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Abstract

Our group has proposed the concept of subharmonic aided pressure estimation (SHAPE) utilizing microbubble-based ultrasound contrast agent signals for the noninvasive estimation of hydrostatic blood pressures. An experimental system for in vitro SHAPE was constructed based on two single-element transducers assembled confocally at a 60° angle to each other. Changes in the first, second and subharmonic amplitudes of five different ultrasound contrast agents were measured in vitro at static hydrostatic pressures from 0–186 mmHg, acoustic pressures from 0.35–0.60 MPa peak-to-peak and frequencies of 2.5–6.6 MHz. The most sensitive agent and optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Logiq 9 scanner (GE Healthcare, Milwaukee, WI). This implementation of SHAPE was then tested under dynamic-flow conditions and compared to pressure-catheter measurements. Over the pressure range studied, the first and second harmonic amplitudes reduced approximately 2 dB for all contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 9–14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r² = 0.98, p < 0.001). Optimal sensitivity was achieved at a transmit frequency of 2.5 MHz and acoustic pressure of 0.35 MPa using Sonazoid (GE Healthcare, Oslo, Norway). A Logiq 9 scanner was modified to implement SHAPE on a convex transducer with a frequency range from 1.5–4.5 MHz and acoustic pressures from 0–3.34 MPa. Results matched the pressure catheter (r² = 0.87). In conclusion, subharmonic contrast signals are a good indicator of hydrostatic pressure. Out of the five ultrasound contrast agents tested, Sonazoid was the most sensitive for subharmonic pressure estimation. Real-time SHAPE has been implemented on a commercial scanner and offers the possibility of allowing pressures in the heart and elsewhere to be obtained noninvasively.

Keywords

Pressure estimation subharmonic signals ultrasound contrast agents

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References

Goldberg

Raichlen

Forsberg

Ultrasound Contrast Agents: Basic Principles and Clinical Applications 2nd ed. (Martin Dunitz Ltd., London 2001).

Forsberg

Shi

Goldberg

Subharmonic imaging of contrast agents.

Ultrasonics 38, 93–98 (2000).

Simpson

Chin

Burns

Pulse inversion Doppler: a new method for detecting nonlinear echoes from microbubble contrast agents.

IEEE Trans Ultrason Ferroelec Freq Contr 46, 372–382 (1999).

Forsberg

Liu

Chiou

Comparison of fundamental and wideband harmonic contrast imaging of liver tumors.

Ultrasonics 38, 110–113 (2000).

Shi

Forsberg

Hall

Subharmonic imaging with contrast agents: initial results.

Ultrasonic Imaging 21, 79–94 (1999).

Shi

Forsberg

Raichlen

Needleman

Goldberg

Pressure dependence of subharmonic signals from contrast microbubbles.

Ultrasound Med. Biol 25, 275–283 (1999).

Forsberg

Piccoli

Merton

Palazzo

Hall

Breast lesions: imaging with contrast-enhanced subharmonic US - initial experience.

Radiology 244, 718–726 (2007).

Forsberg

Liu

Shi

In vivo perfusion estimation using subharmonic contrast microbubble signals.

J Ultrasound Med 25, 15–21 (2006).

Forsberg

Liu

Shi

In vivo pressure estimation using subharmonic contrast microbubble signals: proof of concept.

IEEE Trans Ultrason Ferroelec Freq Contr 52, 581–583 (2005).

10.

Shankar

Krishna

Newhouse

Advantages of subharmonic over second harmonic backscatter for contrast-to-tissue echo enhancement.

Ultrasound Med Biol 24, 395–399 (1998).

11.

Chomas

Dayton

May

Ferrara

Nondestructive subharmonic imaging.

IEEE Trans Ultrason Ferroelec Freq Contr 49, 883–892 (2002).

12.

Goertz

Cherin

Needles

Burns

Foster

High frequency nonlinear B-scan imaging of microbubble contrast agents.

IEEE Trans Ultrason Ferroelectr Freq Contr 52, 65–79 (2005).

13.

Needles

Goertz

Karshafian

Cherin

High-frequency subharmonic pulsed-wave Doppler and color flow imaging of microbubble contrast agents.

Ultrasound Med Biol 34, 1139–1151 (2008).

14.

Strauss

Roth

Rieger

Noninvasive assessment of pressure gradients across iliac artery stenoses:duplex and catheter correlative study

J Ultrasound Med 12, 17–22 (1993).

15.

Reddy

Taffet

Madala

Noninvasive blood pressure measurement in mice using pulsed Doppler ultrasound.

Ultrasound Med Biol 29, 379–385 (2003).

16.

Fairbank

Scully

A new noninvasive technique for cardiac pressure measurement: resonant scattering of ultrasound from bubbles.

IEEE Trans Biomed Eng 24, 107–110 (1977).

17.

Ishihara

Kitabatake

Tanouchi

New approach to noninvasive manometry based on pressure dependent resonant shift of elastic microcapsules in ultrasonic frequency characteristics.

Jap J Appl Phys 27 (Suppl. 27–1), 125–127 (1988).

18.

Bouakaz

Frinking

PJA

de Jong

Bom

Noninvasive measurement of the hydrostatic pressure in a fluid-filled cavity based on the disappearance time of the micrometer-sized free gas bubbles.

Ultrasound Med Biol 25, 1407–1415 (1999).

19.

Postema

Bouakaz

de Jong

Noninvasive microbubble-based pressure measurements: a simulation study.

Ultrasonics 42, 759–762 (2004).

20.

Hök

A new approach to noninvasive manometry: interaction between ultrasound and bubbles.

Med Biol Eng Comput 19, 35–39 (1981).

21.

Shi

Forsberg

Goldberg

Raichlen

Method and system for pressure estimation using subharmonic signals from microbubble-based ultrasound contrast agents. U.S. Patent No. 6,302,845 (2001).

22.

Halldorsdottir

Leodore

Cavanaugh

Forsberg

Initial in vitro study of US pressure measurements for monitoring neoadjuvant chemotherapy of breast cancer (abstract). in Prog RSNA, p. 338 (2009).

23.

Eisenbrey

Dave

Halldorsdottir

Simultaneous grayscale and subharmonic ultrasound imaging on a modified commercial scanner. Ultrasonics (2011, in press).

24.

Katiyar

Sarkar

Forsberg

Modeling subharmonic response from contrast microbubbles as a function of ambient static pressure.

J Acoust Soc Am 129, 2325–2335 (2011).

25.

Andersen

Jensen

Impact of acoustic pressure on ambient pressure estimation using ultrasound contrast agent.

Ultrasonics 50, 294–299 (2010).

26.

Adam

Sapunar

Burla

On the relationship between encapsulated ultrasound contrast agent and pressure.

Ultrasound Med. Biol 31, 673–686 (2005).

27.

Ganor

Adam

Kimmel

Time and pressure dependence of acoustic signals radiated from microbubbles.

Ultrasound Med. Biol 31, 1367–1374 (2005).

28.

Adam

Burla

Blood pressure estimation by processing of echocardiography signals.

Compu Cardiol 28, 609–612 (2001).

29.

Frinking

PJA

Gaud

Brochot

Arditi

Subharmonic scattering of phospholipid-shell microbubbles at low acoustic pressure amplitudes.

IEEE Trans Ultrason Ferroelectr Freq Contr 57, 1762–1771 2010.

30.

Dave

Halldorsdottir

Eisenbrey

In vivo subharmonic pressure estimation of portal hypertension in canines. in Proc IEEE US Symp, pp. 778–781, (2010)

31.

Forsberg

Halldorsdottir

Dave

In vivo noninvasive cardiac subharmonic pressure estimation (abstract).

Ultrasonic Imaging 31, 45–46 (2009).

32.

Halldorsdottir

Dave

Eisenbrey

Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumors: in vitro and in vivo proof of concept (abstract).

J Ultrasound Med 30, S28 (2011).

Subharmonic Contrast Microbubble Signals for Noninvasive Pressure Estimation under Static and Dynamic Flow Conditions

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