Three-Dimensional Ultrafast Ultrasound Reveals Dynamic Vascular Alterations During Intraocular Melanoma Progression in Mice.

Abstract

PURPOSE: The purpose of this study was to investigate the feasibility of three-dimensional contrast-free ultrafast Doppler ultrasound for longitudinal assessment of vascular remodeling in an experimental intraocular melanoma model, and to characterize dynamic microvascular alterations during tumor progression. METHODS: Intraocular melanoma was induced in a mouse model and monitored over 12 days using three-dimensional ultrafast Doppler imaging. Ocular as well as tumor vasculature were segmented from serial volumetric datasets, and multiparametric analysis of vascular volume occupied (VVO), fractional moving blood volume (FMBV), average blood velocity (ABV), and blood velocity variance (BVV) was performed. Wide-field optical coherence tomography angiography (OCTA) was also performed at each time point. RESULTS: Ultrafast Doppler imaging enabled consistent visualization of intraocular tumor vasculature and surrounding blood flow. In ocular structures, VVO and FMBV in both the retina and retrobulbar regions progressively increased during early to mid-stage uveal melanoma (UM), whereas ABV and BVV showed a transient rise in the retina but not in retrobulbar regions. Within the tumor, VVO and FMBV increased significantly during early to mid-stage, but declined in advanced-stage (day 10 vs. day 3, P < 0.01). ABV peaked at day 7 before decreasing, whereas BVV showed a continuous rise, with maximum values at day 7 (P < 0.01 vs. day 3). These findings indicate spatiotemporal heterogeneity of vascular remodeling during intraocular melanoma progression. CONCLUSIONS: Three-dimensional ultrafast Doppler imaging provides a noninvasive and quantitative approach to monitor dynamic vascular changes in intraocular melanoma. This method reveals distinct temporal patterns of angiogenesis and perfusion heterogeneity, highlighting its potential value for early diagnosis and longitudinal evaluation of intraocular tumors.