Βασικές αρχές της Ελαστογραφίας. Εξέλιξη της τεχνολογίας στην Ελαστογραφία ShearWave.

1. Βασικές αρχές της Ελαστογραφίας.Εξέλιξη της τεχνολογίαςστην Ελαστογραφία ShearWave. Αθήνα, 23 Ιανουαρίου 2010 Θανάσης Λούπας, PhDPrincipal Scientist, SUPERSONIC IMAGINE SA, France

2. Elastography Background • In ancient Egypt, a link was established between • a hard mass within the human body & pathology. • In Hippocratic medicine, palpation was • an essential part of a physical examination. • In the 21st century, «remote palpation» by means • of elastographic imaging is becoming a reality.

3. s e Stress Strain E = Young’s Modulus • Palpation  Qualitative estimation of • tissue elasticity • Young’s Modulus E quantifies elasticity in • units of kiloPascals, as the ratio of • the Stress S(compression) applied to a body • divided by • the Strain e (relative deformation) it produces. STRESS STRAIN kPa ELASTICITY High Strain  Easy to deform  Low Elasticity Low Strain  Hard to deform  High Elasticity

4. Soft Tissue Elasticity • Different types of soft tissue have similar density • but exhibit significant variation in elasticity. • Elasticity variations can help detect / characterize focal (e.g. malignant masses) and diffuse (e.g. fibrosis) pathologies. “Remote” Palpation “Virtual” Biopsy

5. Elasticity Imaging R&D • Many R& D techniques have emerged since the 1990s, based on the Ultrasound and Magnetic Resonance imagingmodalities. • Sonoelasticity: KJ Parker et al, 1990 • Ultrasound Strain Elastography: J Ophir et al, 1991 • MR Elastography: R Sinkus et al, 2000 • Shear Wave Elastography: J Bercoff et al, 2004 • All techniques are based on the same principle: • Generate a stress, and then use an imaging technique to map the tissue response to this stress in every point of the image. • but differ substantially in terms of their performance characteristics: • Qualitative / quantitative nature, absolute / relative quantification. • Accuracy / precision / reproducibility, … • Spatial / temporal resolution, sensitivity / penetration, … COMMERCIALYAVAILABLE

6. StrainElastography • Initially introduced by Hitachi, and later on Siemens, • in the early 2000s. • More manufacturers have followed in the last year(s). • The basic principle used is the one proposed • by Ophir’s group in the early 1990s: • Tissue compression (Stress) is induced • manually by the user. • Multiple images are recorded using • conventional imaging at standard frame rates. • The relative deformation (Strain) is estimated • using Tissue Doppler techniques. • The derived strains are displayed as • a qualitativeelasticity image.

7. StrainElastography Processing Pre-compression RF line STRAIN ESTIMATION Post-compression RF lines Pre-compression RF lines dT T Local Cross Correlation Analysis Strain = dT / T • Strain represents relative deformation, • and is expressed in qualitative units • (soft / hard) • Soft objects  High Strain • Hard objects  Low Strain Post-compression RF line

8. StrainElastography Summary • Stress Source  Manual Compression (user-dependent). • Stress Frequency  Static (user-induced vibration < 2 Hz). • Result Type  Qualitative image (E=Stress/Strain, but Stress is unknown). • Relative quantification (Background-to-Lesion-Ratio). • Straightforward implementation on • current scanners (standard acquisition architecture, • plus Tissue-Doppler-like processing). • Stress penetration / uniformity issues. • User-applied compression is attenuated by soft objects & depth, • and cannot penetrate hard-shelled lesions. • User-dependence. • The extent of tissue compression affects the elasticity image.

9. Stress Strain 3 r cS2 E = E = From Strain to Shear Wave Elastography kPa • The Elasticity formula is of little practical relevance because • it is extremely difficult to estimate the Stress applied at each point of the image. • In the late 1990s and early 2000s, an novel approach was pursued in order to achieve quantitative Elastography, by relying on an alternative Elasticity formula: • where • ris the tissue density (~ 1 kg/L) • cS is the speed of a Shear Wave propagating through the medium. kPa • Sarvazyan AP: Method and device for shear wave elasticity imaging. US Patent 5,606,971 1997. • Sarvazyan et al : Shear wave elasticity imaging -- A new ultrasonic technology of medical diagnostics. Ultrasound Med Biol 1998; 24:1419-35. • L Sandrin, S Catheline, M Tanter, C Vinçonneau, M Fink : 2D • Transient Elastography Acoust. Imag., Vol. 25, pp 485-492, 2000. • M Tanter, J Bercoff, L Sandrin, M Fink : Ultrafast compound • imaging for 2D motion vector estimation : Application to transient • elastography IEEE Trans UFFC, Vol. 49, pp 1363-1374, 2002.

10. Shear Waves in Medical Ultrasound • Two types of acoustic waves propagating in the human body: • Longitudinal (or bulk) waves • Propagation direction parallel to tissue motion. • High frequency (typically, > 1 MHz), and high propagation speed (~ 1500 m/s). • Shear (or transverse) waves • Propagation direction perpendicular to tissue motion. • Low frequency (typically, < 1 kHz), and low propagation speed (~ 5 – 10 m/s). Propagation Direction SHEAR WAVE Tissue Motion Propagation Direction Tissue Motion LONGITUDINAL WAVE Until now, Medical Ultrasound imaging has been based entirely on Longitudinal waves.

11. Heart PW Doppler Mechanical force Shear Wave Sources FocusedUltrasound Natural External • SuperSonic Imagine has developed a novel method called SonicTouch, • which is based on focused ultrasound, and can remotely generate • Shear Wave-fronts providing uniform coverage of a 2D area interest.

12. Shear Wave Generation SonicTouch • Focusedultrasound istransmited • at multiple points along • a line of interest. • An individual Shear Wave is • generated andstarts propagating • around each focal point. • The superposition of theindividual • Shear wavescreates a Shear • Wave-frontsimilar tothe • Super Sonic Mach Cone. • The SonicTouch Shear Wave generation process • is completely automated and user-independent.

13. Shear Wave Detection • The typical Shear Wave speed cS in soft tissue is ~ 5 m/s. • This means that the Shear Wave needs 0.2 ms to travel 1 mm. • Thereforein order to have a spatial resolution of 1 mm, • we must image the Shear Wave once every 0.2 ms, i.e. 5000 times per second. 1 mm in 0.2 milliseconds 5000 images per second needed! Almost 100 times more than the frame rates that current ultrasound scanners can offer (best case, 50-100 frames/second). Shear Wave Speed = 5 m/s • SuperSonic Imagine has developed a unique system architecture in order • to achieve the Ultrafast Imaging performance needed • to image the Shear Wave propagation across a 2D area of interest.

14. Shear Wave Detection Ultrafast Imaging • Plane-wave transmissions • are performed, each of them • covering the whole image area. • For each transmission, the data received • from all points of the imageare • processed using advanced reconstruction • techniques to form the full image at once. • One frame is produced for every transmission, • resulting in frame rates of up to20000 Hz. • More than one transmit events may be combined to • improve image quality by trading-off some frame rate.

15. Shear Wave Imaging Steps Step 1Shear Wave generation Step 2Shear Wave Detection Step 3Shear Wave propagation image formation Ultrafast Imaging SonicTouch Longitudinal Waves Shear Waves Uniform-elasticity phantom Total duration: 20 ms ! ~ 100 µs 0.33 ms 60 frames at a frame rate of 3000 Hz

16. 3rcS2 E= Shear Wave Elastography Breast Elastography phantom with uniform background + hard lesion Shear Wave Speed cS Estimation Shear Wave Imaging sequence @ 3000Hz J. Bercoff, M. Tanter, M. Fink: Supersonic shear imaging: A new technique for soft tissue elasticity mapping IEEE Trans Ultrason Ferroelectr Freq Control, pp 396-409, 2004 Key Reference 

17. Shear Wave Elastography Real-time operation

18. Shear Wave Elastography • TRULY-QUANTITATIVE NATURE • Absolute elasticity quantification • High accuracy / precision. Calibrated Elastometer values Shear-Wave Elastography measurements Mean =10.5 kPa StdDev =0.8 kPa (7%) Mean =5.1 kPaStdDev =0.15 kPa (3%) 5 -7 Kpa 10-13 Kpa Accuracy / precision testing using calibrated elasticity phantoms

19. Shear Wave Elastography • TRULY-QUANTITATIVE NATURE • Absolute elasticity quantification • High accuracy / precision • Extensive validations using calibrated tissue-mimicking phantoms.

20. Shear Wave Elastography Axial resolution • High spatial resolution • Typically, ~ 1 mm axially & laterally • for the SL 15-4 linear transducer. Lateral resolution Custom-made two-layer phantoms with multiple elasticity ratios

21. Shear Wave Elastography Phantom with liquid center inside hard lesion • Highly-localized estimation • of tissue elasticity • Especially, inside hard lesions Shear Wave Elastography can “see” inside the hard lesion, because the shear waves can propagate through the hard shell. Strain Elastography interprets the whole lesion as hard, because the applied manual compression cannot penetrate the hard shell.

22. Strain vs. Shear Wave Elastography Strain Elastography tends to produce a binary classification, where the whole lesion is either hard or soft. Shear Wave Elastography provides richer & more complex information with many cases of hard borders plus soft centers. The differences between Strain and Shear Wave Elastography are not surprising, given the very different principles on which they are based.

23. Shear Wave Elastography Summary • Stress Source  Automatically-generated Shear Waves (user-independent). • Stress Frequency  Broadband (typical Shear Waves from 50 to 500 Hz). • Result Type  Fully quantifiable images (kPascal , plus E ratio). • Unique to SuperSonic Imagine, due to need for advanced capabilities (SonicTouch, Ultrafast Imaging), and intellectual property protection. • Rich / complex mapping of hard lesions, with heterogeneous elasticity • in the lesion periphery and/or center.

24. Shear Wave Elastography Applications • SWE is fully-integrated feature of the Aixplorer • premium Ultrasound scanner. • Organs currently targeted by SWE include: • Breast, Thyroid, and Liver. • Work-in-progress encompasses: • Prostate, Musculoskeletal, and 3D Breast applications. • R&D efforts focus on Cardiovascular and Ophthalmology applications.

25. Multi-center Breast ElastographyTrial • Assessment Of The Clinical Benefits Of SuperSonic • Shear Wave Elastography In The Ultrasonic Evaluation • Of Breast Lesions • Dates: Q2 2008 to Q22010 • Sites: 11 centers in Europe & 6 centers in USA • Primary aim: Assess the benefit of Shear Wave • Elastography for the characterization of breast lesions. • Secondary aim: Assess the benefit of Shear Wave • Elastography for the visualisation of breast lesions. • Clinical trial and data analysis currently under way. • Preliminary results very promising. • Improved sensitivity and specificity of breast ultrasound • BIRADS diagnosis with SWE + ECHO versus ECHO only.

26. Clinical Evaluation of SWE for Liver Fibrosis Staging SWE: Fibroscan: Bavu et al, “Non-invasive in-vivo Liver Fibrosis staging using Supersonic Shear Imaging: a Clinical Study”, Gastroenterology, 2010 (in press).

27. CONCLUDING REMARKS • Elastography is a perfect adjunct for Ultrasound Imaging. • Elastography has recently emerged as a new imaging mode in ultrasound systems, • currently targeting Breast, Thyroid, Liver, and Prostate Imaging applications. • Multiple-vendor systems, but only two versions of Elastography Imaging: • Strain Elastography and Shear Wave Elastography. • Strain Elastography has been adopted by many manufacturers, due to its • technological maturity and ease of implementation. • Shear Wave Elastography is based on innovative technologies, developed • in order to expand the capabilities of existing solutions • (full quantification, highly-localized estimation, user-independence). • There is still a long way to go with regards to equipment improvements • and clinical understanding, but the future of Elastography looks bright.

28. Thank you !