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Kidney Week

Abstract: PO1564

Quantifying Murine Total Kidney Volume with Robotic 3D Ultrasound

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Czernuszewicz, Tomasz J., SonoVol, Inc., Durham, North Carolina, United States
  • Beaumont, Nathan, SonoVol, Inc., Durham, North Carolina, United States
  • Holmes, Heather L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Rojas, Juan D., SonoVol, Inc., Durham, North Carolina, United States
  • Gessner, Ryan, SonoVol, Inc., Durham, North Carolina, United States
  • Dayton, Paul, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Kline, Timothy L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Romero, Michael F., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

Polycystic kidney disease (PKD) is a genetic disorder characterized by renal cyst formation and kidney enlargement. Noninvasive staging of PKD can be accomplished by measuring total kidney volume (TKV). While TKV has been readily implemented in the clinic, its adoption in preclinical research with small animals has lagged. In this study, a new high-throughput imaging device, based on robotic ultrasound (US), was evaluated as a complementary approach for measuring TKV in murine models and validated against in vivo and ex vivo gold standards (MRI and Vernier calipers).

Methods

Two cohorts of mice were evaluated in a cross-sectional study. Cohort 1 included a range of mature Pkd1 mice (N = 14 kidneys) that were imaged in 3D with both US and MRI. Cohort 2 included healthy mice (N = 16 kidneys) spanning both sexes and two ages (4&16 wks). Mice from Cohort 2 were imaged with 3D US in vivo, euthanized, and TKV measured ex vivo with Vernier calipers (length/width). Agreement was assessed with correlation and Bland-Altman (BA) analysis. US images were segmented by 4 independent readers and inter-reader reliability was assessed via intraclass correlation coefficient (ICC).

Results

US-TKV correlated strongly with both MRI and caliper measurements (r2 = 0.97 and 0.93, respectively). Against MRI, BA-analysis demonstrated no significant bias and a limit of agreement (LOA) of 70 mm3 between the techniques. Against calipers, a small but statistically significant overestimation was detected of kidney length/width by in vivo US imaging (0.87 mm). Inter-reader agreement for TKV was strong with an ICC of 0.93 (95%CI: 0.83–0.97).

Conclusion

These results show that robotic 3D US, performed by a novice operator, can produce rapid, accurate, and consistent in vivo measurements of TKV in murine models. Future studies will include larger cohort sizes and additional models of kidney disease (e.g. fibrosis) making this approach ideal for therapeutic screening.

(1) 3D US orthoslice views. (2) Matched US and MRI slices. (3) Linear regression. (4) Bland-Altman analysis.

Funding

  • NIDDK Support