Investigation of pediatric anoxic brain injury from nonfatal drowning using magnetic resonance imaging

摘要

Although drowning is a leading cause of unintentional injury in young children and anoxic brain injury a common consequence in survivors, assessment of functional status and long-term prognostication with anoxic injury are extremely clinically challenging. To date, clinical imaging methods have proven inadequate in evaluation of damage and prediction of functional sequelae, particularly in children. Advancements in structural magnetic resonance imaging have facilitated visualization of injury, but are limited in their utility for individual patient prognostication. The substantial motor deficits associated with anoxic injury and lack of reliable assessments of cognitive and functional integrity lead to postulations of minimally conscious/vegetative outcomes. Parents are consequently often recommended to institutionalize their child or withdraw care altogether, but these assessments may well be flawed. Thus, a significant gap remains in the objective functional assessment of patients with post-drowning anoxic brain injury; a novel, more potent imaging protocol is needed. To address this gap, we acquired high-quality anatomical, diffusion, and resting-state functional magnetic resonance imaging data during sleep and extensive behavioral data in 11 children with chronic anoxic brain injury from drowning and 11 age- and gender-matched neurotypical children.;The overall goal of this dissertation was to define the neuropathology and pathophysiology of pediatric anoxic brain injury with drowning and build a clinically implementable imaging protocol for per-subject functional assessment. We hypothesized that consistent evidence for focal motor-system impairments would be established across all imaging modalities and furthermore, that resting-state functional magnetic resonance imaging network-based findings would correlate with behavioral assessments per subject. This was addressed through the following AIMS:;AIM 1 of this dissertation quantified neuropathology in children with anoxic brain injury from drowning. AIM 1a measured consistent anatomical pathology in grey and white matter using voxel-based morphometry implemented on T1-weighted magnetic resonance data. AIM 1b measured consistent white matter microstructural pathology using tract-based spatial statistics implemented on diffusion-weighted magnetic resonance data. These analyses were the first in this population and identified focal, concordant, and highly statistically significant structural pathology.;AIM 2 of this dissertation quantified functional network integrity in children with anoxic brain injury from drowning at both group and individual levels using independent components analysis of resting-state functional magnetic resonance data. Between-group functional connectivity differences were thus identified, and imaging-based functional assessments of each patient were obtained. This analysis was the first in this population and identified focal functional pathology, highly concordant with structural pathology. AIM 2 further established the clinical impact of our image acquisition and analysis protocol.;AIM 3 of this dissertation characterized behavioral deficits in children with anoxic brain injury from drowning and measured imaging-behavioral correlations using resting-state functional magnetic resonance and behavioral data. Behavioral deficits were identified to be focal and concordant with structural and functional imaging findings; behavioral-based assessments overall correlated with corresponding network-based image assessments.;Structural, functional, and behavioral pathology were predominantly limited to the motor system, with relative preservation of perceptual, cognitive, and emotive systems. These striking findings suggest that children with anoxic brain injury from drowning suffer from a variant of locked-in syndrome. Needless to say, several prognostic, therapeutic, and ethical correlates follow.