Abstract: SA-PO113
Super-Resolution Ultrasound to Monitor Microvascular Rarefaction After AKI in Mice
Session Information
- AKI: Mechanisms - AKI-CKD Transition
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Rush, Brittney M., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Chen, Qiyang, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Stocker, Sean D., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Kim, Kang, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Tan, Roderick J., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Background
Acute kidney injury is associated with an increased incidence of chronic kidney disease. One mechanism to explain this is the loss of vascular density in the kidney post-AKI, leading to chronic hypoxia. Current techniques to evaluate the vasculature are limited by a lack of resolution, technique causing harm to the subject, or inability to perform in live subjects. Super-resolution ultrasound (SRU) is an emerging technology to achieve high spatial resolution to identify microvessels in live animals.
Methods
C57BL/6 mice were subjected to unilateral ischemia-reperfusion injury (IRI) survival surgery. At 21 and 42 days after injury, mice were injected with clinical ultrasound contrast agent (Definity) and both the injured and contralateral control kidneys were evaluated in vivo under anesthesia. Using B-mode imaging the kidneys were imaged in the maximal longitudinal plane. Imaging data of 1000 effective frames were acquired using multi-angle ultrasound plane wave imaging at an effective frame rate of 250 Hz. Off-line signal processing was performed in MATLAB with radio-frequency data processed through beamforming, motion compensation, singular value decomposition filter, Richardson-Lucy deconvolution, and frame summation. After imaging, mice were euthanized, kidneys were recovered and subjected to immunohistochemistry to identify CD31 positive blood vessels. Fibrosis was assessed with trichrome and picrosirius red stains. Collagen and vascular endothelial growth factor (VEGF) levels were also assessed.
Results
SRU was capable of the accurate identification of microvessels with a resolution of 32 microns. Using SRU, a clear reduction in vascular density was identified in the IRI kidneys compared to control. SRU measurements correlated favorably with traditional CD31 immunohistochemical staining (R2=0.8). This was accompanied by a reduction in renal blood volume and kidney size. As expected, there was an increase in renal fibrosis that appeared to peak at 21 days. VEGF levels were also decreased after IRI.
Conclusion
SRU was capable of identifying the decrease in microvascular density after IRI in mice at late timepoints after injury. This correlated favorably with traditional immunohistochemistry and could be a method to monitor the progression of kidney disease after AKI.
Funding
- NIDDK Support