Introduction

Kidney transplantation is the best therapy for patients with dialysis-dependent renal insufficiency. Delayed graft function (DGF), various frequencies from 2% to 50%, is a form of acute renal failure that results in post-transplantation oliguria [1]. Various transplant complications might occur in patients with DGF and have further substantial impacts on loss of renal graft function, morbidity or mortality. Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) has been developed to visualize water molecular diffusion and micro-circulation of blood in the capillary network [2]. The tri-exponential IVIM model provides three distinct signal fractions of a pure diffusion, an intermediate and an ultrafast component of pseudo-diffusion. This would be more preferable and sensitive to assess the status of cellular damage and vascular dysfunction induced by the ischemia-reperfusion injury of graft kidneys than the conventional mono-exponential and bi-exponential models [3]. In this study, we aim to evaluate the clinical applicability of the tri-exponential model in identifying DGF with complications immediately after transplantation.

Methods

Twenty-eight patients were enrolled in this study and had their MRI scans for kidney allografts after transplant surgery within 3 to 7 days on a 1.5T MRI. 17 patients were diagnosed as DGF in the experiment, based on a combination of serum creatinine (sCr) greater than 2.5 mg/dL on day 7 or the need for post-transplant hemodialysis in the first week. 8 of 17 patients, who had early post-transplant complications, including 3 acute rejections, 2 acute tubular necrosis, and three perirenal hematomas, were defined as DGF with complication (DGFwC). 10 of 17 patients who had no known complication were defined as DGF without complication (DGFwoC). Other 11 patients who’s sCr decreased below 2.5mg/dL in 7 days, were assigned to the group with early graft function (EGF). Morphological imaging sequences included fast spin echo T1WI (TR/TE=500-550/9-10ms, echo-train-length=3) and T2WI (TR/TE=3000/80ms, echo-train-length=23) in the long-axis coronal section of graft kidneys. IVIM-DWI, using free breathing spin echo-echo planar imaging with nine b values of 0, 10, 20, 30, 50, 100, 300, 500 and 800 s/mm², was also acquired in long-axis coronal section. The diffusion parameters were calculated by using the mono-, bi- and tri-exponential analysis, with the following equations:
S_b = S₀ × exp(-b×ADC) ----------------------------------------------------- [Eq.1]
S_b = S₀ × [(1 – f_f,2) exp(-b×D_s,2) + f_f,2 × exp(-b×D_f,2)]------------------------------------- [ Eq. 2]
S_b = S₀ × [(1 – f_i,3 – f_f,3) exp(-b×D_s,3) + f_i,3 × exp(-b×D_i,3) + f_f,3× exp(-b×D_f,3)]-----------------– [Eq. 3]
where S₀ is the unweighted signal; S_b is the diffusion weighted signal; b is the b-value; where ADC is apparent diffusion coefficient derived from the mono-exponential fit, D_s,2 and D_s,3 are the slow diffusion constants obtained from the bi- and tri-exponential IVIM models; D_f,2 and D_f,3 are the fast diffusion constants obtained from the bi- and tri-exponential IVIM models; D_i,3 is the intermediate diffusion constant obtained from the tri-exponential IVIM models; f_f,2, f_i,3 and f_f,3 are the signal fractions of D_f,2, D_i,3 and D_f,3. The tri-exponential IVIM values were computed by a trust-region based least-squares algorithm with constrained ranges for each parameters (0< slow diffusion <=5μm²/msec, 5μm²/msec < intermediate diffusion <=100μm²/msec, and 100μm²/msec < fast diffusion <= 1000μm²/msec).

Results

The statistical analysis of IVIM parameters in 28 allograft kidneys were listed in Table 1. The pure diffusivities of ADC in each of three groups were the highest, followed by D_s,2 and D_s,3. There exists significant differences of ADC, D_s,2, but no difference of D_s,3 among three groups of allograft kidneys. Our results also illustrate significantly higher mean f_f,2 and f_i,3 of 17.2±2.3% and 27.6±3.8% in the EGF group than those of 13.4±1.8% and 20.3±5.7% in DGFwoC group, 12.0±1.2% and 14.5±4.3% in DGFwC group. However, there is no significant difference of f_f,3 among three groups of allograft kidneys. For analysis of pair-wise comparison of all IVIM parameters, there only exists a significant difference of f_i,3 between all pairs of three groups of allograft kidneys.

Discussion

With higher values of ADC, D_s,2 than D_s,3 allograft kidneys, the findings would suggest that the mono- and bi-exponential analysis does not fully differentiate the contamination of the fast water moving in the blood vessels, capillaries and renal tubules from the pure water diffusion occurred in the allograft kidneys. For no significant difference of D_s,3 among three groups of allograft kidneys, it would reflect no significant micro-structural alternation of allograft renal parenchyma in the consequence of ischemia-reperfusion injury (IRI) immediately after transplantation. For the significant difference of f_i,3 among the three groups of allograft kidneys as well as between the DGFwoC and DGFwC groups, the findings of decreased intermediate fraction would reflect the compounding vascular dysfunction of allograft renal parenchyma in DGFwC, in addition to direct IRI effect immediate after kidney transplantation.

Conclusion

The study illustrated the clinical benefit of the Tri-exponential analysis of IVIM-DWI in evaluation of functional changes in renal allografts. We believed that the f_i,3 value of the intermediate component would provide a good indicator for distinguishing the EGF, DGFwoC and DGFwC. IVIM-DWI would potentially provide a promising indicator for identifying further allograft dysfunction in DGF with complications and likely be suitable for selecting patients with DGF for renal biopsy.

Acknowledgements

Nil.