Role of Quantitative CEUS in the Diagnosis of Peripheral Pulmonary Lesions: A Systematic Review

Background/Objectives: This systematic review describes a largely descriptive synthesis of studies investigating the diagnostic performance of quantitative contrast-enhanced ultrasound (CEUS) in differentiating benign from malignant peripheral pulmonary lesions. Methods: Formal quantitative pooling of effect sizes was not feasible due to variability in outcome measurements and reporting. Results: Combining CEUS parameters with real-time on-site evaluation (ROSE) substantially improved percutaneous biopsy success rates. In one comparative study, biopsy yield reached 97.62% with CEUS, versus 84% using conventional ultrasound, while complications remained minimal. Other investigations focused on the discriminatory value of specific time-based indices (e.g., AT ≥ 10 s, lesion-lung AT difference ≥ 2.5 s) or complex multi-parameter models. A notable large study demonstrated that a six-parameter logistic regression model achieved near-excellent discrimination, with C-statistics exceeding 0.97 for both development and validation cohorts, outperforming single-threshold approaches. Nevertheless, certain findings emphasize that no single indicator—particularly arrival time alone—reliably distinguishes benign from malignant lesions, given the diverse vascular patterns and histological subtypes involved. TDOA-based analyses proved more promising, as malignant lesions generally exhibit a delayed but robust bronchial arterial supply and rapid washout. Heterogeneity in ultrasound systems, operator experience, and patient populations further underscores the need for standardized protocols. Conclusions: Overall, these data suggest that CEUS, particularly when combined with additional sonographic or cytological tools, significantly enhances diagnostic precision for peripheral pulmonary lesions.