Purpose: To examine the feasibility of using intravoxel incoherent motion (IVIM) MRI to measure the changes in kidney diffusion and perfusion in the course of contrast-induced acute kidney injury (CI-AKI).

Methods: The institutional research ethics committee approved this study.Twenty-seven rats received 2.22 g/kg Meglumine Diatrizoate to induce CI-AKI. IVIM MRI was performed on CI-AKI rats (n=6) before and after the onset using a GE 3.0 T MRI scanner. The IVIM DWI was performed using a single-shot diffusion-weighted spin-echo EPI (ten b values: 0, 20, 40, 60, 80, 100, 200, 400, 500 and 600 s/mm2). The lookup table of gradient directions was modified to allow multiple b value measurements in one series. A local shim box covering the kidney region was applied to minimize susceptibility artifacts. The DWI data set was either to fit conventional mono-exponential diffusion model to calculate ADC values or to fit the bi-exponential IVIM model to calculate parameters including pure diffusion coefficient D, pseudo-diffusion coefficient D* and microvascular volume fraction f. All results are reported as mean ± SD. All data were analyzed using SPSS 20.0 (SPSS Inc, Chicago, IL, USA). Two Way Repeated Measures ANOVA and Least Significant Difference (LSD) method for further comparisons between specific group pairs were used. P < 0.05 was considered statistically significant. The Spearman correlation coefficients were calculated to determine the correlation between ADC and D. Histology. Three rats were sacrificed for histological assessment at each time point (total n=21). The pathological images of H&E staining from the right kidney were obtained at 24 h pre-injection and at 12 , 24 , 48 , 72 , and 96 h after the injection of contrast agent.

Results: As shown in Figs. 1a-d, we successfully applied IVIM model to calculate both diffusion and perfusion parameters in the right kidney. Our data shows there is a good correlation between the calculated ADC and D for CO (r =0.775, P < 0.0001), OM (r =0.874, P < 0.0001), IM (r =0.866, P < 0.0001), and for all the regions (r =0.857, P < 0.0001) measured in the present study. The decrease in kidney diffusion first progresses with time, and then reverses at around 48 h. The maximal decrease of the diffusion in CO was at 48 h as compared to its baseline value, i.e., ∆D=25.8% (P < 0.0001) and ∆ADC= 28.2% (P < 0.0001). A similar pattern of decrease and recovery of tissue diffusion was observed in OM and IM. Interestingly, the time to the maximal decrease in the medulla (72 h) is later than that in cortex (48 h). Similar to the pattern of changes in tissue diffusion, all the perfusion-related parameters first decreased and then recovered. In particular, as shown in Figure 4a, the f values in both the cortex and medullar were markedly reduced (33.0%, 31.4% and 39.0% for CO, IM and OM respectively) in the first 48 h, then recovered slowly back to 89.7%, 93.8%, and 96.3% of the baseline value by the end of MRI measurement (96 h). The D* values were also markedly reduced (46.1%, 36.2% and 42.1% for CO, IM and OM respectively) but reached their maximum at an earlier time point (i.e. 24 h), then recovered slowly back to 85.6%, 100.0%, and 78.5% of the baseline value by the end of MRI measurement (96 h). We further compared the perfusion and diffusion changes in different parts of kidney (Figure 5a-c). The changes in ADC, D* and D progressed at almost identical pace in CO, but not in OM and IM. The change in D* was similar in different parts of kidney. All parameters significantly decreased in the first 12 h. D* had the highest degree of signal change (~ 31.4%) in the first 12 h, and in the fist 24 h (~ 42.5%). D* is the most sensitive parameter that showed a recovery at as early as 24 h. The D, D*, and f had no significant differences among CO, OM, and IM (for all, P > 0.05), while the ADC values were statistically different between CO and OM (P = 0.394).

Conclusion: our study demonstrates the feasibility of using IVIM MRI to monitor the progress of CI-AKI in an animal model, implying that IVIM is a useful biomarker in the diagnosis and staging of CI-AKI. Considering IVIM MRI technique has been implemented in the clinical regimes, our approach can be quickly translated to the patient study for monitoring renal pathophysiologic alternations after the administration of iodinated contrast agent, which will greatly benefit elderly patients or patients with pre-existing kidney insufficiency and diabetes.