The SR and PHC values for the malignant invasive ductal carcinoma lesions (n = 214) were 4.67 ± 1.75 and 91.18 ± 11.73, respectively, compared with 2.16 ± 2.14 and 53.93 ± 25.14 for the benign fibroadenomas and 2.54 ± 1.37 and 71.70 ± 23.37 for the benign fibrocystic mastopathy lesions.
3.3 Comparison of the diagnostic performance of CU, SR + CU, and PHC + CU
The Breast Imaging-Reporting and Data System of the American College of Radiology ultrasound criteria were used to evaluate each nodule from CU mode grayscale and Doppler scans. Cut-off values were determined from SR and PHC ROC curves in conjunction with Youden index value calculations.
When SR and PHC were each combined with CU (eg, SR + CU and PHC + CU), the original categories assigned to the lesions were upgraded (or downgraded) (except categories 5 and 2, which remained the same) if the SR was ≥2.69 (or <2.69) and the PHC was ≥82.45 (or <82.45). ROC curve analysis yielded AUC values of 0.956, 0.960, and 0.956 for CU, SR + CU, and PHC + CU, respectively (Tables 2 and 3, Fig. 8). No significant differences were observed among the 3 methods.
When the cut-off points for the 3 methods were compared, the cut-off point used for 4a and 4b categorization was found to improve accuracy and specificity compared with the cut-off point used for 3 and 4a categorization. In contrast, sensitivity did not change significantly. These results are consistent with the findings reported by Hao et al. Consequently, for further comparison between the methods, a cut-off value between 4a and 4b was established.
Accuracy, sensitivity, and specificity were compared for the 3 methods. SR + CU exhibited greater accuracy than PHC + CU, followed by CU. There were no differences in sensitivity and specificity between SR + CU and PHC + CU, while CU exhibited lower sensitivity, yet greater specificity, than SR + CU and SR + PHC (Table 3).
A bivariate correlation analysis showed no correlation between the diagnostic accuracy of maximum diameter and maximum depth parameters. Chi-square tests revealed no significant differences when the maximum diameter and maximum depth values were divided into 4 groups (group I: ≤0.99 cm; group II: 1–1.99 cm; group III: 2–2.99 cm; and group IV: ≥3 cm).
Previous studies have provided evidence of the benefits of sonoelastography as an adjunct procedure to breast ultrasound.[15,16] One of the main methods for evaluating lesion elasticity involves the use of a scoring system with a pseudo-colored map representing the varying stiffness values of a focal tissue. However, this approach is subject to observer-based variations,[5,11] which can result in interobserver variance in scoring of the same lesion. Another widely used method is determination of SR. However, in this approach, selection of reference tissue type, position, and area[17–19] can differ among individuals responsible for the selection criteria. Therefore, here, we measured PHCs and SRs for lesions and then used ROC curve analysis to compare the diagnostic performance of the PHC and SR methods. When only elastography data were used, diagnostic performance did not differ significantly between SR (AUC = 0.821) and PHC (AUC = 0.864). Moreover, when CU was used in combination with elastography data, no significant differences in AUC, sensitivity, or specificity values were observed between SR and PHC. Thus, PHC analysis was reliable for diagnosis of breast cancer and comparable to SR analysis.
When SR and PHC were combined with CU, the number of category 4a lesions decreased (Table 2). Fewer lesions being suspected to be malignant suggests a lessened biopsy risk for benign breast lesions. Thus, measurement of PHC represents a potential new analysis tool for lesion hardness with a similar diagnostic performance as SR. In previous studies, SR values were calculated by using the same layer of glandular tissue, the same layer of adipose tissue, or more commonly, superficial adipose tissue.[7,9,17–19] An advantage of the PHC method is that it does not require selection of a reference tissue.
There are additional advantages provided by the PHC method owing to it being independent of surrounding tissues. First, as described above, PHC does not require the selection of a reference normal tissue. Additionally, only 1 region of interest needs to be drawn. These considerations reduce selection bias, potential variation in selection of a reference normal tissue, and the time needed to obtain measurements. Second, cystic lesions do not need to be excluded from PHC measurements. In the present study, all cystic lesions were diagnosed with great accuracy by PHC. In contrast, cystic lesions cannot be included in calculations of SR because they appear as blue, green, red artifacts. Generally, a diagnosis of cystic lesions by CU is relatively easy. However, when lipid cysts are hypoechoic and not echoless, a diagnosis is not straightforward. An example of this issue is shown in Figure 4(b). In the present study, there were 20 cystic lesions with a mean PHC value of 49.66 ± 14.19 (range, 24.49–80.19). All of these cysts could be diagnosed correctly with 82.45% as the threshold value.
In some studies, a combination of elastography with CU improved differentiation between benign and malignant breast masse.[3,4] However, this result was not observed in the present study. ROC curve analyses showed that the diagnostic efficiencies of CU, SR + CU, and PHC + CU were not significant, yet the accuracy of each was significant according to the McNemar test.
There are several possible reasons for this result. One is a statistics-based consideration. In the McNemar test, when a large number of samples are analyzed, a small difference is often not practically significant. Second, the method of combining 2 different kinds of methods, such as CU and elastography, is a key consideration. Third, during clinical examinations, radiologists use CU to characterize the anatomy of lesions and their surrounding tissues, and these observations are the basis for a diagnosis. If lesion hardness was the only criterion for differentiating benign from malignant lesions, greater divergence among lesions may be observed. Fourth, with the technological improvements of the past 30 years, conventional ultrasonography has made a qualitative leap forward, including markedly improved resolution as well as improved diagnostic accuracy. The efficacy of CU has been demonstrated to be excellent. Fifth, it should be noted that there remains substantial room for improving elastography technology. Finally, it should be noted that our center is a tertiary specialized center with a high frequency of malignant cases and very experienced radiologists. Hence, less experienced radiologists could obtain different results. When we analyzed the correlation between maximum depth and gray maximum diameter with diagnostic accuracy, no obvious correlation was observed. Based on our preference to preserve the quality of the images examined, lesions with a size and depth <1 cm or >3 cm were rarely included. Moreover, in the groups with lesions with a size and depth <1 cm, there was no significant difference between the diagnosis of benign and malignant lesions among the 3 methods. A possible reason for this result is that the small size of these lesions could have precluded the observation of imaging signs; meanwhile, the measurement error of elastic imaging is also large. Generally, lesions with a maximum diameter and depth >3 cm exhibit obvious CU characteristics, making it easy to make a correct diagnosis without elastography. Therefore, a correlation between lesion size and diagnostic accuracy was not observed in the present study, consistent with the results of Carlsen et al.
5 Limitations of the present study
There were several limitations associated with this study. First, since the patients included in this study were recruited from a single tertiary specialized center, they were more likely to have advanced stage malignancies than individuals in the general population, which may have introduced sampling bias. Therefore, additional multicenter studies are needed to validate the usefulness of the PHC method. Second, although quantitative elastography, including shear wave and acoustic radiation force impulse elastography, are available in clinics, semiquantitative quasistatic ultrasound elastography was applied in this study for economic reasons. Thus, additional studies of a larger number of patients, and studies that apply more meticulous techniques, such as shear wave elastography, are needed to confirm the present results. Third, due to image quality control, a few lesions that were larger and at greater depths were excluded. However, for these excluded lesions, their CU features were generally much more obvious and diagnosis by CU was not difficult.
The results of the present study demonstrate that PHC analysis is comparable to SR calculation in providing a differential diagnosis of breast lesions. ROC analyses outcomes did not differ significantly among the CU, SR + CU, and PHC + CU methods.
The authors thank Shandong Medical and Health Science Technology Development Program (2017WSA18002) and the Project of Science and Technology Program of Shandong Academy of Medical Sciences (2017-09) (2017-13) (2017-44).
Conceptualization: Yunling Li.
Data curation: Yan Xue, Hongsheng Zou, Sheng Li, Yun Li.
Formal analysis: Yan Xue, Sheng Li.
Funding acquisition: Yan Xue, Hongsheng Zou, Sheng Li, Yuehuan Zhao.
Investigation: Yuehuan Zhao.
Methodology: Yan Xue, Hongsheng Zou, Yun Li.
Project administration: Yang Ou.
Resources: Yan Xue, Yang Ou.
Software: Hongsheng Zou, Yang Ou, Yun Li.
Supervision: Yunling Li.
Validation: Yunling Li.
Visualization: Yuehuan Zhao.
Writing – original draft: Yan Xue, Yuehuan Zhao, Yunling Li.
Writing – review and editing: Yunling Li.
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Keywords:Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
breast neoplasm; percentage of hard component; quasi-static elastography; strain ratio; ultrasound