PROTEUS: A Physically Realistic Contrast-Enhanced Ultrasound Simulator-Part II: Imaging Applications.

The development of new imaging paradigms in the field of contrast-enhanced ultrasound (CEUS) is hindered by the difficulty to control complex experimental variables in a laboratory setting, such as vascular geometries, nonlinear ultrasound wave propagation in tissue, or microbubble positions within vessels as a function of time. This development would greatly benefit from the ability to control and reproduce independently these conditions in a simulated environment. Here, we report a physically realistic CEUS simulator, PROTEUS, that generates synthetic contrast-enhanced radio frequency (RF) data. In this article, we show that PROTEUS enables flexible investigations of imaging parameters on CEUS, including innovative transducer architecture, such as row-column addressed arrays, microbubble size distribution, pulse sequences, and vascular geometry. We demonstrate how PROTEUS can emulate various 2-D and 3-D imaging modes, such as pulse inversion (PI) or amplitude modulation (AM), echo particle image velocimetry (PIV), or ultrasound localization microscopy (ULM). Finally, in an investigative simulation case study, we evaluate the impact of microbubble size distribution on ULM on a simulated set of 15000 frames. It is released as an open-source tool for the scientific community.