A Phantom Study to Cross-validate Multimodality Shear Wave Elastography Techniques

Hua Xie1, Vijay Shamdasani2, Heng Zhao3, Pengfei Song3, Shiwei Zhou1, Jean-Luc Robert1, James Greenleaf3 and Shigao Chen3

1Philips Research North America, 345 Scarborough Road, Briarcliff Manor, NY 10510 2Philips Healthcare, 22100 Bothell Everett Highway, Bothell, WA 98021

3Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905

Abstract—As various quantitative shear wave elastography techniques are being implemented commercially and used clinically, it is important to understand what elastic modulus is measured by those techniques and to assess technical factors influencing measurement accuracy. Cross-validated in this study were four shear wave elastography techniques including ultrasound elastography point quantification (ElastPQ), magnetic resonance elastography (MRE), 1-D transient elastography (TE), and a Verasonics ultrasound system based elastography feature. ElastPQ is an acoustic radiation force (ARF) based technique implemented on an ultrasound system iU22 for a curvilinear probe C5-1. MRE measurements were made at a shear wave frequency of 100 Hz. The 1-D TE system uses an external mechanical vibrator at 100 Hz to generate shear waves and a 7.5 MHz single element transducer to track shear wave propagation. The Verasonics ultrasound system with a linear probe L7-4 uses a plane wave transmit imaging mode to measure propagation speed of shear waves induced by ARF. Six custom-made elasticity phantoms were measured selectively and were assumed purely elastic by the four techniques. The results show good agreement between two ARF based techniques: ElastPQ and Verasonics based feature. When comparing ElastPQ to 1-D TE, the discrepancy for the hardest phantom could be explained by the diffraction artifact in the latter system. Further improvements on the 1D-TE reconstruction algorithm are ongoing. The overestimation by ElastPQ and Verasonics against MRE could be attributed to frequency dispersion due to slight viscosity in phantoms. MRE measures shear wave speed at a single frequency 100 Hz, whereas the other two estimate an effective group velocity over a larger bandwidth for a broadband shear wave signal. 1-D TE and MRE measurements are in closest agreement due to similar shear wave frequencies. More validation of these techniques is required on real patients in clinical settings. Keywords – ultrasound shear wave elastography, magnetic resonance elastography, shear modulus, shear viscosity, shear wave dispersion

I. INTRODUCTION

Over the last decade multimodality shear wave elastography

techniques have been developed and commercialized to provide quantitative tissue stiffness as additional clinical information to improve diagnostic performance. The most investigated clinical application of shear wave elastography so far is non-invasive liver fibrosis staging [1-10]. Ultrasound and magnetic resonance imaging are two major imaging modalities to host shear wave elastography. Ultrasound based shear wave elastography techniques can be further

distinguished between two ways of generating shear waves, by acoustic radiation force (ARF) [11-14] or external mechanical vibration [15]. They can also be divided into different categories depending on the region of integration for stiffness measurement: point, one – dimensional (1-D), two-dimensional (2-D), or three-dimensional (3-D) stiffness mapping. Magnetic resonance elastography (MRE) predominantly involves the use of external mechanical vibration to induce shear waves and reconstruct stiffness in 2-D [3-6, 9]. As various shear wave elastography techniques are being implemented commercially and used clinically, it is important to understand what elastic modulus is measured by those techniques and to assess technical factors that influence measurement accuracy and precision. Investigated in this study were four shear wave elastography techniques including ultrasound elastography point quantification (ElastPQ), MRE, 1-D transient elastography (TE), and a shear wave elastography system based on Verasonics plane wave transmit imaging mode. Cross-validation was done on tissue mimicking elasticity phantoms.

II. METHODS

A. Four Shear Wave Elastography Techniques

ElastPQ was developed on a commercial ultrasound scanner iU22 (Philips Healthcare, Andover, MA, USA) for a curvilinear transducer C5-1. The scanner software was modified to implement a dedicated shear wave pulse sequence and its associated processing module for reconstruction. The pushing pulse duration is a few hundred micro-seconds. Tracking pulse positions are evenly spaced to produce about 1 mm lateral beam spacing at depth 40 mm. Motion at each tracking position is monitored at pulse repetition of frequency (PRF) of 1.6 kHz. Acoustic output was controlled to ensure that acoustic and thermal output MI (mechanical index) and Ispta comply with FDA safety regulation. An effective group velocity is estimated using a time-of-flight algorithm at several lateral tracking locations and further converted to a stiffness value which is reported in real-time on the scanner screen.

A subset of phantoms were calibrated by MRE in a

previous study using a 3.0T whole-body magnetic resonance imaging system (GE Medical System, Milwaukee, WI, USA) at a shear wave frequency of 100 Hz [16]. A multislice spin echo based echo planar MRE sequence with four phase offsets was used to collect 3-D shear wave data with three orthogonal motion sensitizing directions. After curl filtering to remove the undesired bulk motion, 3-D local frequency estimation

1858978-1-4673-4562-0/12/$31.00 ©2012 IEEE 2012 IEEE International Ultrasonics Symposium Proceedings

10.1109/ULTSYM.2012.0466

inversion was performed to calculate shear wave speed [17]. Shear wave speeds measured at three orthogonal directions were averaged at each voxel to give a single estimate of speed at each spatial location.

In 1-D TE experiments, a single-element, weakly focused

transducer (ECHO Ultrasound, Lewistown, PA, USA) was attached to a mechanical vibrator (V203, Ling Dynamic Systems Limited, Hertfordshire, UK), so that the transducer can vibrate on the phantom surface during pulse-echo motion detection. The transducer operates at 7.5 MHz and has 6.4 mm diameter. Its nominal focal range is 1-7 cm. A single-cycle 100 Hz sinusoidal pulse was used to drive the vibrator for shear wave generation through the transducer into the phantom under test. Radio-frequency (RF) signals were bandpass filtered by 50% bandwidth and digitized at 100 MHz sampling frequency. Relative displacement caused by the transducer motion was removed from shear wave displacement demodulated from RF ultrasound echo signals [15]. In these experiments, 6000 samples were collected in fast time and 1000 ensembles were acquired in slow time with PRF 4.5 kHz lasting about 220 ms.

A shear wave imaging system was implemented on a

Verasonics ultrasound system (Verasonics Inc., Redmond, WA, USA) using its plane wave transmit imaging mode. For this study, a linear transducer L7-4 (Philips Healthcare, Andover, MA, USA) was used to induce a push pulse with duration of 400 μs and detect shear wave propagation at PRF of 4 kHz. MI exceeded the FDA safety limit in this study on phantoms. Phase velocity is estimated by using a shear wave dispersion based technique [14] and averaged in the frequency range of 100 Hz to 800 Hz.

B. Phantom Experiments

Six custom-made homogeneous elasticity phantoms (CIRS, Inc., Norfolk, VA, USA) were used in the study. Phantoms #1 and #2 are shown in Fig. 1 being measured by C5-1 ElastPQ; whereas phantoms #3-#6 are four individual segments contained in the same acrylic housing, as being measured by the 1D-TE setup in Fig. 2. The material of all the phantoms is water-based solid elastic polymer called Zerdine®, which has tissue-mimicking acoustic parameters of speed of sound 1540±10 m/s and attenuation 0.5±0.05 dB/cm/MHz. Zerdine® does not exhibit strong viscous property, therefore it is assumed purely elastic during stiffness reconstruction by the four elastography techniques. Once the shear wave speed C is estimated, Young’s modulus E is calculated as:

23 CE ρ=

where ρ denotes mass density. Density of 1000 kg/m3 is assumed for all tissue mimicking phantoms in this study. Multiple measurements at different locations were made to gain strong statistical power for each phantom. For ElastPQ, five imaging planes were selected and five individual

measurements were made in each plane from depth 25-75 mm. For 1D-TE, shear wave propagation from 7 mm to 40 mm in depth away from the transducer surface was used to calculate shear wave speed. Five trials were performed at five different locations across the phantom surface for each phantom. For the Verasonics based system, shear wave tracking and reconstruction were done in a region that centers axially at the push focus 20 mm with depth of field ± 3 mm and spans laterally from 3 to 18 mm. Three measurements were carried out at 3 random locations in each phantom. MRE measurement was not performed on phantoms #3-#6. For phantoms #1 and #2, their MRE and 1D-TE measurements were derived from a previous study [16].

Fig. 1. Phantoms #1 and #2 being measured by C5-1 ElastPQ.

Fig. 2. Phantoms #3- #6 being measured by the 1D-TE system.

III. RESULTS

A. 15 kPa Phantom

Fig. 3 presents ElastPQ measurements on phantom #4 (manufacturer specification: Young’s modulus 15 kPa) at several positions. In Fig. 3(a), the measurement box is placed at depth 4 cm and the underlying Young’s modulus is reported as 12.2 kPa. In Fig. 3(b) where another imaging plane is selected, the Young’s modulus is 13.3 kPa at depth 7 cm. The lower left corner of Fig. 3(c) summarizes ElastPQ

1859 2012 IEEE International Ultrasonics Symposium Proceedings

measurement statistics (mean and standard deviation) in the first three imaging planes. For 1D-TE, Fig. 4 plots the shear wave displacement along the vibration axis as function of slow time with a display dynamic range [-170, 150] μm based on the Jet color mapping. The black line (schematic) indicates the tracked time-of-arrivals at each depth. Data fitting results in shear wave speed 1.94 m/s and Young’s modulus 11.29 kPa. Fig. 5 plots the shear wave phase velocity estimated in the frequency range of 100-800 Hz for the 15kPa phantom by Verasonics based shear wave imaging feature. Average velocity is 1.98 m/s leading to Young’s modulus 11.98 kPa.

(a) (b)

(c)

Fig. 3. ElastPQ measurements at different locations in phantom #4 (Young’s modulus=15kPa).

Fig. 4. Shear wave displacement along the depth as function of slow-

time by the 1D-TE technique in phantom #4 (Young’s modulus=15kPa).

Fig. 5. Shear wave phase velocity as function of frequency by Verasonics based shear wave system for phantom #4 (Young’s

modulus=15kPa).

B. Measurement Summary

Quantitative Young’s moduli estimated by the four different shear wave elastography techniques are listed in Table I for the six phantoms. Specifications by the manufacturer are also listed for reference. Shear wave signal to noise ratio (SNR) is a major factor to affect measurement precision. Among three ultrasound based techniques, peak shear wave amplitude reaches about 150 μm in 1D-TE for 15 kPa phantoms. In contrast, it is about 10 μm in ElastPQ bounded by FDA acoustic and thermal regulation; and about 30 μm in the Verasonics setup. Because of the significant variation in shear wave SNR among these techniques, standard deviation in Young’s modulus is not provided for comparison as a measure of robustness in this paper.

Table I. Young’s modulus measurements of six phantoms

(unit: kPa). Phantom Specs ElastPQ Verasonics

system 1-D TE

MRE

1 5.8±2.0 7.50 6.93 6.57 6.48 2 9.7±3.0 11.26 11.17 10.72 9.72 3 5.0±1.6 5.17 5.31 4.61 × 4 15.0±3.0 12.23 11.76 11.65 × 5 25.0±5.0 19.41 19.20 23.13 × 6 60.0±8.0 50.42 55.47 191.18 ×

IV. DISCUSSION AND CONCLUSIONS

From the system point of view, there are two key factors that largely affect the accuracy and precision of shear wave elastography measurement. The first centers on the system characteristics of shear wave excitation and tracking, to name a few: shear wave spectrum at the push focus, measurement location with respect to the shear wave origin; shear wave SNR, shear wave tracking frequency, etc. Second, the measurement accuracy also depends on the reconstruction

1860 2012 IEEE International Ultrasonics Symposium Proceedings

algorithm. Several algorithms have been proposed to estimate shear modulus ignoring tissue viscosity including time-to-peak based [7] and cross-correlation based [18] time-of-flight approaches, and wave equation approach [13]. There also exist a few algorithms that take viscosity into account when reconstructing mechanical properties [14, 19]. Critical review and systematic evaluation of those factors are important to drive adoption of various shear wave elastography products in clinical applications [20].

The results in Table I show good agreement between two ARF based techniques: ElastPQ and Verasonics based shear wave elastography feature. When comparing ElastPQ to 1-D TE, the discrepancy for the hardest phantom (60 kPa) could be explained by the diffraction artifact in the latter system [21]. Further improvements on the 1-D TE algorithm are ongoing. The overestimation by ElastPQ and Verasonics against MRE could be attributed to frequency dispersion due to slight viscosity in phantoms. MRE measures shear wave speed at a single frequency 100 Hz, whereas the other two estimate an effective group velocity over a larger bandwidth for a broadband shear wave signal. 1-D TE and MRE measurements are in closest agreement due to similar shear wave frequencies.

The present study has a couple of limitations that should be addressed. First, measurement locations are not exactly the same for all techniques due to difficulty in accessing all the system equipment simultaneously at the same site. Nevertheless, multiple measurements at different locations hopefully average out stiffness spatial variation. Second, the mechanical properties of the phantoms used in this study may not mimic human soft tissues. Biological tissues show both elastic and viscous behavior; they exhibit extremely complex mechanical behaviors. A finite element modeling study has indicated that reconstruction algorithms can behave differently when viscosity is present [22]. More validation of these techniques is required on real patients in clinical settings.

REFERENCES

[1] L. Sandrin, B. Fourquet, J. M. Hasquenoph, S. Yon, C. Fournier, F. Mal, C. Christidis, M. Ziol, B. Poulet, F. Kazemi, M. Beaugrand, and R. Palau, "Transient elastography: a new noninvasive method for assessment of hepatic fibrosis," Ultrasound Med Biol, vol. 29, pp. 1705-13, Dec 2003.

[2] L. Castera, J. Vergniol, J. Foucher, B. Le Bail, E. Chanteloup, M. Haaser, M. Darriet, P. Couzigou, and V. De Ledinghen, "Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C," Gastroenterology, vol. 128, pp. 343-50, Feb 2005.

[3] O. Rouvière, M. Yin, M. Alex Dresner, P. J. Rossman, L. J. Burgart, J. L. Fidler, and R. L. Ehman, " MR Elastography of the Liver: Preliminary Results," Radiology, 240, pp. 440-448, August 2006.

[4] M. Yin, J. A. Talwalkar, K. J. Glaser, A. Manduca, R. C. Grimm, P. J. Rossman, J. L. Fidler, and R. L. Ehman, "Assessment of hepatic fibrosis with magnetic resonance elastography," Clinical Gastroenterology and Hepatology, vol. 5, pp. 1207-1213, Oct 2007.

[5] L. Huwart, C. Sempoux, N. Salameh, J. Jamart, L. Annet, R. Sinkus, F. Peeters, L. C. ter Beek, Y. Horsmans, and B. E. Van Beers, "Liver fibrosis: Noninvasive assessment with MR elastography versus aspartate

aminotransferase-to-platelet ratio index," Radiology, vol. 245, pp. 458-466, Nov 2007.

[6] L. Huwart, C. Sempoux, E. Vicaut, N. Salameh, L. Annet, E. Danse, F. Peeters, L. C. ter Beek, J. Rahier, R. Sinkus, Y. Horsmans, and B. E. Van Beers, "Magnetic resonance elastography for the noninvasive staging of liver fibrosis," Gastroenterology, vol. 135, pp. 32-40, Jul 2008.

[7] M. L. Palmeri, M. H. Wang, J. J. Dahl, K. D. Frinkley, and K. R. Nightingale, “Quantifying hepatic shear modulus in vivo using acoustic radiation force,” Ultrasound in Med. & Biol., vol. 34, no. 4, pp. 546-558, 2008.

[8] M. Muller, J. L. Gennisson, T. Deffieux, M. Tanter, and M. Fink, "Quantitative viscoelasticity mapping of human liver using supersonic shear imaging: preliminary in vivo feasibility study," Ultrasound in medicine & biology, vol. 35, pp. 219-29, Feb 2009.

[9] P. Asbach, D. Klatt, B. Schlosser, M. Biermer, M. Muche, A. Rieger, C. L. kemper, R. Somasundaram, T. Berg, B. Hamm, J. Braun, and I. Sack, “Viscoelasticity-based Staging of Hepatic Fibrosis with Multifrequency MR Elastography," Radiology, 257, pp. 440-448, August 2010.

[10] E. Bavu, J. L. Gennisson, M. Couade, J. Bercoff, V. Mallet, M. Fink, A. Badel, A. Vallet-Pichard, B. Nalpas, M. Tanter, and S. Pol, "Noninvasive In Vivo Liver Fibrosis Evaluation Using Supersonic Shear Imaging: A Clinical Study on 113 Hepatitis C Virus Patients," Ultrasound in Medicine and Biology, vol. 37, pp. 1361-73, 2011.

[11] A. P. Sarvazyan, O. V. Rudenko, S. D. Swanson, J. B. Fowlkes, and S. Y. Emelianov, “Shear wave elasticity imaging—A new ultrasonic technology of medical diagnostic,” Ultrasound Med. Biol., vol. 20, pp. 1419–1436, 1998.

[12] K. Nightingale, M. S. Soo, R. Nightingale, and G. Trahey, “Acoustic radiation force impulse imaging: in vivo demonstration of clinical feasibility,” Ultrasound Med. Biol., vol. 28, pp. 227–235, Feb. 2002.

[13] J. Bercoff, M, Tanter and M. Fink, “Supersonic Shear Imaging: a New Technique for Soft Tissue Elasticity Mapping,” IEEE Trans. Ultrason. Ferroelectr. Freq. Co ntrol, Vol. 51, No. 4, 2004.

[14] S. Chen, M. Fatemi, and J. F. Greenleaf, "Quantifying elasticity and viscosity from measurement of shear wave speed dispersion," JASA, vol. 115, no. 6, pp. 2781-2785, 2004.

[15] L. Sandrin, M. Tanter, JL. Gennisson, S. Catheline, M. Fink, “Shear elasticity probe for soft tissues with 1D transient elastography.” IEEE Trans Ultrason Ferroelec Freq Control, vol. 49, pp. 436–446, 2002.

[16] H. Zhao, P. Song and et al. “Bias observed in time-of-flight shear wave speed measurements using radiation force of a focused ultrasound beam”, Ultrasound in Med. & Biol., vol. 37, no. 11, pp.1884-1892, 2011

[17] A. Manduca, T.E. Oliphant, M.A. Dresner, J.L. Mahowald, S.A. Kruse, E. Amromin, J.P. Felmlee, J.F. Greenleaf, and RL. Ehman, “Magnetic resonance elastography: Noninvasive mapping of tissue elasticity,” Med Image Anal., vol. 5, no. 4, pp. 237–254, 2001.

[18] M. Tanter, J. Bercoff, A. Athanasiou, T. Deffieux, J. Gennisson, G. Montaldo, M. Muller, A. Tardivon,and M. Fink “Quantitative assessment of breast lesion viscoelasticity: initial clinical results using supersonic shear imaging”, Ultrasound Med Biol, vol. 34, pp. 1373-1386, April 2008.

[19] T. Deffieux, G. Montaldo, M. Tanter, and M. Fink, "Shear wave spectroscopy for in vivo quantification of human soft tissues visco-elasticity," IEEE Transactions on Medical Imaging, vol. 34, pp. 313-322, 2009.

[20] http://qibawiki.rsna.org/index.php?title=Ultrasound_SWS_tech_ctte

[21] S. Catheline, F. Wu, and M. Fink, “A solution to diffraction biases in sonoelasticity: The acoustic impulse technique”, J. Acoust. Soc. Am. vol. 105, no. 5, pp. 2941 – 2950, May 1999.

[22] S. Zhou, J. Robert, J. Fraser, Y. Shi, H. Xie and V. Shamdasani, “Finite Element Modeling for Shear Wave Elastography,” IEEE IUS 2011, pp. 2400-2403.

1861 2012 IEEE International Ultrasonics Symposium Proceedings