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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
Diffusion-weighted MRI does not reflect kidney fibrosis in a rat model of fibrosis
Peter Boor1,2,3,4, Michael Perkuhn5,6, Martin Weibrecht5,6
1Institute of Pathology, RWTH University Aachen, Aachen, Germany.
Purpose:
To assess the apparent diffusion coefficient (ADC) derived from diffusion-weighted (DW) magnetic resonance imaging (MRI) as a specific marker of renal fibrosis in rats with unilateral ureteral obstruction (UUO).
Materials And Methods:
Thirteen rats were analyzed in group 1 (n = 4), group 2 (n = 3), and group 3 (n = 6) and measured using a clinical 3.0T MR scanner. Groups 1 and 2 were used to establish the final imaging protocols for group 3. DW imaging with four b-values (0, 50, 300, 800 s/mm(2) ) was conducted before UUO, at days 3 and 5 after UUO, after release of the obstruction, and after sacrifice. Renal cortical ADCs were correlated with histological and ultrastructural analyses.
Results:
ADC values of group 3 are shown as mean ± standard deviation of [10(-3) mm(2) /s]. On day 5, in vivo cortical ADC of obstructed fibrotic kidneys was significantly reduced compared to unobstructed kidneys (1.4 ± 0.086 vs. 1.535 ± 0.087, P = 0.0018). Postmortem ADC dropped by 50% and was significantly increased in obstructed vs. unobstructed kidneys (0.711 ± 0.094 vs. 0.566 ± 0.049, P = 0.0046). Histopathology of obstructed kidneys showed tubular dilation, tubular cell atrophy, and expansion of the interstitial space. Postmortem ADC correlated tightly with tubular lumen area (r = 0.9, P < 0.001), fibronectin (r = 0.8, P = 0.003), collagen type I (r = 0.73, P = 0.007), and interstitial expansion (r = 0.69, P = 0.013).
Conclusion:
Compared to the in vivo measurements, postmortem renal ADCs were considerably reduced and, unlike in vivo, fibrotic kidneys exhibited consistently higher ADC compared to healthy kidney parenchyma. Our data suggest that in vivo ADC is unlikely to be a direct measure of renal fibrosis.
Insights
In vivo apparent diffusion coefficient (ADC) measurements in rats with unilateral ureteral obstruction (UUO) did not accurately reflect renal fibrosis. Postmortem ADC values showed a different pattern, suggesting in vivo ADC is not a direct marker of kidney fibrosis.
Area of Science:
- Nephrology
- Radiology
- Biomedical Engineering
Background:
- Renal fibrosis is a common pathway for chronic kidney diseases.
- Diffusion-weighted (DW) magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) are non-invasive imaging techniques.
- Assessing renal fibrosis non-invasively is crucial for disease management.
Purpose of the Study:
- To evaluate the apparent diffusion coefficient (ADC) from diffusion-weighted (DW) magnetic resonance imaging (MRI) as a specific biomarker for renal fibrosis.
- To investigate the utility of ADC in a rat model of unilateral ureteral obstruction (UUO).
Main Methods:
- Utilized a clinical 3.0T MR scanner for DW imaging in rats.
- Acquired images with four b-values (0, 50, 300, 800 s/mm²) at various time points: pre-UUO, post-UUO (days 3 and 5), post-obstruction release, and post-sacrifice.
- Correlated renal cortical ADC values with histological and ultrastructural analyses of kidney tissue.
Main Results:
- In vivo cortical ADC was significantly reduced in obstructed fibrotic kidneys compared to unobstructed kidneys on day 5 (1.4 ± 0.086 vs. 1.535 ± 0.087, P = 0.0018).
- Postmortem ADC values decreased by 50% and were significantly higher in obstructed kidneys (0.711 ± 0.094 vs. 0.566 ± 0.049, P = 0.0046).
- Postmortem ADC demonstrated strong correlations with histological markers of fibrosis, including tubular lumen area (r=0.9), fibronectin (r=0.8), collagen type I (r=0.73), and interstitial expansion (r=0.69).
Conclusions:
- Postmortem renal ADC measurements showed a significant reduction and an inverse correlation with fibrosis compared to in vivo findings.
- In vivo ADC measurements in fibrotic kidneys were lower than in healthy kidneys, contrary to postmortem results.
- The study suggests that in vivo ADC is not a reliable direct measure of renal fibrosis in this UUO model.

