New Algorithms Based on the Voronoi Diagram Applied in a Pilot Study on Normal Mucosa and Carcinomas

An adequate reproducibility in the description of tissue architecture is still a challenge to diagnostic pathology, sometimes with unfortunate prognostic implications. To assess a possible diagnostic and prognostic value of quantitiative tissue architecture analysis, structural features based on the Voronoi Diagram (VD) and its subgraphs were developed and tested. A series of 27 structural features were developed and tested in a pilot study of 30 cases of prostate cancer, 10 cases of cervical carcinomas, 8 cases of tongue cancer and 8 cases of normal oral mucosa. Grey level images were acquired from hematoxyline‐eosine (HE) stained sections by a charge coupled device (CCD) camera mounted on a microscope connected to a personal computer (PC) with an image array processor. From the grey level images obtained, cell nuclei were automatically segmented and the geometrical centres of cell nuclei were computed. The resulting 2‐dimensional (2D) swarm of pointlike seeds distributed in a flat plane was the basis for construction of the VD and its subgraphs. From the polygons, triangulations and arborizations thus obtained, 27 structural features were computed as numerical values. Comparison of groups (normal vs. cancerous oral mucosa, cervical and prostate carcinomas with good and poor prognosis) with regard to distribution in the values of the structural features was performed with Student's t‐test. We demonstrate that some of the structural features developed are able to distinguish structurally between normal and cancerous oral mucosa (P=0.001), and between good and poor outcome groups in prostatic (P=0.001) and cervical carcinomas (P=0.001). We present results confirming previous findings that graph theory based algorithms are useful tools for describing tis‐ sue architecture (e.g., normal versus malignant). The present study also indicates that these methods have a potential for prognostication in malignant epithelial lesions.

[1]  Martin,et al.  Finite size and dimensional dependence in the Euclidean traveling salesman problem. , 1996, Physical review letters.

[2]  A Llebaria,et al.  Minimal spanning tree analysis of biological structures. , 1987, Journal of theoretical biology.

[3]  Jean Serra,et al.  Image Analysis and Mathematical Morphology , 1983 .

[4]  J. Lillehaug,et al.  Cell transformation and promoter activity of insulation oils in the Syrian hamster embryo cell and in the C3H/10T1/2 mouse embryo fibroblast test systems. , 1987, Journal of toxicology and environmental health.

[5]  E Rivedal,et al.  Retinoids have different effects on morphological transformation and anchorage independent growth of Syrian hamster embryo cells. , 1985, Carcinogenesis.

[6]  Mo,et al.  Hausdorff dimension of critical fluctuations in abelian gauge theories , 2000, Physical review letters.

[7]  H. Danielsen,et al.  Histopathological grading and DNA ploidy as prognostic markers in metastatic prostatic cancer. , 1995, British Journal of Cancer.

[8]  F. Meyer,et al.  Germinal center analysis with the tools of mathematical morphology on graphs. , 1993, Cytometry.

[9]  R. Marcelpoil,et al.  Normalization of the minimum spanning tree. , 1993, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[10]  G Haroske,et al.  Cellular sociology of proliferating tumor cells in invasive ductal breast cancer. , 1996, Analytical and quantitative cytology and histology.

[11]  D. Sulsky,et al.  A model of cell sorting. , 1984, Journal of theoretical biology.

[12]  Godfried T. Toussaint,et al.  PATTERN RECOGNITION AND GEOMETRICAL COMPLEXITY. , 1980 .

[13]  G Anneroth,et al.  Review of the literature and a recommended system of malignancy grading in oral squamous cell carcinomas. , 1987, Scandinavian journal of dental research.

[14]  H. J. G. GUNDERSEN,et al.  Some new, simple and efficient stereological methods and their use in pathological research and diagnosis , 1988, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[15]  R L Sidman,et al.  Cell patterning in vertebrate development: models and model systems. , 1987, Current topics in developmental biology.

[16]  E Bengtsson,et al.  Grading of transitional cell bladder carcinoma by image analysis of histological sections. , 1995, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[17]  K. Kayser,et al.  Minimum Spanning Tree - Voronoi's Tesselation - Johnson-Mehl Diagrams - Human Lung Carcinoma , 1989 .

[18]  T Jarkrans,et al.  Grading of transitional cell bladder carcinoma by texture analysis of histological sections. , 1994, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[19]  Robert E. Tarjan,et al.  Finding Minimum Spanning Trees , 1976, SIAM J. Comput..

[20]  M L Mendelsohn,et al.  THE ANALYSIS OF CELL IMAGES * , 1966, Annals of the New York Academy of Sciences.

[21]  B Stenkvist,et al.  Malignancy grading of epithelial bladder tumours. Reproducibility of grading and comparison between forceps biopsy, aspiration biopsy and exfoliative cytology. , 1977, Scandinavian journal of urology and nephrology.

[22]  S. Mikalsen,et al.  Morphological transformation of Syrian hamster embryo cells induced by mineral fibres and the alleged enhancement of benzo[a]pyrene. , 1988, Carcinogenesis.

[23]  B Stenkvist,et al.  A software system to record and analyze digitized cell images. , 1977, Computer programs in biomedicine.

[24]  G Eklund,et al.  Predicting breast cancer recurrence , 1982, Cancer.

[25]  G A Meijer,et al.  Syntactic structure analysis. , 1995, Pathologica.

[26]  J. Vegelius,et al.  Computerized nuclear morphometry as an objective method for characterizing human cancer cell populations. , 1978, Cancer research.

[27]  S. Verblunsky On the shortest path through a number of points , 1951 .

[28]  A. Karabulut,et al.  Observer variability in the histologic assessment of oral premalignant lesions. , 1995, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[29]  G Anneroth,et al.  Malignancy grading in oral squamous cell carcinoma. I. Squamous cell carcinoma of the tongue and floor of mouth: histologic grading in the clinical evaluation. , 1986, Journal of oral pathology.

[30]  F. B. Sørensen,et al.  Histopathologic, stereologic, epidemiologic, and clinical parameters in the prognostic evaluation of squamous cell carcinoma of the oral cavity , 1996, Head & neck.

[31]  E. Cooper,et al.  Analyses of dna content, nuclear size and cell proliferation of transitional cell carcinoma in man , 1969, Cancer.

[32]  Ewert Bengtsson,et al.  A New Method for Segmentation of Colour Images Applied to Immunohistochemically Stained Cell Nuclei , 1997, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[33]  M L Mendelsohn,et al.  Analysis of tumor growth curves. , 1968, Journal of the National Cancer Institute.

[34]  J L Pasteels,et al.  Characterization of the differentiation of human colorectal cancer cell lines by means of Voronoi diagrams. , 1993, Cytometry.

[35]  P. Rujan,et al.  A geometrical description of horizontal cell networks in the turtle retina , 1993, Brain Research.

[36]  E Rivedal,et al.  Fibrinolytic activity and morphological transformation of hamster embryo cells. , 1982, Carcinogenesis.

[37]  L. Bodenstein,et al.  A dynamic simulation model of tissue growth and cell patterning. , 1986, Cell differentiation.

[38]  R L Sidman,et al.  Positional variations in germinal cell growth in pigment-chimeric eyes of Xenopus: posterior half of the developing eye studied in genetic chimerae and in computer simulations. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[39]  Landini,et al.  Asymptotic fractals in the context of grey‐scale images , 1998, Journal of microscopy.

[40]  Fritz Albregtsen,et al.  A Review of Caveats in Statistical Nuclear Image Analysis , 1998, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[41]  T. Sanner,et al.  Promotional effect of different phorbol esters on morphological transformation of hamster embryo cells. , 1982, Cancer letters.

[42]  J. Beardwood,et al.  The shortest path through many points , 1959, Mathematical Proceedings of the Cambridge Philosophical Society.

[43]  E. Dabelsteen,et al.  New malignancy grading is a better prognostic indicator than Broders' grading in oral squamous cell carcinomas. , 1989, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[44]  Ewert Bengtsson,et al.  Automatic Quantification of Immunohistochemically Stained Cell Nuclei Based on Standard Reference Cells , 1998, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[45]  A Llebaria,et al.  Quantization of directional properties in biological structures using the Minimal Spanning Tree. , 1988, Journal of theoretical biology.

[46]  B Stenkvist,et al.  Image cytometry in malignancy grading of breast cancer. Results in a prospective study with seven years of follow-up. , 1986, Analytical and quantitative cytology and histology.

[47]  J. Prewitt,et al.  Computer analysis of cell images. , 1965, Postgraduate medicine.

[48]  Eric W. Weisstein Minimum Spanning Tree , 2000 .

[49]  Ewert Bengtsson,et al.  Image Analysis Based Grading of Bladder Carcinoma. Comparison of Object, Texture and Graph Based Methods and Their Reproducibility , 1997, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[50]  G Brugal,et al.  Cellular sociology applied to neuroendocrine tumors of the lung: quantitative model of neoplastic architecture. , 1996, Cytometry.

[51]  K Kayser,et al.  Minimum spanning tree, Voronoi's tesselation and Johnson-Mehl diagrams in human lung carcinoma. , 1989, Pathology, research and practice.

[52]  B Stenkvist,et al.  A computerized recording system for cytopathologic diagnoses. , 1977, Acta cytologica.