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Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
Published on: June 23, 2015
Tracking kidney volume in mice with polycystic kidney disease by magnetic resonance imaging
D P Wallace1, Y-P Hou, Z L Huang
1The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas 66160-3018, USA. dwallace@kumc.edu
Abstract:
Polycystic kidney disease is characterized by the progressive enlargement of kidneys due to expanding fluid-filled cysts with the rate of renal volume increase held to be a marker of disease progression. Magnetic resonance imaging (MRI) is used to monitor changes in renal volume in patients with polycystic kidney disease; however, it has not been effectively used in mice to monitor changes in kidney volume during drug treatment studies. We used a powerful 9.4-T horizontal bore magnetic resonance scanner to track changes in kidney volume in pcy/pcy mice, an ortholog of nephronophthisis type 3. Mice were sequentially scanned from 4 to 30 weeks of age and kidney volumes determined from high-resolution images. Kidney volume and maximal cross-sectional surface area correlated positively with kidney weight and the histologic determination of surface area. The increase in kidney volume was exponential up to 20 weeks of age, after which there was a plateau consistent with the replacement of normal parenchyma by fibrotic tissue. Our study demonstrates that MRI accurately determines the rate of kidney volume increase in mice with polycystic kidney disease and hence may be useful in assessing the effectiveness of therapeutic agents to slow disease progression.
Insights
Magnetic resonance imaging (MRI) accurately tracks kidney volume changes in polycystic kidney disease (PKD) mouse models. This method can assess drug effectiveness for slowing PKD progression in mice.
Area of Science:
- Biomedical Imaging
- Renal Pathophysiology
- Animal Models
Background:
- Polycystic kidney disease (PKD) is marked by kidney enlargement due to cyst growth, with renal volume increase indicating disease progression.
- Magnetic resonance imaging (MRI) is crucial for monitoring human PKD but is underutilized in mouse models for drug studies.
Purpose of the Study:
- To evaluate the efficacy of high-field (9.4-T) MRI in accurately measuring kidney volume changes in pcy/pcy mice, a model for cystic kidney disease.
- To establish MRI as a reliable tool for assessing disease progression and therapeutic interventions in preclinical PKD research.
Main Methods:
- Utilized a 9.4-T horizontal bore MRI scanner to perform serial kidney volume measurements in pcy/pcy mice from 4 to 30 weeks of age.
- Correlated MRI-derived kidney volumes and maximal cross-sectional areas with kidney weight and histological assessments.
Main Results:
- MRI accurately quantified kidney volume increase in pcy/pcy mice, showing an exponential growth pattern up to 20 weeks.
- Post-20 weeks, kidney volume plateaued, indicating replacement of normal tissue by fibrosis.
- MRI measurements demonstrated strong positive correlations with kidney weight and histological surface area.
Conclusions:
- High-field MRI is a precise method for determining kidney volume increase rates in mouse models of polycystic kidney disease.
- This MRI approach holds significant potential for evaluating the efficacy of novel therapeutic agents aimed at slowing PKD progression in preclinical studies.

