Peter Ferrazzano, MD – Slide of the Week

Peter Ferrazzano, MD – Slide of the Week

Title: MRI volumetric measures of functional outcome after severe pediatric TBI.

Legend: MRI measures of cerebral atrophy are associated with global neurocognitive function after severe traumatic brain injury (TBI) in adolescents. T1-weighted MRI scans (3D inversion-recovery prepared sequence with a rapid gradient echo readout, ie. MP-RAGE/BRAVO) were obtained in 24 adolescents (11-19 years old) 1-2 years after a severe traumatic brain injury, and in 34 typically developing healthy controls (HC). Ventricle-to-brain ratio (VBR) and corpus callosum (CC) cross sectional area were determined using a combination of Freesurfer software and custom scripts. The Extended Glasgow Outcome Score modified for pediatrics (GOSE-Peds) was determined for each TBI subject (range 1-8, 1=normal function). Study participants were administered the Wechsler Abbreviated Scale of Intelligence – Second Edition to determine IQ score, and the Coding and Symbol Search subtests from the Wechsler Scale of Intelligence for Children – Fourth Edition to determine Processing Speed Index (PSI). VBR was significantly increased and CC cross sectional area was significantly decreased in TBI subjects compared to controls (A). Representative images demonstrating progressive cerebral atrophy are shown in B. After adjusting for age and sex, VBR was significantly associated with GOSE-Peds in the TBI group (C). After adjusting for age, sex, intracranial volume, and brain tissue volume, a significant association was found in the TBI group between CC and IQ (D, left panel, slope = 6.46 ± 2.3, p = 0.007), and between CC and PSI (D, right panel, slope = 8.21 ± 3.5, p = 0.02), while no association between CC and outcome was found in control subject.

Citation: Ferrazzano P, Yeske B, Mumford J, Kirk G, Bigler ED PhD, Bowen K, O’Brien N, Rosario B, Beers SR, Rathouz P, Bell MJ, Alexander AL. Brain MRI volumetric measures of functional outcome after severe TBI in Adolescents. J Neurotrauma. 2021 Jan 23. doi: 10.1089/neu.2019.6918. Epub ahead of print. PMID: 33487126.

Abstract: Adolescent traumatic brain injury (TBI) is a major public health concern, resulting in over 35,000 hospitalizations in the U.S. each year. While neuroimaging is a primary diagnostic tool in the clinical assessment of TBI, our understanding of how specific neuroimaging findings relate to outcome remains limited. Our study aims to identify imaging biomarkers of long-term neurocognitive outcome after severe adolescent TBI. Twenty-four adolescents with severe TBI (Glasgow Coma Scale ≤8) enrolled in the Approaches and Decisions after Pediatric TBI (ADAPT) study were recruited for MRI scanning 1-2 years post-injury at 13 participating sites. Subjects underwent outcome assessments approximately 1-year post-injury, including the Wechsler Abbreviated Scale of Intelligence (IQ) and the Pediatric Glasgow Outcome Scale-Extended (GOS-E Peds). A typically developing control cohort of 38 age-matched children also underwent scanning and neurocognitive assessment. Brain image segmentation was performed on T1-weighted images using Freesurfer. Brain and ventricular CSF volumes were used to compute a Ventricle-to-Brain Ratio (VBR) for each subject, and the corpus callosum cross-sectional area was determined in the midline for each subject. The TBI group demonstrated higher VBR and lower corpus callosum area compared to the control cohort. After adjusting for age and sex, VBR was significantly related with GOS-E Peds score in the TBI group (n=24, p=0.01, cumulative odds ratio = 2.18). After adjusting for age, sex, intracranial volume and brain volume, corpus callosum cross-sectional area correlated significantly with IQ score in the TBI group (partial cor = 0.68, n=18, p=0.007) and with PSI (partial cor = 0.33, p = 0.02). No association was found between VBR and IQ or between corpus callosum and GOS-E Peds. After severe adolescent TBI, the quantitative MRI measures of VBR and corpus callosum cross-sectional area are associated with global functional outcome and neurocognitive outcomes, respectively.

About the Lab: By identifying MRI biomarkers in animal models of pediatric brain injury, Waisman investigator Peter Ferrazzano hopes to provide a means for selecting the patients most likely to benefit from a particular neuroprotective intervention in subsequent clinical trials. Basing patient selection on the physiologic target of therapy rather than simply the disease state will reduce the sample size needed, increase the likelihood of observing a drug effect, and facilitate the translation of promising neuroprotective interventions into clinical use.

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