Traumatic Brain Injury (TBI): Advanced Neuroimaging Jamie Hutchison Professor of Pediatrics, University of Toronto CCCF, Toronto November 10, 2013
Conflicts of Interest Patent on CT tool PI Anne-Marie Guerguerian Patent Electroencephalography synchrony imaging tool Vera Nenadovic and Jose-Luis Perez-Velasquez
Question 1 How many people use CT scan for diagnosis and management of TBI in the ICU? Yes raise your hands
Question 2 How many people use MRI for diagnosis and management of TBI in the ICU? Yes - raise your hands
Question 3 How many people use other neuroimaging technologies (e.g. PET scan or other novel imaging technologies) for diagnosis and management of TBI in the ICU? Yes Raise your hands
Classification of TBI in the Critical Care Unit Current classification Mild (GCS=13-15), moderate (GCS=9-12) and severe (GCS=3-8) This classification is based on the paper by Sir Graham Teasdale from Glasgow in the 1970s A new classification system is needed linking neuroimaging and other acute parameters to how the brain functions during recovery Rationale: For prognosis and implementation of novel therapies
Geoff Manley, UCSF
The CT Scan Tool The tool Quantifies Brain Injury It will be integrating into clinical care to enhance the utility of the CT scan Anne-Marie Guerguerian
International TBI Research Network Have invested in TBI research during recent meetings in Brussels and Vancouver $$$ are committed between the European Union, the National Institutes of Health (NIH-US) and the Canadian Institutes of Health The NIH Common Data Elements provide a template for collaboration in neuroimaging research TRACK-TBI - Geoff Manley $20 million (US) CENTRE-TBI Andrew Mass and David Menon $30 million Euros CIHR Team Grants in Mild TBI in Children and Youth
Magnetic Resonance Imaging Structural MRI (MRI) Diffusion-weighted Imaging (water) Susceptibility weighted Imaging (Hemoglobin) Diffusion Tensor Imaging fmri MR Spectroscopy
6 year old male 11 year old male GCS=12 GCS=3 Struck by bicycle ATV collision
Brian Levine et al. Quantified MRI and cognition in TBI with diffuse and focal damage. Neuroimage: Clinical, 2013
Diffuse axonal injury 10 year old male, GCS=13, TBI Susceptibility- CT T2-weighted MRI weighted MRI Beauchamp et al., 2011, Journal of Neurotrauma.
Attention and TBI study Case report form Recruit Day 5 3 Months 6 Months 12 Months Injury BRIEF MRI BRIEF Helena Frndova
August 2011: Recruitment for Attention and Traumatic Brain Injury Study 140 Total screened Total enrolled ONF Sample (n=60) 120 100 80 60 40 20 Toronto London Start CHEO, Ste Justine, McMaster start 0 D F A J A O D F A J A O D F A J A 2009 2010 2011 August 2011: Complete recruitment
Results: Baseline characteristics (N=58) Parameter Value Age 12.4 ± 3.6 Male 41 (71%) Severity of injury (Glasgow coma scale) Mild 14/53 (27%) Moderate 11/53 (22%) Severe 27/53 (51%) Other Injuries Spinal cord injury 9 (16%) Thoracic 19 (33%) Cardiovascular 1 (1.7%) Abdominal 8 (14%) Genito-urinary 1 (1.7%) Major fracture 24 (41%) Other injuries 25 (43%)
Cognitive changes following TBI Deficits in executive function 1 Ability to plan, carry out, and evaluate behaviour Supported by frontal lobes Particularly vulnerable to injury 2 Problems: Maureen Dennis MRI is more sensitive for detecting injury but is not part of routine care Lack of longitudinal data to predict & characterize course of executive dysfunction 1 Brookshire, Levin, Song, & Zhang (2004); Mandalis, Kinsella, Ong, & Anderson (2007) 2 Bigler (2007)
Study Question Does presence of frontal lobe diffuse axonal injury predict executive dysfunction?
Methods Frontal lobe injury: structural MRI within 5 days of injury (n=25) Diffuse Axonal Injury (DAI): scattered, small hemorrhagic and/or non-hemorrhagic lesions; 3 separate foci of signal abnormality 13 participants had evidence of frontal DAI 12 participants had no evidence of frontal DAI Executive function: parent reports/standardized questionnaire Behaviour Rating Inventory of Executive Function (BRIEF) 3,4 4 time-points: Pre- injury (baseline); 3, 6, and 12 months postinjury 3 Gioia et al. 2000, 4 Guy et al. 2004
Behaviour Rating Inventory of Executive Function (BRIEF) 1. Initiate: Begin activity; generate ideas 2. Working Memory: Hold information in mind 3. Plan/Organize: Anticipate future events; develop step to implement plan 4. Organize Materials: Clean room 5. Monitor: Assess own performance 6. Inhibit: Control impulses; stop behavior 7. Shift: Move from one activity/situation to another; problem-solve; flexibly 8. Emotional Control: Modulate emotional responses appropriately
At Risk P=0.08
At Risk P=0.01
Effect of hyperventilation on cerebral blood flow in patients with TBI PET Scans Coles et al. Crit Care Med 2002
31 yo man 7 days post-tbi CT Scan PET scans PaCO2 (mmhg) 35 26 HypoBV (ml) 141 428 Coles et al. Crit Care Med 2002
Respiratory Support: Normoventilation Hyperventilation : Historical management more harm than good??? CBF pre- hyperventilation CBF post-hyperventilation Originally adapted from research by Skippen et al. (1997) Critical Care Medicine, 25
Focal EEG Synchrony F7 FP1 O1 C4 L R Vera Nenadovic Channel 1
Conclusions A new classification system for TBI using advanced neuroimaging will improve diagnosis, risk stratification and facilitate earlier interventions during recovery This will lead to better designed trials and improved quality-of-life for patients with TBI
Acknowledgements ATBI study coordinators Judy Van Huyse and Sumaira Hussain Co-principal Investigators Russell Schachar Co-investigators Maureen Dennis, Anne-Marie Guerguerian, Vera Nenadovic, Helena Frndova, Miriam Beauchamp, Dean Ferguson, and site investigators CCCTG and CCCTBG - John Marshall, Deborah Cook and Brent Winston Funding ONF, Eli Lily, SickKids and CIHR