Assessment of Physiological Changes Associated with Renal Fibrosis in a Rat Model
Lei Jiang1, Paul Territo1, Brian McCarthy1, Amanda A. Riley1, Sourajit Mustafi1, Yu-Chien Wu1, Bruce Molitoris2, Gary Hutchins1, and Chen Lin1

1Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, 2Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States


The objective of this study is to evaluate the capability of quantitative MRI techniques to measure physiological changes associated with changes in renal function in a rat model. Our investigation suggest that the results of T2* mapping, intra-voxel incoherent motion (IVIM), and T1ρ imaging are comparable to the published results. These techniques can be used to assess and monitor different aspects of physiological changes in kidney fibrosis.


The objective of this study is to evaluate the sensitivity of three quantitative MRI techniques to measure physiological changes associated with renal fibrosis in a rat model. We investigated T2* blood oxygenation level-dependent imaging (T2* BOLD) for renal tissue oxygenation [2], T1ρ imaging for macromolecular composition [3], and intra-voxel incoherent motion (IVIM) imaging for pseudo perfusion (Df) and perfusion fraction (Pf) [4].


The investigation was conducted following the Institutional Animal Care and Use Committee (IACUC) guidelines. Four rats were studied following a unilateral Ischemia-Reperfusion (I/R) intervention. Fibrosis in one of the kidneys was introduced by clamping the pedicle (Artery, Vein and Pelvis) for 50min. Subsequent MRI examinations were performed on a Siemens Tim Trio 3T scanner using an 80mm inner diameter 8-channel rat body coil (RAPID MRI, Germany). Rats were anaesthetized with 2-4% isoflurane (balance medical oxygen) through a dedicated nose cone. The MR imaging protocol included a coronal T2-weighted 3D SPACE sequence (FOV=150mm, Resolution=0.5 x 0.5 x 0.5mm3) for anatomical imaging as well as transverse multi-echo GRE sequence for T2*(10 TEs of 8 - 66ms), T1ρ prepared 3D spoiled GRE sequence for T1ρ (9 spin-lock (SL) times of 5 - 80ms) and diffusion weighted (DW) single-shot EPI sequence for IVIM (10 b-values of 0-750s/mm2). These transverse images have matching slices of FOV 80 x 80mm2, matrix 192 x 192 and 2mm slice thickness. All rats were scanned at early (2-5 days) and late (25-35 days) time points after the surgical intervention. Two types of ROI were drawn: one that covers both the cortex and medulla in each kidney and another one in the paraspinal muscle area. The results from muscle ROI serve as an internal reference in the longitudinal study. Quantitative T1ρ maps (Figure2) are created by fitting the signal intensity of T1ρ-weighted MR images as a function of the SL pulse duration with fixed amplitude. T2* maps (Figure2) are obtained by fitting the signal intensities as a function of TE times. In addition, Df and Pf are computed by bi-exponential fitting the change of MRI signal with b-values using the Levenberg-Marquardt algorithm. Statistical t-test analyses were conducted and p< 0.05 was considered statistically significant.


T2w 3D SPACE Images (Figure 1) shows the typical anatomical images of the injured (left side) and healthy (right side) rat kidneys. The injured kidney atropied after more than one month and its apperance in T2 weighted images changed compared to the healthy kidney, demonstrating the progression of fibrosis. As shown in Table 1 , the T2* values were similar in both healthy and injured kidneys at early time points , whereas significantly decreased T2* values were observed in injured kidney at late time points (p = 0.017). Table 1 also shows significant differences in IVIM Df and Pf values. It appears that the IVIM for injured kidney at early time points is significantly different from healthy kidney (p=0.0122 for Df and 0.0022 for Pf, respectively) and late stage (p=0.044 for Df and 0.0002 for Pf, respectively). However, although we could detect T1ρ increase in the injured kidney, compared to the healthy kidney between the early and late stages, there was no significant difference between healthy vs injured (p=0.8414/0.3734) and early vs late (p=0.1625) for T1p. For the muscle ROIs, there was always no significant difference between early vs. late time points for all three imaging studies.


In this limited pilot study we demonstrated the feasibility of performing high quality quantitative functional imaging in the rat kidney using dedicated imaging coils and advanced imaging techniques originally developed for human applications. The results obtained in this study demonstrate statistically significant changes in multiple MRI derived measures of tissue physiology (T2*, Df, Pf) at both early and late time points following an ischemia/reperfusion intervention. However, we did not observe any significant differences in the data generated using the T1p method. These preliminary results suggest that multiple MRI derived parameters have the potential to provide important information about changes in kidney function shortly after an initial insult and during the progression of kidney disease and increasing levels of fibrotic burden. The sample size of this study was very small and further studies are warranted to confirm these initial observations and establish the utility of MRI derived parameters as biomarkers of kidney disease and disease progression over time.


These findings suggest that the results of IVIM, T2*, and T1p are comparable to the published results[2-4]. Further investigations are needed to improve the T1p method. These techniques may be useful for monitoring changes in kidney physiology associated with kidney disease or injury.


No acknowledgement found.


1. Inoue T, et al. Noninvasive evaluation of kidney hypoxia and fibrosis using magnetic resonance imaging. J Am Soc Nephrol. 2011 Aug;22(8):1429-34.

2. Li LP, et al. Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats by blood oxygen level-dependent magnetic resonance imaging. Invest Radiol. 2014 Jun;49(6):403-10

3. Wang YX, et al. T1rho MR imaging is sensitive to evaluate liver fibrosis: an experimental study in a rat biliary duct ligation model. Radiology. 2011 Jun;259(3):712-9

4. Wu HH, et al. Monitoring the progression of renal fibrosis by T2-weighted signal intensity and diffusion weighted magnetic resonance imaging in cisplatin induced rat models. Chin Med J (Engl). 2015 Mar 5;128(5):626-31


Figure 1: T2w 3D SPACE Images, which shows anatomical images of the obstructed (left side) and healthy (right side) rat kidneys.

Figure 2: T1p mapping (left) and T2* mapping (right) at late stage

Table 1: List of the T2*, T1p and IVIM results, and the statistical analysis between early and late and between injured and healthy (p value < 0.05 statistically significant.)

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)