Korean J Radiol.  2019 May;20(5):830-843. 10.3348/kjr.2018.0757.

Evaluation of Renal Pathophysiological Processes Induced by an Iodinated Contrast Agent in a Diabetic Rabbit Model Using Intravoxel Incoherent Motion and Blood Oxygenation Level-Dependent Magnetic Resonance Imaging

• Wang Y
• Zhang X
• Wang B
• Xie Y
• Wang Y
• Jiang X
• Wang R
• Ren K

• KMID: 2442717
• DOI: http://doi.org/10.3348/kjr.2018.0757

Abstract

OBJECTIVE
To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model.
MATERIALS AND METHODS
Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were calculated.
RESULTS
The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels.
CONCLUSION
A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.

Keyword

Hypoxia-inducible transcription factor-1α; Vascular endothelial growth factor; Medullary hypoxia; Renal vascular dysfunction

MeSH Terms

Acute Kidney Injury
Body Weight
Creatinine
Diffusion
Iohexol
Kidney
Magnetic Resonance Imaging*
Methods
Oxygen*
Perfusion
Rabbits
Relaxation
Vascular Endothelial Growth Factor A
Creatinine
Iohexol
Oxygen
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1 Experimental flow chart.BOLD = blood oxygen level-dependent, BUN = blood urea nitrogen, Cr = serum creatinine, d = day, FBG = fasting blood glucose, h = hour, IVIM = intravoxel incoherent motion

• 

  Fig. 2 Temporal changes in IVIM measurements in two groups.(A–C) DCA group, (D–F) NCA group. Serially measured parameters (baseline, 1 hour, 1 day, 2 days, 3 days, and 4 days after CA injection) in 6 representative animals were recorded. Asterisk indicates p < 0.05 compared with baseline values. CA = contrast agent, CO = cortex, D = pure tissue molecular diffusion coefficient, D* = pseudo-diffusion coefficient, DCA = diabetic rabbits with contrast agent, f = perfusion fraction of voxel, NCA = healthy rabbits with contrast agent, OM = outer medulla

• 

  Fig. 3 Representative IVIM images of two groups at corresponding time points.Maps were produced with same window and level settings. Maximum D and f signal changes appeared after day 1, whereas D* values appeared after 1 hour, followed by gradual recovery toward baseline values at subsequent time points.

• 

  Fig. 4 R2* maps for two groups obtained at each time point.A. R2* maps in DCA group until day 4. B. R2* maps in NCA group until day 4. C, D. Each data point was average of R2* measurements in 6 rabbits from same group at one scan time. For each group, sharp increase in R2* values was observed after day 1 in two anatomical layers; subsequently, R2* values returned to baseline over time. Asterisk indicates p < 0.05 compared with baseline values. R2* = apparent transverse relaxation rate

• 

  Fig. 5 Representative micrographs of hematoxylin and eosin staining of kidney in two groups.(A, B) DCA group, (C, D) NCA group (original magnification, × 400), (E, F) severity of histopathological injury. *p < 0.05 (compared with baseline values).

• 

  Fig. 6 Representative micrographs of kidney with Masson's trichrome staining.(A, C) diabetic rabbits, (B, D) DCA post day 4, (E, G) healthy rabbits, and (F, H) NCA post day 4 (original magnification × 200). In DCA group, Masson's trichrome staining showed gradual increase in percentage of interstitial fibrosis, while in NCA group, small amount of interstitial fibrosis was observed after day 4.

• 

  Fig. 7 Time course of HIF-1α expression after iohexol injection in each group.(A, B) DCA group, (C, D) NCA group (original magnification × 400). (E, F) Nuclear staining score for HIF-1α in two groups. Expression of HIF-1α slightly increased after 1 hour in all anatomical layers and was significantly higher after day 1 compared to baseline in 2 groups. *p < 0.05 vs. baseline values. HIF-1α = hypoxia-inducible transcription factor-1α

• 

  Fig. 8 Representative photomicrographs for VEGF expression in each group.(A, B) DCA group, (C, D) NCA group (original magnification × 400), (E, F) VEGF scores for two groups. *p < 0.05 vs. baseline values. VEGF = vascular endothelial growth factor

• 

  Fig. 9 Correlation between functional MRI parameters and pathological scores in OM.Significant correlations of renal histological scores with D, f, and R2* values (A, C, and D) and fair correlations of renal histological scores with D* values (B). Significant correlations of renal HIF-1α scores with D, D*, f, and R2* values (E–H). Significant correlations of Cr with R2* values (L) and moderate correlations of Cr with D, D*, and f values (I–K).

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