Advancements in Three‐Dimensional Super‐Resolution Ultrasound Imaging

The lack of sensibility of traditional ultrasound (US) imaging to the slow blood flow in small vessels resulted in the development of microbubble (MB) contrast agents. These MBs are given intravenously, and US imaging can detect them quite effectively. This noninvasive imaging method, known as contrast‐enhanced US (CEUS), now makes it possible to accurately assess tissue perfusion and blood flow. Though CEUS offers several benefits, diffraction restricts the spatial resolution of all US imaging systems to length scales equal to roughly half the wavelength of the transmitted US beam. Based on individual MB detection and localization, the recently developed super‐resolution US (SRUS) imaging method has shown unprecedentedly high spatial resolution exceeding the physical diffraction limit. It is now possible to visualize the microvasculature beyond the diffraction‐limited resolution by localizing spatially isolated MBs across several frames. The highest resolution possible at clinical US frequencies can be on the order of several micrometers when tissue and probe motion are not present. Enhancing the functional study of tissue microvascular networks with structural data could lead to improved disease management. Through the localization and tracking of MBs, SRUS may reconstruct images of the microvasculature with resolution exceeding the diffraction limit in both 2‐dimensional (2D) and 3‐dimensional (3D) space. In contrast to the 2D approach, 3D SRUS imaging does not suffer from out‐of‐plane motion and can offer volumetric coverage with super‐resolution in all three dimensions. Research has used two primary methods for 3D SRUS imaging including arrays that can electronically gather volumetric information or mechanically scanning the volume with a linear probe to produce a stack of 2D SRUS images. This manuscript aims to offer a comprehensive review of 3D SRUS imaging, clarifying methodologies, clinical applications, and notable challenges that could motivate future research and help facilitate clinical translation.