Application of superresolution ultrasound imaging for assessing microvascular structure and hemodynamic changes in rabbit VX2 models.

Background: Noninvasive and functional tumor vascular system imaging at the microscopic scale is greatly significant. Using animal models, we investigated the feasibility of using superresolution ultrasound (SR-US) imaging to visualize and quantify the microvessels during tumor growth.

Methods: This study established nine rabbit VX2 tumor models. Conventional US, contrast-enhanced US (CEUS), and SR-US images were acquired on Days 5, 8, and 14 postimplantation in 18 VX2 tumors. The imaging capabilities of CEUS and SR-US were compared, and hemodynamic changes were assessed using SR-US parameters. Pearson's correlation was calculated to analyze the association between the microvessel density (MVD) from histopathology and the vascular density (VD) from SR-US.

Results: SR-US demonstrated superior resolution compared with conventional CEUS. The minimum discernible vessel diameter of 105.2 ± 7.5 μm was observed in the VX2 tumor microvasculature visualized with SR-US. A strong positive correlation (r = 0.82, P = 0.006) was found between MVD and VD. The tumor size progression exhibited distinct stages: stable stage (Days 5 and 8) and growth stage (Days 8-14). Vessel pixels significantly increased throughout all experimental stages (P < 0.05), whereas both the VD and perfusion index demonstrated transient increases during the early stage before returning to baseline levels. The mean velocity and flow direction entropy initially decreased but returned to baseline later. The maximum velocity and fractal dimension significantly increased during the accelerated stage (P < 0.05).

Conclusions: Quantitative SR-US parameters provided a valuable tool for assessing microvascular changes during tumor progression.