Euclidean and fractal geometry of microvascular networks in normal and neoplastic pituitary tissue

In geometrical terms, tumour vascularity is an exemplary anatomical system that irregularly fills a three-dimensional Euclidean space. This physical characteristic and the highly variable shapes of the vessels lead to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients and drugs, and the removal of metabolites. Although these biological characteristics are well known, quantitative analyses of newly formed vessels in two-dimensional histological sections still fail to view their architecture as a non-Euclidean geometrical entity, thus leading to errors in visual interpretation and discordant results from different laboratories concerning the same tumour. We here review the literature concerning microvessel density estimates (a Euclidean-based approach quantifying vascularity in normal and neoplastic pituitary tissues) and compare the results. We also discuss the limitations of Euclidean quantitative analyses of vascularity and the helpfulness of a fractal geometry-based approach as a better means of quantifying normal and neoplastic pituitary microvasculature.

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

[2]  Claudio Eccher,et al.  Microvessel density quantification in breast carcinomas. Assessment by light microscopy vs. a computer-aided image analysis system , 1995 .

[3]  N. Weidner,et al.  Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  C. Sparrow The Fractal Geometry of Nature , 1984 .

[5]  M. Witt,et al.  Galactose and fucose binding sites in anterior pituitary cells of the rat. Detection by means of biotinylated lectins. , 1987, Folia histochemica et cytobiologica.

[6]  George Sugihara,et al.  Fractals: A User's Guide for the Natural Sciences , 1993 .

[7]  James H. Brown,et al.  The fourth dimension of life: fractal geometry and allometric scaling of organisms. , 1999, Science.

[8]  M. Hlastala,et al.  A fractal analysis of the radial distribution of bronchial capillaries around large airways. , 2005, Journal of applied physiology.

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

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

[11]  G. Tsafnat,et al.  A three-dimensional fractal model of tumour vasculature , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[12]  Paolo Gaetani,et al.  Fractal dimension as a quantitator of the microvasculature of normal and adenomatous pituitary tissue , 2007, Journal of anatomy.

[13]  J. Itoh,et al.  Vascular networks and endothelial cells in the rat experimental pituitary glands and in the human pituitary adenomas , 2003, Microscopy research and technique.

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

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

[16]  R. Fahlbusch,et al.  Pituitary microcirculation: physiological aspects and clinical implications. A laser-Doppler flow study during transsphenoidal adenomectomy. , 1991, Neurosurgery.

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

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

[19]  R. Cortvrindt,et al.  Confocal microscopy: principles and applications to the field of reproductive biology. , 2001, Folia histochemica et cytobiologica.

[20]  R. Jain,et al.  Role of tumor vascular architecture in nutrient and drug delivery: an invasion percolation-based network model. , 1996, Microvascular research.

[21]  G. Latini,et al.  Abnormal vascular network complexity: a new phenotypic marker in hereditary non-polyposis colorectal cancer syndrome , 2003, Gut.

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

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

[24]  Pranab Dey,et al.  Basic principles and applications of fractal geometry in pathology: a review. , 2005, Analytical and quantitative cytology and histology.

[25]  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.

[26]  Giorgio Manzi,et al.  Fractal dimension of the middle meningeal vessels: variation and evolution in Homo erectus, Neanderthals, and modern humans. , 2005, European journal of morphology.

[27]  S. Kyriacos,et al.  Dynamic study of the extraembryonic vascular network of the chick embryo by fractal analysis. , 1998, Journal of theoretical biology.

[28]  B. Masters,et al.  Fractal analysis of the vascular tree in the human retina. , 2004, Annual review of biomedical engineering.

[29]  J. Rosai,et al.  Localization of factor VIII-related antigen in vascular endothelial cells using an immunoperoxidase method. , 1980, The American journal of surgical pathology.

[30]  D. Guidolin,et al.  A new image analysis method based on topological and fractal parameters to evaluate the angiostatic activity of docetaxel by using the Matrigel assay in vitro. , 2004, Microvascular research.

[31]  J W Baish,et al.  Fractals and cancer. , 2000, Cancer research.

[32]  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.

[33]  E. Sabo,et al.  Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

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

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

[36]  S. Albelda,et al.  Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule , 1991, The Journal of cell biology.

[37]  Fabio Grizzi,et al.  The complexity of anatomical systems , 2005, Theoretical Biology and Medical Modelling.

[38]  E Oczeretko,et al.  Fractal geometric analysis of lung cancer angiogenic patterns. , 2001, Folia histochemica et cytobiologica.

[39]  E. Weibel,et al.  Fractals in Biology and Medicine , 1994 .

[40]  G. Landini,et al.  Local connected fractal dimensions and lacunarity analyses of 60 degrees fluorescein angiograms. , 1995, Investigative ophthalmology & visual science.

[41]  G. Latini,et al.  Abnormal oral vascular network pattern geometry: a new clinical sign of down syndrome. , 2006, The Journal of pediatrics.

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

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

[44]  G Landini,et al.  Fractal analysis of the normal human retinal fluorescein angiogram. , 1993, Current eye research.

[45]  Bruce J. West,et al.  Fractal physiology , 1994, IEEE Engineering in Medicine and Biology Magazine.

[46]  S. Schmidt,et al.  Quantitation of angiogenesis in the chick chorioallantoic membrane model using fractal analysis. , 1996, Microvascular research.

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

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

[49]  F Pozza,et al.  Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. , 1992, Journal of the National Cancer Institute.

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

[51]  Y. Chung,et al.  Tumor angiogenesis as a predictor of recurrence in gastric carcinoma. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[52]  M. Riley,et al.  IN FRACTAL PHYSIOLOGY , 2022 .

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

[54]  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.

[55]  M Gion,et al.  Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. , 2002, European journal of cancer.

[56]  S. Leurgans,et al.  Tumor Angiogenesis as a Predictor of Recurrence and Survival in Patients with Node‐Negative Colon Cancer , 1995, Annals of surgery.

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

[58]  J. Phillips Entropy Analysis of Multiple Scale Causality and Qualitative Causal Shifts in Spatial Systems , 2005, The Professional Geographer.

[59]  Losa Ga,et al.  Self-similarity and fractal irregularity in pathologic tissues. , 1996 .

[60]  A. Harris,et al.  Quantitation and prognostic value of breast cancer angiogenesis: Comparison of microvessel density, Chalkley count, and computer image analysis , 1995, The Journal of pathology.

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

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

[63]  R. Jain,et al.  Cancer, angiogenesis and fractals , 1998, Nature Medicine.

[64]  S. Groshen,et al.  Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. , 1995, Journal of the National Cancer Institute.

[65]  P. Parsons-Wingerter,et al.  A novel assay of angiogenesis in the quail chorioallantoic membrane: stimulation by bFGF and inhibition by angiostatin according to fractal dimension and grid intersection. , 1998, Microvascular research.

[66]  S. Blacher,et al.  Fractal Quantification of the Microvasculature Heterogeneity in Cutaneous Melanoma , 1999, Dermatology.

[67]  N. Weidner Intratumoral vascularity as a prognostic factor in cancers of the urogenital tract. , 1996, European journal of cancer.

[68]  James B. Bassingthwaighte,et al.  The Fractal Nature of Myocardial Blood Flow Emerges from a Whole-Organ Model of Arterial Network , 2000, Journal of Vascular Research.

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

[70]  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.

[71]  Nicola Dioguardi,et al.  Geometry of Human Vascular System: Is it an Obstacle for Quantifying Antiangiogenic Therapies? , 2007, Applied immunohistochemistry & molecular morphology : AIMM.

[72]  J. Schechter Ultrastructural changes in the capillary bed of human pituitary tumors. , 1972, American Journal of Pathology.

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