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42 T. Ma and Q. Zhou
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the operational frequency of IVUS provides better spatial resolution within limited
depth while sacrificing the CNR, and penetration depth of IVUS images beyond that
depth (Ma et al. 2015b). The radiation pattern of a flat 80-MHz IVUS transducer is
shown in Fig. 2.23b. It can provide good resolution at 3–4 mm, but the intensity is
significantly attenuated beyond the natural focus, causing degradation in CNR.
Mechanical focusing of the IVUS transducer is another approach to achievehigher
resolution within the focus region (Lee et al. 2016). The beam pattern of a 40-MHz
IVUS transducer with a mechanical focus at 3 mm is presented in Fig. 2.23c. Since
the mechanical focal point of 3 mm is beyond the natural focal point of 1.7 mm, further mechanical focusing will only pull the focal zone toward the transducer surface,
which will in turn decrease the sensitivity and lateral resolution in the rest of field
of view (FOV) (Lee et al. 2016). As shown in Fig. 2.23c, narrow beamwidth can be
achieved at 1–2 mm, but the beam diverges beyond that region, where more artery
structure information lies. Moreover, it is practically very challenging to geometri-
2
cally focus the transducer of very small aperture size (e.g., 0.5 × 0.5 mm
).
Given the fact that increasing the center frequency and mechanical focusing
method could only improve the lateral resolution and enhance the CNR within a
certain region of FOV while downgrading the image quality outside of the focal
region, it requires an accurate alignment between the focal zone of IVUS transducer
and the region of interest. However, it is unrealizable to precisely control the exact
position of the IVUS catheter inside the coronary artery with various lumen sizes in
an actual intravascular imaging environment. In this scenario, a feasible image processing approach that will not downgrade with depth would be invaluable.Therefore,
in this study, we applied an image processing method that can enhance the image
quality of single-element IVUS transducer over the entire FOV.
Synthetic aperture focusing technique based on virtual source concept was first
proposed by Passman and Ermert to improve the image quality of strongly focused
transducer (Passmann and Ermert 1996). The virtual source concept (VSSA) focusing was further studied (Frazier and O’Brien 1998; Bae and Jeong 2000;Nikolov
and Jensen 2002) and extended to array transducers. Synthetic aperture sequential
beamforming (SASB) was developed based on the virtual source concept for array
transducers to produce high-resolution ultrasound image at a high speed and at the
same time massively reduce data load for different imaging applications (Kortbek
et al. 2013; Hansen et al. 2014; Hemmsen et al. 2014; Di Ianni et al. 2016). Based on
the assumption that the focal region can be seen as the virtual source of a spherical
wave within a certain angular range, VSSA-focusing method can increase lateral
resolution and extend imaging depth by combining adjacent scanlines that contain
information of the synthesized line (Passmann and Ermert 1996; Liao et al. 2004;
Kortbek et al. 2007). This inspires us to apply VSSA to the mechanical-state IVUS
imaging for improving lateral resolution and SNR.
Even though the VSSA-focusing method improves the resolution by synthesizing
a large aperture, it brings in higher sidelobes, which can cause unwanted artifact
(Frazier and O’Brien 1998; Karaman et al. 1995). Amplitude apodization applied on
the received data can suppress the sidelobe level and increase contrast resolution but
broadening the main lobe, orsacrificinglateral resolution (Frazier and O’Brien 1998).
2 Advances in Multi-frequency Intravascular Ultrasound (IVUS) 43
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Coherence factor based on the coherence of delayed RF signal has been used as a
focusing criterion to quantitativelyevaluatetheimagequality(MallartandFink 1994;
Hollman et al. 1999). Higher coherence factor value indicates delayed RF signals are
more coherent among each other. It has been demonstrated that weighting the delayed
beams adaptivelyusing the coherent factor can reduce the sidelobe level of the VSSAfocused radiation pattern (Li et al. 2004) and to further improve the resolution (Liao
et al. 2004). This method is called coherence factor weighting (CFW). The expected
-6 dB beamwidth contour after VSSA-CFW processing is illustrated by the green
dash–dot line in Fig. 2.23d. The application of this combined method to conventional
IVUS transducer has not yet been investigated.
In this study, the VSSA-CFW beamforming method was extended to IVUS application for improving lateral resolution and CNR through the whole FOV. The applicability of this VSSA-CFW method was first demonstrated through simulations in
Field II (Jensen and Svendsen 1992). Then, the efficacy was explored experimentally on tungsten wire phantom imaging, homogeneous agar-based phantom imaging,
anechoic cyst phantom imaging and ex vivo human artery imaging. Both simulated
and experimental results of wire target imaging demonstrate improvements in lateral
resolution. CNR improvement is also clearly shown in the anechoic cyst phantom
images. Image depth extension was quantitatively measured through in vitro imaging
of the homogeneous phantom. In the human artery image, extended image depth, and
better layer definition are achieved after image processing. To the best of our knowledge, this is the first time VSSA-CFW being used for IVUS imaging. This image
processing method can be integrated into a current imaging system to improve the
image quality of current IVUS imaging catheters. Moreover, it can further refine
the multi-modality intravascular imaging techniques to provide more accurate and
comprehensive information for vulnerable plaque identification.
The experiment results in Fig. 2.24 of rotational scanning also show an increase
in the lateral resolution over the whole imaged range. The resolution results are
summarized in Fig. 2.25. The VSSA-focusing alone does not improve the resolution
of rotational scan mode since the moderate expansion of the synthesized aperture
cannot compensate the beam divergence. However, after applying CFW, the lateral
Fig. 2.24 Experimental results of wire phantom imaging by rotational scanning. Dynamic range:
50dB;scalebar:2mm(Yuetal.2017)
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Fig. 2.25 −6 dB lateral resolution results of wire phantom images by rotational scanning (Yu et al.
2017)
resolutions increase by up to 42% for both simulation and experimental results. The
beam profile of the wire phantom clearly shows the improvement after VSSA-CFW
processing. For instance, 11 dB sidelobe suppression and 2.5° resolution increase
were obtained for the simulated point target at 3.5 mm after CFW.
The experimental result of agar-based anechoic cyst phantom imaging is shown
in Fig. 2.26. The calculated CNR values are summarized in Fig. 2.27.TheCNR
Fig. 2.26 Experimental imaging result of the two agar-based anechoic cyst phantom imaging: top
row shows phantom with 1-mm cyst at different depth; bottom row shows phantom with different
cysts at 3 mm. Dynamic range: 50 dB; scale bar: 2 mm (Yu et al. 2017)
2 Advances in Multi-frequency Intravascular Ultrasound (IVUS) 45
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Fig. 2.27 Contrast-to-noise ratio (CNR) results of the two anechoic cyst phantom images. a CNR
of 1-mm cyst at different depth. b CNR of different cysts at 3 mm (Yu et al. 2017)
improves after applying VSSA. However, the higher sidelobe still creates artifacts
within the cyst region. After applying CFW onto the VSSA focused image, the
CNR further improves, which demonstrates that CFW can effectively suppress the
sidelobes and result in a higher CNR for cyst of different sizes and at different
depths. In the VSSA-CFW image, superior CNR can be observed through the more
distinct boundary between anechoic area and surrounding agar phantom, as well as
at the boundary of the central lumen. IVUS images of the human artery are shown in
Fig. 2.28. The suppressed noise floor and enhanced resolution help to better delineate
media layer structure of the artery wall, as indicated by the yellow arrowheads.
This studydemonstrates that the beamforming method of combining virtual source
synthetic aperture and coherence factor weighting can effectively improve the overall quality of IVUS images, including lateral resolution, imaging depth and CNR.
This is for the first time, to our best knowledge, that the VSSA-CFW is applied to
single-element-based IVUS imaging. The VSSA-CFW beamforming method holds
a promising potential for clinical translation since it can be integrated into the cur-
Fig. 2.28 Experimental result of ex vivo human artery imaging: a raw image, b beamformed image
using VSSA-CFW. Dynamic range: 50 dB; scale bar: 1 mm (Yu et al. 2017)
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rent commercial IVUS imaging system readily to post-process the acquired IVUS.
In summary, VSSA-CFW can effectively improve the image quality in both crosssectional and longitudinal plane beyond the natural focal point, which ensures the full
coverage of the region of interest for vessels of different sizes. It can also be applied
to intravascular photoacoustic imaging, for which lower noise level and better lateral
resolution are highly desired (Liao et al. 2004). The improvement in image quality
will also be a benefit for those increasingly miniaturized IVUS transducers, which
is indispensable for advancing current multi-modality intravascular imaging techniques. IVUS images with improved lateral resolution, extended imaging depth, and
enhanced CNR in both cross-sectional and longitudinal view can assist cardiologists
to acquire more accurate plaque volume measurement, layer structure delineation,
and artery remodeling evaluation.
IVUS Imaging with a Modulated Excitation
TraditionalIVUS technology uses ultrasound with a center frequencyof 20−45 MHz,
but the resulting imaging spatial resolution makes it impossible to delineate the
thin cap or microvessels. A multi-modality intravascular imaging method combining ultrasound with optical coherence tomography (OCT) was employed to improve
both imaging resolution and penetration (Li et al. 2014a), but this had the disadvantage of the high costs of the catheter and the overall system. Recent progress of novel
IVUS imaging techniques has been proposed using micromachined 1-3 composite
(Li et al. 2014b; Yuan et al. 2008), and dual frequency IVUS acoustic angiography
(Ma et al. 2014;Maetal.2015a). In addition, high-frequency ultrasound was proposed for improving the imaging resolution of the IVUS method (Ma et al. 2015b).
Increasing the ultrasound frequency to more than 100-MHz enables the resolution of
IVUS to approach that of optical imaging methods. This means that IVUS could be an
alternative and cost-effective solution to replace OCT-based intravascular imaging.
However, the penetration depth i s sacrificed because the acoustic attenuation in the
tissue increases with the ultrasound frequency. An imaging method for improving
the depth of penetration would be of major clinical interest. It has been demonstrated
that modulated excitation imaging can increase the penetration depth by elongating
the ultrasound wave (Mamou et al. 2008; Qiu et al. 2013), which extends the view for
acquiring structural information of vessel walls (Maresca et al. 2012; Shekhar et al.
2016). In addition, contrast-enhanced imaging with modulated excitation was pro-
posed for visualizing the vasa vasorum using a conventional IVUS catheter (Maresca
et al. 2013). The vulnerability of the plaque could be quantified by the microvasculature within the plaque in the presence of ultrasound microbubbles. Moreover, the
signal-to-noise ratio (SNR) was increased by the application of modulated excitation to pulse-inversion tissue harmonic imaging (Park et al. 2013). The modulatedexcitation-based IVUS (ME-IVUS) imaging technique could increase the efficacy
of ultrasound in assessments of cardiovascular diseases. However, no previous study
has specifically applied high-frequency (>50-MHz) ultrasound to improve the pen-
2 Advances in Multi-frequency Intravascular Ultrasound (IVUS) 47
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etration depth in IVUS. Moreover, no study has proposed a design for a bespoke
ME-IVUS system. Published studies of modulated excitation imaging have mostly
implemented systems that combine different equipment such as commercial functional generators (from suppliers such as Agilent Technologies, Santa Clara, CA,
and B&K Precision Instruments, Yorba Linda, CA) and power amplifiers (from suppliers such as Electronics and Innovation, Rochester, NY and Amplifier Research
Corporation, Souderton, PA) (Maresca et al. 2012, 2013;Parketal.2013; Shekhar
et al. 2016). These evaluation setups were noisy, bulky, and expensive, and so an
ultrasound system specifically optimized for ME-IVUS still needs to be developed.
Qiu et al. proposed an ultrasound system specifically designed for ME-IVUS
(Qiu et al. 2017). An arbitrary-waveform generator was developed using a power
amplifier with a custom-built circuit for switching it off. A digital-to-analog converter
(DAC) and data acquisition circuitry were incorporated for pulse generation and data
processing. A normal swine thoracic aorta specimen was used to evaluate the system
in vitro. The transducer was inserted into the specimen to allow cross-sectional
imaging. Ultrasound images of an aorta fixed in a water tank are shown in Fig. 2.29,
which indicate that the penetration depth was greatly improved by using the chirpbased modulated excitation technique at both ultrasound frequencies (Increases of
Fig. 2.29 Images of a swine aorta specimen in vitro acquired using the proposed system: a 30MHz short pulse, b 30-MHz chirp, c 60-MHz short pulse, and d 60-MHz chirp. Scale bars: 2 mm;
dynamic range: 45 dB (Qiu et al. 2017)
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more than 41 and 63% in penetration depth for 30 and 60-MHz IVUS, respectively),
while the quality of the images was maintained.
This work presents a new IVUS system based on a modulated excitation imaging method. Quantitative measurements demonstrated that the SNR and penetration
depth were increased significantly: there was an improvement in the SNR of about
12 dB, while the penetration depth increased by 47.1% for the 30-MHz chirp ultrasound and 86.7% for the 60-MHz chirp ultrasound, clearly demonstrating good system performance. It would be an alternative method to see deep of the tissue with
the state-of-the-art catheter. Hydrophone scan was performed with a 3D ultrasound
intensity measurement system (UMS3, Precision acoustics, Dorchester, UK). The
peak acoustic pressure for 30-MHz IVUS transducer is about 9 kPa. There is no data
for 60-MHz probe as the hydrophone in our laboratory can only cover up to 40-MHz
ultrasound frequency. It can be predicted that the acoustic pressure is lower than
9 kPa for 60-MHz transducer. A novel ultrasound system has been proposed and
evaluated specifically for ME-IVUS, with the underlying methods, system design,
and imaging results presented in detail. The SNR and penetration depth are increased
significantly when using the proposed system. Test results show that the proposed
system is flexible, and suitable for different applications with a modulated excitation
intravascular imaging method, which could potentially increase the usefulness of
ultrasound in assessments of cardiovascular diseases.
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