4D Ultrafast Ultrasound: the next revolution in biomedical imaging.

Four-dimensional ultrafast ultrasound imaging is emerging as a major paradigm shift in biomedical imaging by enabling the direct visualization and quantification of dynamic physiological processes in three-dimensional space over time. This review provides a comprehensive overview of the principles, technological developments, and applications that underpin this rapidly evolving field. We first describe the foundations of volumetric ultrafast acquisition based on unfocused wave transmissions and coherent compounding, followed by key advances in volumetric beamforming, motion estimation, Doppler imaging, elastography, and ultrasound localization microscopy. Particular emphasis is placed on the hardware challenges associated with matrix array transducers, including channel count limitations, data throughput, and emerging solutions such as microbeamforming, sparse arrays, row-column addressing, and wearable probes. We further highlight the critical role of high-performance computing and artificial intelligence in enabling real-time processing and analysis of large volumetric datasets. Beyond acquisition and reconstruction, this review underscores the importance of advanced visualization and quantification strategies as essential tools for extracting meaningful information from complex 4D data. Applications ranging from in vitro validation to preclinical and early clinical studies in cardiovascular, neurovascular, and abdominal imaging demonstrate the unique capabilities of this modality. Finally, we discuss current limitations and future directions, emphasizing the need for scalable hardware, efficient data handling, and new conceptual frameworks to fully exploit the spatiotemporal richness of 4D ultrafast ultrasound.