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Non-invasive assessment of early stage diabetic nephropathy by BOLD and DTI MRI
Youzhen Feng1, Zhongyuan Cheng1, Xiangran Cai1, and Qian Long2

1Medical Imaging Center, First Affiliated Hospital, Jinan university, guangzhou, China, 2GE Healthcare, MR Research China, Beijing, China

Synopsis

Although the specific pathogenesis of diabetic nephropathy (DN) has not yet been clearly elucidated, it has been acknowledged that the development of kidney hypoxia is an early manifestation of the diabetic kidney. In past decades, blood oxygenation level dependent (BOLD) imaging was extensively applied to assess the tissue oxygenation levels, and diffusion imaging was demonstrated the capacity of detecting the tissue damage induced by acute or chronic hypoxia. Hence, to test whether the early DN patients can be detected using both BOLD and diffusion tensor imaging, in current study, patients with diabetes mellitus, diabetic nephropathy and Health volunteers were analyzed.

Synopsis

Although the specific pathogenesis of diabetic nephropathy (DN) has not yet been clearly elucidated, it has been acknowledged that the development of kidney hypoxia is an early manifestation of the diabetic kidney. In past decades, blood oxygenation level dependent (BOLD) imaging was extensively applied to assess the tissue oxygenation levels, and diffusion imaging was demonstrated the capacity of detecting the tissue damage induced by acute or chronic hypoxia. Hence, to test whether the early DN patients can be detected using both BOLD and diffusion tensor imaging, in current study, patients with diabetes mellitus, diabetic nephropathy and Health volunteers were analyzed.

Introduction

Although the specific pathogenesis of diabetic nephropathy (DN) has not yet been clearly elucidated 1, increasing literatures showed that long-term chronic hypoxia might play a leading role in the pathophysiological changes of DN. As a non-invasive imaging approach, blood oxygenation level dependent (BOLD) imaging was extensively applied to assess the tissue oxygenation levels 2. Additionally, the previous studies 3,4,5 demonstrated that diffusion imaging may account for the tissue damage typically induced by acute or chronic hypoxia. Hence, to test whether the early DN patients can be detected using both BOLD and diffusion tensor imaging (DTI), in current study, patients with diabetes mellitus (NAU, N=15), diabetic nephropathy (MAU, N=15) and Health volunteers (Control, N=15) were analyzed.

Materials and methods

MR images were acquired on a 3.0-Tesla MR system (Discovery MR750, General Electric, Milwaukee, WI, USA). Thirty diabetic patients were divided into NAU (N=15) and MAU (N=15) group based on the absence or presence of microalbuminuria. Fifteen Controls with sex- and age-matched were enrolled in the study. Prior to MRI scan, all participants' ACR values and Estimate the glomerular filtration rate (eGFR) were also calculated.All subjects underwent renal DTI and BOLD acquisition after fasting for 4 hours. Regions of interest (ROIs) were placed in renal medulla and cortex for evaluating ADC, FA and R2* values by two experienced radiologists (Fig. 1). The consistency between the two observations was estimated using intra-group correlation Coefficients (ICC). To test differences in ADC, FA and R2* values across the three groups, the data was analyzed using separate one-way ANOVAs. Post-hoc pair wise comparisons were then performed using t-test. To investigate the clinical relevance of imaging parameters in both regions across the three groups, the correlations of values of the ACR/eGFR and of the ADC/FA/R2* were calculated.

Result

There was a high level of consistency of those ADC, FA and R2* values across the three groups on both renal cortex and medulla measured by the two doctors (Table 1). The FA value of medulla in MAU group was lower than that in Control (P < 0.01). The R2* value of medulla in the NAU group was higher than that in the Control (P < 0.01), and the R2* value of medulla in the MAU group was lower than that in the Control (P=0.009) (Table 2, Fig. 2). Moreover, the current study revealed a decreasing trend in FA values of the renal medulla from the Control group to NAU and MAU groups. Finally, a weak negatively correlation between medullary R2* and ACR was found in current study (Fig. 3).

Discussion and Conclusion

In the clinical practice, the appearance of microalbuminuria is usually considered as the earliest clinical indicator of DN. But this paradigm of early DN has been further questioned because a decrease in the renal function of a diabetic patients is not always accompanied by increased albuminuria4. There is a long silent period without overt clinical signs and symptoms of nephropathy prior to the onset of microalbuminuria. Our results indicated medullary hypoxia (reflected by R2* value) occurring in the earlier stage (normoalbuminuria stage) and then its oxygen consumption decreasing to the close normal level in the clinically early DN stage (microalbuminuria stage). The increased oxygen consumption in renal medulla was thought to be mainly related to an increase in metabolic activity, such as glomerular hyperfiltration, active reabsorption of excess sodium, increased Na+/K+–ATPase activity and so on 5-10. Accordingly, we assumed that the renal progressive pathological changes have developed over a long silent period but this subset of diabetic patients don’t exhibit the proteinuria11. Based on this assumption, Medullary R2* value might be a new more sensitive predictor of early DN. Meanwhile, BOLD imaging detected the medullary hypoxia at the simply diabetic stage, while DTI didn’t identify the medullary directional diffusion changes at this stage. Based on our assumption mentioned above, It’s presumable that BOLD imaging may be more sensitive for assessment of the early renal function changes than DTI.

Acknowledgements

No acknowledgement found.

References

1. Mogensen CE. Early glomerular hyperfiltration in insulin-dependent diabetics and late nephropathy. Scandinavian journal of clinical and laboratory investigation. 1986;46(3):201-206.

2. Feng YZ, Chen XQ, Yu J, et al. Intravoxel incoherent motion (IVIM) at 3.0 T: evaluation of early renal function changes in type 2 diabetic patients. Abdominal radiology (New York). 2018.

3. Chen X, Xiao W, Li X, He J, Huang X, Tan Y. In vivo evaluation of renal function using diffusion weighted imaging and diffusion tensor imaging in type 2 diabetics with normoalbuminuria versus microalbuminuria. Frontiers of medicine. 2014;8(4):471-476.

4. Caramori ML, Fioretto P, Mauer M. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes. 2000;49(9):1399-1408.

5. Ries M, Basseau F, Tyndal B, et al. Renal diffusion and BOLD MRI in experimental diabetic nephropathy. Blood oxygen level-dependent. Journal of magnetic resonance imaging : JMRI. 2003;17(1):104-113.

6. Palm F, Cederberg J, Hansell P, Liss P, Carlsson PO. Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension. Diabetologia. 2003;46(8):1153-1160.

7. Wald H, Scherzer P, Popovtzer MM. Enhanced renal tubular ouabain-sensitive ATPase in streptozotocin diabetes mellitus. The American journal of physiology. 1986;251(1 Pt 2):F164-170.

8. Farman N, Corthesy-Theulaz I, Bonvalet JP, Rossier BC. Localization of alpha-isoforms of Na(+)-K(+)-ATPase in rat kidney by in situ hybridization. The American journal of physiology. 1991;260(3 Pt 1):C468-474.

9. Barthelmebs M, Stephan D, Fontaine C, Grima M, Imbs JL. Vascular effects of loop diuretics: an in vivo and in vitro study in the rat. Naunyn-Schmiedeberg's archives of pharmacology. 1994;349(2):209-216.

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11. Schrijvers BF, De Vriese AS, Flyvbjerg A. From hyperglycemia to diabetic kidney disease: the role of metabolic, hemodynamic, intracellular factors and growth factors/cytokines. Endocrine reviews. 2004;25(6):971-1010.

Figures

Figure 1Examples of ROI measurement on the coronal BOLD image (TE=27.8ms, A1) and DTI (with b=0 sec/mm2, B1) in a 43-year-old female patient. ROIs were positioned in the medulla (yellow) and cortex (blue) in the upper, middle, and lower parts of each kidney. And the ROI had an area of 22–200 mm2 (medulla:50-200 mm2; cortex:22-40 mm2) . The pseudo-color images were R2*map (A2), T2*map (A3), FA map (B2), and ADC map (B3), respectively.

Figure 2A) Box plot of medullary and cortical ADC values in healthy volunteers and patients with diabetic nephropathy. B) Box plot of medullary and cortical FA values in healthy volunteers and patients with diabetic nephropathy. C) Box plot of medullary and cortical R2* values in healthy volunteers and patients with diabetic nephropathy. ** indicates P＜0.01*** indicates P＜0.001.

Figure 3Correlations between ACR and ADC (A), FA (B), R2* (C). Correlations between eGFR and ADC (D), FA (E), R2* (F). The R2* value of the medulla had a weak correlation with ACR, and the other parameters had no correlation with ACR or eGFR. ACR, albumin–creatinine ratio; eGFR, estimated glomerular filtration rate; ADC, apparent diffusion coefficient; FA, Fractional anisotropy; R2*, the rate of spin dephasing.

Table 1 Inter-group correlation analysis of data measured by two observers

Table 2 Comparison of ADC values, FA values and R2* values of cortex and medulla between three groups

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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