Bayly updated Notes 2010

Bayly updated Notes 2010 - The Brain in Motion Brain...

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Unformatted text preview: The Brain in Motion Brain biomechanics and traumatic brain injury Philip Bayly Erik Clayton, Aaron Feng, Ravi Namani, Traci Abney, Ruth Okamoto, Andrew Knutsen, Guy Genin Clayton, Aaron Feng Ravi Namani Traci Abney, Ruth Okamoto, Andrew Knutsen Guy Genin Mechanical Engineering and Materials Science Washington University in St. Louis Outline " #$%&'()&*+)(,&-$&(.')/,&.*).*0-,1 " 23(4,*&5)%,466-,4)&*+).*(4,*&5)674&,)8&946 Biomechanics terminology Forces and torques Linear and angular acceleration Stress and strain ! Fundamental concepts: Newton’s laws Forces cause linear acceleration ;'7&*<4).*)5.*4&,)$=$4*(-$> Torques cause angular acceleration ;'7&*<4).*)&*<-5&,)$=$4*(-$> F F M M dL dt macm dH dt I (in 2D) incompressible material - always have same v olume Stress and strain in 2D Strain?)@4&6-,4)=A)deformation =A)&*)454$4*( Stress?)@4&6-,4)=A)forces =*)&*)454$4*( B B3 B1 B B B1 B3 B " ! C(,&.* xx Lx L L Stress and strain in 2D example B B3 B B B1 B1 " ! B B3 Strain Stress Horizontal lengthening Vertical shortening Horizontal tension Vertical – stress free : shear - deformation w/o change in volume Shear strain in 2D " Shear strain Shear stress Change in angle Tangential forces (Deformation) ! (Force) Shear strain and stretch stress and strain defi ned by coordinate system #$ # C74&,)+4A=,$&(.=*)=A)=/04'()54&+6)(=)6(,4('7.*< Stretch 0 Shortening 0 Mechanical properties of simple materials Elastic?)&3.&5)6(,466)%,=%=,(.=*&5)(=)&3.&5)6(,&.*) 2E<EF)C(445) xx E xx Viscous?)674&,)6(,466)%,=%=,(.=*&5)(=)674&,)6(,&.*),&(4) d 2E<EF)G.5 xy Silly putty is the SHITTTT brain reacts similarly to silly putty xy dt Viscoelastic?)6(,466)+4%4*+6)=*)/=(7)6(,&.*)&*+)6(,&.*),&(4 2E<EF)C.551)H-((1F)I455=F)/,&.*F)J B B3 B B B1 B 1 B B3 D Pressure waves and shear waves pressure waves travel FAST shear waves (up and down) *volume stays the same* H,466-,4)8&946?)H,=%&<&(.=*)%&,&5545)(=) +4A=,$&(.=* C74&,)8&946?)H,=%&<&(.=*)%4,%4*+.'-5&,)(=) +4A=,$&(.=* Strain due to angular acceleration Overview of the Brain shear waves responsible for dynamic deformation of brain tissue shake head very rapidly - deform rapidly in s hear gray matter - cell bodies and glial cells white matter - axons and neural fi bers that c onnect cells thusly have different properties anisoptropic dura (membrane), false (divides hemispheres) K Anatomy and brain suspension old fashion dissection - doesnt show up on MRI shows stiff membrane that separates different compartments of the brain . B4=*&,+=)+&)R.*'.);!KL:S!L!Q> @'@.**M6)N=5=,)O(5&6)=A)P-$&*)O*&(=$1);!QQD> Brain deformation " #$%&'()&*+)(,&-$&(.').*0-,1 Motivation: traumatic brain injury (TBI) " !EL)$.55.=*)TU#)%4,)14&,).*)VC! " LWFWWW)A&(&5) " :DLFWWW)7=6%.(&5.X&(.=*6 " !E!)$.55.=*)4$4,<4*'1),==$)9.6.(6 " !WY)=A)VC)'=$/&()(,==%6)6-6(&.*)TU#E: " :WWFWWW)6%=,(6S,45&(4+)'=*'-66.=*6Z14&,E)D [!\)T7-,$&*)]F)4())&5EF)IE)P4&+)T,&-$&)&*+)^47&/.5.(&(.=*)!QQQ_!K;`>?`W:a!LE [:\)VCO)T=+&1F)I-*4)bF):WW` [D\)C=6.* ]@)4()&5EF)U,&.*)#*0-,1)!QQ`_!W?KcSLK L Concussions in football - 2003 Concussions in football - 2010 very little diagnosis and treatment for c oncussions still an active problem only more intensely covered in the media *major difference* how news spreads injury caused by deformation of the brain axons depolarizes and fl oods brain with neurotransmitters Motivation: traumatic brain injury (TBI) " d]4$4*(.&)%-<.5.6(.'&e)7&6)5=*<)/44*)=/64,94+).*)/=34,6F)494*).*)&/64*'4) =A)'=*'-66.=*6K " N=<*.(.94)+4A.'.(6),4%=,(4+)&$=*<)A=,$4,)%,=A466.=*&5)&*+)&$&(4-,) 6=''4,)%5&14,6ELF` BAHAHAH ZIDANE [K\)I=,+&*)U]E)C4$.*)f4-,=5E):W;:>?!cQSbLF):WWWE) [L\)T169&4,)4()&5EF)O'(&)f4-,=5)C'&*+)bW?!L!S!L`F)!QbQE [`\)@&(64,)4()&5EF)IO@O):b:?Qc!SQcDF)!QQQE) ` accelaration of bone is unimportant Impact and traumatic injury " g7&()&,4)(74)A=,'46)=*)&*+) &''454,&(.=*6)=A)(74)6h-55i " P=8)+=46)(74)/,&.*)+4A=,$i " P=8)+=46)/,&.*)(.66-4),46%=*+)(=) +4A=,$&(.=*i care about the acceleration of the brain and how it deforms Impact and traumatic injury " g7&()&,4)(74)A=,'46)=*)&*+) &''454,&(.=*6)=A)(74)6h-55i " P=8)+=46)(74)/,&.*)+4A=,$i " P=8)+=46)/,&.*)(.66-4),46%=*+)(=) +4A=,$&(.=*i Impact kinematics motion analysis lab c Impact kinematics Impact kinematics j=-,)(,.S&3.&5)&''454,=$4(4,6)$=-*(4+)=*)(74)6-/04'(M6)74&+ Impact kinematics z- forward x- up down y- right left learned this in physics Estimate linear acceleration of mass center and angular acceleration "A "G !A / G !A / G angular acceleration accleration of the c eneter of mass lin. accel ~ 20G Linear acceleration: aG Angular acceleration: !LWS:WW)$Z6: angular accel is very high as well !LWWS:WWW),&+Z6: b Impact and traumatic injury " g7&()&,4)(74)A=,'46)=*)&*+) &''454,&(.=*6)=A)(74)6h-55i " P=8)+=46)(74)/,&.*)+4A=,$i " P=8)+=46)/,&.*)(.66-4),46%=*+)(=) +4A=,$&(.=*i Good or Bad? if soccer ball (soft object deforms) soft tissue will deform too! Brain deformation: MR tagging " N=*(,&6().6)$=+-5&(4+)/1)6.*-6=.+ " k,.+)=A)d(&<)5.*46e)$=946)8.(7)$&(4,.&5 soft tissue will deform tagging superimposes grids on image so you c an trace/track deformation Brain deformation: MR tagging " k45)d%7&*(=$e " ^46=5-(.=* " C%&(.&5?)!EL)$$ " T4$%=,&5?)`)$6) " T&<)6%&'.*<?)b)$$ " l:LW),&+Z6: L)'$ Q MR tagging – methods Brain deformation due to angular acceleration brain continues to move and thusly deforms " C-/04'()!?)O+-5()$&54 " ^46=5-(.=* " C%&(.&5?)!EL)$$ " T4$%=,&5?)`)$6) " T&<)6%&'.*<?)b)$$) " W)'$)&/=94),4A4,4*'4) %5&*4 " l:LW),&+Z6: L)'$ angular acceleration is not as high as soccer player Brain deformation due to angular acceleration " C-/04'()!?)O+-5()$&54 " ^46=5-(.=* " C%&(.&5?)!EL)$$ " T4$%=,&5?)`)$6) " T&<)6%&'.*<?)b)$$) " W)'$)&/=94),4A4,4*'4) %5&*4 " l:LW),&+Z6: L)'$ !W deforms elastically (very good) Analysis of brain deformation identify the relationship of reference triangle to deformed triangle 26(.$&(4)+4A=,$&(.=*) <,&+.4*()(4*6=,)F 26(.$&(4)B&<,&*<.&*) 6(,&.*)(4*6=,)E (you dont need to know this shit) advanced kinematics crap j='-6)=*),&+.&5S '.,'-$A4,4*(.&5)674&,) 6(,&.*) % r [X1,Y1] #% i ( & d$ i , i 1,2,3 (& T & ' ) / 2 #$3 [X3,Y3] [x1,y1] & #$1 [x3,y3] just know how strain is measured #%1 #$2 [X2,Y2] #%3 #%2 [x2,y2] Analysis of brain deformation we see hot spots at point of impact and 180 degrees away you see strain dissipates C-/04'(6)!)&*+):?))#$&<4)%5&*4)m:)'$ Analysis of brain deformation shows how much area of the image deformed above a certain strain level most of brain strain > 0.2 but very little expreiences strain > 0.6 j,&'(.=*)=A).$&<4)&,4&).*)87.'7) r 43'44+6)&)6%4'.A.4+)(7,467=5+F) )E);&>)C-/04'()!E);/>)C-/04'():E . !! Brain deformation due to linear acceleration linear acclereation (still less than soccer player) " O+-5()$&54 " ^46=5-(.=* " C%&(.&5?)!EL)$$ " T4$%=,&5?)`)$6) " T&<)6%&'.*<?)b)$$) " lDW)$Z6: Brain deformation due to linear acceleration " O+-5()A4$&54 " ^46=5-(.=* " C%&(.&5?)!EL)$$ " T4$%=,&5?)`)$6) " T&<)6%&'.*<?)b)$$) " lDW)$Z6: Brain deformation due to linear acceleration deformation observed . k,.+)+.6%5&'4$4*()&$%5.A.4+)Ln ^4A4,4*'4 4A=,$4+ !: plot strain fi elds Brain deformation due to linear acceleration Horizontal, vertical strains &'()*)+,-.%,/016,57*)+,-.8#9,01- Shear strain (*%,*23)45 (3'%*,4)45 observes stretching in horizontal direction in the back and shortening in the front (-) " (+) ! . Brain deformation due to linear acceleration still stretching in back and shortening in the back\ Horizontal, vertical strains &'()*)+,-.%,/016,57*)+,-.8#9,01- (*%,*23)45 (3'%*,4)45 back pulling away from something front bumping in to something Shear strain (+) (-) " ! what is going on? . Brain deformation due to linear acceleration Hypothesis! Bungee jumping analogy everything below belt will stretch, above belt will be compressed Brain suspension plays key role &'()*)+,-.%,/01. 6,57*)+,-.8#9,01- (*%,*23)45 (3'%*,4)45 everything will be in compression if bungee failed maybe brain works the same way protects brain, but we see strain at point of attachment !D Absolute brain-skull motion " O+-5()$&54 " ^46=5-(.=* we see some kind of tethering or attachment moves relative to the points of attachment " C%&(.&5?)!EL)$$ " T4$%=,&5?)`)$6) " T&<)6%&'.*<?)b)$$) " lDW)$Z6: Relative brain-skull motion " O+-5()$&54 " ^46=5-(.=* " C%&(.&5?)!EL)$$ " T4$%=,&5?)`)$6) " T&<)6%&'.*<?)b)$$) " lDW)$Z6: Impact and traumatic injury " g7&()&,4)(74)A=,'46)=*)&*+) &''454,&(.=*6)=A)(74)6h-55i " P=8)+=46)(74)/,&.*)+4A=,$i " P=8)+=46)/,&.*)(.66-4),46%=*+)(=) +4A=,$&(.=*i !K membrane channels open and get depolarization Impact and traumatic injury At high strains and strain rates " C=+.-$).=*6),-67).*(=)'4556 " f4-,=*6),454&64)*4-,=(,&*6$.((4,6 " f4-,&5)A./4,6);&3=*6>)68455)&*+)&3=*&5)(,&*6%=,().6)+.6,-%(4+ " N4,(&.*)d/&+e)%,=(4.*6)&''-$-5&(4)&5=*<)&3=*6); OHH> " O'(-&5),-%(-,4)=A)$4$/,&*4)*=()*4'466&,1) A=,).$%&.,$4*( depolarize -> release neurotrans. causes incoherence, brain confusion, s tate of consciousness gets disrupted ;oE)].h,&*.&*> long term - axons will be disrupted pic - axon 24 hours after disruption, axon is SWOLLEN. accumulation of traffi c in swollen axon. B-APP precursor marker to alzheimers. we observe axon swelling and disruption and axonal transport C8=554*)&3=*&5)/-*+546)!`)7,6)%=6()TU#).*)pjH)$=-64E ;oE)].h,&*.&*> ^46%=*64)(=)6(,&.*?)O3=*&5)#*0-,1 we see accumulation of precursor protein in red dye OHH)A5-=,46'4*( Amyloid Precursor Protein staining 16-24 hrs post TBI. !L ^46%=*64)(=)6(,&.*?)O3=*&5)#*0-,1 EM micrograph of an axonal swelling, 5 hrs post TBI excitatoxic death - secondary not directly due to mechanical strain Excitotoxic cell death :,7#*3"-4,9%'4( ;4<9%,/-4,9%'4( ;4<9%,/-4,9%'4-.=>-)?75,0 LM: 1 m plastic sections from parietal cortex 4 hr post TBI (methylene blue azure II) EM: Cortical neuron exhibiting classic excitotoxic cell death (swelling, chromatin clumping, nuclear degeneration) also secondary, not mechanical strain Apoptotic neurodegeneration: “Cell suicide” A @ dark stains indicate apoptosis damaged axons and kill themselves C A B @ Distribution of caspase-3 positive (apoptotic) neurons 24 hr post trauma in P7 mouse !` Impact and traumatic injury: summary " Skull accelerates during “normal” activity a B.*4&,)&''454,&(.=*):WW)$Z6: a O*<-5&,)&''454,&(.=*):WWW),&+Z6: " Brain deforms due to acceleration of the head a C(,&.*6)=A)WEW:)a WEW`);:YS `Y)6(,4('7>)&,4)*=,$&5 a C%&(.&5)9&,.&(.=*6),4A54'()&*&(=$.'&5)'=*6(,&.*(6 " Brain injury depends on strain and strain rate pressure and shear waves in brain Blast injury and TBI blast causes pressure fi eld H ( 1*&$.')%,466-,4)=6'.55&(.=*6 B.*4&,)6h-55)&''454,&(.=* all four would cause dynamic strain O*<-5&,)6h-55)&''454,&(.=* H4*4(,&(.=* Brain deformation propogating shear waves in brain " 23(4,*&5)%,466-,4)&*+).*(4,*&5)674&,)8&946 " @^)45&6(=<,&%71 ;2,.h)N5&1(=*> !c phase contrast MRI Tissue motion is encoded as phase contrast in the MRI image – sensitive to small motion Traditional Gradient-recalled echo MRE Gradient-recalled echo take normal MRI and add mechanical motion if you oscillate MRI fi eld you could measure v ibration - thusly measure propogating waves #*(4*6.(1) #$&<4 23&$%54?) N-/4)=A)/.=$&(4,.&5 g&94) #$&<4 ;2,.h)N5&1(=*> 3D tissue motion can be imaged non-invasively in vivo 1 1 3 1 3 X cause waves to propogate through harmonic actuator C74&,)8&94) %,=%&<&(.=*)&3.6 C74&,)8&94 +.6%5&'4$4*()&3.6 Spatiotemporal Images of Shear Wave Propagation Container of Gelatin w/ Soft Inclusion we see the wavelength of shear waves c hanging Harmonic actuator (~20 µm peak-to-peak) ;2,.h)N5&1(=*> MR elastography: wave speed depends on stiffness stiff soft material at interface you observe bending because of different material properties !3 :3 23%4,.$4*(?)<45)6&$%54)a :)'=*'4*(,&(.=*6 P=,.X=*(&5)+.6%5&'4$4*()A.45+ KWW)PX ;^&9.)f&$&*.> !b MR elastography can determine shear modulus from this k45)6&$%54)a :)'=*'4*(,&(.=*6 KWW)PX .6%5&'4$4*( C74&,)$=+-5-6 ;^&9.)f&$&*.> Human studies: Acoustic pressure imparts motion to the skull impose direct mechanical forces on brain Actuator : O'=-6(.')%,466-,4)=*)6h-55 Frequency : KL)PXF)K)'1'54)/-,6(6 like sitting in car with the BASS BUMPIN Amplitude : :)<);%4&h>) B4A(Z,.<7()$=(.=*)&%%,=3.$&(451).*S%7&64 23'.(&(.=*)g&94A=,$ rockin so much bass cant even feel my faceeeeeeee Accelerometer ;2,.h)N5&1(=*> Brain motion in space and time sine wave harmonic motion GRE – MRE (1.5T) TR/TE : !DDEDZ:cEL)$6 Voxel : DEW)3)DEW)3)DEW)$$D Motion components : uF)vF)q)w No. Image Slices : ! O$%5.(-+4 Temporal Resolution ?)K)%=.*( : D (.$4 v ! K ;2,.h)N5&1(=*> r$ !Q Brain displacement due to pressure loading XF)w we see "sloshing" XF)w 1F)v 3F)u u 1F)v v 3 MRI is the shit for this kind of imaging cheap, effective, accurate w 3 3 1 1 1 µm Brain displacement due to pressure loading XF)w 3F)u KL)PX probably due to the stiff membrane that s plits the hemispheres 1F)v XF)w wave propogates inward from the skull, but s ome interaction at the back 3F u 1F)v N=*(=-,?)v a +.6%5&'4$4*()'=$%=*4*();r$> 1F v Pressure loading and shear waves in the brain " We can measure displacement and strain due to pressure loading a N=$%54$4*(6)(&<<.*<)6(-+.46 a #55-$.*&(46)4AA4'(6)=A)&*&(=$1)=*)$=(.=* " MR elastography provides estimates of shear modulus in vivo a N7&,&'(4,.X46)5.*4&,)/47&9.=,);6$&55)+4A=,$&(.=*6> :W Summary " U,&.*)+4A=,$&(.=* ;strain>).6)'&-64+)/1),&%.+)74&+) &''454,&(.=*)&*+)'&*)/4)$4&6-,4+)*=*S.*9&6.9451 " @4'7&*.'&5)674&,)8&946)'&*)/4)6(.$-5&(4+)/1 43(4,*&5) %,466-,4)5=&+6)&*+)$4&6-,4+)*=*S.*9&6.9451 " @4'7&*.'&5)%,=%4,(.46 (7,=-<7=-()(74)/,&.*)'&*)/4) 46(.$&(4+)/1)@^)45&6(=<,&%71 Future directions computer models are the future leads the direction of future experiments " P4&+)#$%&'()&*+)TU# " Computer models 8.55)<-.+4)%,494*(.=*)&*+)-*+4,6(&*+.*< " N455-5&,)&*+)$=54'-5&,),46%=*64)(= strain 8.55)/4)6(-+.4+).*)9.(,=) &*+).*)&*.$&5)$=+456 " U5&6().*0-,1)&*+)TU# " Computer models 8.55)/4)-64+)(=)6.$-5&(4)/5&6()%716.'6)&*+) ,46%=*64)=A)/,&.*)(.66-4 " O''-,&(4F),46=594+)$4&6-,4$4*(6)=A)skull and brain mechanical properties &,4)*44+4+ can simulate experiments without physical s tudies but wouldnt be able to trust model without through experimentation and good data Acknowledgements " k,=-%)$4$/4,6 " ^)f&$&*.F)Oo)o*-(64*F)OO)C&/4(F)C@)O(&1F)NB)@&')]=*&5+F)TC)N=74*F) NN)o4664*6F)22)U5&'hF)2,.h)N5&1(=*F)O&,=*)j4*<F))) " N=55&/=,&(=,6 " BO)T&/4,F)II)f4.5F)I)O'h4,$&*F)N])o,=4*h4F) " k@)k4*.*F)]B)U,=+1F)^I)Gh&$=(= " j-*+.*< " f#P?)k,&*(6)^:!)fCWKL:Dc)F)^W!)fCWLLQL!F)^:!)2UWWLbDK " fCj?)k,&*()]@CSWLKWcW! " @']=**455)N4*(4,)A=,)P.<74,)U,&.*)j-*'(.=* " @']=**455)N4*(4,)A=,)N455-5&,)&*+)@=54'-5&,)f4-,=/.=5=<1) :! ...
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