Biomedical subjects

Pai-Chi Li

Publications and source records attributed to Pai-Chi Li.

At least 19 recordsLinked to original sources

PubMed2007

Estimating the blood velocity vector using aperture domain data.

Most conventional blood flow estimation methods measure only the axial component of the blood velocity vector. In this study, we developed a new method for two-dimensional (2-D) velocity vector estimation in which time shifts resulting from blood motion are calculated for the individual channels using aperture domain data. This allows the construction of a time-shift profile along the array direction as a function of channel index, which is approximated by a first-order polynomial whose zeroth-order and first-order terms can be used to determine the axial and lateral velocity components, respectively. The efficacy of the proposed method was verified by simulations and experiments in which the transducer array had 64 elements, an aperture size of 1.96 cm, and a center frequency of 5 MHz. The flow velocity ranged from 5 to 35 cm/s and the Doppler angle ranged from 0 degrees to 90 degrees. The experimental results show that the accuracy of axial velocity estimation is higher for the new method than for the autocorrelation-based conventional method when the signal-to-noise ratio is larger than 0 dB. The mean estimation error for the axial velocity component is 2.18% for the new method, compared to 4.51% for the conventional method. The mean estimation error for the lateral velocity component is 15%, which is comparable to existing methods.

Algorithms↗

PubMed2006

Mechanical unfolding of segment-swapped protein G dimer: results from replica exchange molecular dynamics simulations.

The protein G dimer (pdb code 1Q10) is a mutated dimeric form of the immunoglobulin-binding domain B1 of streptococcal protein G, in which the two monomeric units have swapped elements of their secondary structure. We have used replica exchange molecular dynamics simulations to study how this dimer responds to a mechanical force that pulls the N-terminus of one unit and the C-terminus of the other apart. We have further compared the mechanical response of the dimer to that of the protein G monomer. When the pulling force is low enough, the mechanical unfolding can be viewed as a thermally activated barrier crossing process. For each protein, we have computed the corresponding free energy barrier and its dependence on the pulling force. While the dimer is found to be less resistant to mechanical unfolding than its monomeric counterpart, the two proteins exhibit essentially the same mechanical unfolding mechanism involving separation of the terminal parallel strands. On the basis of our results, we speculate that the mechanical properties of natural adhesives, composites, fibers, and other materials may be optimized not only at a single molecule level but also at the mesoscopic level through the interactions among individual chains.

Bacterial Proteins↗

PubMed2006

Quantitative relations of acoustic inertial cavitation with sonoporation and cell viability.

Ultrasound-induced acoustic cavitation assists gene delivery, possibly by increasing the permeability of the cell membranes. How the cavitation dose is related to the sonoporation rate and the cell viability is still unknown and so this in vitro study quantitatively investigated the effects of cavitation induced by 1-MHz pulsed ultrasound waves and the contrast agent Levovist (containing microbubbles when reconstituted by adding saline and shaken) on the delivery of short DNA-FITC molecules into HeLa cells. The concentrations of cells and DNA-FITC were 2 x 10(5) cells/mL and 40 microg/mL, respectively. The cavitation was quantified as the inertial cavitation dose (ICD), corresponding to the spectral broadband signal enhancement during microbubble destruction. The relations of ICD with sonoporation and cell viability were examined for various acoustic pressures (0.48-1.32 MPa), Levovist concentrations (1.12 x 10(5)-1.12 x 10(7) bubbles/mL) and pulse durations (1-10 cycles). The linear regressions of the sonoporation rate versus ICD and the cell viability versus ICD were y = 28.67x + 10.71 (R(2) = 0.95) and z = -62.83x + 91.18 (R(2) = 0.84), respectively, where x is ICD, y is the sonoporation rate and z is the cell viability. These results show that the sonoporation rate and the cell viability are highly correlated with the ICD, indicating that sonoporation results may be potentially predicted using ICD.

Cell Membrane Permeability↗

PubMed2006

Photoacoustic flow measurements with gold nanoparticles.

The hypothesis that quantitative blood flow measurements are feasible with the time-intensity based method in photoacoustic imaging using gold nanoparticles as contrast agent is experimentally tested. The in vitro results show good linearity between the measurements and the theory, thus suggesting the potential of relative photoacoustic flow measurements with gold nanoparticles.

Letter↗

PubMed2006

Arbitrary waveform coded excitation using bipolar square wave pulsers in medical ultrasound.

This paper presents a new coded excitation scheme that efficiently synthesizes codes for arbitrary waveforms using a bipolar square wave pulser. In a coded excitation system, pulse compression is performed to restore the axial resolution. In order to maintain low range sidelobes, the system needs to transmit signals that have smooth spectra. However, such a transmitter requires the generation of arbitrary waveforms and, therefore, is more expensive. In other words, a trade-off is necessary between the compression performance and the transmitter cost. Here we propose a method that preserves the low-cost advantage of a bipolar pulser while achieving approximately the same compression performance as an arbitrary waveform generator. The key idea of the proposed method is the conversion of a nonbinary code (i.e., requiring an arbitrary waveform generator) with good compression performance into a binary code (i.e., requiring only a bipolar pulser) by code translation and code tuning. The code translation is implemented by sending the nonbinary code into a virtual one-bit, sigma-delta modulator, and the code tuning involves minimizing the root-mean-square error between the resultant binary code and the original nonbinary code by sequential and iterative tuning while taking the transducer response into account. Tukey-windowed chirps are known to have good compression performance. Such chirps of different durations (16, 20, and 24 micros), all with a taper ratio of 0.15, a center frequency of 2.5 MHz, and an equivalent bandwidth of 1.5 MHz, were converted into binary Tukey-windowed chirps that were compared with pseudochirps (i.e., direct binary approximations of the original chirp) over the same spectral band. The bit rate was 40 MHz. Simulation results show that the use of binary Tukey-windowed chirps can reduce the code duration by 20.6% or the peak sidelobe level by 6 dB compared to the commonly used pseudochirps. Experimental results obtained under the same settings were in agreement with the simulations. Our results demonstrate that arbitrary waveform coded excitation can be realized using bipolar square wave pulsers for applications in medical ultrasound.

Algorithms↗

PubMed2006

Vector-velocity estimation in swept-scan using a K-space approach.

The swept-scan technique (i.e., continuously moving a single-crystal transducer during pulse-echo data acquisition) is used in high-frequency, ultrasonic flow imaging. Relative to the conventional step-scan technique, swept scanning improves the rate of data acquisition and enables near-real-time, high-frequency color flow mapping. However, the continuous transducer movement may have non-negligible effects on accuracy of velocity estimation. This paper introduces a spatial frequency domain (i.e., k-space) approach that quantifies the effects of both lateral and axial motions in a swept scan. It is shown that the k-space representation is equivalent to a Doppler-radio frequency (RF) frequency domain representation, and that transducer movement in the swept-scan technique results in a change in Doppler bandwidth. In addition, a vector velocity estimator is developed based on the proposed k-space approach. Both simulations and flow-phantom experiments were performed to evaluate the performance of the proposed vector velocity estimator. A 45-MHz transducer was scanned at 20 mm/s. The Doppler angle ranged from 29 degrees to 90 degrees, and the flow velocities ranged from 15 to 30 mm/s. The results show that the proposed k-space vector velocity estimator exhibited a mean error of 2.6 degrees for flow-direction estimation, with the standard deviation ranging from 2.2 degrees to 8.2 degrees. In comparison, for the conventional spectral-broadening-based vector velocity estimator ignoring the swept-scan effect, the mean error became 15 degrees and the standard deviations were from 2.7 degrees to 6.6 degrees.

Algorithms↗

PubMed2006

ECG triggering and gating for ultrasonic small animal imaging.

Echocardiography (ECG) is routinely used in the clinical diagnosis of cardiac function. The anatomy of the mouse is similar to that of the human, and thus murine ECG has become an effective tool for the assessment of small animal models of human cardiac diseases. Unfortunately, clinical ultrasonic imaging systems are not suitable for murine cardiac imaging due to their limited spatial and temporal resolutions. Murine ECG requires a spatial resolution better than 100 pim, which mandates the use of high-frequency, ultrasonic imaging (i.e., >20 MHz). High-frequency transducer arrays currently are not available, and so such systems use the mechanical scanning of a single-element transducer for which the frame rate is insufficient for directly monitoring the rapid beating of a mouse heart, and thus retrospective image reconstruction is necessary. This paper presents a high-frequency, ultrasonic imaging system for murine cardiac imaging. Two scanning methods have been developed. One is based on ECG triggering and is called the block scanning mode, in which the murine cardiac images from the isovolumic contraction and isovolumic relaxation phases are retrospectively reconstructed within a relatively short data acquisition time using the ECG R-wave as the trigger to the imaging system. The other method is the line scanning mode based on ECG gating, in which both ECG and ultrasound scan lines are continuously acquired over a longer time, enabling images during the entire cardiac cycle to be obtained. It is demonstrated here that the effective frame rate is determined by the pulse repetition frequency and can be up to 2 kHz in the presented system.

Animals↗

PubMed2006

Waveform design for ultrasonic pulse-inversion fundamental imaging.

Pulse-inversion (PI) fundamental imaging exhibits significantly better contrast detection than linear and second-harmonic imaging. PI fundamental imaging involves two firings with inverted waveforms. When the returning echoes from the two firings are summed, the residual signal related to tissue is limited to even-order harmonics, whereas for microbubbles, the fundamental signal is not completely canceled due to the echo under compression differing from that under rarefaction. The efficacy of PI fundamental imaging has been reported previously. In this study, we investigated the performance of PI fundamental imaging using both simulations and in vitro experiments with various transmit waveforms, including coded excitation and asymmetrical waveforms (i.e., asymmetrical between compression and rarefaction). For coded excitation, a longer waveform was found to increase the similarity in the responses to positive and negative pulses, thus lowering the contrast between microbubbles and tissue. In addition, imperfect pulse compression also decreases the contrast because it increases the residue fundamental signal emanating from tissue. Using asymmetrical waveforms noticeably increased the residual microbubble signal in the fundamental band but the nonzero DC component that is inherent in such waveforms also increases the tissue fundamental signal. The combination of these two effects decreases the contrast. From these results, it is concluded that the use of coded excitation is undesirable in PI fundamental imaging and that the waveforms should contain no DC component. Furthermore, the transmit waveform needs to be appropriately windowed in order to reduce spectral leakage. Therefore, a Gaussian pulse with the pulse length determined by the signal-to-noise ratio of the imaging system is generally optimal for PI fundamental imaging.

Artifacts↗

PubMed2005

Photoacoustic flow measurements by use of laser-induced shape transitions of gold nanorods.

A quantitative technique for flow measurements based on a wash-in analysis is proposed. The technique makes use of the shape dependence of the optical absorption of gold nanorods and the transitions in their shape induced by pulsed laser irradiation. The photon-induced shape transition of gold nanorods involves mainly a rod-to-sphere conversion and a shift in the peak optical absorption wavelength. The application of a series of laser pulses will induce shape changes in gold nanorods as they flow through a region of interest, with quantitative flow information being derived from the photoacoustic signals from the irradiated gold nanorods measured as a function of time. To demonstrate the feasibility of the technique, a Nd:YAG laser operating at 1064 nm was used for irradiation and a 1 MHz ultrasonic transducer was used for acoustic detection. The flow velocity ranged from 0.35 to 2.83 mm/s. Excellent agreement between the measured velocities and the actual velocities was demonstrated, with a linear regression correlation coefficient of 0.93. This study is a pioneer work on wash-in flow estimation in photoacoustic imaging.

Acoustics↗

PubMed2005

Liver steatosis classification using high-frequency ultrasound.

High-frequency B-mode images of 19 fresh human liver samples were obtained to evaluate their usefulness in determining the steatosis grade. The images were acquired by a mechanically controlled single-crystal probe at 25 MHz. Image features derived from gray-level concurrence and nonseparable wavelet transform were extracted to classify steatosis grade using a classifier known as the support vector machine. A subsequent histologic examination of each liver sample graded the steatosis from 0 to 3. The four grades were then combined into two, three and four classes. The classification results were correlated with histology. The best classification accuracies of the two, three and four classes were 90.5%, 85.8% and 82.6%, respectively, which were markedly better than those at 7 MHz. These results indicate that liver steatosis can be more accurately characterized using high-frequency B-mode ultrasound. Limitations and their potential solutions of applying high-frequency ultrasound to liver imaging are also discussed.

Fatty Liver↗

PubMed2005

Optical piezoelectric transducer for nano-ultrasonics.

Piezoelectric semiconductor strained layers can be treated as piezoelectric transducers to generate nanometer-wavelength and THz-frequency acoustic waves. The mechanism of nano-acoustic wave (NAW) generation in strained piezoelectric layers, induced by femtosecond optical pulses, can be modeled by a macroscopic elastic continuum theory. The optical absorption change of the strained layers modulated by NAW through quantum-confined Franz-Keldysh (QCFK) effects allows optical detection of the propagating NAW. Based on these piezoelectric-based optical principles, we have designed an optical piezoelectric transducer (OPT) to generate NAW. The optically generated NAW is then applied to one-dimensional (1-D) ultrasonic scan for thickness measurement, which is the first step toward multidimensional nano-ultrasonic imaging. By launching a NAW pulse and resolving the returned acoustic echo signal with femtosecond optical pulses, the thickness of the studied layer can be measured with <1 nm resolution. This nano-structured OPT technique will provide the key toward the realization of nano-ultrasonics, which is analogous to the typical ultrasonic techniques but in a nanometer scale.

Electrochemistry↗

PubMed2005

Ultrasonic computed tomography reconstruction of the attenuation coefficient using a linear array.

The attenuation coefficient distribution and sound velocity distribution in the breast can be used to complement B-mode ultrasound imaging in the detection of breast cancer. This study investigated an approach for reconstructing the attenuation coefficient distribution in the breast using a linear array. The imaging setup was identical to that for conventional B-mode breast imaging, and the same setup has been used for reconstruction of sound velocity distributions in previous studies. In this study, we further developed a reconstruction method for the attenuation coefficient distribution. In particular, the proposed method incorporates the segmentation information from B-mode images and uses the sound velocity distribution to compensate for refraction effects. Experiments were conducted with a setup consisting of a 5-MHz, 128-channel linear array, a programmable digital array system, a phantom, and a computer. The constructed phantom contained materials mimicking the following breast tissues: glandular tissue, fat, cysts, high-attenuation tumors, and irregular tumors. Application of the proposed technique resulted in all the cysts and tumors (including high-attenuation and irregular tumors) being distinguished by thresholding the reconstructed attenuation coefficients. We have demonstrated that it is possible to use the same imaging setup to acquire data for B-mode image, sound velocity distribution, and attenuation coefficient distribution simultaneously. Moreover, the experimental data indicate its potential in improving the detection of breast cancer.

Algorithms↗

PubMed2005

Simulations of optoacoustic wave propagation in light-absorbing media using a finite-difference time-domain method.

Optoacoustic (OA) imaging is an emerging technology that combines the high optical contrast of tissues with the high spatial resolution of ultrasound. Taking full advantage of OA imaging requires a better understanding of OA wave propagation in light-absorbing media. Current simulation methods are mainly based on simplified conditions such as thermal confinement, negligible viscosity, and homogeneous acoustic properties throughout the image object. In this study a new numerical approach is proposed based on a finite-difference time-domain (FDTD) method to solve the general OA equations, comprising the continuity, Navier-Stokes, and heat-conduction equations. The FDTD code was validated using a benchmark problem that has an approximate analytical solution. OA experiments were also conducted and data were in good agreement with those predicted by the FDTD method. Characteristics of simulated OA waveforms and OA images were discussed. The simulator was also employed to study wavefront distortion in OA breast imaging.

Acoustics↗

PubMed2005

Effects of swept scanning on velocity estimation.

The swept-scan technique adopted in high-frequency ultrasound involves mechanically scanning a single-element transducer to acquire image data. Unlike conventional step scanning, where the image data are acquired at discrete positions, the swept-scan technique acquires the image data while the transducer is continuously moving. Such a scanning method is particularly advantageous for Doppler flow estimation because its frame rate is higher than that for the step-scan technique. However, the effects of the transducer motion on the accuracy of velocity estimation have not been studied comprehensively. This study employed a k-space approach to experimentally investigate the effects of swept scanning on both conventional Doppler axial velocity estimation and spectral-broadening-based lateral velocity estimation using a 45-MHz transducer. The results indicate that such effects must be corrected in order to obtain an accurate estimation of flow velocities.

Blood Flow Velocity↗

PubMed2005

Adaptive imaging using an optimal receive aperture size.

Sidelobe contribution from off-axis targets degrades image quality in a coherent array imaging system. In ultrasound imaging, focusing errors resulting from sound-velocity inhomogeneities in human tissue--also known as phase aberrations reduce the coherence of the received signals and elevate the sidelobe level. This paper proposes an adaptive receive-aperture technique based on thresholding of the coherence factor (CF). The CF describes the coherence of the received array signals and can be used as an index of focusing quality. This paper demonstrates that thresholding of the CF allows the mainlobe-dominated signals to be distinguished from the sidelobe-dominated signals, after which the receive-aperture size at each imaging position can be optimally determined so as to enhance the mainlobe-dominated signals and suppress the sidelobe-dominated signals. Thus, image quality degradation resulting from sound-velocity inhomogeneities can be reduced. Simulations and measured ultrasound data are used to evaluate the efficacy of the proposed technique. The characteristics of the proposed technique including the effects of the signal-to-noise ratio (SNR) and the transmit focal depth, and speckle reduction are discussed. The proposed technique is also compared with the parallel adaptive receive compensation algorithm and shown to produce a better improvement in image quality.

Algorithms↗

PubMed2004

Simulation of the mechanical unfolding of ubiquitin: probing different unfolding reaction coordinates by changing the pulling geometry.

Motivated by the recent experimental atomic force microscopy (AFM) measurements of the mechanical unfolding of proteins pulled in different directions [D. J. Brockwell et al., Nat. Struct. Biol. 10, 731 (2003); M. Carrion-Vazquez et al., ibid 10, 738 (2003)] we have computed the unfolding free energy profiles for the ubiquitin domain when it is stretched between its (A) N and C termini, (B) Lys48 and C terminus, (C) Lys11 and C terminus, and (D) N terminus and Lys63. Our results for cases (A) and (B) are in good agreement with the experimental unfolding forces measured for the N-C and Lys48-C linked polyubiquitin, in particular, indicating a considerably lower unfolding force in the latter case. Mechanical unfolding in case (A) involves longitudinal shearing of the terminal parallel strands while in case (C) the same strands are "unzipped" by the force. The computed unfolding forces in case (C) are found to be very low, less than 50 pN for pulling rates typical of AFM experiments. The unfolding free energy barrier found in case (C) is approximately 13 kcal/mol, which corresponds to a zero-force unfolding rate constant that is comparable to the rate of chemical unfolding extrapolated to zero denaturant concentration. The unfolding barrier calculated in case (A) in the limit of zero force is much higher, suggesting that mechanical unfolding in this case follows a pathway that is different from that of thermal/chemical denaturation.

Computer Simulation↗

PubMed2004

Improved synthetic aperture focusing technique with applications in high-frequency ultrasound imaging.

Synthetic aperture focusing using a virtual source was used previously to increase the penetration and to extend the depth of focus in high-frequency ultrasonic imaging. However, the performance of synthetic aperture focusing is limited by its high sidelobes. In this paper, an adaptive weighting technique based on a focusing-quality index is introduced to suppress the sidelobes. The focusing-quality index is derived from the spatial spectrum of the scan-line data along the mechanical scan direction (i.e., the synthetic aperture direction) after focusing delays relative to the virtual source have been applied. The proposed technique is of particular value in high-frequency ultrasound in which dynamic focusing using array transducers is not yet possible. Experimental ultrasound data from a 50-MHz imaging system with a single-crystal transducer (f-number = 2) are used to demonstrate the efficacy of the proposed technique on both wire targets and speckle-generating objects. An in vivo experiment also is performed on a mouse to further demonstrate the effectiveness. Both 50-MHz fundamental imaging and 50-MHz tissue harmonic imaging are tested. The results clearly demonstrate the effectiveness in sidelobe reduction and background-noise suppression for both imaging modes. The principles, experimental results, and implementation issues of the new technique are described in this paper.

Algorithms↗

PubMed2004

Experimental investigation of computed tomography sound velocity reconstruction using incomplete data.

An approach for reconstructing the sound velocity distribution in the breast was previously proposed and verified by simulations, and the present study investigated the approach experimentally. The experimental setup comprised a 5-MHz, 128-channel linear array, a programmable digital array system, a phantom containing objects with differing physical properties, and a computer. The array system was used to collect channel data for simultaneous B-mode image formation and limited-angle tomographic sound velocity reconstruction. The phantom was constructed from materials mimicking the following tissues in the breast: glandular tissue, fat, cysts, high-attenuation tumors, and irregular tumors. The sound velocities in these materials matched those in the corresponding real tissues. The imaging setup is similar to that of x-ray mammography, in which a linear array is placed at the top of the breast and a metal plate is placed at the bottom for reflecting sound waves. Thus, both B-mode images and the sound velocity distribution can be acquired using the same setup. An algorithm based on a convex programming formulation was used to reconstruct the sound velocity images. By scanning the phantom at different positions, nine cases were evaluated. In each of the nine cases, the image object comprised a background (glandular tissue) and one or three regions of interest (fat, tumor, or cyst). The sound velocity was accurately estimated in the nine cases evaluated, with sound velocity errors being less than 5 m/s in 8 of 11 regions of interest. Thus, obtaining the sound velocity distribution is feasible with a B-mode imaging setup using linear arrays. Knowledge of the sound velocity distribution in the breast can be used to complement B-mode imaging and to enhance the detection of breast cancer.

Breast Neoplasms↗