Whole Breast Lesion Detection Using Naive Bayes Classifier for Portable Ultrasound Min-Chun Yang1, Chiun-Sheng Huang2, Jeon-Hor Chen3,4,5, Ruey-Feng Chang1,6* 1 Department of Computer Science and Information Engineering National Taiwan University, Taipei, Taiwan 2 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan 3 Center for Functional Onco-Imaging of Department of Radiological Science, University of California Irvine, California, USA Department of Radiology, China Medical University Hospital, Taichung, Taiwan 5 Department of Medicine, School of Medicine, China Medical University, Taichung, 4 Taiwan 6 Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University, Taipei, Taiwan * Corresponding Author: Ruey-Feng Chang, PhD Professor, Department of Computer Science and Information Engineering National Taiwan University Taipei 10617, Taiwan Telephone: 886-2-33661503 Fax: 886-2-33661504 E-mail: rfchang@csie.ntu.edu.tw Abstract In recent years, the portable PC-based ultrasound (US) imaging systems developed by some companies can provide an integrated computer environment for the computer-aided diagnosis and detection applications. In this paper, an automatic whole breast lesion detection system based on the naive Bayes classifier using the PC-based US system Terason t3000 (Terason Ultrasound, Burlington, MA, USA) with hand-held probe is proposed. In order to easily retrieve the US images for any regions of the breast, a clock-based storing system is proposed to record the scanned US images. A computer-aided detection (CAD) system is also developed to save the physicians’ time for a huge volume of scanned US images. The pixel classification of the US is based on the naive Bayes classifier for the proposed lesion detection system. The pixels of the US are classified into two types: lesions or normal tissues. Then, the connected component labeling is applied to find the suspected lesions in the image. Consequently, the labeled 2-D suspected regions are separated into two clusters and further checked by two-phase lesion selection criteria for the determination of the real lesion while reducing the false-positive rate. The free-response operative characteristics (FROC) curve is used to evaluate the detection performance of the proposed system. According to the experimental results of 31 cases with 33 lesions, the proposed system yields a 93.4% (31/33) sensitivity at 4.22 false positives (FPs) per hundred slices. Moreover, the speed for the proposed detection scheme achieves 12.3 frame per second (fps) with an Intel Dual-Core Quad 3 GHz processor and can be also effectively and efficiently used for other screening systems. Keywords: Portable ultrasound, naive Bayes classifier, lesion detection 1 Introduction 2 Ultrasound (US) is a good complementary imaging modality to the 3 mammography for diagnosing breast cancer. US could perform better than 4 mammography for a breast with dense fibroglandular tissue (Gordon and Goldenberg 5 1995; Buchberger et al. 2000; Kaplan 2001; Kolb et al. 2002; Crystal et al. 2003). 6 Supplemental screening US could depict small, node-negative breast cancers not seen 7 on mammography (Berg et al. 2008). Recently, the American College of Radiology 8 Imaging Network (ACRIN) has a large trial 9 In the trial report for 2809 women (Berg et al. 2008), adding screening US to for the screening US (Berg et al. 2008). 10 mammography will yield an additional 1.1 to 7.2 cancers per 1000 high-risk women 11 but it will also substantially increase the false positive number. The diagnostic 12 accuracy is increased from 78% to 91% for mammography plusUS. 13 In conventional hand-held US, the breast lesions require immediate 14 characterization during the examination. But the demerit of such US screening is the 15 lack of the standardization of sonographic documentation for instant evaluation and 16 the second evaluation on hard copies is needed (Kotsianos-Hermle et al. 2008). 17 Moreover, it also takes time for hand-held US to operate the whole breast examination. 18 In the study of Berg et al. (Berg et al. 2008), a breast screening US takes about 19 19 minutes of physicians’ time. Hence, some automated US breast imaging systems 20 (Shipley et al. 2005; Kotsianos-Hermle et al. 2008) have been proposed to scan the 21 whole breast. Some commercial automated US machines (Ikedo et al. 2007; Chang et 22 al. 2010) are also available. In this study, a freehand whole breast US screening 23 system is proposed without any extra mechanisms to obtain and store the US images 24 for the whole breast. 25 In this study, the portable personal computer (PC) based US imaging system 1 1 (Kim et al. 1997) is used to implement the proposed freehand US screening system. In 2 the system, a Terason t3000 (Terason Ultrasound, Burlington, MA, USA) probe is 3 connected to a PC via a standard FireWire cable to obtain the US images. A 4 clock-based storing method is also proposed to record all the scanning images for 5 later analysis. After the US screening, the physician could diagnose any regions of the 6 breast and retrieve the images easily. If a lesion is found, then its location could be 7 approximately identified by its o’clock direction and the distance from the nipple. 8 Nonetheless, there are several thousand of scanned US images for a patient and 9 the physician still needs a lot of time to diagnose. Hence, the computer-aid detection 10 system (Ikedo et al. 2007; Chang et al. 2010) would be needed for assisting the 11 physician to instantly locate the suspected lesions. Because the scanned US is based 12 on the PC-based imaging system, the computer-aid detection function could be easily 13 installed with the proposed system. This study aims to develop a PC-based 14 computer-aid detection system and offers real-time or off-line lesion detection for 15 physicians. Furthermore, the proposed system with clock-based scanning mechanism 16 might provide multiple observations of the target lesion in different clock regions, 17 thus the lesion can be detected more than one time and diagnosis accuracy can be 18 improved as well. 19 20 Materials and Methods 21 Patients and Lesion Characteristics 22 From January to April 2008, this study collected 33 biopsy-proven lesions (22 23 benign and 11 malignant lesions; size range, 0.52-3.8 cm; mean size 1.48±0.99 cm) 24 from 31 women (age range, 21-79 years; mean age 46.30±11.80 years). All the 31 25 patients are scanned for their whole breast area and the acquired images of each case 2 1 are a series of two-dimensional (2-D) US images with a size of 440×340 pixels. 2 Moreover, the cases have been diagnosed by an experienced radiologist and the 3 locations of possible lesions are identified. The benign lesions include 14 fibrocystic 4 changes, 4 papillomas, and 4 fibroadenomas. The malignant lesions include 8 invasive 5 ductal carcinomas, 1 lobular carcinoma-in-situ (LCIS), 1 mucinous carcinoma, 1 6 infiltrating ductal carcinoma (IDC). Institutional review board approval is obtained 7 for this study and informed consent is obtained from each patient prior to performing 8 a biopsy. 9 Image Data Acquisition 10 In this study, a Terason t3000 (Terason Ultrasound, Burlington, MA, USA) with 11 12L5 small part probe is used to obtain the US images. The frequency of the 12 transducer is between 5MHz and 12MHz and the maximum scanning width and 13 depth are 38mm and 80mm respectively. In the proposed PC-based US screening 14 system, 15 images as shown in Fig. 1. The storage system divides each breast into 12 clock 16 regions; furthermore, the operator selects a clock region to be scanned and then moves 17 the probe from the nipple to outside. In order to reduce the operator-dependent effect 18 of the hand-held probe, the operator is requested to start the scanning process when 19 the probe could move steadily on the skin surface. After the scanning process of the 20 clock region is finished, the operator would check the quality of the scanned image 21 video and decide whether the re-scan process is needed. Moreover, all the scanned 22 images for this region are saved into a file and the whole breast examination for a 23 patient is completed 24 Whole Breast Lesion Detection Based on Naive Bayes Classifier 25 a clock-based storing mechanism is adopted to organize all the scanned after both breasts are scanned. We proposed an automatic approach based on the naive Bayes Classifier 3 1 (Domingos and Pazzani 1997; Cevenini et al. 2011) for the whole breast lesion 2 detection. A novel pre-processing technique (i.e. spatio-temporal resolution 3 down-sampling) is proposed to decrease the processing data and improve the 4 detection robustness. After applying the pre-processing technique, each pixel of the 5 image diagnosed by the naive Bayes Classifier is classified into lesions or normal 6 tissues. Then, the connected component labeling (Rosenfeld and Pfaltz 1966) and 7 hole-filling (Mesev 2001) are applied to find the suspected lesions in the image. 8 Consequently, each labeled suspected region would be further separated into two 9 clusters and checked by two-phase lesion selection criteria to reduce the false positive 10 rate while improving the detection sensitivity. 11 Spatio-temporal Resolution Down-sampling 12 Due to the scanned US image slices for each patient are over three thousands and 13 it is hard to recognize the lesion objects in the US image with the noise effect (Giger 14 et al. 1999; Horsch et al. 2004), the spatio-temporal resolution down-sampling 15 (ST-ReD) is proposed to address these issues. The ST-ReD refers to firstly perform 16 the image spatial resolution reduction followed by synthesizing the compact image 17 from a series of degraded 2-D US images. Firstly, each high-resolution US image is 18 resized by the bicubic down-sampling (Keys 1981) to reduce the spatial resolution. 19 Second, the edge-preserved minimum intensity projection scheme is proposed to 20 preserve the edges of the suspected lesion objects when synthesizes the compact 21 images. The procedure of this step would be depicted as follows. For each spatial 22 resolution degraded 2-D image, the Sobel edge detector (Cherri and Karim 1989) is 23 applied to detect the edges in the image. Therefore, the edge map of each degraded 24 image can be obtained and each pixel of the edge map can be defined as edge or 25 non-edge pixel. Finally, the intensity value of a specific pixel of the compact image 4 1 can be decided by using the following projection scheme. The maximum intensity 2 projection (MIP) (Lagerwaard et al. 2005) of the consecutive degraded images is 3 applied if one or more than one pixel is defined as the edge pixel in the edge maps; 4 otherwise, the minimum intensity projection (mIP) (Beigelman-Aubry et al. 2005) is 5 applied if no edge pixels are defined in this position. More specifically, this step can 6 be formulated as n arg max U ( x , y ) , if Edgei(x,y) 1 i G ( x, y ) i 1,..., n i 1 arg min U i ( x, y ) , otherwise i 1,..., n 7 (1) 8 where the G(x,y) is the projected intensity value of the compact image in pixel (x,y), 9 Ui(x,y) is the intensity value of the slice number i in pixel (x,y) out of n series of 10 degraded images and Edgei(x,y) equals to 1 if the pixel is an edge pixel or 0 represents 11 the non-edge pixel in the edge map. 12 Based on the approach, the detection time of the screening system can be 13 significantly reduced and the suspected lesion objects can be easily identified. 14 Moreover, the compact images with different projection schemes are shown in Fig. 2. 15 Obviously, the lesion and fat region might be misclassified as the same group by most 16 of the clustering algorithms while applying the mIP scheme (Beigelman-Aubry et al. 17 2005). 18 Tissue Feature Extraction 19 In the study, the pixels of the compact US image are defined as lesions or normal 20 tissues. Moreover, two feasible feature parameters are adopted for characterizing the 21 pixels. These feature parameters are, intensity local mean u and intensity local stick s, 22 which are calculated with a 5×5 region mask. Generally speaking, the gray level of 23 the lesion tissues tends to be smaller than that of the surrounding normal tissues. On 24 the other hand, the US images with speckle noise (Rakotomamonjy et al. 2000) might 5 1 affect the pixel classification results. Therefore, the mean feature parameter u 2 calculated from the local average of the mask can be used to characterize the lesion 3 tissue and suppress the speckle noise in the US image (Gonzalez et al. 2008). 4 Furthermore, the stick method (Czerwinski et al. 1999) is applied to enhance the 5 contrast of the edges to differentiate the lesion regions easily from other tissue regions. 6 The stick feature is an optimal line detector that is superior to some traditional 7 edge-detection methods (Haralick 1984; Wagner et al. 1988). More explicitly, if a 8 local square mask with N×N in an image is clipped, there are (2N-2) short lines with N 9 pixels and each short line passes through the center pixel of the mask. The sticks with 10 length five are adopted in our study and the stick feature s can be obtained by 11 searching the maximum value among the line templates (Czerwinski et al. 1999). The 12 stick feature parameter can be used to improve the classification accuracy while the 13 edge pixels between the lesion and fat region are smoothed by the mean feature 14 parameter (i.e. the edge pixels might be misclassified as the lesion tissues). 15 Distribution Model Estimation for Feature Parameters and Pixels Reasoning by 16 Naive Bayes Classification 17 The procedures of constructing the distribution models of the feature parameters 18 for both tissues and pixels reasoning based on naive Bayes Classifier (Domingos and 19 Pazzani 1997) would be drawn in this stage. Moreover, the leave-one-patient-out 20 cross validation (LOPO-CV) (Dundar et al. 2004; Andre et al. 2010) is adopted for the 21 patients’ dataset for objective performance evaluation. In each performance validation, 22 US images from one patient are kept for validation and the others would be used as 23 the training set (including the candidate images with or without the lesions) for 24 constructing the feature distribution models. The level set segmentation (Sethian 25 1996) is applied to segment the candidate images to obtain the lesion regions. 6 1 Afterward, we extract the observed samples with lesions or normal tissues from these 2 training images. Consequently, the feature values u and s can be calculated for the 3 observed samples to obtain the statistical histograms respectively. The statistical 4 histogram for feature parameter stick s of both tissues is depicted in Fig. 3 (a). 5 The Rayleigh distribution is a common distribution for describing the average 6 wind speed (Morgan et al. 2011) and can be used to characterize the Rayleigh-like 7 distribution of the feature parameters in this study. The probability density function 8 (PDF) of Rayleigh distribution for feature variable X with tissue class W can be 9 modeled as follows: X 2 F ( X | w ,W ) 10 X w exp 2 w , X {u , s}, W {L, N }. 2 2 (2) 11 where the feature variable X corresponds to feature parameter u or s, class W 12 corresponds to the tissue type L (Lesion) or N (Normal), and σw is the model 13 parameter to be estimated. 14 The maximum likelihood Rayleigh estimator is adopted to estimate the model 15 parameter σw that can be approximated by the calculation of the σ̂ w (Sijbers et al. 16 1998;Sijbers et al. 1999): n ˆ w 17 X i2 i 1 2n , X {u, s}, W {L, N }. (3) 18 where n is the number of the training samples. The estimated Rayleigh distribution 19 models for stick feature parameter with normal and lesion tissue are depicted in Fig. 3 20 (a). 21 After the Rayleigh-distributed models of feature parameters are constructed for 22 both tissues, the naive Bayes Classifier (Domingos and Pazzani 1997; Cevenini et al. 7 1 2011) is applied to reason the tissue class of each pixel of the test US images. The 2 naive Bayes classifier (Domingos and Pazzani 1997) is the probabilistic model which 3 is based on conditional independence assumption among the features (attributes) of 4 Bayes’ theorem. The equal priori probability of the features (Cevenini et al. 2011) is 5 assumed in this study. Thepixel is classified as the lesion tissue if the corresponding 6 likelihood probability (i.e. the product of the Rayleigh PDF of feature parameters) is 7 higher than that of the normal tissue: P(X| , L) = F(X | L , L) F(u | L , L)F (s | L , L) X {u , s} 8 F(u | N , N)F ( s | N , N ) F(X| N , N ) (4) X {u , s} P(X| , N) 9 where P(X|σ,L) and P(X|σ,N) denote the likelihood probability of the pixel to be 10 classified as a lesion tissue and a normal tissue respectively. The decision boundary 11 exists in the condition when P(X|σ,L) equals to P(X|σ,N). The classification result 12 based on naive Bayes classifier of a compact US image and corresponding decision 13 regions are shown in Fig. 3 (b)-(d). 14 Suspected Lesions Extraction 15 After classifying each pixel of the US images by the naive Bayes classifier, the 16 gray-scale US image is transferred into a binary image. The 2-D connected 17 components labeling (Rosenfeld and Pfaltz 1966) is applied to label the lesion pixels 18 and group the connected labels to obtain the isolated regions in an image. The 19 hole-filling (Mesev 2001) is adopted for filling the holes and gaps inside the regions. 20 Afterward, each suspected region would be evaluated by two-phase selection criteria 21 to determine whether the labeled region is a lesion or not. The two-phase lesion 22 selection criteria referring to each suspected 2-D lesion region would be firstly filtered 8 1 by the 2-D shape feature criteria. Afterward, the candidate 2-D lesions (those satisfy 2 the 2-D shape feature criteria) would be further checked by the region continuity 3 criteria for the final determination of a real lesion. The two-phase lesion selection 4 criteria are adopted for the reduction of false-positive rate of the redundant suspected 5 2-D lesions detected by the neighboring image slices. The detection sensitivity can be 6 improved if part of the real lesion object can satisfy the region continuity criteria. In 7 the experimental results, we would demonstrate the effectiveness of the 2-D whole 8 breast lesion detection mechanism especially for the malignant cases with shadowing. 9 False Positive Rate Reduction via Two-phase Lesion Selection Criteria 10 In the first lesion selection phase, the 2-D shape feature criteria include area size, 11 width-height ratio, region ratio and the compactness (Bribiesca 2008) are applied for 12 filtering the unwanted 2-D regions. The lesion area size Rsize is used to filter out these 13 regions with smaller or larger size caused by speckle noise or shadows. On the other 14 hand, the width-height ratio RW_H used to eliminate the non-lesion regions with 15 lengthy or flat shapes can be defined as 16 RW_H Wb , b H Hb Wb , if H b Wb (5) otherwise 17 where Wb and Hb are the width and height of the minimum-bounding box (the 18 minimum rectangle covers the lesion region) respectively. 19 The region ratio RS_R which describes the cover ratio of the suspected region 20 relatives to the minimum-bounding box can be calculated as 21 RS_R 22 23 Rsize Wb H b (6) Compactness is a shape descriptor which measures the degree of the compact around the margin within an object. Moreover, the 2-D image compactness Rc 9 1 2 introduced by Bribiesca et al. (Bribiesca 2008) can be defined as Rc N pel P / 4 N pel N pel (7) 3 where Npel is the number of pixels in the lesion and the perimeter P is the number of 4 pixels of the sides of a 2-D closed shape object. 5 The 2-D shape features criteria used to characterize the suspected lesions are 6 evaluated by the LOPO-CV with classification trees (Praagman 1985). In the 7 classification tree implementation, the information gain (Quinlan 1987) is adopted as 8 the feature (numeric attribute) selection criteria. The pre-pruning and post-pruning 9 (Bramer 2002; Fournier and Cremilleux 2002) are used to prevent the overfitting of 10 the training data while building the tree. After the tree is constructed, the class label of 11 each leaf is assigned as the lesion or non-lesion candidate. 12 In the second lesion selection phase, the region continuity criteria consider the 13 consecutive connected 2-D lesions in the depth (scan) direction and volume size are 14 adopted for deciding the final lesions. The depth ratio Rd which describes the lesion 15 continuity relatives to its maximum length can be calculated as 16 Rd arg max Lcon les L Ns (8) lices 17 where Nslices represents the number of slices of the connected 2-D lesions and Lcon-les is 18 the longest length between Wb and Hb among all the connected 2-D lesions. Moreover, 19 the volume size Rvol of the lesion can be calculated by summing the total region size 20 of n connected 2-D lesions slices as follows: n 21 Rvol Rsize _ i (9) i 1 22 where Rsize_i is the area size of the slice number i out of n connected candidate 2-D 10 1 lesions. 2 Consequently, the two region continuity criteria for determining the real lesion of 3 a series of candidate 2-D lesions would be also evaluated by the LOPO-CV with 4 classification trees (Praagman 1985). The experimental results would demonstrate the 5 effectiveness of the proposed two-phase lesion selection criteria. 6 Separate Classification of Whole and Partial Lesions for Improving Detection 7 Sensitivity 8 Due to the limited scan width of the probe (only 38mm), the flat-shaped fat or 9 shadow in the sides of the scanned US images might be cut as the partial regions and 10 misclassified as the lesion candidates. Therefore, in order to improve the detection 11 sensitivity, the suspected lesions are split into two clusters: the suspected lesions 12 connected to one side or both sides of the US image would be categorized as the 13 outside cluster; otherwise, the suspected regions would be categorized as the inside 14 cluster. The suspected regions of each cluster are classified by their respective 15 classification trees and the detection sensitivity can be merged by both clusters. The 16 advantage of splitting the detected regions into two clusters is the lesion-like regions 17 (i.e. the shape similar to the real lesions due to the shadow noise or cut flat-shaped fat) 18 of the outside cluster can be recognized as the non-lesion regions without the 19 classification intervention of the real lesions in the inside cluster. Therefore, better 20 detection sensitivity and lower false-positives rate can be achieved. More details 21 would be drawn in the experimental results. 22 23 Results 24 The proposed system of lesion detection for portable US images is implemented 25 by the C++ language under the Visual Studio .NET 2008 (Microsoft, Seattle, WA) 11 1 with Microsoft Windows XP operating system (Microsoft, Seattle, WA). The program 2 is running on an Intel Dual-Core Quad 3 GHz CPU with 4G RAM. 3 Performance Quantitative Evaluation 4 In this experiment, the proposed detection method is evaluated for 29 patients 5 with one lesion and 2 patients with two lesions. In the two-phase lesion selection 6 stages for false-positive reduction, the classification trees (Praagman 1985) are 7 adopted with LOPO-CV. Moreover, the predicted class probabilities of the regions 8 from the classification trees lie between 0 and 1. If the predicting probability of the 9 suspected region is larger than the chosen threshold, the region would be classified as 10 the lesion candidate; otherwise, the region would be regarded as a non-lesion and 11 ignored. 12 (Chakraborty 1989; Yu and Guan 2000) curves can be generated by changing the 13 threshold level of the predicted probability to demonstrate the detection performance 14 of the automatic screening system. Furthermore, the free-response operating characteristics (FROC) 15 In this study, the physicians would examine the whole scanned videos and 16 manually delineate the lesion boundaries. The detected lesion is regarded as a “true 17 positive” if the center of gravity is located inside the delineated lesion region (Ikedo et 18 al. 2007). Otherwise, a “false positive” is considered. Besides, the patient case would 19 be regarded as a TP case if the lesion is detected in one or more than one clock 20 regions. On the other hand, the scanned image slices for different patients are varied 21 in our database; therefore, the false positives (FPs) are counted and evaluated for all 22 the scanned image slices in per patient case, per clock section and per hundred image 23 slices. In the experiment, we would firstly validate the detection performance of the 24 suspected regions with and without the split method and corresponding false-positive 25 rate is shown in per hundred image slices respectively. In the first-phase lesion 12 1 selection stage, the FROC curves of all suspected lesions filtered by the 2-D shape 2 feature criteria are shown in Fig. 4 (a). The sensitivity rate of lesion detection after the 3 first-phase FPs reduction for the non-split method is 96.97% (32/33) at 58.77 FPs per 4 hundred slices and is 96.97% (32/33) at 39.67 FPs per hundred slices for the split 5 method. Moreover, the threshold levels of the classifier with maximum detection 6 sensitivity are chosen; therefore, the 2-D suspected lesions satisfy the threshold would 7 be kept for evaluation of the second-phase lesion selection stage. The FROC curves of 8 the connected 2-D candidate lesions filtered by the region continuity criteria are 9 shown in Fig. 4 (b). The sensitivity rate of lesion detection after the second-phase FPs 10 reduction for the non-split method is 93.94% (31/33) at 10.15 FPs per hundred slices 11 compared to 93.94% (31/33) at 4.22 FPs per hundred slices for the split method (or 12 87.88% (29/33) with 5.65 FPs per hundred slices for the non-split method compared 13 to 84.85% (28/33) with 2.23 FPs per hundred slices for split method). As shown in 14 Fig. 4, the method using two split clusters achieves a better detection sensitivity and 15 lower false-positive rate than the method using one non-split cluster. Therefore, the 16 experimental result shows the efficacy of the split method. 17 To conclude the detection performance of the proposed split method, the 18 sensitivity rates of different sizes for benign, malignant lesions and whole dataset are 19 listed in Table 1. Moreover, we list three FPs measurements (i.e. count in per patient 20 case, per clock section and per hundred image slices) for two detection sensitivity 21 rates in Table 2 to clarify the detection performance. Though the false-positive rate of 22 malignant lesions is higher than that of benign lesions (the malignant lesions may 23 introduce more lesion-like shadowing and regions), the difference is not significant. 24 Moreover, each scanned clock region is partially overlapped with the neighboring 25 clock regions in the proposed clock-based method. Thus, the lesion might exist in 13 1 several clock regions and can be detected multiple times as shown in Fig. 5. This 2 clock-based scanning mechanism presents high detection sensitivity because of 3 offering multiple observations of the target lesion. On the other hand, we can observe 4 that two malignant lesions with shadowing as shown in Fig. 6 can be detected based 5 on the proposed method. The main reason is that if part of the malignant lesion (i.e. 6 several consecutive compact frames) can satisfy the region continuity criteria, and 7 then the real lesion would be considered as well. In our database, there are 5 out of 11 8 malignant lesions and 2 out of 22 benign lesions with shadowing that can be detected 9 based on the proposed mechanism. Moreover, the lesion size of the two false negative 10 cases is below 0.6 cm. Therefore, the real lesions would be classified as the 11 non-lesion regions by the lesion size criterion or region continuity criteria. As shown 12 in Fig. 7, a false negative case with fewer scanned image slices is classified as the 13 non-lesion regions by the region continuity criteria. Furthermore, the detection 14 performance with estimated detection difficulty of the lesions by the physician is 15 reported in Table 3. The estimated items described in the BI-RADS-US (Liberman et 16 al. 1998) including internal echo pattern, margin, calcification and shadowing 17 (including posterior shadows) are listed in our study. In order to simplify and clarify 18 the assessment of the difficulty of the lesions, the physician would examine the scan 19 video and choose the representative frame (i.e. the most easily recognized frame for 20 the real lesion) for each patient case. A positivity is defined if the lesion is difficult to 21 recognize under the specific estimated item (e.g. the margin of the lesion is unclear to 22 be detected); otherwise, a negativity is defined. As observed in Table 3, the benign 23 cases with internal echo pattern (e.g. the echo pattern inside the lesion is bright and 24 inhomogeneous) or unclear margin might lead the detected lesions to be grouped as 25 smaller regions and be eliminated. Besides, the calcification and shadowing would not 14 1 significantly influence the detection results according to the test database. 2 On the other hand, the spatial down-sampling scale factor is 2 and five 3 connective degraded US images are used to synthesize one compact image in the 4 spatio-temporal resolution down-sampling stage. In order to improve the detection 5 robustness, the neighboring compact images have two connective degraded US 6 images in common. The detection frame rate of the proposed screening system is 7 about 12.3 fps (frame rate of the portable machine is set to 10 fps). Thus, the proposed 8 automatic lesion detection system can offer effective and efficient whole breast 9 examination for the operators. 10 11 Discussion 12 Drukker et al. (Drukker et al. 2002; Drukker et al. 2003; Drukker et al. 2005) 13 advocates to the breast US lesion detection for the still images acquired by the initial 14 localization of the physicians. In order to ensure the detection robustness, normal 15 images without lesions were constructed and the lesion detection performance is 16 evaluated with the collected lesions database. Their studies present 94% detection 17 sensitivity at 0.48 false-positives per image (Drukker et al. 2002) and 80% detection 18 sensitivity at 0.25 false-positives per image for malignant lesions that exhibit posterior 19 acoustic shadowing (Drukker et al. 2003). The main limitation of the approach is the 20 lesion detection algorithm only applied and constrained to lesion candidate images 21 localized by the physicians rather than the streaming video acquired from the whole 22 breast US scanners. Moreover, each image analyzed in 1 min (Drukker et al. 2002) is 23 not practical for the whole breast lesion detection with thousands of scanned images. 24 In recent years, the automatic lesion detection mechanism for whole breast US has 25 been investigated (Ikedo et al. 2007; Chang et al. 2010). Ikedo et al. (Ikedo et al. 2007) 15 1 proposed a 2-D detection scheme system with detection rate 80.6% (29/36) at 4.52 2 FPs per hundred slices (84 image slices per case) with the re-substitution method 3 (Theodoridis and Koutroumbas 2009) (i.e. using the same training and test sets) or 4 80.6% (29/36) at 7.85 FPs per hundred slices with the leave-one-out method. In the 5 edge detection stage for the suspected lesions, the vertical edges of the Cooper’s 6 ligaments in the fat tissue and ribs regions would be falsely detected as the lesion 7 candidates. On the other hand, the proposed 2-D detection scheme without 8 considering the 3-D characteristics of the lesions leads to enormous false positive 9 lesions. Chang et al. (Chang et al. 2010) proposed an automatic detection system 10 considers 3-D characteristics (e.g. coronal-view feature) and region continuity criteria 11 for false positive reduction. The detection rate is 92.3% (24/26) at 2.10 FPs per 12 hundred slices (84 image slices per case). The proposed automatic detection system 13 presents high detection sensitivity and very promising false positive rates. 14 Nonetheless, because there are no standards for selecting the threshold of the feature 15 parameters for the suspected lesions, the manual selection of the thresholds by 16 observing all the patient cases might be subjective to the physicians’ experience. 17 Moreover, the exhaustive search for adjusting the threshold level of the feature 18 parameters might not be convenient for the practical use. 19 In this study, an automatic detection is proposed for the whole breast lesion 20 detection. The two-phase false positive reduction offers an objective scheme by the 21 classification trees with LOPO-CV. Besides, the proposed system achieves a real-time 22 detection application due to the aid of the spatio-temporal resolution down-sampling 23 and fast pixel classification using naive Bayes classifier (Domingos and Pazzani 24 1997). Therefore, the proposed detection mechanism can be possibly used for the 25 real-time guidance for the operators during the whole breast examination (e.g. 16 1 real-time alarm for the operator while the lesions are detected or immediate second 2 breast examination is required). The advantage of the clock-based storing method can 3 assist the physicians to easily locate the detected lesions. This mechanism can 4 improve the detection sensitivity and robustness if the target lesion appears in more 5 than one clock regions. 6 There are several limitations in this study. First, the scan speed with the 7 hand-held probe of the operator might not be fixed and the spacing of the whole 8 breast US is unknown, thus the quality of the compact image with the proposed 9 edge-preserved mIP would be influenced. Therefore, the 3-D characteristics such as 10 coronal-view feature (Chang et al. 2010) could not be used for filtering out most of 11 the ribs and shape-flapped fats. Second, the same false positive lesion might be 12 repetitively counted due to that the shape-flapped fats or ribs might appear in several 13 clock regions. Lastly, the test database is relatively small in our experiments. 14 Therefore, a superior mechanism of larger dataset for obtaining the fixed spacing to 15 reduce the redundant false positives should be investigated in our future study. 16 Pending future verification, the proposed detection algorithm can be used for the 17 automated whole breast ultrasound (ABUS) (Chang et al. 2011) and then the robust 18 shape feature of the detected lesions can be extracted (Moon et al. 2011) for diagnosis 19 purpose. Thus, the system could provide a more reliable and robust detection and 20 diagnosis mechanism for clinical applications. 21 22 Acknowledgments 23 The authors would like to thank the National Science Council 24 99-2221-E-002-136-MY3), Ministry of Economic Affairs (100-EC-17-A-19-S1-164) 25 of the Republic of China, and National Taiwan University (10R80919-6) for the 17 (NSC 1 funding support. 2 18 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 References Andre B, Vercauteren T, Buchner AM, Shahid MW, Wallace MB, Ayache N. An image retrieval approach to setup difficulty levels in training systems for endomicroscopy diagnosis. Med Image Comput Comput Assist Interv 2010;13:480-7. Beigelman-Aubry C, Hill C, Guibal A, Savatovsky J, Grenier PA. Multi-detector row CT and postprocessing techniques in the assessment of diffuse lung disease. Radiographics 2005;25:1639-52. Berg WA, Blume JD, Cormack JB, Mendelson EB, Lehrer D, Bohm-Velez M, Pisano ED, Jong RA, Evans WP, Morton MJ, Mahoney MC, Larsen LH, Barr RG, Farria DM, Marques HS, Boparai K. Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA 2008;299:2151-63. Bramer M. Pre-pruning classification trees to reduce overfitting in noisy domains. Intelligent Data Engineering and Automated Learning - Ideal 2002 2002;2412:7-12. Bribiesca E. An easy measure of compactness for 2D and 3D shapes. Pattern Recognition 2008;41:543-54. Buchberger W, Niehoff A, Obrist P, DeKoekkoek-Doll P, Dunser M. Clinically and mammographically occult breast lesions: detection and classification with high-resolution sonography. Seminars in ultrasound, CT, and MR 2000;21:325-36. Cevenini G, Barbini E, Massai MR, Barbini P. A naive Bayes classifier for planning transfusion requirements in heart surgery. J Eval Clin Pract 2011; Chakraborty DP. Maximum likelihood analysis of free-response receiver operating characteristic (FROC) data. Med Phys 1989;16:561-8. Chang JM, Moon WK, Cho N, Park JS, Kim SJ. Radiologists' performance in the detection of benign and malignant masses with 3D automated breast ultrasound (ABUS). Eur J Radiol 2011;78:99-103. Chang RF, Chang-Chien KC, Takada E, Huang CS, Chou YH, Kuo CM, Chen JH. Rapid image stitching and computer-aided detection for multipass automated breast ultrasound. Med Phys 2010;37:2063-73. Cherri AK, Karim MA. Optical symbolic substitution: edge detection using Prewitt, Sobel, and Roberts operators. Appl Opt 1989;28:4644-8. Crystal P, Strano SD, Shcharynski S, Koretz MJ. Using sonography to screen women with mammographically dense breasts. AJR Am J Roentgenol 2003;181:177-82. Czerwinski RN, Jones DL, O'Brien WD, Jr. Detection of lines and boundaries in speckle images--application to medical ultrasound. IEEE Trans Med Imaging 1999;18:126-36. Domingos P, Pazzani M. On the optimality of the simple Bayesian classifier under zero-one loss. Machine Learning 1997;29:103-30. Drukker K, Giger ML, Horsch K, Kupinski MA, Vyborny CJ, Mendelson EB. Computerized lesion detection on breast ultrasound. Med Phys 2002;29:1438-46. Drukker K, Giger ML, Mendelson EB. Computerized analysis of shadowing on breast ultrasound for improved lesion detection. Med Phys 2003;30:1833-42. Drukker K, Giger ML, Metz CE. Robustness of computerized lesion detection and classification scheme across different breast US platforms. Radiology 2005;237:834-40. Dundar M, Fung G, Bogoni L, Macari M, Megibow A, Rao B. A methodology for 19 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 training and validating a CAD system and potential pitfalls. International Congress Series 2004;1268:1010-4. Fournier D, Cremilleux B. A quality index for decision tree pruning. Knowledge-Based Systems 2002;15:37-43. Giger ML, Al-Hallaq H, Huo ZM, Moran C, Wolverton DE, Chan CW, Zhong WM. Computerized analysis of lesions in US images of the breast. Academic Radiology 1999;6:665-74. Gonzalez RC, Woods RE, Masters BR. Digital image processing. Upper Saddle River, New Jersey: Pearson Prentice Hall, 2008. Gordon PB, Goldenberg SL. Malignant breast masses detected only by ultrasound. A retrospective review. Cancer 1995;76:626-30. Haralick RM. Digital Step Edges from Zero Crossing of 2nd Directional-Derivatives. Ieee Transactions on Pattern Analysis and Machine Intelligence 1984;6:58-68. Horsch K, Giger ML, Vyborny CJ, Venta LA. Performance of computer-aided diagnosis in the interpretation of lesions on breast sonography. Academic Radiology 2004;11:272-80. Ikedo Y, Fukuoka D, Hara T, Fujita H, Takada E, Endo T, Morita T. Development of a fully automatic scheme for detection of masses in whole breast ultrasound images. Med Phys 2007;34:4378-88. Kaplan SS. Clinical utility of bilateral whole-breast US in the evaluation of women with dense breast tissue. Radiology 2001;221:641-9. Keys RG. Cubic Convolution Interpolation for Digital Image-Processing. Ieee Transactions on Acoustics Speech and Signal Processing 1981;29:1153-60. Kim Y, Kim JH, Basoglu C, Winter TC. Programmable ultrasound imaging using multimedia technologies: a next-generation ultrasound machine. 1997. Kolb TM, Lichy J, Newhouse JH. Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: An analysis of 27,825 patient evaluations. Radiology 2002;225:165-75. Kotsianos-Hermle D, Hiltawsky KM, Wirth S, Fischer T, Friese K, Reiser M. Analysis of 107 breast lesions with automated 3D ultrasound and comparison with mammography and manual ultrasound. Eur J Radiol 2008; Lagerwaard FJ, Underberg RWM, Slotman BJ, Cuijpers JP, Senan S. Use of maximum intensity projections (MIP) for target volume generation in 4DCT scans for lung cancer. International Journal of Radiation Oncology Biology Physics 2005;63:253-60. Liberman L, Abramson AF, Squires FB, Glassman JR, Morris EA, Dershaw DD. The Breast Imaging Reporting and Data System: Positive predictive value of mammographic features and final assessment categories. American Journal of Roentgenology 1998;171:35-40. Mesev V. Morphological image analysis: principles and applications. Environment and Planning B-Planning & Design 2001;28:800-1. Moon WK, Shen YW, Huang CS, Chiang LR, Chang RF. Computer-aided diagnosis for the classification of breast masses in automated whole breast ultrasound images. Ultrasound Med Biol 2011;37:539-48. Morgan EC, Lackner M, Vogel RM, Baise LG. Probability distributions for offshore wind speeds. Energy Conversion and Management 2011;52:15-26. Praagman J. Classification and Regression Trees - Breiman,L, Friedman,Jh, Olshen,Ra, Stone,Cj. European Journal of Operational Research 1985;19:144-. Quinlan JR. Simplifying Decision Trees. International Journal of Man-Machine 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Studies 1987;27:221-34. Rakotomamonjy A, Deforge P, Marche P. Wavelet-based speckle noise reduction in ultrasound B-scan images. Ultrason Imaging 2000;22:73-94. Rosenfeld A, Pfaltz JL. Sequential Operations in Digital Picture Processing. J ACM 1966;13:471-94. Sethian JA. A fast marching level set method for monotonically advancing fronts. Proc Natl Acad Sci U S A 1996;93:1591-5. Shipley JA, Duck FA, Goddard DA, Hillman MR, Halliwell M, Jones MG, Thomas BT. Automated quantitative volumetric breast ultrasound data-acquisition system. Ultrasound in Medicine and Biology 2005;31:905-17. Theodoridis S, Koutroumbas K. Pattern Recognition. San Diego, CA: Academic Press, 2009. Wagner RF, Insana MF, Smith SW. Fundamental Correlation Lengths of Coherent Speckle in Medical Ultrasonic Images. Ieee Transactions on Ultrasonics Ferroelectrics and Frequency Control 1988;35:34-44. Yu S, Guan L. A CAD system for the automatic detection of clustered microcalcifications in digitized mammogram films. IEEE Trans Med Imaging 2000;19:115-26. 21 1 2 3 Figure Captions Fig. 1 The proposed clock-based storing method. 4 Fig. 2 The compact image obtained from different projection algorithms. (a) The 5 compact image with the highlighted lesion. (b) The compact image with the 6 edge-preserved minimum-intensity projection. (c) The compact image with 7 the minimum intensity projection (mIP). 8 Fig. 3 (a) The calculated statistical histograms and estimated Rayleigh distribution 9 of the stick feature parameter of both tissues. (b) An example compact US 10 image. (c) The classification result based on naive Bayes classification. (d) 11 The decision regions of the proposed feature parameters. The feature 12 parameters of the inference pixels lay in the black decision region would be 13 classified as the lesion tissue. 14 Fig. 4 The FROC curve of the two-phase lesion selection criteria. (a) First-phase: 15 the sensitivity rate for non-split method is 96.97% (32/33) at 58.77 FPs per 16 hundred slices (THnon-split = 0.93) and is 96.97% (32/33) at 39.67 FPs per 17 hundred slices for split method (THsplit_inside = THsplit_outside = 0.94). (b) 18 Second-phase: the sensitivity rate for non-split method is 93.94% (31/33) at 19 10.15 FPs per hundred slices (THnon-split = 0.1) and is 93.94% (31/33) at 4.22 20 FPs per hundred slices (THsplit_inside = 0.11, THsplit_outside = 0.08) for split 21 method. 22 Fig. 5 A series of 2-D compact image slices and corresponding determined lesions. 23 Note that the real lesion is highlighted with solid circle, and the false 24 positive lesion is indicated by the dotted circle. (a) A true-positive case of a 25 1.0 cm invasive ductal carcinoma in the right breast. (i) 10 o’clock region. 26 (ii) 11 o’clock region. (b) A true-positive case of a 0.67 cm fibrocystic 22 1 2 disease in the left breast. (i) 1 o’clock region. (ii) 2 o’clock region. Fig. 6 Two true-positive malignant cases with shadowing. Note that the detected 3 real lesion is highlighted with solid circle and the shadow is indicated by the 4 dotted circle. (a) A true-positive case of a 2.8 cm invasive ductal carcinoma. 5 (b) A true-positive case of a 2.2 cm invasive ductal carcinoma. 6 Fig. 7 7 8 9 10 A false-negative case of a 0.52 cm fibroadenoma in the right breast and the real lesion is indicated by the dotted circle. (a) 10 o’clock. (b) 11 o’clock. Table 1 The sensitivity rates of different sizes of benign, malignant lesions and whole dataset. Benign < 1.0 cm 1.0 - 2.0 cm 2.0 - 3.0 cm ≧3.0 cm Malignant 86.67% (13/15) 100% (2/2) 88.23% (15/17) 100% (5/5) 100% (3/3) 100% (8/8) 100% (3/3) 100% (3/3) 100% (2/2) 100% (3/3) 100% (5/5) 90.09% (20/22) 100% (11/11) 93.94% (31/33) N/A All Whole database 11 12 13 14 Table 2 Three different FPs measurements under two detection sensitivity rates of the proposed split method. 84.85% detection sensitivity: false positive rate (FPs) per case 15 per clock per hundred section slices 93.94% detection sensitivity: false positive rate (FPs) per case per clock per hundred section slices Benign 80.45 3.35 2.21 151.35 6.31 4.16 Malignant 82.64 3.44 2.27 157.36 6.56 4.33 Whole database 81.23 3.38 2.23 153.48 6.40 4.22 Note, 23 1 2 1 patient case = 24 clock sections 1 patient case≒3000 image slices 3 24 1 2 3 4 Table 3 The detection performance with estimated detection difficulty of the lesions by the physician of the proposed split method. Internal echo pattern Margin Calcification Shadowing Positive 84.62%(11/13) 90.00% (9/10) 100% (2/2) 100% (7/7) Negative 100% (20/20) 95.65% (22/23) 93.55% (29/31) 92.31% (24/26) 5 25 1 11 12 1 10 2 9 3 8 4 7 2 3 6 5 Fig. 1 4 26 1 2 3 (a) (b) Fig. 2 4 27 (c) 1 2 3 (a) 4 5 6 (b) (c) (d) Fig. 3 7 28 1 2 3 (a) 4 5 (b) 6 Fig. 4 7 29 1 (i) 2 (ii) 3 4 (a) 5 (i) 6 (ii) 7 8 9 10 (b) Fig. 5 30 1 2 3 (a) 4 5 6 (b) Fig. 6 7 31 1 2 3 4 (a) (b) Fig. 7 32