We aim to determine the features of SWE in normal breast tissue, the parenchymal appearences, SWE characteristics of benign and malignant breast lesions, then to evaluate its usage in premalignant and non-mass lesions and lastly the effect on BIRADS classification. Then, with the support of literature data and in the light of updates we will point some special clues and conclude the role of SWE in breast lesions.

The ARFI method is a less operator dependent technique. Lesions may be compared with the adjacent normal tissues. Mild compression or just touching to the breast surface is needed, because also pre-compression of the tissue may amplify the shear wave velocity (SWVs) [24]. Therefore -compared to other available elastography techniques-measuring the shear wave propagation induced by the automated push pulse is meant to be the most standardized and examiner independent technique.

Kim et al found that the mean elasticity score (3.7 ± 1.0 vs. 1.6 ± 0.8, p < 0.01), SWV (4.23 ± 1.09 m/sec vs. 2:22 ± 0.88 m/sec, p < 0.01) and SR (5.69 ± 1.63 vs. 2.69 ± 1.40, p < 0.01) were significantly higher for malignant lesions than benign lesions with this technique and especially if the ARFI is added, the differential diagnosis in breast lesions reached up to 93.6% [25]. The results for US combined with ARFI elastography and SR values were 97.5% sensitivity, 92.3% specificity, 93.6% accuracy, a 79.6% positive predictive value (PPV), and a 99.1% negative predictive value [25]. In another study, specificity was 62.5 % among the BIRADS 4 breast lesions and 72.9% with addition of virtual touch imaging quantification (VTIQ) to the gray scale. VTIQ qualitative and quantitative elastography has the potential to further characterise B-mode detected breast lesions, increasing specificity and reducing the number of unnecessary biopsies [26].

Clinicopathological features such as histological type, histological grade, tumor size, the presence of lymph node metastasis, and lymphovascular invasion are known as prognostic factors of breast cancer. Regarding SWE, high nuclear and histologic grade, large invasive size and lymphovascular invasion were reported to be associated with increased stiffness of invasive breast cancer [27] [28] [29] [30]. Estrogen receptor negativity, progesterone receptor negativity, p53 positivity, and Ki-67 positivity were significantly associated with a higher E-ratio, and triple-negative and HER2-positive tumors showed greater stiffness than estrogen receptor-positive tumors [29] [30]. Interestingly, some aggressive tumors, such as high grade cancers and triple-negative tumors, are likely to be assessed as BI-RADS category 3 in B-mode ultrasound, but SWE may provide additional information for diagnosing those benign-looking malignancies [30].

In the literature, the cut-off values were also different to distinguish benign and malignant lesions according to type of device and different operators [25] [31]. The cut off value is up to 91% in malignant lesions with SWV exceeds probability and below the 10% - 11% in non-malignant lesions according to recent meta-analysis result [32]. The cut-off value for malignancy was 2.55 m/s level with point shear wave, it has partly elevated and reached to 3.59 m/s level by the help of new technology named VTIQ which can make smaller measurements with ROI in 2-D form [33] [34] [35] [36] [37]. A quantitative data could be measured quantitatively with mild compression by the VTIQ method (Figure 1). In more recent systems, the resolution of B-mode gray scale images are sufficiently high and provides opportunity for quality control of obtained SWV maps by the help of VTIQ quality map [38].

In this modality, cysts have a typical “bull’s eye” appearance (small size, white center, peripheral black circle). Therefore, hypoechoic or hypo-anechoic or complicated cysts, galactoceles with solid appearences can be clearly distinguished regardless of being simple or complicated (Figure 2).

For solid lesions, not only internal structures and peripheral contours, also the reaction in perilesional area can be clearly demonstrated and evaluated in detail, by SWE imaging. In this evaluation, while benign lesions are encoded as a more hyperechoic in gray scale displacement maps, and iso-elastic type colors with background parenchyma and fatty tissue or soft in VTIQ maps. In contrary, non-necrotic components of malignant lesions are encoded with more rigid

dense colors (In our cases, all the rigidity increases toward the red). Also, desmpolastic reaction created by malignant infiltration and ductal extension also could be defined by color or velocity maps as surrounding rigidity which extends beyond the gray scale tumoral margins (Figure 3). As well as these quantified measurements, semiquantitative assessment utilization such as color scale, ratio or index measurements in strain elastography has to be reduced gradually.

Fibrocystic changes and adenosis like hyperplastic changes that can create a premalign impression by mimicking the ductal carcinoma in situ (DCIS)’s usual appearance (Figure 4 and Figure 5). The separation of changes in the fibrocystic complex echo becomes important at this point. For these nonspecific lesions, when the lesional color pattern symbolizing the malignant degree of hardening than the surrounding normal breast tissue, BIRADS categorization will also be upgraded and rather than follow-up, planning for a biopsy will be more possible.

When a biopsy is required within the identified lesion area, the cyto-histopathological sample may be easily obtained with guidance of elastography, instead of using only gray scale images. This feature is not only typical for malignant like lesions, but also for suspicious natured BIRADS 3 lesions (Figure 6). Thus, planning of the medical or surgical treatment and complementary chemoradiotherapy can be performed from the beginning of the diagnostic stage of the disease. Fibrocystic changes starting from simple hyperplasia, adenosis, florid hyperplasia; continue with the flat epithelial atypia, atypical ductal hyperplasia and could terminate at least with a low-high grade DCIS spectrum. All these unfavorable course can be diagnosed with the help of the specific high

resolution colored SWV maps (as mentioned before, in our system it is called VTIQ) (Figure 7). With the new parameters imposed by elastography, the benign lesions such as degenerated fibroadenoma and papilloma which can mimic a malignant lesion, and the changes like fat necrosis and postoperative scar that concerning the operation area can be distinguished (Figure 8). In fact, before capturing the event called blind lesion in radiology, at the same time, after the identification of masses with malignant criteria, screening the other normal-looking quadrants can diagnose the iso echogenic DCIS, in some cases (Figure 9).

Furthermore, not only breast, but also for axillary lymph nodes, especially in the usual oval shape, SWV elastography has benefits in differential dignosis of benign or malignant lymphadenopathy with smooth-edged thin cortex and deterioration in the physiological hilar echo. Although there is not enough compatibility between studies about axillary and other lymphatic chains settled in the superficial lymph nodes, generally when cortical SWV values exceed the cut-off values, decision of biopsy can be given by evaluating also the other morphological findings together [39] [40] [41]. In our unit, for the lymph nodes which are thickened, nodularity gained or deleting the echo hilum of the cortex, SWV cut-off values are accepted meaningful >2.4 m/sec, in terms of malignancy.

Overall, the first produced softwares of strain elastography which were extremely operator-dependent forms, difficult to adjust the manual compression degree are almost out of general clinical use. Adjusting the compression by graphical data and efforts of semiquantifying this system with color index or strain ratio measurements through color scales has led to relatively successful results, by means of the new RTE methods. However, after the spread of SWE method, tissue stiffness become to be measured more comfortably with lesser

operator dependent, quantitative techniques. The stiffness values of SWV measurements are defined as m/s with the most commonly used ARFI system and as kPa with another one. Even though various and gradually renewed versions such as point shear wave, 2-D shear wave, 3-D shear wave; calculation of the microanatomical comppression deggree of tissue by a push-pulse mechanizm and measuring the shear-wave velocity during this push is the valid mechanism [42]. In malignant tissues, tighter cell groups and surrounding desmoplastic reaction leads to increase SWV, and at sizes exceeding a threshold value it is easier to recognize a lesion with benign morphology, such as mucinous carcinoma [43]. On the other hand, recognition of premalignant lesions like ductal carcinoma in-situ (DCIS) and to distinguish the solid lesions from complicated hypoechoic cysts are also facilitated [43] [44]. Therefore, because of the potential to reduce the false positive and/or false negative ultrasound evaluation rates of this method, a more accurate classification of various lesions in BIRADS categorization is feasible.

There are some limitations with this technique. Although quantitative elasticity information obtained by SWE has improved diagnostic performance, false results have been reported in 6.4% - 36.6% of cases, in which the imaging results did not correlate with the pathologic results [45]. Also not easily accessible for the moment, over time, it is specified to take its place among the standard equipment of manufacturers. Utilization principles may be adopted by the appropriate application and short-term experiences. However, it does not have a complicated algorithm and difficult learning curve in terms of different tissues have different characteristics. Overall, though the background resolution persists lower than normal gray scale floor, new developments day by day on this issue are carried out by hardware and software upgrades that are used, currently. Although the activity decreases in deep-seated lesions, generally beyond very large breasts there are not any problem in breast. On the other hand, because of the artifacts caused by reflected waves the activity reduces in the superficial lesions very closed to skin. This problem can be circumvented easily with a suitable gel-pad support. In addition, though various companies use different terminology but the general principles are the same, these small differences can be solved easily by the help of the manufacturer or literature support. It has shown in the literature that VTIQ is a highly reliable method concerning intra- and inter-examiner agreement.