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1
UltrasoundElasticity Imaging
Stanislav (Stas) [email protected]
Department of Biomedical Engineering
2
Outline
• Introduction
• Mechanical properties of tissue
• Approaches in elasticity imaging
• Elasticity imaging systems
• Applications
• Challenges, advantages and limitations
• Future developments
3
NotationsX=(x1,x2,x3)=(x,y,z) – coordinate systemU=(u1,u2,u3) – displacement vectorεij – strain tensor i=1,2,3σij – stress tensor j=1,2,3
δij – Kronecker delta(1 for i=j, 0 otherwise)
Einstein summation convention –summation is implied over the repeated index,for example:
ρ – density (kg/m3)
ν – Poisson’s ratioE – Young’s modulusλ, µ – Lame coefficientsG – shear modulusK – bulk modulusη – shear viscosityξ – bulk viscosity
ct – shear wave speedcl – longitudinal wave speed
332211
3
1
aaaaai
iiii ++==∑=
∑=
=3
1iijiiji baba
313212111
3
1111 bababababaj
iiiii ++==→= ∑
=
323222121
3
1222 bababababaj
iiiii ++==→= ∑
=
333232131
3
1333 bababababaj
iiiii ++==→= ∑
=
ρµλ
ρµ 2
,+== lt cc
4
Elasticity Imaging – Goal
Remote
non-invasive (or adjunct to invasive)
imaging (or sensing) of
mechanical properties of
tissue forclinical applications
2
5
Elasticity Imaging – Glance at History
Wilson and Robinson, 1982Dickinson and Hill, 1982
Krouskop, (Le)vinson, 1987
Lerner and Parker, 1988
Hippocrates, circa 460-377 B.C.
DeJong et al, 1990
Eisensher et al, 1983
Plewes et al, 1995
Meunier and Bertrand, 1989Adler et al, 1989
Tissue Elasticity Ultrasound M RI Other methods
Krouskop et al, 1998
Parker et al, 1990
Oestreicher, 1951
Pereira et al, 1990
Fung, 1981
Sarvazyan et al, 1975
Chenevert et al, 1998
Fowlkes et al, 1995Muthupillai et al, 1995
Sarvazyan et al, 1984
Ophir et al, 1991Sarvazyan and Skovoroda, 1991
Avalanche of papers
Biomechanics(muscle, skin, ...)
Many papers
Yamakoshi et al, 1988
Duck, 1990
Erkamp et al, 1998
Tristam et al, 1986
Fowlkes et al, 1992
Sarvazyan et al, 1995
Frizzell et al, 1976 Thompson et al, 1981
Frank et al, 1948
6
Mechanical Properties of Tissue(i.e., Why Bother)
Elasticity (e.g., bulk and shear moduli)
Viscosity (e.g., bulk and shear viscosities)
Nonlinearity (e.g., strain hardening)
Other (e.g., anisotropy, pseudoelasticity)
7
Elasticity
Hippocrates
Changes in tissue elasticity are related to pathological changes
… Such swellings as are soft, free from pain, and yield to the finger, ...and are less dangerous than the others.... then, as are painful, hard, and large, indicate danger of speedy death;but such as are soft, free of pain, and yield when pressed with the finger,are more chronic than these.
THE BOOK OF PROGNOSTICS, Hippocrates, 400 B.C.
It is the business of the physician to know, in the first place, things similarand things dissimilar; … which are to be seen, touched, and heard; whichare to be perceived in the sight, and the touch, and the hearing, … whichare to be known by all the means we know other things.
ON THE SURGERY, Hippocrates, 400 B.C.
Hippocrates, 400 B.C.
8
Which Elastic Moduli?
=Poisson’s ratio (ν)Bulk modulus (K)
=Shear modulus (µ=G)Young’s modulus (E)
Most soft tissues are incompressible, i.e.,deformation produces no volume change
ρρGK
cG
c lt32+
=<= KG << 0→K
G
2
1→ν
3
9
Relations between various elastic constants
GµG
KΚννEE
Gµµλλ
K, GE, νλ, µCommon Pair
Constant
)21)(1( ννν
−+E
GK 32−
)(
)23(
µλµλµ
++
)1(2 ν+E
GK
KG
+3
9
( )µλµ
µλλ
+−=
+ 25.0
)(2
µλ 32+
)21(3 ν−E
GK
GK
26
23
+−
)1(2 ν+E
Elasticity10
Human sense of touch – what do we feel?
Sarvazyan et al, 1995
Semi-infinite elastic mediumK – bulk modulusµ – shear modulus
Rigid circular die
F
R
W
µRW
K
GK
G
RWGFK
G 8
31
180
1
→
++=
→
−
F1
x1
x2
x3
01 3µε=F
Static deformation of(nearly) incompressible material is
primarily determined byshear or Young’s modulus (!!!),and boundary conditions (?!?)
Incompressible material
11
• Sample preparation
• Deformation method– Static– Oscillatory (low frequency)
• Preconditioning of the tissue
• Load – Displacement measurements
• Strain – Stress calculations
• Elastic modulus evaluation
How to (Directly) MeasureTissue Elasticity
Semi-infinite elastic medium
Rigidcircular
dieF
R
W
µRWF 8=
F
x1
x2
x3
113µε=F
F
x1
x2
x3
12
Direct Elasticity Measurements
Scale
Load – Displacement Tests
Scale
Scale
Rotational stage
Tissue
Erkamp et al, 1998
2-DPositioning
System
15
10 200
30
Strain (%)
Stre
ss(k
Pa)
4
13
Direct Elasticity Measurements
Artann Laboratories, NJwww.artannlabs.com
F0 (force)
Tissue sampleH0
Rigid support plane
Deformation piston
Fi
Hi
Artann Laboratories, NJXie et al. 2004
14
Wellman P.S., Howe R.D., Dalton E., Kern K.A., “Breast TissueStiffness in Compression is Correlated to Histological Diagnosis,”Harvard BioRobotics Laboratory, Technical Report, 1999
Nava A., Mazza E., Haefner O., and Bajka M.“ Experimental Observation and Modeling ofPreconditioning in Soft Biological Tissues,” inProceedings of Medical SimulationInternational Symposium, 2004 Cambridge.
Samani A., Bishop J., Luginbuhl C. and Plewes D.B.,“ Measuring the elastic modulus of ex vivo small tissue samples,”Physics in Medicine and Biology, 48, pp.2183-2198, 2003.
Krouskop T.A., Wheeler T.M., Kallel F., Garra B.S., Hall T.J.,"The elastic moduli of breast and prostate tissues undercompression,“ Ultrasonic Imaging, 20:260-274, 1998.
15Breast Tissue Elasticity and Pathology
8.0-12.02.0-3.01.5-2.51.0-1.50.5-1.5Young’s
Modulus(kPa)
Ductalfibroadenoma
Infiltrative ductal cancerwith fibrous tissue
predominating.
Fibroadenomas ofglandular origin
Infiltrative ductalcancer with alveolar
tissue predominating.
Normalgland
Breast TissueType
Skovoroda et al., 1995, Biophysics, 40(6):1359-1364.
Krouskop et al., 1998, Ultrasonic Imaging, 20:260-274.
16
Wellman et al., 1999, Harvard BioRobotics Laboratory Technical Report.
Samani et al., 2003, Physics in Medicine and Biology, 48:2183-2198.
Breast Tissue Elasticity and Pathology
5
17
McDonald, 1974
Alessandri et al., 1995
Ozolanta et al., 1998
Intengan et al., 1998
Marque et al., 1999
Fung, 1993
For normal physiological conditions of longitudinaltension and distending blood pressure, below 200 mmHg.
M-mode echocardiography in different age groups.
Represents values for various ages (0-80 y.o.) andatherosclerosis conditions in right and left arteries.
Equilibrated at intraluminal pressure of 45 mmHg,media thickness and lumen diameter were measured inthe applied 3 -140 mmHg intraluminal pressure range.
Range includes measurements for normal vsspontaneously hypertensive animals.
Bending experiments were used to impose variousstrains on different layers of tested blood vessels.
300-940980-1,4201,100-3,5001,230-5,500
183-582
1,060-4,110
100-1,500
700-1,600
434.7
447112
24869
human, in vitroThoracic aortaAbdominal aortaIliac arteryFemoral artery
Ascending aorta
Coronary artery
rat, in vitromesenteric small arteries
aortic wall
porcine, in vitrothoracic aorta
intima-medial layeradventitia layer
ascending aortaintima-medial layeradventitia layer
descending aortaintima-medial layeradventitia layer
Artery
ReferenceCommentsE, kPaType of soft tissue
Elastic Properties of ArteriesSarvazyan A.P., 2001,” In: Handbook of Elastic Properties of Solids, Liquids and Gases.
18Elastic Properties of Prostate GlandAglyamov S.R. and Skovoroda A.R., 2000, Biophysics, 2000, 45(6).
19
Contrast in Elasticity Imaging
102 105104103 106 107 108 109 1010
Shear Modulus (Pa)Bone
All Soft Tissues
EpidermisCartilageCornea
DermisConnective TissueContracted MusclePalpable Nodules
Glandular Tissue of BreastLiver
Relaxed MuscleFat
Bone
Liquids
Bulk Modulus (Pa)
BloodVitreous Humor
Sarvazyan et al, 1995
20
Strain hardening
Elastin
Collagen
Stretch ratio (L/L0)1.0 1.1 1.2 1.3
0
10
20
40
30
Stre
ss(k
Pa)
Vessel Composition (Fung, 1988):muscle (soft), elastin (soft), collagen (hard)
Strain hardening in kidney samples(Erkamp et al, 1998)
0 5 10 15
40
80
Strain [%]
You
ng's
mod
ulus
[kPa
]
• Most soft tissues exhibit strain hardening
• Tissues of organs with primary “ mechanical” functions (muscle, skin,tendon, etc.)
• Other tissues (kidney, brain, blood clot, etc.)
• Strain hardening vs. strain softening (strain energy density function)
6
21
Wellman et al., 1999
Strain hardening22
Strain hardening
Krouskop et al, 1998Ophir et al., 2001
This and other graphs as well as other literaturedata suggest that tissuestrain hardening (or nonlinearity in stress-strain relations) can be used for
tissue analysis including composition, differentiation, etc.
23
Anisotropy• Arterial wall: orthotropic material – 9 constants
two orthogonal planes of symmetry• Muscle: transversely isotropic – 5 constants
axis of symmetry• Isotropic – 2 constants
0 5 10 15 200
4
8
12
16
Strain (% )
Str
ess(
kPa)
Alongfibers
Acrossfibers
24
Viscosity
Time
Constant Deformation
Stress RelaxationStre
ssD
efor
mat
ion
Time
Def
orm
atio
nL
oad Constant Load
Creep
Creep Stress Relaxation
• Shear viscosity: shear waves
• Bulk viscosity: longitudinal ultrasound waves
• Viscoelastic models:Maxwell, Voigt, Kelvin, KVFD, etc.
• Is there a characteristic time?
0 30 60 90
4
8
12
Time(min)
Forc
e(N
)
Cornea
7
25
ViscosityS
tres
s
Strain
Loading Cycles
Elongation
Load
1st cycle
5th
>10th cycle
• Hysteresis loops:independent of the rate of loading (most soft tissues)
• Pseudoelastic material:elastic after preconditioning (with hysteresis)
26
Mechanical Properties of Tissue:References
• Duck, F.A. Physical properties of tissues. Academic press; New York, 1990
• Fung YC. Biomechanics – mechanical properties of living tissues. Springer-Verlag; New York, 1981
• Krouskop TA, Wheeler TM, Kallel F, Garra BS, Hall TJ, “The elastic moduliof breast and prostate tissues under compression,” Ultrasonic Imaging vol. 20pp. 260-274, 1998
• Aglyamov SR, Skovoroda AR, “Mechanical properties of soft biologicaltissues,” Biophysics, Pergamon, 45(6):1103-1111, 2000.
• Sarvazyan AP, “Elastic properties of soft tissues,” In: Handbook of ElasticProperties of Solids, Liquids and Gases, Volume III, Chapter 5, 107-127, eds.Levy, Bass and Stern, Academic Press, 2001
• Other text books and archival publications
27
Phantoms for Elasticity Imaging• Tissue-mimicking phantoms
– Gelatin gels
– Agar-agar and gelatin mixtures
– Rubber (plastisol, silicone)materials
– PVA (poly-vinyl alcohol)
– Polyacrilamyde gels
• Tissue-containing phantoms
– Gelatin gels
– Agar-agar and gelatin gels
– Polyacrilamyde gels
Hall et al., 1997Other papers
• Gelatin and Gelatin/Agar-agar
– Easy to prepare
– E ~ Cn, C – concentration, n=[1-2]
– Short shelf life
– Additives are possible
• Plastisol
– Time-stable phantoms
– Requires excessive heating duringpreparation
• PVA
– Freeze-thaw cycles to varyelasticity
– Time-stable
28
• PVA (poly-vinyl alcohol) tissue-mimicking phantom
• Background:8% PVA solution1% silica (40µm diameter)1 freeze/thaw cycle
• Inclusion:10% PVA solution2% silica particles3 freeze/thaw cycles
• Imaging:SONIX RP imaging system(Ultrasonix, Inc.)5-7 MHz, 40 mm linear probe
• Deformationsmanual0.3%
Phantoms for Elasticity Imaging: Preparation
Park et al., 2007
50mm
50mm
50mm
10mm
8
29
Phantoms for Elasticity Imaging:References
• Madsen EL, Frank GR, Krouskop TA, Varghese T, Kallel F, Ophir J,“Tissue-mimicking oil-in-gelatin dispersions for use in heterogeneouselastography phantoms,” Ultrasonic Imaging vol. 25 pp. 17-38, 2003
• Madsen EL, Hobson MA, Frank GR, Shi H, Jiang J, Hall TJ, Varghese T,Doyley MM, Weaver JB, “ Anthropomorphic breast phantoms for testingelastography systems,” Ultrasound Med Biol. vol. 32 pp. 857-874, 2006
• Hall TJ, Bilgen M, Insana MF, Krouskop TA, “Phantom materials forelastography,” IEEE Trans. UFFC, vol. 44 pp. 1355-1365, 1997
• Surry KJM, Austin HJB, Fenster A, Peters TM, “Poly(vinly alcohol) cryogelphantoms for use in ultrasound and MR imaging,” Phys. Med. Biol., vol. 49pp. 5529-5546, 2004
• Other text books and archival publications
• Where to buyATS Laboratories, Inc. (http://www.atslabs.com/)
30
Elasticity Imaging using ...?
Computerized Tomography:spatial distribution of the absorption (density)
MRI:proton spin density and relaxation time constants
Ultrasound Imaging:variation in acoustical impedance(bulk modulus and density)
Optical Imaging:refraction index
31
Elasticity Imaging – Approaches
Static (strain-based, or reconstructive)imaging internal motion under static deformation
Dynamic (wave-based)imaging shear wave propagation
Mechanical (stress-based, also reconstructive)measuring tissue response at the surface
32
How … Static Elasticity Imaging?
Har
d
Sof
t
Displacement Strain
Ra
nge
9
33
How … Static Elasticity Imaging?
• Capture data during deformation
• Estimate displacements
• Compute strain tensor
• Reconstruct mechanical properties
34
Elasticity Imaging – Main Components
• Capture data duringexternally or internally applied
tissue motion or deformation
• Evaluate tissue response(displacement, strain, stress)
• Reconstruct elastic modulus based ontheory of elasticity
Theory of elasticity is common part inall approaches in Elasticity Imaging
35
• Strain
• Stress
• Constitutive relationships
• Equations of equilibrium
Theory of Elasticity(Static Approach)
011
0
L L
Lε −=
L0
L=L0+∆L
FF
S
S0
∂∂
∂∂+
∂∂
+∂∂=
j
k
i
k
i
j
j
iij x
u
x
u
x
u
x
u
2
1ε
11
F
Sσ =
1111 εσ E= E – Young’s modulus ijijiiij µεδλεσ 2+=
333231
232221
131211
εεεεεεεεε
333231
232221
131211
σσσσσσσσσ
11
1
0x
σ∂ =∂
0=+∂∂
∑ ii j
ij fx
σ
General (3-D) case
36
Equations of Equilibrium
0)2())(())(())((
0))(()2())(())((
0))(())(()2())((
33
3
33
2
2
3
23
1
1
3
13
3
2
2
1
1
3
22
3
3
2
32
2
22
1
1
2
13
3
2
2
1
1
2
11
3
3
1
31
2
2
1
21
1
13
3
2
2
1
1
1
=+∂∂
∂∂+
∂∂+
∂∂
∂∂+
∂∂+
∂∂
∂∂+
∂∂+
∂∂+
∂∂
∂∂
=+∂∂+
∂∂
∂∂+
∂∂
∂∂+
∂∂+
∂∂
∂∂+
∂∂+
∂∂+
∂∂
∂∂
=+∂∂+
∂∂
∂∂+
∂∂+
∂∂
∂∂+
∂∂
∂∂+
∂∂+
∂∂+
∂∂
∂∂
fx
u
xx
u
x
u
xx
u
x
u
xx
u
x
u
x
u
x
fx
u
x
u
xx
u
xx
u
x
u
xx
u
x
u
x
u
x
fx
u
x
u
xx
u
x
u
xx
u
xx
u
x
u
x
u
x
µµµλ
µµµλ
µµµλ
Examples (incompressible material)
Small deformations of linear, isotropic (i.e., Hookean) material
F1
x1
x2
x3
01 3µε=FSemi-infinite elastic medium
Rigidcircular
dieF
R
W
µRWF 8=
10
37
References• Landau LD and Lifshitz EM. Theory of elasticity. Pergamon
Press; New York, 1986
• Saada AS. Elasticity Theory and Applications. KriegerPublishing Company; Malabar, Florida, 1993
• Nowazki W. Dynamics of elastic systems. Wiley;New York, 1963
• Nowazki W. Thermoelasticity. Pergamon Press;New York, 1983
• Other text books and archival publications
Beware: most (soft) tissues are (nearly) incompressible
38
Image during Deformation
Transducer
Phantom1-D Motion axis
Deformationplate
• Externally or internally induced deformation
• Continuous deformation while imaging
• Constrained or free-hand transducer
• Various imaging techniques
• Deformation, not translation
39
Displacements
B-Scan Axial (u2) displacement
• Speckle motion↔ Tissue motion↔ Speckle tracking
• Ultrasound Imaging (2-D → 3-D)
• Displacement vector: U=(u1,u2,u3)u1 – lateral componentu2 – axial (along the ultrasound beam)u3 – elevational (out-of-plane) component
• Various speckle tracking techniques
• “Anisotropy” in displacement measurements
40
1-D, 2-D (3-D) Correlation Tracking
AfterDeformation
Kernel Size
Lag
BeforeDeformation
AfterDeformation
BeforeDeformation
Correlation Lag
-0.5
-1
0
0.5
1
Cor
rela
tion
coef
ficie
nt
Lateral lag
Axi
alla
g
Correlation coefficient
Normalized Correlation Coefficient
1-D
2-D
∫∫∫
+⋅
+⋅=
dtltsdtts
dtltstsl
)()(
)()()(ˆ
22
21
2*1ρ
11
41
Strains• Displacement vector → Strain tensor
• Displacement derivatives
• Six (3-D) or three (2-D)independent components
• Sources of error
• Improvement and Optimization
• Effect of strain hardening, anisotropy, etc.
Axial (u2) displacement Normal axial (ε22) strain
∂∂
∂∂+
∂∂
+∂∂=
j
k
i
k
i
j
j
iij x
u
x
u
x
u
x
u
2
1ε
333231
232221
131211
εεεεεεεεε
42
Static or ReconstructiveUltrasound Elasticity Imaging
B-Scan
Deform and image
Displacements
Track internal motion
Strains
Evaluate deformations
Elasticity
ReconstructYoung’s or shearelastic modulus
43
Deformation vs. rotation and translationtranslation – no information about tissue elasticityrotation – no information about tissue elasticity and speckle tracking difficultiesdeformation – consider “ anisotropy” in displacement measurements (example 1)
Volumetric deformation vs. 1-D or 2-D US imagingdeformation – control the deformation state (i.e., plane strain) if possible
Deformation vs. temporal and spatial samplingcontrol deformation rate and/or frame rate and spatial sampling
Deformation vs. distribution and symmetries of elasticityspatial symmetries (if any) must be considered to assist
displacement estimationimaging of strain and interpretation (example 1 and 2)elasticity reconstruction (example 1 and 2)
Deformation: Challenges44
Strain Imaging: ChallengesSources of error in strain images
ultrasound imaging system (electronic SNR, etc.)interpolationstrain induced decorrelationother sources (out-of-plane motion, peak hopping, etc.)
Optimal SNR and CNR in strain imagesshort-time correlation, companding, temporal stretching, strain filter, etc.adaptive strain imaging for large deformations, multi-compression, etc.
Anisotropy in displacement measurementsincompressibility processingother approaches (phase sensitive interpolation, grid slopes, etc.)
Effect of tissue strain hardening on strain imagesutilize as independent parameter of tissue differentiation
12
45
Correlation Lag
-0.5
-1
0
0.5
1C
orre
latio
ncoe
ffici
en
t
Truedisplacement
False PeakJitter
A fundamental limit on delay estimation
Walker and Trahey, 1995
( )
−
+
+≥ 1
11
1
122
32
223230 SNRBBTf ρπ
στ
SNR – root mean squared signal-to-noise ratioρ – correlation coefficientστ – root mean squared time delay estimate error
f0 – center frequencyT – the observation timeB – fractional bandwidth
time↔ distance(via sound velocity)
46
Walker and Trahey, 1995
A fundamental limit on delay estimation
47
Cor
rela
tion
Coe
ffic
ient
Correlation Lag
-0.5
-1
0
0.5
1 RFComplex
0
Cor
rela
tion
Phas
e
BasebandAnalytic
ππππ
π/2π/2π/2π/2
−−−−π/2π/2π/2π/2
−−−−ππππCorrelation Lag
Interpolation Error
O’Donnell et al, 1993Lubinski et al, 1999
Some other approaches are discussed in:Cespedes et al, 1995Cohn et al, 1997Pesavento et al, 1999Geiman et al, 2000
Two-step approach(computationally efficient)
• Correlation peak position ofcomplex baseband signal
• Phase zero-crossing ofanalytic signal correlation
48
Strain Decorrelation
No strainDisplacement error ~ 1 / Kernel Size(Kernel size↔ Observation time ↔Window size)
Strain decorrelationReduce kernel size
Filter correlation functionsSpatial resolution vs. error
Strain � Decorrelation � Displacement Error � Strain Error
T = 1.3 µsec
T = 0.35 µsec (with filter)True strain
40 50 600
1
2
3
4
Time (µsec)
Stra
in(%
)
ρF(t0, t0 +τ)^
τ
tρ(t0, t0 +τ)^
ρ(t0+ ξ1 , t0 + ξ1 +τ)^
ρ(t0- ξ1 , t0 - ξ1 +τ)^
h(t)
Filtered CorrelationCoefficient FunctionCorrelation Filter
Correlation CoefficientFunctions
Σ
t
τ
ττ h(-ξ1)
h(+ξ1)h(0)
Lubinski et al, 1999
13
49
Time Delay Estimation andInterpolation Techniques
Time Delay EstimationDoppler-based techniquesOptical FlowNormalized CovarianceNormalized Cross-correlationHybrid-sign CorrelationPolarity-coincidence CorrelationCross-correlationSum of Squared Differences (SSD)Sum of Absolute Differences (SAD)Mutual InformationMany, many other algorithms
Lubinski et al, 1999
InterpolationParabolicPhase zero crossingCosineSplineGrid slopesAutocorrelation
50Kernel size vs. resolution and SNR
Liu et al., 2003
Resolution
Kernel 0.86 mm
Kernel 0.43 mm
SNR
Formula for optimal kernel size:B – bandwidths – strainf0 – center frequency
Varghese et al., 1998
• Correlation window is longer than pulse length:the axial resolution of elasticity imaging isdetermined by the correlation window.
• Correlation window decreases to pulse length andbelow: spatial resolution is ultimately limited bythe bandwidth of the ultrasonic imaging system.
51
Elasticity Imaging – Approaches
Static (strain-based, or reconstructive)imaging internal motion under static deformation
Dynamic (wave-based)imaging shear wave propagation
Mechanical (stress-based, also reconstructive)measuring tissue response at the surface
52
• Strain
• Stress
• Constitutive relationships
• Equations of motion
Theory of Elasticity(Dynamic Approach)
011
0
L L
Lε −=
L0
L=L0+∆L
FF
S
S0
∂∂
∂∂+
∂∂
+∂∂=
j
k
i
k
i
j
j
iij x
u
x
u
x
u
x
u
2
1ε
11
F
Sσ =
1111 εσ E= E – Young’s modulus
333231
232221
131211
εεεεεεεεε
333231
232221
131211
σσσσσσσσσ
211 1
21
u
x t
σ ρ∂ ∂=∂ ∂
General (3-D) case
2
2
i j ii
i j
uf
x t
σρ
∂ ∂+ =∂ ∂∑
22i j i i i ji jii
i ji j t t
εεξ δσ λ δ ηε µε= +∂∂ ++
∂ ∂
14
53
Example: plane waves• Infinite homogeneous (λ,µ=const) elastic medium (i.e., ignore bulk and shear
viscosities), no body forces (fi=0)
• Assume that u1=u1(x1,t), u2=u2(x1,t), and u3=u3(x1,t)
23
2
3
3
33
2
2
3
23
1
1
3
13
3
2
2
1
1
3
22
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t
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∂∂=
∂∂
∂∂+
∂∂+
∂∂
∂∂+
∂∂+
∂∂
∂∂+
∂∂+
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ρµµµλ
ρµµµλ
ρµµµλ
( )ρ
µλρµλ 2cwhere0
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∂∂→=
∂∂−
∂∂+
t
u
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ρµρµ ==
∂∂
−∂
∂→=
∂∂
−∂
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)3(22
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2
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21
)3(22
cwhere01
0t
u
cx
u
t
u
x
u
t
Longitudinal wave(ultrasound)
Shear wave
54
Catheline, Fink et al. 1999Laboratoire Ondes et Acoustique, Francehttp://www.loa.espci.fr/
Transient ElastographyThe displacement vector is not always orthogonal to the propagation vector:
finite medium, finite size vibratorshear wave is not purely transverse
Transmit low frequency shear wavesmechanical vibration parallel to ultrasound beam
x
z
y
Imagearea
55
Transient ElastographyImage shear waves and measure its velocity using ultrafast imaging and motion tracking
Activeelements
Transmitbeamprofile
Transmitwave front
75m
m
250 beams
Time needed to acquire 1 frame:
lbeam c
Rt
⋅≥ 2
ms25256mm/µm5.1
mm752# ≈⋅⋅=⋅= beamstt beamframe
ConventionalImaging
UltrafastImaging
µs100mm/µm5.1
mm752 ≈⋅== beamframe tt
56
Transient ElastographyEvaluate shear modulus from shear wave velocity
Isotropic, homogeneous, elastic medium
Shear wave propagation equation
Local inversion algorithm
( ) ( ) uut
u rrrrrr
∆+∇∇+=∂∂ µµλρ .
2
2
shearcompression
zy,x,i,2
2
=∆=∂∂
ii u
t
u µρ
( ) ( ) ( ) ( )∑=
−
∂
∂+∂
∂∂
∂=N
ns z
tzxu
x
tzxu
t
tzxu
NzxV
1
1
2
2
2
2
2
2 ,,,,,,1,
15
57
Transient Elastography
-20 0
10
20
30
40
5020
Ultrasound Image
1
2
3
4
5
10
20
30
40
50
-20 0 20
Shear velocity map
m/sBercoff et al. 2003
58
Acoustic Radiation Force Imaging
Nightingale, Trahey et al.Duke University
Dire
ctio
nof
Wav
eP
ropa
gatio
n
1. Focused Acoustic RadiationForce generates localized,impulsive (<0.1 ms) tissueexcitation
2. Track tissue response withsame ultrasonic transducer usedfor force generation
3. Repeat in multiple locationsthroughout 2D FOV
4. Generate images of relativetissue response within theregion of excitation(displacement after forceremoval, recovery time, etc) toassess structural informationabout tissue
RadiationForce
c
IF taα2=
Transducer
59
Bercoff et al. 2004
Shear WaveImaging
60
Bercoff et al. 2004
SupersonicShear Wave Imaging
16
61
Elasticity Imaging Systems(Static / Dynamic)
• Siemens/Acuson Antares
• Hitachi Imaging System
• Sonic RP by UltrasonixMedical, Inc.
• Volcano Therapeutics IVUSImaging
• Winprobe Research Platform
• Other systems
• Supersonic Imaging, Inc.
• Siemens
• Echosens
• Other systems
62
Siemens Sonoline Elegra and Acuson Antares systems
eSie Touch elasticity imaging• Provides additional qualitative information bydemonstrating the typical internal characteristicspattern of three cysts.
eSie Touch elasticity imaging• Improves border delineation of this biopsy-proveninvasive ductal carcinoma. Live dual imagingprovides real time comparison of elastogram tostandard 2D imaging.
www.siemens.com
63
Hall et al, 2006www.engr.wisc.edu/bme/faculty/hall_timothy.htmlwww.medphysics.wisc.edu/medphys_docs/people/hall/hall.html
Fibroadenoma:changing contrastequal lesion size ratio
IDC:constant contrastlarge lesion size ratio
64
Hall, Zhu et al, 2003
17
65
Regner et al. 2006
Lesion size comparison technique
Benign fibroadenoma
WR - size ratios for widthAR - size ratios for area
A, B, C, D, E – five observers
66
Regner et al. 2006
Lesion size comparison techniqueInvasive ductal carcinoma
WR - size ratios for widthAR - size ratios for area
A, B, C, D, E – five observers
67
Regner et al. 2006
Lesion size comparison technique
Benign fat necrosis
WR - size ratios for widthAR - size ratios for area
A, B, C, D, E – five observers
Potential problems: for some lesions it is difficult to distinguish from thesurrounding breast tissue on B-mode images.
68
Regner et al. 2006
Lesion size comparison technique
18
69Hitachi HI Vision 8500/900systems
Nonscirrhous type invasive ductal carcinoma in 29-year-oldwoman
Fibroadenoma with in 39-year-old woman
Itoh et al. 2006
70
Nightingale, Trahey et al.
ARFI image of an in-vivo breast lesion (an infected lymph node) showing differences in displacementand recovery response of different tissues to radiation force excitation
Acoustic Radiation Force Imaging:Breast
In vivo Breast Lymph Node (Reactive, Benign)
Lateral Position (mm)
Dep
th(m
m)
B-mode Max. Disp. (~5µm)
Typical Lymph Node Histology
Reproduced from Wheater’s FunctionalHistology, 4th Ed.
Nightingale et al.; Trahey et al.Duke University
In Vivo Breast LesionsIDAC
B-modeARFI Displacement
(~6.5 µm)
Fibroadenoma
B-modeARFI Displacement
(~1.8 µm)
IDAC Fat Necrosis
Lateral Position (mm) Lateral Position (mm)
Lateral Position (mm)Lateral Position (mm)
B-modeCombined
ARFI ImageB-mode
ARFI Displacement(~5.1 µm)
Nightingale et al.; Trahey et al.
19
73Supersonic Imagine:Elasticity Imaging of Breast
74
Gray-scale transrectalultrasonography
T2-weighted image Dynamic contrast-enhanced image
Color Doppler ultrasonography
Histopathology
Sumura et al., 2007
Elasticity Imaging of Prostate cancerReal-time
elastography
75
Ruhr Center of Competence for Medical EngineeringBochum, Germany (http://www.hf.ruhr-uni-bochum.de)
Real-time (30 fps) Strain Imaging of Prostate:Digital System, 7.5 MHz
76
Varghese et al. 2002
Elastography of Thermal Lesions in the Liverafter RF Ablation
20
77Monitoring liver stiffness after RF ablation
Bharat et al., 2005
normal liverliver with a lesionafter RF ablation
Canine liver tissue in vitro
Ex Vivo RF Liver AblationBefore RF Ablation After RF Ablation
Nightingale et al.; Trahey et al.
Staging of Liver Fibrosis with Radiation Force
Nightingale et al.; Trahey et al.
Key clinical question is degree to which liver fibrosis has occurredBiopsy? Imaging?
Quantitative measure of liver stiffness is neededSWEI: new shear wave speed estimation approach
eliminates 2nd order differentiation
80
Fibroscan
http://www.echosens.com
21
81
Non-invasive staging of liver fibrosis
Friedrich-Rust et al. 2007
A. Real-time elastography; B. Aspartate transaminase-to-platelet ratio index; C. Elasticity- laboratory combination values
82
SuperSonic Imagine:
ShearWave Elastography
Deffieux at al. 2007
In vivo assessment of Young’s modulus in a healthy volunteer
83
Ulrasonix Sonix RPImaging System
www.ultrasonix.com
84
Winprobe Elasticity Imaging System(FPGA-based solution)
www.winprobe.com
-1%
-2%
-1%
-2%
22
85
Characterizing lesions - Palpograms
Cespedes, De Korte et al./Ultrasound in Med. & Biol., Vol. 26, No. 3, pp. 385–396, 2000
86
de Korte, Mastik and van der SteenErasmus Medical Center, Rotterdamhttp://www.eur.nl/fgg/thorax/elasto/
0 20 40 60 80 100 12040
60
80
100
120
140
Frame no.
Intr
a-co
rona
rypr
ess
ure
[mm
Hg]
In vivo acquisition scheme
Strain [%]
1.0
0.0
Eur Heart J 23(5): 405-413 (2002)
87
de Korte, Mastik and van der SteenErasmus Medical Center, Rotterdamhttp://www.eur.nl/fgg/thorax/elasto/
3 Dimensional Elastography:feasibility in a human coronary
88
Vascular Strain Imaging usingArterial Pressure Equalization
Kim et al, Weitzel et alUniversity of Michiganhttp://bul.eecs.umich.edu/
MAP
Strain(%)
Pres
sure
(m
mH
g)40
80
120 } Pulse Pressure
}
23
89
Vascular Strain Imaging usingArterial Pressure Equalization
Kim et al, Weitzel et alUniversity of Michiganhttp://bul.eecs.umich.edu/
90Clinical Data: 5 healthy, 5 diseased arteries
Kim et al, Weitzel et al
healthy diseased
6
12
0
Stra
in (
%)
Stra
in (
%)
30
60
0
healthy diseased
Stra
in R
ate
(Hz)
0.5
1.5
0
1.0
Stra
in R
ate
(Hz)
4
8
0
Phy
siol
ogic
Pre
ssur
eP
ress
ure
Equ
aliz
atio
n
91
CardiacStrain and Strain Rate
Imaging
• Cross-correlation methodhigh sensitivityhigh accuracy2-D or 2.5-Dcomputationally intensive
• Gradient velocity methodfast1-D (axial)aliasing
• Real-time implementation isrequired
D’hooge et al. 2000
92
Different parametric imaging in 3-/4D display, all from a normal subject. Left to right: The red-blue display of tissue velocity, the colored bands of tissuetracking and the yellow-blue display of strain rate. In tissue velocity, lighter color represents higher velocities, showing clearly the velocity gradient from base toapex both in systole and diastole. In tissue tracking, each color represents an interval of 2 mm displacement, as shown by the legend. This means that redrepresents 2 – 4 mm displacement, increasing to magenta showing >14 mm at the base. Strain rate shows shortening in yellow to red, lengthening in blue, darkercolor represents more deformation. Some inhomogeneity is visible due to noise and dropouts. Top to bottom: Bull's eye display both in systole and diastole (excepttissue tracking), M-mode array from all six walls with apex on top and base at the bottom with ECG and a 3D surface reconstruction, velocity and strain rate insystole and diastole. The bull's eye projection shows all of the surface, but the area is distorted; the apex is progressively diminished, while the base is over-represented, the 3D figure shows a representation of the true area, but has to be rotated to see all of the surface. Reconstruction is done from three separate cine-loops, synchronized by means of ECG. The ECG at the left is inverted, but is from the same patient, as may be seen by the end of the cycle, where there is noise inthe ECG signal. The aortic annulus and location of the imaging planes are added for orientation. Støylen, 2003
Cardiac Strain and Strain Rate Imaging
24
93
Deep Vein Thrombosis (DVT) andPulmonary Embolism (PE)
94
Softer ↔ Harder-0.10-0.55
Triplex Ultrasound: Grayscale, Doppler, Elasticity
•• SpragueSprague--DawleyDawley rats (300 g)rats (300 g)
•• Surgically induced clots in IVCSurgically induced clots in IVC
•• Imaging studies clots atImaging studies clots at22--day (acute)day (acute)66--day (subday (sub--acute)acute)99--day (chronic)day (chronic)
•• SiemensSiemens SonolineSonoline ElegraElegra99--13 MHz center frequency13 MHz center frequency
•• 22--D correlation and strain imagingD correlation and strain imaging
Emelianov, Rubin et al, 2000 and 2002
95
Xie et al 2004
Nor
mal
ized
Str
ain
Age (day)2 4 6 8 10 12
0
0.5
1
1.5
2
2.5First Set of Experiments
(learning set, 10 rats)
Second Set of Experiments(4 rats)
• Fitting of data from the first set ofexperiments
ε=e(aD+b)
ε – normalized strainD – age of the clot (day)
• Can first data set predict the age of theclot in the second set of experiments ?
Can elasticityimaging age
DVT ?
True age (day)
Estim
ated
age
(da
y)
2 4 6 8 10 122
4
6
8
10
12
Estimation error:± 0.8 day
96
Elasticity Imaging to Age DVT
Rubin et al., 2006
-60 % -6 %
11m
m
17 mm
Chronic DVT
22m
m
-20 % 0 %
Acute DVT
Strain magnitude Ultrasound backscatter
25
97
3-D StrainImaging
Hall et al, 2006
• Deformation �3-D motion
• Ultrasoundimaging: 2-D
• 3-D tracking isneeded
• Results:– 2-D linear array– Siemens Antares– 5:1 contrast– 1.5% deformation
98
3-D StrainImaging
Hall et al, 2006
• Deformation �3-D motion
• Ultrasoundimaging: 2-D
• 3-D tracking isneeded
• Results:– 2-D linear array– Siemens Antares– 5:1 contrast– 1.5% deformation
99
0 5 10 150
30
60
90
Strain (%)
Ela
stic
Mod
ulus
( kP
a)
Cortex and Medulla
Collective System
Non-linearity in stress-strain relations
13≈∂∂εµ
3≈∂∂εµ
40 kPa
20 kPa
Emelianov et al, 1998Erkamp et al, 1998, 1999
100
Imaging of Tissue Non-linearity
Emelianov et al, 1997Erkamp et al, 1999
26
101
0 10 20 300
1
2
3
4
5
6
Strain(%)
You
ng’s
Mod
ulus
(E/E
0)
0 4 8 120
10
20
30
40
50
60
Strain (%)
You
ng’s
Mod
ulus
(kP
a)Remote (i.e., Elasticity Imaging) Direct (i.e., tissue sample)
Emelianov et al, 1997; Erkamp et al, 1998
102
ViscoelasticityImaging
Strain ↔ Elasticity Creep ↔ Viscosity
103
T1(x)
s tra
in
time
strain image sequence
)))(/exp(1()()(),( 110 xxxx Ttktk ∆−−×+=∆ εεε
x
)(0 xε)()( 10 xx εε +
0 t∆ t∆2 tN∆
Retardance Time Imaging, T1
Gelatin phantomwith inclusionhaving twice thecollagen density
Michael F. Insana et al. University of Illinoisat Urbana-Champaignhttp://ultrasonics.bioen.uiuc.edu
104
In Vivo Patient Studies
Fib
road
enom
a
3
4
5
6
7
820
40
60
80
100
T1:1
-2
0
2
4
6
8
10(sec)10mm T1StrainSonogram
T1:4
0
0
00
2
4
6
8
10
4
6
8
20
40
60
T1StrainSonogram10mm
(sec)
IDC
Two patients with 1-cm, non-palpable lesions detected mammographically. With theretardance time image, malignant and benign lesions can be differentiated because ofdifferences in the collagen ultrastructure between the two lesion types.
Sridhar M, Liu J, Insana MF, “ Elasticity imaging of polymeric media,” ASME J Biomechan Eng (in press)Insana MF, Pellot-Barakat C, Sridhar M, Lindfors K, “ Viscoelastic imaging of breast tumor microenvironment with ultrasound,”
J Mammary Gland Biol Neoplasia. 9: 393-404, 2004Insana MF, “ Elasticity imaging,” In: Wiley Encyclopedia of Biomedical Engineering, M Akay, ed., ISBN: 0-471-24967-X, Hoboken: John
Wiley & Sons, Inc., 2006