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364 HIFU Therapy Planning Using Pretreatment Imaging and Simulation
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Acknowledgments 365
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366 HIFU Therapy Planning Using Pretreatment Imaging and Simulation
CHAPTER 14
MR-Guided HIFU for Kidney and Liver
Applications
Christakis Damianou
14.1 Introduction to HIFU
High-intensity focused ultrasound (HIFU) is a noninvasive procedure for heating
tumors without affecting the normal tissue surrounding the tumor. Therefore, applica-
tion of HIFU is being investigated as an alternative to standard surgical techniques.
Although the idea of using HIFU was proposed in the middle of the twentieth cen-
tury by Lynn et al. [1], its maximum potential for clinical use was established in the
early 1990s due to the development of sophisticated systems [2–5]. HIFU has been
proven for nearly 60 years to be an effective and efficient method for ablating soft
tissue, but its commercial success is still under trial.
The use of HIFU has been explored in almost every tissue that is accessible by ultra-
sound. Examples of some applications explored include the eye [6], prostate [7, 8], liver
[9], brain [10–12], and kidney [13–15]. Recently, the technology of HIFU systems has
been improved because advancements have been made in the use of guided imaging
with the ultrasonic therapy. Ultrasonic imaging is a simple and inexpensive method,
but it offers poor contrast between soft tissues. In contrast, MR imaging offers superior
contrast, but is more expensive. Several studies have been conducted in the area of
ultrasonic imaging [16, 17] and in the area of MR imaging [18–20], thus enhancing the
potential of HIFU.
The main goal of HIFU is to maintain a temperature between 50ºC and 100ºC
for a few seconds (typically <10 seconds) in order to cause tissue necrosis. Typically,
a focal peak intensity between 1,000 and 10,000 W/cm
2
is used with a pulse dura-
tion between 1 and 10 seconds and a frequency of 1 to 5 MHz.
This chapter focuses on the following concepts of HIFU:
1. Effect of thermal dose on attenuation.
2. Ablation of kidney without MRI guidance. This was done in order to gain
experience in kidney ablation using HIFU.
3. Ablation of kidney with MRI guidance. This was done mainly to determine
MRI parameters that improve the contrast between necrotic and normal
tissue in kidney.
367
4. Same concept as in items 2 and 3, but applied to liver tissue.
5. Investigation of the effect of tissue interfaces in HIFU ablation under MRI
guidance.
14.2 Ultrasonic System and Various Measurement Systems
14.2.1 Attenuation Measurement
The attenuation coefficient can be measured based on the transmission and recep-
tion method described by Kossoff et al. [21]. The system consists of a signal genera-
tor (HP 33120A, Hewlett Packard, now Agilent Technologies, Englewood,
Colorado), a 12-bit, 50-MHz analog-to-digital (A/D) acquisition card (CS1250,
GAGE, Lachine, Canada), and two identical flat/circular transducers made from
piezoelectric ceramic PZT4 (Etalon, Lebanon, Indiana), 10 mm in diameter. The
transducers operate at 4 MHz. Figure 14.1 shows a block diagram of the system
illustrated with actual photos of the instruments. One transducer is connected to the
signal generator and functions as the transmitter. The transmitter is attached in a
small container, which is filled with degassed water. The tissue under measurement
is placed inside the small container. In the other side of the container and opposite
the transmitter, the other transducer (receiver) is placed. The output of the receiver
is connected to the A/D acquisition card. Circulating thermally regulated water
though a heating coil controlled the temperature of the tissue. A 50-μm-diaweter
T-type copper-costantan thermocouple (Physitemp) was inserted in the tissue in
order to measure tissue temperature. Based on the elapsed time and measured tem-
perature, a thermal dose referenced at 43°C was estimated. The temperature was
measured using an HP 7500 series B system and an HP 1326B multimeter.
One useful hint when measuring attenuation is that the lower the value, the
more reliable the data. A high attenuation coefficient implies air inclusions or reflec-
tions in some interfaces, which should not be included in the ultrasonic path when
measuring a specific type of tissue.
368 MR-Guided HIFU for Kidney and Liver Applications
Signal generator
Temperature reader
A/D card
PC
Thermocoupler
T1 T2
Water
Figure 14.1 System for measuring attenuation.
14.2.2 Ultrasonic System
Figure 14.2 shows a block diagram of the HIFU system with photographs of the
actual instruments (final version assembled in May 2006). The system consists of a
signal generator (HP 33120A), an RF amplifier (LA 100-CE, Kalmus, Bothell,
Washington), a 3-D MR compatible positioning system, and a spherically shaped
bowl transducer made from piezoelectric ceramic PZT4. The transducer operates at
4 MHz, has a focal length of 10 cm, and a diameter of 4 cm. The transducer is rig-
idly mounted on the 3-D positioning system.
The 3-D MR compatible robotic system and the transducer were placed inside
an MRI scanner (Signa 1.5 T, by General Electric). The coil used was one that is
used commercially for spinal imaging. The signal generator, the RF amplifier, and
the PC were placed outside the MRI scanner.
For the kidney ablation the system was utilized outside the MRI scanner. The
system in Figure 14.2 also includes the system for monitoring cavitation (see Sec-
tions 14.7 and 14.8).
14.2.3 Acoustical Monitoring of Cavitation
For acoustical monitoring of cavitation, we used the acoustical method of Lele [22].
Figure 14.2 shows the arrangement for detecting cavitation acoustically using the
actual photographs of the devices. This method includes a receiver, which is placed
perpendicular to the beam of the HIFU transducer. Because the HIFU protocol is
applied inside the magnet of an MRI scanner, the receiver must be MR compatible.
The receiver diameter was 10 mm, its radius of curvature was 10 cm, and it oper-
ated with a bandwidth of 11 MHz. The receiver was mechanically coupled to the
14.2 Ultrasonic System and Various Measurement Systems 369
RF amplifier
Signal
generator
PC
Temperature
reader
PCI A/D
card
Interface
cables
RF
cables
Trigger
CH1
MRI room
MRI scanner
Receiver
HIFU
Positioning
device
Figure 14.2 Block diagram of the HIFU system.
HIFU transducer. The signal from the receiver was fed to the CS1250 A/D PCI card.
The A/D card was synchronized to receive the signal when the HIFU transducer was
activated. The received signal was stored in a PC.
The HIFU exposure was controlled so that the temperature never exceeded
100°C (i.e., the temperature causing boiling). Therefore, any cavities that could be
created were associated with the occurrence of cavitation and not with boiling,
which causes tissue evaporation that results in creation of cavities.
14.2.4 Software
A user-friendly program written in MATLAB was developed to control the system.
Different versions of software have been written since 1999. Figure 14.3 shows the
May 2006 version of the main window of the software. The software serves six main
tasks through various windows or menus: (1) displaying of MR images, (2) trans-
ducer movement (the user may move the robotic arm in a specific direction or cus-
tomize the automatic movement of the robotic arm in any formation by specifying
the pattern, the step, and the number of steps), (3) messaging (starting time, treat-
ment time left, and so forth), (4) patient data (age, weight, and so forth), (5) display
of motor position, and (6) display of the contents of an MR compatible camera.
14.2.5 Acoustical Field Measurement
The size of the focal region produced by this transducer was obtained by mapping
the acoustic pressure field with a needle hydrophone (Specialty Engineering Associ-
ates, San Jose, California) having an active element of 1 mm in diameter. The trans-
ducer under test was driven by a pulser/receiver (Panametrics 5050R, Waltham,
Massachusetts). The hydrophone was connected to the receiver input of the
370 MR-Guided HIFU for Kidney and Liver Applications
Figure 14.3 Latest version of the software that controls the MRI-guided HIFU system.
pulser/receiver. The output of the pulser/receiver was connected through the
CS1250 A/D card to the PC for signal processing. The transducer was moved auto-
matically by the 3-D robotic system. The block diagram of the system that measures
the acoustical field of the ultrasonic transducers is shown in Figure 14.4 and is illus-
trated with actual photographs of the instruments. Raum and O’Brien [23] describe
in more detail the principles used.
The full width at half-maximum intensity (D) of the beam was estimated from
the measured acoustical field. The spatial average in situ intensity was estimated by
the following equation:
IPD
SAL
= 087
2
.
(14.1)
where P is the acoustic power of the transducer [24]. The total power delivered by
the transducer was measured with an ultrasound power meter (UPM-DT-100N,
Ohmic Instruments, Easton, Maryland). The estimation of the spatial average
intensity is strongly affected by the measurement of D. The maximum error for the
intensity measurement was estimated to be 5%.
14.2.6 In Vitro Experiments
The tissue under ablation was placed in the water tank of the system shown in Fig-
ure 14.2. Boiling the water to 100°C degassed the water. The tissue was placed on
top of an absorbing material (rubber pad) in order to shield adjacent tissue from
stray radiation from the bottom of the plastic water tank. The transducer was
placed on the 3-D robotic arm and immersed in the water tank, thus providing good
acoustical coupling between tissue and transducer. Any bubbles that may have col-
lected under the face of the transducer were removed in order to eliminate any
reflections. The sample was gently massaged to remove any trapped air bubbles and
14.2 Ultrasonic System and Various Measurement Systems 371
Trigger
CH1
O/P
A/D acquisition card
PC
3-D robotics
3-D movement
Hydrophone
HIFU transducer
Water tank
Pulse/receiver
SYNC
Degassed water
Receive
Transmit
Figure 14.4 Acoustical field measurement system.
the experiment was initiated 10 to 20 minutes after placing the sample in the tank.
Although it is difficult to assess whether this procedure was sufficient to remove very
small air bubbles, in several samples where this procedure was not followed the
presence of air bubbles was easily detected from the resulting lesion appearance.
14.2.7 In Vivo Experiments
The coupling arrangement during animal experiments (Figure 14.5) was slightly dif-
ferent from the method used in the in vitro experiments. An 8 cm × 8cm× 10-cm
rectangular container was made out of plastic. A special holder was designed to hold
the container in the laboratory table. The top and the bottom sides of the container
were left open so that a low attenuation bag filled with degassed water could be
inserted. The transducer was placed inside the water-filled bag (on the top side). The
lower side was placed on the animal that lay on a surgical table. The animal was
shaved before the experiment. In between the shaved animal and the lower side of
the bag, ultrasound gel was placed to ensure that no localized heating at that inter-
face was produced due to reflections.
14.3 Simulation Model
14.3.1 Estimation of Temperature
The temperature versus time history was obtained by numerically solving the
bioheat equation by Pennes [25]. The explicit form of this equation is given by:
()
ρ
tt
bb
a
c
dT
dt
kTwcTT q=∇ − − +
2
(14.2)
where ρ
t
is the density of the tissue, c
t
is the specific heat of the tissue, T is the
temperature of the tissue, t is the time, k is the thermal conductivity of the tissue, w
b
is
the blood perfusion rate, c
b
is the specific heat of the blood, T
a
is the arterial bloodtem-
perature, and q is the ultrasonic absorbed power density in the tissue. The first term rep-
resents the temperature elevation, the second the conduction, and the third the
convection effect due to blood. The blood perfusion is modeled as a uniform heat sink
with blood supplied by vessels into the tissue volume at body temperature T
a
and
exiting at a tissue temperature T. The fourth term represents the absorbed power den-
372 MR-Guided HIFU for Kidney and Liver Applications
Animal
Water filled bag
Container
To HIFU system
Transducer
Figure 14.5 Experimental setup for the in vivo experiments.
sity due to the ultrasonic source. The bioheat equation was solved by using finite differ-
ence methods with spatial step of 0.1 mm and time step of 0.02 second.
14.3.2 Estimation of Thermal Dose
The effect of hyperthermia depends onthe temperature and the durationof the heat-
ing. If a constant temperature could be maintained, then the duration of heating
would be a reasonable way of expressing thermal dose, with units of time. In reality,
however, a constant temperature is not maintained, so it is necessary to find a
method of relating a treatment to an equivalent time at a specified reference temper-
ature. A mathematical relation between time and temperature was described by
Dewey et al. [26] and given by:
(
)
ttR
TT
21
21
=
−
(14.3)
where T
1
, T
2
are temperatures at times t
1
and t
2
, respectively, and R is a constant.
The calculation of the thermal dose for changing temperature exposure was
done by using the technique suggested by Sapareto and Dewey [27]. The technique
uses numerical integration to calculate the time that would give an equivalent ther-
mal dose at a reference temperature under different temperature profiles. The refer-
ence temperature of 43°C was chosen because this is the standard temperature used
as a reference [27]. For any temperature profile the dose can be found by
(
)
tRt
T
t
t
final
43
43
0
=
−
∑
Δ
(14.4)
where t
43
is the equivalent time at 43°C , T
t
is the average temperature during Δt.The
default value of R equal to 0.25 was chosen for temperatures smaller than 43°C and a
value equal to 0.5 for temperatures higher than 43°C [27]. The temperature after the
power was turned off was also considered because during the decay part of the thermal
dose is contributed.
14.3.3 Estimation of Lesion Size
The kidney attenuation used in the simulation model depended on the amount of
the accumulated thermal dose. It is known that the thermal dose threshold of necro-
sis referenced at 43°C for kidney is 50 minutes [28]. For a thermal dose below 50
minutes at 43°C, the attenuation at body temperature was used. For a thermal dose
higher than 50 minutes at 43°C, the attenuation of necrotic tissue was used (mea-
sured using the attenuation method described in this chapter).
14.3.4 Effect of Attenuation
Attenuation α affects the power deposition density Q, which is given by the follow-
ing equation:
QIe
x
=
−
2
2
α
α
(14.5)
14.3 Simulation Model 373