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. 2018 Apr;79(4):2216-2227.
doi: 10.1002/mrm.26849. Epub 2017 Jul 24.

Assessment of unilateral ureter obstruction with multi-parametric MRI

Feng Wang  1   2 , Keiko Takahashi  3 , Hua Li  1   2 , Zhongliang Zu  1   2 , Ke Li  1   2 , Junzhong Xu  1   2   4 , Raymond C Harris  3 , Takamune Takahashi  3 , John C Gore  1   2   4
Affiliations

Assessment of unilateral ureter obstruction with multi-parametric MRI

Feng Wang et al. Magn Reson Med. 2018 Apr.

Abstract

Purpose: Quantitative multi-parametric MRI (mpMRI) methods may allow the assessment of renal injury and function in a sensitive and objective manner. This study aimed to evaluate an array of MRI methods that exploit endogenous contrasts including relaxation rates, pool size ratio (PSR) derived from quantitative magnetization transfer (qMT), chemical exchange saturation transfer (CEST), nuclear Overhauser enhancement (NOE), and apparent diffusion coefficient (ADC) for their sensitivity and specificity in detecting abnormal features associated with kidney disease in a murine model of unilateral ureter obstruction (UUO).

Methods: MRI scans were performed in anesthetized C57BL/6N mice 1, 3, or 6 days after UUO at 7T. Paraffin tissue sections were stained with Masson trichrome following MRI.

Results: Compared to contralateral kidneys, the cortices of UUO kidneys showed decreases of relaxation rates R1 and R2 , PSR, NOE, and ADC. No significant changes in CEST effects were observed for the cortical region of UUO kidneys. The MRI parametric changes in renal cortex are related to tubular cell death, tubular atrophy, tubular dilation, urine retention, and interstitial fibrosis in the cortex of UUO kidneys.

Conclusion: Measurements of multiple MRI parameters provide comprehensive information about the molecular and cellular changes produced by UUO. Magn Reson Med 79:2216-2227, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Keywords: apparent diffusion coefficient (ADC); chemical exchange saturation transfer (CEST); multi-parametric MRI (mpMRI); nuclear Overhauser enhancement (NOE); pool size ratio (PSR); relaxation; renal injury; unilateral ureter obstruction (UUO).

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Figures

Figure 1
Figure 1
Representative histological sections from normal and UUO kidney cortices (Masson trichrome stain). The urine retention and tubular dilation substantially increased, as indicated by destructive morphology of renal tubules (*), tubular atrophy (green arrows), tubules with denuded basement membrane (blue arrows), and interstitial fibrosis (light blue areas indicated by black arrows).
Figure 2
Figure 2
Representative mapping of ADC and relaxation. (a) ADC from fitting. The regional signals of cortex, OM, IM+P, and pelvis are indicated by circles, squares, triangles, and diamonds, respectively. The curves represent the mono-exponential fitting results. Only b-values > 300 s/mm2 were used in fitting. CL-contralateral, UUO-unilateral ureter obstruction. (b) ADC, R1 and R2 maps. T1W: T1-weighted, T2W: T2-weighted. ROIs were identified in T1W and T2W images. 1-cortex, 2-OM, 3-IM+P, 4-pelvis with obstructed urine. Data were from a mouse 3 days after UUO.
Figure 3
Figure 3
Comparison of representative cortical distributions of measured MRI parameters of CL and UUO kidneys. Cortical Mean ± SD (standard deviation) values across voxels were shown, with CL in gray and UUO in red. *p < 0.05, and **p < 0.01. Data were from a mouse 3 days after UUO.
Figure 4
Figure 4
QMT imaging. (a) Image with magnetization transfer contrast (MTC) and PSR map. 1-cortex, 2-OM, 3-IM+P, 4-pelvis with obstructed urine. ROIs were defined in the respective T1-weighted image, and then applied to MTC image and PSR map (solid white outlines). The contrast between OSOM and ISOM is big, indicated by the dashed white outlines. (b) The fitting of the model to in vivo MT data of cortical tissues in the CL and UUO kidneys at two flip angles of 820° and 220°. Curves were normalized to maximum intensity. (c) Cortical PSR distributions across voxels in CL (gray) and UUO (red) kidneys, with regional Mean ± SD values of PSR shown. Data were from a mouse 6 days after UUO.
Figure 5
Figure 5
Renal Z-spectroscopic features of UUO. (a) T1-weighted image and PCC map showing Pearson correlation coefficient between Z-spectra at each voxel. The averaged Z-spectrum of CL cortex was selected as the seed for correlation analysis. ROIs were defined in T1-weighted image (solid white outlines). 1-cortex, 2-OM, 3-IM+P, 4-pelvis with obstructed urine. The contrast between OSOM and ISOM is big, indicated by the dashed white outlines. (b) Characteristic spectroscopic features of normal cortical tissue. Asterisks indicate CEST effects, 1-head arrows indicate NOE effects, and 2-head arrow indicates semi-solid MT effect. Pool I, II, III, IV, V and VI were separated from 6-peak Lorentzian fitting. (c) Comparison of the regional spectra in UUO and CL kidneys. Black circles: cortex, blue squares: OM, purple triangles: IM+P, and red crosses: pelvis with obstructed urine. Data were from a mouse 6 days after UUO.
Figure 6
Figure 6
Multi-parametric maps of UUO mouse on day 6 after surgery. T1-weighted (T1W) and magnetization transfer contrast (MTC) images showed hypointensity and hyperintensity respectively for the pelvis with obstructed urine in UUO kidney (red arrows). NOE, DS and CEST effects were peak amplitudes from the fitting of CEST Z-spectra. RF offsets for NOE, DS, and CEST effects were indicated.
Figure 7
Figure 7
Cortical MRI measures 6 days after UUO surgery. Boxplots show the comparison between CL and UUO kidneys. Middle lines indicate median and circles indicate mean values across subjects (N=8). RF offsets for NOE, DS, and CEST effects were indicated. *p < 0.05, **p < 5x10−3, ***p < 5x10−4, and ****p < 5x10−5 vs. CL measures.
Figure 8
Figure 8
Correlations between cortical changes in MRI parameters 6 days after UUO surgery. Correlation coefficient r is shown with respective p value. Note that p value in dark red is not significant (p ≥ 0.05). In the r and p plots, 1-PSR, 2-R1, 3-R2, 4-ADC, 5-NOE (-3.5 ppm), 6-NOE (-1.6 ppm), 7-DS (0.0 ppm), 8-CEST (1.2 ppm), 9-CEST (2.2 ppm), 10-CEST (3.5 ppm).
Figure 9
Figure 9
Temporal variations of selected MRI measures. CL cortical measures showed consistent values over time and were used as controls for comparison. *p < 0.05, **p < 1x10−2, ***p < 1x10−3, and ****p < 1x10−4.
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