Contrast-enhanced ultrasonography of cervical carcinoma: perfusion pattern and relationship with tumour angiogenesis

Abstract

Objective: This study aimed to investigate the use of contrast-enhanced ultrasonography (CEUS) and time-intensity curves to assess angiogenesis in cervical cancer.

Methods: 60 patients who were scheduled to undergo radical surgery for biopsy-proven cervical cancers underwent CEUS. Surgical tissue sections from 32 patients who did not receive neoadjuvant chemotherapy were analyzed with CD34 staining to estimate intratumoral microvessel density (MVD). CEUS images were analyzed for maximum intensity (IMAX), rise time (RT), time to peak (TTP) and mean transit time.

Results: Cervical lesions had a higher IMAX and shorter RT and TTP (p < 0.001) than reference regions. There was a linear association between the IMAX of the cervical lesion and the mean intratumoral MVD (r = 0.624, p < 0.001). There were no significant differences in CEUS variables according to histological type, grade and stage.

Conclusion: Quantitative CEUS variables have potential use for monitoring perfusion changes in tumours after non-surgical therapy for advanced cervical cancer.

Advances in knowledge: The article demonstrates the capability and value of quantitative CEUS as a non-invasive strategy for detecting the perfusion and angiogenic status of cervical cancer. Quantitative CEUS variables have potential use for monitoring tumour response to non-surgical therapy.

Figure 1.

Flow diagram for the study. CEUS, contrast-enhanced ultrasonography; MVD, microvessel density; US, ultrasound.

Figure 2.

Time–intensity curve (TIC) after bolus injection of contrast agent: the TIC of the analysis region of interest (ROI) (in green) and reference ROI (in yellow) are plotted according to video intensity and fitted with a mathematic equation model for bolus kinetics. The variables are calculated from the fitted model. IMAX, maximum intensity; RT, rise time; TTP, time to peak. For colour image see online.

Figure 3.

Cervical carcinoma in a 41-year-old female. (a) In the greyscale sonography image with an endovaginal probe, ultrasonography showed a hypoechoic lesion (arrows) in the cervix. (b) Colour Doppler flow imaging showed spotted intratumoral blood flow signals.

Figure 4.

Cervical carcinoma in a 58-year-old female. (a) In the greyscale sonography image, ultrasonography showed a 3.38 × 2.35-cm isoechoic lesion in the cervix. (b–d) Serial contrast-enhanced ultrasonography (CEUS) images of the same lesion (arrows) obtained at the same level. Cervical carcinoma showed hyperenhancement at 16 s in the arterial phase (b) hypoenhancement in the earlier and later venous phases (c, d). Dist. distance.

Figure 5.

Screenshot of SonoLiver (TomTec Imaging Systems, Unterschleissheim, Germany) contrast-enhanced ultrasonography (CEUS) in the arterial phase and time–intensity curves (TIC) of a cervical carcinoma fitted by the bolus perfusion model. (a) Native sequence of CEUS image. Three regions of interest (ROIs) were drawn: a square ROI delimiting the region where motion compensation was applied, a reference ROI (left oval) and an analysis ROI (right oval). (b) Output TIC for cervical cancer (in green) and myometrium (in yellow). CPS, contrast pulse sequencing. For colour image see online.

Figure 6.

Representative sections of cervical cancer immunohistochemically stained for CD34 (×200) (arrows).

Figure 7.

Scatter plot showing the relationship between maximum intensity (IMAX) and mean intratumoral microvessel density (MVD) in cervical lesions. IMAX increases as mean intratumoral MVD increases (r = 0.624, p < 0.001).