Cum Laude Poster Award

A Support Vector Machine Designed to Identify Breasts at High Risk Using Multi-probe Generated REIS Signals: A Preliminary Assessment
David Gur 1 , Bin Zheng 1 , Dror Lederman 1 , Sreeram Dhurjaty 2 , Jules Sumkin 1 , Margarita Zuley 1
1

Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213 2 Dhurjaty Electronics Consulting LLC, Rochester, NY 14618
ABSTRACT

A new resonance-frequency based electronic impedance spectroscopy (REIS) system with multi-probes, including one central probe and six external probes that are designed to contact the breast skin in a circular form with a radius of 60 millimeters to the central (“nipple”) probe, has been assembled and installed in our breast imaging facility. We are conducting a prospective clinical study to test the performance of this REIS system in identifying younger women (< 50 years old) at higher risk for having or developing breast cancer. In this preliminary analysis, we selected a subset of 100 examinations. Among these, 50 examinations were recommended for a biopsy due to detection of a highly suspicious breast lesion and 50 were determined negative during mammography screening. REIS output signal sweeps that we used to compute an initial feature included both amplitude and phase information representing differences between corresponding (matched) EIS signal values acquired from the left and right breasts. A genetic algorithm was applied to reduce the feature set and optimize a support vector machine (SVM) to classify the REIS examinations into “biopsy recommended” and “non-biopsy” recommended groups. Using the leave-one-case-out testing method, the classification performance as measured by the area under the receiver operating characteristic (ROC) curve was 0.816 ± 0.042. This pilot analysis suggests that the new multi-probe-based REIS system could potentially be used as a risk stratification tool to identify pre-screened young women who are at higher risk of having or developing breast cancer. Keywords: Electrical impedance spectroscopy (EIS), resonance frequency, risk stratification, breast cancer, support vector machine, technology assessment.

I. INTRODUCTION
Developing a non-radiation based, low cost, easy to operate, and highly performing prescreening tool to identify younger women (< 50 years old) with higher risk of having or developing breast cancer has been attracting research interest for a long time. Electrical Impedance Spectroscopy (EIS) technology is one of the approaches that have been explored for this purpose. When applying EIS technology to detect breast abnormalities, the system applies alternating low power electric signals to the breast skin (tissue) and measures the tissue’s response. The breast tissue impedance is determined by analyzing the difference between the applied “excitation” and the response electrical signals. Differences in electrical conductivity and capacitance between neo-plastic and normal breast tissue have been shown in the 1920s and have been assumed to be primarily the result of changes in cellular water content, amount of extracellular fluid, and membrane proteins [1]. Cancer cells exhibit altered local dielectric properties as compared with normal cells. A study performed in the 1980s reported that the conductivity and capacitance in malignant human breast tissue was 20 to 40 fold higher than the normal breast tissue. Based on such experimental results, a prototype EIS system was tested in the hope of detecting breast abnormalities [2]. Since then, a number of studies followed and improved EIS systems that include both system hardware and classification algorithms have been developed and reported [3-8]. A commercial EIS system (T-Scan 2000, Mirabel Medical Systems, Austin, TX) was approved by the U.S. Food and Drug Administration (FDA) as an adjunct modality to mammography and several laboratory and clinical studies have been conducted to assess the performance and clinical utility of this EIS system [9, 10].

Medical Imaging 2010: Image Perception, Observer Performance, and Technology Assessment, edited by David J. Manning, Craig K. Abbey, Proc. of SPIE Vol. 7627, 76271B © 2010 SPIE · CCC code: 1605-7422/10/$18 · doi: 10.1117/12.844452 Proc. of SPIE Vol. 7627 76271B-1

In the last several years, we have been working on developing and evaluating a different type of EIS technology [11-13]. The EIS system consists of paired detection probes and produces continuous multi-frequency electrical pulse sweeps over a wide range of frequencies. From the recorded EIS signal sweeps, we focus on using primarily EIS signals specifically at and near the resonance frequency for the breast tissue being measured. Using these signals we build machine learning classifiers to identify breasts depicting highly suspicious abnormalities. Hence, we termed our new approach REIS (for the resonance frequency we focus on). In a previous study, we tested a prototype REIS system with one pair of probes that enabled contact with the nipple and a single lateral contact point at the lateral mid-outer portion of the breast skin with a fixed distance of 60 mm to the center (“nipple”) probe. We also built an EIS signal feature based artificial neural network (ANN) to classify cases that ultimately warranted a biopsy due to detection of a highly suspected abnormality during diagnostic imaging workups and cases that were not recommended for a biopsy. The overall performance of that classifier as measured by the area under the ROC curve was 0.707 ± 0.033, which is significantly better than chance [12]. After demonstrating the feasibility of using the single probe REIS based approach, we developed, assembled, and installed a new multi-probe REIS system in our clinical imaging facility [13]. Under an IRB-approved protocol, we are currently conducting a prospective clinical study to assess the performance of this new multi-probe REIS system. In this preliminary analysis, we selected an initial set of 100 acquired REIS measurements (examinations) with verified diagnostic results. This group includes women with negative screening examinations and women recommended for a biopsy as a result of the diagnostic workup. An initial set of multi-probe based EIS features (values) were used combined with a genetic algorithm to reduce the number of redundant values and build a support vector machine (SVM) based classifier to classify these women into positive (“recommended for biopsy”) and negative (“not recommended for biopsy”) groups. The experimental procedures and classification results are described and reported herein.

II. MATERIALS AND METHODS
Under an exclusive contract between the University of Pittsburgh and Dhurjaty Electronics Consulting LLC (Rochester, NY), a multi-probe based REIS system to measure and record multichannel EIS signal sweeps (including amplitude, phase, and combined magnitude) was specially designed, assembled, and installed in our clinical breast imaging facility [13]. In brief, the system consists of a mechanical support, an electronic box, and two interchangeable sensor cups depending on breast size. It is driven by a notebook computer housing the programs to control the system and data acquisition. The sensor cups include seven mounted metallic probes with one probe located in the center of the cup and the other six probes are distributed along a circle located in the 12, 2, 4, 6, 8, and 10 o’clock positions, respectively (Fig. 1). The distance between the external probes and the center probe is 60 mm. During an REIS examination, the center probe makes contact with the nipple and the other six probes make contact with six points on the breast skin surface. The maximum electric voltage and current applied to the sensor probes (breast skin) are less than 1.5V and 30mA, respectively. The application of this sensor cup to the breast is similar to manually holding a 1.5V battery; hence, as expected, and our previous study showed, that the majority of participants (>98%) did not feel an electrical tingling during the examination [13].

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All REIS examinations are performed by trained health care professionals. During each examination a technologist in our clinical imaging facility selects a sensor cup based on the participant’s breast size and adjusts the sensor box position along a vertical rail of the REIS system to fit the height of the breast and then locks it in place. The center probe is positioned slightly higher than the naturally positioned level of the participant’s nipple. The woman is then asked to “lift” her breast with her hand and position the nipple to make sure it touches (makes good contact with) the center probe and then to “pull herself” into the cup by holding one or both sidebars of the REIS system. The technologist types in a digital ID number specific to the REIS examination in question. Once the system detects that all seven probes have “satisfactory” contact with the breast, the measurement and signal acquisition starts. The complete examination of each breast takes 12 seconds. The same measurement procedure is repeated on both breasts during each REIS examination. The multiple REIS signal sweeps generated between different pairs of sensor probes are automatically recorded and saved in a specific data file named with the test ID number in a database. Each EIS signal sweep records 121 output signals including signal amplitude (a), signal phase (p), and signal magnitude ( I =

a 2 + p 2 ) ranging from 200 KHz to 800 KHz at a 5 KHz increment. The resonance frequency of each EIS

signal sweep is detected at a frequency at which the signal magnitude reaches the minimum value and at this frequency phase crosses the zero line (e.g. converting from negative to positive values). Under an IRB approved protocol, we are currently acquiring REIS data aimed to enable an investigation of the possible performance and reliability of applying this technology to classify young women (between ages of 30 and 50 years old) into “positive” and “negative” groups. The “positive” group represents the cases that had been recommended for biopsy due to suspicious findings during the imaging based diagnostic workup, and the “negative” group represents negative screening cases that had been rated “negative” during screening and/or a diagnostic workup. Because REIS is a non-imaging type of examination, there is no restriction (nor identification) regarding the type of abnormality in question (i.e., mass, micro-calcification clusters, asymmetry, and etc.), nor of the abnormality location within the breast (in “positive” cases). This preliminary analysis included an initial dataset of 100 REIS examinations (cases). Among these, half (50) were “positive” and the other half “negative”. In each REIS examination multiple EIS signal sweeps are generated and recorded. To develop the machine learning classifiers to classify test cases, we first computed a relatively large number of EIS signal features extracted from six sets of EIS sweeps for all six pairs between the center probe and each of the six “external” probes (Fig. 1). Based on the expectations that similar to the known symmetry between breast tissue patterns observed on mammograms; hence, the two breasts of each woman should have a higher level of electrical impedance symmetry in the normal (negative) cases than in the abnormal (positive) cases [8], we used EIS signal differences (subtraction) between the corresponding signal values extracted from two matched EIS sweeps acquired from the left and right breasts (in a location based mirrored fashion). Our initial feature pool included a total of 33 EIS signal related features. Most of these features represented the absolute difference (subtraction) of two corresponding EIS signal values computed for the two breasts. Using figures 2 and 3 as an example, we describe the definitions, computational methods, and resulting units for the 33 EIS signal difference related features. We first identified the resonance frequency values of all six EIS signal sweeps and computed the maximum range of these six resonance frequency values for each breast ( Δf = Max | f i − f j | , i ≠ j = 1,2, K ,6 ). Thus, feature 1 is defined as the absolute difference of these two values computed from the left (L) and right (R) breasts ( F1 = | Δf L − Δf R | ). In the sweeps shown in Fig. 2, the maximum resonance frequency ranges for the two breasts are Δf L = 420 – 280 = 140 KHz, and Δf R = 405 – 280 = 125 KHz. Thus, F1 = (140 – 125) = 15 KHz. The remaining 32 features are divided into two groups each containing 16 values. In the first group, we first computed an average value of the six EIS signal values extracted from the six EIS signal sweeps acquired from one breast. We then computed either average (1 value) or absolute differences (15 values) of the two matched averaged signal values between the two breasts. Thus, the 16 features in this group can be described as follows: 1. We computed the average resonance frequency (

f = ( ∑ f i ) / 6 ) for each breast. As shown in Fig. 2 f L = (390 +
i =1

6

405 + 330 + 300 + 280 + 320) / 6 = 337.5 (KHz) and f R = (420 + 405 + 305 + 285 + 300 + 360) / 6 = 345.8 (KHz).

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From these two average resonance frequency values, we defined two features. Feature 2 is the average of the two values ( F2 = ( f L + f R ) / 2 ) representing the overall resonance frequency of the case and Feature 3 is the absolute difference between the two values ( F3 = | f L − f R | ). In Fig. 2, F2 = 341.7 KHz and F3 = 8.3 KHz, respectively.

(a)

(b)

(c)

(d)

Figure 2: Six sets of recorded EIS signal magnitude sweeps and six phase sweeps for the left and right breast of one examination. The minimum, average, and maximum resonance frequencies of the six sweeps are shown for comparison in (a) and (b), respectively. Six sets of EIS output signal phase sweeps of the right and left breast, as well as the frequencies at which the phase signals reaches a plateau are shown in (c) and (d), respectively.

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2.

We identified EIS signal magnitude ( I ( f ) ) at resonance frequencies and computed the average value (I =(

∑ I ( f ) ) / 6 ) at all six resonance frequencies for each breast. We defined Feature 4 as the absolute
i =1 i

6

difference of the two averaged values between the two breasts: F4 = | I L − I R | . As shown in Fig. 2 (a) and (b),

I L = (5576 + 5384 + 5555 + 5439 + 5334 + 5202) / 6 = 5415 (mV), and I R = (5433 + 5187 + 5346 + 5351 + 5688 + 5769) / 6 = 5462.3 (mV). Thus, F4 = 47.3 (mV).

(a)

(b)

Figure 3: A mirror-matched pair of EIS signal sweeps (magnitude –left and phase –right) that have the largest difference in resonance frequency between the right and left breasts as shown in Fig. 2. 3. Near the resonance frequency of each EIS sweep, we extracted six signal values of an EIS sweep ( I ( f i ) ) at six specific frequencies. These included values at two frequencies that are lower by 5 and 10 KHz than the identified resonance frequency ( f −10 = f − 10 KHz and f −5 = f − 5 KHz) and values at frequencies that are higher by 5, 10, 15 and 20 KHz than the identified resonance frequency (from f 5 = f + 5 KHz to f 20 = f + 20 KHz at 5 KHz increment). At each of these frequencies we computed the EIS signal magnitude value ( I ( f i ) ) and subtracted these values from the EIS signal magnitude value at the resonance frequency ( I ( f i ) ). Specifically, we computed the following six values ΔI i = I ( f i ) − I ( f ) , i = −10, − 5, 5, 10, 15, 20 KHz. After averaging the six EIS signal magnitude differences ( ΔI i ) over the six probe pairs ( ΔI i =

∑ ( ΔI )
k =1

6

i k

), we defined six features (Features

5 to 10) by computing the absolute differences for the EIS signal magnitude values computed from the two breasts ( F j = | ΔI ( f i ) L − ΔI ( f i ) R | , where j = 5, 6, K10 and i = −10, − 5, 5, 10, 15, 20 KHz below and above the resonance frequency). For example, at f −10 = f − 10 KHz the EIS signal magnitude values acquired from the right breast (Fig. 2(a)) are 5670, 5286, 5503, 5475, 5993, and 5937 for the six EIS sweeps, respectively. After subtracting EIS magnitude values at the resonance frequency [ I ( f ) ] for the same EIS sweep, we computed the

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average magnitude difference among six EIS sweeps: ΔI ( f −10 ) R = (237 + 99 + 157 + 124 + 305 + 168) / 6 = 181.7 (mV). Using the same approach we computed the six corresponding EIS sweep magnitude values (5665, 5544, 5785, 5505, 5475, and 5373) from the signal of the left breast and computed ΔI ( f −10 ) L = (89 + 160 + 230 + 66 + 141 + 171) / 6 = 142.8 (mV) for the left breast (Fig. 2(b)). Thus, F5 = 38.9 (mV) and so on. 4. From the EIS signal phase sweeps (Fig. 2 (c) and (d)), we computed the following seven feature values. In each EIS phase sweep, we identified the frequency [ f ( p then computed the average values ( f ( p
Max Max 6

)] at which the EIS phase signal (p) reaches a “plateau”. We

) = ∑ f ( piMax ) / 6 ) of the six EIS phase sweeps for both the left and
i =1 Max Max ) − f ( p R ) | ). Max

right breast and defined Feature 11 as the absolute difference of the two values ( F11 = | f ( p L In the example we present (Fig. 2 (c) and (d)), f ( p L for the left breast and f ( p
Max R

) = (505 + 520 + 455 + 430 + 430 + 455) / 6 = 466 (KHz)

) = (535 + 525 + 440 + 420 + 430 + 480) / 6 = 472 (KHz) for the right breast. Thus,

F11 = (472 – 466) = 6 (KHz).
5. Similar to feature values 5-10 we computed EIS signal phase value differences rather than the EIS signal magnitude value differences for the same set of six frequencies of interest. Features 12 to 17 are defined as the absolute differences of the two averaged phase values at the six specific frequencies between two breasts ( F j = | p ( f i ) L − p ( f i ) R | , where j = 12, 13, K17 , and i = −10, − 5, 5, 10, 15, 20 KHz. For example, to compute feature F12 from the EIS phase sweeps shown in Fig. 2(c) and (d), we computed p ( f i ) R = [(-1525) + (1178) + (-1257) + (-923) + (-1558) + (-1364)] / 6 = -1300.8 (mV) and p ( f i ) L = [(-1147) + (-1377) + (-1415) + (1072) + (-1126) + (-1305)] / 6 = -1240.3 (mV). As a result, F12 = 60.5 (mV) and so on. The second group of 16 feature values (18-33) is computed in a similar manner to feature values (2-17) with the exception that only one mirror-matched pair of EIS signal sweeps (rather than averages of all six sweeps) from left and right breasts is selected. The selected matched pair of EIS signal sweeps is the one that has the largest difference in the two resonance frequency values as compared with all other five matched pairs. In the example shown in Fig. 2, the matched pair of EIS sweeps at 10 o’clock on the left breast and 2 o’clock on the right breast has the maximum resonance frequency difference (40 KHz). Discarding the other five EIS pairs, we plotted this matched pair of EIS sweeps in Fig. 3. Similar to computing the 16 feature values from the difference of the averaged data of the six EIS sweeps, we computed the second set of 16 EIS signal features using the same definitions albeit computed solely based on the selected matched pair of EIS sweeps ( F18 to F33 ). For example, as shown in Fig. 3 (a), features 18 to 20 are computed as: F18 = (320 + 360) / 2 = 340 (KHz), F19 = (360 – 320) = 40 (KHz), and F20 = (5769 – 5202) = 567 (mV), respectively. Table I summarizes the definitions of all 33 EIS signal based feature values selected as an initial pool. To classify between “positive” and “negative” examinations (case based) we built a support vector machine (SVM) based classifier. The SVM is a popular machine learning classifier based on statistical learning theory [14] which has been used in a number of classifiers designed for computer-aided detection schemes [15]. We modified a publicly available SVM software package (SVM-Light) [16] to build our classifier. The SVM-Light software package provides for 10 model (kernel) options including linear, polynomial, radial basis, sigmoid, and others. In this analysis, a polynomial function based statistic model [ s = ( a ∗ b + c ) ] was selected.
d

To select a small (“optimal”) set of effective features and remove (discard) redundant features in our initial feature pool and to define an optimal parameter (d) used in the polynomial function, a genetic algorithm (GA) [17] was applied. The binary coding method with 35 genes was applied to represent a GA chromosome in which the first 33 represent all initially computed EIS signal related feature values and the last two genes represent the parameter (d) used in the polynomial function. In the first 33 genes, 1 indicates that the feature represented by this gene is selected and 0

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indicates that the feature is discarded from the SVM classifier. The last two gene codes represent d value ranging from 2 to 5. A unique GA fitness function that includes the SVM learning and the ROC curve fitting was designed and implemented. The performance summary index used to select (fitness index) highly performing GA chromosomes in each training generation was the area under the ROC curve ( Az ). Chromosomes that produce higher Az values have higher probabilities of being selected for generating new chromosomes using the crossover and mutation method. The GA operation was terminated when it reached either a global maximum performance level or a pre-determined maximum number of growth generations (i.e., 100). The best GA selected chromosome was used to build the SVM classifier, the result of which are reported in this paper. Table I: A list of the initial set of 33 EIS signal based features. With the exception of features #2 and #18 that represent an average of two feature values computed from two breasts, all other features represent the absolute difference of two corresponding EIS signal values computed from the signals obtained from two breasts. Feature 1 2 3 4 5 - 10 11 12 - 17 18 19 20 21 - 26 27 28 – 33 Feature Description Difference in the range of six resonance frequencies Average of two averaged resonance frequencies Difference of two averaged resonance frequencies Difference of two averaged EIS signal magnitude values at corresponding resonance frequencies Difference of two averaged EIS signal magnitude values near the resonance frequency ranging from -10 to +20KHz at 5KHz increments Difference of two averaged frequency values when EIS phase signal reaches a plateau The difference of two averaged EIS signal phase values near the resonance frequency ranging from -10 to +20KHz at 5KHz increments Average of two resonance frequencies exhibiting the maximum resonance frequency difference between mirror-matched pair of probes Difference between two resonance frequencies of the selected matched pair of probes Difference between two EIS signal magnitude values at the two matched resonance frequencies Difference between two EIS signal magnitude values of the matched probe pair near the resonance frequencies ranging from -10 to +20KHz at 5KHz increments Difference between two frequency values when EIS phase signal reaches a plateau Difference between two EIS signal phase values of the matched probe pair near the resonance frequencies ranging from -10 to +20KHz at 5KHz increments Feature unit KHz KHz KHz mV mV KHz mV KHz KHz mV mV KHz mV

Performance assessment of the classifier was performed using the leave-one-case-out testing method due to the limited size of the REIS dataset. During each testing iteration, 99 examinations were used to train the coefficients using the SVM classifier with a fixed number of EIS signal features and a given classification function while the remaining examinations were used to test the SVM performance. This process was repeated 100 times, hence, each examination was used once as a test case. As a result, 100 testing (classification) scores that indicate the likelihood of the case being positive were generated. Using these classification scores the SVM overall performance level was measured as the area under the ROC curve ( AZ value), which is frequently used for this purpose as a summary index, and was computed using a publicly available ROC program (ROCKIT [18]).

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III. RESULTS
A set of 12 EIS signal features were selected by the GA from the initial pool of 33 features. Thus, the SVM based classifier built, tested, and presented in this study included 12 EIS signal related features and a parameter d = 2 for the polynomial function based classification hyper-plane. Among the 12 REIS selected features, seven were extracted from the average values of the six probe pairs (the first group). These features included F2 , F4 , F6 , F8 , F9 , F10 , and

F12 . The remaining five features were computed from a single mirror-matched probe pair showing the largest difference in resonance frequencies (the second group) and included F17 , F19 , F21 , F28 , and F32 . Two of the features were
related to frequency differences, seven were associated with EIS signal magnitude differences, and three were related to the computed phase differences. The testing (classification) performance of the SVM classifier when applied to our dataset of 100 examinations achieved an AZ = 0.816 ± 0.042 (Fig. 4). The 95% confidence interval of the computed

AZ for this dataset was [0.722, 0.887].

Figure 4: The SVM actual detection performance data points and the fitted ROC curve classifying between 50 positive (biopsy) cases and 50 negative (non-biopsy) examinations. The area under ROC curve ( AZ ) is 0.816 ± 0.042.

IV. DISCUSSION
To date, EIS technology has attracted but limited interest as an adjunct examination modality to mammography [9, 10]. We are focused on the development and assessment of a different approach to using EIS signals. The unique characteristic of our approach is that it is primarily based on differences in measurements of multiple EIS signals at and near the detected resonance frequencies. We have assembled and tested two REIS systems. The first prototype REIS system consisted of only one pair of sensor probes (one EIS signal detection channel) and the second system includes

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seven sensor probes that can result in multiple pairs of EIS signal detection channels. In our previous study we demonstrated the feasibility of applying REIS signal related feature values for classifying “biopsy” recommended and “non-biopsy” recommended examinations [12]. The purpose of developing and testing the current (multi-probe) REIS system is to improve the clinical utility of the same underlying REIS concept. The new REIS system can not only generate multi-channel EIS signal sweeps, but it was also much easier to use and more reliable operationally. The system automatically detects the adequacy of all contacts thereby avoiding the need for repeated scans. The total EIS signal scanning time for each breast is substantially reduced from approximately 48 seconds to 12 seconds using this system. This helps reduce the impact of unexpected patient movement during the examination. However, as the new REIS system generates and records a substantially larger number of data than the previous single probe pair based REIS system, selection of a small set of effective features is more effort consuming, albeit the classification performance is significantly better. This paper describes the first preliminary study that assessed the possible use of a SVM based machine learning classifier for this purpose. We note that the initial feature pool of 33 EIS signal related features was reduced to 12 that were used to build the SVM classifier. Both EIS signal magnitude and phase values were ultimately included in the SVM classifier. Although we cannot directly compare our performance level to that achieved in the previous study ( AZ = 0.707 ± 0.033) [12] as different datasets were used, we believe that the multi-probe pair based REIS system has the potential to achieve a substantially higher classification performance. Our initial testing results are quite encouraging but we need to emphasize that this was a very preliminary study with but a small set of 100 REIS examinations. Additional work and further tests of this REIS approach using a significantly larger number of diverse cases combined with repeated optimization of feature selection are needed before this technology can be seriously considered as acceptable for routine clinical use. The possible advantages of the REIS system and approach are many, such as low-cost, non-radiation based, and easy to use, but the system’s possible use as a prescreening risk stratification tool (e.g. an office based system to be used in conjunction with CBE) in identifying younger women (i.e., ≤ 50 years old) with higher risk of having or developing breast cancer remains far from reality at this point in the development.

V. ACKNOWLEDGEMENT
This work is supported in part by Grant 1R21/R33 CA127169 to the University of Pittsburgh from the National Cancer Institute, National Institutes of Health. The authors also thank the Magee-Womens Research Institute & Foundation, Glimmer of Hope Fund, for supporting this effort.

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10. A. Stojadinovic, O. Moskovitz, G. Gallimidi, and et al, “Prospective study of electrical impedance scanning for identifying young women at risk for breast cancer,” Breast Cancer Res Treat; 97, 179-189 (2006). 11. J.H. Sumkin, B. Zheng, M. Gruss, and et al, “Assembling a prototype resonance electrical impedance spectroscopy system for breast tissue signal detection: preliminary assessment,” Proc SPIE 6917, 691716-1-8 (2008). 12. B. Zheng, M.L. Zuley, J.H. Sumkin, et al, “Detection of breast abnormalities using a prototype resonance electrical impedance spectroscopy system: A preliminary study,” Med Phys 35, 3041-3048 (2008). 13. D. Gur, B. Zheng, S. Dhurjaty, G. Wolfe, M. Fradin, R. Weil, J. Sumkin, M. Zuley, “Developing and testing a multi-probe resonance electrical impedance spectroscopy system for detecting breast abnormalities,” Proc SPIE 7263, 72631F-1-8 (2009). 14. V.N. Vapnik, Statistical Learning Theory, Wiley, New York, 1998. 15. W.J. Wu, W.K. Moon, “Ultrasound breast tumor image computer-aided diagnosis with texture and morphological features,” Acad Radiol 15, 873-880 (2008). 16. T. Joachims, Support vector machine, Department of Computer Science, Cornell University, https://www.cs.cornell.edu/people/tj/svm_light/ (2004). 17. M. Kantrowitz, Prime time freeware for AI, issue 1-1: selected materials from the Carnegie Mellon University, Artificial Intelligence Repository. Prime Time Freeware, Sunnyvale, CA, (1994). 18. C.E. Metz, ROCKIT 0.9B Beta Version, University of Chicago, http://www-radiology.uchicago.edu/krl/, (1998).

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