Non-invasive assessment of early stage diabetic nephropathy by DTI and BOLD MRI

Abstract

Objective: Patients with diabetes mellitus, diabetic nephropathy (DN) and healthy donor were analyzed to test whether the early DN patients can be detected using both blood oxygenation level dependent (BOLD) and diffusion tensor imaging.

Methods: This study was approved by the Ethics Committee of our hospital. MR images were acquired on a 3.0-Tesla MR system (Discovery MR750, General Electric, Milwaukee, WI). 30 diabetic patients were divided into NAU (normal to mildly increased albuminuria, N = 15) and MAU (moderately increased albuminuria, N = 15) group based on the absence or presence of microalbuminuria. 15 controls with sex- and age-matched were enrolled in the study. Prior to MRI scan, all participants were instructed to collect their fresh morning urine samples for quantitative measurement of urinary microalbumin and urinary creatinine. Then, the estimations of serum creatinine, serum uric acid, HbAlc and fasting plasma glucose as well as fundus examinations were performed in all subjects. Then, the values of albumin-creatinine ratio (ACR) and estimated glomerular filtration rate were also calculated. All subjects underwent renal diffusion tensor imaging (DTI) and BOLD acquisition after fasting for 4 h. Regions of interest were placed in renal medulla and cortex for evaluating apparent diffusion coefficient (ADC), fractional anisotropy (FA) and R2* values by two experienced radiologists. The consistency between the two observations was estimated using intragroup correlation coefficients. To test differences in ADC, FA and R2* values across the three groups, the data were 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/estimated glomerular filtration rate and of the ADC/FA/R2* were calculated.

Results: 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. 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) . 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.

Conclusion: 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. These imaging techniques are more accurate and practical than conventional tests.

Advances in knowledge: Non-invasive MRI was used to detect renal function changes at early DN stage.

Figure 1.

Example of ROI measurement on the coronal BOLD image (TE = 27.8 ms, (A1) and DTI (with b = 0 s/mm², (B1) in a 43-year-old female. ROIs were positioned in the medulla (yellow) and cortex (blue) in the upper, middle, and lower parts of each kidney. The ROI had an area of 22–200 mm² (medulla: 50–200 mm²; cortex: 22–40 mm²). The pseudocolor images are R2*map (A2), T2*map (A3), FA map (B2), and ADC map (B3). ADC,apparent diffusion coefficient; BOLD, blood oxygenation level dependent; DTI, diffusiontensor imaging; FA, fractional anisotropy; ROI, region of interest.

Figure 2.

(A) Box plot of medulla and cortical ADC values in healthy volunteers and patients with diabetic nephropathy. (B) Box plot of medulla and cortical FA values in healthy volunteers and patients with diabetic nephropathy. (C) Box plot of medulla and cortical R2* values in healthy volunteers and patients with diabetic nephropathy. *** indicates p＜0.001 ** indicates p＜0.01. ADC,apparent diffusion coefficient; FA, fractional anisotropy.

Figure 3.

Correlations 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 has 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.