ROLE OF MOISTURE CONTENT INROLE OF MOISTURE CONTENT IN MECHANICAL CHARACTERIZATION 

OF BRAIN TISSUE

HENRY W. HASLACH, JR.DEPARTMENT OF MECHANICAL ENGINEERINGDEPARTMENT OF MECHANICAL ENGINEERING

CENTER for ENERGETICS CONCEPTS DEVELOPMENTUNIVERSITY OF MARYLAND

COLLEGE PARK, MD 20742 USA

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INTRODUCTIONINTRODUCTION

A. RAT BRAIN SERVES AS AN ANIMAL MODEL FOR mTBI

B. FOR A FEM, CHARACTERIZE THE MECHANICAL RESPONSE

C. SEEK MECHANICAL CAUSE OF mTBI

D. INCLUDE MOISTURE CONTENT OF THE TISSUE

1. QUESTION NEGLECTED BY MOST OTHER RESEARCHERS

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ROLE OF MOISTUREROLE OF MOISTURE

A. ROLE OF MOISTURE CONTENT IS A KEY TO UNDERSTANDING THE DAMAGE CAUSED BY SHOCK WAVES

1. MOISTURE CONTRIBUTES TO THE VISCOELASTIC (TIME‐DEPENDENT) MECHANICAL RESPONSE TO LOADSDEPENDENT) MECHANICAL RESPONSE TO LOADS

2. SHOCK WAVES MAY MOVE INTERNAL TISSUE MOISTURE

3. CAN EFFECT GLASS TRANSITION OF TISSUE PROTEINS

B. WE MEASURED MOISTURE CONTENT BY WEIGHT AS 81.5%

1 BRAIN TISSUE DENSITY IS ABOUT 1 04 g/cc1. BRAIN TISSUE DENSITY IS ABOUT 1.04 g/cc. 

2. MOISTURE CONTENT BY VOLUME IS ABOUT THE SAME AS MOISTURE CONTENT BY WEIGHT

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EVAPORATION TESTA. HOW SOON AFTER HARVEST MUST THE TEST BE PERFORMED 

IF SPECIMEN IS NOT KEPT IN PBS TO REHYDRATE

B. AMBIENT 30% RELATIVE HUMIDITY

20.00%

25.00%

Experiment 1: Left Hem.

Experiment 2: Right Hem.

Experiment 3 Left hemisphere

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Experiment 3: Left hemisphere

"Experiment 4: Right hemisphere"

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RESULTS IN THE BIOMECHANICS LITERATURERESULTS IN THE BIOMECHANICS LITERATURE

A. PROPOSED MATHEMATICAL MODELS

1. LINEAR VISCOELASTIC (SUPERPOSITION HOLDS)

2. STRESS‐STRAIN TESTS SHOW

a. BRAIN TISSUE IS NONLINEAR VISCOELASTIC

e. g.  MILLER AND CHINZEI 2002

b. AD HOC NONLINEAR VISCOELASTIC BASED ON RUBBER

3. IGNORE ROLE OF MOISTURE CONTENT

B EXPERIMENTALB. EXPERIMENTAL

1. INDENTERS FOR LOAD‐DEFORMATION RELATION

a. CAN ONLY GIVE LINEAR VISCOELASTIC a. CAN ONLY GIVE LINEAR VISCOELASTIC  

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2 HOPKINSON BAR FOR HIGH STRAIN RATES2. HOPKINSON BAR FOR HIGH STRAIN RATES

a. ONLY GIVES COMPRESSION AND ONLY AT CONSTANT RATES

Zhang et al., 2011

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SMALL‐SIZED SAMPLE TESTSSMALL SIZED SAMPLE TESTS

A. DETERMINE STRESS‐STRAIN CURVES IN COMPRESSION AND IN SHEAR 

1. SUCH LOADS BELIEVED RELATED TO mTBI

2. CONFINED COMPRESSION TESTS

3. TRANSLATIONAL SHEAR TESTS

B MEASURE PERMEABILITY TO ACCOUNT FOR MOISTURE ROLEB. MEASURE PERMEABILITY TO ACCOUNT FOR MOISTURE ROLE

C. FIT WITH NEW NONLINEAR VISCOELASTIC MODEL

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I. CONFINED COMPRESSION TESTI. CONFINED COMPRESSION TEST

A. METHOD TO DETERMINE UNIAXIAL PERMEABILITY

B. APPARATUS – SPECIMEN IN CYLINDER

0.25”

filterPlunger

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specimen

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PROPERTIES TO MEASURE

A. UNDER LINEARLY INCREASING COMPRESSION, HOW DOES RATE INFLUENCE LOAD RESPONSERATE INFLUENCE LOAD RESPONSE

B. IS TISSUE STRAIN HARDENING OR SOFTENING?

1. REFLECTED IN CONCAVITY OF LOAD CURVE

2. INERTIA OF INTERCELLULAR WATER OR PORE CLOSING?

C. PERMEABILITY AS A FUNCTION OF STRAIN AND STRAIN RATE

1. MEASURED BY FITTING SOLUTION TO THE BIPHASIC PDE TO A STRESS RELAXATION CURVE

2. PERMEABILITY INCREASES IF STRAIN SOFTENING

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QUASI‐STATIC CONFINED COMPRESSIONQUASI STATIC CONFINED COMPRESSION

A. STRAIN RATE IS 6.4 X 10-4/s (16 HRS), INNER SAGITTAL SLICEB DAMAGE APPARENTB. DAMAGE APPARENTC. STRAIN SOFTENING

brain40511e

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QUASI‐STATIC UNCONFINED COMPRESSIONQUASI STATIC UNCONFINED COMPRESSION

A. MILLER‐CHINZEI:    SWINE CORTEX 30 mm DIA, 10 mm HIGH AT 6.4 X 10‐4/sIS STRAIN HARDENING

B. DUE TO MULTI‐AXIAL MOISTURE FLOW? RADIAL EXPANSION OBSERVED

Miller02 brain test 4c

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EVIDENCE OF DAMAGE AND MOISTURE FLOWEVIDENCE OF DAMAGE AND MOISTURE FLOW

A. STRAIN 5%, THEN STRESS RELAX brain41211a

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REPEAT CYCLES FOR STRAIN TO 10, 15, 20, 25%

B. PLATEAU AT END OF LINEARLY -40

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INCREASING DEFORMATION REGION TO 10%

C. DAMAGE IN PLATEAU REGION

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sample number

IS TYPICAL OF DRYING (AT PLUNGER)

AND SHIFTING OF SOLID MATERIAL

D STRESS RELAXATION REGION

brain32211b

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D. STRESS RELAXATION REGION, WATER REDISTRIBUTES

E. PATTERN REPEATS AT ALL STRAIN LEVELS 10 15 20 25 % 80

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LEVELS 10,15,20 25 % -80sample number

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LOAD SEGMENT OF LOAD‐RELAXATIONLOAD SEGMENT OF LOAD RELAXATION 

A. STRAIN SOFTENING IN COMPRESSION (0.001 mm/s)

B. FROM 0.2 TO 0.29 GLOBAL STRAIN, LENGTH = 3mm

Brain 121710g

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-100

sample number (displacement)

SHEAR FIXTURESHEAR FIXTURE

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QUASI‐STATIC TESTQUASI STATIC TEST

A. STRAIN RATE IS 3.2 X 10-4/s (16 HOUR TEST)B. INNER SAGITTAL SLICE: 6x6x4 mm

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C. FAILURE AT 10% - DUE TO DEHYDRATION?15

ARTERY TISSUEARTERY TISSUEA. THE AORTA IS A LOAD BEARING MATERIALB SOFTENS WHEN SHEARED PARALLEL TO COLLAGEN FIBERSB. SOFTENS WHEN SHEARED PARALLEL TO COLLAGEN FIBERS

AORTA - CIRCUMFERENTIAL

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LOAD‐RELAXATIONLOAD RELAXATION

A. RELAXATION ALSO OCCURS IN SHEAR

shear50311b

B. 1mm/s RATE, 12x6x3mm, INNER SAGITTAL SLICE

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-4sample number

HALF SINE DISPLACEMENT

A. SINUSOIDAL RAMP TO

. shear51011m

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INVESTIGATE VARIABLE STRAIN RATE

TOP: 0 1 mm/s 7x6x3 mm 10

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TOP: 0.1 mm/s, 7x6x3 mm, INNER SAGITTAL SLICE

1. SLIP WITHIN SPECIMEN,

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stretch

,LARGE DAMAGE AT 10 %

BOTTOM: 10 mm/s 5x6x3 mm

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a)BOTTOM: 10 mm/s, 5x6x3 mm INNER SAGITTAL SLICE

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stretch

NONLINEAR NON-EQUILIBRIUM PROCESSESA. BRAIN TISSUE MATHEMATICAL MODEL CANNOT BE AD HOC

B. BASED ON NONLINEAR THERMODYNAMICS OF SOLIDS

C. DYNAMIC RESPONSE ORGANIZED BY EQUILIBRIUM STATES1. THIS IS WHY QUASI-STATIC RELATIONS NEEDED

D. SUPPLEMENTS THE SECOND LAW BY A MAXIMUM DISSIPATION PRINCIPAL TO GIVE PROCESS DIRECTION

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THERMODYNAMIC MODELTHERMODYNAMIC  MODELE. THERMODYNAMIC MODULUS, k, DEFINES SPEED

F. LONG-TERM HYPERELASTIC STRAIN ENERGY DENSITY WHERE x IS STATE VARIABLE (e.g. STRESS)AND y IS CONTROL VARIABLE (e.g. STRAIN)y ( g )

G. GIVES A UNIQUE NON-EQULIBRIUM EVOLUTION EQUATION

1. CONTRAST TO CONTINUUM THERMODYNAMICS CLAUSIUS-DUHEM INEQUALITY WHICH DOES NOT DETERMINE THE

RESPONSE2. THE SMALLER k, THE MORE VISCOUS

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POSSIBLE PRIMARY MECHANICAL CAUSE OF TBImTBI

A. AXON STRAIN (WHITE TISSUE) ‐ DIFFUSE AXONAL INJURY (DAI)( ) ( )

1. DYNAMIC STRETCH OF AXON MAY INDUCE SWELLING BULBS ALONG THE AXON

2. BULBS ARE FOCUS OF DEGENERATION

(SMITH AND MEANEY, 2000)

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THRESHOLD CRITERIA FOR mTBI?THRESHOLD CRITERIA FOR mTBI?

A. SMALL STRAINS KNOWN TO REDUCE AXON CONDUCTIVITY

B. SWELLINGS IN RAT SPINAL NERVE ROOTS ACCUMULATE AMYLOID PRECURSER PROTEIN (‐APP), A MARKER FORAMYLOID PRECURSER PROTEIN ( APP), A MARKER FOR 

IMPAIRED TRANSPORT (SINGH ET AL., 2006).

1. COMPLETE IMPAIRMENT AT 9% STRAIN AT 15 mm/s

C. DAI DUE TO INERTIAL LATERAL ROTATIONAL LOAD

1. 5‐10% STRAIN COMPLETE IMPAIRMENT 

(MARGULIES AND THIBAULT, 1992) 

D EVEN SMALLER STRAINS CAUSE DAMAGED. EVEN SMALLER STRAINS CAUSE DAMAGE

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HYPOTHESISA. INTERCELLULAR MOISTURE FLOW FROM PRESSURE DEFORMS 

AXON TRACTS

1. KEY: MECHANICAL RESPONSE OF SUBSTRUCTURES

B. LEADS TO AXON STRAIN AND DAMAGEB. LEADS TO AXON STRAIN AND DAMAGE

1. SECONDARY BIOCHEMICAL CHANGES

C IN RAT TEST HIPPOCAMPUS AND CORPUS CALLOSUM FORC. IN RAT, TEST HIPPOCAMPUS AND CORPUS CALLOSUM FOR AXON MOTION UNDER HIGH STRAIN RATE

D CHANGE IN OSMOTIC PRESSURE MAY CAUSE CELL DEATHD. CHANGE IN OSMOTIC PRESSURE MAY CAUSE CELL DEATH

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SOME OPEN QUESTIONSI. HOW ARE MECHANICAL PROPERTIES OF BRAIN TISSUE

RELATED TO mTBI?

A. THREE CAUSES OF PRIMARY MECHANICAL INJURY1. SHOCK WAVE, 2. IMPACT, 3. INERTIAL ACCELERATION

B. HOW DO LOCAL FLUID PRESSURE, STRAIN, STRAIN RATE, VARIABLE STRAIN RATE AFFECT PERMEABILITY?

C. HOW IS STRAIN SOFTENING RELATED TO mTBI?

D. HOW DOES PERMEABILITY RELATE TO STRESS WAVE SPEED AND AMPLITUDE IN TISSUE?SPEED AND AMPLITUDE IN TISSUE?

E. HOW DO LOCAL INTERCELLULAR FLUID PRESSURE AND FLOW RELATE TO AXON DAMAGE?FLOW RELATE TO AXON DAMAGE?

F. DOES SHOCK WAVE DEHYDRATE LOCAL REGIONS?24

OPEN QUESTIONSOPEN QUESTIONS

II. HOW CAN A FINITE ELEMENT MODEL PREDICT mTBI?

A. WHAT LEVEL OF SUBSTRUCTURES MUST BE INCLUDED IN A FEM?

B. IS THERE REALLY A THRESHOLD CRITERION?

1. OR JUST A THRESHOLD AT WHICH mTBI IS IMMEDIATELY NOTICEABLE?

C. FEM MUST ACCOUNT FOR INTERCELLULAR FLUID BEHAVIORBEHAVIOR

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RAT BRAIN SCHEMATICRAT BRAIN SCHEMATIC

From http://learn.genetics.utah.edu/content/addiction/genetics/images/brains_large.jpg

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