Home Comparison of T1 Mapping and T1rho Values with Conventional Diffusion-weighted Imaging to Assess Fibrosis in a Rat Model of Unilateral Ureteral Obstruction
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Comparison of T1 Mapping and T1rho Values with Conventional Diffusion-weighted Imaging to Assess Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

Rationale and Objectives

The aim of this study was to investigate the potential of magnetic resonance imaging (MRI) T1 mapping and T1 relaxation time in the rotating frame (T1rho) for assessment of renal fibrosis in a rat model of unilateral ureteral obstruction (UUO).

Materials and Methods

UUO was created in 36 rats. Six rats were scanned at each of the six time points (on days 0, 1, 3, 5, 10, and 15 after UUO). The contralateral kidneys were examined as controls. Hematoxylin-eosin, Masson’s trichrome, and alpha-smooth muscle actin (α-SMA) antibody staining assays were performed. MRI data obtained with a 3.0T scanner were analyzed with α-SMA expression and Masson’s staining.

Results

The T1 relaxation times and T1rho values increased, and the mean apparent diffusion coefficient (ADC) values decreased with time after UUO. Simple regression analysis indicated that the mean ADCs, T1 relaxation times, and T1rho values had strong correlations with the α-SMA expression levels (R 2 = 0.34, R 2 = 0.66, R 2 = 0.71, respectively; P < .001) and positive Masson’s staining (R 2 = 0.38, R 2 = 0.67, R 2 = 0.65, respectively; P < .001).

Conclusions

The T1 mapping and T1rho parameters had better correlations with α-SMA expression and Masson’s staining than ADC values.

Introduction

Chronic kidney disease has become a global public health problem. Renal fibrosis is the common outcome and major pathologic basis for the progression of chronic kidney disease to end-stage renal failure . Therefore, assessment of renal fibrosis is important in determining the diagnosis, assessing the prognosis, and guiding treatment. Ideally, pathologic changes of the kidneys should be observed by renal biopsy. However, this is an invasive procedure, so it cannot be used repeatedly to monitor disease changes . In addition, serologic markers lack sufficient specificity and sensitivity to be useful in clinical practice .

Magnetic resonance imaging (MRI) may provide information regarding the structure and function of the kidneys . Diffusion-weighted imaging (DWI) reflects the random Brownian motion of water molecules in tissues, quantified by the apparent diffusion coefficient (ADC), which indirectly reflects the microstructure. Recently, some studies have shown that renal ADC values strongly correlate with histologic measures of fibrosis . However, the use of ADC to evaluate renal fibrosis is still controversial .

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Materials and Methods

Animal Protocol

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MRI

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MRI Data Analysis

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Figure 1, (a) Histopathologic examination of rat kidneys cut in half lengthwise in order to match the magnetic resonance imaging (MRI). (b) The left kidney was examined by T2-weighted MRI. (c) Regions of interest were manually placed over the renal parenchyma to reveal the three layers of the kidney–cortex (CORT), outer stripe of the medulla (OSOM), and inner stripe of the outer medulla (ISOM). (d) The left kidney and the normal right kidney were examined by T2-weighted MRI on day 10 after UUO. (e) The regions of interest were displaced to match the deformation of the renal parenchyma. (Color version of figure is available online.)

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Histopathologic Examination

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Statistical Analysis

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Results

Histopathologic Examination

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Figure 2, Examples of typical hematoxylin-eosin staining (a) , Masson's trichrome staining (b) , and α-SMA immunohistochemistry (c) on day 0 (before UUO, baseline) and on days 1, 3, 5, 10, and 15 after UUO (200 × magnification). The positively stained areas by Masson's trichrome staining are indicated by thin arrows, and the expression of α-SMA is indicated by thick arrows. UUO, unilateral ureteral obstruction. (Color version of figure is available online.)

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ADC Values, T1 Relaxation Times, and T1rho Values on the Kidney with UUO

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TABLE 1

Mean Apparent Diffusion Coefficient (ADC) Values, T1 Relaxation Times, and T1rho Values of the Renal Parenchyma Before and After Unilateral Ureteral Obstruction (UUO) (mean ± SD) for the UUO Kidney

Time (d) n (35) ADC (×10 −3 mm 2 /s) T1 Relaxation Time (ms) T1rho Value (ms) 0 6 1.83 ± 0.15 1183 ± 72 142 ± 9.6 1 6 1.49 ± 0.08 1290 ± 93 149 ± 10.2 3 6 1.50 ± 0.06 1543 ± 112 175 ± 16.2 5 6 1.46 ± 0.09 1552 ± 152 187 ± 19.9 10 6 1.42 ± 0.06 1698 ± 97 212 ± 22.8 15 5 1.36 ± 0.06 1852 ± 137 228 ± 26.9P value <.001 <.001 <0.001

Figure 3, Examples of typical T1 mapping (a) , T1rho mapping (b) , ADC mapping (c) , and the corresponding immunofluorescence of α-SMA (d) on day 0 (before UUO, baseline) and on days 1, 3, 5, 10, and 15 after UUO. The T1 mapping images on day 15 are shown, with “red” representing the renal pelvis with expansion and “yellow” indicating the renal parenchyma. α-SMA, alpha-smooth muscle actin. ADC, apparent diffusion coefficient; UUO, unilateral ureteral obstruction. (Color version of figure is available online.)

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Relationships Between ADC, T1 Mapping, and T1rho with α-SMA Expression and Masson’s Trichrome Staining

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Figure 4, The percentages of areas positively stained by α-SMA immunohistochemistry and Masson's trichrome as analyzed by simple regression analysis of the mean ADC values, T1 relaxation times, and T1rho values with the α-SMA expression levels. Correlations of (a) ADC values with the α-SMA expression levels; (b) T1 relaxation times with the α-SMA expression levels; and (c) T1 rho values with the α-SMA expression levels. (d) ADC values, (e) T1 relaxation times, and (f) T1 rho values with the percentages of areas positively stained with Masson's trichrome. α-SMA, alpha-smooth muscle actin. ADC, apparent diffusion coefficient

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Contralateral Side (Control) Kidneys

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TABLE 2

Mean Apparent Diffusion Coefficient (ADC) Values, T1 Relaxation Times, and T1rho Values of the Renal Parenchyma (mean ± SD) for Contralateral (Control) Kidneys

Time (d) n (35) ADC (×10 −3 mm 2 /s) T1 Relaxation Time m(ms) T1rho Value (ms) 0 6 1.85 ± 0.14 1184 ± 78 142 ± 8.4 1 6 1.85 ± 0.15 1214 ± 61 139 ± 7.4 3 6 1.91 ± 0.21 1149 ± 58 143 ± 9.4 5 6 1.87 ± 0.15 1171 ± 43 146 ± 8.2 10 6 1.87 ± 0.15 1161 ± 39 144 ± 8.2 15 5 1.90 ± 0.07 1158 ± 57 146 ± 8.9P value .984 .458 .708

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Discussion

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Conclusions

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