Contrast-enhanced ultrasound for the preoperative assessment of laryngeal carcinoma: a preliminary study

Abstract

Background

Contrast-enhanced ultrasound (CEUS) is considered an attractive imaging technique to evaluate tumor microcirculation. However, the validity of CEUS for assessing laryngeal carcinoma is unclear.

Purpose

To compare the performance of CEUS with conventional US and contrast-enhanced computed tomography (CECT) in the diagnosis and preoperative T-staging of laryngeal carcinoma.

Material and Methods

Forty-one consecutive patients with laryngeal carcinoma underwent conventional high-frequency US, CEUS, and CECT before surgery. The CEUS characteristics of laryngeal carcinoma were recorded. The imaging findings of CEUS and conventional US were compared with CECT findings and the postoperative pathological examination.

Results

CEUS showed hyperenhancement in 38 cases and isoenhancement in three cases. Homogeneous distribution of contrast agent was found in 20 cases and heterogeneous distribution in 21 cases, of which 16 cases showed local perfusion defects. In the enhanced phase, rapid entry was observed in 37 cases, synchronous entry was observed in two cases, and slow entry was observed in two cases. Rapid exit was observed in 25 cases and slow exit was observed in 16 cases. The pretherapeutic T-staging accuracy was not significantly different between conventional US, CEUS, and CECT (P ≥ 0.500). A high sensitivity and specificity were achieved by CEUS in the evaluation of involvement of thyroid cartilage.

Conclusion

Compared with conventional US and CECT, CEUS has a reliable initial T-staging accuracy and diagnostic properties for detecting laryngeal cartilage invasion.

Keywords

Contrast-enhanced ultrasound contrast-enhanced computed tomography laryngeal carcinoma tumor staging

Introduction

Laryngeal carcinoma is one of the most common malignant tumors of the head and neck, accounting for approximately 25% of malignant head and neck tumors (1). Because the larynx has important functions, such as phonation and breathing, accurate preoperative Tumor–Node–Metastasis (TNM) staging is the primary reference for the selection of surgical, radiotherapy, and/or chemotherapy treatment strategies, and is an important factor for predicting therapeutic efficacy in patients with laryngeal carcinoma.

High-frequency ultrasound (US) is the preferred imaging modality for examining the superficial tissue of the head and neck, such as the thyroid and cervical lymph nodes. Previous studies (2) have suggested that high-frequency sonography can reveal important structures, such as vocal cords and false vocal cords, in the larynx. Bozzato et al. (3) reported that although thyroid cartilage has a certain degree of ossification, the majority of laryngeal lesions are clearly visualized by US. Previous studies have confirmed that US can accurately determine the location of laryngeal cancer and provide important information, including submucosal, paraglottic space, laryngeal cartilage, and extralaryngeal involvement (4,5). There was no significant difference in the accuracy of preoperative T-staging for laryngeal carcinoma between conventional US and magnetic resonance imaging (MRI) or enhanced computed tomography (CT). The most significant advantage of US is that it can observe and evaluate the movement of vocal cords in real time and provide an important reference for the accurate preoperative T-staging of laryngeal cancer.

Contrast-enhanced ultrasound (CEUS) is a promising non-invasive technique that can more intuitively and efficiently reveal the blood supply or perfusion characteristics of tumors. CEUS has been widely used to distinguish between benign and malignant lesions in the breast, thyroid, liver, and other organs, and it has also been used to monitor tumor response after neoadjuvant chemotherapy and to evaluate the effect of radiofrequency or microwave ablation (6 –11). However, there was no report on the assessment of laryngeal cancer by CEUS. The international guidelines regarding the use of CEUS still do not take into consideration the use of CEUS for the study of the larynx. Thus, the aim of the present study was to investigate the value of CEUS in the diagnosis and preoperative T staging of laryngeal carcinoma compared with conventional US, contrast-enhanced CT (CECT), and pathological findings.

Material and Methods

Patients

The study was performed with the approval of the Institutional Review Board of the hospital and informed consent was obtained from all participants (IRB No. KYLC-2013-01). Forty-one consecutive male patients (median age = 61 years, age range = 42–84 years) with laryngeal cancer were enrolled in the study between April 2013 and January 2019. The inclusion criteria included the following: (i) confirmation by laryngoscopic biopsy; and (ii) no history of previous laryngeal surgery, radiotherapy, or chemotherapy. Before surgery, conventional US, CEUS, and CECT were performed in all patients. During the subsequent week, 30 patients underwent total or partial laryngectomy, seven patients underwent laryngoscopic laser resection, and four patients received radiotherapy or radio-chemotherapy treatment.

Conventional US technique

Conventional US and CEUS examinations were performed using a GE Logiq E9 ultrasound system (GE Healthcare Life Sciences, Chicago, IL, USA) with a 6–15 MHz linear transducer. The patients were in the supine position with the neck extended. US images were acquired from the base of the tongue to the trachea (Fig. 1). The larynx and surrounding structures were screened in longitudinal, transverse, and oblique sections. Tumor location, size, boundaries, shape, and infiltration to pre-epiglottic space, paraglottic space, laryngeal cartilage, and adjacent tissue (thyroid, extralaryngeal soft tissue, etc.) were recorded.

Fig. 1.

Normal sonograms of the larynx of a 22-year-old woman. (a) Transverse sonogram at the base of the tongue. (b) Transverse sonogram at the hyoid level (hollow arrows). Transverse sonograms of abducted (c) and adducted (d) status of false vocal cords (black asterisk). The false vocal cord appears hyperechoic and symmetrically stretches from the thyroid cartilage to the triangular-shaped hypoechoic arytenoid cartilage (triangle arrowheads). Posterior hypoechoic structure is the cricoid lamina (arrows). Transverse sonograms of abducted (e) and adducted (f) status of the vocal cords (white asterisk). The vocal cord appears hypoechoic and lies inferior to the false vocal cord. (g) Transverse sonogram at the cricoid cartilage level (thin arrows). (h) Longitudinal sonogram of the larynx. The laryngeal ventricle is the cavity between the false vocal cord (black asterisk) and true vocal cord (white asterisk) and contains some hyperechoic air.

Vocal cord mobility was observed with additional maneuvers during breath-holding or phonation of “E.” Generally, vocal cords were inverse V-shaped, paired structures that appeared hypoechoic, and false vocal cords were located immediately above the vocal cords and appeared as hyperechoic on the ultrasonogram. The vocal cords and false vocal cords abduct symmetrically during quiet breathing, and adduct to the midline during breath-holding (Fig. 1). Fixation of the vocal cord was determined when the vocal cord and arytenoid cartilages had an immobile or fixed status during breath holding or phonation maneuvers.

CEUS examination

After conventional US examination, the conditions were switched to CEUS mode with a frequency of 9 MHz and a mechanical index (MI) of 0.08. The contrast agent used in the present study was one dose of lyophilized SonoVue powder (Bracco SpA, Milan, Italy) mixed with 5 mL of 0.9% sodium chloride solution, and gently shaken into a microbubble suspension. The patients were told to avoid swallowing movements, and ultrasonic sections were selected in the area that exhibited the largest size or most abundant blood supply of the tumors. A bolus of 2.0 mL of contrast agent was injected quickly via the superficial vein of the elbow, and immediately followed by a flush of 5 mL saline. Simultaneously, dynamic perfusion of the tumor was observed and recorded in the machine’s hard drive for approximately 3 min. If necessary, patients with suspected laryngeal cartilage involvement were reinjected with SonoVue for a secondary contrast examination. To avoid the effects of residual microbubbles on image analysis, the interval between two contrast examinations was ≥8 min.

CECT scanning

CT examinations were performed using a Philips Brilliance iCT scanner (Philips Healthcare, Best, The Netherlands) with the following parameters: 120 kVp; 200 mAs; collimation = 128 × 0.625 mm; field of view = 180 mm; and matrix = 512 × 512. During scanning, the patients were instructed to breathe quietly and to refrain from coughing or swallowing. Axial slices were oriented parallel to the plane of the true vocal cords from the skull base to the bottom of the neck. Contrast-enhanced images were acquired with a 60-s delay after intravenous administration of 60 mL of Iopromide (Ultravist 300; Bayer Schering Pharma AG, Berlin, Germany) at a rate of 5 mL/s followed by a 30-mL saline flush. Images were reconstructed for axial, sagittal, and coronal sections, with a slice thickness of 1 mm in the axial plane and 3 mm in the sagittal and coronal planes.

Image analysis

Conventional US and CEUS examinations and image analyses were performed by two radiologists (with >5 years of experience in head and neck US and CEUS). They were blinded to the clinical information and the results of the corresponding CECT findings of the patients. In cases of discrepancies, the two reviewers reanalyzed and discussed together to reach a consensus.

CECT findings were interpreted by consensus by another two head and neck radiologists (with >10 years of experience in head and neck radiology). They were blinded to the clinical information and the results of the corresponding US or CEUS findings of the patients.

The enhanced features of laryngeal cancer were compared with the surrounding normal tissues: (i) according to the enhanced intensity at the peak, the lesions were divided into hyperenhancement, isoenhancement, and hypoenhancement; (ii) according to the evenness of contrast agent distribution, the lesions were divided into homogeneous enhancement and heterogeneous enhancement; (iii) rapid entry, synchronous entry, and slow entry were defined as the enhancement of the lesion that appears earlier, at the same time as, or later than the peritumoral tissue, respectively; and (iv) rapid exit, synchronous exit, and slow exit were defined according to the fading of contrast agent in the lesion as faster than, equal to, or slower than the peritumoral tissue, respectively.

The determination of the extent of tumor invasion refers to the recommended criteria described in previous studies (5,12,13). Supraglottic invasion was demonstrated by the involvement of the laryngeal ventricle or more superiorly to the epiglottis. Subglottic spread was defined as tumor infiltration >1 cm below the vocal cords. Invasion of pre-epiglottic and paraglottic space was considered when the hyperechoic fatty tissue replaced with a hypoechoic tumor. Laryngeal cartilage invasion is manifested as the interruption of the continuity of a linear intense echo of the internal or external surface of normal laryngeal cartilage. Erosion of thyroid cartilage was defined as invasion beyond the inner cortex without reaching the outer cortex, and penetration of thyroid cartilage was defined as involvement of both inner and outer layer of thyroid lamina (14).

T-staging of laryngeal cancer was determined according to the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) 7th Edition guidelines (15,16). The mobility of the vocal cords assessing by ultrasonography was compared with the laryngoscopic findings.

Statistical analysis

SPSS 17.0 (SPSS Inc, Chicago, IL, USA) statistical software package was used in this study. McNemar’s test was used to analyze the accuracy of sonography in the assessment of vocal cord mobility and to compare the tumor detection rate, the T staging diagnostic properties, and the sensitivity, specificity, and accuracy of conventional US, CEUS, and CECT in the evaluation of laryngeal cartilage involvement. P < 0.05 was considered statistically significant.

Results

All 41 tumors were proven squamous cell carcinomas with different degrees of differentiation. Based the tumor location, there were nine cases of supraglottic carcinoma, 26 cases of glottic carcinoma, two cases of subglottic carcinoma, and four cases of transglottic carcinoma. Final T-staging was as follows: eight cases were classified as stage T1; 10 cases as stage T2; 12 cases as stage T3; and 11 cases as stage T4. In the 30 patients who underwent surgical resection, laryngeal cartilage involvement was included: 14 cases of thyroid cartilage invasion; four cases of cricoid cartilage invasion; and 11 cases of arytenoid cartilage invasion.

Both conventional US and CEUS identified the majority (40/41, 97.6%) of laryngeal carcinomas; only one case of stage T1 vocal cord cancer with a diameter of approximately 5 mm was missed. Laryngeal carcinoma in conventional US presented as a hypoechoic mass with irregular shape. Due to the presence of strong echogenic gas in the laryngeal cavity, the boundary of the hypoechoic tumor was often clear. Color Doppler showed a dot or rod-like blood flow signal within and around the tumor (Fig. 2).

Fig. 2.

A 66-year-old man with stage T1 glottic carcinoma. (a) Conventional grayscale sonography showing a hypoechoic tumor in the right vocal cord (arrowheads). (b) Color Doppler in the same section revealed a small amount of dotted blood flow signal within the tumor. (c) On axial contrast-enhanced computed tomography, the right-sided glottic tumor is slightly enhanced (hollow arrowhead).

On conventional US, two cases of stage T2 laryngeal cancer were underestimated as stage T1, one case of stage T1 cancer was overestimated as stage T2, one case of stage T3 cancer was underestimated as stage T2 due to the false-negative assessment of retrolaryngeal subsite involvement, and two cases of stage T3 cancer were overestimated as stage T4 due to false-positive judgment of thyroid cartilage destruction. For the assessment of vocal cord mobility, sonography had an accuracy rate of 87.8% (36/41 cases); no significant difference was found in this regard between sonography and laryngoscopy (P = 0.375).

On CEUS, one case of stage T1 laryngeal carcinoma was overestimated as stage T2, one case of stage T2 was underestimated as stage T1, one case of stage T3 tumor was underestimated as stage T2, and one case of stage T3 tumor was overestimated as stage T4. CEUS showed hyperenhancement in 38 cases and isoenhancement in three cases. Homogeneous distribution of contrast agent was found in 20 cases and heterogeneous distribution in 21 cases, of which 16 cases showed local perfusion defects. In the enhanced phase, rapid entry was observed in 37 cases, synchronous entry was observed in two cases, and slow entry was observed in two cases. Rapid exit was observed in 25 cases and slow exit in 16 cases (Table 1).

Table 1.

Contrast-enhanced ultrasound features of laryngeal carcinoma.

Parameters	n
Enhanced intensity
Hyperenhancement	38
Isoenhancement	3
Hypoenhancement	0
Enhanced evenness
Homogeneous	20
Heterogeneous	21
Enhanced phase
Rapid entry	37
Synchronous entry	2
Slow entry	2
Fading phase
Rapid exit	25
Equal exit	0
Slow exit	16

On CECT, all of the tumors (100%) were identified. The detection rate was not statistically significantly between CECT and US/CEUS (P = 1.000). Two cases of stage T2 were underestimated as stage T1, one case of stage T4 was underestimated as T3 due to the false-negative assessment of neoplastic infiltration of the thyroid cartilage, and one case of T2 tumor was overestimated as stage T3 due to the false-positive assessment of the paraglottic space involvement. The pretherapeutic T-staging accuracy was not significantly different, with an accuracy of 82.9% for conventional US, 87.8% for CEUS, and 90.2% for CECT, respectively (P ≥ 0.500, Table 2).

Table 2.

Comparison of T-staging between conventional US, CEUE and CECT in laryngeal carcinoma.*

Modality	Confirmed (n)	Over-stage (n)	Under-stage (n)	Misdiagnosis (n)	Accuracy (%)
Conventional US	34	3	3	1	82.9
CEUS	36	2	2	1	87.8
CECT	37	1	3	0	90.2

*The T-staging accuracy was not significantly different with US, CEUS. and CECT.

CECT, contrast-enhanced computed tomography; CEUS, contrast-enhanced ultrasound.

The diagnostic properties of conventional US, CEUS, and CECT for detecting cartilage invasion are summarized in Table 3. There were no statistical differences between these three modalities (Figs. 3 and 4). CEUS detected one case of arytenoid cartilage invasion and one case of thyroid cartilage erosion that were misdiagnosed by conventional US and corrected two cases of false-positive results of thyroid cartilage destruction by conventional US. A high sensitivity and specificity were achieved by CEUS in the evaluation of involvement of thyroid cartilage. The sensitivity, specificity, and accuracy in the detection of thyroid cartilage involvement were 85.7%, 75.0%, and 80.0% for conventional US, 92.9%, 87.5%, and 90.0% for CEUS, and 78.6%, 87.5%, and 83.3% for CECT, respectively (P ≥ 0.250).

Table 3.

Comparison of cartilage involvement between conventional US, CEUS, and CECT.*

	n	TP	TN	FP	FN	Sensitivity (%)	Specificity (%)	Accuracy (%)
Thyroid cartilage
Conventional US	30	12	12	4	2	85.7	75.0	80.0
CEUS	30	13	14	2	1	92.9	87.5	90.0
CECT	30	11	14	2	3	78.6	87.5	83.3
Arytenoid cartilage
Conventional US	30	9	16	3	2	81.8	84.2	83.3
CEUS	30	10	17	2	1	90.9	89.4	90.0
CECT	30	10	18	1	1	90.9	94.7	93.3
Cricoid cartilage
Conventional US	30	3	23	3	1	75.0	88.5	86.7
CEUS	30	3	23	3	1	75.0	88.5	86.7
CECT	30	3	25	1	1	75.0	96.2	93.3

*The diagnostic properties were not significantly different between these three modalities in detecting cartilage invasion.

CECT, contrast-enhanced computed tomography; CEUS, contrast-enhanced ultrasound; FN, false-negative findings; FP, false-positive findings; TN, true-negative findings; TP, true-positive findings.

Fig. 3.

A 64-year-old man with stage T4 transglottic carcinoma. (a) Conventional US at the glottic level showing that the right-sided hypoechoic tumor (asterisk) infiltrated the right thyroid cartilage (arrows). The right arytenoid cartilage has been replaced with the hypoechoic tumor, suggesting that the arytenoid cartilage has been invaded. (b) CEUS showing a hyperenhancement feature with local perfusion defect in the tumor. The middle part of the right-side thyroid cartilage is replaced by the hyperenhanced tumor, suggesting that the thyroid cartilage has been invaded (arrowheads). (c) Time-intensity curve of CEUS demonstrates rapid entry in the enhanced phase and rapid exit in the fading phase. (d) Axial CECT image obtained from the same patient showing that the right thyroid cartilage (hollow arrow) is invaded by the tumor (hollow asterisk). CECT, contrast-enhanced computed tomography; CEUS, contrast-enhanced ultrasound.

Fig. 4.

An 83-year-old man with stage T4 glottic carcinoma. (a) Conventional US at the glottic level showing that the bilateral hypoechoic tumor (asterisks) disrupted the anterior thyroid cartilage (arrows). (b) CEUS showing a hyperenhancement feature in the tumor. The anterior thyroid cartilage is invaded by the hyperenhanced tumor (arrow). (c) Axial CECT image obtained from the same patient corresponding to the conventional US and CEUS findings that the anterior thyroid cartilage (arrow) is infiltrated by the hyperintense tumor (hollow asterisk). (d) Conventional US at the cricoid cartilage level showing that the right cricoid cartilage has been replaced with the hypoechoic tumor, suggesting that the cricoid cartilage has been invaded (arrowheads). (e) CEUS showing that the right-side cricoid cartilage is infiltrated by the hyperenhanced tumor (arrowheads). (f) Axial CECT corresponding to the sonographic findings show that the right-side cricoid cartilage is invaded by the tumor (arrowheads). CECT, contrast-enhanced computed tomography; CEUS, contrast-enhanced ultrasound.

Discussion

In the present study, both conventional US and CEUS yielded promising results for the detecting of laryngeal neoplasms. Of the laryngeal cancers, 40/41 (97.6%) were detected by ultrasonography, even in male adults with different ossification of thyroid cartilage. Previous evidence has shown that 50.0% or less calcification occurs in 40.0% of male patients, which makes it possible for the satisfactory examination of the laryngeal structures (17). Furthermore, the thyrohyoid membrane and cricothyroid membrane can be acoustic windows for laryngeal sonography (5). One of the advantages of US is that it can assess vocal cord mobility in real time. This feature appears to be even more important when a large tumor obstructs the supraglottic region and the vocal cord cannot be displayed adequately by laryngoscopy. Vocal cord mobility is a key part of tumor staging and is included in the ultrasonic T-staging of the present study. In the present study, US/CEUS correctly identifies four cases with impaired or fixation of the vocal cord that CT did not. US/CEUS had an accuracy rate of 87.8% (36/41 cases) for the assessment vocal cord mobility. This finding was consistent with a previous study in which sonography had a sensitivity of 83.3% and a specificity of 100.0% for the identification of larynx fixation (5).

Invasion of laryngeal cartilage is a key factor affecting the treatment strategy, prognosis, and response to radiotherapy (18). Once cartilage invasion occurs, it often becomes a contraindication for partial laryngectomy and radiotherapy, and the probability of tumor recurrence increases accordingly. Rothberg et al. (19) reported that sonography was superior to routine CT in the evaluation of cartilage invasion. In a study by Rzepakowska et al. (4), the sensitivity of ultrasound for laryngeal cartilage invasion was 75% and the specificity was 88.9%. Consistent with previous reports (4,5), both conventional US and CEUS showed a reliable diagnostic value for evaluating of cartilage invasion in the present study. Due to the non-enhancement of normal laryngeal cartilage in CEUS, which is obviously different from the hyperenhancement of laryngeal carcinoma, CEUS can more clearly reveal the continuous integrity of the inner and outer surface of laryngeal cartilage (Fig. 5). A high sensitivity and specificity were achieved by CEUS in the evaluation of involvement of thyroid cartilage. The sensitivity, specificity, and accuracy in the detection of thyroid cartilage involvement were 85.7%, 75.0%, and 80.0% for conventional US, 92.9%, 87.5%, and 90.0% for CEUS, and 78.6%, 87.5%, and 83.3% for CECT, respectively. One case of arytenoid cartilage invasion and one case of thyroid cartilage erosion were false-negatives by conventional US, and two cases of thyroid cartilage destruction were false-positives on conventional US; however, these cases were correctly diagnosed by CEUS. However, due to the relatively small number of patients included, the diagnostic properties of detecting laryngeal cartilage invasion were not significantly different between conventional US and CEUS in the present study (P ≥ 0.250).

Fig. 5.

A 68-year-old man with stage T2 glottic carcinoma. (a) Transverse sonogram at the glottis level showing a hypoechoic mass in the right vocal cord. The arytenoid cartilage is legible without involvement (hollow arrowheads). The anterior of the right-side thyroid cartilage is suspected of tumor involvement (arrows). (b) CEUS showing the anterior of right-side thyroid cartilage (arrowheads) is hypoenhanced, and the inner and outer surface of laryngeal cartilage is integrated. (c) Axial CECT image obtained from the same patient corresponding to the CEUS findings that the thyroid cartilage (hollow arrow) and arytenoid cartilage (black hollow arrowhead) are continuous without invasion. CECT, contrast-enhanced computed tomography; CEUS, contrast-enhanced ultrasound.

Tumor angiogenesis is not only the essential foundation for the proliferation and growth of primary tumor cells, but it is also a necessary condition for tumor invasion and metastasis (20). Previous evidence has suggested that angiogenesis is closely associated with the microvessel density (MVD) of tissue and the clinical aggressiveness of the tumor (21). High MVD is associated with metastasis, recurrence, and poorer five-year survival in head and neck squamous cell carcinoma (22,23). CEUS has advantages in that it is non-invasive and simple to perform; it can enhance the sensitivity of conventional US to detect low-speed blood flow signals, enhance the echo signal intensity of the lesions, and improve the quality of sonographic images. The basic principle of CEUS is the use of the velocity and dose of the contrast agent microbubbles that reach the tissue to reflect the microcirculatory perfusion of the lesion. Mori et al. (24) reported that the enhancement area ratios in both peak and delayed phases in advanced breast cancer were highly significantly correlated with tumor MVD. The results of Guo et al. (25) indicated that the time-intensity curve parameters of CEUS could reflect the MVD of bladder urothelial carcinomas and help to evaluate tumor angiogenesis. The CEUS of laryngeal carcinoma is mainly characterized by rapid and hyperenhancement, suggesting that angiogenesis of malignant tumors increased rapidly. The local perfusion defects in the contrast-enhancement of large tumors are speculated to be associated with the insufficient blood supply, reduced angiogenesis, and different degrees of necrosis inside large tumors. The features of CEUS in laryngeal carcinoma are consistent with the characteristics of tumor angiogenesis reported in the literature. Szafarowski et al. (26) reported that the MVD inside the laryngeal tumors was significantly higher than that in nonmalignant control tissues, and the MVD of stage T3–T4 tumors was significantly lower than that of stage T1–T2 tumors. Similarly, some scholars have stated that tumor angiogenesis of human laryngeal carcinoma tumor xenografts is significantly higher in small tumors than in medium and large tumors. This topic may be an area of focus for further investigating the relationship between CEUS parameters and MVD of laryngeal carcinoma.

A limitation of the present study was that the imaging interpretation was performed by consensus instead of by independent readings, which may have led to a potential bias in the results. Further study is needed to analyze the inter-observer agreement between the sonologists and radiologists. In addition, there is a relatively small number of tumors in the present study; further studies with a large number of patients are required to determine the value of CEUS in the detection of laryngeal cartilage involvement. Moreover, another limitation of the present study is that we only explored the features of CEUS in laryngeal cancer; the value of quantitative parameters of CEUS in differentiating benign and malignant lesions of the larynx needs further investigation.

CEUS has certain limitations with regard to the evaluation of laryngeal carcinoma. First, only one region of interest can be examined at a time. Contrast agent reinjection is necessary when we need to visualize more than one region in evaluating tumor involvement. Second, the ability of CEUS to detect very early stage laryngeal cancer is still insufficient. If the tumor is mainly ulcerative with no obvious protruding mass bulge, the lesion will not be detectable by US, which is similar to the defects of other imaging methods. Third, retrolaryngeal structures may not be well visualized when extensive calcification present in the thyroid cartilage.

In conclusion, compared with conventional US and CECT, CEUS has a reliable initial T-staging accuracy and diagnostic properties for detecting laryngeal cartilage invasion. CEUS can be a non-invasive complementary modality for the detection and pretherapeutic staging of laryngeal carcinoma.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received the following financial support for the research, authorship, and/or publication of this article: This study was supported by the National Natural Science Foundation of China (Nos. 81660292, 81260223) and Guangxi medical high-level personnel training “139” project. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

ORCID iD

Shang Yong Zhu

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