Global and regional brain mean diffusivity changes in patients with heart failure

Abstract

Heart failure (HF) patients show gray and white matter changes in multiple brain sites, including autonomic and motor coordination areas. It is unclear whether the changes represent acute or chronic tissue pathology, a distinction necessary for understanding pathological processes that can be resolved with diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures. We collected four DTI series from 16 HF (age 55.1 ± 7.8 years, 12 male) and 26 control (49.7 ± 10.8 years, 17 male) subjects with a 3.0-Tesla magnetic resonance imaging scanner. MD maps were realigned, averaged, normalized, and smoothed. Global and regional MD values from autonomic and motor coordination sites were calculated by using normalized MD maps and brain masks; group MD values and whole-brain smoothed MD maps were compared by analysis of covariance (covariates; age and gender). Global brain MD (HF vs. controls, units × 10(-6) mm(2) /sec, 1103.8 ± 76.6 vs. 1035.9 ± 69.4, P = 0.038) and regional autonomic and motor control site values (left insula, 1,085.4 ± 95.7 vs. 975.7 ± 65.4, P = 0.001; right insula, 1,050.2 ± 100.6 vs. 965.7 ± 58.4, P = 0.004; left hypothalamus, 1,419.6 ± 165.2 vs. 1,234.9 ± 136.3, P = 0.002; right hypothalamus, 1,446.5 ± 178.8 vs. 1,273.3 ± 136.9, P = 0.004; left cerebellar cortex, 889.1 ± 81.9 vs. 796.6 ± 46.8, P < 0.001; right cerebellar cortex, 797.8 ± 50.8 vs. 750.3 ± 27.5, P = 0.001; cerebellar deep nuclei, 1,236.1 ± 193.8 vs. 1,071.7 ± 107.1, P = 0.002) were significantly higher in HF vs. control subjects, indicating chronic tissue changes. Whole-brain comparisons showed increased MD values in HF subjects, including limbic, basal-ganglia, thalamic, solitary tract nucleus, frontal, and cerebellar regions. Brain injury occurs in autonomic and motor control areas, which may contribute to deficient function in HF patients. The chronic tissue changes likely result from processes that develop over a prolonged period.

Keywords: autonomic; chronic injury; diffusion tensor imaging; dyspnea; insula cerebellum.

Figure 1

Brain regions with significantly increased MD values in HF (n = 16) over healthy control (n = 26) subjects (uncorrected threshold, p = 0.005) are shown in glass brain format, with projections across the 3D onto 2D axial, sagittal, and coronal views.

Figure 2

Brain sites with significantly increased MD values in HF over controls. Significantly increased MD values in HF appeared in brain sites, including the frontal white matter (a), external and internal capsules (b, i), ventral hippocampus (c), cerebellar cortices (d), parietal cortices (e), mid and posterior cingulate cortices (f, g), occipital gray and white matter (h, s), septum/bed nuclei (j), putamen (k), insular cortices (l), caudate nuclei (m), posterior corpus callosum (n, p), ventral white matter (o), and anterior and posterior thalamus (q, r). All brain images are in neurological convention (L = Left, R = Right), and the color scale shows t-statistic values.

Figure 3

Brain regions with increased MD values in HF, compared to control subjects. Brain sites with increased MD values in HF included the genu of cingulate (a), extending to hypothalamus (b), ventrolateral tegmental area (c), cerebellar vermis (e), cerebellar cortices (d), extending to deep nuclei (i), raphe, extending to nucleus of the solitary tract (h), and inferior cerebellar peduncles (k). Figure conventions are the same as in Figure 2.