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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5800_Библиотеки_им_академика_М_И_Перельмана.pdf
xii
successful; the parents readily agreed to the procedure as carefully explained
by the referring clinical team, the children had no fear of the “test” in the
friendly supported examination room and furthermore the accuracy of the test
matched that being seen in adults. The issue of “off-licence” was elegantly
detailed to the parent by the referring clinical team; most drug intervention is
“off-licence” in children but we do it for the betterment of healthcare for our
children.
We published our results, as did other groups across Europe, many using
this technique on an “ad hoc” basis, with an international questionnaire indicating this was not an uncommon occurrence. The application of intravesical
contrast ultrasound (licenced application) was relatively common practice,
with intravenous applications in many organs documented by this survey.
Subsequently, the application of contrast ultrasound in the assessment and
follow-up of blunt abdominal trauma began to emerge in the adult population,
with almost immediate transfer to the management of trauma in children.
This seems to be an obvious option to apply contrast-enhanced ultrasound to
the follow-up of a resolving focal solid single organ injury, avoiding the need
to do repeated computed tomography examinations in the child. This has now
also become accepted practice in many trauma centers in Europe.
Many other groups have developed the applications of contrast-enhanced
ultrasound in children, and this book summarizes this experience. We are at
the beginning, and as we look back over the last 20 years of our own practice
and see how far we come, we are sure the transformation over the next 20
years will be unrecognizable today. We owe it to the children to image gently
and ultrasound is ideal for this. Adding a contrast agent to an ultrasound
examination avoids all the aspects of computed tomography and magnetic
resonance imaging procedures that may not always be needed or even be
detrimental to the child.
Preface
London, UK PaulS.Sidhu
London, UK MariaE.Sellars
London, UK AnnamariaDeganello
Contents
1 Physics of Microbubble Contrast Agents . . . . . . . . . . . . . . . . . . . 1
Kirsten Christensen-Jeffries and Robert J. Eckersley
2 Safety of Contrast-Enhanced Ultrasound . . . . . . . . . . . . . . . . . . . 13
Gail ter Haar
3 Quantitative Contrast-Enhanced Ultrasound . . . . . . . . . . . . . . . 19
Martin Krix
4 Artifacts in Contrast-Enhanced Ultrasound
Examinations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Paul S. Sidhu, Gibran T. Yusuf, Cheng Fang,
and Vasileios Rafailidis
5 How to Perform an Intravenous Contrast-Enhanced
Ultrasound (CEUS) Examination in a Child.
Methodology and Technical Considerations . . . . . . . . . . . . . . . . . 39
Benjamin Leenknegt, Zoltan Harkanyi, Annamaria Deganello,
and Paul S. Sidhu
6 How to Set Up a Contrast- Enhanced
Ultrasound Service for Children . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Paul D. Humphries
7 Pediatric Focal Lesions in the Liver:
A Clinical Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Emer Fitzpatrick
8 Contrast-Enhanced Ultrasound of Pediatric
Focal Liver Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Maciej Piskunowicz, Cheng Fang, Annamaria Deganello,
Maria E. Sellars, and Paul S. Sidhu
9 Pediatric Contrast-Enhanced Ultrasonography
(CEUS): Pediatric Transplantation . . . . . . . . . . . . . . . . . . . . . . . 85
Doris Franke
10 Blunt Abdominal Trauma in Children:
Clinical Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Erica Makin
xiii
xiv
11 Contrast-Enhanced Ultrasound in Blunt
Abdominal Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Margherita Trinci, Annamaria Deganello, and Vittorio Miele
12 Contrast-Enhanced Ultrasound of the Pediatric
Kidneys. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Jeevesh Kapur and Zoltan Harkanyi
13 Pediatric Contrast-Enhanced Ultrasonography
(CEUS) of the Spleen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Doris Franke and Zoltan Harkanyi
14 Contrast-Enhanced Voiding Urosonography
(ceVUS): Current Experience and Advanced Techniques . . . . . . 141
Susan J. Back, Kassa Darge, and Aikaterini Ntoulia
15 Contrast-Enhanced Ultrasound in the Pediatric Scrotum . . . . . 159
Vasileios Rafailidis, Dean Y. Huang, Maria E. Sellars,
and Paul S. Sidhu
16 Contrast-Enhanced Ultrasound in
Childhood Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Vasileios Rafailidis, Annamaria Deganello,
Maria E. Sellars, and Paul S. Sidhu
Contents
17 Contrast-Enhanced Ultrasound in Inflammatory
Bowel Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Damjana Ključevšek
18 Contrast-Enhanced Ultrasound in Childhood Oncology . . . . . . 205
Judy Squires, Abhay Srinivasan, and M. Beth McCarville
19 Intraoperative Contrast-Enhanced Ultrasound in the
Pediatric Neurosurgical Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
Ignazio G. Vetrano, Laura Grazia Valentini, Francesco
DiMeco, and Francesco Prada
20 Contrast-Enhanced Ultrasound in
Pediatric Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
Abhay Srinivasan and Dean Y. Huang
21 Cost-Effectiveness of CEUS in Pediatric Practice . . . . . . . . . . . . 259
Gibran T. Yusuf, Annamaria Deganello, Maria E. Sellars,
and Paul S. Sidhu
22 Recent Advances in Neonatal CEUS . . . . . . . . . . . . . . . . . . . . . . . 265
Misun Hwang
About the Editors
Paul S. Sidhu, BSc, MBBS, MRCP, FRCR,
DTM&H is Professor of Imaging Sciences at
King’s College London and a Consultant
Radiologist in the Department of Radiology at
King’s College Hospital. He qualied from St.
Mary’s Hospital Medical School (now part of
Imperial College London) in 1982, with Honors.
He completed his internship at St. Mary’s
Hospital in Paddington on the Professorial
Medical Unit, before completing Senior House
Ofcer Positions at the Brompton Hospital,
Hammersmith Hospital, Hospital for Tropical
Diseases and Guy’s Hospital. He did his radiology training at the Hammersmith Hospital and
King’s College Hospital. He was appointed a
Consultant Radiologist at King’s College
Hospital in 1996, with a role in Ultrasound and
Interventional Radiology. He was made Professor
of Imaging Sciences in 2012. He is Clinical
Director of Radiology at King’s College Hospital,
London. He has published extensively on many
aspects of ultrasound particularly in relation to
male health and liver transplantation and has pioneered the introduction of contrast-enhanced
ultrasound in the United Kingdom. He is recognized as an authority in the application of
contrast- enhanced ultrasound in clinical practice.
He is the Editor of 6 books and has published
over 600 scientic articles, book chapters, and
conference abstracts. He lectures widely with
over 500 presentations at national and international meetings. He is currently the Editor of the
European Journal of Ultrasound and previously
the Deputy Editor of the British Journal of
Radiology. He is an Associate Editor of
Radiology. He is Past-President of the British
Medical Ultrasound Society and the Past-
xv
xvi
About the Editors
President of the Section of Radiology of the
Royal Society of Medicine. He is recent PastPresident of the European Federation of Societies
in Ultrasound in Medicine and Biology. His current research interests include the application of
contrast-enhanced ultrasound to the testis, radiation dose reduction in children, and non-invasive
ultrasound in the assessment of liver disease.
MariaE.Sellars, MBChB, FRCR is a consultant pediatric radiologist at King’s College
Hospital London since 2002. After completing
her medical training and Internship in 1991 at the
University of Cape Town, she spent ve years
working in Emergency Medicine while lecturing
in Anatomy at the University of Cape Town. She
began specialist training in Radiology at Groote
Schuur Hospital in Cape Town, joining the training program in the Department of Radiology at
King’s College in London, where she was
awarded the FRCR in 2000. She has a special
interest in the imaging of pediatric hepatobiliary
disease in particular complex hepatobiliary, pancreatic/pediatric surgical disorders and pediatric
liver transplantation and pediatric trauma. She is
the author and co-author of a number of peerreviewed publications and has lectured at national
and international meetings.
Annamaria Deganello, MD is a Consultant
Pediatric Radiologist in the Department of
Radiology at King’s College Hospital, London,
and an Honorary Senior Lecturer at King’s
College London. She qualied in 2004 from the
Faculty of Medicine and Surgery of the University
of Padova (Italy), having also trained for a year at
the Faculty of Medicine of the University of
Granada (Spain). She trained in Clinical
Radiology at the Policlinico Universitario
Hospital of Padova and at King’s College
Hospital, and she was awarded the Specialization
Diploma in Clinical Radiology in Italy in 2009.
She subspecialized in Pediatric Radiology at
King’s College Hospital and worked at the
Evelina Children’s Hospital in London. She was
appointed Consultant Radiologist at King’s
College Hospital in 2013, with a role in pediatric
radiology and hepatobiliary pediatric imaging.
About the Editors
xvii
Dr. Deganello has a special interest in the imaging of pediatric hepatobiliary diseases and liver
transplantation and pediatric trauma. She is the
author and co-author of over 40 peerreviewedpublications and book chapters; she has
been a Visiting Professor at the Children’s
Hospital of Philadelphia and an invited lecturer
for her expertise at over 30 national and international congresses. She is a member of the
Editorial Board of the Journal of Ultrasound and
a co-opted member of Council of the British
Medical Ultrasound Society.
Physics ofMicrobubble Contrast
Agents
KirstenChristensen-Jeries
andRobertJ.Eckersley
1
1.1 Introduction
Ultrasound (US) has become a routine clinical
imaging modality due to its ability to provide
safe, non-invasive, real-time images of soft tissue
structures, with costs far below that of other common clinical imaging techniques. Furthermore,
detecting blood ow in patients has been facilitated through the use of Doppler US.Nevertheless,
ow within small vessels or vessels at depth has
been limited due to the poor reectivity of blood
and the strong echoes from the tissue.
Visualization of the vasculature in clinical US
has since been greatly enhanced with the development of microbubbles as ultrasound contrast
agents (UCAs) [1–3].
Both the advancement in microbubble engineering [4] and the improved understanding of
microbubble behavior [5] has facilitated the progress of contrast-enhanced ultrasound (CEUS)
imaging into a routine diagnostic procedure [6].
Comprehensive reviews of the mechanical properties, acoustic response, application, challenges
and future directions of microbubbles have been
published, which demonstrates the wide recogni-
tion of these UCAs as a valuable diagnostic tool
[5–7]. In this chapter, a summary of the physics of
microbubbles for CEUS is provided.
1.2 Microbubble Contrast Agents
Microbubble UCAs are injected into the bloodstream to enhance the backscatter signal from the
blood. Microbubble UCAs have gained increasing interest since their introduction, and CEUS
has become a rapidly evolving eld with extensive clinical applications, including the assessment of the macro- and micro-vasculature, the
quantication of organ perfusion, and the identication and characterization of abdominal
lesions. This has been achieved due to the safe
prole and the increased stability of microbubbles, which are able to persist in the bloodstream
for several minutes. Furthermore, the availability
of specialized contrast-specic US imaging techniques has allowed considerable improvement in
the contrast resolution and signal suppression
from stationary tissues.
K. Christensen-Jeffries (*) · R. J. Eckersley
Department of Biomedical Engineering, School
of Biomedical Engineering and Imaging Sciences,
King’s College London, St Thomas’ Hospital,
London, UK
e-mail: kirsten.christensen-jeffries@kcl.ac.uk;
robert.eckersley@kcl.ac.uk
© Springer Nature Switzerland AG 2021
P. S. Sidhu et al. (eds.), Contrast-Enhanced Ultrasound in Pediatric Imaging,
https://doi.org/10.1007/978-3-030-49691-3_1
1.2.1 Ecacy ofMicrobubbles
asContrast Agents
The blood itself is a weak scatterer of US.In 1968,
before the introduction of commercial agents, the
1
2
K. Christensen-Jeries and R. J. Eckersley
increased backscattering effect caused by gas bubbles was observed during cardiac catheterization,
where gas bubbles were formed during the injection of saline solution [8]. Ultrasound insonation
of gas bubbles not only creates increased backscattering due to the presence of gas within the surrounding media, but its compressibility allows
bubbles to undergo compression and expansion in
response to the peaks and troughs of the acoustic
wave. This produces a strong backscattered signal,
which can provide a bright contrast within the
blood pool. Nevertheless, gas cavities such as
these are unstable and unlikely to survive the pulmonary circulation. Nowadays, bubbles are engineered using different shell and core compositions
to improve both their persistence in the bloodstream and their effectiveness as contrast agents.
1.2.2 Composition ofMicrobubble
Contrast Agents
Microbubble UCAs are typically 1–7 μm in size,
and are composed of a gas core encapsulated by a
shell. Currently, many engineered commercial
microbubbles are available worldwide, with
varying compositions and attributes depending
on their desired application (Table1.1).
1.2.2.1 Core
Air bubbles of this size are inherently unstable
because of the surface tension between the gas
core and surrounding liquid; the gas tries to dif-
fuse into the liquid. By using a core gas with a
lower solubility and lower diffusivity than air
(e.g., peruorocarbon or sulfur hexauoride), the
microbubble stability is increased. Commercial
agents are typically created with a low-density
gas core. This choice of gas has another benet
that it creates a large impedance mismatch
between the bubble and its surrounding media,
and thus increases the resulting backscatter when
it is hit with an ultrasound wave. At the end of the
bubble’s lifetime, this gas from the core dissolves
in the blood and is exhaled via the lungs (around
10–15min after injection).
1.2.2.2 Shell Types
The microbubble shell also helps to stabilize the
bubble. These usually have a thickness of around
10–200nm and are usually composed of biocompatible materials, including proteins, lipids, or
biopolymers [9]. These can make the shell stiff
(e.g., polymers, denaturated albumin) or exible
(e.g., phospholipids). Therefore, the properties of
the shell (as well as the gas core) affect the microbubble response to acoustic radiation. For example, stiff polymer-coated microbubbles do not
expand and contract at low acoustic pressures,
and buckle when acoustic pressure is high, while
a exible phospholipid shell will allow the microbubble to strongly oscillate in response to low
pressure acoustics without rupturing [10]. The
returning echo is thus much stronger than that
from similar- sized incompressible objects, such
as red blood cells.
Table 1.1 The core gas and shell material of commercial microbubble contrast agents
Company name Agent Gas Shell
Mallinckrodt Albunex Air (Nitrogen) Albumin
Schering Echovist Air (Nitrogen) Galactose
Levovist Air (Nitrogen) Galactose
Sonavist Air (Nitrogen) Cyanoacrylate
Quadrant Myomap Air (Nitrogen) Albumin
Quantison Air (Nitrogen) Albumin
Bracco SonoVue Sulfur hexauoride Phospholipid
BR14 Peruorobutane Phospholipid
Bristol–Myers Squibb Medical
Imaging
Alliance Imagent–Imavist Peruorohexane Phospholipid
GE Healthcare Optison Peruorobutane Albumin
Information acquired from [8]
Denity Octauoropropane Phospholipid
Sonazoid Peruorobutane Phospholipid
Phospholipid
Gas Core
Expansion
1 Physics ofMicrobubble Contrast Agents
3
1.2.2.3 Size
Microbubbles have a similar size to red blood
cells, which is advantageous for two reasons.
Firstly, this means the microbubbles remain
within the vascular space: acting as a microvascular marker and allowing multiple passages
through the lungs [1]. Secondly, their size means
they have a resonance frequency that falls within
the medical US frequency range [11], resulting in
a dramatic increase in the amplitude of their
response. This will be described further in the
following section.
1.2.3 Microbubble Behavior
inAcoustic Fields
The high compressibility typical of microbubbles means that they are capable of large volumetric oscillations in response to an acoustic
pulse [2]. When a wave hits the microbubble,
the bubble alternately compresses and expands
due to the positive and negative sections of the
wave respectively, as shown for SonoVue™
(Bracco SpA, Milan) microbubbles (Fig.1.1).
This volume pulsation causes the surrounding
medium to oscillate. The returning echo is
much stronger than that from similar-sized
incompressible objects, such as red blood cells.
1.2.3.1 Linear Response
At low acoustic pressures, the expansion and compression phases of the microbubble are equal in
response to the incident wave. This is known as linear oscillation and results in symmetrical scattered
signals with the same frequency as the transmitted
pulse. This volume pulsation is frequencydependent. Volumetric oscillations are at a maximum at a specic frequency, which is referred to as
the natural resonant frequency of the microbubble,
and this is inversely related to its size. At the resonant frequency, the microbubble absorbs and scatters sound very efciently. This is illustrated further
within models described in Sect. 1.2.4.
1.2.3.2 Nonlinear Response
If the insonation pressure is sufciently high, the
microbubble can vibrate with asymmetrical oscillations, where the expansion and compression
amplitudes become unequal [5, 12]. This “nonlinear” response to the acoustic pressure wave
generates a broad spectrum of radiated energy at
multiples and integer sub-multiples of the
insonating frequency, termed harmonics and subharmonics [11]. The nonlinear response of microbubbles is not typically shown by tissue, and thus
this offers the possibility of separating the
response of bubbles from that of surrounding tissue. There have been many signal processing
Layer
SF
6
Sulfur Hexafluride
Fig. 1.1 SonoVue™ microbubble and its response to a
sound wave. Microbubbles are comprised of a phospholipid monolayer and a sulfur hexauoride (SF6) gas core.
When insonated with an acoustic wave, the bubble under-
Acoustic
Pressure
Compression
goes compression and expansion phases, resulting in the
creation of a backscatter echo. https://kclpure.kcl.ac.uk/
portal/files/83192542/2017_Christensen_Jeffries_
Kirsten_Mia_1254928_ethesis.pdf
4
r
hs
RR
,
è
ø
--
2
42
R
R
¨
R
RR
22
ë
û
sh
,
g
.
K. Christensen-Jeries and R. J. Eckersley
techniques developed to detect these echoes,
which will be discussed in Sect. 1.3.3.
1.2.3.3 Microbubble Destruction
At even higher acoustic pressures, the microbubble shell is compromised at a threshold negative pressure and the microbubbles are
destroyed. Disruption of the microbubble shell
allows the contained gas to be released and dissolution occurs. This phenomenon, though
unfavorable in many imaging strategies, can be
advantageous in certain situations. The destruction of the microbubble causes the scattering
level to increase for a short period of time, as
well as being highly nonlinear, which can allow
its detection [13]. Furthermore, techniques
such as destruction–replenishment, where, following disruption, the replenishment of microbubble ow into a region of interest is monitored
in real time, allow the estimation of dynamic
blood ow and volume information in a tissue
region [14].
1.2.4 Models ofMicrobubble
Dynamics
Since 1917, a variety of theoretical models have
been developed to study gas bubble dynamics in
liquids. A fundamental equation of bubble
dynamics was developed by Rayleigh and Plesset
[15–18], which models the simplest case of a free
microbubble driven by a low amplitude sound
eld in an innite uid. Rayleigh-Plessetbased
equations have been used extensively in the eld
to model the behavior of contrast agents. By
neglecting liquid compressibility effects for an
unshelled bubble, and assuming that the gas pressure in the bubble is uniform and obeys the polytropic law, this can be given by:
¨
3
æ
RR Rptppt
ç
where
ö
2
and
=
÷
--
()
gi
()
0
represent respectively the rst-
+
and second-order time derivatives of the bubble
radius
, p0 is the hydrostatic pressure, pi(t) is the
incident ultrasound pressure in the liquid at an
R
(1.1)
innite distance, p
(t) is the uniform gas pressure
g
within the bubble and ρ,σ, and η are the density,
surface tension, and viscosity of the bulk uid,
respectively.
Using a small-amplitude oscillation assumption, the Rayleigh–Plesset equation has been
widely applied to study many aspects of bubble
dynamics such as acoustic scattering characteristics and thermal damping effects. Furthermore, at
these small amplitudes of displacement where the
bubble radius is approximated by simple harmonic
oscillation, the bubble will have its own resonance
frequency. When the US driving frequency is at
this resonance frequency, the bubble will oscillate
vigorously. The acoustic resonance frequency,f0,
of a single bubble can be given by [19, 20]:
é
123
f
=-
00
R
pgrg
æ
1
P
ê
ç
3
è
ù
ö
1
-
ú
÷
ø
2
æ
ö
ç
÷
r
è
ø
(1.2)
where γ is the adiabatic ideal gas constant and
P0 is the ambient uid pressure. Neglecting the
effects of surface tension and viscosity, the
expression simplies to
1
f
»
0
R
2
p
0
r
(1.3)
P
3
This shows that the resonance frequency is
inversely proportional to the bubble radius.
Indeed, such models contain many assumptions,
while real-life situations often involve more complex situations, such as those involving encapsulated bubbles traveling within small blood vessels
often containing high concentrations of red blood
cells and driven by high amplitude sound elds.
In order to accurately model the behavior of
microbubbles in vivo, and improve agreement
between theory and measurements, a series of
increasingly complex models have been developed which are not included here. These still
include a number of assumptions and simplications in each case, but may be more complete
models for specic scenarios. A Rayleigh–
Plesset-based model describing the dynamics of
encapsulated microbubbles has been developed
by Church, which relates backscatter and attenuation coefcients to shell parameters such as its
thickness and rigidity [21]. Hoff etal. [22] developed a model using viscous and elastic properties