CEUS is currently a widely used diagnostic method allowing real-time evaluation of microvascular architecture. CEUS is mostly used to assess lesions of liver, kidneys and inflammatory bowel conditions. The possibility of incorporating CEUS into the diagnostic algorithm of breast lesions is still a subject of investigation. Malignant tumours in our study showed statistically significantly lower TTP parameters (sensitivity 77.6%, specificity 52.7%) and higher WIS values (sensitivity 74.6%, specificity 66.4%) than benign tumors. Enhancement degree also proved to be statistically well discriminating as 55.2% of malignant lesions had a rich vascularity (sensitivity 89.6% and specificity 48.6%). The combination of quantitative analysis parameters (TTP, WIS) with enhancement degree did not result in higher accuracy in distinguishing between malignant and benign breast lesions.
We expect that CEUS will become an effective tool in evaluation of breast lesions with unclear findings on conventional ultrasound, i.e. in distinguishing lesions BI-RADS category 3 and 4. Thus, CEUS may reduce the number of core-needle biopsies of benign lesions in the future. Compared to magnetic resonance, CEUS is a relatively easily accessible, fast and cost-effective method well-suited to become a part of the diagnostic algorithm of breast examination before biopsy.
Newly formed tumor blood vessels are different from normal capillaries, they are characterized by irregular shape, abnormal calibre, fenestrated endothelium and formation of perivascular spaces. All of these changes lead to different perfusion, increased permeability and deregulation [6,7,8]. The expression of vascular endothelial growth factor (VEGF) and its receptor belongs among prognostic factors for breast cancer together with the tumor size and histological grade [9,10,11]. Generally, we can expect higher perfusion of breast lesions compared to the surrounding tissue and different characteristics of perfusion parameters according to the aggressiveness of the tumor. This knowledge has already been employed in the evaluation of Breast MRI. The study by Ricci [12] compared the results of the CEUS and MRI examinations and described CEUS as a reliable method for differential diagnostic algorithm as CEUS shows typical enhancement characteristics of lesions including perfusion curves which are comparable with MRI TI curves. Differences between benign and malignant breast lesions can also be found in unenhanced Doppler ultrasound. In our study, we observed a rich vascularization in 19.2% of benign lesions and in 55.2% of malignant lesions, based on MVI technology assessment. In some cases, benign and malignant lesions differ in other characteristics such as perfusion homogeneity and the type of vascular supply. Qualitative analysis of CEUS of malignant lesions was studied by Cao [13], the authors also associate the following characteristics with malignancy: perfusion defect, penetrating blood vessels, heterogeneous enhancement and centripetal enhancement. They concluded that these parameters can predict breast cancer prognosis in vivo.
In our study, differences in vascular perfusion kinetics were demonstrated based on TI curves. Significantly lower TTP values and significantly higher WIS values were associated with malignant tumors. These findings can be explained by earlier and faster onset of enhancement of malignant lesions. A similar conclusion can be found in Szabo´s study [8] which focused only on CEUS characteristics of verified breast cancer and demonstrated earlier peak enhancement (analogical to TTP and WIS parameters) and faster elimination of microbubbles in more aggressive forms of cancer associated with a poor prognosis. These findings may be explained by high occurrence of arteriovenous shunts in malignant tumors [14,15]. In our study, evaluating the other qualitative (type of vascularization, perfusion homogeneity) and quantitative parameters (PI, AUC) did not significantly improve the ability to differentiate between benign and malignant lesions.
Qualitative, quantitative and combined analysis of CEUS of breast lesions was also studied by Wan et al [16]. Their results show better diagnostic performance of qualitative and combined analysis than quantitative analysis, despite the fact that quantitative analysis appears at first sight to be more reliable due to its objectivity.
When assessing breast lesions, it is necessary to base the assessment not only on the results from the CEUS examination but on the conventional B-mode imaging as well. This subject has been studied in Du´s work [17], which states that the combined use of conventional B-mode sonography and CEUS provides greater diagnostic efficacy than either of these methods alone. The sensitivity of the combined examination is 81.8% and the specificity is 78.6%, these results are comparable to those achieved with MR.
In order to interpret the findings accurately, the main limitations of CEUS need to be acknowledged. It is a very operator-dependent technique therefore an experienced operator is needed. Timing of the examination is important, because the onset of perfusion depends on cardiac output. Difficulty may be caused by the variation in the level of basal perfusion between individual mammary glands. There may be changes depending on menstrual cycle which have to be considered, as it is in magnetic resonance examinations. Caution must be taken when compressing the target area with a probe, the neo-vessels of tumors are usually fragile and easily compressible, stronger compression would in consequence devalue the results. An obvious limitation of two-dimensional CEUS perfusion imaging is the acquisition of information from a single slice of tissue. A different approach would have to be chosen to examine the whole lesion (for example, to assess only qualitative parameters of images and to move the probe slightly while recording a video-loop). Also, there is the possibility of three-dimensional perfusion imaging, which has already been studied with positive results in the Jia et al. study [5].
A deficiency of the quantitative analysis in our study is that we focused on the initial changes of perfusion of lesions when evaluating the time-intensity curve. The only parameter that partly reflected the character and type of perfusion in the later phases of examinations was the AUC (area under curve). The main reason is that the Qlab software does not automatically calculate the value of the parameter describing the decrease in perfusion (washout) from the curve. These values can be obtained manually after establishing the maximum intensity (PI), however, this evaluation was beyond the scope of our study at this time.