Fractal dimension as a quantitator of the microvasculature of normal and adenomatous pituitary tissue

It is well known that angiogenesis is a complex process that accompanies neoplastic growth, but pituitary tumours are less vascularized than normal pituitary glands. Several analytical methods aimed at quantifying the vascular system in two‐dimensional histological sections have been proposed, with very discordant results. In this study we investigated the non‐Euclidean geometrical complexity of the two‐dimensional microvasculature of normal pituitary glands and pituitary adenomas by quantifying the surface fractal dimension that measures its space‐filling property. We found a statistical significant difference between the mean vascular surface fractal dimension estimated in normal versus adenomatous tissues (P = 0.01), normal versus secreting adenomatous tissues (P = 0.0003), and normal versus non‐secreting adenomatous tissues (P = 0.047), whereas the difference between the secreting and non‐secreting adenomatous tissues was not statistically significant. This study provides the first demonstration that fractal dimension is an objective and valid quantitator of the two‐dimensional geometrical complexity of the pituitary gland microvascular network in physiological and pathological states. Further studies are needed to compare the vascular surface fractal dimension estimates in different subtypes of pituitary tumours and correlate them with clinical parameters in order to evaluate whether the distribution pattern of vascular growth is related to a particular state of the pituitary gland.

[1]  F. Pansera.  Fractals and cancer. , 1994, Medical hypotheses.

[2]  A Vacca,et al.  New non-angiogenesis dependent pathways for tumour growth. , 2003, European journal of cancer.

[3]  G Landini,et al.  Fractal dimensions of the epithelial-connective tissue interfaces in premalignant and malignant epithelial lesions of the floor of the mouth. , 1993, Analytical and quantitative cytology and histology.

[4]  Gabriele A. Losa,et al.  Nuclear patterns of human breast cancer cells during apoptosis: characterisation by fractal dimension and co-occurrence matrix statistics , 2005, Cell and Tissue Research.

[5]  M. Sharma,et al.  Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis , 2005, Histopathology.

[6]  J. Folkman,et al.  Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. , 1991, The New England journal of medicine.

[7]  L. Pan,et al.  Magnetic resonance imaging and biological markers in pituitary adenomas with invasion of the cavernous sinus space , 2005, Journal of Neuro-Oncology.

[8]  G Landini,et al.  HOW IMPORTANT IS TUMOUR SHAPE? QUANTIFICATION OF THE EPITHELIAL–CONNECTIVE TISSUE INTERFACE IN ORAL LESIONS USING LOCAL CONNECTED FRACTAL DIMENSION ANALYSIS , 1996, The Journal of pathology.

[9]  J. Folkman.  What is the evidence that tumors are angiogenesis dependent? , 1990, Journal of the National Cancer Institute.

[10]  B. Scheithauer,et al.  Vasculature in nontumorous hypophyses, pituitary adenomas, and carcinomas: A quantitative morphologic study , 1995, Endocrine pathology.

[11]  J. Hardy.  Transphenoidal microsurgery of the normal and pathological pituitary. , 1969, Clinical neurosurgery.

[12]  Paul A. Bottomley,et al.  19F magnetic resonance imaging , 1977 .

[13]  P. Carmeliet.  Angiogenesis in health and disease , 2003, Nature Medicine.

[14]  S. Cross,et al.  Quantitation of the renal arterial tree by fractal analysis , 1993, The Journal of pathology.

[15]  M. Zamir.  On fractal properties of arterial trees. , 1999, Journal of theoretical biology.

[16]  G. Giannattasio,et al.  Microvasculature of human micro- and macroprolactinomas. A morphological study. , 1986, Neuroendocrinology.

[17]  F Grizzi,et al.  Correspondence re: E. Sabo et al., Microscopic Analysis and Significance of Vascular Architectural Complexity in Renal Cell Carcinoma. Clin. Cancer Res., 7: 533-537, 2001. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[18]  Barbara Franceschini,et al.  Quantitative evaluation and modeling of two-dimensional neovascular network complexity: the surface fractal dimension , 2005, BMC Cancer.

[19]  F Grizzi,et al.  Fractal geometry: a useful tool for quantifying irregular lesions in human liver biopsy specimens. , 2001, Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia.

[20]  G. Yancopoulos,et al.  Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. , 1999, Science.

[21]  G Landini,et al.  Morphometrical differences between pseudo‐epitheliomatous hyperplasia in granular cell tumours and squamous cell carcinomas , 2006, Histopathology.

[22]  M. Niveiro,et al.  Immunohistochemical analysis of tumor angiogenic factors in human pituitary adenomas. , 2005, Human pathology.

[23]  B. Hogan,et al.  Organogenesis: Molecular Mechanisms Of Tubulogenesis , 2002, Nature Reviews Genetics.

[24]  M Buyse,et al.  Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis. , 1997, The American journal of pathology.

[25]  M. Gasperi,et al.  Microvascular density and vascular endothelial growth factor expression in normal pituitary tissue and pituitary adenomas , 2003, Journal of endocrinological investigation.

[26]  A. Harris,et al.  Angiogenesis in pituitary adenomas - relationship to endocrine function, treatment and outcome. , 2000, The Journal of endocrinology.

[27]  S S Cross,et al.  FRACTALS IN PATHOLOGY , 1997, The Journal of pathology.

[28]  Luigi Pannarale,et al.  Fractal and Fourier analysis of the hepatic sinusoidal network in normal and cirrhotic rat liver , 2005, Journal of anatomy.

[29]  O. Clausen,et al.  Resectable adenocarcinomas in the pancreatic head: the retroperitoneal resection margin is an independent prognostic factor , 2008, BMC Cancer.

[30]  A. Harris,et al.  Proliferation, bcl-2 expression and angiogenesis in pituitary adenomas: relationship to tumour behaviour , 2000, British Journal of Cancer.

[31]  M. Krasnow,et al.  Tube Morphogenesis Making and Shaping Biological Tubes , 2003, Cell.

[32]  Rakesh K Jain,et al.  Molecular regulation of vessel maturation , 2003, Nature Medicine.

[33]  J. Folkman,et al.  Anti‐Angiogenesis: New Concept for Therapy of Solid Tumors , 1972, Annals of surgery.

[34]  S S Cross,et al.  The application of fractal geometric analysis to microscopic images. , 1994, Micron.

[35]  B. Scheithauer,et al.  Effect of dopamine agonists on lactotroph adenomas of the human pituitary , 2000, Endocrine pathology.

[36]  B. Scheithauer,et al.  Tumors of the Pituitary Gland , 1990 .

[37]  B. Scheithauer,et al.  Vascularity in nontumorous human pituitaries and incidental microadenomas: A morphometric study , 2000, Endocrine pathology.

[38]  K. Kovacs,et al.  Subclinical adenomas of the human pituitary. New light on old problems. , 1983, Archives of pathology & laboratory medicine.

[39]  D. S. Coffey.  Self-organization, complexity and chaos: The new biology for medicine , 1998, Nature Medicine.

[40]  T. Stephenson,et al.  Fractal geometric analysis of the renal arterial tree in infants and fetuses. , 1995, Pediatric pathology & laboratory medicine : journal of the Society for Pediatric Pathology, affiliated with the International Paediatric Pathology Association.

[41]  A. Nicholson,et al.  Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas , 2002, British Journal of Cancer.

[42]  S. Cross,et al.  Fractal geometric analysis of colorectal polyps , 1994, The Journal of pathology.

[43]  Janusz Skrzat,et al.  Error estimation of the fractal dimension measurements of cranial sutures , 2006, Journal of anatomy.

[44]  M Zamir,et al.  Fractal dimensions and multifractility in vascular branching. , 2001, Journal of theoretical biology.

[45]  Bruce J. West,et al.  Fractals in physiology and medicine. , 1987, The Yale journal of biology and medicine.

[46]  M. Benjamin,et al.  Regional variations in human patellar trabecular architecture and the structure of the proximal patellar tendon enthesis , 2006, Journal of anatomy.

[47]  M. Pawlikowski,et al.  Immunocytochemical investigations on the vascularization of pituitary adenomas , 1997, Endocrine pathology.

[48]  K. Kovacs,et al.  Microvascular structural entropy: A novel approach to assess angiogenesis in pituitary tumors , 2003, Endocrine pathology.

[49]  T F Nonnenmacher,et al.  Self-similarity and fractal irregularity in pathologic tissues. , 1996, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[50]  Benoit B. Mandelbrot,et al.  Fractal Geometry of Nature , 1984 .

[51]  J. Schechter.  Ultrastructural changes in the capillary bed of human pituitary tumors. , 1972, The American journal of pathology.

[52]  P. Hahnfeldt,et al.  Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn't tell us. , 2002, Journal of the National Cancer Institute.

[53]  A. Harris,et al.  Angiogenesis in pituitary adenomas and the normal pituitary gland. , 2000, The Journal of clinical endocrinology and metabolism.

[54]  E R Weibel,et al.  Resolution effect on the stereological estimation of surface and volume and its interpretation in terms of fractal dimensions , 1981, Journal of microscopy.

[55]  D J Ruiter,et al.  Quantitative immunohistological analysis of the microvasculature in untreated human glioblastoma multiforme. Computer-assisted image analysis of whole-tumor sections. , 1994, Journal of neurosurgery.

[56]  Gabriel Landini,et al.  Quantification of the global and local complexity of the epithelial-connective tissue interface of normal, dysplastic, and neoplastic oral mucosae using digital imaging. , 2003, Pathology, research and practice.

[57]  B. Scheithauer,et al.  Microvessel density in pituitary adenomas and carcinomas , 2001, Virchows Archiv.