A mechanism of rapidly reversible cerebral ventricular enlargement independent of tissue atrophy

Abstract

Ventricular enlargement, a common in vivo marker of aging, disease, and insult, is presumed to reflect atrophy of surrounding brain regions. Pathological mechanisms underlying ventricular enlargement, however, are likely specific to the condition under investigation. Here, multimodal imaging, incorporating structural magnetic resonance imaging (MRI), MR spectroscopy (MRS), and diffusion weighted imaging (DWI), was used in rats exposed to binge ethanol (EtOH) to provide insight into a mechanism of reversible ventricular enlargement. During intoxication, MRI revealed expansion of ventricles, but volume changes in dorsal or ventral hippocampi, caudate-putamen, or thalamus were not detectible. MRS of whole-brain parenchyma showed decreases in N-acetylasparate (NAA) and tissue water T2, and increases in choline-containing compounds (Cho). DWI showed decreased diffusivity selective to the thalamus. All MR parameters returned to baseline with 7 days of recovery. Rapid recovery of ventricular volume and the absence of detectable tissue volume reductions in brain regions adjacent to ventricles argue against atrophy as a mechanism of ventricular expansion. Decreased tissue water T2 and decreased thalamic diffusivity suggest lower tissue water content and a role for both NAA and Cho, as osmolytes is proposed. Together, these data support a model of fluid redistribution during acute EtOH intoxication and recovery to account for rapid ventricular volume changes.

Figure 1

(a) Weights of EtOH (red circles) and Dex (gray squares) animals across the course of the experiment. (b) BALs on each day of treatment and immediately following the binge MR scan. (c) Correlation between BALs and time of last EtOH dose. (d) Correlation between BALs and in vivo brain EtOH measures by MRS. For weights *P⩽0.005, for *BALs P⩽0.0001. BALs, blood alcohol levels; Dex, dextrose; EtOH, ethanol; MR, magnetic resonance; MRS, MR spectroscopy. Note: ‘binge scan' weight and BAL measurements took place within 9.5 h of the last EtOH dose (ie, at end of scan on day 5), while weight and BAL measurements during treatment were collected at 11:00 (ie, 11:00 of day 4). The color reproduction of this figure is available on the Neuropsychopharmacology online.

Figure 2

(a) FSE and (b) DWI images from an exemplary EtOH animal at each of the three scans demonstrating ventricular enlargement at the binge scan. (c) Quantification of ventricular volume in EtOH (red) and Dex (gray) animals based on DWI images at each of the three times points. Dex, dextrose; DWI, diffusion weighted images; EtOH, ethanol; FSE, fast spin-echo images; *P⩽0.05. The color reproduction of this figure is available on the Neuropsychopharmacology online.

Figure 3

(a) MRS voxel placement in rat axial, sagittal, and coronal planes. (b) Averaged spectra from eight EtOH (red) and ten Dex (gray) animals. (c) Means±SEM of the four metabolites, EtOH, and tissue water T2 in EtOH (red) and Dex (gray) animals at baseline, binge, and recovery scans. Cho, choline-containing compounds; Dex, dextrose; EtOH, ethanol; Glx, combined resonances of glutamate and glutamine; MRS, magnetic resonance spectroscopy; NAA, N-acetylasparate; tCr, total Creatine; *P⩽0.05. The color reproduction of this figure is available on the Neuropsychopharmacology online.

Figure 4

Quantification of MD in (a) thalamus and (b) cortex of EtOH (red) and Dex (gray) animals; figure includes outlines of regions of interest used for quantification of MD on both FSE and DWI images. Dex, dextrose; DWI, diffusion weighted images; EtOH, ethanol; FSE, fast spin-echo images; MD, mean diffusivity. *P⩽0.05.

Figure 5

Graphs presenting correlations between various MR variables at the binge time point. Cho, choline-containing compounds; MD, mean diffusivity; MR, magnetic resonance; NAA, N-acetylasparate. The color reproduction of this figure is available on the Neuropsychopharmacology online.