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Kidney Week

Abstract: PO1268

Comparison of Imaging Approaches for Quantifying Total Kidney Volume (TKV) and Fibrosis in a Mouse Model of Polycystic Kidney Disease (PKD)

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Sussman, Caroline R., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Holmes, Heather L., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Thao, Ka, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Gregory, Adriana, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Meloche, Ryan J., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Mkhaimer, Yaman Ghassan, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Wells, Harrison H., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Macura, Slobodan, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Harris, Peter C., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Kline, Timothy L., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Romero, Michael F., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
Background

3D imaging and histology are critical tools for assessing PKD in patients and animal models. Magnetic resonance (MR) imaging provides µm resolution, but is time consuming, expensive, and access to equipment and expertise is limiting. Robotic ultrasound (US) imaging is lower resolution but fast. Similarly, picrosirius red (PR) staining and standard light microscopy is used to assess fibrosis; however, alternative methods for quantifying PR staining have been shown in other tissues to allow greater sensitivity and more detailed characterization.

Methods

Pkd1RC/RC mice were compared to Pkd1+/+ (WT). TKV was quantified from US and MRI (7T and 16T) at 1, 3, and 4 months old. US measurements of kidney and heart were made using the robotic Vega system from SonoVol. Inter-observer variation was assessed using Bland-Altman analysis. PR-stained kidneys were imaged using standard light microscopy, circularly (c) polarized light with binning into four categories of collagen thickness, and fluorescent imaging with analysis using ctFire. Renal cAMP and BUN were measured using standard approaches, and GFR was measured using a transdermal fluorescent sensor (MediBeacon).

Results

US detected increased TKV at 1 month and was similar to MR (7T or 16T). Inter-observer variability (2 observers) was greater for US than MR, but still able to detect differences between genotypes and time points. US allowed scanning in 2-5 minutes/mouse while MR required 20-30 minutes. Cpolarized light showed a greater percentage of the thickest collagen fibers in RC/RC mice, and a corresponding lower percentage of each of 3 categories of thinner collagen fibers. Preliminary data using fluorescence and ctFire showed a higher density of collagen fibers in RC/RC mice vs. WT. Analysis of collagen fiber angle, length, straightness, and width is ongoing. RC/RC had a lower GFR, higher BUN, and elevated cAMP vs WT. No differences were observed in cardiac function (ejection fraction, heart rate, or cardiac output).

Conclusion

These studies demonstrate the utility of US and alternative approaches of quantifying fibrosis using PR.

Funding

  • NIDDK Support