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On Nonlinear Acoustics in Contrast Echocardiography
Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ultrasound is one of the most commonly used noninvasive medical imaging techniques. Ultrasound contrast agents (UCA), consisting of encapsulated gas-filled microbubbles, have shown to increase the diagnostic precision in selected low echogenic patients. UCA also holds promise for bedside evaluation of myocardial perfusion quantification, but is not yet reproducible and specific enough for clinical use. In addition risks have been addressed when used, as first recommended, together with high mechanical index (MI) for reperfusion assessment by contrast destruction. We clinically observed increased myocardial velocities after UCA-administration when applied simultaneously with color tissue Doppler imaging (CTDI) arising the question if this increase was due to physiological factors or physical changes in the backscattered signals when UCA were present.

The aims of the thesis was to explain this velocity shift and simultaneously to contribute to a future safe and contrast specific application by further characterizing the non-linear acoustic properties of UCA when located in an acoustic field. Of specific interest was to evaluate in which way nonlinear wave propagation affects the response from UCA and if a change in pulse shape, length or polarity can be utilized to increase the nonlinear signal contribution.

Twelve patients with ischemic heart disease were examined with CTDI before and after UCA-administration in order to verify the change in peak systolic velocity. An experimental in vitro model including flow and tissue phantoms for UCA was established for CTDI. Raw data from single-element transducers and clinical ultrasound systems were collected for three different UCA and analyzed to determine if the observed velocity shift could be reproduced in vitro and to find a possible cause. Our results show in vivo and in vitro that UCA will affect the autocorrelation phase shift estimator used for CTDI in terms of contribution from rupturing UCA microbubbles, which explains the velocity shift. CTDI during contrast infusion should therefore be avoided unless it can be performed at low MI where the majority of the UCA are intact.

The computational model for spatial superposition of attenuated waves was modified to include an operator for pulse distortion from nonlinear wave propagation. The Matlab™ toolbox Bubblesim based on a modified Rayleigh-Plesset-equation and with insonation parameters such as frequency, pressure amplitude, pulse length and polarity was used to study the response from single microbubbles either for simulated pulses or for pulses generated by clinical ultrasound systems and single element transducers. The combination of the two models also provided a computational platform to asses pulse distortion from nonlinear wave propagation, the response of the UCA bubble and the linear backscatter of the low amplitude bubble echo. When evaluating the harmonic response in simulations and in vitro, the interaction of the excitation pulses with the contrast bubbles was identified as the main cause of nonlinear scattering, and a 2-3 dB increase of the second harmonic amplitude depends on nonlinear distortions of the incident pulse. By applying small changes of short (<3.5 cycles) and fragmented transmitted wideband pulses of 2-2.5 MHz, it is shown that inverted pulse polarity considerably modulates power without affecting a low and safe MI (<0.4), and the results lodged promise to further to enhance a contrast response.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2010. , 114 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1338
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:liu:diva-65418ISBN: 978-91-7393-315-5 (print)OAI: oai:DiVA.org:liu-65418DiVA: diva2:395517
Public defence
2010-11-12, Eken, Campus US, Linköpings universitet, Linököping, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2011-02-07 Created: 2011-02-07 Last updated: 2011-02-07Bibliographically approved
List of papers
1. Effects of ultrasound contrast agents on doppler tissue velocity estimation
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2006 (English)In: Journal of the American Society of Echocardiography, ISSN 0894-7317, E-ISSN 1097-6795, Vol. 19, no 2, 154-164 p.Article in journal (Refereed) Published
Abstract [en]

The combination of Doppler tissue imaging and myocardial contrast echocardiography has the potential to provide information about motion and perfusion of the myocardium in a single examination. The purpose of this study was to establish how the presence of ultrasound contrast agent (UCA) affects measurements of Doppler tissue velocities in vivo and in vitro. We performed echocardiography in 12 patients with ischemic heart disease before and immediately after a slow intravenous infusion of the UCA Optison, using color Doppler tissue imaging to examine the effect of contrast agents in vivo. The myocardial peak systolic velocities and their integrals were analyzed in digitally stored cineloops before and after contrast administration. To distinguish between methodologic and physiologic factors affecting the measurement of tissue velocity in vitro, experiments with a rotating disk and a flow cone phantom were also carried out for the 3 contrast agents: Optison, Sonovue, and Sonazoid. In vivo results show that the values for peak systolic velocity increased by about 10% during contrast infusion, from mean 5.2 ± 1.8 to 5.7 ± 2.3 cm/s (P = .02, 95% confidence interval 2%-16%). The increase in myocardial peak systolic velocities was verified in experimental models in which the UCA increased the estimated mean velocity in the order of 5% to 20% for the motion interval of 5 to 7 cm/s, corresponding to the myocardial velocities studied in vivo. The response was similar for all 3 contrast agents and was not affected by moderate variations in concentration of the agent. We have shown that the presence UCA will affect Doppler tissue measurements in vivo and in vitro. The observed bias is presumed to be an effect of harmonic signal contribution from rupturing contrast agent microbubbles and does not indicate biologic or physiologic effects. Copyright 2006 by the American Society of Echocardiography.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28716 (URN)10.1016/j.echo.2005.09.025 (DOI)13885 (Local ID)13885 (Archive number)13885 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2011-02-07
2. Contrast Biases the Autocorrelation Phase Shift Estimation in Doppler Tissue Imaging
Open this publication in new window or tab >>Contrast Biases the Autocorrelation Phase Shift Estimation in Doppler Tissue Imaging
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2009 (English)In: Ultrasound in Medicine and Biology, ISSN 0301-5629, Vol. 35, no 3, 447-457 p.Article in journal (Refereed) Published
Abstract [en]

Quantitative assessment of regional myocardial function at rest and during stress with Doppler tissue imaging (DTI) plays an important role in daily routine echocardiography. However, reliable visual analysis is largely dependent on image quality and adequate border delineation, which still remains a challenge in a significant number of patients. In this respect, an ultrasound contrast agent (UCA) is often used to improve visualization in patients with suboptimal image quality. The knowledge of how DTI measurements will be affected by UCA present in the tissue is therefore of significant importance for an accurate interpretation of local myocardial motion. The aim of this paper was to investigate how signal contribution from UCA and nonlinear wave propagation influence the performance of the autocorrelation phase shift estimator used for DTI applications. Our results are based on model experiments with a clinical 2-D grayscale scanner and computational simulations or the DTI velocity estimator for synthetically-derived pulses, simulated bubble echoes and experimentally-sampled RF data of transmitted pulses and backscattered contrast echoes. The results show that destruction of UCA present in the tissue will give rise to an apparent bidirectional velocity bias of individual velocity estimates, but that spatial averaging of individual velocity measurements within a region-of-interest will result in a negative bias (away from the transducer) of the estimated mean or mean peak velocity. The UCA destruction will also have a significant impact on the measured integrated mean velocity over time, i.e., displacement. To achieve improved visualization with UCA during DTI-examinations, we either recommend that it is performed at low acoustic powers, mechanical index <= 0.3, thereby minimizing the effects from bubble rupture, or that each Doppler pulse package is preceded by a destruction burst similar to "Flash imaging" to clear the target area of contrast microbubbles.

Keyword
Ultrasound, Tissue Doppler, Contrast, Microbubbles, Velocity estimation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17277 (URN)10.1016/j.ultrasmedbio.2008.09.012 (DOI)
Available from: 2009-03-16 Created: 2009-03-16 Last updated: 2011-02-07
3. Modelling of nonlinear effects and the response of ultrasound contrast micro bubbles: simulation and experiment
Open this publication in new window or tab >>Modelling of nonlinear effects and the response of ultrasound contrast micro bubbles: simulation and experiment
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2004 (English)In: Ultrasonics, ISSN 0041-624X, E-ISSN 1874-9968, Vol. 42, no 01-Sep, 301-307 p.Article in journal (Refereed) Published
Abstract [en]

The propagation of diagnostic ultrasonic imaging pulses in tissue and their interaction with contrast micro bubbles is a very complex physical process, which we assumed to be separable into three stages: pulse propagation in tissue, the interaction of the pulse with the contrast bubble, and the propagation of the scattered echo. The model driven approach is used to gain better knowledge of the complex processes involved. A simplified way of field simulation is chosen due to the complexity of the task and the necessity to estimate comparative contributions of each component of the process. Simulations are targeted at myocardial perfusion estimation. A modified method for spatial superposition of attenuated waves enables simulations of low intensity pulse pressure fields from weakly focused transducers in a nonlinear, attenuating, and liquid-like biological medium. These assumptions enable the use of quasi-linear calculations of the acoustic field. The simulations of acoustic bubble response are carried out with the Rayleigh-Plesset equation with the addition of radiation damping. Theoretical simulations with synthesised and experimentally sampled pulses show that the interaction of the excitation pulses with the contrast bubbles is the main cause of nonlinear scattering, and a 2-3 dB increase of second harmonic amplitude depends on nonlinear distortions of the incident pulse. (C) 2004 Elsevier B.V. All rights reserved.

Keyword
ultrasound, simulation, nonlinear, contrast agents
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-46245 (URN)10.1016/j.ultras.2004.01.023 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2011-02-07
4. Ultrasound contrast response to variation of incident pulse length and polarity
Open this publication in new window or tab >>Ultrasound contrast response to variation of incident pulse length and polarity
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Microbubbles are used as ultrasound contrast agents (UCA) in diagnostic ultrasound as they considerably enhance the backscattered signal and generate specific signal characteristics that can be used to isolate echoes that originate from the blood volume. Emerging new advanced contrast specific insonation techniques have shown to better discriminate the backscattered UCA-signal but has not gained clinical practice due to their complexity and the need for additional soft- and hardware, or due to the debated safety aspects regarding microbubble cavitation at mechanical index (MI >>0.4). In this study we investigate a simplified approach to improve the nonlinear signal contribution from UCA at low MI < 0.4 by utilizing the asymmetry between positive and negative peak pressures for pulse lengths ≤3.5 cycles. In vitro registrations of the transmitted pulse peak pressure asymmetry from a single element transducer were obtained with a needle hydrophone after a transducer excitation pulse with increasing length from 0.5 to 5 cycles. A computational model (Bubblesim) was used to investigate the response from a single microbubble after interaction with transmitted pulse with variations of length, shape and polarity. Our results show that small changes (quarters of a pulse cycle) will change the transmitted pulse shape and distribution of peak pressures and that this effect can be used to change the scattering behavior of UCA in simulations and in vitro. This effect will increase with decreasing pulse lengths <5 cycles. The best case scenario for differentiation of harmonic UCA response with polarity change at MI <0.4 and real time imaging can for transducer frequencies of 2-2.5 MHz be found for pulse lengths of 2.25 and 2.75 cycles in the acoustic pressure interval of 300-500 kPa.

Keyword
Ultrasound contrast agents, nonlinear imaging, harmonic imaging, contrast echocardiography
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-65417 (URN)
Available from: 2011-02-07 Created: 2011-02-07 Last updated: 2011-02-07

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