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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5835_Библиотеки_им_академика_М_И_Перельмана.pdf
cular with diameter of nearly 2 mm. Regarding the T
1
-weighted FSE pulse sequence,
the best contrast is obtained with TR between 200 and 400 ms. Regarding the
T
2
-weighted FSE pulse sequence, the best contrast is obtained with TE between 16
and 32 ms.
The structure and water content of necrotic tissue is different compared to kid-
ney tissue and, as a result, the spins diphase more rapidly, resulting in a reduction of
T
2
and consequently a reduction of the signal intensity of T
2
-weighted images. Thus,
necrotic tissue appears darker than kidney tissue. The opposite happens with the
other relaxation constant (T
1
). The value of T
1
probably increases, and therefore
lesions appear brighter than kidney tissue. The increase of T
1
was reported by
Dickinson et al. [40].
The FSE methods provided very good contrast and good SNR, however the
acquisition time is long (2 to 4 minutes). Therefore, these techniques are useful for
monitoring at various instances the development of necrosis during the application
of a specific therapeutic protocol. However, to monitor the focal position (initiation
of the therapeutic protocol) a faster imaging technique is needed. To find the focal
point, a low-intensity pulse that does not causes necrosis is applied for a short period
(5 to 10 seconds), and then during that interval an image in the focal plane is
acquired. By monitoring the signal changes, it is possible to identify the location of
the focal point [15]. Fast techniques are also needed to monitor the growth of
necrosis dynamically.
The T
1
-weighted FSPGR pulse sequence was investigated for fast imaging. All
parameters used are shown in Table 14.2, row 3. Figure 14.17 shows the effect of
TR (50, 100, 150, and 300 ms) on the image quality of ablated kidney. Figure 14.18
shows various MR images (the plane is parallel to the beam) of ablation in pig kid-
ney using different ablation exposures. The lesion in Figure 14.18(a) was created
based on pure thermal mechanisms. T
2
-weighted FSE was chosen to monitor the
various HIFU exposures, because air spaces in the necrotic volume are visible, as
oppose to T
1
-weighted FSE, where the contrast between air and necrotic tissue is
poor. The lesion in Figure 14.18(b) was presumably created with stable cavitation.
384 MR-Guided HIFU for Kidney and Liver Applications
0 200
20
30
40
50
Signal intensity
60
400 600 800
TR E (ms)
020
0
10
20
30
Signal intensity
40
40 60
TR E (ms)
(a) (b)
Lesion
Lesion
Kidney
Kidney
Figure 14.16 (a) Signal intensity plotted against TR. (b) Signal intensity plotted against TE.
This is indicatedby thecavities observed in the image. The possibility that these cav-
ities were the result of airbubbles, trappedin the kidney cortex, isexcluded, because
the sample was degassed prior to the experiment. We speculate that this is the result
of stable cavitation, because there was no unexpected tissue destruction (which can
normally result because of transient cavitation). Figure 14.18(c) shows a large
lesion volume, which includes one lesion affected by transient cavitation (in situ
spatial average intensity was 4,000 W/cm
2
applied for 5 seconds). That lesion
includes violent tissue disruption, which is visible in the MR image and in the gross
examination. A huge cavity (signal enhancement) in that spot provides additional
confirmation of violent cavitation. All the parameters used are shown in Table 14.2,
row 2.
14.6 Kidney Ablation Under MRI Guidance 385
(c) (d)
(a) (b)
Figure 14.17 MR images using T
1
-weighted FSPGR. (a) TR = 50 ms. (b) TR = 100 ms. (c) TR =
150 ms. (d) TR = 300 ms.
Stable cavitation
Transient cavitation
(c)
(a) (b)
Figure 14.18 MR images of HIFU ablation using T
2
-weighted FSE demonstrating the detection of
various tissue destruction modes. (a) Thermal. (b) Stable cavitation. (c) Transient cavitation.
14.7 Liver Ablation
Liver metastases and primary liver cancer are one of the main causes of death [73].
The traditional surgical methods may be curative for some cases, but they are not
effective for all cases [74]. Therefore, research efforts in the area of HIFU ablation of
liver guided by MRI are essential.
A lot of clinical work has been done for the case of liver using laser ablation [75,
76] and for RF ablation [77]. It has been proven that thermal therapies can be uti-
lized for alternative treatments of liver cancer. Therefore, HIFU, which is the least
invasive ofall thermal therapies, can be a promising technology for thermal ablation
of liver cancer.
A lot of work has been done in many directions 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. [78, 79]. This information is very useful, because the
intensity needed to create lesions was defined. The thermal effects of HIFU in liver
have been well documented [9, 80]. Chen et al. [81, 82] analyzed extensively the
effect of HIFU ablation in liver and cancerous liver using histology. The effective
delivery of HIFU protocols in real oncological applications of liver was achieved by
implanting tumor cells in liver [83–87]. The first attempt to monitor the effect of
HIFU using MRI wasreported by Rowlandet al. [61], whodemonstrated that moni-
toring of thermal lesions in liver is feasible.
In this section the goal was to investigate the effectiveness of MRI to monitor
therapeutic protocols of HIFU in liver in vitro. The goal was to create large lesions
that included boththermal and cavitational lesions. Therefore, MRI pulse sequences
were investigated in order to discriminate between liver and lesion and between
thermal and cavitational lesions.
14.7.1 HIFU Parameters
The in situ spatial average intensity used for creating lesions was between 2,000 and
3,500 W/cm
2
for 5 seconds—an exposure that may create either thermal or
cavitational lesions. To create large lesions, a grid pattern of 4 × 4 overlapping
lesions was used. The spacing between successive transducer movements was 3 mm,
which creates overlapping lesions for the intensity and pulse duration used [88]. The
delay between successive ultrasound firings was 10 seconds.
If in a grid of, say, 4 × 4 lesions of a specific exposure, one lesion was created
under the mechanism of cavitation, then the probability of cavitation (POC) is 1/16
or 6.25%.
14.7.2 MRI Analysis
The MRI parameters used for the various pulse sequences are listed in Table 14.3.
The signal intensity was measured by placing a circular ROI of approximately 10
mm in diameter. The contrast-to-noise ratio (CNR) was obtained by dividing the
signal intensity difference between the ROI in the lesion and in the ROI of normal
liver tissue bythe standard deviation of thenoise in theROI ofnormal liver tissue.
386 MR-Guided HIFU for Kidney and Liver Applications
14.7.3 Results
Figure 14.19 shows the POC as a function of in situ spatial average intensity for a
5-second pulse duration in liver. Note that by using an intensity between 2,000 and
3,500 W/cm
2
, it is possible to create both thermal and cavitational lesions. The pre-
ferred location for cavitation lesions is at the interfaces between liver and the
water-filled blood vessels [78, 89]. The threshold of 100% cavitation in liver, which
is about 3,500 W/cm
2
, is similar to that found for kidney.
This observation is in agreement with Frizell et al. [78] who stated that what-
ever constitutes the nuclei for the cavitation events may be common to most soft tis-
sues. The POC increases with intensity, and above a certain threshold the POC is 1.
Significant POC (above 20%) is caused with an intensity above 2,500 W/cm
2
at 5
seconds. For the case of porcine liver in vitro this threshold of 100% cavitation is
about 3,500 W/cm
2
at 5 seconds. The trend of POC as a function of spatial in situ
intensity is similar to that found in the study of kidney ablation [88]. Also the length
14.7 Liver Ablation 387
50004000
35003000
25002000150010005000
0.00
0.20
0.40
0.60
0.80
1.00
POC
1.20
Intensity (W/cm )
2
Figure 14.19 POC as a function of in situ spatial average intensity for a 5-second pulse duration
in liver.
Table 14.3 Parameters Used for the Various MRI Pulse Sequences
Name TR (ms) TE (ms)
Slice
Thickness
(mm) Matrix
FOV
(cm) NEX BW (kHz) ETL
Flip
Angle
T
1
-weighted
FSE
100, 200,
300, 400,
500, 700,
1,000
9.1 3 (gap 0.3
mm)
256 × 256
16 1 31.25 8 —
T
2
-weighted
FSE
2,500 10, 15,
20, 30,
40, 45,
60
3 (gap 0.3
mm)
256 × 256
16 1 31.25 8 —
FSPGR
T
1
-weighted
50, 100,
150, 300
2.8 3 (gap 0.3
mm)
256 × 256
16 1 62.50 — 50º
of a single lesion in liver at an intensity of 2,000 W/cm
2
for 5 seconds, which is
around 20 mm, is very close to the lesion measured in kidney [88]. This is not sur-
prising because liver and kidney have similar absorption [29].
Initially, the two traditional FSE techniques (T
1
-weighted, and T
2
-weighted)
were evaluated. The T
1
-weighted FSE technique was explored by using different TR
(100, 200, 300, 400, 500, 700, and 1,000 ms). Figure 14.20(a) shows the CNR
between lesion and liver plotted against TR. All parameters used are shown in Table
14.3, row 1. The T
2
-weighted FSE technique was explored by using seven different
TE (10, 15, 20 30, 40, 45, and 60 ms). Figure 14.20(b) shows the CNR between
lesion and liver plotted against TE. All parameters used are shown in Table 14.3,
row 2. Figure 14.20(c) shows the CNR between lesion and liver plotted against TR
using T
1
-weighted FSPGR. All parameters used are shown in Table 14.3, row 3.
388 MR-Guided HIFU for Kidney and Liver Applications
11001000900800700600500400300200100
0
2
4
6
8
10
12
0
TR (ms)
(c)
(b)
(a)
TE (ms)
CNR
CNR
0
0
2
4
6
8
10
20 40 60 80
TR (ms)
CNR
0
0
2
4
6
8
100 200 300 400
Figure 14.20 (a) CNR between lesion and liver plotted against TR using T
1
-weighted FSE. (b)
CNR between lesion and liver plotted against TE using T
2
-weighted FSE. (c) CNR between lesion
and liver plotted against TR using T
1
-weighted FSPGR.
The contrast between lesion and normal liver tissue is acceptable when
T
1
-weighted FSE is used. The best contrast is observed for TR between 200 and 400
ms. This was proved by evaluating the CNR between lesion and liver as a function
of TR. The difference in the signal of the lesion and liver is significant in this range.
The window that maximizes contrast in liver is much smaller than that for kidney
[90]. MRI could detect the lesion 1 to 2 minutes after the ablation.
A similar evaluation was conducted for the T
2
-weighted FSE pulse sequence.
The best contrast can be achieved for TE up to 20 ms, with better contrast at lower
TE, indicating that pulse duration might be the best pulse sequence for the case of
liver in vitro. Similar to what was seen for T
1
-weighted FSE, the TE window that
maximizes contrast is narrow in liver compared to kidney [90]. The T
2
-weighted
FSE sequence was proven to be the best pulse sequence for detecting cavitational
activity. This advantage is attributed to the significant difference in signal intensity
between the water-filled air spaces and necrotic tissue. Water-filled air spaces
appear brighter than thermal lesions. Therefore, for therapeutic protocols created
using the cavitational mode, T
2
-weighted FSE maybe the optimum pulse sequence
to use.
Mack et al. [91] and Morrison et al. [92] have shown that T
1
and T
2
-weighted
FSE and gradient echo sequences can effectively monitor lesions created by
laser-induced thermotherapy in patients with liver cancer. Therefore, we anticipate
that the pulse sequences evaluated in this study will also be successful for treatments
in vivo. In the in vivo case, the CNR between the thermal lesion and normal liver tis-
sue will be improved by using contrast-enhanced techniques [93]. Because of the
motion artifacts, other techniques should be evaluated, for example, the fast
low-angle shot (FLASH) technique. Tsuda et al. [94] used T
1
- and T
2
-weighted FSE
to monitor lesions created in rabbit liver in vivo using RF ablation. They found that
the contrast was optimized at TR of 500 ms, which is close to what was found in our
study.
Figure 14.21(a) shows the MR image (in a plane perpendicular to the trans-
ducer beam) using T
2
-weighted FSE with TE = 15 ms. This large lesion was created
using a spatial average in situ intensity of 2,500 W/cm
2
for 5 seconds. By using this
intensity, 4 out of the 16 lesions (POC = 0.25) were created under the mechanism of
cavitation. Figure 14.21(b) shows a cavitation map, which shows a specific grid of
single lesions (volume lesion or large lesion) having four lesions, which are created
under the mechanism of cavitation. A lesion was classified as cavitational if during
the firing of the ultrasonic transducer, the frequency spectrum included
subharmonic emissions. Figure 14.21(c) shows a typical frequency spectrum during
the creation of a cavitational lesion. The cavitational map was also verified using
MRI imaging [Figure 14.21(a)] and using gross examination. With T
2
-weighted
FSE, the contrast of the cavitational lesion within the large thermal lesion is excel-
lent. The cavitational lesion appears as a scattered bright spot.
The cavitational map was also verified using MRI imaging and using gross
examination. This tool can be very useful for evaluating cavitation at different
exposures (frequency, intensity, and pulse duration) and at different locations (close
to blood vessels, interfaces, tissue type). At the moment we cannot think of any sig-
nificant use of the cavitational map in the clinical setting, but it may be a very
important research tool especially for cavitation studies.
14.7 Liver Ablation 389
Figure 14.22(a) shows the lesion in a plane parallel to the transducer beam using
T
2
-weighted FSE. This large lesion was created using a spatial in situ intensity of
2,500 W/cm
2
for 5 seconds. With this pulse sequence, it is possible to identify the
lesion created under the mechanism of cavitation. Figure 14.22(b) shows a photo-
graph after slicing. In this photograph, the void indicates a site influenced by the
mechanism of cavitation (already confirmed with harmonic emission and MRI).
14.8 Effect of Interfaces in HIFU Ablation
MRI monitoring enhances the effective application of HIFU, but issues remain to be
resolved regarding the treatment strategy. This chapter focuses on the effect of inter-
faces on the effectiveness of HIFU ablation for the case of in vivo kidney. This issue,
390 MR-Guided HIFU for Kidney and Liver Applications
0
0
20
40
60
80
(a)
(b)
(c)
Spectral power (mW)
123
45
6
7
8 9 10 11 12 13
Frequency (MHz)
TTC
C
C
C
TTTT
TT
TTT
T
Figure 14.21 (a) MR images (in a plane perpendicular to the transducer beam) of a large lesion
using T
2
-weighted FSE showing cavitational lesions. (b) Cavitational map of the large lesion. (c)
Typical frequency spectrum acquired during the occurrence of a cavitational lesion.
(a) (b)
Figure 14.22 (a) MR image (in a plane parallel to the transducer beam) of large lesion using
T
2
-weighted FSE with TE = 15 ms. (b) Photograph after slicing.
which is very critical, was never explored experimentally. Theoretically, it was
explored by Fan and Hynynen [95], who developed a computer model that takes
into account the refraction and reflection of HIFU beams at tissue interfaces.
To locate the focus point, the MRI pulse sequence T
1
-weighted FSPGR was
used. This imaging pulse sequence is the most widely accepted pulse sequence [57,
96], because it is acquired in a few seconds. Using FSPGR, the proton resonant fre-
quency is extracted, which is considered to be the most reliable method for estimat-
ing tissue temperature. FSPGR gives an indication of heating (decreased signal) and,
therefore, it is mainly used to identify the location of the focus using low intensity,
which does not cause any irreversible damage to the tissue. It can be used also to
estimate the thermal dose during the application of ultrasound [57]. In this study, it
was sufficient to study the shape of the temperature changes, which is qualitative
information adequately given by FSPGR. The accurate estimation of temperature
for quantitative information extracted from the proton resonant frequency shift,
although possibly useful for this study, was not considered. The effect of interfaces
on temperature is a subject of another study that is under way and will be analyzed
using the proton resonant frequency shift.
To create a large lesion, the transducer is scanned in a rectangular or square grid
pattern. In this study, two scans were utilized. During the first scan, low-intensity
ultrasound was used, which elevates the tissue temperature by 2ºC to 5°C. During
this diagnostic scan, FSPGR is used to indicate whether ultrasound penetration is
acceptable. Then a second scan was performed using HIFU. If, during the first scan,
all of the grid points showed a visible decrease of signal (black spot) indicating heat-
ing, then, during the second scan, lesions were created at every point in the grid. The
first scan, which is used for diagnostic purposes, is a useful tool for evaluating ultra-
sound penetration. Our intention was to use this diagnostic tool for evaluating
ultrasound penetration through an interface. The main goal in this study was to
investigate the effect of interfaces on lesion size. MRI adequately estimates the
shape of the thermal lesion. Chen et al. [59] confirmed that the lesion estimated by
MRI was in good agreement with the lesion measured using histology.
Because the studies by Coleman and Saunders [89] and Frizzell [79] showed
that at interfaces there is increased occurrence of cavitation, cavitation was moni-
tored using acoustical methods and using the MRI pulse sequence T
2
-weighted FSE,
which was proven to be a useful pulse sequence for monitoring cavitation lesions in
kidney [90].
Various studies have shown that MRI can enhance the guidance of HIFU [19,
20]. However, issues related to treatment planning remain to be resolved. Thus far,
however, many of the issues have been resolved and, therefore, the clinical applica-
tion of ultrasound has been enhanced. For example, Billard et al. [29] showed that,
by using short pulse duration, the effect of perfusion is minimized. Damianou and
Hynynen [37] and Malcolm and ter Haar [24] demonstrated that the right spacing
of the transducer must be used in order to create complete necrosis. Hynynen [38]
suggested that, by using a higher frequency, the threshold of cavitation will be
higher and therefore cavitation can be avoided. Hynynen et al. [97] showed that
ultrasound can penetrate through the intact skull, by using the appropriate ablating
techniques. These are only few examples of studies that focus on treatment plan
-
ning. We believe that treatment planning is now the major area to be resolved in
14.8 Effect of Interfaces in HIFU Ablation 391
order to convince clinicians about the effectiveness of HIFU. In this section, particu-
lar attention is given to the problem of interfaces. For the case of kidney, two types
of interfaces are usually encountered: muscle–kidney and fat–kidney interfaces.
14.8.1 MRI Analysis
Two different pulse sequences were used: T
1
-weighted FSPGR for fast imaging and
T
2
-weighted FSE for high-quality imaging. The following parameters were used for
T
1
-weighted FSPGR: TR = 50 ms, TE = 2.7 ms, FOV = 16 cm, matrix = 256 × 256,
flip angle = 50°, BW = 62.5 kHz, and NEX = 1. The following parameters were used
for T
2
-weighted FSE: TR = 2,500 ms, TE = 32 ms, FOV = 16 cm, matrix = 256 × 256,
ETL = 8, BW = 31.25 kHz, and NEX = 1. The evaluation of temperature in fat was
monitored using the MRI methods described by Hynynen et al. [62].
14.8.2 Results
Figure 14.23 shows an MR image using a T
2
-weighted FSE of lesions in a plane per-
pendicular to the beam, in rabbit kidney in vivo using different in situ spatial aver-
age intensities (1,000, 1,500, 2,500, and 3,500 W/cm
2
). Note that, with 3,500
W/cm
2
, the lesion was created under the mechanism of cavitation.
To estimate the POC through an interface, multiple lesions were created by
moving the transducer in a grid formation (5 × 4). The spacing between the lesions
was 5 mm, so as to create discrete lesions. The pulse duration was 5 seconds. The
spatial average intensity was varied for each set of discrete lesions. The intensities
were varied between 500 and 4,000 W/cm
2
, with a step of 500 W/cm
2
. If, out of the
20 lesions, 1 is created under the mechanism of cavitation, then the POC is 5%. The
cavitation was confirmed by using four different methods: MRI imaging, detection
of harmonic emission, temperature monitoring, and gross examination. Figure
14.24 shows the POC as a function of intensity at 5 seconds, through a muscle kid-
ney interface. In the same figure the POC is plotted for kidney in vitro from a previ-
ous study [90] for the same pulse duration (5 seconds) and frequency (4 MHz).
Figure 14.25 shows nine MRI images in a plane perpendicular to the beam
acquired by using T
1
-weighted FSPGR. The transducer was moved in a 3 × 3 pattern
and the intensity used was 100 W/cm
2
for 10 seconds. This intensity was used in Sec-
tion 14.5 in vitro and the produced temperature was 2ºC to 5°C, which means that
392 MR-Guided HIFU for Kidney and Liver Applications
Figure 14.23 Lesions in kidney at different spatial average in situ intensities (1,000, 1,500, 2,500,
and 3,500 W/cm
2
).
there was no tissue damage with this exposure. These images show that in every one
of the ninefirings, there is good penetration, because heating is observed (black spot
of 1 to 2 mm in diameter). Therefore, this proves that ultrasound penetration
through this particular muscle–kidney interface is excellent in all nine locations.
Following this diagnostic scan, the intensity was increased to 1,500 W/cm
2
and the
nine locations were ablated using a 5-second pulse.
14.8 Effect of Interfaces in HIFU Ablation 393
50004000
35003000
2500
Through
In vitro
2000150010005000
0.00
0.20
0.40
0.60
0.80
1.00
POC
1.20
Intensity (W/cm )
2
Figure 14.24 POC as a function of in situ spatial average intensity for 5-second pulse duration in
kidney in vitro and kidney in vivo through muscle-kidney interface.
Figure 14.25 MR images using T
1
-weighted FSPGR of the focus beam during a 3 × 3 scanning
process that used low intensity.