Experimental study of intravoxel incoherent motion diffusion imaging combined with ultrasound renal resistance index in contrast-induced nephropathy

Abstract

Objective: This study explored the application of Intravoxel Incoherent Motion (IVIM) diffusion imaging combined with Ultrasound Renal Resistance Index (RRI) for monitoring the pathophysiological changes associated with early contrast-induced nephropathy (CIN).

Methods: In this study, forty-two male Sprague-Dawley (SD) rats were equally divided into two groups: a contrast media (CM) group and a control group, each containing 21 animals. The CM group was administered a tail vein injection of ioversol (370 mg I/ml, 1.5 ml/kg), while the control group received a saline solution in a similar volume. Assessments using IVIM-MRI and Doppler ultrasound were performed 24 h before and at 1, 24, 48, and 72 h post-injection. These assessments aimed to evaluate the true diffusion coefficient (D), pseudo-diffusion coefficient (D^*), perfusion fraction (f), apparent diffusion coefficient (ADC), and RRI. Concurrently, three rats from each group were sacrificed at these time points for renal histopathology, hypoxia-inducible factor-1α (HIF-1α) expression analysis, and the quantification of serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was analyzed to evaluate the diagnostic performance of IVIM and RRI in predicting CIN.

Results: Post-ioversol administration, significant declines were noted in the D, D^*, f, ADC across the renal cortex (CO), outer medulla (OM), and inner medulla (IM) from 1 to 48 h (P < 0.05), with the lowest values observed at 48 h. These parameters began to recover after 72 h. Conversely, RRI values escalated from 1 to 48 h, peaking at 48 h (P < 0.05), and then diminished gradually after 72 h. The control group showed no significant changes in these parameters. Furthermore, a negative correlation was observed between RRI, histopathological grades, HIF-1α expression levels, and the levels of SCr and BUN. In contrast, RRI exhibited a positive correlation with these pathological scores and the levels of SCr and BUN. ROC curve analysis revealed that the combined predictive performance of IVIM and RRI was superior to that of individual parameters.

Conclusion: The synergistic application of IVIM and RRI techniques offers a non-invasive approach for early detection of renal damage after ioversol exposure and is a potent method for observing the pathophysiological shifts associated with early-stage CIN.

Keywords: Acute kidney injury; Contrast-induced nephropathy; Intravoxel incoherent motion; Renal resistance index.

Fig. 1

Flowchart of the contrast media group

Fig. 2

Regions of interest images of rat kidneys: (a) A representative T2-weighted image; (b) An enlarged view of the right kidney T2-weighted image, showing three regions of interest (ROIs): the green dashed line indicates the cortex region of interest (CO-ROI), the blue dashed line indicates the outer medulla region of interest (OM-ROI), and the red dashed line indicates the inner medulla region of interest (IM-ROI); (c) An anatomical diagram of the right kidney, showing the corresponding cortex, outer medulla, and inner medulla anatomical divisions

Fig. 3

Coronal cross-sectional parameter images of renal IVIM in the contrast media group of rats at baseline and at 1 h, 24 h, 48 h, and 72 h after contrast media injection

Fig. 4

Doppler ultrasound images of blood flow signals in the contrast media group of rats, as well as renal resistance index value images at 1 h, 24 h, 48 h, and 72 h after contrast media injection. RRI =(peak-systolic velocity − end-diastolic velocity)/peak-systolic velocity

Fig. 5

D, D^*, f and ADC values in the cortex, outer medulla, and inner medulla at each time point for the contrast media group and the control group. The changes in IVIM parameters in the CM group were most significant at 48 h. **P < 0.05

Fig. 6

The RRI values at different time points for the contrast media group and the control group. The changes in RRI in the contrast media group were most significant at 48 h. **P < 0.05

Fig. 7

Hematoxylin-eosin stain images of the renal cortex and medulla at different time points after contrast media injection. The main observations included vacuolar degeneration of tubular epithelial cells (black arrow), infiltration of inflammatory cells in the interstitium (green arrow), and proliferation of some capillary endothelial cells (blue arrow). The renal injury score was most pronounced at 48 h

Fig. 8

After contrast media injection, the expression of HIF-1α in the cortex and medulla gradually increased, with the most significant nuclear staining observed at 48 h (black arrow)

Fig. 9

The IVIM parameters are significantly negatively correlated with RRI

Fig. 10

RRI is significantly positively correlated with renal injury scores, HIF-1α expression, SCr, and BUN

Fig. 11

The ROC curves of IVIM, RRI, SCr, and the combined IVIM and RRI index. The combined index shows higher efficacy in predicting CIN than individual indicators