Differential effects of radiation and age on diffusion tensor imaging in rats

Abstract

Greater than 50% of adults and approximately 100% of children who survive >6 months after fractionated partial or whole-brain radiotherapy develop cognitive impairments. Noninvasive methods are needed for detecting and tracking the radiation-induced brain injury associated with these impairments. Using magnetic resonance imaging, we sought to detect structural changes associated with brain injury in our rodent model of fractionated whole-brain irradiation (fWBI) induced cognitive impairment and to compare those changes with alterations that occur during the aging process. Middle aged rats were given a clinically relevant dose of fWBI (40 Gy: two 5 Gy fractions/week for 4 weeks) and scanned approximately 1 year post-irradiation to obtain whole-brain T2 and diffusion tensor images (DTI); control groups of sham-irradiated age-matched and young rats were also scanned. No gross structural changes were evident in the T2 structural images, and no detectable fWBI-induced DTI changes in fractional anisotropy (FA) were found in heavily myelinated white matter (corpus callosum, cingulum, and deep cortical white matter). However, significant fWBI-induced variability in FA distribution was present in the superficial parietal cortex due to an fWBI-induced decline in FA in the more anterior slices through parietal cortex. Young rats had significantly lower FA values relative to both groups of older rats, but only within the corpus callosum. These findings suggest that targets of the fWBI-induced change in this model may be the less myelinated or unmyelinated axons, extracellular matrix, or synaptic fields rather than heavily myelinated tracts.

Conflict of interest statement

Conflict of Interest Notification: None of the authors have any conflict of interests to report.

2010 Elsevier B.V. All rights reserved.

Figures

Fig. 1. Region of Interest Locations

ROI overlays of Slice 2 are shown on images used to elucidate borders. A: ROIs of Bilateral Parietal Cortex are composed of Superficial (SCtx) and Deep (DCtx) Parietal Cortex and were defined on the unsmoothed EPI image as described in the methods. B: ROIs of Bilateral Cingulum (Cg), Corpus Callosum (CC) and Bilateral Deep Cortical White Matter (wm) were defined on the color-coded FA maps. C: For comparison the myelin-stained section corresponds anatomically to the cortical ROI diagram and illustrates the various amounts of myelin in the investigated ROIs. Superficial cortex (SCtx) has less myelin stain than deep cortical ROI (DCtx), which is in turn less stained than deep cortical white matter (wm).

Fig. 2. Mean FA values in Superficial Parietal Cortex within each slice

Slice 2 is the most anterior section and fWBI have significantly less FA than Sham rats (F1,30 = 6.44, *p<0.02). The heterogeneity between these slices call for voxel-wise analysis of cortical DTI measures to accurately evaluate radiation-induced changes.

Fig. 3. DTI Slice Prescription

The anterior commissure was centered in the 3rd slice for each animal to align the anterior to posterior slice acquisition. ROIs were drawn on slices 2-5 of the color-coded directional FA maps and prescribed as detailed in figure 1.