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Kidney Week

Abstract: TH-PO694

Early Imaging Biomarkers of ADPKD: Longitudinal Study of Quantitative MRI and Texture Analysis in a Murine Model

Session Information

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic

Authors

  • Kline, Timothy L., Mayo Clinic, Rochester, Minnesota, United States
  • Constans, Megan M., Mayo Clinic, Rochester, Minnesota, United States
  • Edwards, Marie E., Mayo Clinic, Rochester, Minnesota, United States
  • Metzger, Andrew J., Mayo Clinic, Rochester, Minnesota, United States
  • Jiang, Kai, Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic, Rochester, Minnesota, United States
  • Torres, Vicente E., Mayo Clinic, Rochester, Minnesota, United States
  • Harris, Peter C., Mayo Clinic, Rochester, Minnesota, United States
  • Macura, Slobodan, Mayo Clinic, Rochester, Minnesota, United States
  • Erickson, Bradley J., Mayo Clinic, Rochester, Minnesota, United States
Background

Currently, only a fraction of the wealth of information that could be disclosed by radiological imaging is used to assess disease status and follow progression of ADPKD. Advanced MR imaging techniques can be used to measure renal structural and functional properties. We hypothesized that advanced MRI acquisitions and image analysis methods detect renal tissue alterations preceding changes in TKV in the Pkd1RC/RC mouse model in different backgrounds.

Methods

Pkd1RC/RC model mice (C57BL/6 and C57Bl6 x 129s6Svev/Tac ‘F1’ background, n=7 each), as well as wild-type (C57BL/6 and ‘F1’ background, n=5 each) were imaged at 3, 6, and 12-weeks of age. Mice imaging was performed under anesthesia with a 16.4T NMR spectrometer. TKV and texture were measured on T2-weighted images, and T1 relaxation maps were calculated and measured within the kidneys. Regions-of-interest were drawn to cover cortical and medullary regions.

Results

Figure 1 shows TKV progression for the four phenotypic groups, as well as the 3-week means of TKV, T1 relaxation, and entropy texture feature (a measure of tissue heterogeneity). The fast progressing group (‘F1’) exhibited a significant increase in TKV compared to wild-type, whereas the C57BL/6 model did not. In contrast, T1 relaxation and texture properties were found to clearly differentiate the model mice from corresponding wild-type.

Conclusion

Quantitative MR parameters and texture features can serve as early biomarkers of PKD. These parameters could be useful for pre-screening in trials as they inform on early disease. Moreover, they may afford more parameters to evaluate treatment benefits, which may be detectable over shorter study durations.

Top panel – volume progression of the four groups in this study. Bottom panel – boxplot comparisons of TKV (left), T1 relaxation (middle), and Entropy texture feature (right) at three-week time point.

Funding

  • NIDDK Support