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. 2023 Sep;90(3):1151-1165.
doi: 10.1002/mrm.29679. Epub 2023 Apr 24.

Severity of polycystic kidney disease revealed by multiparametric MRI

Feng Wang  1   2   3 , Seo Yeon Lee  4 , Fatemeh Adelnia  1 , Keiko Takahashi  3   4 , Kevin D Harkins  1   2   5 , Lilly He  4 , Zhongliang Zu  1   2 , Philipp Ellinger  6 , Manuel Grundmann  6 , Raymond C Harris  3   4 , Takamune Takahashi  3   4 , John C Gore  1   2   5
Affiliations

Severity of polycystic kidney disease revealed by multiparametric MRI

Feng Wang et al. Magn Reson Med. 2023 Sep.

Abstract

Purpose: We aimed to compare multiple MRI parameters, including relaxation rates ( R 1 $$ {R}_1 $$ , R 2 $$ {R}_2 $$ , and R 1 ρ $$ {R}_{1\rho } $$ ), ADC from diffusion weighted imaging, pool size ratio (PSR) from quantitative magnetization transfer, and measures of exchange from spin-lock imaging ( S ρ $$ {S}_{\rho } $$ ), for assessing and predicting the severity of polycystic kidney disease (PKD) over time.

Methods: Pcy/Pcy mice with CD1 strain, a mouse model of autosomal dominant PKD, were imaged at 5, 9, and 26 wk of age using a 7T MRI system. Twelve-week normal CD1 mice were used as controls. Post-mortem paraffin tissue sections were stained using hematoxylin and eosin and picrosirius red to identify histological changes.

Results: Histology detected segmental cyst formation in the early stage (week 5) and progression of PKD over time in Pcy kidneys. In T 2 $$ {T}_2 $$ -weighted images, small cysts appeared locally in cystic kidneys in week 5 and gradually extended to the whole cortex and outer stripe of outer medulla region from week 5 to week 26. Regional PSR, R 1 $$ {R}_1 $$ , R 2 $$ {R}_2 $$ , and R 1 ρ $$ {R}_{1\rho } $$ decreased consistently over time compared to normal kidneys, with significant changes detected in week 5. Among all the MRI measures, R 2 $$ {R}_2 $$ and R 1 ρ $$ {R}_{1\rho } $$ allow highest detectability to PKD, while PSR and R 1 $$ {R}_1 $$ have highest correlation with pathological indices of PKD. Using optimum MRI parameters as regressors, multiple linear regression provides reliable prediction of PKD progression.

Conclusion: R 2 $$ {R}_2 $$ , R 1 $$ {R}_1 $$ , and PSR are sensitive indicators of the presence of PKD. Multiparametric MRI allows a comprehensive analysis of renal changes caused by cyst formation and expansion.

Keywords: MRI; diffusion weighted imaging; magnetization transfer; polycystic kidney disease (PKD); relaxation; spin-lock.

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Figures

Figure 1.
Figure 1.. Representative histopathologic features of PKD from H&E stains.
Cyst is identified as white color areas (indicated by black arrows). Urinary casts are indicated by asterisks. Histologic sections are from a normal CD1 mouse of 12 weeks and representative Pcy/Pcy mice of 5, 9, and 26 weeks.
Figure 2.
Figure 2.. Anatomical MRI images in different contrasts.
T1-weighted (T1W) images, T2-weighted (T2W) images, spin-lock prepared (SL) images and images with magnetization transfer contrast (MTC) were compared between normal CD1 and Pcy/Pcy mice of different age. Arrows indicate the formation of cysts in the early stage. Urinary casts are indicated by the diamond-headed arrows.
Figure 3.
Figure 3.. Multiple MRI parametric maps of cystic and normal kidneys.
T2-weighted (T2W) images zoomed on kidneys (top row). R2,R1ρ (locking frequency 1000 Hz), R2*,R1, PSR, MTR, and ADC maps are compared. PKD mice of 5, 9, and 26 weeks are compared to normal CD1 mouse of 12 weeks. Urinary casts are indicated by red arrows.
Figure 4.
Figure 4.. Group comparison of MRI measures of the CR+OSOM region between cystic and normal kidneys.
Changes of mean values of PSR, MTR, ADC, R1,R1ρ at locking frequency 1000 Hz, R2, and R2* in the CR+OSOM region which was indicated by the red arrow in the T2-weighted (T2W) image. *p < 0.05, **p < 10−3, ***p < 10−5, and ****p < 10−8 vs. respective values of normal CD1 kidneys.
Figure 5.
Figure 5.. Group comparison of MRI parameters from R1ρ dispersion of the CR+OSOM region between cystic and normal kidneys.
The subplot on the top-left shows the fitting of representative R1ρ dispersion curves of 12-week normal CD1 kidney, 5-week Pcy kidney (5wks), 9-week Pcy kidney (9wks), and 26-week Pcy kidney (26wks). Markers indicate raw data and lines from Chopra model. In the boxplots, circles indicate mean values and middle lines indicate median across subjects. Crosses indicate outliers. Asterisks indicate significant parametric differences between Pcy and normal kidneys. **p < 10−3, ***p < 10−5, and ****p < 10−8 vs. respective values of normal CD1 kidneys.
Figure 6.
Figure 6.. Group comparison of conventional pathological indices between cystic and normal kidneys.
(A) Fibrosis scores obtained from picrosirius red stains. (B) Cyst index obtained from H&E stains. (C) Ratio of kidney weight to body weight (KW/BW). (D) Ratio of kidney size to body weight (KS/BW). In the boxplots, circles indicate mean values and middle lines indicate median across subjects. Crosses indicate outliers. Asterisks indicate significant parametric differences between cystic and normal kidneys. *p < 0.05, **p < 10−3, ***p < 10−5, and ****p < 10−8 vs. respective values of normal CD1 kidneys.
Figure 7.
Figure 7.. Correlations between MRI measures in CR+OSOM region and conventional pathological indices.
In the correlation matrices, values are correlation coefficients (r) and crosses indicate nonsignificant correlations (p > 0.05). Thirty-eight kidneys with both histological and MRI measures were included in correlation analysis. CI, cyst index; FS, fibrosis score; KW/BW, kidney weight to body weight; KS/BW, kidney size to body weight.
Figure 8.
Figure 8.. Predict the conventional pathological indices from multiple linear regression (MLR).
Results using the number of regressors are shown for reaching the maximum adjusted R2. Raw data showing the variations of fibrosis score (FS), cyst index (CI), ratio of kidney weight to body weight (KW/BW), and ratio of kidney size to body weight (KS/BW) with pool size ratio (PSR) are in blue, and the predicted values from MLR are in orange. Adjusted R2 from MLR modeling for predicting FS, CI, KW/BW and KS/BW are shown in each plot to indicate the goodness of predication.
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