Pediatric TBI and DAI: Normal Appearing Brain is Not Normal

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DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is the leading cause of death and disability in the pediatric population. Diffuse axonal injury (DAI) with hemorrhagic/non-hemorrhagic shearing lesions is universally recognized as a consequence of TBI that results in long-term neurologic (NL) and neuropsychological (NP) deficits. Currently, injury may go unrecognized and untreated because conventional CT and MRI underestimate the extent of these lesions. Our overall hypothesis is that 2 new MR techniques, susceptibility-weighted imaging (SWI) and proton magnetic resonance spectroscopic imaging (MRSI), are capable of detecting DAI in areas that appear normal on conventional MRI and can predict long-term outcome. SWI is a 3D-high-resolution gradient echo MRI technique that is 6 times more sensitive for detecting hemorrhagic DAI lesions than conventional MRI. MRSI detects metabolite changes (reduced N-acetylaspartate) that reflect neuronal injury and has provided evidence of diffuse damage in over 60% of brain that appears normal even on SWI. This application proposes a prospective, controlled, longitudinal study to evaluate 3D SWI/MRSI in 11 brain regions in 90 children (4-16 years) with moderate to severe (GCS< 13) TBI, 7-14 days after injury and 90 non-head injured age-matched controls. These ages were selected to facilitate standardized NP testing. Measurements will be compared regionally, globally (all regions combined) and as 3 pooled brain regions (cortical, subcortical, and posterior fossa). The specific aims are: 1) to determine if SWI will detect an increased number/volume of hemorrhagic DAI lesions not visible with conventional MRI and will better predict 3 and 12 month NL and global NP (i.e. IQ, memory, attention) outcomes; 2) to determine if significant injury measured by initial MRSI metabolite changes is present in normal-appearing brain following TBI; 3) to determine if SWI and MRSI data individually or combined are more predictive of NL/NP outcomes and 4) to repeat SWI/MRSI at 12 months after injury in order to categorize regional patterns of neuronal degeneration, recovery and plasticity as measured by interval changes of ratios with functional long-term outcome. These advanced MR techniques hold promise of becoming new standards of care by significantly improving detection of injury and understanding of recovery. This will be of importance to diagnostic and therapeutic management of TBI, particularly in children in whom injury is underestimated, unrecognized and untreated.