Synopsis

Intravoxel incoherent motion (IVIM) DWI is able to simultaneously detect diffusion and perfusion characteristics of renal tissue, which provides more sensitive measurement of renal function than serum creatinine. This study investigates the feasibility of using IVIM DWI to evaluate renal diffusion and perfusion changes in ischemic AKI animals. IVIM DWI was performed on rabbits prior to (24 hours before surgery) and after the surgery (1 hour, 3 hours, 1 week and 2 weeks after surgery). After injection of 0.8 mg microspheres, a noticeable change of renal diffusion and perfusion can be seen in the cortex immediately after the surgery. Pathological results also confirmed the renal injury with findings of ischemic and wrinkled features with dilated change of Bowman’s capsule.

Background

Purpose

Materials and Methods

Animal Model:

All procedures used in this study were approved by our local Research Ethics Committee. Six male New Zealand rabbits with body weights of 2.5-3.5 kg were included in the study. To establish ischemic AKI model, we injected 0.8 mg microspheres (acryl beads, 40 to 120 μm in diameter) into the ostium of the right renal artery under anesthesia condition. MRI scan was performed at different time to evaluate progressive changes of the AKI kidney. Four weeks after the surgery, pathological images of H&E staining were obtained.

MR Imaging:

IVIM DWI was performed on rabbits (n = 6) prior to (24 hours before surgery) and after the surgery (1 hour, 3 hours, 1 week and 2 weeks after surgery) using a 3.0 T MRI scanner (Achieva, Philips Medical Systems). During the MRI experiments, anesthesia was induced with isoflurane (1.0 L/min) delivered by a facemask. DWI was performed using a single-shot spin-echo echo-planar (EPI) sequence (coronal,
 TR = 3000 ms, TE = 65 ms, acquired matrix = 98 × 80, FOV = 150 × 150 mm², slice thickness = 5 mm, gap = 1.0 mm, SNESE factor = 2). The following b-values were used for acquisition: 0, 20, 40, 60, 80, 100, 150, 200, 300, 400, 500, 600, 700, 800, 900 and 1000 sec/mm². Respiratory triggering was applied to make the images motion insensitive. Quantitative Analysis: Before parameter fitting, a two-dimensional affine registration was performed to mitigate respiratory motion artifacts using an in-house software. According to the IVIM model, the DWI signal can be related as follows:

$$ S_b/S_0=（1-f）\cdot\exp(-bD)+f\cdot\exp(-bD*) $$

where S₀ is the signal intensity at b = 0, S_b is the signal intensity at nonzero b value, D is the true diffusion coefficient, D* is the pseudodiffusion coefficient, and f is the fraction of microvascular volume. All the parameters were estimated using the least squares fitting algorithm. ADC was calculated using a monoexponential model with all b values. The changes in the diffusion (ADC, D) and perfusion parameters (D* and f) were analyzed in renal cortex, medulla and injuried renal region manually selected in T2w images.

Results

Fig 1 shows representative T2w and DWI images acquired before and after AKI surgery (1 hour, 3 hours, 1 week and 4 weeks after AKI surgery). Once in the bloodstream, micro-emboli lodged in small arteries and produced a microcrystalline angiitis, characterized by endothelial inflammatory reaction developing in a stepwise pattern (Fig 1, red arrows). Fig 2 shows the renal parametric maps of IVIM-metrics (ADC, D, D*, and f maps) of an AKI rabbit. The results show a clearly higher baseline diffusion rate (ADC) in healthy renal cortex (1.58 ± 0.03 ×10^-3 mm²/s) than that in the medulla (1.45 ± 0.03 ×10^-3 mm²/s), which is consistent with previous reports [4]. After injection of 0.8 mg microspheres, a noticeable change of renal diffusion and perfusion can be seen in the cortex immediately after the surgery (Fig 2, Hour 1, red arrows). Pathological results also confirmed the renal injury with findings of ischemic and wrinkled features with dilated change of Bowman’s capsule (Fig 3).

In the AKI cortex, D reduced progressively after surgery (Pre:1.34 ± 0.04 × 10^-3 mm²/s; Hour 1: 0.95 ± 0.03 × 10^-3 mm²/s; Hour 2: 0.93 ± 0.05 × 10^-3 mm²/s) and increased starting after one week (Fig 4b). D* decreased to the bottom at the first hour after surgery (6.26 ± 2.18 ×10^-3 mm²/s) and started to recover 3 hours after surgery (6.47 ± 2.37 × 10^-3 mm²/s, Fig 4d). f fell from 0.24 ± 0.02 (Pre) to 0.04 ± 0.01 (Hour 1, P < 0.01), and returned 0.14 ± 0.02 after two weeks of recovery (Fig 4c).

Conclusions

Acknowledgements

References

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3. Hörbelt M, Lee S Y, Mang H E, et al. Acute and chronic microvascular alterations in a mouse model of ischemic acute kidney injury. American Journal of Physiology Renal Physiology, 2007, 293(3):688-695.

4. Notohamiprodjo M, Chandarana H, Mikheev A, et al. Combined intravoxel incoherent motion and diffusion tensor imaging of renal diffusion and flow anisotropy. Magn Reson Med 2015, 73:1526–1532