Ultrasound super-resolution imaging provides a noninvasive assessment of renal microvasculature changes during mouse acute kidney injury

Abstract

Acute kidney injury (AKI) is a risk factor for the development of chronic kidney disease (CKD). One mechanism for this phenomenon is renal microvascular rarefaction and subsequent chronic impairment in perfusion. However, diagnostic tools to monitor the renal microvasculature in a noninvasive and quantitative manner are still lacking. Ultrasound super-resolution imaging is an emerging technology that can identify microvessels with unprecedented resolution. Here, we applied this imaging technique to identify microvessels in the unilateral ischemia-reperfusion injury mouse model of AKI-to-CKD progression in vivo. Kidneys from 21 and 42 day postischemia-reperfusion injury, the contralateral uninjured kidneys, and kidneys from sham-operated mice were examined by ultrasound super-resolution and histology. Renal microvessels were successfully identified by this imaging modality with a resolution down to 32 mm. Renal fibrosis was observed in all kidneys with ischemiareperfusion injury and was associated with a significant reduction in kidney size, cortical thickness, relative blood volume, and microvascular density as assessed by this imaging. Tortuosity of the cortical microvasculature was also significantly increased at 42 days compared to sham. These vessel density measurements correlated significantly with CD31 immunohistochemistry (R 2 [0.77). Thus, ultrasound super-resolution imaging provides unprecedented resolution and is capable of noninvasive quantification of renal vasculature changes associated with AKI-to-CKD progression in mice. Hence, this technique could be a promising diagnostic tool for monitoring progressive kidney disease.

Super-Resolution Imaging with Ultrasound for Visualization of the Renal Microvasculature in Rats Before and After Renal Ischemia: A Pilot Study

“…To our knowledge, the presented images reveal the highest level of detail of the renal vascular tree of rats obtained with modified clinical ultrasound platforms. Some studies using ultrasound SR imaging on rodent kidneys have not visualized the vasa recta, which could be due to short scan times or out-of-plane motion [ 17 , 35 ]. SR imaging for visualization of the slowly flowing blood in the vasa recta requires data acquisition to be lengthy to fill as many of the small vessels with MBs as possible for an adequate microvascular representation [ 23 ].…”

“…Other ultrasound techniques and imaging modalities are competing with the SR imaging setup presented in this paper. Ultrasound plane-wave techniques are commonly used to obtain SR images at a higher framerate [ 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. To facilitate a faster implementation of SR imaging in the clinic, we used focused beam transmission which is an established technology in commercial ultrasound platforms.…”

“…Another limiting factor is the lack of quantitative estimations of microvascular blood flow alterations during reperfusion. In chronic kidney disease the architecture of the vessels changes, resulting in reduced vessel density, decreased branching, or increased tortuosity [ 2 , 3 , 17 ]. The image assessment of the SR images in this study illustrated how the microvascular flow changes in an acute setup were not detectable by visual image evaluation.…”

“…The healthy microvasculature of rodent organs and tissues has been visualized with SR imaging [ 8 , 9 , 10 , 11 , 12 , 13 ]. SR imaging can also visualize and quantify the pathological microvascular patterns in rodent and chicken embryo tumors [ 14 , 15 , 16 ] and the later stages of acute kidney injury in mice [ 17 ]. With a rich and anatomically distinctive vasculature [ 18 ], the kidneys are attractive organs for SR imaging.…”

Super-resolution Ultrasound Imaging of the Renal Microvasculature in Rats with Metabolic syndrome

“…Super-resolution ultrasound imaging (SRI) is a new US technique that makes it possible to visualize the microvasculature in vivo. Studies have shown the ability to do in vivo SRI of organs and tissues in different animals, but the literature on pathological changes is still sparse [1]- [6]. Obese Zucker Rats (OZR) has a mutation in the leptin receptor gene which results in obesity, hyperinsulinemia, poorly regulated blood glucose giving them hyperlipidemia and glomerulosclerosis at an early age.…”