Biomedical subjects

H G Bartels

Publications and source records attributed to H G Bartels.

At least 19 recordsLinked to original sources

PubMed2005

Karyometry in the early detection and chemoprevention of intraepithelial lesions.

The ideal chemopreventive agent targets pre-neoplastic changes and intraepithelial neoplasia, preventing progression over time without notable side effects. Assessment of success of chemopreventive intervention in the short and medium term remains a challenge, and in this review the suggestion is investigated that karyometric measurements constitute suitable markers of chemopreventive efficacy. Karyometry provides the sensitivity required to detect small differences amidst relatively high biological variability. It can help establish progression curves of intraepithelial neoplasia (IEN) to invasive cancer, and thus detect chemopreventive effects. Such effects can be observed in two ways, at the group level (intervention vs. placebo), and at the case (or patient) level. The latter is more difficult to establish, necessitating the development of specialised statistical methods. Analysis of between-case and within-case heterogeneity can reveal useful information about cancer progression and prevention. We suggest that karyometry can objectively quantify IEN progression, providing a framework for statistically securing chemopreventive effects. It can act as an integrating biomarker by detecting chemopreventive activity even when the mechanism for a given progression pathway is unknown, or when multiple pathways exist. The sensitivity of karyometric detection can help optimise the design of clinical trials of novel chemopreventive agents by decreasing trial duration and/or sample size.

Antineoplastic Agents↗

PubMed2002

Transcontinental communication and quantitative digital histopathology via the Internet; with special reference to prostate neoplasia.

OBJECTIVE: To describe practical experiences in the sharing of very large digital data bases of histopathological imagery via the Internet, by investigators working in Europe, North America, and South America. MATERIALS: Experiences derived from medium power (sampling density 2.4 pixels/microm) and high power (6 pixels/microm) imagery of prostatic tissues, skin shave biopsies, breast lesions, endometrial sections, and colonic lesions. Most of the data included in this paper were from prostate. In particular, 1168 histological images of normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) were recorded, archived in an image format developed at the Optical Sciences Center (OSC), University of Arizona, and transmitted to Ancona, Italy, as JPEG (joint photographic experts group) files. Images were downloaded for review using the Internet application FTP (file transfer protocol). The images were then sent from Ancona to other laboratories for additional histopathological review and quantitative analyses. They were viewed using Adobe Photoshop, Paint Shop Pro, and Imaging for Windows. For karyometric analysis full resolution imagery was used, whereas histometric analyses were carried out on JPEG imagery also. RESULTS: The three applications of the telecommunication system were remote histopathological assessment, remote data acquisition, and selection of material. Typical data volumes for each project ranged from 120 megabytes to one gigabyte, and transmission times were usually less than one hour. There were only negligible transmission errors, and no problem in efficient communication, although real time communication was an exception, because of the time zone differences. As far as the remote histopathological assessment of the prostate was concerned, agreement between the pathologist's electronic diagnosis and the diagnostic label applied to the images by the recording scientist was present in 96.6% of instances. When these images were forwarded to two pathologists, the level of concordance with the reviewing pathologist who originally downloaded the files from Tucson was as high as 97.2% and 98.0%. Initial results of studies made by researchers belonging to our group but located in others laboratories showed the feasibility of making quantitative analysis on the same images. CONCLUSIONS: These experiences show that diagnostic teleconsultation and quantitative image analyses via the Internet are not only feasible, but practical, and allow a close collaboration between researchers widely separated by geographical distance and analytical resources.

Computers↗

PubMed2001

Karyometry of secretory cell nuclei in high-grade PIN lesions.

BACKGROUND: The goal of this study was a karyometric characterization of secretory cell nuclei in high-grade prostatic intraepithelial neoplasia (PIN) lesions. Specifically, the hypothesis is tested that distinctly different subgroups of nuclei exist in these lesions. METHODS: High-resolution images of 1,713 nuclei from high-grade PIN lesions were recorded. Karyometric features were computed. Discriminant function scores against normal reference nuclei, and nuclear abnormality values were derived. Data sets were processed by a nonsupervised learning algorithm to establish the presence of subgroups of nuclei with statistically different nuclear chromatin distributions. RESULTS: Three sets of nuclei were formed, facing an intact basal cell layer, a near vanishing basal cell layer, and a gap in the basal cell layer. For each set, a nonsupervised learning algorithm formed three statistically different subgroups of approximately equal sizes. Each subgroup is found in every one of the three sampling locations. The total optical density distribution of nuclei in two subgroups suggests an aneuploid distribution, the third subgroup has a near diploid distribution. CONCLUSIONS: Secretory cell nuclei in high-grade PIN lesions are a heterogeneous population, forming statistically different subgroups. Studies aimed at characterizing the progression of such lesions should consider the inhomogeneous nature of these nuclei.

Algorithms↗

PubMed2001

Progression curves for endometrial lesions.

OBJECTIVE: To derive a numeric measure for the progression of endometrial lesions as a baseline study for an eventual assessment of chemopreventive intervention efficacy. STUDY DESIGN: Tissue sections from normal endometrium at the proliferative and secretory phase, simple hyperplasia, atypical hyperplasia from cases free of concomitant adenocarcinoma and adenocarcinoma of the endometrium were recorded at high spatial resolution. Six cases from each diagnostic category were chosen as "typical," and 60 epithelial nuclei were randomly selected for measurement for each case. Discriminant analyses were carried out to derive a direction of progressive change in feature space and to correct the progression curve for the presence of cells not expressing progressive change among the random sample of nuclei. RESULTS: A well-conditioned progression curve was derived based on the mean discriminant function scores for each diagnostic category and the mean nuclear abnormality of the nuclei in each category, as expressed by their deviation in feature values from normal reference nuclei. The lesion signatures showed a clear trend toward extension into the range of higher nuclear abnormalities with increasing progression. There was an indication that abnormal endometrial lesions may comprise cases with distinctly different degrees of nuclear abnormality. CONCLUSION: A numeric assessment of lesion progression for endometrial lesions, based on karyometric measurements, is possible. The data suggest that additional analysis may provide further characterizing information for individual lesions.

Adenocarcinoma↗

PubMed2001

Quantitative study of ductal breast cancer progression: nuclear signatures for evaluation of progression grade.

The evaluation of progressive morphological changes, with 93 morphometric parameters in tissue lesions representative of ductal breast cancer progression, has been performed in order to define in great detail the profile of chromatin texture (nuclear signature) changes. A gradual, distinctive increase in nuclear signature alterations from hyperplasia to infiltrating carcinoma has been found. The nuclear signatures' analysis of microinfiltrating foci in comedo DCIS showed sharp differences compared with those of comedo DCIS they derived from: these foci consist of cells with smaller and also more homogeneous nuclei. Opposite to the prominent heterogeneity of those of comedo DCIS: they appear to express a reduced clonality in the new, more progressed, cell population. Digital analysis of chromatin patterns seems to be useful, beyond mere extraction of individual features of value, in getting objective data for individual grading and prognosis of breast cancer.

Breast Neoplasms↗

PubMed2000

Data representation and reduction for chromatin texture in nuclei from premalignant prostatic, esophageal, and colonic lesions.

BACKGROUND: To identify nuclei and lesions with great specificity, a large set of karyometric features is arranged in the form of a linear profile, called a nuclear signature. The karyometric feature values are normalized as z-values. Their ordering along the profile axis is arbitrary but consistent. The profile of the nuclear signature is distinctive; it can be characterized by a new set of variables called contour features. A number of data reduction methods are introduced and their performance is compared with that of the karyometric features in the classification of prostatic, colonic, and esophageal lesions. METHODS: Contour characteristics were reduced to descriptive statistics of the set of z-values in the nuclear signature and to sequence information. The contour features derived were (1) relative frequencies of occurrence of z-values and of their differences and (2) co-occurrence statistics, run lengths of z-values, and statistics of higher-order dependencies. Performance was evaluated by comparing classification scores of diagnostic groups. RESULTS: Rates for correct classification by karyometric features alone and contour features alone indicate equivalent performance. Classification by a combined set of features led to an increase in correct classification. CONCLUSIONS: Image analysis and subsequent data reduction of nuclear signatures of contour features is a novel method, providing quantitative information that may lead to an effective identification of nuclei and lesions.

Cell Nucleus↗

PubMed2000

Quantitative study of ductal breast cancer progression: signatures of nuclei in proliferating breast lesions and in situ cancer.

AIMS: The objective of this study is to derive highly specific nuclear signatures (NS's) for the characterization of nuclei of ductal breast epithelium in proliferative lesions and in situ cancers in order to evaluate if nuclear structural changes are able to describe the main events of ductal cancer progression and if the method can be used for objective grading. METHODS: A total of 82 different features descriptive of the nuclear chromatin patterns were computed in nuclei from normal glandular breast tissue, florid hyperplasia, and ductal carcinoma in situ (DCIS) and of DCIS with microinfiltration. The feature values were arranged to form a profile or signature. Measures of difference to a standard profile derived from normal glandular breast tissue were defined. One may then compute a standardized distance measure for a nucleus from "normal". Lesions can be characterized in the same manner, on the basis of the mean profile for all of their nuclei, and on the basis of the distribution of distances of their constituent nuclei from normal. RESULTS: The selected histopathologic patterns on which the diagnostic categories for DCIS are based were found to have corresponding distinctive patterns in the chromatin of the lesion's nuclei. A monotonic trend of ductal neoplastic progression was found. In addition, lesions histologically assessed as belonging to the same diagnostic category were found to offer substantially different distribution patterns. CONCLUSIONS: The full utilization of nuclear texture features allows the derivation of highly specific signatures for nuclei so that a reproducible grading can be performed for prognostic purposes.

Breast↗

PubMed1999

Tissue architecture analysis in prostate cancer and its precursors: An innovative approach to computerized histometry.

AIMS: It is the aim of these studies to derive a numerically defined progression index for prostatic intraepithelial neoplasia (PIN) lesions. METHODS: Histometric and karyometric features were automatically extracted from images of histopathologic sections by a machine vision system. RESULTS: Both histometric and karyometric measures lend themselves to the defining of a progression index. Karyometric features were found to be more sensitive. They allow the detection of very early change. CONCLUSIONS: It is possible to measure progression of PIN lesions with precision. The methodology would lend itself for measurement of regression due to chemopreventive intervention.

Artificial Intelligence↗

PubMed1999

Chromatin texture in high grade prostatic intraepithelial neoplasia and early invasive carcinoma.

OBJECTIVE: To evaluate individual nuclei from high grade prostatic intraepithelial neoplasia (PIN) lesions with early invasive carcinoma foci in the area of microinvasion and in the gland in which the microinvasion originated. STUDY DESIGN: High-resolution, digitized images of nuclei from defined locations were recorded and segmented, and karyometric variables were computed. These included a set of 93 features, which form a nuclear signature characterizing the spatial and statistical distribution of the nuclear chromatin. Nuclei in the glandular epithelium were recorded sequentially, along the basal cell layer, at increasing distances from the point of microinvasion and by random selection in the region of microinvasion. RESULTS: At a distance > 60 nuclear locations from the point of microinvasion, the nuclear signatures corresponded to those seen in high grade PIN. Between 40 and 20 nuclear locations removed from the microinvasion focus the signatures began to change gradually until at a distance of 15-5 locations they strongly resembled the signatures seen in adenocarcinoma. The total optical density decreased to values seen in adenocarcinoma, and the nuclear chromatin had finer granularity. While nuclei in high grade PIN followed a widely dispersed total optical density distribution suggestive of wide-ranging aneuploidy, the nuclei in the region of microinvasion exhibited a less dispersed and bimodal total optical density distribution. CONCLUSION: The chromatin texture signatures showed a clear trend: there was an obvious attenuation as the measured nuclei approached the microinvasion area. The decrease in total optical density at the microinvasion might suggest the emergence of one or two clones that can be responsible for the invasive phenotype.

Adenocarcinoma↗

PubMed1998

Machine vision in the detection of prostate lesions in histologic sections.

OBJECTIVE: To explore the utility of N-gram encoding for the automated detection and delineation of regions of histologic abnormality in tissue sections of prostate. STUDY DESIGN: Digitized imagery of tissue sections from normal prostate glandular tissue, stroma and regions of well- and poorly differentiated lesions was recorded and successively subdivided into square subregions of 256 x 256 to 16 x 16 pixels. N-grams of N = 2 to N = 6 were computed, with each element assuming a value representing an optical density interval 0.30 units wide, covering the range from optical density = 0.0 to 1.80. Then, from a large database, prototype frequency histograms of the different N-grams were established. For each subregion the Euclidean distances to the different prototype histograms were computed and defined as "distance to prototype" features. Standard discriminant analyses and a nonparametric classifier were used to assign subregions to the different tissue categories. RESULTS: Classification of subregions was achieved for most discrimination tasks at a correct recognition rate ranging from 85% to 100% on both training set and test set data, with a few exceptions. N-grams of N > 4 had considerable discriminatory power. CONCLUSION: N-gram encoding has the potential to provide highly discriminating, texture-based characterization of subregions of digitized imagery of prostate lesions and may be very useful in the development of decision procedures for the automated detection of prostate lesions by a machine vision system.

Algorithms↗

PubMed1998

Nuclear chromatin texture in prostatic lesions. I. PIN and adenocarcinoma.

OBJECTIVE: To document changes in the chromatin pattern in secretory cell nuclei from prostates with prostatic intraepithelial neoplasia (PIN) or adenocarcinoma. STUDY DESIGN: High-resolution images of nuclei were recorded, and a set of features descriptive of the chromatin texture and spatial distribution was computed. From this data set, features undergoing a monotonic trend of progression were selected and plotted to reveal trends in lesion progression. RESULTS: The nuclear chromatin in secretory cells in prostates with either PIN or malignant adenocarcinoma undergoes distinct and statistically significant changes in its texture and spatial distribution. Two trends of progressive change were observed. First, the values of a number of features descriptive of the clumpiness of the chromatin increase from values found in normal prostates to those recorded for nuclei from low grade to high grade PIN lesions. The second trend is a decrease in the values of the same features from those found in nuclei from high grade PIN still facing an intact basal cell layer to those no longer facing such a layer. This may be the first detectable step in progression towards development of a malignant lesion. There is a further decrease in nuclei in glands immediately adjacent to adenocarcinoma and in malignant lesions themselves. CONCLUSION: The described changes may lend themselves to the monitoring of lesion progression or of response to treatment or to chemopreventive intervention.

Adenocarcinoma↗

PubMed1998

Nuclear chromatin texture in prostatic lesions. II. PIN and malignancy associated changes.

OBJECTIVE: The objective of this study was to identify and document prostatic intraepithelial neoplasia (PIN) and malignancy associated changes in secretory cell nuclei from visually normal appearing tissue regions of prostates harboring PIN or adenocarcinoma. STUDY DESIGN: High-resolution digitized images of nuclei were recorded in histologically normal appearing tissue regions at defined distances from the margin of PIN or malignant lesions. Features descriptive of nuclear chromatin texture were computed and used to derive a discriminant function score for each nucleus. RESULTS: Secretory cell nuclei in prostates harboring either PIN or adenocarcinoma were shown to have statistically significantly different chromatin texture from secretory cell nuclei recorded in prostates free from any such lesion. The expression of PIN or malignancy associated changes was documented for distances up to 10 mm from the margin of a lesion. CONCLUSION: The finding of characteristic changes in nuclear chromatin texture of nuclei from histologically normal appearing tissue in prostates with PIN or adenocarcinoma offers the potential for higher sensitivity of detection of such lesions and for earlier detection of changes potentially preceding the development of clinically significant disease.

Cell Nucleus↗

PubMed1998

Chromatin texture signatures in nuclei from prostate lesions.

OBJECTIVE: To characterize nuclei from prostatic lesions in a highly specific manner by developing a nuclear chromatin texture signature and to characterize lesions by means of their composition of nuclei with diverse degrees of deviation from normal. STUDY DESIGN: High-resolution digitized imagery of nuclei from normal prostates, from prostatic neoplastic lesions of low and high grade and from histologically normal appearing regions of prostates with low and high grade prostatic intraepithelial neoplasia (PIN) lesions were recorded. A set of 65 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus. These features were arranged and processed to form a distinctive signature. A distance metric from "normal" was defined and computed for each nucleus. RESULTS: Profiles of feature values can, after suitable scaling, be presented as distinctive feature value signatures. For many practical applications, profiles based on a standardized distance from normal nuclei may be more useful. Such profiles allow the derivation of a progression curve, showing increasing distances for diagnostic groups with increasing lesion progression up to high grade PIN lesions. Within each diagnostic group different cases show distinctive distributions of nuclei with differing degrees of deviation from normal, allowing the derivation of a lesion signature. CONCLUSION: Nuclear chromatin texture signatures may be of value for the characterization of both nuclei and lesions. They are based on a more comprehensive use of information offered by the nuclear chromatin pattern than that included in classification methods. While these signatures offer a more specific characterization of a clinical sample, they also are subject to more variability within a diagnostic category. This may not be due to randomness but may reflect some actual differences between lesions.

Adenocarcinoma↗

PubMed1996

Analysis of the capillary architecture in the precursors of prostate cancer: recent findings and new concepts.

OBJECTIVE: To report on recent findings and new concepts in the remodeling of the capillary architecture in the precursors of prostate cancer. METHODS: Immunohistochemical methods have been adopted in prostate cancer and in its precursors (prostatic intra-epithelial neoplasia) to investigate capillary pattern changes-which were mainly analyzed as capillary frequency- and the degree of endothelial cell proliferation. Several features related to the capillary architecture have been considered. Manual, semiautomatic, and automatic (machine vision) types of evaluation have been used to quantify the features. RESULTS: The data available indicate that: (1) Going from normal prostate through prostatic intra-epithelial neoplasia up to invasive adenocarcinoma, an increasing proportion of capillaries becomes shorter, with open lumen and undulated external contour and with greater proliferation of the endothelial cells and greater expression of type IV collagenase. The highest proportion of touching capillaries is seen in normal prostate, while the lowest is found in invasive adenocarcinoma, being intermediate in prostatic intra-epithelial neoplasia. (2) When total androgen ablation is induced, there is no proliferation of the endothelium, whereas the capillaries are reduced in frequency and represented by small vessels lined by flat endothelial cells and with an open lumen. (3) Automation in the evaluation of the capillary architecture is feasible with a machine vision system. CONCLUSIONS: The progression in prostate carcinogenesis is associated with changes in the capillary architecture. There are some preliminary data indicating that total androgen ablation can inhibit the angiogenesis in precursors of prostate cancer.

Cell Division↗

PubMed1996

Knowledge-guided histometry of the basal cell layer in prostatic intraepithelial neoplasia.

OBJECTIVE: To define a procedure for the fully automated evaluation of histopathologic sections of prostatic intraepithelial neoplasia. STUDY DESIGN: The design is based on expert system-guided scene segmentation, the construction of a knowledge file and the defining of histometric measures for assessment of the basal cell layer. RESULTS: A knowledge file specifying a total of 263 entities was constructed. Of 73 multimegapixel-sized images of cribriform glands, 71 were correctly and completely processed. A histometric measure allowing precise indexing of the degree of lesion progression, based on the deterioration of the basal cell layer, was derived. CONCLUSION: The combination of image analytic and immunohistochemical procedures and fully automated processing provides a quantitative measure for evaluating prostatic intraepithelial neoplasia lesion progression and the effects of intervention.

Expert Systems↗

PubMed1995

Prostatic intraepithelial neoplasia. Quantitation of the basal cell layer with machine vision system.

The aim of this paper is to report on a fully automated procedure to quantify the epithelial cell components in prostatic intraepithelial neoplasia with particular emphasis on the basal cell layer (BCL). Scene segmentation was guided by a knowledge-based system of digitized images recorded from histological section immunostained against high molecular weight keratin and counterstained with hematoxylin and eosin. Scene segmentation involved two major stages. First, the system located and identified the duct and segmented the scene, resulting in "intermediate segmentation products." This stage was followed by a reconstruction process in which the segmentation products (i.e., the lumen and the darkly and lightly stained epithelial cell components) were assembled to form the microscopic structure to achieve working unity. Following this, histometric measurements were made of the reconstructed scene. Computed were the percentage of the duct contour with BCL (90%), and the number and length of gaps in the BCL (19, ranging from 10 to 90 microns). Automated analysis of the BCL is accurate and provides information not readily identified by human examination.

Basement Membrane↗

PubMed1995

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↗

PubMed1995

Image segmentation of cribriform gland tissue.

OBJECTIVE: To develop procedures for the segmentation of cribriform prostatic glands. STUDY DESIGN: A knowledge-guided procedure following a model-based reasoning process was developed in the context of a set of interacting expert systems for machine vision in histometry. RESULTS: With 78 entities in the knowledge file, fully automated, correct segmentation of approximately 70-80% of cribriform glands was attained--i.e., outlining of histologic components agreed with visual assessment. Measurement of gland size, shape, lumen area, number of lumina per gland, epithelial layer thickness, degree of cribriformity and determination of completeness of lining of a gland by a basal cell layer could be taken from the correctly segmented images. CONCLUSION: The automated procedure allows a histometric characterization of premalignant and malignant prostatic lesions. Extension of system capabilities to the utilization of spectral information is expected to allow an increase in the correct segmentation rate.

Humans↗