MRI markers of brain network integrity relate to neurological outcome in postanoxic coma

Abstract

Aim: Current multimodal approaches leave approximately half of the comatose patients after cardiac arrest with an indeterminate prognosis. Here we investigated whether early MRI markers of brain network integrity can distinguish between comatose patients with a good versus poor neurological outcome six months later.

Methods: We performed a prospective cohort study in 48 patients after cardiac arrest submitted in a comatose state to the Intensive Care Unit of two Dutch hospitals. MRI was performed at three days after cardiac arrest, including resting state functional MRI and diffusion-tensor imaging (DTI). Resting state fMRI was used to quantify functional connectivity within ten resting-state networks, and DTI to assess mean diffusivity (MD) in these same networks. We contrasted two groups of patients, those with good (n = 29, cerebral performance category 1-2) versus poor (n = 19, cerebral performance category 3-5) outcome at six months. Mutual associations between functional connectivity, MD, and clinical outcome were studied.

Results: Patients with good outcome show higher within-network functional connectivity (fMRI) and higher MD (DTI) than patients with poor outcome across 8/10 networks, most prominent in the default mode network, salience network, and visual network. While the anatomical distribution of outcome-related changes was similar for functional connectivity and MD, the pattern of inter-individual differences was very different: functional connectivity showed larger inter-individual variability in good versus poor outcome, while the opposite was observed for MD. Exploratory analyses suggested that it is possible to define network-specific cut-off values that could help in outcome prediction: (1) high functional connectivity and high MD, associated with good outcome; (2) low functional connectivity and low MD, associated with poor outcome; (3) low functional connectivity and high MD, associated with uncertain outcome.

Discussion: Resting-state functional connectivity and mean diffusivity-three days after cardiac arrest are strongly associated with neurological recovery-six months later in a complementary fashion. The combination of fMRI and MD holds potential to improve prediction of outcome.

Keywords: Cardiac arrest; Diffusion Weighted Imaging; Functional MRI; Postanoxic coma.

Fig. 1

Spatial maps and mean functional connectivity within the ten identified resting state networks per subject, grouped by outcome. P-values are corrected for study site and framewise displacement. Correction for multiple comparisons was applied using the false discovery rate (Benjamini and Yekutieli, 2001).

Fig. 2

Normalized connectivity strength for individual patients across networks, grouped by outcome. High or low connectivity appears to be consistent across the different resting state networks. DMN: default monde network; ECN: Executive control network; FPN: frontoparietal network.

Fig. 3

Spatial maps and average mean diffusivity within the location of the identified resting state networks per subject, grouped by neurological outcome. P-values are corrected for study site. Correction for multiple comparisons was applied using the false discovery rate (Benjamini and Yekutieli, 2001).

Fig. 4

Effect sizes, represented as Cohen’s D, for mean diffusivity against the effect sizes of functional connectivity. Networks with high effect size of functional connectivity typically also show high effect sizes of mean diffusivity.

Fig. 5

A: mean normalized mean diffusivity (MD) against functional connectivity of the three networks with Cohen’s D > 1 for both fMRI and MD, for patients with good and poor neurological outcome. B: global relation of mean diffusivity and functional connectivity in relation to outcome, and the number of subjects in each category. Green: associated with good outcome, orange: associated with indeterminate outcome, red: associated with poor outcome. Thresholds are based on eyeballing of the scatterplots.