from a cervical scrape, diagnostically significant cells may not be adequately represented or may elude detection by the automated technology. An approach is needed that extracts additional quantitative information from cervical smears beyond what the cell-by-cell approach can provide. A new methodology, contextual analysis, was developed to extract global quantitative information about cells, cell clusters, and background debris. This pilot study was designed to compare the efficacy of contextual analysis with high-resolution, single cell analysis and the analysis of intermediate cell markers. Thirty-four samples prepared as monolayers and stained with the Feulgen-Thionin/Congo Red stain were measured. Contextual analysis alone was able to classify 91% of the smears correctly; single cell analysis classified 94% of the cells correctly; and the intermediate cell analysis correctly identified the smear diagnosis for 84% of the cells. When all three analysis methods were combined into a simple smear level classifier, the overall smear classification accuracy was improved over those obtained using the three methodologies alone.

Biomarkers↗
PubMed1991

High-resolution and contextual analysis for the diagnosis of fine needle aspirates of breast.

A study was undertaken to confirm earlier work on a smaller number of patients that had suggested that medium-resolution contextual analysis complements high-resolution individual cell analysis for cytomorphometric classification of fine needle aspirate smears of breast. The objectives of this study were to improve and verify the method. Sixty-one biopsy-confirmed hematoxylin and eosin-stained aspirate smears of breast were restained using the Feulgen technique. Individual nuclei were digitized at a resolution of 0.25 micron. Features describing size, shape, density and texture were extracted from the images. Individual cell analysis correctly classified 84% of cases, contextual analysis correctly classified 70% of cases, and the combined use of both techniques resulted in 87% classification accuracy. However, if fibroadenoma cases are excluded, the combined correct classification rate is 93%. Geometric and densitometric features contributed most to correct classification in individual cell analysis, while the most important contextual feature was the number of clusters per scene. We conclude that the addition of quantitative measures of smear patterns, termed "contextual analysis," improves automated classification schemes.

Biopsy, Needle↗
PubMed1991

An image analysis method for assessment of prognostic risk in prostate cancer: a pilot study.

Fully automated computerized image analysis at medium resolution (1 micron per pixel space) was applied in a study of 17 patients with stage D1 prostate cancer. For this pilot study, patients were selected on the basis of very good or very poor outcome. This selection was made in the hope of identifying morphometric features that are useful in prognostic assessment. Nine patients with good outcome were alive after 7 or more years of follow-up and eight patients with poor prognosis were dead of disease in less than 3 years. All patients were treated with 125I seed implantation to the prostate and pelvic lymph node dissection. Hormone therapy was not administered until the time of distant failure. Routine hematoxylin and eosin tissue sections of lymph nodal tissue bearing metastatic neoplasm were used for this analysis. A minimum of eight scenes per case was analysed. Of 50 measured parameters on each cluster, five (gray level distribution, number of cell clusters per scene, bending energy, average cluster area and cluster polarity) were useful to distinguish patients with good outcome from those with a poor outcome. Thirteen of the 17 patients were correctly classified by image analysis (P = 0.044, Fischer's exact test). By comparison, flow cytometry of the identical tissue samples correctly classified 14 of 17 patients (diploid, good outcome; aneuploid, poor outcome; P = 0.009). Only one patient was incorrectly classified by both image analysis and flow cytometry, implying a complementary prognostic role for the two methods. The encouraging result, successful identification of useful morphometric features, justifies a larger study of unselected patients.

DNA↗
PubMed1991

Automated analysis of rat breast tumors. Comparison of four methods.

Chemically-induced malignant rat breast tumors pose diagnostic dilemmas since the majority are well-differentiated, noninvasive papillary lesions that are barely distinguishable from benign papillary lesions. This study compared several automated modalities to see which best separated benign from malignant breast tumors. Thirty-three carcinogen-induced rat breast tumors (13 adenomas, 10 papillary carcinomas and 10 invasive carcinomas) were evaluated by static (image) cytometry (ICM) of integrated optical density, by flow cytometry (FCM) and by two automated morphometric protocols, contextual analysis and single-gland analysis. DNA ploidy analysis, by either ICM or FCM, did not discriminate between the benign and malignant tumors. Contextual analysis correctly identified 11 of 13 benign and 17 of 20 malignant lesions (P less than .01). Single-gland analysis correctly identified all 13 benign and 17 of 20 malignant lesions (P less than .01). No method distinguished invasive from noninvasive carcinomas. The data suggest that architectural features are more important than nuclear features in differentiating benign from malignant rat breast tumors.

Animals↗
PubMed1990

Aldosterone induces apical vesicles in rat distal colon.

Mineralocorticoid steroids markedly alter ion transport in responsive epithelia. Increases in absorption of Na+ and secretion of K+ and H+ are accompanied by increases in surface area of the basolateral membrane. The basolateral membrane changes are associated with increased Na(+)-K(+)-ATPase activity and increased numbers of Na(+)-K(+)-ATPase pump sites. It is thought that H+ secretion is mediated by H+ pumps contained in apical vesicles that are added to the luminal membrane in response to acidifying stimuli. Whether there are changes in the number or volume of apical vesicles in response to aldosterone has not been evaluated. To this purpose, we evaluated apical membrane morphology in rat distal colon, a mineralocorticoid-responsive epithelium. We found that aldosterone infused for 4-7 days by osmotic minipump significantly increased the number, surface density, and total volume of apical vesicles. Exposure of tissues to 5% CO2 for 15 min before fixation resulted in significant decreases in vesicle number, surface density, and volume in aldosterone-stimulated tissues. After CO2, apical vesicles in aldosterone-stimulated tissues tended to be closer to the luminal membrane; apical membrane surface density was increased but not to a significant degree. Fluorescence microscopy demonstrated acridine orange accumulation in discrete points under the lumen, suggesting the presence of acidic vesicles in this location. We propose that aldosterone increases the activity of a membrane shuttle system that is regulated by CO2 as found in other H(+)-secreting epithelia. This system may mediate aldosterone-induced changes in colonic H+ transport.

Aldosterone↗
PubMed1990

Computer-assisted grading of adenocarcinoma in prostatic aspirates.

Conventional cytologic grading of fine needle aspirates of prostatic adenocarcinoma has been shown neither to be reproducible nor to correlate well with histologic grading. This study developed a tumor grade classification based on computerized cytomorphometric features and compared the results to conventional grading of companion tissue sections. The image analysis system evaluated architectural features of the aspirates (mainly cell cluster features and interrelationships) as well as nuclear features. Thirty-five prostatic adenocarcinomas (8 well, 19 moderately and 8 poorly differentiated) were evaluated. Discriminant functions based on data collected at medium and high resolution distinguished between aspirates from low-grade (well-differentiated) and high-grade (poorly differentiated) adenocarcinomas with 81% accuracy. Moderately differentiated cancers could not be classified as a distinct group. This study suggests that accurate grading of prostatic adenocarcinoma in fine needle aspirate smears requires the evaluation of medium-resolution features related to specimen cellularity and uniformity or crowding of cell clusters as well as of high-resolution features of nuclear area, perimeter and coarseness of chromatin texture. These findings are compared to those of other schemes for the cytologic grading of prostatic aspirates.

Adenocarcinoma↗
PubMed1989

Computerized microscopic analysis of prostatic fine needle aspirates. Comparison with breast aspirates.

Computerized image analysis was employed to analyze fine needle aspiration smears of the prostate and breast using both high-resolution images of individual cells and medium-resolution images of scenes and clusters (contextual analysis). A linear discriminant analysis was used to demonstrate the computer's ability to discriminate between benign and malignant categories for both types of tissue. Correct classification as benign or malignant using contextual analysis was achieved in 22 of 26 prostatic aspirates and in 15 of 18 breast aspirates, as determined by comparison with histology. The addition of high-resolution single-cell analysis resulted in correct classification of 24 of 26 prostatic aspirates and all breast aspirates. For virtually all features, the distinction between benign and malignant was more subtle for prostatic than for breast tissue. The data indicate that contextual analysis may be less effective as an adjunct to high-resolution single-cell microscopy of prostatic specimens than it is for breast specimens.

Biopsy, Needle↗
PubMed1988

Contextual analysis complements single-cell analysis in the diagnosis of breast cancer in fine needle aspirates.

Image analysis techniques were used to characterize individual nuclei of cells and entire clusters of cells in hematoxylin-and-eosin-stained smears of fine needle aspirates of the breast to determine the ability of these techniques to distinguish benign from malignant cases. Analysis of the individual nuclear features showed significant differences in nuclear area, shape (bending energy), texture and integrated darkness between benign and malignant samples. Analysis of the clusters demonstrated that the benign clusters were fewer in number, more cellular (average gray level) and larger than malignant clusters. A statistical classifier was constructed to test the discriminatory accuracy for benign and malignant cases. Good discrimination was found for both the individual nuclei and the clusters when analyzed separately, although a few cases were misclassified by each type of analysis. When combined, the two classifiers achieved a completely accurate classification. This suggests the complementary nature of high-resolution single-cell analysis and the more global cluster analysis techniques.

Adenofibroma↗
PubMed1987

Evaluation of contextual analysis for computer classification of cervical smears.

A procedure for automated analysis of cervical smears has been implemented in an image cytometry system. Smears are described exclusively in terms of global and contextual information extracted by pattern-recognition algorithms and represented by a vector of proportions of cellular object types. Linear discriminant functions, based on a Fisher criterion, are derived to classify smears with a cross-section of diagnoses into two broad categories, normal and abnormal. Results obtained from 83 smears indicate 78% correct classification. In contrast to most automated systems, good classification results were obtained in normal smears with benign changes caused by inflammation and with postmenopausal atrophia and in abnormals with mild dysplasia. These findings suggest that contextual analysis may be sensitive to subtle changes in cellular morphology and to progressive patterns of dysplasia. When used with standard isolated cell analysis, contextual analysis may provide additional complementary information for automated cervical prescreening.

Cervix Uteri↗
PubMed1986

Sexual dimorphism in the preoptic/anterior hypothalamic area of ferrets: effects of adult exposure to sex steroids.

The organization of neuronal cell bodies in the caudal preoptic area (POA) and rostral anterior hypothalamic area (AH) was studied in Nissl-stained brain sections from adult male and female ferrets. Computer-assisted image-analysis procedures were developed to help estimate the areas of cellular density and the sizes of individual perikarya. At the junction of the POA and AH, a bilateral dorsal-medial group of neurons was apparent only in male ferrets (dorsal nucleus). At the same coronal level, a ventral-medial group of neurons was apparent bilaterally in both males and females (ventral nucleus). The mean somal area of cells in the dorsal nucleus of males was significantly greater than the mean somal area of cells in the corresponding dorsal region of females or in the ventral nucleus of both sexes. The dorsal nucleus was clearly discernible in adult males regardless of their hormonal status, although cells in the dorsal nucleus were larger in intact breeding males or gonadectomized males given testosterone, estradiol or dihydrotestosterone than in gonadectomized males given no gonadal hormones or given progesterone. Neither the grouping of large cells nor the steroid-induced increase in cell size, characteristic of the male dorsal nucleus, was seen in the comparable dorsal region of females. The sex difference in cellular organization observed in the ferret at the junction of the POA and AH is the first difference of this type to be seen in the POA/AH of a non-rodent mammalian species. Its identification will, hopefully, aid in the analysis of the neural mechanisms that control various sex-specific behaviors in this species.

Animals↗
PubMed1986

Cytopress: automated slide preparation of cytologic material from suspension.

This paper describes a new automated system to prepare slides of cytological material from suspension. The system collects material on a filter tape by filtration and transfers it to glass slides by means of pressure-fixation. Using cervical cells as a model, results show that a well-defined cell number is evenly deposited over a standardized area, while a small number of cells is retained on the tape and a negligible number lost in the filtrate. Contamination is very small. Application of the system to other cytological material (fine needle aspirations, monolayer and cell suspension cultures, agar cultures, and isolated nuclei) is shown. In general, more than one slide can be made from one sample. Several histological staining procedures as well as immunofluorescence labeling protocols can be applied to the preparations obtained in this way. This system thus introduces a method that will standardize specimen preparation, is quick, saves operator time, and can be used for both diagnostic and research applications.

Autoanalysis↗
PubMed1986

Spectral bandwidth in automated leukocyte classification.

Investigators have repeatedly pointed out the importance of spectral information in the automated classification of white blood cells. In general, monochromatic images recorded through two or three color filters are used to extract this information. Although it has generally been thought that the use of narrow band filters provides "cleaner" color information than is obtainable through wide band filters, the choice has not been fully investigated and the question is far from being settled. The use of wide band filters has the clear practical advantage of increased light levels at the detector, resulting in higher signal-to-noise ratio with less demand on light source design. In order to investigate this issue, a series of 681 leukocytes of the most frequently occurring types were digitized by the use of both narrow (10 nm) and wide (90 nm) band filters. Parameters were extracted independently from both sets of images. These parameters were then used to develop a classifier for each set of images. The choice of features and classifier results indicate that there are no major performance differences between the two types of filters.

Cytological Techniques↗
PubMed1986

Differentiation in male ferrets of a sexually dimorphic nucleus of the preoptic/anterior hypothalamic area requires prenatal estrogen.

Experiments were conducted to determine when during perinatal development testicular steroids act in ferrets to promote the organization of a bilateral nucleus in a medial position at the border of the preoptic area (POA) and anterior hypothalamus (AH), henceforth referred to as the male nucleus of the POA/AH (MN-POA/AH). The formation of the MN-POA/AH was promoted in female offspring by treating their mothers with testosterone over the last 11 days of the 42-day gestation period, whereas MN-POA/AH formation was not disrupted in males castrated within 1, 2 or 5 days of birth. Additional experiments were conducted to determine whether the active hormone which induces differentiation of the MN-POA/AH in the male ferret is an androgen or an estrogen. MN-POA/AH formation was inhibited in males deprived prenatally of estrogenic stimulation via maternal ovariectomy and subcutaneous implantation of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) on gestational day 30. By contrast, MN-POA/AH formation was not disrupted in males exposed prenatally to the antiandrogen flutamide. These results imply that estrogen, derived from the neural aromatization of circulating testosterone, acts prenatally to promote the organization of the MN-POA/AH in male ferrets. The development of sex-dependent features of forebrain morphology may depend on the neural action of estrogen in males of diverse mammalian species.

Androstatrienes↗