J. Biomedical Science and Engineering, 2010, 3, 241-246
doi:10.4236/jbise.2010.33032 Published Online March 2010 (http://www.SciRP.org/journal/jbise/
Published Online March 2010 in SciRes. http://www.scirp.org/journal/jbise
Evaluation of fast spin echo MRI sequence for an MRI guided
high intensity focused ultrasound system for in vivo rabbit
Nicos Mylonas1,2, Kleanthis Ioannides3, Venediktos Hadjisavvas1,4, Dimitris Iosif2,
Panayiotis A. Kyriacou1, Christakis Damianou2,4
1City University, London, UK;
2Frederick University, Limassol, Cyprus;
3Polikliniki Ygia, Limassol, Cyprus;
4MEDSONIC LTD, Limassol, Cyprus.
Email: firstname.lastname@example.org; email@example.com; firstname.lastname@example.org; email@example.com;
Received 11 December 2009; revised 28 December 2009; accepted 6 January 2010.
The effectiveness of magnetic resonance imaging
(MRI) to monitor thermal lesions created by High
Intensity Focused Ultrasound (HIFU) in rabbit liver
in vivo is investigated. The MRI sequences of T1-
weighted, and T2-weighted fast spin echo (FSE) were
evaluated. The main goal in this paper was to find the
range of repetition time (TR) and range of echo time
(TE) which maximizes the contrast to noise ratio
(CNR). An ultrasonic transducer operating at 2 MHz
was used, which is navigated using a positioning de-
vice. With T1W FSE the range of TR under which
CNR is maximized ranges from 400 to 900 ms. The
maximum contrast measured is approximately 25.
With T2W FSE the range of TE that establishes
maximum contrast is between 40 ms and 80 ms, with
CNR of approximately 14. T1W FSE is much better
than T2W FSE in detecting thermal lesions in liver.
Both T1W and T2 W FSE were proven successful to
image thermal lesions created by HIFU in rabbit
liver in vivo.
Keywords: Ultrasound; Liver; MRI; Lesion; Ablation
Surgical resection is considered the therapy of choice for
liver cancer. However, the percentage of patients who
are good candidates for surgery is low . Surgical re-
section is only feasible in 10–20% of the patients result-
ing to 5-year survival rates in the region of 40% .
Moreover, the incidence of new metastases after resec-
tion is high, and the success rate after multiple resections
is low . Because of the above disadvantages of surgi-
cal resection the development of several less invasive
local ablative therapies for liver tumors is imperative.
These approaches have included percutaneous ethanol
injection , cryotherapy , radiofrequency , mi-
crowave , and laser ablation [6,7]. These local thera-
pies have produced survival rates similar to those with
surgical resection in the treatment of metastases , but
unfortunately high local recurrence rate is also reported
Therefore thermal ablation methods could possibly
become a main treatment option for liver cancer, espe-
cially if recurrence rate is minimized. Another ablative
method that could be used for liver cancer treatment is
High Intensity Focused Ultrasound (HIFU). HIFU is the
only non-invasive local therapy to be proposed to date. If
HIFU is proven equivalent to surgical resection, this
minimally invasive approach may be able to replace
surgery as the treatment of choice.
A lot of work has been done in many directions since
the 80’s in the area of liver ablation using HIFU. The
threshold of intensity that is needed to cause irreversible
damage in liver, was suggested by Frizell et al. 1987 
and Frizell 1988 . This information is very useful,
because the intensity needed to create lesions was de-
fined. The thermal effects of HIFU in liver were well
documented by ter Haar et al. 1989 , and Sibile et al.
1993 . In the two studies by Chen et al. 1993 ,
and Chen et al. 1999 , the effect of HIFU ablation in
liver and cancerous liver using histology were analysed
extensively. The effective delivery of HIFU protocols in
real oncologigal applications of liver was achieved by
implanting tumour cells in liver [16,17,18,19,20].
This work was supported by the Research Promotion Foundation (RPF)
of Cyprus under the contract ERYAN/2004/1, ΑΝΑΒΑ Θ ΜΙΣΗ/
ΠΑΓΙΟ/0308/05, and ΕΠΙΧΕΙΡΗΣΕΙΣ/ ΕΦΑΡΜ /0308/01.
242 N. Mylonas et al. / J. Biomedical Science and Engineering 3 (2010) 241-246
Copyright © 2010 SciRes. JBiSE
Since the 90’s clinical work has been initiated for liver
cancer. Vallancien et al.  treated two patients with
solitary liver metastases prior to surgical resection. The
team headed by Wu in 1999 reported a clinical study for
treating 68 patients with liver malignancies . The
same group reported a clinical study with 474 patients
with Hepatocelular Carcinoma (HCC) treated using HIFU
in combination with transarterial chemo-embolisation
. HIFU ablation has also been used for palliation in
100 patients with advanced-stage liver cancer . Fol-
lowing treatment, symptoms, such as pain and lethargy,
were relieved in 87% of the patients.
Without an imaging system that allows for online
monitoring of the deposition of ultrasound energy or the
creation of induced lesion, it is impossible to predict the
precise location of the HIFU beam, to monitor the tem-
perature changes, or to control the deposited thermal
dose. In the past, these major constraints limited the de-
velopment of HIFU as a noninvasive surgical technique.
In recent years, however, integration of HIFU with MRI,
which allows high-sensitivity tumor detection and the
ability to monitor temperature in real time, has increased
the potentials of HIFU.
MRI-guided HIFU has generally been reserved for the
treatment of uterine fibroids  and breast adenomas
. However, it is very likely that this mode of treat-
ment monitoring and delivery will have a role in the
treatment of liver tumours. Recently, a non-randomised
clinical trial is under way  to assess the safety and
efficacy of the MRI guided HIFU system ExAblate 2000
(InSightec, Haifa, Israel) in the treatment of liver tu-
mours. It was reported that a small number of patients
has been treated to date with promising results .
The first attempt to monitor the effect of HIFU using
MRI in liver was reported by Rowland et al. 1997 ,
who demonstrated that monitoring of thermal lesions in
liver is feasible. The MRI appearance of lesions in liver
created using HIFU was also studied by Jolesz et al.
2004  and Kopelman et al. 2006 .
In this paper the goal is to investigate the effective-
ness of MRI to monitor therapeutic protocols of HIFU in
rabbit liver in vivo. The two basic and most important
MRI sequences of T1-weighted fast spin echo (FSE),
and T2-weighted FSE are investigated. The goal was to
create large lesions and use MRI to discriminate between
liver tissue and lesion. With T1W FSE the signal inten-
sity vs. repetition time (TR) is evaluated and based on
this analysis, the contrast to noise ratio (CNR) is esti-
mated, in order to find the range of TR that produces
maximum contrast. Similarly for T2W FSE the range of
echo time (TE) is found that maximizes the contrast. A
spherically focused transducer operating at 2 MHz was
used, which is navigated inside MRI using an MRI
2.1. HIFU/MRI System
Figure 1 shows the block diagram of the HIFU/MRI
system which includes the following subsystems:
a) HIFU system, b) MR imaging, c) Positioning de-
vice (robot) and associate drivers, and d) MRI compati-
2.1.1. HIFU System
The HIFU system consists of a signal generator (HP
33120A, Agilent technologies, Englewood, CO, USA), a
RF amplifier (250 W, AR, Souderton, PA, USA), and a
spherically shaped bowl transducer made from piezo-
electric ceramic of low magnetic susceptibility (Etalon,
Lebanon, IN, USA). The transducer operates at 2 MHz,
has focal length of 10 cm and diameter of 5 cm. The
transducer is rigidly mounted on the MRI-compatible
positioning system (MEDSONIC LTD, Limassol, Cy-
prus) which is described shortly.
2.1.2. MRI Imaging
The 3-d positioning device and the transducer were
placed inside a MRI scanner (Signa 1.5 T, by General
Electric, Fairfield, CT, USA). A spinal coil (USA in-
struments, Cleveland, OH, USA) was used to acquire the
2.1.3. Positioning Device/Robot Drivers
The robot has been developed initially for three de-
grees-of-freedom, but it can be easily developed for 5
degrees of motion. Since the positioning device is
placed on the table of the MRI scanner its height is
around 55 cm (bore diameter of the MRI scanner). The
length of the positioning device is 45 cm and its width
30 cm. The weight of the positioning device is only 6 kg
and therefore it can be considered portable. Figure 2
shows the schematic the positioning device illustrating
the 3 stages, transducer, and coupling method. The
Figure 1. HIFU system under MRI guidance showing the
various functionalities of the HIFU/MRI system.
N. Mylonas et al. / J. Biomedical Science and Engineering 3 (2010) 241-246
Copyright © 2010 SciRes.
Figure 2. Schematic of the robot showing all of its stages.
positioning device operates by means of 3 piezoelec-
tric motors (USR60-S3N, Shinsei Kogyo Corp., Tokyo,
Japan). More details of this positioning device can be
found in . Moreover, the positioning system in-
cludes optoelectronic encoders (not shown in any of
the figures) for providing signals indicating the rela-
tive positions of the movable elements in the position-
ing system. The resolution of all 3 axes of the posi-
tioning device is 0.1 mm.
The box hosting the motor drivers is placed outside
the MRI room since magnetic materials are involved. A
DC supply (24V, 6A) is used to drive the Shinsei drivers.
Wires from the Shinsei drivers are connected to a PCI
6602 interface card (National instruments, Austin, Texas,
USA) via a connecting block. The PCI 6602 interface
card includes timing and digital I/O modules. The inter-
face is connected in a PC (Dell Inc. Round Rock, Texas,
2.1.4. MRI Compatible Camera
In order to monitor the condition of the animal or hu-
mans (future use), an MRI compatible camera (MRC
Systems GmbH, Heidelberg, Germany) was mounted on
the system. The camera was interfaced by means of a
video card. With the aid of the MRI compatible camera,
the researcher can monitor the welfare of the animal.
2.2. In Vivo Experiments
For the in vivo experiments, New Zealand adult rabbits
were used weighting approximately 3.5-4 kg. Totally 7
rabbits were used in the experiments. The rabbits were
anaesthetized using a mixture of 500 mg of ketamine
(100 mg/mL, Aveco, Ford Dodge, IA), 160 mg of xy-
lazine (20 mg/mL, Loyd Laboratories, Shenandoah, IA),
and 20 mg of acepromazine (10 mg/mL, Aveco, Ford
Dodge, IA) at a dose of 1 mL/kg. The animal experi-
ments protocol was approved by the national body in
Cyprus responsible for animal studies (Ministry of Ag-
riculture, Animal Services).
2.3. HIFU Parameters
The in situ spatial average intensity was estimated based
on the applied power and the half-power width of the
beam of the transducer. The attenuation used was 4 Np/
m-MHz. The half-power length of the beam is 15.6 mm
and the half-power width is 1.2 mm. The details of the
intensity estimation can be found in . In order to
create large lesions, a square grid pattern of 4x4 over-
lapping lesions was used. The spacing between succes-
sive transducer movements was 2 mm, which creates
overlapping lesions for the intensity and pulse duration
used. In all the exposures the ultrasound was turn on for
5 s. The in situ spatial average intensity used was 1000
W/cm2. The delay between successive ultrasound firings
was 10 s.
2.4. MRI Processing
The following parameters were used for T1-W FSE: TR
was variable from 100-1000 ms, TE = 9 ms, slice thick-
ness = 3 mm (gap 0.3 mm), matrix = 256 × 256, FOV =
16 cm, NEX = 1, and ETL = 8. For T2-W FSE: TR =
2500 ms, TE was variable from 10 ms to 160 ms, slice
thickness = 3 mm (gap 0.3 mm), matrix = 256 × 256,
FOV = 16 cm, NEX = 1, and ETL = 8.
The contrast to noise ratio (CNR) was obtained by di-
viding the signal intensity difference between the Region
of Interest (ROI) in the lesion and in the ROI of normal
liver tissue by the standard deviation of the noise in the
ROI of normal liver tissue. The ROI was circular with
diameter of 3 mm.
The tissue temperature change (T) has been esti-
mated using the proton resonance frequency method
given by the equation stated in Chung et al. 1996
=B0T TE (1)
where is the temperature-dependent phase shift
which is the phase acquired before and during tempera-
ture elevation and which accumulates during the echo
time TE using fast spoiled gradient (FSPGR). The other
terms are which is the gyromagnetic ratio of proton,
42.58MHz/T, is the average proton resonance fre-
quency coefficient, and B0 is the flux density of the static
magnetic field. The measured temperature elevation can
be added to the base-line temperature to obtain the ab-
solute temperature. The average proton resonance fre-
quency coefficient for the frequency shift was taken to
be -0.0105ppm/oC as determined by the method de-
scribed by Vykhodtseva et al. 2000 .
The goal in this study was to use T1W FSE using dif-
ferent TR (from 100 to 1000 ms) and then evaluate the
effect of TR on the CNR. Figure 3 shows a large lesion
in liver in vivo using T1-w FSE (TR = 400 ms). This
lesion was created using in situ spatial average intensity
Y- a x i s
244 N. Mylonas et al. / J. Biomedical Science and Engineering 3 (2010) 241-246
Copyright © 2010 SciRes. JBiSE
Figure 3. Large lesion in liver in vivo using T1-w FSE.
of 1000 W/cm2 for 5 s. Since the step size of this 4 × 4
lesion was 2 mm, the size of this lesion is approximately
8 mm × 8mm. The MRI estimated maximum tempera-
ture in this lesion was 65oC. Since the estimated tem-
perature is below 100oC, the occurrence of boiling was
excluded. The thermal lesion appears bright and the con-
trast with liver tissue is excellent.
Figure 4 shows the photograph of the lesion of Fig-
ure 3 after the animal was sacrificed in a plane perpen-
dicular to the transducer face.
Figure 5 shows the CNR between lesion and liver
plotted against TR for the MRI image of Figure 3. The
same trend of CNR was seen in all the remaining 6 rab-
bits. Also the maximum CNR between liver and lesion
of the other 6 rabbits was also close to 25, and thus we
are confident that this typical graph represents the be-
haviour of CNR vs. TR for rabbit liver ablation in vivo.
The relaxation time T1 of the lesion is 250 ms, and re-
laxation time T1 of the liver is 600 ms. The proton den-
sity of the lesion increases by 20 % compared to the host
Figure 6 shows the MRI image of the lesion of Fig-
ure 3 using T1-w FSE demonstrating the excellent
propagation deep in the liver (i.e. in plane parallel to the
transducer beam axis).
The second goal in this study was to explore T2W
FSE using different TE (from 10 to 140 ms) and then
evaluate the effect of TE on the CNR. Figure 7 shows
the MRI images of the same lesion as in Figure 3 using
T2W FSE (TE = 60 ms).
Figure 8 shows the CNR between lesion and liver
plotted against TE for the liver and lesion of the MRI
image of Figure 7. The relaxation time T2 of lesion is 35
ms and the relaxation time T2 of the liver is 50 ms. The
proton density of the lesion decreases by 5 % compared
to the host tissue.
Figure 4. Photograph of the lesion of Figure 3.
0200400 600 80010001200
Figure 5. CNR vs TR.
Figure 6. MRI image of the lesion of Figure 3 using T1W FSE.
In this paper the goal was to measure the CNR of FSE
MRI sequences in detecting thermal lesions created by
HIFU in rabbit liver in vivo. Both T1-w FSE and T2-W
FSE have been proven successfully for providing ex-
cellent contrast between liver and thermal lesion in
rabbit in vivo.
The CNR with T1-w FSE is significantly higher than
N. Mylonas et al. / J. Biomedical Science and Engineering 3 (2010) 241-246
Copyright © 2010 SciRes.
Figure 7. MRI images of the same lesion as in
Figure 3 using T2W FSE.
020406080100 120 140 160
Figure 8. CNR vs TE for the MRI image shown in Figure 7.
T2-w FSE (25 with T1-w compared to 14 with T2-w).
With T1W FSE the range of TR under which CNR is
high and ranges from 400 to 900 ms. Obviously one
should use TR of 400 ms in order to minimize the imag-
ing time. Thus, the optimum TR to be used is 400 ms.
The maximum contrast measured is approximately 25.
The maximum CNR obtained for liver is the highest
we measured after 17 years of experience in this field.
The relaxation time T1 of lesion (250 ms) is much lower
than the T1 of the host tissue (liver) which is 600 ms.
The greater the difference, the greater the CNR. How-
ever, one might not ignore the significant role that the
value of proton density plays in the CNR. The proton
density of the lesion is increased by 20%.
The trend of CNR vs TR starts to increase then it be-
comes flat and then at high TRs it starts to decrease
again. This trend is justified because at low TR, the dif-
ference in signal intensity between lesion and liver is
low at the beginning and therefore CNR is lower. At
higher TR the signal intensity of lesion and tissue
reaches their maxima and therefore the signal difference
is lower and hence the CNR drops again.
With T2-w the range of TE that establishes maximum
contrast is between 40 ms and 80 ms. This range was
estimated by assuming that a CNR value of 10 is ac-
ceptable. Note that the maximum CNR value with T2-w
FSE is around 14 which is much lower than the value
obtained with T1-w FSE. The relaxation time T2 of le-
sion (35 ms) is lower than the T2 of the host tissue (liver)
which is 50 ms. Therefore, in T2 W FSE the variation of
signal intensity between lesion and liver is small (5%)
and therefore the factor dominating the CNR in T2-w
FSE is the T2 relaxation time. The trend of CNR vs TE
starts to increase then it becomes flat and then at high
TEs it starts to decrease again. The same explanation
holds as in the case of T1-w FSE.
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