Extending ULM to 3D is essential to capture vascular architecture, flow dynamics, and microcirculatory remodeling, and has been demonstrated in multiple preclinical models. However, existing 3D ULM systems, based on matrix, sparse, multiplexed, or row–column arrays, suffer from limited field of view, high channel counts, and restricted penetration, limiting clinical translation. To overcome these limitations, we developed a large-aperture array using large piezoelectric elements to improve sensitivity and volumetric coverage. As large elements exhibit strong acoustic directivity, we introduced custom acoustic lenses that reduce directivity via Snell’s law, enabling wide divergence and effective synthetic focusing while preserving sensitivity. This concept was validated through simulations and in vitro experiments, followed by a full-scale prototype applied to large organs, demonstrating unprecedented volumetric coverage. Most recently, we achieved transcranial imaging of the complete Circle of Willis in primates, highlighting robustness in highly aberrating environments. These advances remove major limitations in 3D ULM, enabling large fields of view, improved penetration, reduced hardware complexity, and compatibility with clinical constraints. Future work will focus on clinically deployable 3D ULM systems for whole-organ imaging, including the kidney, heart, and brain.
