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M Bibbo

Publications and source records attributed to M Bibbo.

At least 19 recordsLinked to original sources
PubMed1992

Bayesian belief networks in quantitative histopathology.

Bayesian belief networks have a dynamic range and numeric response characteristics that make them uniquely suitable for descriptive classification schemes. Features showing considerable overlap of tolerance regions may be used, in a cumulative manner, to derive unequivocal classification decisions. The numeric response characteristics of Bayesian belief networks are analyzed, and their application as control modules in automated scene segmentation in histopathology is demonstrated.

Bayes Theorem↗
PubMed1992

Prognostic significance of ploidy determination in rectal cancer.

Between 1965 and 1981, 154 patients with potentially curable rectal adenocarcinoma underwent surgical treatment at the University of Chicago Medical Center. In 134 cases, enough histological material was available to perform determinations of DNA content by the cytophotometric method (n = 108), or by the flow cytometric technique (n = 109). In 83 cases, DNA content was analyzed in the same specimen with both techniques, and in 77 of these cases the sections obtained from the paraffin blocks were contiguous. When using flow cytometry, 62% of stage B and 74% of stage C lesions were classified as aneuploid on the basis of a DNA index greater than 1. This correlation was statistically significant (p = 0.002). Patients with diploid tumors had an actuarial five-year survival equal to 62% in comparison with a 46-51% five-year survival for patients with aneuploid tumors. This difference was not statistically significant and it was explained by the tendency for aneuploid tumors to be in an advanced histopathological stage.

Adenocarcinoma↗
PubMed1992

Comparison of estrogen receptor immunocytochemical assay in frozen and paraffin sections.

Frozen and paraffin sections of 11 breast carcinomas were stained for estrogen receptors (ER) using the same rat monoclonal primary antibody, D75P3, as the marker and alkaline phosphatase as the chromogen-linking enzyme. The results of this staining process were assessed visually and with the microTICAS image analysis system to determine the degree of correlation between frozen and paraffin-embedded tissue. In all specimens, some fraction of the nuclei stained positively. This included two specimens selected for their biochemically negative assay; one of them stained strongly positively with D75P3. The results of quantitative analysis support the visually apparent correlation between the two types of samples in terms of both overall staining pattern and intensity of nuclear staining. Although the conclusions of this pilot study are limited because of the small number of cases, this method of staining establishes the feasibility of representative ER determination in archival paraffin-processed material. The additional information provided by this method is potentially useful in stratifying patients in prospective studies on the basis of the efficacy of hormonal therapy in biochemically ER positive breast tumors.

Antibodies, Monoclonal↗
PubMed1991

Correlation between visual clues, objective architectural features, and interobserver agreement in prostate cancer.

Three pathologists evaluated a number of designated architectural features to assign grades to 41 cases of well- to moderately differentiated adenocarcinoma, and their opinions were compared. The consensus opinion was obtained and evaluated against objective measurements of glandular architecture that were obtained by morphometric techniques. The observers agreed on gland size, gland uniformity, and the number of glands per field in only 49%, 31%, and 39% of cases, respectively. There were significant differences in the Gleason grades assigned by observers. Paired matching of individual Gleason grades showed agreement among observers in 44% (18 of 41), 56% (23 of 41), and 75% (31 of 41) of cases, respectively. This level of interobserver disagreement occurred even though cases with predominant patterns were selected carefully and those with variable patterns were excluded. A direct relationship appears to exist between increasing Gleason grade and increasing glandular variability, and there is an inverse relationship between Gleason grade, gland lumen area, and the number of glandular nuclei, as assessed by a group of pathologists.

Humans↗
PubMed1991

Value of the cribriformity factor in grading prostatic carcinoma.

Architectural and histometric features for the objective grading of prostate adenocarcinoma in histologic specimens were analyzed in five cases each of Gleason primary grades 2, 3A, 3B, 3C, 4A and 4B, selected as "typical" for the histopathologic images. Tissue sections from the selected cases were stained by the Feulgen method. Fifteen fields for each grade, for a total of 4,430 glands, were digitized by a video-based microphotometer at low resolution (pixel spacing of 2 microns). Outer and inner outlines of the glandular epithelium were traced manually using a mouse. For each field the number of glands, the gland area, the lumen area, the area of the glandular epithelium and the cribriformity factor were computed. The gland area and its variance proved to be useful indicators for lower-grade lesions, whereas the variance of cribriformity resulted in an excellent grading indicator in the Gleason 3-4 range when cribriform glands were present.

Adenocarcinoma↗
PubMed1991

Karyometric features in nuclei near colonic adenocarcinoma. Statistical analysis.

The normal mucosa adjacent to colonic adenocarcinoma (marginal or transitional mucosa) has been shown to have subtle alterations of architecture, surface glycoproteins and proliferative activity. To evaluate possible changes in nuclear configurations in this marginal mucosa, a large set of cytometric features was evaluated using a computer-assisted video analysis system. Preliminary statistical analysis of the measurements identified six nuclear features useful for discriminating marginal mucosa nuclei from normal (control) mucosa nuclei: total optical density (OD), nuclear area, chromatin texture (from gray value cooccurrence matrix), chromatin coarseness, average OD of nuclear staining and peripheral tendency of the chromatin in the nucleus. An analysis of variance revealed that both patient-to-patient and gland-to-gland variation would limit the usefulness of any one feature as a screening tool. As a group, however, these six features should be investigated further as markers of preneoplastic changes in histologically normal-appearing mucosa.

Adenocarcinoma↗
PubMed1991

Histometric features for the grading of prostatic carcinoma.

Histometric features for the objective grading of prostatic adenocarcinoma in histologic specimens were analyzed in five cases each of well, moderately and poorly differentiated lesions. Tissue sections from the selected cases were stained by the Feulgen method and digitized by a video-based microphotometer. Twenty total fields were recorded for each grade: ten at high resolution (an image sampling of 0.5 micron per pixel) and ten at low resolution (0.8 micron per pixel), with two fields per case recorded at each resolution. The images were segmented by an automated expert system-guided scene segmentation procedure. The performance of that procedure was measured by comparing the automated counts of nuclei in the segmented fields to the visual counts made by a pathologist in the same fields. For well, moderately and poorly differentiated cases, respectively, the nuclear counts made by the expert system at high resolution were 2.7%, 4.2% and 4.7% higher than the visual counts (as estimated from a total of 6,628 nuclei), but 1.2%, 2.5% and 1.1% lower at low resolution (10,329 nuclei). High-resolution features and tissue textural features were computed for each case. The high-resolution features showed good separation between the three groups of cases. The tissue textural features showed consistent separation between well and moderately differentiated cases. The relaxation of the spatial resolution (to 0.8 micron/pixel spacing) did not affect the selection of features, but led to less separation between the data from different grades. In conclusion, the automated system performed satisfactorily in distinguishing sections of prostatic tumors of varying degrees of differentiation.

Adenocarcinoma↗
PubMed1990

Cytophotometric DNA measurements in medullary thyroid carcinoma.

The prognostic significance of objectively measured karyometric variables (ploidy pattern, nuclear roundness, area, elongation, chromatin texture, and nearest nucleus distance) was investigated in relation to clinical (stage and type of disease) and morphologic (histologic patterns) variables in 27 patients with the diagnosis of medullary thyroid carcinoma (MTC). The DNA and karyometric measurements of Feulgen-stained nuclei were made with a video cytometry system. The five-year and ten-year adjusted survival rates were 74.4 +/- 10.1% and 59.5 +/- 15.6%, respectively. Cox's survival analysis for mortality showed that only stage, age, sex, and 5N exceeding rate had predictive value (overall P = 0.0012) in decreasing order. Patients with the best prognosis were young females with clinical Stage I disease and low 5N exceeding rate tumors. When karyometric and histometric variables were considered by themselves survival correlates with the standard deviation (SD) of the nearest nuclear distance and nuclear elongation; that is, patients with crowded, high cellularity tumors and elongated cells had the worst prognosis. In univariate analyses only clinical stage correlated with adjusted survival rate. Multivariate survival analysis for morbidity showed that patients in Stages greater than or equal to II and high SD of ploidy values were free of symptoms for short intervals. When morphometric data were considered alone, patients with high variance in the chromatin texture and highly variable nuclear areas had shorter asymptomatic intervals.

Adolescent↗
PubMed1990

Karyometric marker features in normal-appearing glands adjacent to human colonic adenocarcinoma.

The expression of nuclear marker features in normal-appearing tissue adjacent to colonic adenocarcinoma was investigated. Formalin-fixed, paraffin-embedded tissue sections of colon from 9 patients with adenocarcinoma and from 9 normal controls were cut 4 microns thick, Feulgen stained, and measured by a cell image analysis system using a Matrox MVP-AT/NP imaging board. Thirty nuclei in the tumor region, 30 nuclei 2 mm into the histologically normal-appearing distal margin, and the same number at 5, 10, 20, and 50 mm into the margin were measured for each patient. An additional 30 nuclei were recorded from 9 patients each free from colonic disease. Nuclear features were selected to discriminate between tumor nuclei and nuclei from normal control subjects and between nuclei measured in the histologically normal-appearing margin next to the tumor and control nuclei. Eight micromorphometric measures were found to be statistically significantly different in nuclei measured in the margin site, including features describing staining density (total absorbance, average absorbance 20% below mean, average absorbance 20% above mean) chromatin texture (cooccurrence matrix, run length, and peripheral tendency) and nuclear area. The category differences are statistically highly significant.

Adenocarcinoma↗
PubMed1990

Karyometric marker features in fine needle aspirates of invasive follicular carcinoma of the thyroid.

Karyometric measurements were performed on fine needle aspirates of clearly identifiable tumor areas and adjacent normal-appearing areas in the surgical specimens from ten patients with invasive follicular carcinoma of the thyroid. Similar measurements were performed on aspirates from nine patients free of thyroid disease (controls). A total of 95 karyometric features were evaluated for each nucleus. Analysis of variance of optical density values indicated (1) a similarity between tumor and normal-appearing nuclei from carcinoma cases, (2) a significant difference between those nuclei and control nuclei and (3) that most of the differences were due to the differences of tissue origin. Stepwise linear discriminant analysis selected ten features that produced a statistically highly significant separation of tumor nuclei from control nuclei. A similar analysis selected six features that produced a statistically highly significant discrimination of normal-appearing nuclei from control nuclei; the validity of those karyometric features as markers of malignancy in normal-appearing nuclei from tissues adjacent to invasive follicular carcinomas of the thyroid was demonstrated by analysis in further training and control sets of nuclei. This analysis in thyroid aspirates identified more marker features than did a previous similar analysis using tissue sections.

Adenocarcinoma↗
PubMed1990

Karyometric marker features in fine needle aspirates of microinvasive follicular carcinoma of the thyroid.

Karyometric measurements were performed on fine needle aspirates of clearly identifiable tumor areas and adjacent normal-appearing areas in the surgical specimens from ten patients with microinvasive follicular carcinoma of the thyroid. Similar measurements were performed on aspirates from nine patients free of thyroid disease (controls). A total of 95 karyometric features were evaluated for each nucleus. As compared with the control nuclei, the normal-appearing nuclei showed a 6% increase in total nuclear optical density (OD) while the tumor nuclei showed a 14% increase. Analysis of variance indicated a significant difference between the normal-appearing nuclei and the control nuclei, with most of the difference due to the differences of tissue origin. Discriminant analysis selected nine features that produced a statistically highly significant separation of tumor nuclei from control nuclei. A similar analysis selected five features that produced a statistically highly significant discrimination of normal-appearing nuclei from control nuclei; the validity of those karyometric features as markers of malignancy in normal-appearing nuclei from tissues adjacent to microinvasive follicular carcinomas of the thyroid was demonstrated by analysis in further training and test sets of nuclei.

Adenocarcinoma↗
PubMed1990

Artificial intelligence-guided analysis of cytologic data.

A design for the integration of artificial intelligence (AI) technology with large databases of clinical and objective cytologic data, such as are on file at the University of Chicago, is presented. Among the key features of this approach are the use of a knowledge representation structure based upon an associative network, the use of a Bayesian belief network as a method of managing uncertainty in the system, and the use of neural networks and unsupervised learning algorithms as a means of discovering patterns within this database. Such an automated approach is necessary, given the complexity and interdependence of these data, to gain an understanding of their dependence structure and to assist in their exploration and analysis.

Algorithms↗
PubMed1990

Architectural, morphometric and photometric features and their relationship to the main subjective diagnostic clues in the grading of prostatic cancer.

Novel software was developed to perform quantitative measurements of architectural and nuclear features in tissue sections. A pilot study was then undertaken to determine the diagnostic relevance of these quantitative features in prostatic tissue and the relationship of these objective features to the subjective clues used by practicing pathologists in the grading of prostatic adenocarcinoma. From a group of 82 cases of adenocarcinoma of the prostate with long-term follow-up, a subset of 15 cases that included 5 each in Mostofi grades I, II and III was carefully selected for analysis. Consecutive sections from each case were stained with hematoxylin and eosin or the Feulgen stain for visual and cytometric evaluations, respectively. The most important differences in the objective architectural features observed between the Mostofi grade I and II cases were the number of nuclei per gland and their distance from the glandular center. Significant differences were also noted in gland size and the variation in gland size. The Mostofi grades were also significantly different in terms of quantitative high-resolution features measuring nuclear size and its variation, total nuclear DNA content and the proportion of very aneuploid nuclei. There was a fairly good agreement between many of the subjective diagnostic clues and their corresponding quantitative architectural and nuclear features. This work (1) significantly extended the capabilities of our PC-based microphotometer system to analyze glandular tissue specimens, (2) provided insight into the objective bases for the expert diagnosis of adenocarcinomas of the prostate and (3) gave preliminary evidence of the ability of quantitative architectural features and high-resolution cytometric features to discriminate between the major diagnostic categories of these lesions.

Adenocarcinoma↗
PubMed1990

Karyometric marker features in fine needle aspirates of follicular adenoma of the thyroid.

Karyometric measurements were performed on fine needle aspirates of clearly identifiable adenomatous areas and adjacent normal-appearing areas in the surgical specimens from ten patients with follicular adenomas of the thyroid. Similar measurements were made on aspirates from nine patients free of thyroid disease. A total of 95 karyometric features were evaluated for each nucleus. Analysis of variance of optical density values did not show a significant difference between the three types of nuclei. Discriminant analysis selected seven karyometric features that produced a statistically highly significant separation of adenoma nuclei from control nuclei. A similar analysis selected six features that produced a statistically highly significant discrimination of normal-appearing nuclei from control nuclei. The validity of these markers for distinguishing control nuclei from adenoma nuclei and normal-appearing nuclei adjacent to adenomas was demonstrated by analysis in further training and test sets. These findings parallel those previously demonstrated for invasive and microinvasive follicular carcinomas of the thyroid.

Adenoma↗
PubMed1990

Tissue architectural features for the grading of prostatic carcinoma.

In research for the development of a computer-aided workstation for the objective grading of prostatic carcinoma, tissue architectural (histometric) features were analyzed in ten cases each of well-differentiated, moderately differentiated and poorly differentiated carcinoma (as subjectively graded by the consensus of a panel of experts). Sections were cut at 4 microns, stained by the Feulgen reaction and digitized by two different video-based photometric systems. Some images were interactively segmented, considering the histometric clues to be studied; others were automatically segmented by an expert system-guided technique. The latter procedure produced good results, with over 90% of the nuclei judged to be correctly segmented in 64% of the fields studied and over 80% in another 24% of the fields. While the number of nuclei per field provided some separation of well-differentiated from other lesions, the number of nuclei per gland distinguished between well-differentiated and moderately differentiated lesions. Simplicial decomposition of the images also provided a measure of the degree of differentiation, as did the "texture" of the nuclear placement, based on two run-length statistics. Combination of the run-length features distinguished the three categories of lesions with statistical significance. The results of this study provided insights into the problems (such as the effect of field boundaries) faced in the design of an computer-aided grading system. They also showed the value of expert system-guided scene segmentation and of such histometric features as the field cellularity and the number of nuclei per gland for the discrimination between lesions of different grades of differentiation.

Cell Nucleus↗
PubMed1990

Nuclear deoxyribonucleic acid content (ploidy) of endodermal sinus (yolk sac) tumor.

Paraffin sections from 30 endodermal sinus (yolk sac) tumors were Feulgen-stained, and nuclear DNA content (ploidy) was assessed through DNA cytophotometry using the microTICAS image analysis system. The series consisted of 20 ovarian, 8 testicular, 1 sacrococcygeal, and 1 mediastinal tumors. Of the 30 endodermal sinus (yolk sac) tumors 29 were shown to be aneuploid, whereas the remaining tumor which exhibited the recently described primitive intestinal or enteric pattern was diploid and may thus be considered a neoplasm showing a somewhat higher degree of differentiation as compared to tumors showing the other histologic patterns of endodermal sinus (yolk sac) tumors.

Aneuploidy↗
PubMed1989

Correlation between automated karyometric measurements of squamous cell carcinoma of the esophagus and histopathologic and clinical features.

The clinical staging of esophageal carcinoma is unreliable currently, making it difficult to select patients for aggressive therapy. To further refine staging criteria, the nuclear characteristics of a series of 31 patients with squamous cell carcinoma of the esophagus were studied using a computerized image analysis system (MicroTICAS). Karyometric measurements, including total nuclear DNA content, nuclear area, and nuclear roundness were compared with various clinical and histologic variables. Nearly all tumors (30 of 31) were aneuploid. Tumors with nuclear areas greater than 70 microns2 were associated with transmural esophageal penetration (P less than 0.05) and to a lesser extent with poor survival (less than 6 months; P = 0.06). Surprisingly, nuclear ploidy did not correlate with either variable. These data support a role for nuclear analysis on preoperative biopsy specimens as an adjunct in clinical staging.

Aneuploidy↗