This study aimed to investigate the feasibility of diffusion tensor imaging (DTI) and T2-mapping to assess temporal renal damage in deoxycorticosterone acetate–salt (DOCA-salt) hypertensive rats and compare the results with histopathologic and immunohistochemical findings.
After baseline renal magnetic resonance imaging (MRI), 24 out of 30 uninephrectomized Sprague-Dawley rats with DOCA-salt-induced hypertension were divided equally into four groups. Group 1 had renal MRI at weeks 2, 4, 6, and 8, and groups 2, 3, and 4 had MRI at weeks 2, 4, and 6, respectively. The remaining 6 rats were used as sham controls. The renal cortex and outer and inner stripes of the outer medulla were examined over time using fractional anisotropy (FA), apparent diffusion coefficient (ADC), and T2-mapping, and the results were compared with baseline values. The degree of glomerular and tubular injury, endothelial cell thickening, hyaline arteriolosclerosis, macrophage infiltration, microcyst formation, and fibrosis in different zones at different time points in the DOCA-salt rats were compared with controls.
Compared with baseline values, DOCA-salt rats demonstrated a significant decrease in renal cortical FA from week 4 to week 8 (0.244 ± 0.015 vs 0.172 ± 0.014–0.150 ± 0.016, P = 0.018–0.002), corresponding to significantly more glomerular damage, arteriolosclerosis, macrophage infiltration, and fibrosis. The DOCA-salt rats had significantly increased cortical ADC and T2 values at weeks 6 and 8 (1.778 ± 0.051 × 10−3 mm2/s vs 1.872 ± 0.058–1.917 ± 0.066 × 10−3 mm2/s; 93.7 ± 4.9 ms vs 98.0 ± 2.9–100.7 ± 4.0 ms, respectively, all P < 0.05), consistent with excessively fluid-filled microcysts (aquaporin-2+). Despite DOCA-salt rats harbored markedly increased fibrosis in outer and inner stripes of the outer medulla at weeks 6 and 8, only nonsignificant decreases in FA were observed in comparison with the controls suggesting that only limited microstructural changes were present.
Renal cortical FA is useful for the early detection and monitoring of renal damage in DOCA-salt hypertensive rats.
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The authors would like to thank Dr. You-Lin Tain for providing the facility and his assistance in the measurement of blood pressure.
This study was funded by the Ministry of Science and Technology, Taiwan (grant number MOST 106-2314-B-182A-021).
The experiments in this study were approved by the Institutional Animal Care and Use Committee (IACUC number: 2016121695). All the institutional regulations and national guidelines for the care and use of animals were followed.
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Ko, S., Yip, H., Zhen, Y. et al. Renal Damages in Deoxycorticosterone Acetate–Salt Hypertensive Rats: Assessment with Diffusion Tensor Imaging and T2-mapping. Mol Imaging Biol 22, 94–104 (2020). https://doi.org/10.1007/s11307-019-01364-z
- Hypertensive kidney injury
- Diffusion tensor imaging
- Fractional anisotropy
- Mean diffusivity