Value of High Frame Rate Contrast-enhanced Ultrasound in Evaluating Vascular Morphology of Renal Cell Carcinoma

Background: Different subtypes of renal cell carcinoma (RCC) exhibit distinct tumor vascular morphological features. However, current imaging techniques still have limitations in delineating the vascular morphology of RCC. Objective: This study aimed to evaluate the value of high-frame-rate contrast-enhanced ultrasound (H-CEUS) in assessing the vascular morphology of RCC. results: Comparative analysis of US parameters between ccRCC and nccRCC groups revealed a significant difference in intra-nodal blood flow (χ²=11.755, p=0.008). No significant differences were observed in other parameters, including patient gender, age, nodule laterality, location, diameter, echogenicity, margin, shape, and calcification (all p > 0.05). Type III (peripheral nodular enhancement) was the predominant manifestation in both ccRCC and nccRCC groups under both C-CEUS and H-CEUS imaging modalities. In the ccRCC group, Type III accounted for 45.8% (49/107) and 62.6% (67/107) of cases under C-CEUS and H-CEUS, respectively, with a significant difference (χ²=6.099, p=0.014). Type IV (diffuse enhancement) was the primary manifestation in the nccRCC group, accounting for 58.9% (33/56) and 44.6% (25/56) of cases under C-CEUS and H-CEUS, respectively, without a significant difference (χ²=2.289, p=0.130). In tumors ≤4 cm, the early perfusion vascular morphology in the ccRCC group under C-CEUS was as follows: Type I (0 cases), Type II (3 cases), Type III (26 cases), Type IV (15 cases), and Type V (14 cases). Under H-CEUS, the distribution was: Type I (1 case), Type II (7 cases), Type III (36 cases), Type IV (8 cases), and Type V (6 cases). This difference was statistically significant (χ²=9.307, p=0.038). In the nccRCC group, no significant difference was observed in vascular morphology between C-CEUS and H-CEUS modalities (p > 0.05). For tumors >4 cm, no significant differences were found in vascular morphology between ccRCC and nccRCC groups under either imaging modality (p > 0.05). Inter-observer agreement for vascular morphology evaluation was substantial for both C-CEUS (Kappa coefficient = 0.751, p<0.001) and H-CEUS (Kappa coefficient = 0.657, p<0.001). Methods: A retrospective analysis was conducted on 163 RCC patients who were classified postoperatively into clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC) groups. All patients underwent conventional US, conventional CEUS (C-CEUS), and H-CEUS preoperatively. Vascular morphology during the early phase of CEUS perfusion was categorized into five types (I-V). Differences in vascular morphology were compared using the x2 test or Fisher's exact test, and inter-observer agreement was evaluated using the Kappa coefficient. Results: A significant difference in CDFI was observed between the ccRCC and nccRCC groups (x2=11.755, P=0.0088). Type III was the predominant vascular morphology in ccRCC on both C-CEUS and H-CEUS, with proportions significantly higher on H-CEUS (62.6% vs. 45.8%; x2=6.099, P=0.014). Type IV was the most common vascular morphology in nccRCC, with no significant difference between C-CEUS (58.9%) and H-CEUS (44.6%) (x2=2.289, P=0.130). Discussion: H-CEUS revealed significant vascular morphological differences in ccRCC ≤4 cm (x2=9.307, P=0.038), but not in nccRCC ≤4 cm or in any tumors >4 cm. Inter-observer agreement for vascular morphology evaluation was substantial for both C-CEUS (κ=0.751) and H-CEUS (κ=0.657) (both P<0.001). Conclusion: H-CEUS shows superior visualization capabilities in evaluating vascular morphology for ccRCC lesions ≤4 cm, which provides valuable insights into its potential as a non-invasive imaging modality for differentiating RCC subtypes and tailoring treatment strategies.