Implementation of Shear Wave Elastography on Pediatric Cardiac Transducers with Pulse-inversion Harmonic Imaging and Time-

aligned Sequential Tracking

Pengfei Song1*, Xiaojun Bi2,3*, Daniel C. Mellema1, Armando Manduca1, Matthew W. Urban1, Shigao Chen1, James F. Greenleaf1

1Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA 2Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA 3Department of Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China * indicates co-first authorship

Abstract— Monitoring myocardial stiffness changes with shear wave elastography (SWE) has promising potential for assessing chemotherapy-induced cardiotoxicity for pediatric cancer patients. While ultrasound B-scan with adult cardiac probes on children is commonly acceptable, SWE can be challenging due to the narrow intercostal spaces of children, which hinders the effective transmission of the push beam and detection beam for shear wave generation and shear wave detection. This study aimed at addressing this challenge by implementing cardiac SWE on a pediatric cardiac probe (P7-4) with pulse-inversion harmonic imaging (PIHI) and time-aligned sequential tracking (TAST). The performance of the proposed pediatric cardiac SWE sequence (P7-4 PIHI-TAST) was systematically compared with an adult cardiac transducer equipped with the same PIHI and TAST cardiac SWE sequence (P4-2 PIHI-TAST), and a pediatric cardiac SWE sequence with fundamental imaging TAST shear wave detection (P7-4 Fundamental-TAST). In vivo transthoracic scans in healthy pediatric volunteers demonstrated substantial improvement of shear wave signal quality using the P7-4 PIHI-TAST sequence, as compared to the adult P4-2 PIHI-TAST sequence and the pediatric P7-4 Fundamental-TAST sequence. The results showed higher increase in SWE success rate among younger children when using the pediatric transducer. Also agreeing with previous studies, this study demonstrated that PIHI shear wave detection could substantially improve the shear wave signal quality as compared to fundamental imaging shear wave detection.

Keywords—shear wave detection; harmonic imaging; dual-frequency; mechanical vibration; acoustic radiation force

I. INTRODUCTION The long-term goal of this study is to assess chemotherapy-

induced cardiotoxicity using cardiac ultrasound shear wave elastography (SWE) for pediatric cancer patients. It is hypothesized that chemo-induced cardiotoxicity may change the passive stiffness of the myocardium, which can be noninvasively and quantitatively measured by ultrasound SWE. Previous studies have shown the feasibility of transthoracically measuring diastolic myocardial stiffness for

adults [1, 2]. To date, pediatric implementation of cardiac SWE has not been established and its feasibility has not been demonstrated. Pediatric echocardiography typically provides better ultrasound signals than adult echocardiography due to the shallower imaging depth and the thinner chest wall, so that higher frequency ultrasound can be used for better resolution and the subcutaneous tissue-induced clutter noise is significantly less. As a result, pediatric cardiac SWE should be less challenging than adult SWE because less penetration is required and there is also less clutter noise contamination to the ultrasound detection signal.

One typical challenge of pediatric echocardiography, however, is the narrow intercostal spaces of children, which can block effective transmission of ultrasound and cause acoustic shadowing to the heart wall. For pediatric cardiac SWE, the ribs can deteriorate both the push beam and detection beam, which results in poor myocardial shear wave signal. Consequently, a pediatric cardiac transducer with smaller footprint may be necessary for successful pediatric cardiac SWE. Another meaningful investigation is whether pulse-inversion harmonic imaging (PIHI), which has been established to be essential in adult cardiac SWE [1], is still necessary for pediatric cardiac SWE, in which higher fundamental frequency ultrasound can be used for better shear wave detection. Eliminating PIHI can increase the shear wave detection frame rate (FR) by a factor of 2, which is attractive if PIHI shear wave detection improvement over fundamental imaging is marginal for children. The goals of this study, therefore, were to implement cardiac SWE on a pediatric cardiac transducer, and: 1. systematically compare the SWE performance of the pediatric transducer with an adult transducer; 2. investigate the significance of PIHI for shear wave detection for pediatric cardiac SWE.

II. MATERIALS AND METHOD

A. Cardiac SWE sequences Three cardiac SWE sequences were designed in this study:

the pediatric cardiac SWE sequence with PIHI and time-aligned sequential tracking (TAST) on a pediatric cardiac transducer P7-4 (Philips Healthcare, Andover, MA), P7-4 PIHI-TAST; the pediatric cardiac SWE sequence on the same P7-4 with fundamental imaging shear wave detection and TAST, P7-4 Fundamental-TAST; and the adult cardiac SWE

978-1-4799-8182-3/15/$31.00 ©2015 IEEE 2015 IEEE International Ultrasonics Symposium Proceedings

10.1109/ULTSYM.2015.0037

sequence on an adult cardiac transducer P4-2 (Philips Healthcare, Andover, MA) with PIHI and TAST, P4-2 PIHI-

TAST. The specific imaging parameters of the three sequences have been listed in Table I. The PIHI-TAST cardiac shear wave tracking has been introduced in [2], to achieve a balance between harmonic excitation and the width of the shear wave detection region. P7-4 Fundamental-TAST also used the TAST sequence to achieve fair comparisons with the harmonic sequences. A Verasonics Vantage system (Verasonics Inc., Kirkland, WA) was used in this study. A real-time B-mode imaging with interactive user selection of the push and detection beams was designed for all the SWE sequences. Subjects’ ECG signal was used to trigger the Verasonics system, in order to measure myocaridal stiffness in late-diastole.

B. Subjects

Four healthy pediatric volunteers were scanned in this study: Subject 1 (female, age 13); Subject 2 (female, age 10); Subject 3 (male, age 8); Subject 4 (female, age 5). The study was approved by the institutional review board of Mayo Clinic and was also compliant with the Health Insurance Portability and Accountability Act. Each participating subject provided written consent and assent. Standard clinical echocardiography settings including patient and transducer positions were used in this study. For Subject 1 and Subject 2, only P4-2 PIHI-TAST and P7-4 PIHI-TAST were used for the scan. For Subjects 3 and 4, all three scan sequences were tested. For each subject, the parasternal long-axis view and the parasternal short-axis view of the basal interventricular septum (IVS) were used for cardiac SWE (as shown in Figs. 1-6). The two views used in this study require approximately 90° rotation of the transducer; therefore providing different probe orientations with respect to the intercostal spaces.

C. Shear wave signal processing The shear wave signal was extracted from the myocardium by manually selecting contours on the heart wall, following the shear wave propagation path. The red dashed boxes in Figs. 1-6 represent the locations in the myocardium where the

shear wave signals were extracted. A time-to-peak-based shear wave speed calculation method based on RANSAC was used to measure shear wave speed [3], indicated by the black lines superimposed on the shear wave signal plots in Figs. 1-6. Failed measurements with shear wave speed outside the range of 0.5-10 m/s were marked as N/A.

III. RESULTS AND DISCUSSION

A. Adult P4-2 PIHI-TAST Vs. Pediatric P7-4 PIHI-TAST Figures 1-4 show the comparison results between the adult

P4-2 transducer and the pediatric P7-4 transducer, using the same PIHI and TAST shear wave detection sequence. All P7-4 PIHI-TAST detections showed marked improvement of shear wave signal quality over the P4-2 PIHI-TAST sequence. The P4-2 transducer struggled more with younger children (Subjects 3 and 4 in Figs. 3 and 4) due to decreased intercostal space, especially for the parasternal short-axis view where the long-axis of the transducer is perpendicular to the rib and consequently severe acoustic shadowing can be observed in

Table I. Summary of the cardiac SWE sequences used in this study

Figure 1. Adult P4-2 PIHI-TAST compared with pediatric P7-4 PIHI-TAST on Subject 1.

Figure 2. Adult P4-2 PIHI-TAST compared with pediatric P7-4 PIHI-TAST on Subject 2.

the IVS. Table I summarizes the success rate (defined by number of successful shear wave speed measurements divided by total number of measurements) of each sequence. Combining long-axis and short-axis measurements, the P7-4 PIHI-TAST has much higher success rates than the P4-2 PIHI-TAST sequence.

For Subject 1, although acoustic shadowing was greatly alleviated by the P7-4 transducer, the short-axis measurements were noisier than the long-axis measurements due to the increased depth of the myocardium. The lowest push frequency for the P7-4 is 3 MHz, which may be significantly attenuated at depth greater than 40 mm. For P4-2, however, although the shear wave imaging depth is much deeper than the P7-4, the acoustic shadowing was significant and no robust short-axis measurements could be obtained. This dilemma remains as a challenge for pediatric cardiac SWE. A lower-frequency pediatric transducer can be a potential solution to

this challenge. For Subjects 3 and 4, acoustic shadowing in the IVS was still present under short-axis view for the P7-4. Therefore, the short-axis shear wave signal quality for both subjects is inferior to the long-axis shear wave signal.

B. P7-4 PIHI-TAST Vs. P7-4 Fundamental-TAST Figures 5 and 6 show the comparison results between the

pediatric P7-4 Fundamental-TAST shear wave detection sequence and the P7-4 PIHI-TAST shear wave detection sequence, using identical shear wave push beams. Corroborating prior in vivo adult transthoracic scans [1], harmonic imaging shear wave detection demonstrated substantial improvement of shear wave signal quality as compared to fundamental imaging. Although a higher-frequency fundamental frequency (5 MHz) was used for shear wave detection, the ultrasound signal was severely contaminated by the strong clutter noise (Figs. 5 and 6) and the IVS was hardly discernible for both subjects. Consequently, no shear wave signals could be detected at all

Figure 3. Adult P4-2 PIHI-TAST compared with pediatric P7-4 PIHI-TAST on Subject 3.

Figure 4. Adult P4-2 PIHI-TAST compared with pediatric P7-4 PIHI-TAST on Subject 4.

Figure 5. P7-4 Fundamental-TAST compared with P7-4 PIHI-TAST on Subject 3.

Figure 6. P7-4 Fundamental-TAST compared with P7-4 PIHI-TAST on Subject 4.

for all the trials under both scan views for both subjects. In contrary, using the same transducer but with PIHI shear wave detection, good quality shear wave signals could be obtained for the long-axis view with robust shear wave speed measurements. The improvement of shear wave signal using PIHI is probably due to the effective suppression of the clutter noise by the harmonic signals [4]. For the short-axis views, as discussed above, shear wave detection still suffers from acoustic shadowing caused by the rib, and therefore the shear wave signal quality was lower than that from the long-axis view. Table I summarizes the success rate of the two sequences: P7-4 Fundamental-TAST had a 0% success rate in shear wave detection for both subjects, while the P7-4 PIHI-TAST had an averaged 50% and 66.7% success rate for subjects 3 and 4, respectively.

C. Summary of shear wave speed measurements

Table III lists the diastolic myocardial shear wave speed measurements for the three sequences. The pediatric P7-4 PIHI-TAST sequence could provide successful shear wave speed measurements for all the subjects for all the scan views, while the adult P4-2 PIHI-TAST failed at short-axis for subjects 3 and 4, and the pediatric P7-4 Fundamental-TAST completely failed. The long-axis shear wave speed measurements are consistent between the adult P4-2 and pediatric P7-4 transducers. The short-axis and long-axis shear wave speed values are slightly lower than a previous open-chest sheep study [5] and in vivo human study [2], which suggests that children heart wall may be softer in late-diastole than adults and sheep. In addition, it is consistent with the literature that the short-axis shear wave speed is higher than the long-axis shear wave speed due to myocardial anisotropy: shear wave propagates along the myocardial fiber under short-axis view (results in higher shear wave speed), and across the myocardial fiber under long-axis view (results in lower shear wave speed).

IV. CONCLUSIONS This study implemeted cardiac SWE on a pediatric cardiac transducer using the PIHI and TAST shear wave detection technique, and showed substantial improvement of shear wave signal quality from in vivo healthy children when using the pediatric P7-4 PIHI-TAST as compared to the adult P4-2 PIHI-TAST and P7-4 Fundamental-TAST sequences. It was shown that harmonic imaging shear wave detection is still essential for pediatric cardiac SWE. The results suggest that

pediatric transducers may suffer from poor penetration due to the relatively high frequency compared to the adult cardiac transducer. A lower-frequency pediatric transducer with small footprint would be more ideal for pediatric cardiac SWE.

ACKNOWLEDGMENT AND DISCLOSURES This work was supported by American Heart Association (AHA) award 14POST20000009. Daniel C. Mellema acknowledges fellowship funding from Mayo Graduate School. The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHA. Mayo Clinic and some of the authors have financial interest in the cardiac SWE technology described here.

REFERENCES [1] P. Song, H. Zhao, M. W. Urban, A. Manduca, S. V.

Pislaru, R. R. Kinnick, et al., "Improved shear wave motion detection using pulse-inversion harmonic imaging with a phased array transducer," IEEE Transactions on Medical Imaging, vol. 32, pp. 2299-2310, 2013.

[2] P. Song, M. W. Urban, S. Chen, A. Manduca, H. Zhao, I. Z. Nenadic, et al., "In Vivo Transthoracic Measurement of End-diastolic Left Ventricular Stiffness with Ultrasound Shear Wave Elastography," in IEEE International Ultrasonics Symposium, Chicago, IL, 2014, pp. 109-112.

[3] M. H. Wang, M. L. Palmeri, V. M. Rotemberg, N. C. Rouze, and K. R. Nightingale, "Improving the robustness of time-of-flight based shear wave speed reconstruction methods using RANSAC in human liver in vivo," Ultrasound in Medicine & Biology, vol. 36, pp. 802-813, 2010.

[4] G. F. Pinton, G. E. Trahey, and J. J. Dahl, "Sources of image degradation in fundamental and harmonic ultrasound imaging using nonlinear, full-wave simulations," IEEE transactions on ultrasonics, ferroelectrics, and frequency control, vol. 58, pp. 754-65, Apr 2011.

[5] M. Couade, M. Pernot, E. Messas, A. Bel, M. Ba, A. Hagège, et al., "In vivo quantitative mapping of myocardial stiffening and transmural anisotropy during the cardiac cycle," IEEE Transactions on Medical Imaging, vol. 30, pp. 295-305, 2011.

Table II. Summary of the success rate for the 3 cardiac SWE sequences

Table III. Summary of shear wave speed measurements (mean (SD), m/s)