Passive Cavitation Mapping for Monitoring Ultrasound Therapy

244 Pages·2010·10.43 MB·English

Passive Cavitation Mapping for
Monitoring Ultrasound Therapy
Mikl´os Gy¨ongy
Department of Engineering Science
University of Oxford
A thesis submitted for the degree of
Doctor of Philosophy
2010
Acknowledgements
In my last year as an undergraduate, a tutor had taunted me: “have you ever
built a submarine”? I was more apt at example sheets than practical exercises,
and he scored a sore point. The water tanks in our laboratory are too small for a
submarine, but there is cavitation noise and now passive sonar to locate it, so his
question no longer taunts me. When I joined the Life Sciences Interface Doctoral
Training Centre in 2005, I had little idea of what research I wanted to do. Now,
at the end of my doctoral studies, I have found an area of research I am passionate
about. Both examples illustrate the guidance and example of my primary supervisor
Constantin-C. Coussios, to whom I am deeply grateful for the skills he has taught
me as a researcher and for the confidence that this has given me. I am also grateful
to my other supervisor Alison J. Noble who, though not as directly involved with
my research, has helped and encouraged me throughout.
Nearly everyone in Constantin’s group has helped me in some way or another,
but I would like to mention particularly Manish Arora and Jamie Collin. Their the-
oretical and experimental expertise have helped me out more times than I can count,
and I am thankful for the engaging discussions I have had with them. Similarly,
though only visiting Oxford for a year, it has been a pleasure to discuss with Ron
Roythesubtletiesofcavitation, andhisexperimentaltipsandideashaveencouraged
me try out new things, giving them a chance to succeed.
The latter part of my experimental work was carried out in collaboration with
Rob Ritchie, a highly able doctor and scientist, who showed a patience beyond what
could be expected during our difficult and sometimes frustrating work with animal
tissue. I am grateful to him, Eleonora Mylonopoulou, and the rest of the lab for
their tolerance of my increasingly demanding personality towards the last months
of my research.
SomeoftheequipmentandsoftwareIusedwasmadespecificallyforthisresearch.
Many thanks to Jim Fisk and Roger Lewis, the departmental technicians, who
made the sample and transducer holders, as well as Bassel Rifai, who designed the
two-channel phantom holder. Larry Mo (formerly of Zonare) was also invaluable
in helping to explain the quirks of the ultrasound system, and in ensuring our
instrumentation needs were incorporated into the ultrasound operating system. I
was honoured to meet him in person at a conference.
My family, my wife’s family, and friends have been a source of great moral and
practical support during my studies and research. Without wishing to embarass
anyonebymentioningnames, manyhavebeenamodelofkindnesstomethroughout
mylifeandhaveledmetobelieve, perhapsfoolishlybutstillimplacably, inthetruth
of this University’s motto.
I would like to dedicate this thesis to my wife Kinga. Many words can be used
to describe her, but none more so than fun.
Abstract
Cavitationisaphenomenonpresentduringmanyultrasoundtherapies, including
the thermal ablation of malignant tissue using high intensity focused ultrasound
(HIFU). Inertial cavitation, in particular, has been previously shown to result in
increased heat deposition and to be associated with broadband noise emissions that
can be readily monitored using a passive receiver without interference from the main
ultrasound signal. The present work demonstrates how an array of passive receivers
can be used to generate maps of cavitation distribution during HIFU exposure,
uncovering a new potential method of monitoring HIFU treatment.
Using a commercially available ultrasound system (z.one, Zonare, USA), pulse
transmission can be switched off and data from 64 elements of an array can be
simultaneously acquired to generate passive maps of acoustic source power. For
the present work, a 38 mm aperture 5-10 MHz linear array was used, with the 64
elements chosen to span the entire aperture. Theory and simulations were used to
show the spatial resolution of the system, the latter showing that the broadband
nature of inertial cavitation makes passive maps robust to interference between
cavitating bubbles.
Passive source mapping was first applied to wire scatterers, demonstrating the
ability of the system to resolve broadband sources. With the array transversely
placed to the HIFU axis, high-resolution passive maps are generated, and emissions
fromseveralcavitatingbubblesareresolved. Thesensitivityofpassivemappingdur-
ing HIFU exposure is compared with that of an active cavitation detector following
exposure.
ThearraywasthenplacedwithinarectangularopeninginthecentreoftheHIFU
transducer, providing a geometric setup that could be used clinically to monitor
HIFU treatment. Cavitation was instigated in continuous and disjoint regions in
agar tissue mimicking gel, with the expected regions of cavitation validating the
passive maps obtained. Finally, passive maps were generated for samples of ox
liver exposed to HIFU. The onset of inertial cavitation as detected by the passive
mapping approach was found to provide a much more robust indicator of lesioning
than post-exposure B-mode hyperecho, which is in current clinical use. Passive
maps based on the broadband component of the received signal were able to localize
the lesions both transversely and axially, however cavitation is generally indicated
5 mm prefocal to the lesions. Further work is needed to establish the source of this
discrepancy.
It is believed that with use of an appropriately designed cavitation detection
array, passive mapping will represent a major advance in ultrasound-guided HIFU
therapy. Not only can it be utilized in real-time during HIFU exposure, without the
need to turn the therapeutic ultrasound field off, but it has also been shown in the
context of the present work to provide a strong indicator of successful lesioning and
high signal-to-noise compared to conventional B-mode ultrasound techniques.
Contents
1 Introduction 1
1.1 Interaction of ultrasound with tissue . . . . . . . . . . . . . . . . . . 3
1.1.1 Linear propagation of pressure waves . . . . . . . . . . . . . . 3
1.1.2 Non-linear propagation . . . . . . . . . . . . . . . . . . . . . . 3
1.1.3 Thermal effects . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.1.4 Acoustic cavitation . . . . . . . . . . . . . . . . . . . . . . . . 8
1.1.5 Other mechanical effects . . . . . . . . . . . . . . . . . . . . . 16
1.2 Tissue ablation by High Intensity Focussed Ultrasound (HIFU) . . . . 17
1.3 HIFU treatment monitoring . . . . . . . . . . . . . . . . . . . . . . . 21
1.3.1 Monitoring by Magnetic Resonance Imaging (MRI) . . . . . . 22
1.3.2 Monitoring by active ultrasound . . . . . . . . . . . . . . . . . 25
1.3.3 Cavitation monitoring . . . . . . . . . . . . . . . . . . . . . . 31
1.4 Summary of contributions of the current work . . . . . . . . . . . . . 34
2 Theory and Simulations of Passive Cavitation Mapping 36
2.1 The forward model . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
2.1.1 Propagation of radiated pressure waves . . . . . . . . . . . . . 38
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2.1.2 Modelling bubbles as acoustic sources . . . . . . . . . . . . . . 39
2.1.3 Power radiated by cavitating bubbles . . . . . . . . . . . . . . 40
2.1.4 Detection of radiated pressure waves . . . . . . . . . . . . . . 41
2.1.5 The role of attenuation . . . . . . . . . . . . . . . . . . . . . . 42
2.2 The inverse problem . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
2.2.1 Passive beamforming for single source reconstruction . . . . . 44
2.2.2 Beamforming for source field reconstruction . . . . . . . . . . 46
2.2.3 Reconstruction of discrete point sources . . . . . . . . . . . . 50
2.3 Passive source mapping with a linear array . . . . . . . . . . . . . . . 54
2.3.1 Choosing the right algorithm . . . . . . . . . . . . . . . . . . 54
2.3.2 Implementation on a linear array . . . . . . . . . . . . . . . . 57
2.3.3 Spatial resolution . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.3.4 Simulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
2.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
3 Experimental Methods for Passive Cavitation Mapping 82
3.1 Overview of experimental rationale . . . . . . . . . . . . . . . . . . . 82
3.2 Passive mapping from array channel data . . . . . . . . . . . . . . . . 84
3.3 Experimental apparatus . . . . . . . . . . . . . . . . . . . . . . . . . 87
3.3.1 Test tank . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
3.3.2 Source transducers . . . . . . . . . . . . . . . . . . . . . . . . 89
3.3.3 Active and passive source detection . . . . . . . . . . . . . . . 92
3.3.4 Agar tissue-mimicking gel . . . . . . . . . . . . . . . . . . . . 93
3.3.5 Tissue preparation . . . . . . . . . . . . . . . . . . . . . . . . 98
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3.3.6 Thermometry . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
3.4 Passive mapping of time-invariant scatterers . . . . . . . . . . . . . . 102
3.5 Bistatic passive cavitation mapping . . . . . . . . . . . . . . . . . . . 107
3.6 Monostatic passive cavitation mapping . . . . . . . . . . . . . . . . . 110
3.6.1 Cavitation mapping in agar gel . . . . . . . . . . . . . . . . . 111
3.6.2 Cavitation mapping during tissue ablation . . . . . . . . . . . 115
3.7 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
4 Passive Mapping of Time-Invariant Scatterers 117
4.1 Calibration of the linear array on receive . . . . . . . . . . . . . . . . 118
4.1.1 Frequency-dependent sensitivity of array elements . . . . . . . 118
4.1.2 Spatial calibration of the array . . . . . . . . . . . . . . . . . 119
4.2 Passive mapping of insonated scatterers . . . . . . . . . . . . . . . . . 123
4.2.1 Discrete sources in cross formation . . . . . . . . . . . . . . . 123
4.2.2 Semi-continuous linear source . . . . . . . . . . . . . . . . . . 126
4.3 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
5 Bistatic Passive Cavitation Mapping 128
5.1 Mapping of discrete bubble distributions . . . . . . . . . . . . . . . . 130
5.2 Resolution of discrete source signatures . . . . . . . . . . . . . . . . . 133
5.3 Comparison with pulse-echo . . . . . . . . . . . . . . . . . . . . . . . 137
5.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
6 Monostatic Passive Cavitation Mapping 142
6.1 Cavitation in agar tissue-mimicking phantoms . . . . . . . . . . . . . 142
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6.1.1 Cavitation in a contiguous region . . . . . . . . . . . . . . . . 142
6.1.2 Cavitation source power versus focal temperature . . . . . . . 146
6.1.3 Cavitation in disjoint regions . . . . . . . . . . . . . . . . . . 149
6.2 Cavitation in tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
6.2.1 Extending passive cavitation mapping to tissue . . . . . . . . 151
6.2.2 Comparison of cavitation-based and hyperecho-based moni-
toring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
6.2.3 Prediction of lesion shape using passive dose maps . . . . . . . 161
6.3 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170
7 Conclusions 172
7.1 Summary of achievements . . . . . . . . . . . . . . . . . . . . . . . . 172
7.2 Suggestions for future work . . . . . . . . . . . . . . . . . . . . . . . 176
7.2.1 High-resolution passive cavitation mapping and source recon-
struction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
7.2.2 Cavitation monitoring during ultrasound therapy . . . . . . . 177
A Channel Data Acquisition on a Commercial Ultrasound System 181
A.1 Setting imaging parameters via communication with the ultrasound
scan engine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
A.2 Data acquisition path . . . . . . . . . . . . . . . . . . . . . . . . . . . 186
A.3 Pre-processing of channel data in Matlab . . . . . . . . . . . . . . . . 190
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List of Figures
1.1 Proposed method of monitoring therapeutic ultrasound by passive
cavitation mapping . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Simulations of an inertially cavitating contrast agent microbubble . . 10
1.3 Schematic of non-invasive tumour ablation by HIFU . . . . . . . . . . 17
2.1 The linear array used to generate passive maps . . . . . . . . . . . . . 57
2.2 The passive mapping algorithm . . . . . . . . . . . . . . . . . . . . . 59
2.3 Parametric single source localisation . . . . . . . . . . . . . . . . . . 62
2.4 Resolution of passive beamforming . . . . . . . . . . . . . . . . . . . 70
2.5 Comparison of simulated and theoretical imaging resolution in the
clinically-relevant imaging setup . . . . . . . . . . . . . . . . . . . . . 72
2.6 Simulation of imaging resolution with two 7.5 MHz sources on the
array central axis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
2.7 Simulation of imaging resolution with two 7.5 MHz sources on either
side of the array central axis . . . . . . . . . . . . . . . . . . . . . . . 75
2.8 Simulation of imaging resolution with two 5-10 MHz noise sources on
the array central axis . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
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