Visualization of kidney fibrosis in diabetic nephropathy by long diffusion tensor imaging MRI with spin-echo sequence

Jun-Ya Kaimori,Sosuke Miyoshi,Akira Fujimori,Yoshitaka Isaka,Satoko Yamamoto,Toshiki Moriyama,Akihiko Fujikawa,Naotsugu Ichimaru,Takashi Yokawa,Hiromi Rakugi,Kagayaki Kuroda,Masaki Hatanaka,Hiroshi Shibata,Shiro Takahara

doi:10.1038/s41598-017-06111-4

Abstract

Renal fibrosis (RF) is an indicator for progression of chronic kidney disease (CKD). Although diabetic nephropathy (DN) is the leading cause of CKD and end-stage renal disease in Western populations, the ability of MRI to evaluate RF in DN patients has not been determined. As a first step to identify possible MRI methods for RF evaluation, we examined the use of diffusion tensor imaging (DTI) MRI to evaluate RF in a rat model of DN (SHR/NDmcr-cp(cp/cp): SHR/ND). The signal-to-noise ratio in DTI MRI was enhanced using a spin-echo sequence, and a special kidney attachment was developed for long-term stabilization. The changes in renal temperature and blood flow during measurement were minimal, suggesting the feasibility of this method. At 38 weeks of age, RF had aggressively accumulated in the outer stripe (OS) of the outer medulla. FA maps showed that this method was successful in visualizing and evaluating fibrosis in the OS of the SHR/ND rat kidney (r = 0.7697, P = 0.0126). Interestingly, in the FA color maps, the directions of water molecule diffusion in RF were random, but distinct from conventional water diffusion in brain neuron fibers. These findings indicate that DTI MRI may be able to evaluate RF in CKD by DN.

Highlights

Renal fibrosis (RF) is an indicator for progression of chronic kidney disease (CKD)
In a rat model of RF caused by urethral obstruction (UUO), the apparent diffusion coefficients (ADCs) did not reflect the extent of RF12, suggesting that the ADC alone cannot be used for evaluation of RF in all kidney diseases
SHR/ND rats showed extreme obesity and hypertension, with the kidney tissue of older rats showing massive fibrotic changes concentrated in the outer stripe (OS) of the outer medulla (Supplementary Fig. S1a,b)

Summary

Introduction

Renal fibrosis (RF) is an indicator for progression of chronic kidney disease (CKD). diabetic nephropathy (DN) is the leading cause of CKD and end-stage renal disease in Western populations, the ability of MRI to evaluate RF in DN patients has not been determined. In the FA color maps, the directions of water molecule diffusion in RF were random, but distinct from conventional water diffusion in brain neuron fibers These findings indicate that DTI MRI may be able to evaluate RF in CKD by DN. The FA value in the inner medulla (IM) of rats with DN plus unilateral nephrectomy was found to be negatively correlated with interstitial fibrosis[19] This body of evidence suggests that it is very difficult to visualize and evaluate RF using DTI in a similar manner to neuronal fibers, in DN tissue where intracellular or interstitial edema affects the manner of water molecule diffusion. We report successful visualization of RF in diabetic rats with enhanced fibrosis (SHR/NDmcr-cp(cp/cp): SHR/ND) using our DTI MRI method with spin-echo sequence and long duration measurement enabled by a special kidney attachment

Methods

Results

Conclusion