Time-Intensity Curve Analysis of Contrast-Enhanced Ultrasound for Non-Ossified Thyroid Cartilage Invasion in Laryngeal Squamous Cell Carcinoma

Abstract

Objective: This study aimed to assess the diagnostic value of contrast-enhanced ultrasound (CEUS) time-intensity curve (TIC) parameters in detecting non-ossified thyroid cartilage invasion in patients with laryngeal squamous cell carcinoma (SCC). Methods: A CEUS TIC analysis was performed on 32 cases from 27 patients with histologically confirmed laryngeal SCC. The diagnostic performance of time to peak (TTP), peak intensity (PI), wash-in slope (WIS), area under the curve (AUC), and their quantitative differences (∆TTP, ∆PI, ∆WIS, and ∆AUC) to discriminate between the invaded and the non-invaded non-ossified thyroid cartilage was determined using ROC analysis. A logistic regression analysis was employed to identify significant predictors. Results: In an ROC analysis, of all TIC parameters analyzed separately, ∆TTP showed the greatest diagnostic performance (AUC: 0.85). A ∆TTP cut-off of ≤ 8.9 s differentiated between the invaded and the non-invaded non-ossified thyroid cartilage with a sensitivity of 100%, specificity of 76.9%, and accuracy of 81.3%. A combination of ∆TTP and PI increased the AUC to 0.93, specificity to 100%, and accuracy to 96.8%, but reduced the sensitivity to 83.3%. Meanwhile, the visual assessment of enhancement on CEUS to detect cartilage invasion had 83.3% sensitivity and 84.6% specificity. In a univariate logistic regression, only ∆TTP was a significant predictor of non-ossified thyroid cartilage invasion (OR: 0.80; 95% CI: 0.64-1.00). For every second increase in ∆TTP, the probability of thyroid cartilage invasion decreased by 20%. Conclusions: CEUS TIC parameters, particularly a combination of ∆TTP and PI, showed high diagnostic performance in the detection of non-ossified thyroid cartilage invasion in laryngeal SCC.

Keywords: contrast-enhanced ultrasound; diagnostic performance; laryngeal squamous cell carcinoma; non-ossified thyroid cartilage invasion.

Figure 1

Laryngeal cancer on the left with the partially ossified thyroid cartilage (white arrows). The ROI marked by the blue rectangle frame was placed on the non-ossified thyroid cartilage and the ROI marked by the orange rectangle frame, on the adjacent tumor. Qualitative TIC analysis of wash-out was conducted by describing a wash-out curve as shallow (slow wash-out) or steep (rapid wash-out).

Figure 2

Right laryngeal SCC on CEUS. The red arrows indicate poor enhancement of thyroid cartilage. Postoperative histopathological analysis confirmed the absence of invasion.

Figure 3

Time–intensity curve analysis of left laryngeal SCC at 28 s. (a) The ROI marked by the yellow rectangle frame indicates the enhancing tumor adjacent to the thyroid cartilage; (b) the ROI marked by the green rectangle frame shows the histologically proven invaded thyroid cartilage with enhancement; (c) the ROI marked by the blue rectangle frame shows non-ossified, non-enhanced cartilage without invasion.

Figure 4

Receiver operating characteristics analysis of the time–intensity curve parameters of non-ossified thyroid cartilage with suspected tumor invasion. PI = peak intensity; AUC = area under the curve; TTP = time to peak; ∆TTP = quantitative difference in TTP between the tumor and the thyroid cartilage; black dots represent the Youden index.