Biomechanical Aspects of Spinal Cord Injury Thomas R
Biomechanical Aspects of Spinal Cord Injury Thomas R. Oxland Ph. D PEng Professor & Director Division of Orthopaedic Engineering Research Departments of Orthopaedics & Mechanical Engineering The University of British Columbia Vancouver Coastal Health Research Institute
UBC – The University of British Columbia • 40, 000 students • 4, 000 faculty
UBC Department of Orthopaedics • 65 faculty members • 5 teaching hospitals • basic & clinical research • seven Divisions – – – – Athletic Injuries Lower Limb Reconstruction Upper Limb Reconstruction Pediatrics Spine Trauma Orthopaedic Engineering Research
Orthopaedic Engineering Research (DOER) • the application of engineering principles to clinically relevant problems in the field of Orthopaedics
DOER at UBC • • • Thomas Oxland David Wilson Heather Mc. Kay Karim Khan Peter Cripton Steve Robinovitch Rizhi Wang Goran Fernlund Gail Thornton • • • Clive Duncan Bassam Masri Don Garbuz Marcel Dvorak Brian Kwon Charles Fisher Pierre Guy Peter O’Brien Robert Mc. Cormack Bill Regan
Research Themes • Mechanisms of Spine and Spinal Cord Injury [Oxland, Cripton, Kwon, Dvorak, Tetzlaff] • Etiology of Osteoarthritis [Wilson, Mac. Kay, Cibere] • Hip Fracture Prevention [Mc. Kay, Khan, Robinovitch, Guy] • Surgical Solutions in presence of Bone Loss – osteoporotic spine [Oxland, Cripton, Dvorak, Fisher] – revision hip [Oxland, Duncan, Masri, Fernlund]
SCI Epidemiology • ~11, 000 new injuries/year in North America (40/million) • 200, 000 chronic injuries • Average 32 • $9. 73 billion/year – hospitalization, rehabilitation, medication, equipment, loss productivity -Spinal Cord Injury Information Network - www. spinalcord. uab. edu
ICORD – new home for Spinal Research Centre in Vancouver • Vancouver General Hospital • 51 principal investigators • 120, 000 square feet • Spinal clinics • Rehabilitation research February 2008 • Molecular Biology • Bioengineering • Neuropysiology October 2008
Theme 3 Develop novel animal models of SCI where damage can be induced within an enclosed vertebral column, thereby more accurately mimicking human SCI. Can only be achieved through the combined efforts of spine surgeons, biomechanical engineers and neuroscientists working side-by-side.
Theme 3 - Overview Spinal cord injury represents a mechanical insult that triggers a biological response which results in a wide range of clinical sequelae.
Type of Vertebral Injury 40% Fracture Dislocation Burst Fracture 30% SCIWORET 10% SCIWORA 5% 5% Dislocation 10% Minor Fracture Sekhon & Fehlings Spine 2001
Spinal Injury FRACTURE DISLOCATION BURST FRACTURE FLEXIONDISTRACTION
Clinical Observation • the mechanism of column damage correlates with the neurological deficit – Marar 1974, Tator 1983 …. but current treatments do not incorporate injury mechanism!
Methods – Cord/Column • Surrogate Cord – Silicone gel – In vivo-like in tension • Barium Sulfate added • Oval shaped Saari MASc 2006
Methods – Specimen Preparation • Human cervical spines occiput to T 2 (n = 6) • Surrogate head attached to occiput Saari MASc 2006
Methods – Imaging • High Speed X-ray – Industrial X-ray source • 75 k. V, 5 m. A – 9” image intensifier – Internal high speed camera • 1000 frames per second • 256 x 240 pixels Image Intensifier X-ray Source Saari MASc 2006
Saari MASc 2006
Effect of Constraint Flexion-compression injury model Zhu 2008
Compression to the Specimen 35 msec Zhu 2008
Flexion-Compression (constrained)
Flexion-Compression (unconstrained) Zhu 2008
Canal Occlusion Zhu 2008
Column-Canal Relationships constrained unconstrained Zhu 2008
Pro-Neck-Tor. TM Standard Helmet Dr. Peter Cripton http: //injury. mech. ubc. ca http: //www. pronecktor. com
Proof of Concept Study – Results: • Axial Force Escape-Angle Interaction 56% reduction 15º, Med Stiffness, Extension Escape, Vimpact ~3. 2 m/s
C 4 C 5 C 6 Greaves 2008
Von Mises Strain Compression dorsal ventral Greaves 2008
Von Mises Strain Distraction dorsal ventral Greaves 2008
Von Mises Strain Dislocation dorsal ventral Greaves 2008
Different Cord Strain Patterns Greaves Annals BME 2008
Contusion
Theme 3 - Overview Spinal cord injury represents a mechanical insult that triggers a biological response which results in a wide range of clinical sequelae.
Spinal Injury FRACTURE DISLOCATION FLEXIONDISTRACTION BURST FRACTURE Do these well-known spinal column injury patterns create different spinal cord injuries?
Injury Models Transection Weight drop -Allen 1911 g-cm -Albin 1970 d, OSU -Noyes 1980 m F, IH -Scheff 1990 2004 d h clip -Tator NYU -Gruner Lateral Distraction Dislocation -Maiman -Fiford
Contusion Paradigm … central cavitation with peripheral rim of spare white matter … Figure from Mc. Donald & Belegu. J Neurotrauma 2006
Type of Vertebral Injury 40% Fracture Dislocation Burst Fracture 30% SCIWORET 10% SCIWORA 5% 5% Dislocation 10% Minor Fracture Sekhon & Fehlings Spine 2001
Experimental Animal Model Compression/Contusion Shear/Dislocation Distraction Choo Ph. D 2006
UBC SCI Test System Actuator 12 mm LVDT (0. 001 mm) accelerometer (50 & 500 G) Load Cell (22 & 225 N) Choo Ph. D 2006
Contusion 4 2 1 Cord surface force (N) displacement (mm) velocity (m/s) 3 0 -1 -2 Choo Ph. D 2006
Dislocation 30 20 15 10 force (N) displacement (mm) velocity (m/s) 25 5 -5 -10 Choo Ph. D 2006
displacement (mm) velocity (m/s) 20 10 force (N) Distraction 40 30 0 Choo Ph. D 2006
Hemorrhage Choo Ph. D 2006
Anatomy &
Study 1: Primary Injury
Membrane Integrity
Membrane Integrity
Membrane Damage Neuronal Cell Bodies Neu. N Axons
Primary Injury • • • 275 -325 g Sprague-Dawley rats Infused 0. 375 mg 10 k. D fluorescein dextran into cisterna magna Incubated for 1 hour + 30 min surgery Injury ~100 cm/s @ C 4/5 5 min sacrifice – primary damage Mechanism N Severity Contusion 9 1. 1 mm Dislocation 9 2. 5 mm Distraction 9 4. 1 mm Shams 8 -
Membrane Damage Neuronal Cell Bodies Injury Lesion Rostral Choo J. Neurosurg. 2007
Membrane Damage Axons Injury Lesion Rostral Choo J. Neurosurg. 2007
Rostro-Caudal Distribution
Study 2: Early Secondary Injury
Early Secondary Injury • • • 275 -325 g Sprague-Dawley rats Infused 0. 375 mg 10 k. D fluorescein dextran into cisterna magna Incubated for 1 hour + 30 min surgery Injury @ ~100 cm/s 0. 75 mg 10 k. D cascade-blue dextran @ 2 hrs – detect persistent membrane permeability • 3 hrs sacrifice – early secondary Mechanism N Severity Contusion 10 1. 1 mm Dislocation 10 2. 5 mm Distraction 10 4. 1 mm Shams 7 - Dextran Controls 3 -
Membrane Integrity at 3 hrs Pre-injury Dextran Post-injury Dextran Merged Image Choo Exp. Neurol. 2008
Secondary Axonal Injury (βAPP)
Secondary Axonal Injury
Secondary Axonal Injury
Microglial Activation
Activation Microglial Activation Choo Exp. Neurol. 2008
Overall Patterns of Tissue Damage
Tissue Damage ≈ Mechanics?
Limitations • Early time-points for analysis • Comparable severities? • Behaviorial differences? • No therapies tested
Summary • SCI is a high-speed event that we are characterizing from a biomechanical perspective – Cadaver models – Mathematical models – Small animal models • Ultimate goal is a clinically relevant subclassification of SCI
Next Steps…. . • Further characterize primary injury & secondary changes; • Assess behavioural differences between mechanisms; • Determine the effectiveness of imaging (MRI) in differentiating between injury mechanisms; • Evaluate the efficacy of novel therapeutic strategies for spinal cord injury (e. g. neuroprotective, remyelination)
Collaborators • • Anthony Choo Carolyn Sparrey Carolyn Greaves Simon Sjovold Liz Clarke (AUS) Amy Saari (PC) Shannon Reed (PC) • Tim Bhatnagar • Colin Russell • • Wolfram Tetzlaff Peter Cripton Marcel Dvorak Brian Kwon Charles Fisher Mohamed Gadala Piotr Kozlowski Lynne Bilston (AUS) • • • Qingan Zhu Jie Liu Clarrie Lam Chad Larson Darrell Goertzen Andrew Yung
Acknowledgements Canadian Institutes of Health Research Canada Research Chairs Program Rick Hansen Man in Motion Fund George W. Bagby Research Fund BC Leading Edge Endowment Fund
Professor Manohar Panjabi Yale University 1970 -2006
Professor Clive Duncan Chairman of Orthopaedics at UBC from 1996 -2006
Thank you!
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