Altered brain diffusion tensor imaging indices in adolescents with the Fontan palliation

Abstract

Purpose: Single ventricle heart disease (SVHD) patients show injury in brain sites that regulate autonomic, mood, and cognitive functions. However, the nature (acute or chronic changes) and extent of brain injury in SVHD are unclear. Our aim was to examine regional brain tissue damage in SVHD over controls using DTI-based mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) procedures.

Methods: We collected two DTI series (3.0-T MRI), mood and cognitive data, from 27 SVHD and 35 control adolescents. Whole-brain MD, AD, RD, and FA maps were calculated from each series, realigned and averaged, normalized to a common space, smoothed, and compared between groups using ANCOVA (covariates, age and sex; false discovery rate, p < 0.05). Region-of-interest analyses were performed to calculate MD, AD, RD, and FA values for magnitude assessment between groups.

Results: SVHD patients showed impaired mood and cognitive functions over healthy adolescents. Multiple brain sites in SVHD showed increased MD values, including the insula, caudate, cingulate, hypothalamus, thalamus, medial prefrontal and frontal cortices, parahippocampal gyrus, hippocampus, precentral gyrus, amygdala, cerebellum, corpus callosum, basal forebrain, mammillary bodies, internal capsule, midbrain, fornix, and occipital, parietal, and temporal cortices, indicating chronic tissue changes. Similar areas showed either increased AD or RD values, with RD changes more enhanced over AD in SVHD compared to controls. Few brain regions emerged with increased or decreased FA values in SVHD patients over controls.

Conclusion: SVHD adolescents, more than a decade from their last surgical procedure, show widespread brain abnormalities in autonomic, mood, and cognitive regulatory areas. These findings indicate that brain injury is in a chronic stage in SVHD with predominantly myelin changes that may result from previous hypoxia/ischemia- or developmental-induced processes.

Keywords: Brain injury; Cognition; Diffusion tensor imaging; Single ventricle heart disease.

Fig. 1:

Brain sites with increased mean diffusivity (MD) values in SVHD compared to control subjects. Brain regions showed increased MD values in the bilateral insular cortices (a), bilateral caudate nuclei (b), anterior (f), mid (g), and posterior (c) cingulate cortices, midbrain (d), hypothalamus (e), fornix (h), bilateral mid-corona radiata (i), bilateral parietal cortices (j), bilateral thalamus (k), bilateral medial prefrontal cortices (l), para-hippocampal gyrus (m), bilateral hippocampus (n), precentral gyrus (o), frontal gyrus (p), amygdala (q), cerebellar cortices (r), bilateral occipital cortices (s), corpus callosum (t), basal forebrain (u), bilateral prefrontal cortices (v), and bilateral mammillary bodies (w), in SVHD over controls. All images are in neurological convention (L = Left; R = Right). Color bar indicates t-statistic values.

Fig. 2:

Brain regions with increased axial diffusivity and radial diffusivity values in SVHD over control subjects. These sites included the bilateral prefrontal cortices (a, d, j, m), bilateral insula (b, c, k, l), left anterior (e, n), mid (g, p) and posterior (f, o) cingulate, and bilateral occipital cortex (h, i, q, r). Figure conventions are same as in Figure 1.

Fig. 3:

Brain areas with decreased or increased FA values in SVHD over controls. Lower FA values emerged in the bilateral corpus callosum (a), hippocampus (b), anterior insula (c), and amygdala (d), and higher FA values appeared in the posterior insula (e), putamen (f), prefrontal cortices (g), cerebellar cortices (h), and posterior cerebellar peduncle (i) in SVHD over controls. Figure conventions are same as in Figure 1.