Skip to main content Accessibility help
×
Home

Fractal and Image Analysis of the Microvasculature in Normal Intestinal Submucosa and Intestinal Polyps in ApcMin/+ Mice

  • John W. Fuseler (a1), Adam Bedenbaugh (a2), Krishna Yekkala (a3) and Troy A. Baudino (a2)

Abstract

Tumors are supported by the development of a unique vascular bed. We used fractal dimension (Db) and image analysis to quantify differences in the complexity of the vasculature in normal intestinal submucosa and intestinal polyps. ApcMin/+ mice and wild-type mice were perfused with a curable latex compound, intestines sectioned, and images collected via confocal microscopy. The images were analyzed and area (A), perimeter (P), and integrated optical density (IOD) of the normal and tumor vascular beds were measured. The Db, a quantitative descriptor of morphological complexity, was significantly greater for the polyp vasculature from ApcMin/+ mice than controls. This indicates that the polyp microvasculature is more chaotic than that of the controls, while the IOD and average vascular density values displayed no differences. This suggests the mass of blood volume is equivalent in normal and polyp microvasculature. The lower vascular area-perimeter ratios expressed by the polyp microvasculature suggest it is composed of smaller, more tortuous vessels. These data demonstrate that fractal analysis is applicable for providing a quantitative description of vascular complexity associated with angiogenesis occurring in normal or diseased tissue. Application of Db, IOD, and average density provides a clearer quantification of the complex morphology associated with tissue microvasculature.

Copyright

Corresponding author

Corresponding author. E-mail: tbaudino@medicine.tamhsc.edu

References

Hide All
Abraham, R. & Shaw, C. (1992). Dynamics, The Geometry of Behavior, 2nd Ed.Reading, MA: Addison-Wesley.
Baish, J.W., Gazit, Y., Berk, D.A., Nozue, M., Baxter, L.T. & Jain, R.K. (1996). Role of tumor vascular architecture in nutrient and drug delivery: An invasion percolation-based network model. Microvasc Res 51, 327346.
Baish, J.W. & Jain, R.K. (2000). Fractals and cancer. Cancer Res 60, 36833688.
Barclay, K.D., Klassen, G.A. & Young, C. (2000). A method for detecting chaos in canine myocardial microcirculatory red cell flux. Microcirculation 7, 335346.
Cross, S.S. (1997). Fractals in pathology. J Pathol 182, 18.
De Felice, C., Latini, G., Bianciardi, G., Parrini, S., Fadda, G.M., Marini, M., Laurini, R.N. & Kopotic, R.J. (2003). Abnormal vascular network complexity: A new phenotypic marker in hereditary nonpolyposis colorectal cancer syndrome. Gut 52, 17641767.
Di Ieva, A., Grizzi, F., Ceva-Grimaldi, G., Russo, C., Gaetani, P., Aimar, E., Levi, D., Pisano, P., Tancioni, F., Nicoloa, G., Tschabitscher, M., Dioguardi, N. & Baena, R.R. (2007). Fractal dimension as a quantitator of the microvasculature of normal and adenomatous pituitary tissue. J Anat 211, 673680.
Dokoumetzidis, A., Iliadis, A. & Macheras, P. (2001). Nonlinear dynamics and chaos theory: Concepts and applications relevant to pharmacodynamics. Pharm Res 18, 415426.
Fernandez, E. & Jelinek, H.F. (2001). Use of fractal theory in neuroscience: Methods, advantages, and potential problems. Methods 24, 309321.
Fuseler, J.W., Merrill, D.M., Rogers, J.A., Grisham, M.B. & Wolf, R.E. (2006). Analysis and quantitation of NF-kappa β nuclear translocation in tumor necrosis factor alpha (TNF-alpha) activated vascular endothelial cells. Microsc Microanal 12, 269276.
Fuseler, J.W., Millette, C.F., Davis, J.M. & Carver, W. (2007). Fractal and image analysis of morphological changes in the actin cytoskeleton of neonatal cardiac fibroblasts in response to mechanical stretch. Microsc Microanal 13, 133143.
Gazit, Y., Baish, J.W., Safabakhsh, N., Leunig, M., Baxter, L.T. & Jain, R.K. (1997). Fractal characteristics of tumor vascular architecture during tumor growth and regression. Microcirculation 4, 395402.
Gazit, Y., Berk, D.A., Leunig, M., Baxter, L.T. & Jain, R.K. (1995). Scale-invariant behavior and vascular network formation in normal and tumor tissue. Phys Rev Lett 75, 24282431.
Glenny, R.W., Robertson, H.T., Yamashiro, S. & Bassingthwaighte, J.B. (1991). Applications of fractal analysis to physiology. J Appl Physiol 70, 23512367.
Grizzi, F., Russo, C., Colombo, P., Franceschini, B., Frezza, E.E., Cobos, E. & Chiriva-Internati, M. (2005). Quantitative evaluation and modeling of two-dimensional neovascular network complexity: The surface fractal dimension. BMC Cancer 5, 1423.
Guiot, C., Delsanto, P.P., Carpinteri, A., Pugno, N., Mansury, Y. & Deisboeck, T.S. (2006). The dynamic evolution of the power exponent in a universal growth model of tumors. J Theor Biol 240, 459463.
He, T.C., Sparks, A.B., Rago, C., Hermeking, H., Zawel, L., da Costa, L.T., Morin, P.J., Vogelstein, B. & Kinzler, K.W. (1999). Identification of c-myc as a target of the APC pathway. Science 281, 15091512.
Heymans, O., Blacher, S., Bouers, F. & Pierard, G.E. (1999). Fractal quantifications of the miscrovasculature heterogeneity in cutaneous melanoma. Dermatology 198, 212217.
Karshafian, R., Burns, P.N. & Henkelman, M.R. (2003). Transit time kinetics in ordered and disordered vascular trees. Phys Med Biol 48, 32253237.
Kikuchi, A., Kozuma, S., Sakamaki, K., Saito, M., Marumo, G., Yasugi, T. & Taketani, Y. (2002). Fractal tumor growth of ovarian cancer: Sonographic evaluation. Gynecol Oncol 87, 295302.
Kinzler, K.W. & Vogelstein, B. (1996). Lessons from hereditary colorectal cancer. Cell 87, 159170.
Korinek, V., Barker, N., Morin, P.J., van Wichen, D., de Weger, R., Kinzler, K.W., Vogelstein, B. & Clevers, H. (1997). Constitutive transcriptional activation by a βcatenin-Tcf complex in APC−/– colon carcinoma. Science 275, 17841787.
Mandelbrot, B.B. (1982). The Fractal Geometry of Nature, pp. 1419. New York: W.H. Freeman and Company.
Mandelbrot, B.B., Passoja, D.E. & Paully, A.J. (1984). Fractal character of fractures surfaces of metals. Nature 308, 721724.
Molenaar, M., van de Wetering, M., Oosterwegel, M., Peterson-Maduro, J., Godsave, S., Korinek, V., Roose, J., Destree, O. & Clevers, H. (1996). XTcf-3 transcription factor mediates β-catenin-induced axis formation in Xenopus embryos. Cell 86, 391399.
Morin, P.J., Sparks, A.B., Korinek, V., Barker, N., Clevers, H., Vogelstein, B. & Kinzler, K.W. (1997). Activation of β-catenin-Tcf signaling in colon cancers by mutations in β-catenin or APC. Science 275, 17871790.
Moser, A.R., Pitot, H.C. & Dove, W.F. (1990). A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247, 322324.
Nezadal, M., Zemeskal, O. & Buchnicek, M. (2001). The Box-Counting: Critical Study, 4th Conference on Prediction, Synergetic and More. The Faculty of Management, Institute of Information Technologies, Faculty of Technology, Tomas Bata University in Zlin, October 25–26, p. 18. HarFA software available at http://www.fch.vutbr.cz/lectures/imagesci.
Orel, V., Kozarenko, T., Galachin, K., Romanov, A. & Morozoff, A. (2007). Nonlinear analysis of digital images and Doppler measurements for trophoblastic tumor. Nonlinear Dynamics Psychol Life Sci 11, 309331.
Rogers, J.A. & Fuseler, J.W. (2007). Regulation of NF-kappaB activation and nuclear translocation by exogenous nitric oxide (NO) donors in TNF-alpha activated vascular endothelial cells. Nitric Oxide 16, 379391.
Sabo, E., Boltenko, A., Sova, Y., Stein, A., Kleinhaus, S. & Resnick, M.B. (2001). Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma. Clin Cancer Res 7, 533537.
Shoemaker, A.R., Gould, K.A., Luongo, C., Moser, A.R. & Dove, W.F. (1997). Studies of neoplasia in the Min mouse. Biochim Biophys Acta 1332, F25–48.
Smith, K.J., Johnson, K.A., Bryan, T.M., Hill, D.E., Markowitz, S., Willson, J.K., Paraskeva, C., Petersen, G.M., Hamilton, S.R., Vogelstein, B. & Kinzler, K.W. (1993). The APC gene product in normal and tumor cells. Proc Natl Acad Sci USA 90, 28462850.
Vico, P.G., Kyriacos, S., Heymans, O., Louryan, S. & Cartilier, L. (1998). Dynamic study of the extraembryonic vascular network of the chick embryo by fractal analysis. J Theor Biol 195, 525532.
Walter, R.J. Jr. & Berns, M.W. (1986). Digital image processing and analysis. In Video Microscopy, Inoue, S. (Ed.), pp. 327392. New York, London: Plenum Press.
Yambe, T., Nanka, S., Kobayashi, S., Tanaka, A., Owada, N., Yoshizawa, M., Abe, K., Tabayashi, K., Takeda, H., Nishihira, T. & Nitta, S. (1999). Detection of the cardiac function by fractal dimension analysis. Artif Organs 23, 751756.
Yekkala, K. & Baudino, T.A. (2007). Inhibition of intestinal polyposis with reduced angiogenesis in Apc Min/+ mice due to decreases in c-Myc expression. Mol Cancer Res 5, 12961303.
Zhang, L., Liu, J.Z., Dean, D., Sahgal, V. & Yue, G.H. (2005). A three dimensional fractal analysis method for quantifying white matter structure in human brain. J Neurosci Methods 150, 242253.

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed