Ultrasound Biomarkers: Contrast-enhanced Ultrasound and Nakagami Imaging to Differentiate Benign and Malignant Choroidal Tumor

Purpose: We hypothesized that contrast-enhanced ultrasound (CEUS) using a microbubble technique to quantify microvascular changes and Nakagami imaging for tissue characterization would provide a new approach for diagnosing and differentiating benign and malignant choroidal lesions. Methods: Five patients with choroidal melanoma (CM) and five patients with choroidal hemangioma (CH) were selected. Definity®, which contains perflutren microbubbles, was administered as a slow IV bolus (1 ml). CEUS was performed for 1 min postinjection of the contrast agent with ultrasound radiofrequency data acquired from 10 s to 60 s. The contrast value was calculated for the whole tumor region. A gradient magnitude method was used for each postcontrast frames with 1-second interval, and the time-averaged value in pixel intensity gradient of postinjection frames was estimated and reported. Based on the Nakagami statistical distribution model, two Nakagami parameters, m and Ω, where m (shape parameter), representing tissue heterogeneity, and Ω (scale parameter), representing the average energy of backscattered signals, were studied. Results: CEUS analysis showed that the time-averaged estimated contrast was significantly higher (p = 0.008) for CH compared to CM. Furthermore, the time-averaged contrast within the normal choroidal region was significantly higher than the choroidal tumor region for both CH and CM (p = 0.001 for CH cases and p < 0.0001 for CM cases). Nakagami analysis showed that the m estimates were significantly higher (p = 0.032) for CH (m = 0.61) than for CM (m = 0.28), indicating that CH is a more heterogeneous tumor than CM. The Ω estimates were significantly higher (p = 0.0019) for CH (Ω = 0.15) compared to CM (Ω = 0.03). These results may be due to the more vascular structures in CH compared to CM. Conclusions: Quantitative intensity-based perfusion analysis using CEUS and backscattering tissue analysis using Nakagami imaging can provide valuable insights to differentiate benign and malignant choroidal lesions.