Brain white matter microstructural alterations in patients with diabetic retinopathy: an automated fiber-tract quantification study

Abstract

Background: Cognitive decline may occur in patients with diabetic retinopathy (DR), yet the mechanism underlying the relationship between cognitive decline and DR remains unclear. This study applied an automated fiber-tract quantification (AFQ) technique based on diffusion tensor imaging (DTI) to identify alterations in specific segments of brain white matter fiber tracts in patients with DR, and analyze their correlation with cognitive test scores and clinical biochemical indicators.

Methods: A total of 19 patients with DR and 20 age-, sex-, and education-matched healthy controls (HCs) were included. Clinical and imaging data were prospectively collected. The AFQ technique was applied to track the whole brain white matter fiber tracts of each participant, and each fiber tract was segmented into 100 equidistant nodes. The fractional anisotropy (FA), mean diffusion (MD), axial diffusion (AD), and radial diffusion in 100 nodes of each fiber tract were calculated and compared between the two groups. Partial correlation analysis was performed to analyze the correlation between altered DTI metrics in segments of the fiber tracts and cognitive test scores, as well as clinical biochemical indicators in patients with DR.

Results: Compared with the HC group, the DR group showed significantly reduced FA values in nodes 81-100, increased MD values in nodes 39-50, and reduced AD values in nodes 91-100 of the left cingulum cingulate (CGC) [P<0.05, false discovery rate (FDR) corrected], they also showed increased AD values in the left superior longitudinal fasciculus (SLF; nodes 1-23, 37-50, and 66-99), and the right SLF (nodes 1-36 and 79-100) (P<0.05, FDR corrected). Correlation analysis revealed a positive correlation between the FA values in nodes 82-98 of the left CGC and Montreal Cognitive Assessment scores (MoCA scores, r=0.760, P<0.05/P=0.021), and a positive correlation between the AD values in nodes 37-41 in the left SLF and glycated hemoglobin A1c (HbA1c) levels (r=0.559, P<0.05/P=0.039).

Conclusions: Our findings demonstrated alterations in the white matter fiber tracts at the point-wise level in patients with DR using AFQ analysis. These alterations may be associated with cognitive impairment in DR. The AFQ technique can accurately detect the damage to the integrity of the brain white matter fiber tracts in patients with DR, and have high clinical application value in the diagnosis and evaluation of DR, which can deepen our understanding of brain white matter microstructural abnormalities in patients with DR.

Keywords: Diabetic retinopathy (DR); automated fiber-tract quantification (AFQ); cognitive impairment; diffusion tensor imaging (DTI).

Figure 1

Significant differences in DTI metrics in different segments of the left CGC observed between the DR and HC groups. (A) Midsagittal view of the left CGC. The colored bands represent the distribution of FA values. (B-D) Compared with the HC group, the DR group showed significantly decreased FA values in nodes 81–100, increased MD values in nodes 39–50, and reduced AD values in nodes 91–100 of the left CGC (all P<0.05, FDR corrected). The solid line indicates the mean value, and the dashed line indicates the standard deviation. DTI, diffusion tensor imaging; CGC, cingulum cingulate; DR, diabetic retinopathy; HC, healthy control; FA, fractional anisotropy; MD, mean diffusion; AD, axial diffusion; FDR, false discovery rate.

Figure 2

Significant differences in the AD values in different segments of the left and right SLF observed between the DR and HC groups. (A,B) Midsagittal view of the left and right SLF. The colored bands represent the distribution of FA values. (C,D) Compared with the HC group, the DR group showed increased AD values in nodes 1–23, 37–50, and 66–99 of the left SLF and nodes 1–36 and 79–100 of the right SLF (all P<0.05, FDR corrected). The solid line indicates the mean value, and the dashed line indicates the standard deviation. SLF, superior longitudinal fasciculus; DR, diabetic retinopathy; HC, healthy control; AD, axial diffusion; FDR, false discovery rate; FA, fractional anisotropy.

Figure 3

The correlations between the mean FA values in nodes 82–98 of the left CGC and MoCA scores in the DR group. DR, diabetic retinopathy; CGC, cingulum cingulate; FA, fractional anisotropy; MoCA, Montreal Cognitive Assessment.

Figure 4

The correlations between the mean AD values in nodes 37–41 of the left SLF and HbA1c levels in the DR group. DR, diabetic retinopathy; SLF, superior longitudinal fasciculus; HbA1c, glycated hemoglobin; AD, axial diffusion.