High connectivity between reduced cortical thickness and disrupted white matter tracts in long-standing type 1 diabetes

Abstract

Objective: Previous studies have observed disruptions in brain white and gray matter structure in individuals with type 1 diabetes, and these structural differences have been associated with neurocognitive testing deficiencies. This study investigated the relationship between cerebral cortical thickness reductions and white matter microstructural integrity loss in a group of patients with type 1 diabetes and in healthy control subjects using diffusion tensor imaging (DTI).

Research design and methods: Twenty-five subjects with type 1 diabetes for at least 15 years and 25 age- and sex-matched control subjects underwent structural T1 and proton-density and DTI on a 3.0 Tesla scanner. Fractional anisotropy measurements were made on major cerebral white matter tracts, and DTI tractography was performed to identify cortical regions with high connectivity to these tracts.

Results: Posterior white matter tracts with reduced fractional anisotropy (optic radiations, posterior corona radiata, and the splenium region of the corpus callosum) were found to have high connectivity with a number of posterior cortical regions, including the cuneus, precuneus, fusiform, and posterior parietal cortical regions. A significant reduction in cortical thickness in the diabetic group was observed in the regions with high connectivity to the optic radiations and posterior corona radiata tracts (P < 0.05).

Conclusions: The direct relationship between white and gray matter structural pathology has not been previously demonstrated in subjects with long-standing type 1 diabetes. The relationship between posterior white matter microstructural integrity disruption and lower cortical thickness demonstrated using a novel DTI connectivity technique suggests a common or interrelated pathophysiological mechanism in type 1 diabetes.

FIG. 1.

Automated white matter image analysis technique resulting in tract-specific regions of interest: corona radiata (red), superior longitudinal fasiciculus (yellow), cungulum bundle (green) (left), six corpus callosum subdivisions (middle), and the optic radiations (right). (A high-quality digital representation of this figure is available in the online issue.)

FIG. 2.

A: Connectivity maps taken from a representative subject. The white matter tract regions of interest in red are used as starting seeds for connectivity mapping, and diffusion MRI data are used to generate connectivity maps. Yellow voxels in these images indicate high connectivity to the original region of interest. The connectivity maps and starting seeds are shown for the optic radiations white matter tract (top left), posterior corona radiata (top right), and splenium of corpus callosum (bottom). A representative axial (on the left) and coronal view (on the right) is shown for each case. B: The overlap between the connectivity map and cortical regions is used to determine which cortical regions have high connectivity with the original white matter regions of interest. In this representative subject, the lateral occipital gyral cortical boundary is shown in blue in the upper image, and overlap with the optic radiations connectivity map is shown in yellow in the lower image. (A high-quality digital representation of this figure is available in the online issue.)

FIG. 3.

The average fractional anisotropy for the posterior corona radiata white matter region of interest (left) and optic radiations (right) is plotted against average cortical thickness for cortical regions found to have high connectivity to each of these seed regions. Diabetic subjects are denoted by ○; control subjects are denoted by ×.