Super-Resolution Ultrasound Imaging Using the Erythrocytes—Part I: Density Images

Abstract

A new approach for vascular super-resolution (SR) imaging using the erythrocytes as targets (SUper-Resolution ultrasound imaging of Erythrocytes (SURE) imaging) is described and investigated. SURE imaging does not require fragile contrast agent bubbles, making it possible to use the maximum allowable mechanical index (MI) for ultrasound scanning for an increased penetration depth. A synthetic aperture (SA) ultrasound sequence was employed with 12 virtual sources (VSs) using a 10-MHz GE L8-18i-D linear array hockey stick probe. The axial resolution was ${1.20}\lambda ~\text {(185.0}~\mu $ m) and the lateral resolution was ${1.50}\lambda ~\text {(231.3}~\mu $ m). Field IIpro simulations were conducted on 12.5- $\mu $ m radius vessel pairs with varying separations. A vessel pair with a separation of $70~\mu $ m could be resolved, indicating a SURE image resolution below half a wavelength. A Verasonics research scanner was used for the in vivo experiments to scan the kidneys of Sprague-Dawley rats for up to 46 s to visualize their microvasculature by processing from 0.1 up to 45 s of data for SURE imaging and for 46.8 s for SR imaging with a SonoVue contrast agent. Afterward, the renal vasculature was filled with the ex vivo micro-computed tomography (CT) contrast agent Microfil, excised, and scanned in a micro-CT scanner at both a 22.6- $\mu $ m voxel size for 11 h and for 20 h in a 5- $\mu $ m voxel size for validating the SURE images. Comparing the SURE and micro-CT images revealed that vessels with a diameter of $28~\mu $ m, five times smaller than the ultrasound wavelength, could be detected, and the dense grid of microvessels in the full kidney was shown for scan times between 1 and 10 s. The vessel structure in the cortex was also similar to the SURE and SR images. Fourier ring correlation (FRC) indicated a resolution capability of $29~\mu $ m. SURE images are acquired in seconds rather than minutes without any patient preparation or contrast injection, making the method translatable to clinical use.