32nd Annual International Conference of the IEEE EMBS Buenos Aires, Argentina, August 31 - September 4, 2010

Application of Fractal Analysis to Mammography

Grazia Raguso1, Antonietta Ancona2, Loredana Chieppa1, Samuela L'Abbate1, Maria Luisa Pepe3, Fabio Mangieri4, Miriam De Palo1, and Rangaraj M. Rangayyan5
contours and ill-defined edges are more likely to be malignant tumors. A malignant tumor is often characterized by the presence of spicules (a stellate lesion typical of infiltrative ductal carcinoma, for example) and by a poorly defined irregular contour, one that could be considered to be a fractal pattern. The term carcinoma, from the Greek word (crab), was coined by Hippocrates, and indicates the infiltrative characteristics of a tumor as well as its ability to attack neighboring structures. Regardless, there are cases of malignant tumors with regular contours and benign masses with fractal-like contours; such cases are challenging for a physician to diagnose and make it difficult to build a classification model, leading to false negatives and false positives. These observations have led to the idea of applying the concept of fractal dimension (FD) to analyze the contours of breast lesions. As we demonstrate in this paper, fractal analysis can characterize the degree of complexity of a contour or shape, and can provide parameters to discriminate between benign masses and malignant tumors. On the basis of the differences in shape between benign masses and malignant tumors, shape factors such as compactness (cf), fractional concavity (fcc), spiculation index (SI), and a Fourier-descriptor-based factor (ff) have been proposed for their classification [1, 2]. Subtle textural differences have also been observed between benign masses and malignant tumors, with the former being mostly homogeneous and the latter showing heterogeneous texture. Several studies have proposed measures of texture and edge sharpness to discriminate between benign masses and malignant tumors [1, 3-6]. Sahiner et al. [4] and Alto et al. [6] explored several combinations of morphological and texture measures to classify breast masses. The notion of fractal analysis [7-13] is useful in studying the complexity of 1-dimensional (1D) functions, 2-dimensional (2D) contours, as well as gray-scale images. A few studies have examined the application of fractals to classify breast masses based on the irregularity exhibited in their contours. Matsubara et al. [14] reported 100% accuracy in the classification of 13 benign masses and malignant tumors using FD. The method of Matsubara et al. involved the computation of a series of FD values for several contours of a given mass obtained by thresholding the mass at many levels; the change in FD of the given mass was used to categorize it as benign or malignant. A study by Pohlman et al. [15] obtained greater than 80% classification accuracy with fractal analysis of signatures of

Abstract We report on a morphological study of 192 breast masses as seen in mammograms, with the aim of discrimination between benign masses and malignant tumors. From the contour of each mass, we computed the fractal dimension (FD) and a few shape factors, including compactness, fractional concavity, and spiculation index. We calculated FD using four different methods: the ruler and box-counting methods applied to each 2-dimensional (2D) contour and its 1-dimensional signature. The ANOVA test indicated statistically significant differences in the values of the various shape features between benign masses and malignant tumors. Analysis using receiver operating characteristics indicated the area under the curve, Az, of up to 0.92 with the individual shape features. The combination of compactness, FD with the 2D ruler method, and the spiculation index resulted in the highest Az value of 0.93.

I. INTRODUCTION The practical utility of computational biology is far reaching and involves various aspects concerned with the understanding of biological phenomena in general, and with gaining insights in the areas of health, biotechnology, and the environment, among others. In recent years, several international research projects have been directed toward the health sector, with many of them having the aim of studying mathematical and computational methods for computeraided detection or diagnosis (CAD) of various diseases. At present, the most effective screening technique for breast cancer is mammography, which helps to identify significant variations in breast tissue and symptoms of tumoral lesions. Several CAD systems have been developed to support radiologists in the area of mammography; such systems can identify anomalous regions and masses with unusual morphological structure. When assessing a breast mass or lesion, the following parameters are taken into consideration: shape, definition or sharpness of the edges, roughness of the contour, density, and size. The regularity of the contour of a mass is the first parameter to be assessed: benign masses are often smooth, rounded, well-circumscribed, and surrounded by a halo of fairly low-density fat, whereas lesions with irregular
This work was supported by Fondazione Cassa di Risparmio di Puglia, Italy. We thank Thanh M. Nguyen and Naga R. Mudigonda for their contributions to this work. Department of Mathematics, University of Bari, Bari, Italy. Head of Radiology Unit, San Paolo Hospital of Bari, Bari, Italy. Department of Radiology, University Hospital - Policlinico of Bari, Bari, Italy. 4 Radiology Unit, San Paolo Hospital of Bari, Bari, Italy. 5 Department of Electrical and Computer Engineering, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
2 3 1

978-1-4244-4124-2/10/$25.00 2010 IEEE

3182

contours of breast masses. However, the signature of a contour was derived as a function of the radial distance from the centroid to the contour versus the angle of the radial line over the range [0, 360], which could lead to a multivalued function in the case of an irregular or spiculated contour; the signature computed in this manner would also have ranges of undefined values in the case of a contour for which the centroid falls outside the region enclosed by the contour. Dey and Mohanty [16] used fractal geometry to study breast lesions on cytology smears and found that FD may be useful in discriminating between benign and malignant cells. Fractal analysis can also be used to characterize the complexity of gray-scale variations associated with texture. Zheng and Chan [17] used fractals in a preprocessing step to select abnormal regions in mammograms. Guo et al. [18] computed FD to characterize the complexity of regions of interest in mammograms, and used a support vector machine for the detection of abnormal regions related to breast masses. Caldwell et al. [19] and Byng et al. [20] computed FD of breast tumors by applying a modified box-counting method that represents gray-scale values of the surfaces of the tumors as boxes of variable height. Such a fractal measure can be used to represent the complexity of density variations and texture in breast tissue. Byng et al. [20] showed that a gray-scale-based fractal measure may be used to complement histogram skewness to relate breast density to the risk of development of breast cancer. Other works have reported on the use of FD as a feature for the classification of tumors in magnetic resonance images of the brain [21], ultrasonic images of the liver [22], and images related to colonic cancer [23]. Lee et al. [24] compared several shape factors, including FD, in a study on the irregularity of the borders of melanocytic lesions. Kikuchi et al. [25] investigated the change in FD at different stages of ovarian tumor growth. Nam and Choi [26] computed the FD of regions in mammograms by using the box counting method, and found that regions with higher FD indicated the presence of calcification. Rangayyan and Nguyen [27] presented a study of four methods to compute the FD of the contours of breast masses, including the ruler method and the box counting method applied to 1D and 2D representations of the contours. The methods were applied to a dataset comprising 111 contours of breast masses in mammograms, including 65 of benign masses and 46 of malignant tumors. FD was observed to complement other shape factors, in particular fcc, in the representation of the complexity of the contours. The combination of FD with fcc yielded the highest area (Az) under the receiver operating characteristic (ROC) curve of 0.93; the two measures, on their own, resulted in Az values of 0.89 and 0.88, respectively. The aim of the present study is to employ fractal analysis for the classification of breast masses by using only their contours [27]. Even though fractal analysis has been widely used in the analysis of biomedical images, only a few studies

have specifically applied the method to study and classify mammographic masses (as reviewed above). FD may be used as a quantitative measure of the complexity of the contour or boundary of an object. Benign masses and malignant tumors differ significantly in shape complexity, and therefore, it should be possible to differentiate between them by using FD. II. FRACTAL GEOMETRY In his pioneering work on The Fractal Geometry of Nature [7], the mathematician Benot Mandelbrot states that The world around us is full of fractals. Fractals are capable of representing a wide variety of objects and phenomena in nature: not just a stretch of coastline, the branches or roots of a tree, and clouds, but also the ramifications of a lightning bolt, the bronchial and vascular systems, and, we believe, the contour of a tumor. Fractal geometry is, as Mandelbrot says, the geometry of nature, because it is more suitable for describing the complexity and variety of shapes in the world around us. Fractal geometry investigates the morphology of the amorphous. The correspondence between fractals and chaos is by no means accidental; rather, it is the sign of a profound relationship: fractal geometry is the geometry of chaos. The most important fractals include the Cantor set, the Von Koch curve, the Sierpinski triangle, the Mandelbrot set, and the Lorenz attractor. Fractals are irregular figures, and can be generated by the iteration of linear or nonlinear functions (Julia and Mandelbrot sets). Sometimes they are self-similar, and have a fine structure which reveals new details at every level of magnification [28]. III. FRACTAL ANALYSIS In order to measure the degree of complexity or irregularity of a fractal, the concept of FD was introduced. This concept is derived from the more general notion of the Hausdorff dimension [29]. For a subset F of the plane, the sdimensional Hausdorff measure is defined as follows:
s H s ( F ) = lim H 0

(1)

with
s (2) j j =1 where s , and are positive real numbers and j are j H s (F)= inf

the diameters of a family of circles which makes up a cover (countable) of F. The Hausdorff dimension of F is the number D such that if s<D (3) H s (F ) = { . 0 if s>D The measure of F depends on the dimension of the space in which we imagine F to be immersed, whereas its dimension

3183

is a number, even a fraction, intrinsic to F. Such a definition can be applied to a fractal figure, and hence the Hausdorff dimension is also called the fractal dimension. Now we consider the self-similarity dimension and its relationship with the Hausdorff dimension. Without entering into the mathematical complexities, it is common intuition that the (topological) dimension of a point is 0, that of a line is 1, that of a rectangle is 2, and that of a parallelepiped is 3. If we consider, therefore, a rectangle made up of m copies of itself, reduced by a scale factor of 1/s, the power law which links the dimension, D (=2), of the figure with the number of its parts, m (=9), and the scale factor, 1/s (=3) is m=(1/s)D. So, in agreement with the above, it is reasonable to define the self-similarity dimension [8] of a self-similar figure made up of m copies of itself reduced by a scale factor 1/s as log m (4) D sim = . log 1 s When s varies, and therefore, so does m, the set of points on the plane(log 1/s, log m) on a log-log scale, is approximated by the regression straight line whose slope provides an estimate of D sim via (4). For self-similar figures, the self-similarity dimension coincides with the Hausdorff dimension. The Hausdorff dimension generalizes the concept of self-similarity dimension in the sense that it is applicable to any set of the plane, and therefore, to a fractal set that is not strictly selfsimilar. The difficulties involved in defining the Hausdorff dimension have led many authors to find alternative methods for estimating FD. The commonest alternatives are the boxcounting method and the ruler method which have been extensively described in the literature [8, 27]. IV. SIGNATURES OF CONTOURS AND SHAPE Each point P of a contour or curve C can be represented, in the plane, either with its Cartesian coordinate pair (x, y), or by indexing the points as pairs (x, f(x)) in which f is a function defined on the indices of the contour point x. An example of f is the Euclidean distance between the point under consideration and a reference, such as the centroid of the object enclosed by the contour. The first representation of C mentioned above is in 2D, whereas the second representation is in 1D and is known as the signature of C. Various measures can be associated with a contour or curve: these are the so-called shape factors, which have proven to be effective in describing shapes in many research fields, in particular in the medical field [30]. The shape factors used in the present paper are cf, fcc, SI, and FD; these measures have been proven to be effective in the classification of breast masses [1, 2, 27, 30]. See Rangayyan and Nguyen [27] and Rangayyan [30] for details on the shape factors.

V. MAMMOGRAPHIC DATA ACQUISITION A total of 192 mammograms were obtained from 192 patients at the Senology Unit, San Paolo Hospital, Bari, Italy, ASL Ba/4 (medical group). The patients were diagnosed to have breast disease via mammography and confirmed histologically; 163 of the cases were malignant and 29 benign. The most useful mammographic projections were selected to analyze the contours of lesions. During an initial phase, contours of the mammary lesions present on the film images were traced by a team of radiologists specializing in mammography, using a colored grease pencil. The contoured image was then placed on a Wacom Intuos3 A4 graphic tablet, and using an optical pen, the part of interest was retraced so as to obtain a digital representation of the contour. Each contour was saved in a text file as a list of points, corresponding to the x and y coordinates of the contour. The contour was then resampled so as to achieve a uniform distribution of points. In the second phase, a custom CAD environment was implemented in MATLAB, with a graphical user interface made up of a full-screen window and a drop-down menu for the draw and save commands. The commands available in the menu were also activated by the optical pen to make the process of contour data acquisition simpler and quicker. Figure 1 shows the contours of a benign mass and a malignant tumor: the former has a smooth shape whereas the latter has microlobulations and spicules.

(a)

(b)

Figure 1: (a) Contour of a benign mass; FD =1.0195 by the 2D ruler method. (b) Contour of a malignant tumor; FD =1.2412 .

VI. EXPERIMENTS AND RESULTS ROC analysis was performed with each shape feature to determine the diagnostic accuracy achievable in the task of discriminating between benign masses and malignant tumors. ROC curves were obtained by plotting the fraction of true positives (sensitivity) along the y axis and the fraction of false positives (1 specificity) along the x axis. The area Az under the ROC curve was obtained to serve as a measure of the diagnostic accuracy of the feature. Table 1 lists the Az values obtained for the various shape factors studied. High levels of performance in diagnostic classification can be observed with cf (Az = 0.923), FD calculated using the 2D ruler method (Az = 0.919), and SI (Az = 0.912). The combined use of the shape parameters led to slight improvements in terms of accuracy: the combination of FD calculated using the 2D ruler method with cf and SI gave the highest Az of 0.927. However, the combinations do not have significant differences between one another.

3184

[6]

The important contribution of the shape parameters of contours in the classification of breast masses was also confirmed by the results obtained from the ANOVA test, which showed statistically significant differences in the values of the various shape parameters between benign masses and malignant tumors. Of particular note are the extremely low p-values obtained with cf (2.2e-16), FD using the 2D ruler method (5.819e-14), and SI (6.815e-16). VII. CONCLUSION From an analysis of the experimental results, it is reasonable to conclude that using various shape parameters derived from the contours of breast masses is a valid method to assist in the process of diagnosis of breast cancer. The results obtained in the present study confirm the validity of similar studies conducted by Rangayyan and Nguyen [27], but with a larger dataset of different composition. Further tests will be conducted in the future on the selection of optimal feature sets and with advanced pattern classification methods. Work is also in progress on the application of the shape factors studied in the present paper to automatically extracted contours of breast masses in digital mammograms. The methods should make important contributions to CAD of breast cancer.
TABLE 1 AREAS UNDER THE ROC CURVE FOR THE VARIOUS SHAPE FACTORS SINGLE SHAPE
FACTOR

[7] [8] [9] [10] [11] [12] [13] [14]

[15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26]

AREA AZ 0.891 0.919 0.889 0.865 0.923 0.691

COMBINATIONS OF SHAPE FACTORS FD-ruler 2D, SI FD-ruler 2D, fcc FD-ruler 2D, cf cf, fcc fcc , SI cf , SI FD-ruler 2D, SI, fcc FD-ruler 2D, SI, cf FD-ruler 2D, SI, fcc cf

AREA AZ 0.924 0.919 0.925 0.925 0.919 0.926 0.924 0.927 0.926

FD-ruler 1D FD-ruler 2D FD-box-c.1D FD-box-c. 2D cf fcc

SI

0.912

REFERENCES
[1] [2] [3] [4] Rangayyan RM, El-Faramawy NM, Desautels JEL, Alim OA: Measures of acutance and shape for classification of breast tumors. IEEE Trans Med Imag 16(6):799-810, 1997 Rangayyan RM, Mudigonda NR, Desautels JEL: Boundary modelling and shape analysis methods for classification of mammographic masses. Med Biol Eng Comput 38:487-496, 2000 Mudigonda NR, Rangayyan RM, Desautels JEL: Gradient and texture analysis for the classification of mammographic masses. IEEE Trans Med Imag 19(10):1032-1043, 2000 Sahiner BS, Chan HP, Petrick N, Helvie MA, Hadjiiski LM: Improvement of mammographic mass characterization using spiculation measures and morphological features. Med Phys 28(7): 1455-1465, 2001 Mudigonda NR, Rangayyan RM, Desautels JEL: Detection of breast masses in mammograms by density slicing and texture flow-field analysis. IEEE Trans Med Imag 20(12):1215-1227, 2001 [27] [28] [29] [30]

Alto H, Rangayyan RM, Desautels JEL: Content-based retrieval and analysis of mammographic masses. J Electron Imaging 14(2):1-17, 2005 Mandelbrot BB: The Fractal Geometry of Nature. San Francisco, CA: WH Freeman, 1983 Peitgen HO, Jurgens H, Saupe D: Chaos and Fractals: New Frontiers of Science. New York, NY: Springer, 2004 Liu SH: Formation and anomalous properties of fractals. IEEE Eng Med Biol Mag 11(2):28-39, 1992 Deering W, West BJ: Fractal physiology. IEEE Eng Med Biol Mag 11(2):40-46, 1992 Schepers HE, van Beek JHGM, Bassingthwaighte JB: Four methods to estimate the fractal dimension from self-affine signals. IEEE Eng Med Biol Mag 11(2):57-64, 1992 Fortin C, Kumaresan R, Ohley W, Hoefer S: Fractal dimension in the analysis of medical images. IEEE Eng Med Biol Mag 11(2):65-71, 1992 Goldberger AL, Rigney DR, West BJ: Chaos and fractals in human physiology. Sci Am 262:42-49, 1990 Matsubara T, Fujita H, Kasai S, Goto M, Tani Y, Hara T, and Endo T. Development of new schemes for detection and analysis of mammographic masses. Proc. IASTED Intl Conf Intelligent Information Systems, pp 63-66, Bahamas, December 1997 Pohlman S, Powell KA, Obuchowski NA, Chilcote WA, GrundfestBroniatowski S: Quantitative classification of breast tumors in digitized mammograms. Med Phys 3(8):1337-1345,1996 Dey P, Mohanty SK: Fractal dimensions of breast lesions on cytology smears. Diagn Cytopathol 29(2):85-86, 2003 Zheng L, Chan AK: An artificial intelligent algorithm for tumor detection in screening mammogram. IEEE Trans Med Imag 20(7): 559-567, 2001 Guo Q, Ruiz V, Shao J, Guo F: A novel approach to mass abnormality detection in mammographic images. Proc. IASTED Intl Conf Biomed Eng, pp 180-185, Innsbruck, Austria, February 2005 Caldwell CB, Stapleton SJ, Holdsworth DW, Jong RA, Weiser WJ, Cooke G, Yaffe MJ: Characterization of mammographic parenchymal pattern by fractal dimension. Phys Med Biol 35(2):235-247, 1990 Byng JW, Boyd NF, Fishell E, Jong RA, Yaffe MJ: Automated analysis of mammographic densities. Phys Med Biol 41: 909-923, 1996 Iftekharuddin KM, Jia W, Marsh R: Fractal analysis of tumor in brain MR images. Mach Vis Appl 13:352-362, 2003 Wu CM, Chen YC, Hsieh KS: Texture features for classification of ultrasonic liver images. IEEE Trans Med Imag 11(2):141-152, 1992 Esgiar AN, Naguib RNG, Sharif BS, Bennett MK, Murray A: Fractal analysis in the detection of colonic cancer images. IEEE Trans Inf Technol Biomed 6(1):54-58, 2002 Lee TK, McLean DI, Atkins MS: Irregularity index: a new border irregularity measure for cutaneous melanocytic lesions. Med Image Anal 7:47-64, 2003 Kikuchi K, Kozuma S, Sakamaki K, Saito M, Marumo G, Yasugi T, Taketani Y: Fractal tumor growth of ovarian cancer: sonographic evaluation. Gynecol Oncol 87:295-302, 2002 Nam SH, Choi JY: A method of image enhancement and fractal dimension for detection of microcalcifications in mammogram. Proc 20th Ann Intl Conf IEEE Eng Med Biol Soc, pp 1009-1011, Hong Kong, 1998 Rangayyan RM, Nguyen TM, Fractal analysis of contours of breast masses in mammograms, J Digital Imaging, 20(3): 223-237, 2007 Peitgen H-O, Richter PH, The Beauty of Fractals- Images of Complex Dynamical Systems, Springer, Berlin, Germany, 1986 Falconer KJ, The Geometry of Fractal Sets, Cambridge University Press, Cambridge, UK, 1985 Rangayyan RM, Biomedical Image Analysis, CRC Press, Boca Raton, FL, 2005

[5]

3185