Title: SCIB HeadBrain Work Group University of Pennsylvania
1SCIB Head/Brain Work GroupUniversity of
Pennsylvania
David Meaney and Susan Margulies
2Southern Consortium for Brain Injury
BiomechanicsOverall Objective
- The primary objective of the consortium is to
generate the scientific foundation for a new
method of predicting the probability of brain
injury, given an applied input loading condition
to the head
3University of PennsylvaniaOverall Objective
- To acquire experimental data for developing and
validating the finite element model used in the
NHTSA SIMon program - Brain Injury Thresholds
- Boundary Conditions
- Material Properties of Brain Tissue
- Cell based models of Brain Tissue
4Brain Injury Thresholds Progress
- To determine if a specific and serious injury,
the breakdown of the blood brain barrier, can be
predicted by the mechanical response of a simple
finite element model of the rat brain - DCD model and data obtained - completed
- idealized FEM development - completed
- injury threshold derivation - completed
- development of FEM - completed at Wayne State
5Brain Injury ThresholdsOutcome
- A simple animal model is used to study the
threshold for brain injury (contusion) - examine
the usefulness of different predictors for injury - The FEM is used to study other experimental TBI
models (cortical impact) with other SCIB members - Continued cross-correlation of experimental
models - one threshold does not seem to
universally match
6University of PennsylvaniaOverall Objective
- To acquire experimental data for developing and
validating the finite element model used in the
NHTSA SIMon program - Brain Injury Thresholds
- Boundary Conditions
7Skull-Brain Boundary Conditions Specific Goals
- To measure the relative motion of the brain
within the skull to provide more validation data
for the SIMon model as it begins to transform
from a research tool into a technology that is
the basis for a new head impact protection
standard.
8Experimental Methods
SPAtial Modulation of Magnetization
High Resolution T1-weighted Image
N14 sets (from 11 subjects)
N47 images from 5 subjects
9Postures and Motion Sequences
Extension supine (ES)
Neutral supine (NS)
Flexion supine (FS)
Neutral prone (NP)
Flexion prone (FP)
10Boundary Conditions Progress Outcomes
- Progress
- SPAMM - completed. paper published
- High Resolution T1 - completed. manuscript
published - Outcomes
- Cerebellum rotates 1-4 brainstem moves 1mm
out of the foramen magnum during moderate neck
flexion - Foramen magnum should NOT be modeled as a no-slip
condition
11University of PennsylvaniaOverall Objective
- To acquire experimental data for developing and
validating the finite element model used in the
NHTSA SIMon program - Brain Injury Thresholds
- Boundary Conditions
- Material Properties of Brain Tissue
12Brain Material Properties Specific Goals
- To provide biofidelic mechanical responses of the
living brain that can be incorporated in finite
element models of the head (like SIMon). - In vivo, in situ, in vitro indentation tests
- Finite shear properties of Brainstem
13In Vivo Testing
Mechanical properties are determined by quickly
indenting the exposed brain surface to a depth d
with a rigid indentor while recording force P(t)
and displacement d on computer. Assuming that the
brain is a linear viscoelastic half-space, the
shear modulus G can be calculated from the
relationship
Lee ? Radok (1960) The contact problem for
viscoelastic bodies. J. Appl. Mech., 27 438-444
14Comparing in vivo, in situ, in vitro
IN VIVO testing
Sodium pentobarbital overdose
IN SITU testing
IN VITRO testing
15Major Findings
- Preconditioning did not have a significant effect
on the living brain, but significantly reduced
the shear moduli in vitro. - Shear moduli in vitro are consistently lower than
in situ (likely due to skull confinement). - The same boundary conditions exist in vivo and in
situ, and there were no significant differences
between these two comparable conditions.
Overall, we conclude that the mechanical behavior
of a living brain is similar to that of a dead
brain
16Brain Material Properties Specific Goals
- To provide biofidelic mechanical responses of the
living brain that can be incorporated in finite
element models of the head (like SIMon). - In vivo, in situ, in vitro indentation tests
- Brainstem undergoing large strains
17Brainstem properties (Finite shear)
- 4-week porcine brainstems (N15)
- 3 specimens per subject
parallel or perpendicular
cross-sectional
18Methods Brainstem Testing in Simple Shear
- Simple Stress Relaxation
- Shear strains 50, 40, 30, 20, 10, 5, 2.5, then
50 - Two preconditioning runs
Arbogast et al., J Biomech. 1997
19Results
Anisotropic strain energy functions for
instantaneous response
WWmatrix Wfiber
G0 initial shear modulus of matrix-controlled
material g1, g2 relative shear relaxation moduli
t1, t2 characteristic times q stiffness
of axonal fibers
20Brainstem Finite Shear Properties
- Parameters fit simultaneously to 50 test data in
all 3 directions predicted data from all other
strains well (average R2 85) - Fiber stiffness at finite deformation is nearly
10x stiffer than brainstem matrix - previously
we reported fiber 3x stiffer than matrix at 2.5
strain Arbogast and Margulies, 1999 - Brainstem matrix component is the most compliant
brain tissue region with a instantaneous shear
modulus of 12.7 Pa. Previously we reported
average cerebrum tissue modulus of 526.9 Pa
Prange and Margulies, 2002
21Brain Material Properties Progress
- To provide biofidelic mechanical responses of the
living brain that can be incorporated in finite
element models of the head (like SIMon). - In vivo, in situ, in vitro tests - completed,
paper published - Brainstem - completed studies, manuscript
submitted
22Cell-based Models of Brain TissueSpecific Goals
- To provide approximations of the variation in
cellular strains that occur within the brain
during impact, estimates that can be incorporated
in finite element models of the head (like SIMon).
23Studying cellular kinematics in vitroOrganotypic
Cultures
- Use P4-P6 rat pups
- Transverse sections 350 mm thick
- Cultured on 0.005 think laminin treated silastic
membranes - Fed 3X per week with Neurobasal-A supplemented
with B27, glucose, and L-glutamine - Incubated for 10 days on a rocker (2 rocks per
minute)
24Tracking bead/nuclei movement in gels and cultures
Silicone gel or Organotypic tissue
Labeled beads or nuclei
Deformed Substrate
Microscope Objective
25Approximating the constructs and tissue
mm
mc
RVE
26Assumptions
- Cells follow hookean-type elastic behavior
- Mechanical properties of the CNS matrix are
similar to other soft tissues
27Nodal equation and solution
28The fraction of moving nuclei in organotypic
tissue increases with applied strain
29Predicted coefficient of variance indicates cells
are much stiffer than extracellular matrix
Non-linear matrix KcellKmatrix 16 sKcell.2
Applied strain
30Softening of brain tissue at finite strainsAre
the cells softening?
- Measured under simple shear conditions
- Repeatable behavior
- Prevents use of linear formulations
- Approximate 35 decrease in tangential stiffness
- Mechanism cytoskeletal re-alignment/failure?
Prange and Margulies, 2002
31Brain Injury ThresholdsMajor Outcome
- Thresholds for brain injury can be predicted with
finite element approaches, but the
cross-correlation of predictions among animal
models continues - Brainstem motions indicate a mobile/free boundary
condition at the foramen magnum - Brain properties measured from in vitro testing
are reasonable approximations of the in vivo
properties - Composite models suggest a very soft
extracellular component integrated with stiffer
cellular components
32Brain Injury ThresholdsFuture Directions
- Continue the development of animal models - in
vivo imaging to track cell motion during impact - Material property testing - influence of age
- Using material properties and finite element
models - new physcial model validation studies to
confirm model predictions - Developing better transformations between
individual cell types and tissue - are individual
cell populations at risk
33Acknowledgements
- Southern Consortium for Injury Biomechanics
- Ashton Foundation