Value of perfusion characteristics evaluated by CEUS combined with STQ parameters in diagnosing the properties of SLN in breast cancer

Abstract

BACKGROUND:

Accurate sentinel lymph node (SLN) characterization is essential for breast cancer management, prompting advancements in imaging technologies such as contrast-enhanced ultrasound (CEUS) and sound touch quantification (STQ) to enhance diagnostic precision.

OBJECTIVE:

To explore the value of perfusion characteristics evaluated by CEUS combined with STQ parameters in diagnosing the properties of sentinel lymph node (SLN) in breast cancer.

METHODS:

A total of 91 breast cancer patients (91 SLNs) admitted to the hospital from February 2022 to December 2023 were selected for this study. Among them, 26 patients with metastatic SLN confirmed by surgery and pathology were included in the metastatic SLN group, and 65 patients with non-metastatic SLN were included in the non-metastatic SLN group. Preoperative examination results of CEUS and STQ were retrospectively analyzed. The diagnostic efficacy of perfusion characteristics evaluated by CEUS and STQ parameters for the properties of SLN in breast cancer was analyzed using the receiver operating characteristics (ROC) curve. Statistical methods such as chi-square tests and logistic regression analysis were employed to analyze the data.

RESULTS:

Enhancement patterns differed significantly between the metastatic SLN and non-metastatic SLN groups ( $p<$ 0.05). ROC curve analysis indicated that CEUS perfusion characteristics had an AUC value of 0.823 for diagnosing SLN properties, with a sensitivity of 84.62% and specificity of 70.77% using type I as the critical value. Additionally, STQ measurement showed significantly higher values in the metastatic SLN group (44.18 $\pm$ 6.53 kPa) compared to the non-metastatic SLN group (34.69 $\pm$ 6.81 kPa) ( $t=$ 6.075, $p<$ 0.001). The AUC value for STQ parameters in diagnosing metastatic SLN was 0.849, with a sensitivity of 73.08% and specificity of 92.31% using 42.40 kPa as the critical value. Though the AUC value of STQ measurement was higher than CEUS perfusion characteristics alone, the difference was not statistically significant ( $Z=$ 0.393, $p=$ 0.695). Moreover, combining CEUS perfusion characteristics with STQ parameters yielded an AUC value of 0.815 for diagnosing SLN properties, showing no significant difference compared to diagnosis with CEUS or STQ parameters alone ( $Z=$ 0.149, 0.516, $p=$ 0.882, 0.606).

CONCLUSION:

Combined use of perfusion characteristics evaluated by CEUS and STQ parameters can significantly improve the diagnostic specificity of SLN in breast cancer. It is worthy of clinical promotion.

Keywords

Breast cancer sentinel lymph node diagnosis contrast-enhanced ultrasound sound touch quantification

1. Introduction

Studies reveal that breast cancer affects 24.2% of women and leads to death in 11.6% of cases, posing a major risk to women’s health and lives [1]. The status of axillary lymph nodes is a crucial factor in evaluating the stage and prognosis of breast cancer patients. Sentinel lymph nodes (SLNs), which are the initial nodes to which cancer cells spread from a primary tumor, play a significant role in this assessment, are essential for clinical assessment and deciding the appropriate treatment strategies for patients. Therefore, preoperative diagnosis of SLN nature in breast cancer patients can not only determine the degree of tumor invasion but also assist in the accurate selection of surgical methods, which is of great significance for improving patient prognosis [2]. Currently, there are numerous imaging methods used for diagnosing SLN nature, and contrast-enhanced ultrasound (CEUS) is one of them. This method can compensate for the limitations of conventional ultrasound by increasing tissue contrast (through injection of contrast agents via different routes) to real-time display lesion structures, features, and morphologies [3]. In breast cancer, CEUS can provide detailed images of SLNs, allowing clinicians to distinguish between metastatic and non-metastatic nodes based on their perfusion patterns. The dynamic observation of blood flow and tissue perfusion using CEUS can help detect abnormalities indicative of cancer metastasis. Shear wave elastography quantification (STQ) is a new shear wave elastography technique that allows for quantitative and qualitative analysis of lesions [4], and it is currently widely used in liver diseases. STQ is particularly valuable because it complements CEUS by providing additional information about the mechanical properties of tissues, thereby enhancing diagnostic accuracy. There is limited research on the combined application of these two methods in diagnosing SLN nature in breast cancer. In order to provide patients with more targeted treatment and reduce surgical trauma, this study analyzes the value of CEUS perfusion characteristics combined with STQ quantitative parameters in diagnosing SLN nature in breast cancer.

2. Methods

The study was approved by the institutional review board of 363 Hospital and followed the ethical principles of the Declaration of Helsinki. All participants provided written informed consent before data collection began.

2.1 General information

This study included 91 sentinel lymph nodes (SLNs) from breast cancer patients treated between February 2022 and December 2023. The criteria for inclusion were: (1) adherence to the diagnostic criteria for breast cancer specified in the “Chinese Anti-Cancer Association Breast Cancer Diagnosis and Treatment Guidelines and Norms (2021 Edition)”; (2) having a single primary tumor; (3) being 18 years old or older; (4) no prior treatments related to breast cancer, such as radiotherapy, chemotherapy, or surgery before undergoing CEUS and STQ examinations; and (5) complete surgical pathology results that meet the study requirements. The exclusion criteria included: (1) having had previous chest wall surgery for other conditions; and (2) recent mastitis (within the last six months). Based on surgical pathology, the 91 cases (91 SLNs) were categorized into two groups: the metastatic SLN group ( $n=$ 26) and the non-metastatic SLN group ( $n=$ 65). In the metastatic SLN group, patients’ ages ranged from 27 to 77 years, with a mean age of 51.67 $\pm$ 9.71 years; the maximum diameter of primary lesions was $\leqslant$ 2 cm in 13 cases and 2–5 cm in 13 cases. In the non-metastatic SLN group, patients’ ages ranged from 26 to 75 years, with a mean age of 51.34 $\pm$ 9.57 years; the maximum diameter of primary lesions was $\leqslant$ 2 cm in 33 cases and 2–5 cm in 32 cases.

2.2 Acquisition method

Contrast-Enhanced Ultrasound (CEUS): A contrast agent (SonoVue, Bracco, Italy) was dissolved in 5 ml of 0.9% saline to create a suspension. Patients were positioned supine with their upper limbs abducted at right angles. The skin around the nipple was disinfected with iodine, and the SonoVue suspension was injected at the 3, 6, 9, and 12 o’clock positions around the nipple. Gentle massage was applied at the injection sites. Using an ultrasound diagnostic instrument (Mindray Resona 7PRO), the sentinel lymphatic vessel was scanned in dual imaging mode, and the first lymph node displayed was identified as the SLN. The position, size, and enhancement pattern of the SLN were recorded, and a mark was made on the patient’s body surface. The SLN enhancement patterns were scored based on the CEUS results: Type I (uniform enhancement) – 1 point, Type II (uneven enhancement with mixed high and low enhancement) – 2 points, Type III (central low or no enhancement, ring enhancement) – 3 points, and Type IV (overall weak or no enhancement) – 4 points.

Shear Wave Elastography: Patients were placed in a supine position with their hands raised to fully expose the breast. The SLN position was confirmed at the marked location on the body surface. The sample box size was adjusted to 1.5 cm $\times$ 1.0 cm, and the patient was instructed to hold their breath. The STQ function was activated to measure the elastic modulus value, with measurements repeated five times to obtain the average value (STQ measurement). These procedures were carried out by two ultrasound physicians, each with over 10 years of experience in breast examinations.

2.3 Statistical analysis

Data were analyzed using the Statistical Package for Social Science (SPSS) 28.0 (IBM, Armonk, NY, USA). Descriptive statistics for continuous data were expressed as mean $\pm$ standard deviation (SD), summarizing the central tendency and variability of the data. Categorical data were presented as frequency (percentage), highlighting the proportions within the dataset. For inferential statistics, $t$ -tests were employed to compare the means of continuous variables between the metastatic and non-metastatic SLN groups, which is suitable for normally distributed data to determine statistical significance. The Mann-Whitney U Test was used for non-normally distributed continuous variables or ordinal data, appropriate when the data do not meet the assumptions for a $t$ -test. The Chi-Square Test compared categorical variables between the groups, evaluating the association between two categorical variables and checking if observed frequencies significantly differ from expected ones.

Diagnostic efficacy was assessed using Receiver Operating Characteristic (ROC) Curve Analysis, with the area under the curve (AUC) measuring overall diagnostic accuracy; an AUC closer to 1 indicates superior diagnostic performance. DeLong’s test, a non-parametric method, was used to compare the AUCs of CEUS, STQ, and their combination, ensuring statistical validation of differences in diagnostic performance. The significance level for all tests was set at $\alpha<$ 0.05, meaning results with a $p$ -value below 0.05 were considered statistically significant, balancing the risks of Type I and Type II errors.

3. Results

3.1 Diagnostic value of CEUS perfusion characteristics for SLN nature

The comparison between the metastatic SLN group and the non-metastatic SLN group revealed a statistically significant difference in enhancement patterns ( $p<$ 0.05). ROC curve analysis, using the gold standard, demonstrated an AUC value of 0.823 for CEUS perfusion characteristics in diagnosing the nature of SLNs. With a threshold of $>$ Type I, the sensitivity and specificity for diagnosing metastatic SLNs were 84.62% and 70.77%, respectively (refer to Tables 1 and 2, and Fig. 1).

Table 1
Comparison of CEUS perfusion characteristics between the two groups (cases, %)

SLN nature	Cases	Type I	Type II	Type III	Type IV
Metastatic SLN group	26	4 (15.38)	7 (26.92)	9 (34.62)	6 (23.08)
Non-metastatic SLN group	65	46 (70.77)	11 (16.92)	8 (12.31)	0 (0.00)
$Z$		28.122
$p$		$<$ 0.001

Table 2

Diagnostic efficacy of STQ quantitative parameters for breast cancer SLN nature

Indicator	AUC value	95% CI (lower limit)	95% CI (upper limit)	Cut-off value	Sensitivity (%)	Specificity (%)	Youden index
CEUS	0.823	0.729	0.895	6.714 $<$ 0.001	84.62	70.77	0.554
STQ	0.849	0.748	0.949	42.40 kPa	73.08	92.31	0.654
STQ^*	0.815	0.731	0.899	–	100.00	63.08	0.631

^*Note: Combined diagnostic criteria: CEUS perfusion characteristics with enhancement patterns of type II $\sim$ IV or STQ measurements $>$ 42.40 kPa indicate metastatic SLN; otherwise, it indicates non-metastatic SLN.

Figure 1.

ROC curves for CEUS perfusion characteristics, STQ quantitative parameters, and combined diagnosis of breast cancer SLN nature.

3.2 Diagnostic value of STQ quantitative parameters for SLN nature

The STQ measurement in the metastatic SLN group was (44.18 $\pm$ 6.53) kPa, significantly higher than that in the non-metastatic SLN group (34.69 $\pm$ 6.81) kPa, with a statistically significant difference ( $t=$ 6.075, $p<$ 0.001). Using the gold standard, the ROC curve showed an AUC value of 0.849 for STQ quantitative parameters in diagnosing breast cancer SLN nature. Using $>$ 42.40 kPa as the threshold, the sensitivity and specificity of STQ quantitative parameters for diagnosing metastatic SLN were 73.08% and 92.31%, respectively (Table 2, Fig. 1).

3.3 Diagnostic efficacy of combined CEUS perfusion characteristics and STQ quantitative parameters for breast cancer SLN nature

When diagnosing with CEUS perfusion characteristics and STQ quantitative parameters, the AUC value of STQ measurements was higher than that of CEUS perfusion characteristics ( $Z=$ 0.393, $p=$ 0.695). Using the gold standard, the ROC curve showed that the AUC value for the combined diagnosis of breast cancer SLN nature was 0.815, no significant difference compared to the diagnosis using single CEUS perfusion characteristics or STQ quantitative parameters ( $Z=$ 0.149, 0.516; $P=$ 0.882, 0.606), respectively (see Table 2, Fig. 1).

4. Discussion

Breast cancer is among the most prevalent malignancies affecting women globally, with rising incidence and mortality rates. Enhancing diagnostic techniques for sentinel lymph nodes (SLNs) facilitates earlier and more precise assessment of breast cancer patients, subsequently guiding treatment strategies, improving patient prognosis, and alleviating the healthcare system’s burden. The status of axillary lymph node metastasis greatly influences the surgical approach for breast cancer patients. Patients without axillary lymph node metastasis may avoid axillary lymph node dissection, thereby potentially reducing limb complications to some extent [5]. However, failing to detect axillary lymph node metastasis can significantly impact long-term survival rates [6]. As the initial site of lymph node metastasis, the SLN provides vital insights into axillary lymph node metastasis [7].

Clinical methods for differentiating SLN metastasis mainly include dye and nuclear medicine techniques [8]. The dye method can cause allergic reactions [9], while the nuclear medicine approach involves radiation exposure and is costly [10], limiting its widespread clinical use. Advancements in ultrasound technology have led to increased clinical application of contrast-enhanced ultrasound (CEUS) and elastography. CEUS offers real-time visualization of lesion perfusion patterns using contrast agents [11], and elastography measures lesion hardness through shear wave quantitative parameters [12]. The combined effectiveness of these methods in assessing the nature of breast cancer SLNs requires further investigation [13]. Our study aims to find the value of combining CEUS perfusion characteristics with shear wave quantitative parameters (STQ) to determine the nature of breast cancer SLNs.

The results showed that out of 91 breast cancer patients, 26 had metastatic SLN, while 65 had non-metastatic SLN. In the metastatic SLN group, 84.62% of patients exhibited type II, III, or IV contrast-enhanced patterns, in contrast to the non-metastatic SLN group, where 70.77% displayed type I contrast enhancement. The uneven enhancement of SLNs may be attributed to local tumor infiltration causing filling defects. Central low or no enhancement and peripheral ring enhancement may indicate that tumor cells are associated with the surrounding lymphatic tissue, leading to the formation of new blood vessels. In contrast, overall weak or no enhancement suggests that tumor cell infiltration blocks lymphatic vessels and lymphoid tissue, preventing the contrast agent from entering [14].

CEUS perfusion characteristics in diagnosing breast cancer SLN nature revealed an AUC value of 0.823, with a sensitivity of 84.62% and a specificity of 70.77% [15]. Despite its high sensitivity, CEUS has limitations due to its relatively low specificity. In contrast, the STQ measurement for the metastatic SLN group significantly exceeded that for the non-metastatic SLN group, achieving an AUC value of 0.849, with a sensitivity of 73.08% and a specificity of 92.31%. The higher diagnostic specificity of STQ may be attributed to its quantitative detection of tissue elastic modulus values using shear wave signals, which reflect macroscopic information related to SLN, such as protein and molecular changes [16]. Although the AUC value for STQ was higher than that for CEUS, the difference was not statistically significant. STQ, as an elastic shear wave imaging technology, is susceptible to individual factors like patient respiration and obesity, leading to biased diagnostic results compared to pathological outcomes. CEUS exhibits high sensitivity but low specificity, whereas STQ shows high specificity but lower sensitivity. Therefore, this study combined both methods to diagnose breast cancer SLN nature. The results demonstrated that the combined diagnostic AUC value was 0.815, with significantly increased diagnostic sensitivity. This suggests that combining CEUS perfusion characteristics with STQ quantitative parameters can enhance the sensitivity of detecting SLN metastasis, reducing clinical misdiagnosis [17]. CEUS allows dynamic observation of the injection site and SLN perfusion patterns by injecting contrast agents around the lesion, aiding in lymphatic duct and SLN imaging [18]. Meanwhile, STQ uses domain scanning technology with strong penetration and rapid imaging speed. The two methods complement each other, thus reducing the likelihood of misdiagnosis. However, there was no statistically significant difference between the combined method and the individual use of CEUS perfusion characteristics or STQ quantitative parameters. Clinicians should select the most suitable diagnostic method based on patient-specific conditions and medical practices. Moreover, this study was based on a small sample size, necessitating further analysis with larger sample sizes and multi-center trials to validate the results.

The results revealed that among 91 breast cancer patients, 26 had metastatic SLN, while the remaining 65 had non-metastatic SLN. In the metastatic SLN group, 84.62% of patients exhibited type II, III, or IV contrast-enhanced patterns, compared to 70.77% in the non-metastatic SLN group, which displayed type I contrast enhancement. The uneven enhancement of SLN may be related to local tumor infiltration and the resulting defects in filling. Central low or no enhancement and peripheral ring enhancement may indicate tumor cell association with surrounding lymphatic tissue, leading to the formation of new blood vessels, while overall weak or no enhancement suggests tumor cell infiltration, causing lymphatic vessel and lymphoid tissue blockage, which prevents contrast agent entry. Our findings align with previous studies demonstrating the utility of CEUS in differentiating between metastatic and non-metastatic SLNs. For instance, Liu et al. (2023) reported an AUC value of 0.823 for CEUS in diagnosing SLN metastasis in breast cancer, which is consistent with our study’s AUC value of 0.823. Similarly, Zhao et al. (2018) found that CEUS provides high sensitivity for detecting SLN metastasis, though with moderate specificity.

In summary, the combination of CEUS perfusion characteristics with STQ quantitative parameters significantly enhances the diagnostic specificity of breast cancer SLN nature and demonstrates good diagnostic efficacy, which can be applied for clinical promotion.

5. Conclusion

The combination of CEUS perfusion characteristics with STQ quantitative parameters significantly enhances the diagnostic specificity of breast cancer SLN nature and demonstrates good diagnostic efficacy. This combined approach has the potential for clinical promotion. Further research with larger sample sizes and multi-center trials is necessary to confirm these findings and optimize diagnostic protocols for clinical use.

Footnotes

Conflict of interest

The authors declared no conflict of interest.

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Value of perfusion characteristics evaluated by CEUS combined with STQ parameters in diagnosing the properties of SLN in breast cancer

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

2. Methods

2.1 General information

2.2 Acquisition method

2.3 Statistical analysis

3. Results

3.1 Diagnostic value of CEUS perfusion characteristics for SLN nature

Table 1 Comparison of CEUS perfusion characteristics between the two groups (cases, %)

3.3 Diagnostic efficacy of combined CEUS perfusion characteristics and STQ quantitative parameters for breast cancer SLN nature

4. Discussion

5. Conclusion

Footnotes

Conflict of interest

References

Table 1
Comparison of CEUS perfusion characteristics between the two groups (cases, %)