Shear Wave Elastography Using Ultrasound

Shear Wave Elastography

Using Ultrasound

Mickael Tanter, PhD

Institute Langevin

Ecole Supérieure de Physique et Chimie Industrielles (ESPCI)

Paris, France

Disclosure: M. Tanter is co-founder and shareholder of Supersonic Imagine company

Fibrotic

lesion

Carcinoma

Grade II

Viscous Cyst

A limitation of Ultrasound Imaging

Benin Benin Malignant

Example of Breast Cancer Diagnosis

Tanter M, Bercoff J, Athanasiou A, et al. Ultrasound in Medicine and Biology, 34(9), 1373-1386 ,Sep. 2008

2 autres coefficients mécaniques sont très utilisés pour définir l’élasticité d’un solide

K module de compression volumique pratiquement constant, de l’ordre 109 Pa, quasi incompressible

µ module de cisaillement, très hétérogène, dépend beaucoup de la pathologie, entre 10 2 et 10 7 Pa

K >> m

K

m

E 3 µ

E = s

e e

s

Un module : le module d’Young E E

Palpation et Elasticité

µ

µ

-

- =

K

K m

4 3

Ondes mécaniques et élasticité

Les ondes de compression se propagent à

Les ondes de cisaillement à

m=sc

KcP ( 1500 m.s-1)

( 1-10 m.s-1)

Deux types d’ondes qui se propagent à des vitesses complètement

différentes !!

Les ultrasons se propagent uniquement sous la forme d’ondes de compression

Les ondes de cisaillement ne se propagent qu’aux basses fréquences < 500 Hz

Heart

Le vent

ultrasonore

D

F

Conventional Imaging Ultrafast Imaging

RAM

Parallel Processing Processing

128 to 512 transmits for a full image

(typically 10 to 50 ms)

1 single transmit for a full image

(typically 100 to 500 µs)

The key concept of ultrafast Imaging is plane wave transmission

M. Tanter, J. Bercoff, L. Sandrin, M. Fink. IEEE Transactions on Ultrasonics, 49 (10), pp 1363-1374, 2002

L. Sandrin, S. Catheline, M. Tanter, X. Hennequin, M. Fink, Ultrasonic Imaging 21(4), 259—272, 1999

First Ultrafast scanner built in 1998

(128 Channels)

The first Ultrafast Ultrasound Scanner at Institute Langevin

The great thing in 1998 :

• 128 fully independent electronic channels

• Analog Log/lin Amplifiers

• 9 Bits A/D converters • 256 MBytes Embedded memory

• up to 10000 frames/s Acquisition

• Acq of 100 ms Ultrafast imaging sequences

The bad thing in 1998 … :

• 40 minutes of processing

(Data transfer + beamforming process)

L. Sandrin, M. Tanter, S. Catheline, M. Fink. IEEE Transactions on Ultrasonics, 49 (4), pp 426-435, 2002

L. Sandrin, S. Catheline, M. Tanter, X. Hennequin, M. Fink, Ultrasonic Imaging 21(4), 259—272, 1999

M. Tanter, J. Bercoff, L. Sandrin, M. Fink. IEEE Transactions on Ultrasonics, 49 (10), pp 1363-1374, 2002

~ 100 µs

Step 1

Shear wave generation by remote palpation

Plane wave insonification at

some kHz

Texp=20 ms ~ 0.3 ms

Step 2

Ultrafast imaging

A kind of Human Body Sismology

J. Bercoff, M. Tanter, M. Fink.

IEEE Transactions on Ultrasonics, Ferroelectrics And Frequency Control., Vol 51(4), pp 396-409, April 2004.

Combining Ultrafast Imaging and Acoustic Radiation Force palpation

Ultrafast imaging of the shear wave propagation

10000 frames/second in a US Phantom

Frame to frame correlation

M. Fink, M. Tanter, “Multiwave Imaging and Superresolution”

Physics Today, 63(2), 28-33, Feb. 2010

J. Bercoff, M. Tanter, M. Fink.

IEEE Transactions on Ultrasonics, Ferroelectrics And Frequency Control ., Vol 51(4), pp 396-409, April 2004.

J. Bercoff, M. Tanter, M. Fink

Applied Physics Letters, 84(12), pp 2202-2204, March 2004

6 m/s

2 m/s

Transducer

A complete experiment in less time than a conventional US image

Conventional US time

0 s 1 s

Transducer

A 30 ms Experiment !!

Ultrafast US

The local Shear Wave speeed gives access to mechanical properties

m/s or kPa

• Freehand / does not change anything to the echographic exam

• Quantitative

• The palpation is Operator independent = reproducible

• Ultrafast / Insensitive to motion artefacts and boundary conditions.


True assessment of tissue stiffness

Hard lesion with a liquid center

Superresolution in Multiwave Imaging

Elasticity

contrast

Axial Res

(mm)

Lateral Res

(mm)

2 1 1.1

3 1.2 1.2

10 1.3 1.1

Lateral resolution

Axial resolution

kPa

No artefacts

Smaller variance

Elasticity Quantification

Comparison between Shear Wave Elastography and Static Elastography

E = s/e

True assessment of tissue stiffness

Hard lesion with a liquid center

Comparison between Shear Wave Elastography and Static Elastography

First Clinical Evaluation (breast) on 25 patients in 2007

c (ms-1)


SuperSonic Imagine

Startup funded by Mathias Fink, Mickael Tanter, Jacques Souquet and Claude Cohen-Bacrie end of 2005.

Aix en Provence

120 employees today

102 M€ fund Raising

More than 650 imaging systems sold worlwide since 2009

From a research platform to a clinical product

Aixplorer ©,2008

1996-2002 2004-2005

(CE and FDA marked) M. Fink, M. Tanter, “Multiwave Imaging and Superresolution”

Physics Today, 63(2), 28-33, Feb. 2010

A new paradigm for Ultrasound Imaging

1980 1990 1995 2010

Echographic System with Real-time and Quantitative elastography

First SSI experiments : 2000-2002

45 Minutes processing

SSI Prototype 2006

some seconds processing

October 2007

0.2 seconds processing

Moore’s Law fastened by Video Game Industry

Breast imaging examples

Conclusion :

Adding SW elastographic features to BI-RADS feature analysis improved specificity of breast US mass assessment without loss of sensitivity.

Results :

By using visual color stiffness to selectively upgrade category 3 and lack of stiffness to downgrade category 4a masses, specificity

improved from 61.1% (397 of 650) to 78.5% (510 of 650) (P < .001); AUC increased to 0.962 (P = .005).

BE1 study : September 2008 – September 2010

Clinical proof : SWE multicentric study on 939 breast masses

Specificity Sensitivity PPV3 of 4a

biopsies

Maximum

Value +26% No loss +122%

Color-Coding +28% No loss +155%

1,800 patients over 17 sites worldwide (USA, France,

Italy, Germany, UK)

Conducted under the leadership of Professor David

Cosgrove (Imperial College of Medicine, London)

Ultrafast Imaging gives key features

to Shear Wave Elastography :

Real time and quantitative imaging

Monitoring of therapeutic treatments

= 2.04

cm

≈ 1.80 cm = 1.64 cm ≈ 0.1 cm

(Collaboration Alexandra Athanasiou & Anne Tardivon, Curie Institute, Paris, France)

June/2011 July/2011 August/2011 October/2011

coil

Preliminary investigations for the monitoring

of breast chemotherapy treatments

Staging liver fibrosis using SWE

-

Bavu E., Gennisson J.-L., Couade, M. Bercoff j., Mallet V., Fink M. Vallet-Pichard A., Nalpas B., Tanter M., Pol S.

Non-invasive liver fibrosis staging using supersonic shear imaging: A clinical study on 113 HCV patients.,

Ultrasound in Medicine and Biology, 2011

Preliminary study on 113 HCV patients

Shear Wave Elastography for Liver fibrosis Staging

F 3 versus F 4

Clinical Study on 118 patients with

Hepatitis C

Fibroscan®

S.W.E.

Bavu E., Gennisson J.-L., Couade, M. Bercoff j., Mallet V., Fink M. Vallet-

Pichard A., Nalpas B., Tanter M., Pol S. Non-invasive liver fibrosis staging

using supersonic shear imaging: A clinical study on 113 HCV patients.,

under review, 2010.

2000 frames

per second

50

mm

36 mm

26 Years old healthy volunteer

In vivo Quantitative imaging of liver elasticity for Fibrosis Staging

Muscle

E = 120 +/- 14 kPa

Liver

E = 6.4 +/- 0.4 kPa

Muller M, Gennisson JL, Deffieux T, Tanter M. and Fink M.

Quantitative Viscoelasticity mapping of human liver using Supersonic Shear Imaging

ULTRASOUND IN MEDICINE AND BIOLOGY, 35 Issue: 2 Pages: 219-229 FEB 2009

Shear Wave Spectroscopy using Shear Wave Dispersion

2.7 ms

-0.05

0

0.05

-0.05

-0.04

-0.03

-0.02

-0.01

0

0.01

0.02

0.03

0.04

0.05

4.6 ms

-0.05

0

0.05

-0.05

-0.04

-0.03

-0.02

-0.01

0

0.01

0.02

0.03

0.04

0.05

6.5 ms

-0.05

0

0.05

-0.05

-0.04

-0.03

-0.02

-0.01

0

0.01

0.02

0.03

0.04

0.05

Z

X

0 100 200 300 400 500 600 7000

1

2

3

4

5

6

Frequency (Hz)

She

ar W

ave

Spe

ed

Shear Wave Phase Speed (m.s-1)

Versus Frequency

0 100 200 300 400 500 600 7000

1

2

3

4

5

6

Frequency (Hz)

She

ar W

ave

Spe

ed

0 100 200 300 400 500 600 7000

1

2

3

4

5

6

Frequency (Hz)

She

ar W

ave

Spe

ed

Low Visc. Gel In vivo Liver

High Visc. Gel

Deffieux T, Montaldo G, Tanter M, and Fink M.

IEEE TRANSACTIONS ON MEDICAL IMAGING, 28(3), 313-322 MAR 2009

Prostate – multiwave imaging

Suspicious lesion: much harder in SWE

Prostate : Biopsy guidance ?

Courtesy Jean Michel Correas, Necker

Carotid Plaque Stifness

Dynamics of Muscle Contraction

Gastrocnemius

Contraction

Soleus

Contraction

Shinohara S., Sabra K., Genisson J.-L., Fink M., Tanter M.

"Real-time visualization of muscle stiffness distribution with ultrasound SWI during muscle contractions », Muscle and Nerve, June 2010

Quantitative Monitoring of Uterin Contraction during Pregnancy

O. Ami, J-L. Gennisson, M. Tanter

Coll. CHU Antoine Beclere, Service Pr. Friedman

Real Time Elasticity Changes of in vivo Cardiac Muscle (Sheep Model)

M. Couade, M. Pernot, P. Matteo, B. Crozatier, R. Fischmeister and M. Tanter

Ultr. Med. Biol., Oct. 2010

5000 fps

Pernot M, Matteo P., Couade M., Crozatier B., Fischmeister R., Tanter M.

Journal of the American College of Cardiology , 2011

In vivo pig kidney during surgery

Seringe inserted the uretra

to control urinary pressure

Influence of Urinary Pressure : In Vivo pig experiments

0,00

20,00

40,00

60,00

80,00

100,00

120,00

140,00

160,00

180,00

10 20 30 40

E //

(kP

a)

Pressure (mmHg)

J.L Gennisson, N. Grenier, M. Tanter

Occlusion of the renal vein Occlusion of the renal artery

Influence of the Bloodstream : In Vivo pig experiments

• Arterial ischemia/ infarction

- reduced interstitial pressure

• Renal vein thrombosis

- major increase in interstitial pressure


3D Ultrasonic Wobbler Probe

JL Gennisson, N. Felix, Bercoff J. IEEE Proc. Ultrasonics, Beijing 2008

In vivo 3D Breast Shear Wave Imaging

MultiPlanar Display of BIRADS 5 lesion

3D Breast Imaging

Monitoring of RF ablation using Supersonic Shear Wave Imaging

• RF ablation in the liver

(sheep), bipolar needle

electrode 4W, 1min

The link between elasticity changes and the necrosis threshold

is independent of the temperature-time curve

Experimental results for different animals and temperature-time curves

N = 7 animals

Sapin-de Brosses E., Pernot M., Tanter M., ' The link between tissue elasticity and thermal dose in vivo', Physics in

Medicine and Biology, 2012

Shear Wave Elastography During RF Ablation on Patients

Courtesy Pr. E. Leen, Hammersmith Hospital, London

Small Animal

Shear Wave Elastography

Liver Elasticity on a control Rat during one Month

220210

030310

150310

Stable Young’s Modulus :

E ~ 10 kPa

N. Grenier, J.-L. Gennisson, B. Larrat, M. Derieppe, M. Tanter

20 MHz probe (256 elements)

E= 70 kPa

E= 21 kPa 20 MHz probe (256 elements)

SWE Imaging on a rat Liver fibrosis model during one Month

N. Grenier, J.-L. Gennisson, B. Larrat, M. Derieppe, M. Tanter

E= 35 kPa

Elastography in mice

Elastograph

y

Elasticity

[kPa]

B-mode (acq. ┴ and ═)

Volume

[mm3]

HES

staining

Chalkley

Count

Masson’s

Trichrome

Histo-Pathological studies

% Cellularity

and % necrosis % Vascularity % Fibrosis

Coll. F. Chamming’s, H. Latorre-Ossa,J.-L. Gennisson, M-A Le Frère-Belda , L. Fournier,

C.A. Cuenod, O. Clément, HEGP, PARCC, Paris

0

10

20

30

40

50

60

70

80

90

100

0 10 20 30 40 50 60 70 80 90

Me

dia

n t

um

or

ela

stic

ity

(kP

a)

Time (Days)

Tumour heterogeneity increases with size

Ø = 6.9 mm

E = 13.6 kPa

Ø = 7.8 mm

E = 21.1 kPa

Ø = 10.5 mm

E = 36.3 kPa

Ø = 14.1 mm

E = 56.9 kPa

Ø = 15.8 mm

E = 107.6 kPa

Elasticity increases with time

Coll. F. Chamming’s, H. Latorre-Ossa, J.-L. Gennisson, M-A Le Frère-Belda ,

L. Fournier, C.A. Cuenod, O. Clément, HEGP, PARCC, Paris

Elastic Tensor Imaging :

An ultrasonic analog of

DTI imaging using MRI ?

W.-N. Lee et al, Elastic tensor imaging with ultrasound: comparison with MR Diffusion Tensor Imaging in the myocardium

Physics in Medicine and Biology, 2012

Axial plane Radial plane

Quantitative Elasticity imaging of biceps muscle using SSI

Biceps Brachii

θ

: wave propagation direction

: fiber coordinates

x1

x2

x3

Deffieux, T.; Gennisson, J.-L.; Tanter, M. & Fink, M. (2008), Ieee Trans. On Ultr. Ferr.and Freq. Ctrl 55(10), 2177--2190.

Gennisson, J.-L.; Deffieux, T.; Mace, E.; Montaldo, G.; Fink, M. & Tanter, M. (2010), Ultrasound In Medicine and Biology 36(5), 789--801.

Shinohara, M.; Sabra, K.; Gennisson, J.-L.; Fink, M. & Tanter, M. (2010), Muscle & Nerve 42(3), 438--441.

-90 -45 0 45 902

2.5

3

3.5

4

4.5

5

v (

m/s

)

(degrees)

//v

v

1009080706050403020100

7o

-32o-24o-15o

-37o

-1o

-42o

14o 21

o 42

o 49o 57

o 67o 72

o

1009080706050403020100

-6o

-41o

-13o

-49o

-34o

1o 14o 21

o 33

o 45o 60

o 63o

Fiber Tracking using

Elastic Tensor Imaging

Based on Ultrafast Ultrasound

Fiber Tracking using

Diffusion Tensor Imaging

Using MRI

Fiber tracking in the myocardium : ex vivo experiment

W.-N. Lee et al, Elastic tensor imaging with ultrasound: comparison with MR Diffusion Tensor Imaging in the myocardium

Physics in Medicine and Biology, 2012

200 µm

3D

200 µm

3D

Elastic Tensor Imaging using Ultrasound

scan

u Polarization

k

Propagation

k

Propagation

u Polarization

Sagittal Coronal

E. Macé, G. Montaldo, I. Cohen, M. Fink, M.Tanter

u k y u

k x

sag

sagcor

c

cc -=

Fractional anisotropy

index

Corpus callosum 80%

- 80%

0%

80%

- 80%

0%

80%

- 80%

0%

In vivo maps of the brain « shear anisotropy » using Ultrasound

5 mm

1

4

9

16

25 kPa

1

16

25

1

4

9

16

25 kPa

1

16

25

E. Macé, G. Montaldo, I. Cohen, Miles R., Fink M. ,Tanter M.

IEEE Trans. Medical Imaging, in proofs, 2011

Elastic Tensor Imaging using Ultrasound

Conclusions

• ShearWave Elastography is a reliable quantitative modality

• Many applications under clinical evaluation

Breast, liver, kidney, thyroid, arteries, heart, brain, tendons …

• Shear Wave Elastography is also giving access to new information :

Elasticity anisotropy correlated with Diffusion Tensor Imaging in MRI

Systolic Elasticity correlated with contractility in cardiology

Elasticity changes correlated with the thermal dose and thermal changes

Elasticity changes correlated with pressure changes

Concluding Remarks

Shear Wave Elastography Already in clinics

(breast, liver, thyroid, muscle,…) Real Time and Quantitative Imaging

Tissue

Motion

fUS imaging of brain Activity Great new imaging tool in Neuroscience

Portable fUS imaging on chronic and awake animals Transfontanellar and peroperative fUS

Neurovascular

coupling

Ultrafast Doppler Imaging Both Imaging and quantification

Cardiovascular applications Tumor vascularization imaging

Blood

Motion

Ultrafast Ultrasonic Imaging Reaching the physical limits of Ultrasound

Ultrasound Technology Evolution

Multicore CPU

GPU

Real time imaging

Doppler imaging Compound Harmonic

Portable devices

Ultrafast Imaging

2010 2000 1990 1980 1970

DSP Low cost A/D

Innovation

Technology enabler

Broadband Transducers

Microprocessor Miniaturization

Ne pas imiter, Ne pas suivre

Innover très en amont, Prendre des risques scientifiques

De l’expérience de «coin de table» au succès clinique

Conclusion

Science is only human interactions

Many Thanks to

M. Couade, Miguel Bernal, Patricia Daenens, Mathias Fink, Thomas Deffieux, Benoit Larrat, Wojiceck Kwieciscki, Bastien Arnal, Heldmuth Latorre, Emmanuel Bossy, Olivier Couture, Yan Desailly,

Arnaud Tourin, Philippe Annic, Youliana Younan, Christelle Jacquet, Jean-Luc Gennisson, Mathieu Pernot,

Charlie Demene, Clement Papadacci, Thu-Mai Nguyen, Jean-Francois Aubry, Weining Lee, ...

2000 frames

per second

50

mm

36 mm

26 Years old healthy volunteer

In vivo Quantitative imaging of liver elasticity for Fibrosis Staging

Muscle

E = 120 +/- 14 kPa

Liver

E = 6.4 +/- 0.4 kPa

Muller M, Gennisson JL, Deffieux T, Tanter M. and Fink M.

Quantitative Viscoelasticity mapping of human liver using Supersonic Shear Imaging

ULTRASOUND IN MEDICINE AND BIOLOGY, 35 Issue: 2 Pages: 219-229 FEB 2009

Shear Wave Spectroscopy using Shear Wave Dispersion

2.7 ms

-0.05

0

0.05

-0.05

-0.04

-0.03

-0.02

-0.01

0

0.01

0.02

0.03

0.04

0.05

4.6 ms

-0.05

0

0.05

-0.05

-0.04

-0.03

-0.02

-0.01

0

0.01

0.02

0.03

0.04

0.05

6.5 ms

-0.05

0

0.05

-0.05

-0.04

-0.03

-0.02

-0.01

0

0.01

0.02

0.03

0.04

0.05

Z

X

0 100 200 300 400 500 600 7000

1

2

3

4

5

6

Frequency (Hz)

She

ar W

ave

Spe

ed

Shear Wave Phase Speed (m.s-1)

Versus Frequency

0 100 200 300 400 500 600 7000

1

2

3

4

5

6

Frequency (Hz)

She

ar W

ave

Spe

ed

0 100 200 300 400 500 600 7000

1

2

3

4

5

6

Frequency (Hz)

She

ar W

ave

Spe

ed

Low Visc. Gel In vivo Liver

High Visc. Gel



Shear Wave Spectroscopy : a Broadband approach for Elasticity

Shear Wave Bandwidth

Static elastography

Dynamic elastography

SSI

50 150 250 350 450 550 0 650 Hz



Fibroscan

1

0

2

0

3

0

5

1

0 1

5 2

0 2

5 3

0 3

5 4

0 4

5

(a

)

Agar gel

Viscous gel

Frequency in Hertz Lateral position in mm

100 200 300 400 500 600 0

2

4

6

8 b

Agar gel

Viscous inclusionl

Agar gel

Viscous inclusion P

hase v

elo

city in

m/s

Dep

th in

mm

A new paradigm for Ultrasound Imaging

1980 1990 1995 2010

Safety and Efficiency issues in Elastography

A Key difference between SSI and ARFI is ULTRAFAST IMAGING

SSI ARFI ARFI- SWS

« Flash » Imaging

+

Limited nb of « push »

Imaging only at push location

+

High number of pushes

Synthetic building

of «flash» sequence

+ repeated local «Push»

Real Time

Quantitative

No motion artefacts

Qualitative

Quantitative

Not Real Time

Potential motion Artefacts

Ultrafast ultrasound gives access to real time SWE

A limited number of « push »

imaged by Ultrafast plane wave Imaging

It optimally satisfies the ALARA principle

« As low as Reasonably Achievable »

The arterial stiffness varies with

blood pressure (diastole/systole)

- Carotid • 13 successive 20 ms experiment every 120 ms = 13 elasticity per

cardiac cycle

The Urinary Tract Obstruction : In Vivo pig experiments

Outer Cortex Medulla Inner Cortex

E

(k

Pa

) E

// (k

Pa

)

In vivo Stiffness Estimates averaged on N=6 kidneys

2,3 kPa/mmHg 3,2 kPa/mmHg 1,3 kPa/mmHg

1,3 kPa/mmHg 1,4 kPa/mmHg 1,4 kPa/mmHg


Ultrafast imaging of the pulse wave

along the carotid • Frame rate : 3.000 frames/second

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

time after R-wave (s)E

CG

late

ral p

ositio

n a

lon

g th

e a

rte

ria

l se

gm

en

t (m

m)

Wall motion (mm/s)

5

10

15

20

25-6

-4

-2

0

2

4

6

8

10

12

image n°

ligne n°

406080100120140

50

100

150

200

250

300

350PWV ~ 5 m/s (carotid) 0.08 0.1 0.12 0.14 0.16 0.18 0.2

0

1

2

3

4

5

6

time (s)

depth

(m

m)

INC

REF

Shear Wave Elastography Using Ultrasound

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