Optically Validated Microvascular Phantom for Super-Resolution Ultrasound Imaging

Super-resolution ultrasound (SRUS) visualizes microvasculature beyond the ultrasound (US) diffraction limit (wavelength( $\lambda $ )/2) by localizing and tracking spatially isolated microbubble (MB) contrast agents. SRUS phantoms typically consist of simple tube structures, where diameter channels below ${100}~{\mu }$ m are not available. Furthermore, these phantoms are generally fragile and unstable, have limited ground truth validation, and their simple structure limits the evaluation of SRUS algorithms. To aid SRUS development, robust and durable phantoms with known and physiologically relevant microvasculature are needed for repeatable SRUS testing. This work proposes a method to fabricate durable microvascular phantoms that allow optical gauging for SRUS validation. The methodology used a microvasculature negative print embedded in a Polydimethylsiloxane (PDMS) to fabricate a microvascular phantom. Branching microvascular phantoms with variable microvascular density were demonstrated with optically validated vessel diameters down to ${\sim } 60~{\mu }$ m ( $\lambda \text {/}{5.8}$ ; ${\lambda ={\sim }{350}}~{\mu }$ m). SRUS imaging was performed and validated with optical measurements. The average SRUS error was ${15.61}~{\mu }$ m ( $\lambda \text {/22}$ ) with a standard deviation error of ${11.44}~{\mu }$ m. The average error decreased to ${7.93}~{\mu }$ m ( $\lambda \text {/44}$ ) once the number of localized MBs surpassed 1000 per estimated diameter. In addition, less than 10% variance of acoustic and optical properties and the mechanical toughness of the phantoms measured a year after fabrication demonstrated their long-term durability. This work presents a method to fabricate durable and optically validated complex microvascular phantoms which can be used to quantify SRUS performance and facilitate its further development.