Super-resolution (SR) imaging has the potential of visualizing the microvasculature down to the 10- $\mu \text{m}$ level, but motion induced by breathing, heartbeats, and muscle contractions are often significantly above this level. This article, therefore, introduces a method for estimating tissue motion and compensating for this. The processing pipeline is described and validated using Field II simulations of an artificial kidney. In vivo measurements were conducted using a modified bk5000 research scanner (BK Medical, Herlev, Denmark) with a BK 9009 linear array probe employing a pulse amplitude modulation scheme. The left kidney of ten Sprague-Dawley rats was scanned during open laparotomy. A 1:10 diluted SonoVue contrast agent (Bracco, Milan, Italy) was injected through a jugular vein catheter at 100 $\mu \text{l}$ /min. Motion was estimated using speckle tracking and decomposed into contributions from the heartbeats, breathing, and residual motion. The estimated peak motions and their precisions were: heart: axial— $7.0~\pm ~0.55~\mu \text{m}$ and lateral— $38~\pm ~2.5~\mu \text{m}$ , breathing: axial— $5~\pm ~0.29~\mu \text{m}$ and lateral— $26~\pm ~1.3~\mu \text{m}$ , and residual: axial—30 $\mu \text{m}$ and lateral—90 $\mu \text{m}$ . The motion corrected microbubble tracks yielded SR images of both bubble density and blood vector velocity. The estimation was, thus, sufficiently precise to correct shifts down to the 10- $\mu \text{m}$ capillary level. Similar results were found in the other kidney measurements with a restoration of resolution for the small vessels demonstrating that motion correction in 2-D can enhance SR imaging quality.

Super resolution ultrasound imaging using the erythrocytes (SURE) has recently been introduced. The method uses erythrocytes as targets instead of fragile microbubbles (MBs). The abundance of erythrocyte scatterers makes it possible to acquire SURE data in just a few seconds compared to several minutes in ultrasound localization microscopy (ULM) using MBs. A high number of scatterers can reduce the acquisition time, however, the tracking of uncorrelated and high-density scatterers is quite challenging. This paper hypothesizes that it is possible to detect and track erythrocytes as targets to obtain vascular flow images. A SURE tracking pipeline is used with modules for beamforming, recursive synthetic aperture imaging, motion estimation, echo canceling, peak detection, and recursive nearest neighbor tracker. The SURE tracking pipeline is capable of distinguishing the flow direction and separating tubes of a simulated Field II phantom with 125 to 25 μm wall-to-wall tube distances, as well as a 3D-printed hydrogel micro-flow phantom with 100 to 60 μm wall-to-wall channel distances. The comparison of an in-vivo SURE scan of a Sprague-Dawley rat kidney with ULM and micro-CT scans with voxel sizes of 26.5μm and 5μm demonstrated consistent findings. A microvascular structure composed of 16 vessels exhibited similarities across all imaging modalities. The flow direction and velocity profiles in the SURE scan were found to be concordant with those from ULM.

This review looks at highlights of the development in ultrasound, ranging from interventional ultrasound and Doppler to the newest techniques like contrast-enhanced ultrasound and elastography, and gives reference to some of the valuable articles in Acta Radiologica. Ultrasound equipment is now available in any size and for any purpose, ranging from handheld devices to high-end devices, and the scientific societies include ultrasound professionals of all disciplines publishing guidelines and recommendations. Interventional ultrasound is expanding the field of use of ultrasound-guided interventions into nearly all specialties of medicine, from ultrasound guidance in minimally invasive robotic procedures to simple ultrasound-guided punctures performed by general practitioners. Each medical specialty is urged to define minimum requirements for equipment, education, training, and maintenance of skills, also for medical students. The clinical application of contrast-enhanced ultrasound and elastography is a topic often seen in current research settings.

Obesity is a risk factor of chronic kidney disease (CKD), leading to alterations in the renal vascular structure. This study tested if renal vascular density and tortuosity was quantifiable in vivo in obese rats using microbubble-based super-resolution ultrasound imaging. The kidneys of two 11-week-old and two 20-week-old male obese Zucker rats were compared with age-matched male lean Zucker rats. The super-resolution ultrasound images were manually divided into inner medulla, outer medulla, and cortex, and each area was subdivided into arteries and veins. We quantified vascular density and tortuosity, number of detected microbubbles, and generated tracks. For comparison, we assessed glomerular filtration rate, albumin/creatinine ratio, and renal histology to evaluate CKD. The number of detected microbubbles and generated tracks varied between animals and significantly affected quantification of vessel density. In areas with a comparable number of tracks, density increased in the obese animals, concomitant with a decrease in glomerular filtration rate and an increase in albumin/creatinine ratio, but without any pathology in the histological staining. The results indicate that super-resolution ultrasound imaging can be used to quantify structural alterations in the renal vasculature. Techniques to generate more comparable number of microbubble tracks and confirmation of the findings in larger-scale studies are needed.

Individuals with diabetes at risk of developing diabetic kidney disease (DKD) are challenging to identify using currently available clinical methods. Prognostic accuracy and initiation of treatment could be improved by a quantification of the renal microvascular rarefaction and the increased vascular tortuosity during the development of DKD. Super-resolution ultrasound (SRUS) imaging is an in vivo technique capable of visualizing blood vessels at sizes below 75 µm. This preclinical study aimed to investigate the alterations in renal blood vessels’ density and tortuosity in a type 2 diabetes rat model, Zucker diabetic fatty (ZDF) rats, as a prediction of DKD. Lean age-matched Zucker rats were used as controls. A total of 36 rats were studied, subdivided into ages of 12, 22, and 40 weeks. Measured albuminuria indicated the early stage of DKD, and the SRUS was compared with the ex vivo micro-computed tomography (µCT) of the same kidneys. Assessed using the SRUS imaging, a significantly decreased cortical vascular density was detected in the ZDF rats from 22 weeks of age compared to the healthy controls, concomitant with a significantly increased albuminuria. Already by week 12, a trend towards a decreased cortical vascular density was found prior to the increased albuminuria. The quantified vascular density in µCT corresponded with the in vivo SRUS imaging, presenting a consistently lower vascular density in the ZDF rats. Regarding vessel tortuosity, an overall trend towards an increased tortuosity was present in the ZDF rats. SRUS shows promise for becoming an additional tool for monitoring and prognosing DKD. In the future, large-scale animal studies and human trials are needed for confirmation.