[Show abstract][Hide abstract] ABSTRACT: We demonstrate a novel non-contact method: acoustic radiation force impulse microscopy via photoacoustic detection (PA-ARFI), capable of probing cell mechanics. A 30 MHz lithium niobate ultrasound transducer is utilized for both detection of phatoacoustic signals and generation of acoustic radiation force. To track cell membrane displacements by acoustic radiation force, functionalized single-walled carbon nanotubes are attached to cell membrane. Using the developed microscopy evaluated with agar phantoms, the mechanics of highly- and weakly-metastatic breast cancer cells are quantified. These results clearly show that the PA-ARFI microscopy may serve as a novel tool to probe mechanics of single breast cancer cells.
[Show abstract][Hide abstract] ABSTRACT: In this Letter, we present a trimodality imaging system and an intravascular endoscopic probe for the detection of early-stage atherosclerotic plaques. The integrated system is able to acquire optical coherence tomography (OCT), fluorescence, and ultrasound images and simultaneously display them in real time. A trimodality intravascular endoscopic probe of 1.2 mm in diameter and 7 mm in length was fabricated based on a dual-modality optical probe that integrates OCT and fluorescence imaging functions and a miniature ultrasound transducer. The probe is capable of rotating at up to 600 rpm. Ex vivo images from rabbit aorta and human coronary arteries showed that this combined system is capable of providing high resolution, deep penetration depth and specific molecular fluorescence contrast simultaneously.
[Show abstract][Hide abstract] ABSTRACT: We report the multiple micro-particle trapping and manipulation by a single-beam acoustic tweezer using a high-frequency array transducer. A single acoustic beam generated by a 30 MHz ultrasonic linear array transducer can entrap and transport multiple micro-particles located at the main lobe and the grating lobes. The distance between trapped particles can be adjusted by changing the transmit arrangement of array-based acoustic tweezers and subsequently the location of grating lobes. The experiment results showed that the proposed method can trap and manipulate multiple particles within a range of hundreds of micrometers. Due to its simplicity and low acoustic power, which is critical to protect cells from any thermal and mechanical damages, the technique may be used for transportation of cells in cell biology, biosensors, and tissue engineering.
[Show abstract][Hide abstract] ABSTRACT: Tools that are capable of manipulating micro-sized objects have been widely used in such fields as physics, chemistry, biology, and medicine. Several devices, including optical tweezers, atomic force microscope, micro-pipette aspirator, and standing surface wave type acoustic tweezers have been studied to satisfy this need. However, none of them has been demonstrated to be suitable for in vivo and clinical studies. Single beam acoustic tweezers (SBAT) is a technology that uses highly focused acoustic beam to trap particles toward the beam focus. Its feasibility was first theoretically and experimentally demonstrated by Lee and Shung several years ago. Since then, much effort has been devoted to improving this technology. At present, the tool is capable of trapping a microparticle as small as 1 μm, as well as a single red blood cell. Although in comparing to other microparticles manipulating technologies, SBAT has advantages of providing stronger trapping force and deeper penetration depth in tissues, and producing less tissue damage, its potential for in vivo applications has yet been explored. It is worth noting that ultrasound has been used as a diagnostic tool for over 50 years and no known major adverse effects have been observed at the diagnostic energy level. This paper reports the results of an initial attempt to assess the feasibility of single beam acoustic tweezers to trap microparticles in vivo inside of a blood vessel. The acoustic intensity of SBAT under the trapping conditions that were utilized was measured. The mechanical index and thermal index at the focus of acoustic beam were found to be 0.48 and 0.044, respectively, which meet the standard of commercial diagnostic ultrasound system.
[Show abstract][Hide abstract] ABSTRACT: Piezoelectric single crystals, which have excellent piezoelectric properties, have extensively been employed for various sensors and actuators applications. In this paper, the state–of–art in piezoelectric single crystals for ultrasonic transducer applications is reviewed. Firstly, the basic principles and design considerations of piezoelectric ultrasonic transducers will beaddressed. Then, the popular piezoelectric single crystals used for ultrasonic transducer applications, including LiNbO3 (LN), PMN–PT and PIN–PMN–PT, will be introduced. After describing the preparation and performance of the single crystals, the recent development of both the single–element and array transducers fabricated using the single crystals will be presented. Finally, various biomedical applications including eye imaging, intravascular imaging, blood flow measurement, photoacoustic imaging, and microbeam applications of the single crystal transducers will be discussed.
Progress in Materials Science 10/2014; · 23.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Myocardial infarction results in scar tissue and irreversible loss of ventricular function. Unlike humans, zebrafish has the capacity to remove scar tissue after injury. To assess ventricular function during repair, we synchronized microelectrocardiogram (μECG) signals with a high-frequency ultrasound pulsed-wave (PW) Doppler to interrogate cardiac hemodynamics. μECG signals allowed for identification of PW Doppler signals for passive (early [E]-wave velocity) and active ventricular filling (atrial [A]-wave velocity) during diastole. The A wave (9.0±1.2 cm·s(-1)) is greater than the E wave (1.1±0.4 cm·s(-1)), resulting in an E/A ratio <1 (0.12±0.05, n=6). In response to cryocauterization to the ventricular epicardium, the E-wave velocity increased, accompanied by a rise in the E/A ratio at 3 days postcryocauterization (dpc) (0.55±0.13, n=6, p<0.001 vs. sham). The E waves normalize toward the baseline, along with a reduction in the E/A ratio at 35 dpc (0.36±0.06, n=6, p<0.001 vs. sham) and 65 dpc (0.2±0.16, n=6, p<0.001 vs. sham). In zebrafish, E/A<1 at baseline is observed, suggesting the distinct two-chamber system in which the pressure gradient across the atrioventricular valve is higher compared with the ventriculobulbar valve. The initial rise and subsequent normalization of E/A ratios support recovery in the ventricular diastolic function.
[Show abstract][Hide abstract] ABSTRACT: The ultrasonic transducer is one of the core components of ultrasound systems, and the transducer's sensitivity is significantly related the loss of electronic components such as the transmitter, receiver, and protection circuit. In an ultrasonic device, protection circuits are commonly used to isolate the electrical noise between an ultrasound transmitter and transducer and to minimize unwanted discharged pulses in order to protect the ultrasound receiver. However, the performance of the protection circuit and transceiver obviously degrade as the operating frequency or voltage increases. We therefore developed a crossed SMPS (Switching Mode Power Supply) MOSFET-based protection circuit in order to maximize the sensitivity of high frequency transducers in ultrasound systems.The high frequency pulse signals need to trigger the transducer, and high frequency pulse signals must be received by the transducer. We therefore selected the SMPS MOSFET, which is the main component of the protection circuit, to minimize the loss in high frequency operation. The crossed configuration of the protection circuit can drive balanced bipolar high voltage signals from the pulser and transfer the balanced low voltage echo signals from the transducer.
[Show abstract][Hide abstract] ABSTRACT: We report a flexible shaft-based mechanical scanning photoacoustic endoscopy (PAE) system that can be potentially used for imaging the human gastrointestinal tract via the instrument channel of a clinical video endoscope. The development of such a catheter endoscope has been an important challenge to realize the technique's benefits in clinical settings. We successfully implemented a prototype PAE system that has a 3.2-mm diameter and 2.5-m long catheter section. As the instrument's flexible shaft and scanning tip are fully encapsulated in a plastic catheter, it easily fits within the 3.7-mm diameter instrument channel of a clinical video endoscope. Here, we demonstrate the intra-instrument channel workability and in vivo animal imaging capability of the PAE system.
Journal of Biomedical Optics 06/2014; 19(6):66001. · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We present a cross-beam nonlinear photoacoustic microscopy technique with enhanced axial resolution. By combining cross-beam illumination with optical nonlinearity, an axial resolution of 8.7 µm is measured experimentally.
[Show abstract][Hide abstract] ABSTRACT: We have developed fully motorized optical-resolution photoacoustic microscopy (OR-PAM), which integrates five complementary scanning modes and simultaneously provides a high imaging speed and a wide field of view (FOV) with 2.6 μm lateral resolution. With one-dimensional (1D) motion-mode mechanical scanning, we measured the blood flow through a cross section of a blood vessel in vivo. With two-dimensional (2D) optical scanning at a laser repetition rate of 40 kHz, we achieved a 2 kHz B-scan rate over a range of 50 μm with 20 A-lines and 50 Hz volumetric-scan rate over a FOV of 50 μm×50 μm with 400 A-lines, which enabled real-time tracking of cellular dynamics in vivo. With synchronized 1D optical and 2D mechanical hybrid scanning, we imaged a 10 mm×8 mm FOV within three minutes, which is 20 times faster than the conventional mechanical scan in our second-generation OR-PAM. With three-dimensional mechanical contour scanning, we maintained the optimal signal-to-noise ratio and spatial resolution of OR-PAM while imaging objects with uneven surfaces, which is essential for quantitative studies.
[Show abstract][Hide abstract] ABSTRACT: The purpose of protection circuits in ultrasound applications is to block noise signals from the transmitter from reaching the transducer and also to prevent unwanted high voltage signals from reaching the receiver. The protection circuit using a resistor and diode pair is widely used due to its simple architecture, however, it may not be suitable for very high frequency (VHF) ultrasound transducer applications (>100 MHz) because of its limited bandwidth. Therefore, a protection circuit using MOSFET devices with unique structure is proposed in this paper. The performance of the designed protection circuit was compared with that of other traditional protection schemes. The performance characteristics measured were the insertion loss (IL), total harmonic distortion (THD) and transient response time (TRT). The new protection scheme offers the lowest IL (-1.0 dB), THD (-69.8 dB) and TRT (78 ns) at 120 MHz. The pulse-echo response using a 120 MHz LiNbO3 transducer with each protection circuit was measured to validate the feasibility of the protection circuits in VHF ultrasound applications. The sensitivity and bandwidth of the transducer using the new protection circuit improved by 252.1 and 50.9 %, respectively with respect to the protection circuit using a resistor and diode pair. These results demonstrated that the new protection circuit design minimizes the IL, THD and TRT for VHF ultrasound transducer applications.
Journal of Medical Systems 04/2014; 38(4):34. · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Photoacoustic (PA) endoscopy for human urogenital imaging has the potential to diagnose many important diseases, such as endometrial and prostate cancers. We have specifically developed a 12.7 mm diameter, rigid, side-scanning PA endoscopic probe for such applications. The key features of this endoscope are the streamlined structure for smooth cavity introduction and the proximal actuation mechanism for fast scanning. Here we describe the probe's composition and scanning mechanism and present in vivo experimental results suggesting its potential for comprehensive clinical applications.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the limiter circuits used in the ultrasound imaging systems is to pass low-voltage echo signals generated by ultrasonic transducers while preventing high-voltage short pulses transmitted by pulsers from damaging front-end circuits. Resistor-diode-based limiters (a 50 Ω resistor with a single cross-coupled diode pair) have been widely used in pulse-echo measurement and imaging system applications due to their low cost and simple architecture. However, resistor-diode-based limiters may not be suited for high-frequency ultrasound transducer applications since they produce large signal conduction losses at higher frequencies. Therefore, we propose a new limiter architecture utilizing power MOSFETs, which we call a power MOSFET-diode-based limiter. The performance of a power MOSFET-diode-based limiter was evaluated with respect to insertion loss (IL), total harmonic distortion (THD), and response time (RT). We compared these results with those of three other conventional limiter designs and showed that the power MOSFET-diode-based limiter offers the lowest IL (-1.33 dB) and fastest RT (0.10 µs) with the lowest suppressed output voltage (3.47 Vp-p) among all the limiters at 70 MHz. A pulse-echo test was performed to determine how the new limiter affected the sensitivity and bandwidth of the transducer. We found that the sensitivity and bandwidth of the transducer were 130% and 129% greater, respectively, when combined with the new power MOSFET-diode-based limiter versus the resistor-diode-based limiter. Therefore, these results demonstrate that the power MOSFET-diode-based limiter is capable of producing lower signal attenuation than the three conventional limiter designs at higher frequency operation.
[Show abstract][Hide abstract] ABSTRACT: We have developed a novel integrated optical coherence tomography (OCT)-intravascular ultrasound (IVUS) probe, with a 1.5 mm-long rigid-part and 0.9 mm outer diameter, for real-time intracoronary imaging of atherosclerotic plaques and guiding interventional procedures. By placing the OCT ball lens and IVUS 45MHz single element transducer back-to-back at the same axial position, this probe can provide automatically co-registered, co-axial OCT-IVUS imaging. To demonstrate its capability, 3D OCT-IVUS imaging of a pig's coronary artery in real-time displayed in polar coordinates, as well as images of two major types of advanced plaques in human cadaver coronary segments, was obtained using this probe and our upgraded system. Histology validation is also presented.
[Show abstract][Hide abstract] ABSTRACT: The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the diseased arterial wall. As lesions become more vulnerable, different cholesterol species accumulate in the plaque. Understanding unstable atherosclerosis as a pharmacological and interventional therapeutic target requires chemically specific imaging of disease foci. In this study, we aim to image atherosclerotic plaque lipids and other vessel wall constituents with spectroscopic intravascular photoacoustics (sIVPA). sIVPA imaging can identify lipids in human coronary atherosclerotic plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components. Using reference spectra acquired on pure compounds, we analyzed sIVPA data from human coronary plaques ex vivo, to image plaque composition in terms of cholesterol and cholesterol ester content. In addition, we visualized the deeper lying connective tissue layers of the adventitia, as well as the fatty acid containing adipose cells in the peri-adventitial tissue. We performed simultaneous coregistered IVUS imaging to obtain complementary morphological information. Results were corroborated by histopathology. sIVPA imaging can distinguish the most prevalent lipid components of human atherosclerotic plaques and also visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the peri-adventitial tissue.
Journal of Biomedical Optics 02/2014; 19(2):26006. · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Photoacoustic ophthalmoscopy (PAOM) is a high-resolution in vivo imaging modality that is capable of providing specific optical absorption information for the retina. A high-frequency ultrasonic transducer is one of the key components in PAOM, which is in contact with the eyelid through coupling gel during imaging. The ultrasonic transducer plays a crucial role in determining the image quality affected by parameters such as spatial resolution, signal-to-noise ratio, and field of view. In this paper, we present the results of a systematic study on a high-frequency ultrasonic transducer design for PAOM. The design includes piezoelectric material selection, frequency selection, and the fabrication process. Transducers of various designs were successfully applied for capturing images of biological samples in vivo. The performances of these designs are compared and evaluated.
Journal of Biomedical Optics 01/2014; 19(1):16015. · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multiparticle-trapping offers diverse opportunities and applications in biotechnology. It can be applied to creating various functional materials or organizing reactive particles. In this paper, we demonstrate that it is possible to trap and manipulate multi-particles in an annular pattern with a 24 MHz focused ring-type single element ultrasound transducer. Acoustic ring trap can be useful in undertaking biotropism studies due to an equal-distance condition from the center. Also, this ring trap could serve as a force shield to protect analysis area from other cells. The experimental results showed the capability of the proposed method as a multi-cell manipulator in formatting specific patterns of small cells like sperms.
[Show abstract][Hide abstract] ABSTRACT: Lipid deposition inside the arterial wall is a key indicator of plaque vulnerability. An intravascular photoacoustic (IVPA) catheter is considered a promising device for quantifying the amount of lipid inside the arterial wall. Thus far, IVPA systems suffered from slow imaging speed (~50 s per frame) due to the lack of a suitable laser source for high-speed excitation of molecular overtone vibrations. Here, we report an improvement in IVPA imaging speed by two orders of magnitude, to 1.0 s per frame, enabled by a custom-built, 2-kHz master oscillator power amplifier (MOPA)-pumped, barium nitrite [Ba(NO3)2] Raman laser. This advancement narrows the gap in translating the IVPA technology to the clinical setting.
[Show abstract][Hide abstract] ABSTRACT: We designed and developed a confocal acoustic radiation force optical coherence elastography system. A ring ultrasound transducer was used to achieve reflection mode excitation and generate an oscillating acoustic radiation force in order to generate displacements within the tissue, which were detected using the phase-resolved optical coherence elastography method. Both phantom and human tissue tests indicate that this system is able to sense the stiffness difference of samples and quantitatively map the elastic property of materials. Our confocal setup promises a great potential for point by point elastic imaging in vivo and differentiation of diseased tissues from normal tissue.