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Objective: To identify the SEDL gene mutation in a Chinese family with X-linked spondyloepiphyseal dysplasia tarda (SEDL) and to establish a genotyping assay for rapid diagnosis of this X-linked recessive disorder., Methods: Clinical diagnoses were made based on physical examination, radiological examination and pedigree analysis for this family. Four primer pairs flanking the SEDL exons 3-6 including their exon/intron boundaries were designed. A rapid genotyping assay based on denaturing high performance liquid chromatography (DHPLC) was established to screen the point mutations of the SEDL gene. Genomic DNA was extracted by standard methods from 18 members in the three generations of the pedigree and subjected to PCR-denaturing high performance liquid chromatography (PCR-DHPLC) assay followed by direct DNA sequencing., Results: A c.218C>T mutation in exon 4 of the SEDL gene, which resulted in a substitution of serine 218 with leucine, was identified in this family. Among the 18 members, 3 patients, 5 obligate female carriers and 2 unmarried young females were found to have the missense mutation, and other 8 healthy individuals were not detected to carry the mutation, in which genotype-phenotype correlations were well established in each member investigated in this family., Conclusion: A c.218C>T missense mutation in the SEDL gene was firstly reported in Chinese population and the results of this study expand the spectrum of SEDL mutations. The PCR-DHPLC assay is a useful tool to rapidly detect the SEDL mutation in clinical and prenatal diagnosis.

Genetic recombination is a well-known phenomenon for enteroviruses. In this study, we determined the phylogenetic relationships of five distinct regions of the EV71 genome for 73 EV71 isolates from 1986 and from 1998 to 2005 in Taiwan. Phylogenetic analyses showed that the 5'-UTR, VP4-VP2, VP1, and 3D regions of EV71 isolated in 2004 and 2005 were grouped into genotype C. However, the 2B region of these isolates differed in that it grouped with genotype B, indicating recombination within EV71 had occurred. This intratypic recombination was first seen in 2002 and became predominant in 2004 and 2005. The simplot and bootscan analyses identified two recombination points located at the 3'-termini of the 2A and 3C regions. This intratypic recombination was identified among naturally circulating EV71 isolates in Taiwan, therefore, it suggests that nonstructural genes may recombine to produce new EV71 variants.

An outbreak of human metapneumovirus (hMPV) among children in southern Taiwan in 2004 prompted the investigation of the molecular epidemiology of hMPV from September 2003 to August 2005. Respiratory specimens that were culture negative for a panel of respiratory viruses were examined for the presence of hMPV by RT-PCR. The results indicated that 59 out of 546 (10.8%) children were hMPV-positive. The majority of these hMPV-positive children were less than 2 years old (59.4%), females (61%), and inpatients (67.8%). Infections occurred throughout the year, but peaked during the spring and/or summer months. Sequence analysis of the fusion gene from the isolates revealed two phylogenetic groups with five possible lineages (A1, A2a/A2b, B1, and B2). Among these co-circulating strains, A2 strains were most frequently observed and demonstrated the greatest divergence. Deduced amino acid sequence analysis identified several variant amino acids specific to the A2 lineage. Lineage-specific amino acid substitutions were noted at aa233, aa286, aa312, aa348, and aa296. This study indicated that genetically divergent strains of hMPV which caused respiratory disease and hospitalization were circulating among children in Taiwan.

Thermal strain imaging (TSI) is demonstrated in two model systems mimicking two potential clinical applications. First, a custom ultrasound (US) microscope produced high-resolution TSI images of an excised porcine coronary artery. Samples were placed in a temperature-controlled water chamber and scanned transversely and longitudinally. Phase-sensitive, correlation-based speckle tracking was applied to map the spatial distribution of temporal strain across the sample. TSI differentiated fatty tissue from water-based arterial wall and muscle with high contrast and a spatial resolution of 60 microm for a 50-MHz transducer. Both transverse and longitudinal TSI images compared well with B-scans of arterial wall structures, including intima, media, adventitia, and overlying fatty tissue. A second model system was used to test the hypothesis that US can produce the heating pattern required for TSI of internal structures. A 2-D phased array with independent drive electronics was combined with a conventional US scanner (iU22, Philips, Bothell, WA) for these studies. This 513-element array, originally designed for the US therapy, acted as the US heat source. To quantify the temporal strain induced by this system, TSI was performed on a homogeneous rubber phantom. TSI temperature estimates were within 3% error for a 3.2 degrees C temperature rise produced within 2 s using a specially designed beamformer and pulse sequencer. The system was then used to produce TSI scanning of an excised kidney containing an intact piece of fat below the collecting system. These images were validated using an magnetic resonance imaging (MRI) pulse sequence designed for lipid quantification. TSI scans matched well MRI scans and histology both anatomically and quantitatively. Finally, to test the potential of US-induced TSI for a significant clinical problem, images were obtained on an excised canine aorta with fatty tissue inside the lumen. Both longitudinal and transversal TSI agreed well with anatomy. These in vitro results demonstrate the potential of high-resolution US-induced TSI with a small temperature change (<1 degrees C) for plaque characterization.

We describe an inexpensive alternative to conventional hydrophones for measuring ultrasonic fields. The hydrophone, composed of common laboratory supplies, depends on the acoustoelectric (AE) effect, a well-known interaction between electrical current and pressure. Beam patterns of a 540 kHz annular transducer captured using a bowtie graphite hydrophone were consistent with patterns obtained using conventional, more expensive hydrophones. The AE signal was proportional to both the applied bias current (1.83 µV/mA) and pressure (13.3 µV/MPa) with sensitivity better than 50 kPa. Disposable AE hydrophones may be an attractive alternative for clinical applications that require close monitoring of high intensity acoustic fields.

The aim of this study was to determine the efficacy of using sound velocity and tissue attenuation to clinically discriminate breast cancer from healthy tissues. The methods for reconstructing the sound-velocity and attenuation-coefficient distributions were previously proposed and tested on tissue-mimicking phantoms. The methods require only raw channel data acquired by a linear transducer array and can therefore be implemented on existing clinical systems. In this paper, these methods are tested on clinical data. A total of 19 biopsy-proven cases, consisting of five carcinomas (CAs), seven fibroadenomas (FAs), six adipose tissue (fat) and one oil cyst, were evaluated. A single imaging setup consisting of a 5-MHz, 128-channel linear array was used to simultaneously obtain B-mode image data, time-of-flight data and attenuation data. The sound velocity and attenuation coefficient can be reconstructed inside and outside a region of interest manually selected in the B-mode image. To reduce distortion caused by tissue inhomogeneities, an optimal filter derived from pulse-echo data-with water replacing the breast tissue-is applied. We found that the sound velocities in CA, FA and fat tissues relative to those in the surrounding tissues were 49.8 +/- 35.2, 2.6 +/- 27.3 and -25.1 +/- 44.9 m/s (mean +/- SD), respectively, whereas the relative attenuation coefficients were 0.21 +/- 0.58, 0.27 +/- 0.62 and -0.02 +/- 0.59 dB/cm/MHz. These results indicate that CA can be discriminated from FA and fat by choosing an appropriate threshold for the relative sound velocity (i.e., 18.5 m/s). However, the large variations in the attenuation within the same type of tissue make simple thresholding ineffective. Nevertheless, the method described in this paper has the potential to reduce negative biopsies and to improve the accuracy of breast cancer detection in clinics.

In this study, photoacoustic flow measurement methods based on wash-in analysis are presented. These methods use the rod-to-sphere shape transformations of gold nanorods induced by pulsed-laser irradiation. Due to the shape dependence of the optical absorption of the gold nanorods, these shape transitions are associated with a change in the peak optical absorption wavelength. Pulsed-laser irradiation at the wavelength corresponding to the peak optical absorption of the original gold nanorods allows the particles that undergo shape changes to be viewed as "being destructed" by the laser irradiation at that wavelength, hence, flow information can be derived from the change in ultrasound intensity that is directly related to the wash-in rate of the gold nanorods and the laser intensity. Two flow estimation methods based on the wash-in analysis are described. The first method first applies high-energy laser pulses that induce shape changes in all the nanorods. A series of low-energy pulses then are applied to monitor the acoustic signal change as new nanorods flow into the region of interest. The second method uses single-energy laser pulses such that the "destruction" and "detection" are performed simultaneously. The simulation results show that it is valid to fit the time-intensity curves by exponential models. To demonstrate the validity of the proposed methods, an Nd:YAG pulsed laser operating at 1064 nm was used for optical irradiation, and a 1-MHz ultrasonic transducer was used for acoustic detection. Gold nanorods with a peak optical absorption at 1018 nm and a concentration of 0.26 nM were used to estimate flow velocities ranging from 0.35 to 2.83 mm/s. The linear regression results show that the correlation coefficients between the measured velocities and the true values are close to unity (> or = 0.94), thus demonstrating the feasibility of the proposed photoacoustic techniques for relative flow estimation.

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.

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.

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.

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.

An approach based on limited-angle transmission tomography for reconstruction of the sound velocity distribution in the breast is proposed. The imaging setup is similar to that of x-ray mammography. With this setup, the time-of-flight data are acquired by a linear array positioned at the top of the compressed breast that both transmits and receives, and a metal plate is placed at the bottom as a reflector. The setup allows acoustic data acquisition for simultaneous B-mode image formation and the tomographic sound velocity reconstruction. In order to improve the sound velocity estimation accuracy, a new reconstruction algorithm based on a convex programming formulation has been developed. Extensive simulations for both imaging and time-of-flight data based on a 5-MHz linear array were performed on tissues with different geometries and acoustic parameters. Results show that the sound velocity error was generally 1-3 m/s, with a maximum of 5.8 m/s. The radii of the objects under investigation varied from 2 to 6 mm, and all of them were detected successfully. Thus, the proposed approach has been shown to be both feasible and accurate. The approach can be used to complement conventional B-mode imaging to further enhance the detection of breast cancer.

B-mode images of 20 fresh postsurgical human liver samples were obtained to evaluate ultrasound ability in determining the grade of liver fibrosis. Image features derived from gray level concurrence and nonseparable wavelet transform were extracted to classify fibrosis with a classifier known as the support vector machine. Each liver sample subsequently underwent histologic examination and liver fibrosis was graded from 0 to 5 (i.e., six grades total). The six grades were then combined into two, three, four and six classes. Classifications with the extracted image features by the support vector machine were tested and correlated with histology. The results revealed that the best classification accuracy of two, three, four and six classes were 91%, 85%, 81% and 72%, respectively. Thus, liver fibrosis can be noninvasively characterized with B-mode ultrasound, even though the performance declines as the number of classes increases. The elastic constants of 16 samples out of a total of 20 were also correlated with the image features. The Pearson correlation coefficients indicated that the image features are more strongly correlated with the fibrosis grade than with the elastic constant.