Journal Papers



Y.-H. Wang and P.-C. Li
Ultrasonic Imaging
Vol. 33, pp. 189-196, July, 2011.

Ultrafast photoacoustic imaging and its application to real–time 3d imaging with improved focusing


The restricted temporal resolution of photoacoustic imaging due to limited frame rates often prohibits its applications in areas such as real-time 3D imaging. This paper presents an ultrasound/photoacoustic multimodality imaging system that provides an ultrafast frame rate and consists of an ultrasound transducer array with plane wave excitation and a laser with pulse repetition frequency up to 2000 Hz. Its application to real-time 3D photoacoustic imaging is demonstrated and a synthetic-aperture focusing technique is applied to improve the elevational focusing quality of the mechanically-scanned 1D array. A 3D frame rate of 12 Hz in a volume covering a 19.2 mm x 19.2 mm scanning surface is demonstrated.






Y.-F. Li and P.-C. Li
Ultrasonic Imaging
Vol. 33, pp. 109-118, April, 2011
Software beamforming: comparison between a phased array and synthetic transmit aperture


The data-transfer and computation requirements are compared between software-based beamforming using a phased array (PA) and a synthetic transmit aperture (STA). The advantages of a software-based architecture are reduced system complexity and lower hardware cost. Although this architecture can be implemented using commercial CPUs or GPUs, the high computation and data-transfer requirements limit its real-time beamforming performance. In particular, transferring the raw rf data from the front-end subsystem to the software back-end remains challenging with current state-of-the-art electronics technologies, which offset the cost advantage of the software back end. This study investigated the tradeoff between the data-transfer and computation requirements. Two beamforming methods based on a PA and STA, respectively, were used: the former requires a higher data transfer rate and the latter requires more memory operations. The beamformers were implemented in an NVIDIA GeForce GTX 260 GPU and an Intel core i7 920 CPU. The frame rate of PA beamforming was 42 fps with a 128-element array transducer, with 2048 samples per firing and 189 beams per image (with a 95 MB/frame data-transfer requirement). The frame rate of STA beamforming was 40 fps with 16 firings per image (with an 8 MB/frame data-transfer requirement). Both approaches achieved real-time beamforming performance but each had its own bottleneck. On the one hand, the required data-transfer speed was considerably reduced in STA beamforming, whereas this required more memory operations, which limited the overall computation time. The advantages of the GPU approach over the CPU approach were clearly demonstrated.






S.-Y. Su and P.-C. Li
Optics Express
Vol. 19, No. 2, pp.1174-1182, January, 2011
Coded Excitation for Photoacoustic Imaging Using a High-Speed Diode Lase


A Q-switched Nd:YAG laser providing nanosecond pulse durations and millijoule pulse energies is suitable for typical biomedical PA applications. However, such lasers are both bulky and expensive. An alternative method is to use a diode laser, which can achieve a higher pulse repetition frequency. Although the energy from a diode laser is generally too low for effective PA generation, this can be remedied by using high-speed coded laser pulses, with the signal intensity of the received signal being enhanced by pulse compression. In this study we tested a version of this method that employs coded excitation. A 20-MHz PA transducer was used for backward-mode PA detection. A frequency-coded PA signal was generated by tuning the interval between two adjacent laser pulses. The experimental results showed that this methodology improved the signal-to-noise ratio of the decoded PA signal by up to 19.3 dB, although high range side lobes were also present. These side lobes could be reduced by optimizing the compression filter. In contrast to the Golay codes proposed in the literature, the proposed coded excitation requires only a single stimulus.






B.-Y. Hsieh, S.-L. Chen, T. Ling, L. J. Guo, and P.-C. Li
Optics Letters
Vol. 35, No. 17, pp. 2892–2894, September, 2010
An integrated intravascular ultrasound and photoacoustic imaging scan head


The combination of intravascular ultrasound and intravascular photoacoustic imaging has been proposed for improving the diagnosis of arterial diseases. We describe a novel scan-head design for implementing  such multimodality imaging. The proposed device has   the potential to achieve a sufficiently small size for    clinical intravascular applications. The design aims for efficient image data acquisition for facilitating real-time three-dimensional imaging and reducing the required laser pulse repetition frequency. The integrated scan  head consists of a single-element, ring-shaped  transducer for sideward ultrasound transmission, a multimode fiber with a cone-shaped mirror for optical illumination, and a single polymer microring with mechanical scanning. The phantom imaging and some experimental results are presented. A microring array   can be realized in the future to achieve high-frame-rate intravascular multimodality imaging.





A.-H. Liao, C.-C. Shen and P.-C. Li
IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control
Vol. 57, No. 2, pp. 317-326, February, 2010
Potential Contrast Improvement in Ultrasound Pulse Inversion Imaging Using EMD and EEMD


Ultrasound nonlinear imaging using microbubble-based contrast agents has been widely investigated. Nonetheless, its contrast is often reduced by the nonlinearity of acoustic wave propagation in tissue. In   this paper, we explore the use of empirical mode decomposition (EMD) and ensemble empirical mode decomposition (EEMD) in the Hilbert-Huang transform (HHT) for possible contrast improvement. The HHT is designed for analyzing nonlinear and nonstationary data, whereas EMD is a method associated with the HHT that allows decomposition of data into a finite number of intrinsic modes. The hypothesis is that the nonlinear  signal from microbubbles and the tissue nonlinear signal can be better differentiated with EMD and EEMD, thus making contrast improvement possible. Specifically, we tested this method on pulse-inversion nonlinear imaging, which is generally regarded as one of the most effective nonlinear imaging methods. The results show that the contrast-to-tissue ratios at the fundamental and second-harmonic frequencies were improved by 10.2 and 4.3 dB, respectively, after EEMD. Nonetheless, image artifacts also appeared, and hence further investigation is needed before EMD and EEMD can be applied in practical applications of ultrasound nonlinear imaging





L.-C. Chen, C.-W. Wei, J. S. Souris, S.-H. Cheng, C.-T. Chen, C.-S. Yang, P.-C. Li,* and L.-W. Lo*
Journal of Biomedical Optics
Vol. 15, 016010, February, 2010
Enhanced Photoacoustic Stability of Gold Nanorods by Silica Matrix Confinement


Photoacoustic tomography (PAT) has garnered much attention for its high contrast and excellent spatial resolution of perfused tissues. Gold nanorods (GNRs) have been employed to further enhance the imaging contrast of PAT. However, the photon fluences typically needed for PA wave induction often also result in GNR shape changes that significantly reduce the efficiency of acoustic wave generation. In this work, we propose, synthesize, and evaluate amorphous silica-coated gold nanorods (GNR-Si) in an effort to improve contrast agent stability and ameliorate efficiency loss during photoacoustic (PA) wave induction. TEM and optical absorption spectra measurements of GNR and GNR-Si show that encasing GNRs within amorphous silica provides substantial protection of nanorod conformation from thermal deformation. PA signals generated by GNR-Si demonstrate considerably greater resistance to degradation of signal intensity with repetitive pulsing than do uncoated GNRs, thereby enabling much longer, high-contrast imaging sessions than previously possible. The prolongation of high-contrast imaging, and biocompatibility and easy surface functionalization for targeting ligands afforded by amorphous silica, suggest GNR-Si to be potentially significant for the clinical translation of PAT





Y.-H. Chuang, P.-W. Cheng, S.-C. Chen, J.-L. Ruan and P.-C. Li
Ultrasonic Imaging
Vol. 32, pp. 33-47, January, 2010
Effects of Ultrasound-Induced Inertial Cavitation on Enzymatic Thrombolysis


Cavitation induced by ultrasound enhances enzymatic fibrinolysis by increasing the transport of reactants. However, the effects of cavitation need to be fully understood before sonothrombolysis can be applied clinically. In order to understand the underlying mechanisms, we examined the effects of combining ultrasound, microbubbles and thrombolytic enzymes on thrombolysis. First, we evaluated the relations between inertial cavitation and the reduction in the weight of a blood clot. Inertial cavitation was varied by changing the amplitude and duration of the transmitted acoustic wave as well as the concentration of microbubbles used to induce cavitation. Second, we studied the combined effects of streptokinase and inertial cavitation on thrombolysis. The results show that inertial cavitation increases the weight reduction of a blood clot by up to 33.9%. With linear regression fitting, the measured differential inertial cavitation dose and the weight reduction had a correlation coefficient of 0.66. Microscopically, enzymatic thrombolysis effects manifest as multiple large cavities within the clot that are uniformly distributed on the side exposed to ultrasound. This suggests that inertial cavitation plays an important role in producing cavities, while microjetting of the microbubbles induces pits on the clot surface. These observations preliminarily demonstrate the clinical potential of sonothrombolysis. The use of the differential inertial cavitation dose as an indicator of blood clot weight loss for controlled sonothrombolysis is also possible and will be further explored.





S.-L. Wang and P.-C. Li
Journal of Engineering in Medicine
Vol. 224 (H2), pp. 143–154, 2010 (invited paper)
Aperture-Domain Processing and its Applications in Ultrasound Imaging: a Review

This paper provides a review of advanced algorithms for ultrasound image formation and signal processing that are based on aperture-domain data (i.e. the data recorded by individual channels prior to beam  summation). First aperture-domain data are defined and their properties described, then two specific examples of phase-aberration correction and vector velocity  estimation are presented. For phase-aberration correction, sidelobe-reduction techniques based on the coherence of the received aperture-domain data were tested with clinical breast data; the mean improvements  in the contrast and contrast-to-noise ratios were 6.9 dB and 23.2 per cent, respectively. For flow estimation, a conventional scanner can only estimate the flow velocity parallel to the beam axis. The proposed flow estimation technique uses aperture-domain data for two-dimensional flow-velocity estimation. The experimental results demonstrate that the estimation errors for the proposed technique are 2.18 per cent and 18.11 per cent in the axial and lateral velocity components, respectively. Other applications in which aperture-domain data can be used are also discussed.





S.-C. Chen, J.-L. Ruan, P.-W. Cheng, Y.-H. Chuang, and P.-C. Li
 Ultrasonic Imaging
Vol. 31, pp. 235-246, October, 2009
In vitro Evaluation of Ultrasound-Assisted Thrombolysis Using Targeted Ultrasound Contrast Agents


The thrombus-targeted ultrasound contrast agent with tirofiban, a glycoprotein IIb/IIIa antagonist that can specifically bind to activated platelets in the thrombus, was designed to enhance both the image contrast and the cavitation effect. The targeting ability to thrombi was confirmed by microphotography and high frequency ultrasound (40 MHz) images (3.34plusmn0.30 dB enhancement). Our inertial cavitation induction system showed that the enhancement of percent weight loss was about 10%, and it was further examined by using a microscope. We conclude that the targeted microbubbles are applicable not only for molecular imaging of   thrombus but also improving effectiveness of ultrasound-assisted thrombolysis





S.-L. Wang and P.-C. Li
IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control
Vol. 56, No.10, pp. 2097-2110, October, 2009
MVDR-Based Coherence Weighting for High-Frame-Rate Adaptive Imaging


Some success has been demonstrated in the extensive studies of adaptive imaging, but these approaches are generally not suitable for high-frame-rate (HFR) imaging where broad transmit beams are required. In this study, we propose an effective adaptive imaging method suitable for HFR imaging based on coherence-factor  (CF) weighting and the minimum-variance-distortionless-response (MVDR) method. The CF is an index of  focusing quality estimated from receive-channel data in which the amplitude of each image pixel is weighted by the corresponding CF so as to reduce the unwanted sidelobes. Direct implementation of CF weighting in HFR imaging does not provide satisfactory results because  the broad transmit beams required for HFR imaging reduce the accuracy of CF calculations. In this study, we alleviated this problem by applying the MVDR method. We test the proposed method with the synthetic transmit aperture method where only 8 firings are required to form an image. Both simulations and clinical breast imaging data were used, and the proposed method enhanced the mean contrast by around 4.6 dB and the mean contrast-to-noise ratio by around 20%. The results demonstrate that the proposed method is effective at improving the image quality.





L.-W. Chang, K.-H. Hsu and P.-C. Li
 IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control
Vol. 56, No.9, pp. 1856-1869, September, 2009
GPU-Based High-Frame-Rate Color Doppler Ultrasound Processing


Color Doppler ultrasound is a routinely used diagnostic tool for assessing blood flow information in real time. The required signal processing is computationally intensive, involving autocorrelation, linear filtering, median filtering, and thresholding. Because of the large amount of data and high computational requirement, color Doppler   signal processing has been mainly implemented on custom-designed hardware, with software-based implementation—particularly on a general-purpose CPU—not being successful. In this paper, we describe the use of a graphics processing unit for implementing signal-processing algorithms for color Doppler ultrasound that achieves a frame rate of 160 fps for frames comprising 500 scan lines × 128 range samples, with each scan line being obtained from an ensemble size of  8 with an 8-tap FIR clutter filter.





Y.-L. Sheu and P.-C. Li
IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control
Vol. 56, No.5, pp. 1104-1112, May, 2009
Simulations of Thermally Induced Photoacoustic Wave Propagation Using a Pseudospectral Time-Domain Method


Most physical models used to evaluate thermally induced photoacoustic waves in biomedical applications are approximations based on assumptions necessary to obtain analytical results, such as thermal and stress confinements. In contrast, using numerical methods to solve the general photoacoustic wave equations gives detailed information on the wave phenomenon without requiring as many assumptions to be made. The photoacoustic wave generated by thermal expansion is characterized by the heat conduction theorem and the state, continuity, and Navier-Stokes equations. This study developed a numerical solution in axis-symmetric cylindrical coordinates using a pseudospectral time-domain scheme. The method is efficient for large-scale simulations since it requires only 2 grid points per minimum wavelength, in contrast to conventional methods such as the finite-difference time-domain method requiring at least 10-20 grid points. The numerical techniques included Berenger's perfectly matched layers for free wave simulations, and a linear-perturbation analytical solution was used to validate the simulation results. The numerical results obtained using 4 grid points per minimum wavelength in the simulation domain  agreed with the theoretical estimates to within an  absolute difference error of 3.87 x 10(-2) for a detection distance of 3.1 mm





S. Emelianov, P.-C. Li and M. O’DDonnell
 Physics Today
pp. 34-39, May 2009.(invited paper)
Photoacoustics for Molecular Imaging & Therapy


Sound waves generated by light are the basis of a sensitive medical imaging technique with applications to cancer diagnosis and treatment.






X. Cheng, J. Chen, C. Li, J.-H. Liu, I-M. Shen and P.-C. Li
IEEE Sensors Journal
Vol. 9, No. 5, pp. 569-577, May, 2009
A Miniature Capacitive Ultrasonic Imager Array


This paper describes the development of a miniature capacitive micromachined ultrasonic transducer (CMUT) array suitable for minimally invasive medical imaging and diagnosis. In contrast to conventional laboratory-scale CMUT platforms, which are generally integrated on a silicon substrate thicker than 550 mum, this imager array is integrated on a probe shaped silicon substrate with a typical shank dimension of 60 mum(width) times 40 mum(thickness) times 4-10 mm(length) for 1-D arrays, and 0.4-2.3 mm(width) times 100 mum(thickness) times 6-12 mm(length) for 2-D arrays. Such miniature CMUT arrays are suitable for implantation into tissue through a fine incision or by being placed inside an organ for close-range imaging. In a close-range diagnosis made possible by using such miniature CMUT arrays, ultrasound of a higher frequency can be used and the conflict associated with the penetration depth and image resolution can be resolved. This imager array was fabricated using a two-layer polysilicon surface micromachining process followed by a double-sided deep silicon etching for substrate shaping. The total mask count was eight. The central frequency of ultrasound transmitted by a circular 46 mum-diameter transducer was 3.8 MHz, while its fractional bandwidth was 116% in water. A simple transducer-fluid model was used to predict the acoustic characteristics of  this device in water. Preliminary B-mode imaging using a 21-element 1-D array was demonstrated.






J.-H. Liu, S.-Y. Chen and P.-C. Li
IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control
Vol. 56, No.2, pp. 379-386, February, 2009
A Single-Element Transducer with Nonuniform Thickness for High-Frequency Broadband Applications


The design, fabrication, and evaluation of a high-frequency single-element transducer are described. The transducer has an annular geometry, with the thickness of the piezoelectric material increasing from the center to the outside. This single-element annular transducer (SEAT) can provide a broader frequency range than a conventional single-element transducer with a uniform thickness (single-element uniform transducer, or SEUT). We compared the characteristics of a SEAT and a SEUT. Both transducers used 36°-rotated, Y-cut lithium niobate (LiNbO3) material. The SEAT had a diameter of 6 mm and comprised 6 subelements of equal area (electrically connected by a single electrode on each side) whose thickness ranged from 60 μm (center) to 110 μm (outside), which resulted in the center frequency of the subelements varying from 59.8 MHz to 25 MHz. The overall center frequency was 42.4 MHz. The annular pattern was constructed using an ultrasonic sculpturing machine that reduced the root-mean-square value of the surface roughness to 454.47 nm. The bandwidth of the SEAT was 19% larger than that of the SEUT. However, compared with the SEUT, the 2-way insertion loss of the SEAT was increased by 3.1 dB. The acoustic beam pattern of the SEAT was also evaluated numerically by finite-element simulations and experimentally by an ultrasound beam analyzer. At the focus (10.5 mm from the transducer surface), the -6 dB beam width was 108 μm. There was reasonable agreement between the data from simulations and experiments. The SEAT can be used for imaging applications that require a wider transducer bandwidth, such as harmonic imaging, and can be manufactured using the same techniques used to produce transducers with multiple frequency bands.