White matter changes after stroke in type 2 diabetic rats measured by diffusion magnetic resonance imaging

Abstract

Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize white matter of brain. We hypothesize that entropy of diffusion anisotropy may be most effective for detecting therapeutic effects of bone marrow stromal cell treatment of ischemia in type 2 diabetes mellitus rats. Type 2 diabetes mellitus was induced in adult male Wistar rats. These rats were then subjected to 2 h of middle cerebral artery occlusion, and received bone marrow stromal cell (5 × 10⁶, n = 8) or an equal volume of saline (n = 8) via tail vein injection at three days after middle cerebral artery occlusion. Magnetic resonance imaging was performed on day one and then weekly for five weeks post middle cerebral artery occlusion. The diffusion metrics complementarily permitted characterization of axons and axonal myelination. All six magnetic resonance imaging diffusion metrics, confirmed by histological measures, demonstrated that bone marrow stromal cell treatment significantly (p < 0.05) improved magnetic resonance imaging diffusion indices of white matter in type 2 diabetes mellitus rats after middle cerebral artery occlusion compared with the saline-treated rats. Superior to the fractional anisotropy metric that provided measures related to organization of neuronal fiber bundles, the entropy metric can also identify microstructures and low-density axonal fibers of cerebral tissue after stroke in type 2 diabetes mellitus rats.

Keywords: White matter; diabetes; diffusion; magnetic resonance imaging; stroke.

Figure 1.

Evolution of changes for the six diffusion-related parametric maps, fraction anisotropy of diffusion (a), entropy of diffusion anisotropy (b), mean kurtosis (c), axonal water fraction (d), axial (e) and radial (f) apparent diffusion coefficient in recovery ROI from one day to five weeks after stroke in T2DM rats with or without BMSC treatments. Two scatter plots of all the metrics at the five weeks after stroke were presented for both BMSC (g) and saline (h) treated rats, the diversity of diffusion metrics probably depended on initial ischemic damage after stroke for both treated and control rats.

Figure 2.

Demonstration of evolution of the six diffusion and one T₂ maps (right column), obtained from one day to five weeks after stroke, of the representative saline-treated (c) T2DM rat. Recovery ROI for this rat is loaded onto the five weeks T₂ map.

Figure 3.

Demonstration of evolution of the six diffusion and one T₂ maps (right column), obtained from one day to five weeks after stroke, of the representative BMSC-treated (T) T2DM rat. Recovery ROI for this rat is loaded onto the five weeks T₂ map.

Figure 4.

A T₂ map (a) showed the location of ischemic lesion at five weeks after stroke. The red arrow heads in both FA (b) and entropy (c) maps, obtained at five weeks after stroke, indicated higher values in the ischemic boundary, corresponding tissue with black color in BLFB staining image ((d), red arrow heads), which was the red frame part in panel A. The 40× magnified (e) picture, from yellow rectangle in (d), demonstrated relative higher density of axonal fibers in the area. The entropy map, but not FA map, identified some structures of cerebral tissue, indicated by the purple arrow heads in (b), (c), and (d). The enlarged picture (F, ×40) of the purple rectangle in (d) showed cerebral tissue without dense axonal fibers. By overlapping the orientation map on entropy maps (g), diffusion orientation in the area was not restricted along single direction. It was clearer in the zoomed map ((h), purple arrow heads). FA exhibited low values (dark), as indicated with the yellow arrow heads in the zoomed orientation map (i).