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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3835_Библиотеки_им_академика_М_И_Перельмана
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32 T. Ma and Q. Zhou
https://t.me/medicina_free
compared to 5 mm with the 35-MHz transducer, was observed at 90 and 120-MHz,
respectively. At the same time, the CNRs of the images at 90 and 120-MHz dropped
to 2.1 and 1.6, respectively. Figure 2.14d shows the phantom image generated by the
150-MHz transducer. Although the resolution of t he image was further improved, the
image could only penetrate less than 500 µm in depth and provided weaker contrast
for the strong acoustic reflectors, such as surface of polyimide tube and boundary
of graphite rod. Thus, it appears that transducer at such frequency is not suitable for
IVUS imaging applications.
Despite the decreased penetration depth and CNR, IVUS transducers of 90 and
120-MHz are still capable of providing valuable high-resolution information around
the inner lumen area. The fused phantom images captured by 35/90-MHz catheter
and 35/120-MHz catheter are shown in Fig. 2.15a, b, respectively. The image co-
registration in each imaging pair is accomplished by simply rotating one of the IVUS
images by 180°. These results suggest that the multi-frequency catheters can achieve
a better characterization of the artery tissue by integrating the deep imaging depth
of lower frequency transducer and high-resolution of higher frequency transducer.
To further investigatethe feasibility of the multi-frequency catheters in a setup that
is closer to the clinical settings, tissue-mimicking phantom imaging was performed
with the presence of blood. The center lumen of the phantom was filled with fresh
swine blood and the polyimide tube was still filled with DI water. As expected, a
slightly decreased penetration depth of 4 mm and a reduced CNR value of 3.2 were
obtained in the image at 35-MHz (Fig. 2.16a) due to the strong attenuation of the
blood in the lumen. As shown in Fig. 2.16b–d, the much stronger attenuation of the
higher frequency ultrasonic waves in the blood dramatically limits the imaging depth
and degrades the image quality. These results indicate that to improve imaging depth
with a high-frequency transducer may require the temporal removal of luminal blood
during the in vivo imaging, similar to the flushing mechanism in OCT, which is an
intrinsic drawback of multi-frequency IVUS imaging.
Fig. 2.15 Fused tissue-mimicking phantom images captured by a 35/90-MHz multi-frequency
IVUS catheter and b 35/120-MHz multi-frequency IVUS catheter. White color: 35-MHz ultrasound
image; orange color: 90-MHz ultrasound image; green color: 120-MHz ultrasound image; dynamic
range: 45 dB; scale bar: 1 mm (Ma et al. 2015b)
2 Advances in Multi-frequency Intravascular Ultrasound (IVUS) 33
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Fig. 2.16 Tissue-mimicking phantom images in the presence of blood at a 35-MHz, b 90-MHz,
c 120-MHz, and d 150-MHz. Dynamic range: 45 dB; scale bar: 1 mm (Ma et al. 2015b)
Fig. 2.17 IVUS images of the human coronary artery at a 35-MHz, b 90-MHz, and c 120-MHz.
Dynamic range: 50 dB; scale bar: 1 mm (Ma et al. 2015b)
Human cadaver coronary artery images acquired at 35, 90, and 120-MHz are displayed in Fig. 2.17. The 35-MHz transducer provides more complete morphological
information of the coronary artery owing to the deep penetration depth (Fig. 2.17a).
With the 90-MHz transducer, the three-layer structure (intima, media and adventitia) pointed by the red arrow is identified in Fig. 2.17b because of the improved
axial resolution. However, it is blurred and not apparent in Fig. 2.17b. In Fig. 2.17c,
although the 120-MHz transducer can only image through the intima layer due to the
limited penetration depth, an improvement in both axial resolution and lateral resolution is achieved, indicated by a reduced speckle size in the image of intima layer.
The fused image pairs acquired by the 35/90 and 35/120-MHz integrated catheters
were shown in Fig. 2.18a, b respectively. The integrated i mage pairs, combining
the advantages of the high-resolution superficial image of lumen area offered by the
high-frequency IVUS transducer (90 or 120-MHz) and the deep penetration image
of the entire artery wall provided by the low-frequency transducer (35-MHz), yield
a more comprehensive visualization of the artery wall and plaque volume.
Summary
We have successfully developed and prototyped multi-frequency IVUS imaging system catheters with three different frequency combinations prepared by PMN-PT and
34 T. Ma and Q. Zhou
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Fig. 2.18 Fused IVUS images of human coronary artery captured by a 35/90-MHz multi-frequency
IVUS catheter and b 35/120-MHz multi-frequency IVUS catheter. White color: 35-MHz IVUS
image; orange color: 90-MHz IVUS image; green color: 120-MHz IVUS image; dynamic range:
50dB;Scalebar:1mm(Maetal.2015b)
LiNbO3single-crystals. The multi-frequency IVUS catheter, with a clinical compatible size of 0.95 mm in diameter, is featured by the back-to-back arrangement of
a conventional IVUS transducer and a high-frequency IVUS transducer to achieve
accurate co-registration of two IVUS images. The performance of the high-frequency
IVUS transducer at different frequency ranges (90, 120, and 150-MHz) was evaluated
and compared to find the optimal frequency range for the high-frequency transducer
in the multi-frequency IVUS catheter, considering imaging depth, imaging resolution, and CNR. Tissue-mimicking phantom imaging with and without the presence of
blood shows that the multi-frequency catheter carries the complementary strengths
of the deep imaging depth of the conventional IVUS and the high-resolution of the
high-frequency transducer. On the other hand, these results also point out a potential
weakness of the multi-frequency catheter, which is flushing of the luminal blood is
required to ensure the functionality of this technique. The in vitro human cadaver
coronary artery imaging demonstrates the capability of the multi-frequency catheter
to provide more comprehensive visualization of the vascular structure and to facilitate the assessment of the vulnerable plaque. Compared to other multi-modality
intravascular imaging techniques, the multi-frequency IVUS imaging capitalizes the
advantage of cost-effectiveness because only a moderate modification of the current
commercial IVUS system is needed. Besides, the apparent clinical utility of this
ultrasound-only technology can be promptly explored during the translational stage
since most of the interventional physicians are familiar with the ultrasound technology.The future translation of the multi-frequency IVUS imaging into clinical use will
not only consolidate the leading status of the IVUS technology in the interventional
cardiology practice, but also prosperously lead to patient benefits.
2 Advances in Multi-frequency Intravascular Ultrasound (IVUS) 35
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Some Advances in High-Frequency IUVS
Introduction
The performance of the multi-frequency IVUS transducers used in Section “Multi-
-frequency IVUS Imaging” is summarized in Fig. 2.19, including center frequency,
imaging depth, imaging contrast, and imaging resolution. The results are in agreement with the classic ultrasound theory that increasing the center frequency of the
transducer results in better imaging resolution and decreased imaging depth. Even
though different piezoelectric materials were selected to fabricate the IVUS transducers at different center frequencies, there was still some electrical impedance mismatch between the IVUS transducers and electrical system due to the fact that the
transducer aperture size was set to be 0.5 mm. Future implementation of a matching
circuit into the system will potentially solve this issue and improve the overall performance of multi-frequency IVUS catheter. There is a significant gap between the
conventional IVUS and the competitive technology OCT, indicated by the red dot,
regarding the image resolution and penetration depth. Combining a higher frequency
IVUS transducer in a frequency range of 90–120-MHz with the conventional IVUS
catheter is a more feasible and simpler solution to reduce the controversy caused
by insufficient resolution and fill the gap between the conventional IVUS and OCT.
However, the requirement of temporal removalof luminal blood with the aim of eliminating the stronger attenuation effect for higher frequency ultrasound is a weakness
of this technology that needs to be addressed in the future. Although further increasing the center frequency of the transducer to 150-MHz or higher could theoretically
Fig. 2.19 Summaries of IVUS transducers’ performances at different center frequencies in this
study, including imaging depth, imaging contrast, and imaging resolution. Red dot: OCT; dashed
blue dot: 1-3 composite IVUS transducer (Ma et al. 2015b)
36 T. Ma and Q. Zhou
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reach the resolution level of OCT, the extremely shallow imaging depth and reduced
imaging contrast will dramatically degrade the image quality. Thus, it may not be
worthwhile to use the transducer with such high frequencies for IVUS applications.
As discussed in Section “Multi-frequency IVUS Imaging”, owing to its broadband
characteristics, the 90-MHz transducer exhibits a better axial resolution than the 120MHz transducer. This suggests that the integration of a broader bandwidth transducer
is favorable to further renovate the multi-frequency IVUS catheters.
Therefore, one direction to advance IVUS technology is to implement the stateof-the-art composite materials. The newly developed micromachined PIN-PMN-PT
single-crystal 1-3 composite transducer at 40-MHz for IVUS application, providing
an improvedaxial resolution of 43 µm and a comparable penetration depth to conventional IVUS transducers, was investigated (Li et al. 2014a; Yuan et al. 2008). For the
possible implementation of 1-3 composite material in multi-frequency IVUS imaging, the proposed 1-3 composite transducers in a frequency range of 60–90 MHz,
indicated by the blue dashed dot in Fig. 2.19, serves as a more promising substitute
for the high-frequency transducers in the multi-frequency IVUS catheters so that the
enhanced resolution can be achieved without excessively sacrificing imaging depth.
Moreover, it is the fact that lateral resolution of the multi-frequency IVUS catheter
system is almost three to four times worse than the axial resolution, which is also
the technical barrier and natural shortcoming of all other IVUS systems. The images
quality of ultrahigh-frequency IVUS in the deeper region because of the further
downgraded lateral and contrast-to-noise ration. Some beamforming techniques that
combine virtual source synthetic aperture (VSSA) focusing and coherence factor
weighting (CFW) are reported to have the possibility to improve the lateral resolution of IVUS imaging. Furthermore, as discussed previously, a further increase
of operating frequency will allow for the improvement of axial resolution, while
the penetration depth of IVUS will be sacrificed. Thus, an imaging method that
improves the penetration depth of high-resolution IVUS would also be of major
clinical importance. Modulated excitation imaging is known to allow ultrasound
waves to penetrate further. Qiu et al. recently reported an ultrasound system specifically for modulated-excitation-based IVUS imaging (Qiu et al. 2017). The system
incorporates a high-voltage waveform generator and an image processing board that
is optimized for IVUS applications. The results show that the modulated excitation
IVUS system was able to provide increases of 86.7% in penetration depth and 9.6 dB
in the signal-to-noise ratio for 60-MHz IVUS. In this section, we will introduce three
advances of ultrahigh-frequency IVUS technology including the implementation of
broadband 1-3 composite IVUS transducer to enhance axial resolution, utilization of
virtual source synthetic aperture focusing techniques to improve lateral resolution,
as well as the modulated excitation method to increase the penetration depth.
2 Advances in Multi-frequency Intravascular Ultrasound (IVUS) 37
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Development of PIN-PMN-PT 1-3 Composite IVUS
Transducer
Imaging resolution is inversely proportional to the frequency bandwidth of the transducers. Transducers with higher center frequency and broader bandwidth can provide
better image resolution (Foster et al. 2000b). In our previous work, 80-MHz IVUS
transducers were investigated and could provide axial resolution of 35 µm and penetration of 2 mm (Li et al. 2011). The fine resolution is critical for detecting certain
vulnerable plaques such as thin-cap fibroatheroma (TCFA), which has a cap thickness less than 65 µm (Kolodgie et al. 2001). The drawback of working at 80-MHz
is the shallow penetration depth resulting from the strong attenuation in blood and
vessel wall. An alternative method to improve resolution without sacrificing penetration depth is to use transducers with broader bandwidth at relatively lower frequency
(40-MHz). Moreover, a broadband transducer is advantageous for multi-frequency
signal processing to differentiate blood and vessel (Li et al. 2008).
To achieve optimal imaging performance, the piezoelectric material of
an IVUS transducer must be carefully chosen. Conventionally, Pb(Zr,Ti)O
(PZT)-based ceramics, such as PZT-5H, have been used for fabricating IVUS
transducers. Recently, binary-relaxor-based ferroelectric single-crystal
Pb(Mg
1/3Nb2/3
high-frequency ultrasonic transducers (Rhee 2007; Yuan et al. 2006). Compared
with PZT ceramics, PMN-PT crystal demonstrated improved sensitivity and bandwidth, resulting from its higher piezoelectric coefficient (d
electromechanical coupling coefficients (k
and Shrout 1997b; Tian et al. 2007a; Zhang and Shrout 2010). Ceramic or crystal
1-3 composite material exhibits even broader bandwidth than monolithic materials
because of composite’s very high coupling coefficient and low acoustic impedance
(Smith 1989). However, composites for transducers operating above 20-MHz cannot
be made using traditional dice-and-fill technique because of the thickness limitation
of the dicing saw blade, which is no less than 10 µm (Cheng et al. 2003; Zhang et al.
2011; Zhou et al. 2011a). Mechanical dicing can also produce highly stressed and
damaged surface layers, thereby degrading the properties of 1-3 composites (Lee
et al. 2010). For 1-3 composites, the frequency of the first lateral mode is empirically
expressed as
)-PbTiO3(PMN-PT) has also been investigated for fabricating
~ 2000 pm/V), and
33
~ 0.58, k33~ 0.9) (Luo et al. 2000;Park
t
3
where flis the frequency of first lateral mode resonance, VTis the shear wave
velocity of filler, and d
However, previously reported micromachined 1-3 composites were fabricated from
PMN-PT crystal. The binary PMN-PT crystal has relatively low coercive field (E
2.5 kV/cm), depoling temperature (T
130 to 178 °C) (Park and Shrout 1997a; Tian et al. 2007b; Ye and Dong 2000; Zhang
V
T
=
f
√
l
is the kerf width (Jiang et al. 2006;Tianetal.2007a).
P
2d
2
P
~ 60 to 95 °C), and Curie temperature (Tc~
R/T
~
c
38 T. Ma and Q. Zhou
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et al. 2008). Higher Ecwould allow transducers to be driven in a higher electrical
field and higher T
for a broader temperature usage range (Tian et al. 2007b; Zhang
R/T
et al. 2008). During the fabrication process, transducers are frequently incubated at
elevated temperatures (40–90 °C) for epoxy curing, wax bonding, electrode sputtering, etc., which can cause PMN-PT depoling. Depoling can make testing transducer
during fabrication inconvenient. In addition, an IVUS catheter must go through a
sterilization process before entering the market. Some sterilization processes, such
as steam sterilization, work at relatively high temperature (90 °C). After sterilization,
it is difficult to repole the IVUS transducer without taking the catheter out of the sterilized pouch. Therefore, thermal instability of PMN-PT may degrade transducers’
performance during fabrication and sterilization processes. By adding lead indium
niobate (PIN) into the PMN-PT system, the ternary crystal PIN-PMN-PT was found
to have superior electrical and thermal stability (E
to 130 °C, T
~ 160 to 200 °C) to overcome the aforementioned drawbacks, while
c
maintaining the excellent piezoelectric properties (d
~ 5.5 to 6 kV/cm, T
c
~ 900 to 1900 pm/V, k33~0.83
33
R/T
~ 120
to 0.92) (Tian et al. 2007b; Zhang et al. 2008). PIN-PMN-PT has been investigated
for high-frequency ultrasonic applications and demonstrated reduced temperature
dependence of performance and minimal depolarization during fabrication (Chen
et al. 2012; Sun et al. 2009). Composites based on PIN-PMN-PT crystal inherit the
improvements of the thermal and electrical properties (Tian et al. 2010). Considering
the merits of higher usage temperature range and coercive field, PIN-PMN-PT could
be more advantageous than PMN-PT to fabricate micromachined 1-3 composite for
high-frequency IVUS applications. In this paper, we report the use of micromachined
PIN-PMN-PT 1-3 composite material for IVUS application. Miniature side-looking
needle transducers and flexible IVUS catheters were built from the composite to operate at 40-MHz. Ex vivo experiments were conducted to demonstrate the superiority
of the composite for IVUS application.
PIN-PMN-PT crystal 1-3 composite was fabricated using inductively coupled
plasma (ICP)-enhanced DRIE technique by H. C. Materials Corp. (Tian et al. 2010).
Polished PIN-PMN-PT crystal plate was first coated with Cr/Au as the seed layer for
subsequent nickel electroplating. Photolithography was used to lay out the etching
pattern over the Cr/Au layer. A 4- to 5-µm-thick nickel mask was then electroplated
with the inverse pattern of the photoresist. Crystal parts with the patterned nickel
mask were loaded in ICP-enhanced plasma (Oxford Instruments, PlasmaLab 100,
Abingdon, Oxford, UK) for DRIE. Following etching, kerfs in the etched crystals
were filled with epoxy (EPO-TEK 301, Epoxy Technology Inc. Billerica, MA).
After epoxy cures, the composite was lapped from both sides to the final thickness.
The composite plate was sputtered with Cr/Au electrodes on both sides and then
deposited with a thick conductive backing material. A cross-sectional micrograph of
the composite on top of a thick conductive backing material is shown in Fig. 2.20.
The thickness of the composite is around 27 µm and the kerf width is less than 5 µm.
DRIE produces a near vertical etched profile with a side wall angle greater than 85°.
Side-viewing needle-type IVUS transducers and flexible catheter-type IVUS
transducers were fabricated based on the PIN-PMN-PT 1-3 composite. The measured f
was 41-MHz and BW was 86%. BW is comparable to the reported PMN-PT
c
2 Advances in Multi-frequency Intravascular Ultrasound (IVUS) 39
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Fig. 2.20 PIN-PMN-PT 1-3
composite with conductive
backing (Li et al. 2014b)
composite transducer (77–90%) (Yuan et al. 2006, 2008; Sun et al. 2010; Jiang et al.
2008), but almost doubled that of a PMN-PT crystal transducer (45%) (Zhou et al.
2007b). Tungsten wire targets with 6-µ m OD were imaged to determine axial and
lateral resolutions of the transducer, as shown in Fig. 2.21a. For comparison, the
wire targets were also imaged by a 40-MHz PMN-PT single-crystal transducer (two
2
matching layers; one backing layer; 0.5 × 0.4 mm
aperture; unfocused; 47% BW
(Zhou et al. 2007b), as shown in Fig. 2.21b. The axial and lateral resolutions were
determined from the −6 dB envelope width from the wire located at 1.3 mm, which
is close to the transducer’s natural focus (1.1 mm). For the PIN-PMN-PT composite
Fig. 2.21 Wire phantom images from a PIN-PMN-PT composite transducer; and b PMN-PT
single-crystal transducer (Li et al. 2014b)
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transducer, axial and lateral resolutions were 43 and 226 µm, respectively. For the
PMN-PT single-crystal transducer, axial and lateral resolutions were 62 and 278 µm.
As shown in Fig. 2.21, the wire phantom images of the composite transducer were
much thinner than those of the single-crystal transducer because of the improved
axial resolution. Images are displayed with 50 dB dynamic range.
An ex vivo IVUS image from the composite transducer is shown in Fig. 2.22a. For
comparison, an image of the artery from the PMN-PT crystal transducer of the same
cross section is shown in Fig. 2.22b. Both images are capable of differentiating the
thickened intima (I), media (M), and adventitia (A) layers, as well as visualizing the
calcified plaques (Ca, high-intensity areas followed by acoustic shadow). However,
because of the improved axial resolution of composite transducer, Fig. 2.22a displays
higher clarity (finer speckles) of all the three layers. The boundaries of IM and MA
(denoted by green arrows) were identifiable by the composite transducer in Fig. 2.22a
but are blurred in Fig. 2.22b and even unidentifiable at 9 to 11 o’clock. The improved
resolution is also helpful to accurately determine the percentage of calcified plaque
over the entire lumen circumference.
The micromachined PIN-PMN-PT single-crystal 1-3 composite material demonstrated improved effective electromechanical coupling coefficient k
(eff) compared
t
with monolithic single-crystal. The usage temperature of the composite is at least
30 °C higher than PMN-PT. The acoustic impedance is as low as 20 MRayl. Using
the composite, needle-type and flexible-type IVUS transducers were fabricated and
tested. 41-MHz transducers with 86% bandwidth were achieved, which resulted in
43-µm axial resolution. The characterization results of PIN-PMN-PT crystal composite showed superior piezoelectric properties which were comparable to that of
PMN-PT-based crystal composite, as well as improved thermal property compared
with that of PMN-PT based composite. PIN-PMN-PT crystal can be an alternative
approach for fabricating high-frequency composite. Ex vivo IVUS imaging was con-
Fig. 2.22 IVUS image of human coronary artery at 40-MHz from a PIN-PMN-PT composite
transducer; and b PMN-PT single-crystal transducer. I = intima; M = media; A = adventitia; Ca
= calcified plaque. Green arrows denote the boundaries of IM and MA (Li et al. 2014b)
2 Advances in Multi-frequency Intravascular Ultrasound (IVUS) 41
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ducted to demonstrate the superiority of improved axial resolution. The composite
transducer was able to identify the three layers of a human coronary artery specimen
with high definition, whereas the image from a single-crystal transducer showed
lower clarity of the layered structures.
IVUS with Virtual Source Synthetic Aperture Focusing
and Coherence Factor Weighting
As a widely recognized clinical tool for intravascular imaging and the irreplaceable
technical basis of most multi-modality intravascular imaging techniques, however,
IVUS itself still requires further improvement in the overall performance including
spatial resolution and contrast-to-noise ratio (CNR) over the whole range of interest.
Several approaches that have been reported to improve the IVUS image quality are
illustrated in Fig. 2.23 by simulating the two-way beam pattern of single-element
IVUS transducers with a 0.5-mm active aperture size in PZFlex (Weidlinger Associates, Cupertino, CA). Figure 2.23a shows the two-way beam pattern of a conventional flat 40-MHz IVUS transducer that is naturally focused at 1.7 mm. Increasing
Fig. 2.23 Simulated two-way beam patterns and −6 dB beamwidth contour (black dashed line) of
IVUS transducers with 0.5 mm active aperture size: a 40-MHz IVUS transducer with flat aperture,
b 80-MHz IVUS transducer with flat aperture, c 40-MHz IVUS transducer with mechanical focusing
at 3 mm. d Simulated beam pattern from (a) with expected −6 dB beamwidth contour (green
dash–dot line) after VSSA&CFW processing. The x-axis is lateral direction, and the z-axisisaxial
direction (Yu et al. 2017)
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