Image Anal Stereol 2004;23:121-135 Original Research Paper A PRELIMARY APPROACH FOR THE AUTOMATED RECOGNITION OF MALIGNANT MELANOMA Ezzeddine Zagrouba1 and Walid Barhoumi2 1De´partement des sciences de l’informatique, Laboratory LIP2, Faculte´ des Sciences de Tunis (FST), Campus Universitaire, 1060 Tunis, Tunisia, 2Groupe du Recherche en Images et Formes de Tunisie (GRIFT), Laboratory CRISTAL, Ecole Nationale des Sciences de l’Informatique (ENSI), Campus Universitaire, 2080 La Manouba, Tunisia e-mail: ezzeddine.zagrouba@fsm.rnu.tn, walid.barhoumi@laposte.net (Accepted March 15, 2004) ABSTRACT In this work, we are motivated by the desire to classify skin lesions as malignants or benigns from color photographic slides of the lesions. Thus, we use color images of skin lesions, image processing techniques and artificial neural network classifier to distinguish melanoma from benign pigmented lesions. As the first step of the data set analysis, a preprocessing sequence is implemented to remove noise and undesired structures from the color image. Second, an automated segmentation approach localizes suspicious lesion regions by region growing after a preliminary step based on fuzzy sets. Then, we rely on quantitative image analysis to measure a series of candidate attributes hoped to contain enough information to differentiate melanomas from benign lesions. At last, the selected features are supplied to an artificial neural network for classification of tumor lesion as malignant or benign. For a preliminary balanced training/testing set, our approach is able to obtain 79.1% of correct classification of malignant and benign lesions on real skin lesion images. Keywords: fuzzy region growing, Karhunen-Loe`ve transform, melanoma recognition, neural networks. INTRODUCTION The malignant melanoma is the most dangerous human skin disease. It is the deadliest form of all skin cancers and arises from cancerous growth in pigmented skin lesion. The incidence has increased dramatically during the last years. In the US, the incidence of melanoma is rising more rapidely than any other cancer. Data base available on the internet (e.g. Nidus Information Services (2001): http://www.ucdmc.ucdavis.edu/) report that since the early seventies, the melanoma has increased 126% in USA. In Europe, the malignant melanoma incidence is increasing by 5% every year and it is responsible of 91% of deathly skin cancer (Sboner et al., 2001). If early recognized, the melanoma can be excised and the patient can recover completely. So one should intensify the awareness of all citizens. Indeed, the curability of skin melanoma is nearly 100% if recognized early enough, and treated surgically (Pehamberger et al., 1987). The early diagnosis of malignant melanoma is therefore a crucial issue for dermatologists. As a step towards improving early interpretation, a number of diagnostic checklists have been proposed, including UK “Seven Point checklist” (Healsmith et al., 1994), the American “ABCD” list (Stolz et al., 1994), and “ABCDE” list (Fitzpatrick et al., 1988). The lists specify visual features associated with malignant lesions symptoms. Unfortunately, it can be difficult to interpret visually these features and then to recognize malignant pigmented lesion. Even experienced dermatologists have difficulties for distinguishing melanoma from other pigmented lesions of the skin, such as typical and atypical lesions whose are benign. In fact, correct detection rates based on clinical visual investigation is commonly about 65% (Lee, 2001). This problem has stimulated interest in adjunctive diagnostic modalities that might facilitate clinical recognition of melanoma, including the automated interpretation of dermatoscopic color images with computerized image analysis. Thus, there has been increasing interest in computer-aided systems (CAD) for the clinical diagnosis of melanoma as a support for the dermatologists in different analysis steps, such as the lesion boundary detection, the quantification of diagnostic features, the classification in different types of lesions, the visualization, etc. Over the last few years, many works have developed allowing diagnostically useful systems based on image processing and recognition algorithms for atypical melanoma lesion. Readers interested in the current state of the art in computer aided image analysis in melanoma research, can refer to our precedent paper (Zagrouba and Barhoumi, 2003a). Typically, the whole process for color image processing for melanoma detection includes four 121 Zagrouba E et al: Automated melanoma recognition main steps: image formation and preprocessing, segmentation, features extraction and classification of the lesion. In fact, after the acquisition and preprocessing of color images of the skin, the next step of the whole image analysis process is the segmentation of the lesion from the surrounding skin. The lesion areas and boundaries being clearly identified, various attributes of the lesion characteristic of the malignity symptoms must be measured. Such characteristic features will then be the raw input to a recognition algorithm classifying the lesion as melanoma or not. For a classification system to be successful, all four sub-tasks must be performed with care. The four steps are addressed in the next sections. IMAGE FORMATION AND PREPROCESSING DATA DESCRIPTION Dermatologists commonly use slides for lesion image storage and visual comparison. In this work, these slides were digitalized with a 35mm film scanner Nikon LS-1000. The resulting images that we used are BMP-format and are coded on 24 bits storing the three color components r (red), g (green) and b (blue). These rgb images are 150 x 150 x 3 pixels in size, stored in 67 KBytes, with a spatial resolution of 0.0264 cm x 0.0264 cm per pixel. Each image has one or more lesions located near the center and the lesions are surrounded by normal skin of variable hue. Lesions can vary in size, shape, color and saturation. Fig. (1) shows the images of 4 different lesions. Lesions a and b are benign nevus, however, lesions c and d are malignant melanomas (Fig. 1). Other features, such as hairs and pigments, can be observed in the images which can confuse the further analysis of the images. Thus, a preprocessing step is needed in order to ameliorate the image quality. It consists in reducing noise, strongly present in dermatoscopic images, and to enhance edges in order to eventually facilitate the separation between the lesion and the surrounding skin. In our system, we applied a median filtering for minimizing the influence of small structures (like thin hairs) and isolated islands of pixels (like small air bubbles) in the segmentation result. For images including thick hairs with a color hue similar to the one of the lesion and thus irremovable by the median filter (e.g. Fig. 1d), a specific hair removal technique (called DullRazor (Lee et al, 1997)) is applied. The last preprocessing step in our system is the application of the Karhunen-Loe`ve transform that enhances the edges towards making easier the extraction of the lesion from the surrounding skin. (a) (b) (c) (d) Fig. 1. Color images of lesions. (a-b): benign nevus, (c-d): melanomas. MEDIAN FILTERING Small structures and artifacts should be removed from skin images towards reducing the over-segmentation while at the same time preserving edges. These artifacts can be considered as impulsive noise and can be reduced using a median filter (Hintz-Madsen et al, 1996) (e.g. Fig. 2). (a) (b) Fig. 2. Median filtering. (a) original image. (b) result after median filtering: inner structures and thin hairs have been smoothed out. 122 Image Anal Stereol 2004;23:121-135 THICK HAIRS REMOVAL This process is necessary only for images covered by thick hairs where the median filtering is insufficient for hair suppression (e.g. Fig. 3). For these images, more than 50% of the pixels in the current 5x5 pixel neighborhood scanned by the median filter could be hair pixels. The median value would be then representative of the hairs. Thus, the median filtering can intensify the undesired pixels which may degrade the segmentation process. global binary hair mask (H) is the union © of all three hair masks H = Hr®Hg®Hb (e.g. Fig. 4a). \/k G r,g,b, \/p, Gk{p) =| bk(p)-max(cp) \, cp = {[bk»e0](p),[bk»e45](p), [bk»e90](p),[b»e135](p)} , (1) •e135](p) where • denotes the grayscale closing operation. Fig. 3. Insufficiency of median filtering with a fixed 5x5 neighborhood for thick hair removal. (a) original image. (b) result after median filtering: some hair structures are intensified. Of course, shaving the hairs before imaging sessions may be a solution. However, this solution not only adds extra costs and time to the image session, but also is uncomfortable and impractical especially for multiple lesions or total-body nevus imaging (Voight and ClaBen, 1995). Hence, in spite of its algorithmic complexity, the preprocessing technique called DullRazor (Lee et al, 1997) appeared to us as the best solution, from a practical point of view, for thick hair removal. It consists in identifying hair areas and replacing hair pixels with nearby non-hair pixels. In fact, for every pixel p a generalized grayscale morphological closing operation is applied on the three color bands separately in order to localize the dark hairs. In practice, for every color band bk (k G {r, g, b}), this operation approximates thick hairs shapes by smoothing out low intensity values along fixed-size structure elements in horizontal, diagonals and vertical directions (e0, e45, e135 and e90) representing classical hair forms. The generalized grayscale closing image Gk is obtained by taking the maximum response from the individual closing operations for each color band (Eq. 1). Then, a binary hair mask Hk image is created by thresholding Gk. This hair mask divides the hair and non-hair regions into disjoined areas. Finally, the Fig. 4. Tick hairs removal. (a) hair mask H of Fig. 3a. (b) the cleaned mask H' relatively to H. (c) cleaned image of Fig. 3a. Before the replacement is performed, each pixel in the hair mask is checked to ensure that it is located within a thick and long structure (i.e hair structure); otherwise, the pixel is rejected as noise. In fact, for each pixel inside the hair region H, line segments are drawn in 8 directions, up, down, left, right and the four diagonals, radiating from the concerned pixel until the line segment reaches the non-hair region. These 8 line segments form 4 straight lines centred at the pixel. The length of each line is calculated and the longest one is noted. In our experiments, the longest line must be longer than 75 pixels and other lines must be shorter than 35 pixels (e.g. Fig. 4b). Then, a cleaned mask H' is obtained. In the last step, every pixel Im(i, j) verified to be inside a hair structure is replaced by the bilinear (c) 123 Zagrouba E et al: Automated melanoma recognition interpolation In(i, j) of the two nearby non-hair pixels Im(i1, j1) and Im(i2, j2) along the shortest line (Eq. 2). In(i,j)=Im(h,j1)* d2((i,j),(i2,j2)) d2((i,j),(i,ji)) + + Im(i2,j2)* d2((i,j),(i,ji)) d2((i, j), (i2, j2)) with d2 is the euclidean distance defined by (Eq. 3): (2) d2((hji),(i2,j2)) = \h-h\2 + \j2-ji\2- (3) KARHUNEN-LOE`VE TRANSFORM The next preprocessing step consists in applying the Karhunen-Loe`ve transform aiming to facilitate the segmentation process by enhancing the edges in the image. The Karhunen-Loe`ve transform, also called principal components analysis (Loe`ve, 1998), is the projection of the three color components on the eignvectors of their covariance matrix. The covaraince matrix Cov of the three channels (RGB) is computed as expressed by Eq. (4): Cov V-V'-mv-m'y BAB' x-y (4) where (x,y) is the size of each color channel, V is a 3 x xy matrix of pixel-realizations of the 3 color channels (Eq. 5), mv is the vector mean of the color channels (Eq. 6), B = [b1 b2 b3] is a matrix whose columns are the eigenvectors of the covariance matrix and A a diagonal matrix containing the eigenvalues of Cov in decreasing order: Ai > A2 > A3. V r(1,1) g(1,1) b(1,1) mV r(1,y) g(1,y) b(1,y) 1 x y -¦it xy i'=i./=i r(2,1) g(2,1) b(2,1) r(i, j) g(i, j) b(i, j) r(x,y) g(x,y) b(x,y) (5) (6) The Karhunen-Loe`ve transformation is given by (Eq. 7): Vke{1,2,-",xy}, zk = Bf (vk-mv) and T = (zi z2 • • • zxy) t2 t3 (7) where vk is the kth column vector in V and T contains what is known as the principal components. The kth (k = 1,3) row of T, noted tk, is referred to as the kth principal component. Due to the decreasing ordering of the eigenvalues and corresponding eignvectors, the first principal component h will contain the maximum variance. Since most variation occurs at edges between lesion and surrounding skin, the first principal component is a natural choice for segmentation. In fact, most of the texture and structure information will be mapped onto the first principal component (e.g. Fig. 5). However, although others principal components contain a small portion of the total variation, they may express features hidden in the original images. Fig. 5. Results of the Karhunen-Loe`ve transform: (a) the original median filtered color image, (b) the first principal component accounting for 92.29% of the total variance, (c) the second principal component – 7.63%, (d) the third principal lesion – 0.08%. SEGMENTATION PROCESS Several studies in the literature address the segmentation of dermatoscopic images, with most of them relying on color and grayscale thresholding (Khanfir et al., 2002). However, the majority of these techniques are unable to define a criterion to separate with precision the pigmented lesion from the background healthy skin. It is due to the low contrast and the fuzzy nature of the boundaries of malignant melanomas. We propose an automated segmentation (a) b) (c) (d) _ _ t1 _ 124 Image Anal Stereol 2004;23:121-135 approach to localize suspicious lesion region in dermatoscopic images. It consists in determining the boundary of the lesion by region growing after an initial step based on fuzzy sets to enhance the lesion region of interest (ROI). PREPROCESSING BASED ON FUZZY SETS A typical first principal component of a median filtered dermatoscopic image consists of a very light background and a dark skin lesion with even darker areas inside. Herein, and as done elsewhere (Zagrouba and Barhoumi, 2002; Rangayyan et al, 1997), we have decided to characterize the lesion ROI working directly and only on the gray level intensities rather than using other measurements (e.g. local gradients). Then, a representative gray level gl of the lesion must be chosen. In agreement with the intuitive idea that the relevant classes may correspond to the dominant peaks in the gray level histogram, our objective is to obtain a non ambiguous bimodal histogram expressing the two following classes: lesion (class 1) and surrounding skin (class 2). Along that line, starting from the noisy bimodal histogram h of the h image (Fig. 6a), we applied a succession of local smoothings of type Eq. (8), yielding to the smoothed bimodal curve (Fig. 6b). This curve is characterized by two significant peaks hi and h2 and their corresponding gray levels gh and gl 2 assumed to be representative of the gray levels of the two classes. Since the lesion is always darker than the surrounding skin, its gray level gl shall be the lower, i.e. the minimum of gh and gh. h(i) 1 [h(i-1)+h(i)+h(i+1)]. (8) (b) Fig. 6. histogram smoothing. (a) histogram of the first principal component image, (b) the smoothed bimodal The enhancement of the ROI may be achieved by defining an appropriate membership function that evaluates the similarity between the properties of any current pixel and those of the ROI itself (gl). Thus, the original image t1 will be mapped to a fuzzy set according to a symmetric membership function, decreasing monotonically from 1 to 0, and assigning a membership of 1 to pixels of gray level gl. The selected function has been defined after a study of many classical membership functions (Zagrouba and Barhoumi, 2003b) and is expressed by Eq. (9) where ß defines the opening of the membership function. The contrast of the ROI in the resulting image depends strongly upon the ß value. The larger ß, the more the function is strict; the smaller ß, the more the function is permissive. Fig. (7) expresses the resulting fuzzy set obtained with a small value for ß (ß = 0.007). The obtained fuzzy set represents pixels whose properties are close to the lesion with a high membership degree. mS(p) 2-ß2\gl(p)-gl\2 1 + ß\gl(p)-gl\ (9) curve. Fig. 7. Enhancement of the ROI: white pixels are close to 1. Note that the fuzzy image has been rescaled to enhance the visual quality. LESION DETECTION BY REGION GROWING We propose to obtain the lesion ROI and its associated boundary by performing region growing upon the obtained fuzzy set image. Region growing is a segmentation technique that gathers pixels into an homogeneous region according to a similarity criterion. This algorithm needs a seed pixel that lies inside the ROI and a threshold ? as a stopping condition. It starts with the seed pixel which represents the first approximation of the ROI. Four-connected neighboring pixels that are above the threshold are labeled as one, the neighbors of these pixels _ 3 (a) 125 Zagrouba E et al: Automated melanoma recognition are inspected and the procedure continues. If the connected pixel is less than the threshold, it is labeled as zero, indicating a boundary pixel, and its neighborhood are not processed. The recursive process continues until all connected pixels fail the test of inclusion in the region. In order to optimize the region growing results, we wish to select the center of a homogeneous area as the seed pixel. For this, given the set L of pixels having gl as gray level, the seed pixel S is selected according to the criterion defined by Eq. (10) (Fig. 8). \gl-m(S)\=mm\gl-m(p)\. (10) pein Where m(p) is the mean gray level of a 5 x 5 pixel neighborhood V (p) centered at pixel p. (a) (b) Fig. 8. Seed pixel determination. (a) the set Ç of lesion pixels having gh as gray level, (b) the seed pixel location. After the region growing process, a postprocessing step of Dilatation-Erosion is done in order to remove isolated pixels inside the lesion’s region (e.g. Fig. 9). At the end, the out-put of the lesion extraction procedure is the so-called binary plane (Fig. 9c) that separates lesion from the healthy surrounding skin. The resulting binary image (lesion vs. healthy surrounding skin) will be then treated by an algorithm of follow-up (Barhoumi and Zagrouba, 2002) applied to the border pixels of the lesion characterized by a local maximum of gradient. It allows the definition of a polygon representing an approximation of the lesion contour C. (a) (b) (c) Fig. 9. Region growing process. (a) original image, (b) detection of the ROI lesion by region growing, (c) ROI after postprocessing of Dilatation-Erosion. The parameters used in our segmentation algorithm, ß and 0, must be adequately chosen in order to stop region growing at the boundaries of well-circumscribed lesions, where the membership values are expected to drop sharply across the lesion boundary (e.g. Figs. 10-11). In our study, optimal results are obtained with the values ß = 0.007 and 0 = 0.75. In conclusion, our algorithm of segmentation is simple and easy to implement and will always produce connected region and closed boundary. The binary object and its closed boundary are the basis to compute the vector of numerical features, which is the purpose of the feature extraction module. (a) (b) (c) Fig. 10. Original rgb image superimposed with the boundary for various ß values (? = 0.75). (a) ß = 0.007, (b) ß = 0.012, (c) ß = 0.016. 126 Image Anal Stereol 2004;23:121-135 (a) (b) (c) Fig. 11. Original rgb image superimposed with the boundary for various ? values (ß = 0.007). (a) ? = 0.5, (b) ?= 0.7, (c) ?= 0.95. DERMATOSCOPIC FEATURE DESCRIPTION The essential difficulty in melanoma recognition systems is to design robust and relevant parameters describing the lesions in order to ensure the separation between melanoma and benign lesions, in particular atypical benign ones which may be clinically mistaken for melanoma. We used the mnemonic device, ABCD, to describe several features that help to distinguish melanomas from noncancerous growths. The choice for the ABCD rule is based primarily on the fact that the dermatologists we are working with use such rule. It shall be noticed that some studies report that the ABCD rule may not yield the highest performance in melanoma diagnostic compared to alternative strategies such as stratification methods (Lorentzen et al., 2000). Yet, the diagnostic performance depends more on the selected attributes to represents the rule criteria, charaterizing the malignity symptoms, than on the used rule itself (Ganster et al., 2001) so that identifying the relevant ABCD features is definitely worth the effort. The different letters stand for the following criteria: – Asymmetry (A): about half the time, a melanoma develops in an existing mole; in other cases, it arises as a new lesion that can resemble an ordinary mole. A noncancerous mole, however, is generally symmetric and circular in shape, while melanoma usually grows in an irregular, asymmetric manner. – Border Irregularity (B): benign lesions generally have clearly defined borders. A melanoma, in contrast, often shows notched or indistinct borders that may signal ongoing growth and spreading of the cancer. – Color Variation (C): one of the earliest signs of melanoma may be the appearanceof various colors within the lesion. Because melanomas arise within pigment-forming cells, they are often varicolored lesions of tan, dark brown, or black, reflecting the production of melanin pigment at different depths within the skin. – Diameter (D): early melanomas tend to grow larger than common moles and show typically at least a diameter of about 6mm. ABCD rules are commonly used by dermatologists. Yet a diagnosis made by a dermatologist based on the visual and qualitative evaluation of such criteria may be subjective (Schmid-Saugeon et al., 2003). Thus, our main purpose is to charaterize the ABCD criteria by quantitative attributes measured by image analysis and then used as input to an automate classifier. In the literature, many attributes have been used to describe these features. A previous study by the authors (Zagrouba and Barhoumi, 2003a) of various attributes revealed some correlation between every single attribute and the melanoma diagnosis. However, each attribute alone is not sufficient to diagnose a lesion precisely. In other words, a combination of a set of p (p > 1 in general) relevant attributes is necessary for the quantification of every feature and then for the diagnostic decision. In Zagrouba and Barhoumi (2003b), we used 14 parameters describing the ABCD rule and yielding 83% correct classification using a neural network classifier. This rate is related to a test subset of a series of images randomly selected from a database of 200 lesion images. However, this high number of attributes increases the classification complexity and the CPU time. We decided accordingly to define a reduced number of well-selected attributes permitting to obtain a higher correct classification rate while reducing the complexity and the CPU time by removing the redundant information. We will present, relatively to every feature, the adequate attributes that were chosen after many experiments and discussions with dermatologists. In fact, we realized a statistical study of 15 parameters (the 14 used in Zagrouba and Barhoumi (2003b) along with the diameter) representing the four criteria (Barhoumi et al., 2003). We classified a set of 100 lesion images by using a neural network classifier considering every attribute separately. For simplicity reasons, we chose a simple training set of images composed of 50 significant melanomas, 50 significant benign lesions and 0 atypical lesions images. Then, we measure for every attribute the correct classification rate (TCR) relatively just to the chosen training set (this could explain the realtively high recorded TCR values of 127 Zagrouba E et al: Automated melanoma recognition some attributes, e.g. Fig. 12). We kept only the attributes having a correct classification rate greater or equal to mTCR with mTCR is the mean value of the 15 TCR. In other words, we do not keep the attributes whose shall decrease the global diagnostic performance. Besides, we decided not to use the lesion diameter (attribute number 5) since it is indirectly integrated in the other attributes. Thus, the set of 9 attributes discussed below was selected. ni- :0.691 TCR Fig. 12. Statical study of the correct classification rates of 15 attributes using a NN classifier. ASYMMETRY QUANTIFICATION In order to measure asymmetry, we rely hereafter on geometrical properties called inertial moments (Sonka et al., 1993). Such inertial moments are used to calculate two features: the asymmetry index AI and the lengthening index A°. Asymmetry index As far as asymmetry quantification is concerned, the origin of the local Cartesian basis is the center of mass G of a current lesion L described by a binary function z(i, j) (z(i, j) = 1 if (i, j) ? L, 0 otherwise). The quadratic inertial centred moment I(?) of the lesion L with respect to an arbitrary axis through G showing an angle ? with the horizontal Cartesian axis ? is given by Eq. (11): I(