Cerebral circulation ensures the proper functioning of the entire human body, and its interruption, i.e. stroke, leads to irreversible damage. However, tools for observing cerebral circulation are still lacking. Although MRI and CT scans serve as conventional methods, their accessibility remains a challenge, prompting exploration into alternative, portable, and non-ionizing imaging solutions like ultrasound with reduced costs. While Ultrasound Localization Microscopy (ULM) displays potential in high-resolution vessel imaging, its 2D constraints limit its emergency utility. This study delves into the feasibility of 3D ULM with multiplexed probe for transcranial vessel imaging in sheep brains, emulating human skull characteristics. Three sheep underwent 3D ULM imaging, compared with angiographic MRI, while skull characterization was conducted in vivo using ultrashort bone MRI sequences and ex vivo via micro CT. The study showcased 3D ULM's ability to highlight vessels, down to the Circle of Willis, yet within a confined 3D field-of-view. Future enhancements in signal, aberration correction, and human trials hold promise for a portable, volumetric, transcranial ultrasound angiography system.
Ultrasound contrast agents have been used as vascular reporters for the past 40 years. The ability to enhance vascular features in ultrasound images with engineered lipid-shelled microbubbles has enabled break-throughs such as the detection of tissue perfusion or super-resolution imaging of the microvasculature. However, advances in the field of contrast-enhanced ultra-sound are hindered by experimental variables that are difficult to control in a laboratory setting, such as complex vascular geometries, the lack of ground truth, and tissue nonlinearities. In addition, the demand for large datasets to train deep learning-based computational ultrasound imaging methods calls for the development of a simulation tool that can reproduce the physics of ultrasound wave interactions with tissues and microbubbles. Here, we introduce a physically realistic contrast-enhanced ultrasound simulator (PROTEUS) consisting of four inter-connected modules that account for blood flow dynamics in segmented vascular geometries, intravascular microbubble trajectories, ultrasound wave propagation, and nonlinear microbubble scattering. The first part of this study describes numerical methods that enabled this development. We demonstrate that PROTEUS can generate contrast-enhanced radiofrequency data in various vascular architectures across the range of medical ultrasound frequencies. PROTEUS offers a customizable framework to explore novel ideas in the field of contrast-enhanced ultrasound imaging. It is released as an open-source tool for the scientific community.
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