The Importance of Breast Elastography Added to the BI-RADS R (5 th Edition) Lexicon Classification

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1 ORIGINAL ARTICLE J Surg Ultrasound 2016;3:46-52 JSU Journal of Surgical Ultrasound The Importance of Breast Elastography Added to the BI-RADS R (5 th Edition) Lexicon Classification Alvinlyle Kim, Chang Wan Jun, Dong Won Ryu Department of Surgical, Kosin University Gospel Hospital, Busan, Korea Received October 10, 2016 Revised October 23, 2016 Accepted October 28, 2016 Correspondence to: Dong Won Ryu Department of Surgery, Kosin University Gospel Hospital, 262 Gamcheonro, Seo-gu, Busan 49267, Korea Tel: Fax: lovebreast@naver.com Purpose: This study was conducted to investigate the addition of elastography to the BI-RADS R lexicon for the classification of breast lesions. Methods: A total of 301 patients diagnosed with breast lesions from January 2015 to September 2015 were included in our study. Acoustic radiation force impulse (ARFI) elastography and strain ratio (SR) evaluations were performed on 301 lesions. We compared the diagnostic performance of breast ultrasonography alone and the combination of breast ultrasonography, ARFI elastography, and SR evaluations. The patients were classified according to the fifth edition of the breast imaging and reporting data system (BI-RADS) lexicon, which includes elastographic findings. Results: Among the 301 lesions, 38 were malignant and 263 were benign. The addition of elastographic findings to the BI-RADS lexicon improved the sensitivity, specificity, and diagnostic accuracy of ultrasound during assessment of breast lesions, which increased from 94.7, 66.7, and 70.4 to 92.1, 88.5 and 89.3%, respectively. Conclusion: These findings suggest that the addition of elastography to the 4 th BI-RADS lexicon will improve the specificity and diagnostic accuracy of ultrasonography in the screening of breast lesions. Therefore, ARFI elastography and SR evaluations can be used as complementary modalities to make more accurate breast lesion diagnoses. Keywords: Breast neoplasms, Ultrasonography, Elastography, Specificity, Accuracy INTRODUCTION Breast cancer is the most frequent cancer among women worldwide and the second most common cancer in Korean women.(1) Early detection is critical for the successful man-agement of breast cancer. B-mode ultrasonography has been used to accurately estimate breast lesion whether it is malignant or not.(2) While breast ultrasonography can be a useful method to differentiate breast lesions, this modality has the unavoidable limitation of low specificity reported about 87.7%.(3) To overcome this limitation, elastography was introduced.(4) The fifth edition of the breast imaging and reporting data system (BI-RADS), an ultrasound atlas, was updated to include the assessment of the elasticity of breast lesions using elastography. Elastography was developed as an additional tool for ultrasound studies in the 1990s.(5) The first corresponding clinical studies were conducted in the early 2000s, and elastography was eventually included in the latest edition of the BI-RADS lexicon.(6) The addition of elastography to the lexicon aimed to improve the specificity of ultrasound, because low specificity is currently a major Journal of Surgical Ultrasound is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c 2016 by The Korean Surgical Ultrasound Society ISSN

2 Alvinlyle Kim, et al.: The Importance of Breast Elastography Added to the BI-RADS R (5 th Edition) Lexicon Classification barrier to the wide application of ultrasound in clinical practice.(7) Our study assessed the elasticity of breast lesions, using elastography combined with conventional findings that are suggested in the BI-RADS lexicon.(8) In addition, Our study investigated the impact of elastography in routine testingelastography is a noninvasive imaging modality to evaluate the stiffness of soft tissues. In general, benign breast lesions tend to be softer than malignant lesions.(9) This general characteristic provides the basis for using elastography to differentiate breast lesions.(10) The most frequently used elastography technique in the breast is strain elastography, which requires external compression.(11) Because external compression is performed manually, strain elastography is operator-dependent which influences its reproducibility. Instead of using manual compression, a new trend of applying acoustic radiation force impulse (ARFI) imaging to elastography has arisen. ARFI elastography has the advantage of being objective, reproducible, and less operator-dependent.(12) With this modality, ultrasonography scanners are used to generate short-duration acoustic radiation forces that impart small, localized displacements in the tissue and create a static map of the relative stiffness of the tissues.(13) Strain ratio (SR) is a semiquantitative measurement to determine the firmness of tissue and to differentiate benign and malignant lesions by comparing the difference in compliance between a breast lesion and adjacent fatty tissue.(14) Previous studies have proven that SR is a highly valuable and more objective parameter for differentiating malignant and benign breast lesions.(15) The aim of this study was to evaluate whether the combination of breast ultrasonography, ARFI elastography, and SR improves the diagnostic performance of differentiating malignant and benign breast lesions. METHODS 1. Patients Between January and September 2015, patients who visited to the outpatient clinic for breast mass, pain and screening study were evaluated. So Total of 301 lesions with breast lesions was included in our study. Regardless of the ultrasonographic findings, each lesion in the study underwent a histological examination with the consent of the patient. In patients with benign lesions diagnosed by core needle biopsy, an excisional biopsy was subsequently per-formed when the patient opted for surgical removal. Breast ultrasonography, ARFI elastography, and SR examinations were performed before surgery and biopsy. After the radiologic examinations, each breast lesion was diagnosed pathologically by radical surgery (38/301, 12.6%), excisional biopsy (5/301, 1.6%), or vacuum-assisted breast biopsy (258/301, 85.7%). 2. Imaging techniques Breast ultrasonography, ARFI elastography, and SR evaluations were performed with a Siemens ACUSON S2000 US system (Siemens Medical Solutions, Mountain View, USA) with a linear probe (9L4; Siemens Medical Solutions) by one operator with 9 years experience in breast imaging. First, we obtained breast ultrasonographic images of the lesions. The lesion was described by using the BI-RADS lexicon of ultrasonographic descriptors of mass shape, orientation, margin, lesion boundary, echo pattern, and posterior acoustic features. Next, ARFI elastography sequences were performed to evaluate the elasticity scores of the breast lesions in Virtual Touch TM imaging (VTI) mode by displaying the target lesion on breast ultrasonography, setting a region of interest (ROI) around the lesion, and ensuring that adequate surrounding breast tissue was included in the ROI. During the ARFI elastography examination, patients were instructed to continue breathing 47

3 J Surg Ultrasound Vol. 3, No. 2, 2016 normally. In Virtual Touch TM quantification (VTQ) mode, an acoustic impulse and detection pulses were used to calculate shear wave velocity (SWV). To perform VTQ, a target region was identified with a fixed-size ROI of 5 5 mm. For the measurement, the marginal areas of the mass and surrounding tissues were included in the ROI, and the SWV was measured 3 times in these areas when measurements were feasible. The shear waves were detected by ultrasonographic detection pulses; numeric SWV values were calculated and displayed on the monitor. When measurements were outside the allowable range (0-9 m/sec) for SWV calculations, the SWV might be displayed as X.XX. The SR was measured on a static image including coupled B-mode and elastographic images. The calculation of the SR was based on a comparison of the average strain measured in the lesion and adjacent fatty tissue at the same depth. The strain of the lesion was determined by selecting an ROI from the lesion. The SR was automatically calculated and displayed on the monitor. 3. Image analysis Breast ultrasonography images were assigned to 1 of 5 categories according to BI-RADS: category 1, negative findings; category 2, benign findings; category 3, probably benign findings; category 4, suspicious of malignancy; and category 5, highly suggestive of malignancy. To classify VTI-mode images, we evaluated the color-mapped pattern both in the lesion and in the surrounding breast tissue (i.e., the pectoral muscle and rib were excluded). The ARFI elastography image was displayed as a color map with each voxel representing the degree of strain within the ROI by using a scale ranging from purple (softest components) to blue (intermediate components) and red (hardest components). The lesions were first classified according to the 4 th edition of BI-RADS lexicon and, then, classified based on the elastographic findings according to the 5 th edition of BI-RADS lexicon. The masses were classified according to the BI-RADS lexicon criteria. And then using the elastographic criteria, the lesions were classified as soft, intermediate, or hard. The techniques that were used in the elastographic classification have been previously described. The final classification of the lesions was based on the BI-RADS ultrasound assessment categories and the elastographic findings. The positive predictive value, negative predictive value, sensitivity, specificity, and diagnostic accuracy of the BI-RADS classification, with and without the elastographic data, were determined and compared. 4. Statistical analysis All statistical analyses were performed using SPSS version 18.0 (SPSS Inc., Chicago, USA). Differences in sensitivity, specificity, accuracy, positive predictive value, and negative predictive value between evaluation methods were assessed by Student t-test. The mean SWV and SR values were calculated using ANOVA. A P-value of < 0.05 was considered to indicate statistical significance. RESULTS 1. Pathologic diagnosis Of the 301 lesions, 38 (12.6%) were malignant and 263 (87.3%) were benign. The pathologic diagnoses of these lesions are shown in Table 1. The most common malignant and benign tumors were invasive ductal carcinoma (n = 34) and fibrocystic changes (n = 257), respectively. 2. ARFI elastography and SR for breast lesions Distributions of elasticity scores according to pathologic diagnosis when ARFI elastography was displayed in VTI mode are shown in Table 2 and Table 3. The hard elasticity score was significantly higher for malignant lesions (55.3%) than for benign lesions 48

4 Alvinlyle Kim, et al.: The Importance of Breast Elastography Added to the BI-RADS R (5 th Edition) Lexicon Classification (5.0%) (Table 4). Of the 38 malignant lesions, 21 (55.3%) lesions had a hard elasticity scores. In this group, 13 lesions (34.2%) had a soft elasticity scores. Of the 263 benign lesions, 228 (86.7%) had a soft elasticity scores. 19 lesions (7.2%) had a intermediate elasticity scores. There was a high correlation between elasticity score and malignancy (P = 0.001) (Table 4). In VTQ mode, the mean SWV value of benign lesions (1.22 ± 0.88 m/sec) was lower than that of malignant lesions (2.54 ± 1.09 m/sec, P < 0.01). The SWV cutoff point for malignant lesions was estimated as 2.37 m/sec. The mean SR value of benign lesions (1.54 ± 1.40) was significantly lower than that of malignant lesions (3.42 ± 1.63, P < 0.001). Table 1. Pathologic Diagnosis of the Examined Malignant and Benign Breast Lesions Pathologic diagnosis Number of lesions (%) in 301 patients Malignant (n = 38) Invasive ductal carcinoma 34 (89.4%) Invasive lobular carcinoma 1 (0.3%) Ductal carcinoma in situ 3 (1.0%) Benign (n = 263) Fibrocystic disease 257 (97.7%) Hyperplastic disease 1 (0.3%) Intraductal papilloma 3 (1.1%) Atypical ductal hyperplasia 2 (0.7%) Table 3. The Distribution of Elasticity Scores in Malignant Breast Lesions Elasticity Score in Malignant lesions The number of lesions Rate Soft % Intermediate % Hard % Total % Table 2. The Distribution of Elasticity Scores in Benign Breast Lesions Table 4. Comparison of Elasticity Scores According to Pathologic Diagnosis Elasticity score in benign lesions The number of lesions Rate Malignant No. (%) Benign No. (%) Total No. (%) P-value Soft % Intermediate % Hard % Missed date 3 1.1% Total % Elasticity score Soft 13 (34.2) 228 (86.7) 241 (80.1) Intermediate 4 (10.5) 19 (7.2) 23 (7.6) Hard 21 (55.3) 13 (5.0) 34 (11.3) Total 38 (100) 263 (100) Table 5. The 5th BI-RADS R Classification of Breast Lesions After the Addition of Elastographic Findings to the 4th BI-RADS R Classification 4th BI-RADs 5th -BI-RADs II III IVa IVb IVc V III No Rate (%) IVa No Rate (%) IVb No Rate (%) IVc No Rate (%) V No Rate (%) Total No Rate (%)

5 J Surg Ultrasound Vol. 3, No. 2, Diagnostic performance of BUS alone and a combination of BUS, ARFI elastography, and SR evaluations for breast lesions Table 5 shows the comparison of the number of breast lesions in each 4 th edition and 5 th edition of BI-RADS lexicon. Among the 79 lesions with the 4 th edition of BI-RADS score of 4a, 66 cases (83.5%) were adjusted to 5 th edition of BI-RADS score of 3 and 8 cases (10.1%) were re-categorized as a 5 th edition of BI-RADS score of 4b. And among the 178 lesions with the 4 th edition of BI-RADS R score of 3, 8 cases (4.5%) were adjusted to 5 th edition of BI-RADS R score of 4a (Table 5). According to 4 th edition of BI-RADS lexicon, Breast ultrasonography showed Table 6. Frequency of the 4 th BI-RADS R Categories for the Lesions that were Classified Without (BI-RADS R ) Elastographic Findings 4 th BI-RADs III 4 th BI-RADs IV 4 th BI-RADs V True positive 16 (15.8%) 20 (90.9%) True negative 176 (98.8%) False positive 85 (84.2%) 2 (9.1%) False negative 2 (1.1%) Total N PPV 15.8% 90.9% NPV 98.8% Sensitivity 94.7% Specificity 66.9% Accuracy 70.4% PPV = positive predictive value; NPV = the negative predictive value. 94.7% sensitivity, 66.9% specificity, 70.4% accuracy, a 15.8% positive prediction value, and a 98.8% negative prediction value for malignant lesions (Table 6). In the same way, according to 5 th edition of BI-RADS lexicon, Breast ultrasonography presented 92.1% sensitivity, 88.5% specificity, 89.3% accuracy, 53.3% positive prediction value, and a 99.4% negative prediction value for differentiating breast lesions (Table 7). The specificity, accuracy, and PPV of breast ultrasonography combined with ARFI elastography and SR were higher than those of breast ultrasonography alone. DISCUSSION The introduction of elastographic findings into the BI-RADS lexicon serves as an additional tool to improve the specificity and diagnostic accuracy of ultrasound in the screening of breast lesions.(5) The low specificity of current ultrasound techniques has led to a large number of false positive results, which often necessitate diagnostic biopsies. The low specificity of ultrasound hinders its use in the routine diagnostic screening of breast lesions.(16) Elastography requires the coupling of specific software and an ultrasound device to assess the softness of tissue in areas of interest.(17) This method is based on the assumption that benign lesions tend to Table 7. Frequency of the 5 th BI-RADS R categories for the lesions that were classified with (BI-RADS R Elastography) 5 th BI-RADS II 5 th BI-RADS III 5 th BI-RADS IV 5 th BI-RADS V True positive 21 (55.3%) 14 (93.3%) True negative 153 (99.4%) 80 (97.6%) False positive 29 (58.0%) 1 (6.7%) False negative 1 (2.6%) 2 (2.4%) Total N 154 (51.2%) 82 (27.2%) 50 (16.6%) 15 (5.0%) PPV 55.3% 93.3% NPV 99.4% 97.6% Sensitivity 92.1% Specificity 88.5% Accuracy 89.3% PPV = Positive predictive value; NPV = The negative predictive value. 50

6 Alvinlyle Kim, et al.: The Importance of Breast Elastography Added to the BI-RADS R (5 th Edition) Lexicon Classification be softer than malignant lesions.(18) Elastography software is currently included in most commercial ultrasound devices; however, this software has not been standardized.(19) This software may be used for a qualitative assessment of lesions, which is based on the visual evaluation of changes in color in the area of interest; however, this type of assessment is subjective.(20) In a quantitative assessment, the degree of hardness in a lesion is estimated using objective data. Compressions to induce the required deformation may be performed manually or using specific probes, such as ARFI and shear-wave imaging.(21) Even with the introduction of these new technologies, there seems to be a convergence in the literature to adopt the qualitative criteria for the evaluation of breast masses as a standard, rather than quantitative criteria.(22) The reason for this is that ultrasound is, in essence, a sub-jective method of image interpretation, which depends on the experience and training of the examiner.(18) Lesions deeper than 2 cm are less accurately characterized by means of shear-wave elastography. The latest edition of the BI-RADS atlas includes elastographic findings, and lesions are classified as soft, intermediate, or hard. Fibroadenomas include both soft and hard lesions. It was observed that the most indolent fibroadenomas (hypocellular with collagen) appeared softer on elastographic assessment, whereas the complex and hypercellular lesions were harder. Elastography allows for an unequivocal diagnosis in complicated cysts. Because of the inclusion of elastographic data in the BI-RADS lexicon, in this study, a large number of lesions that would have been classified as BI-RADS category 3 (most likely benign and soft) were reclassified as BI-RADS category 2 (benign). Elastography may impact lesions that are classified as BI-RADS category 4a, which include lesions that meet most of the criteria for benign lesions, but would benefit from further investigation with diagnostic methods or short-term follow-up. The classification of soft lesions would shift from category 4a to category 3, for which short-term follow-up (usually 6 months) is recommended. The risk of malignancy in lesions that are classified in the BI-RADS lexicon as category 4a varies from 2-10%. CONCLUSION The results of this study demonstrate that the use of elastography as recommended in the latest edition of the BI-RADS R lexicon improved the specificity and accuracy of ultrasonography, which increased from 66.7 to 88.5% and from 70.4 to 89.3%, respectively. The sensitivity of this method did not significantly changes from 94.7 to 92.1%. But this study was conducted at a single center for patients with breast lesions. So Further studies needed to validate the results. The use of elastographic findings according to the recommendations in the 5 th edition of the BI-RADS R lexicon may improve the specificity and diagnositic accuracy of breast ulatrasonography in the screening of breast cancer. ACKNOWLEDGEMENTS This article is presented in 67th congress of the Korean Surgical Society. This article was supported by Kosin Medical colleage. REFERENCES 1. Min SY, Kim Z, Hur MH, Yoon CS, Park EH, Jung KW. The basic facts of Korean breast cancer in 2013: results of a nationwide survey and breast cancer registry database. J Breast Cancer 2016;19: Fausto A, Rubello D, Carboni A, Mastellari P, Chondrogiannis S, Volterrani L. Clinical value of relative quantification ultrasound elastography in characterizing breast tumors. Biomed Pharmacother 2015;75: Ohuchi N, Suzuki A, Sobue T, Kawai M, Yamamoto S, Zheng YF, et al. Sensitivity and specificity of mammography and adjunctive ultrasonography to screen 51

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