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Objective: For accurate diagnosis of atherosclerosis, the high spatial and contrast resolutions of intravascular ultrasound (IVUS) images are a key requirement. Increasing the center frequency of IVUS is a simple solution to meet this requirement. However, this leads to a reduction in imaging depth due to the frequency-dependent attenuation of ultrasound. Here, we report a recently developed dual-element IVUS transducer for tissue harmonic imaging (THI) and frequency compounding to increase the spatial and contrast resolutions of IVUS images, while maintaining the imaging depth to assess the overall morphological change of blood vessels. Methods: One 35-MHz element is used for producing general IVUS images and the other 70-MHz element is for receiving the second harmonic signals induced by the 35-MHz ultrasound. The fundamental and second harmonic signals can also be used for frequency compound imaging to further improve contrast resolution. The spatial and contrast resolutions achieved by the developed transducer were evaluated through wire and tissue-mimicking phantom imaging tests. Additionally, the images of a stent deployed in a tissue-mimicking phantom and an excised pig artery were acquired to assess clinical usefulness of the transducer. Results: The results demonstrated that the developed IVUS transducer enables us to simultaneously examine the overall morphological change of blood vessels by the 35-MHz ultrasound images and the near vessel layers such as the intima, the media, and the adventitia by either THI or compound images with high spatial and contrast resolutions. In addition, the developed transducer facilitates the simultaneous acquisition of 35- and 70-MHz fundamental images when needed. Conclusion: The developed dual-element IVUS transducer makes it possible to fully realize the potential benefits of IVUS in the diagnosis of atherosclerosis. [ABSTRACT FROM AUTHOR]

Although transrectal ultrasound (TRUS) imaging is widely used for screening and diagnosing prostate cancer, it is often not found on TRUS images, depending on its stage, size, and location. In addition, due to the weak echo signal and the low contrast of TRUS images, it is difficult to diagnose early-stage prostate cancers and distinguish malignant tumors from benign prostatic hyperplasia. For this reason, TRUS image-guided biopsy is mandatory to confirm the malignancy of the suspicious tumor, but the diagnostic accuracy of initial biopsy is only 20%–30%, so that the patients inevitably undergo repeated biopsies. TRUS-photoacoustic (TRUS-PA) imaging is one way to resolve those problems. However, the development of a TRUS-PA probe, in which an ultrasound array transducer and optical fibers are integrated, is demanding because the overall size of the probe should be as small as possible for the convenience of the patients, while providing the desired performances. Here, we report a recently developed TRUS-PA probe. The core element of the TRUS-PA is a miniaturized 128-element, 7-MHz convex array transducer of which size in the lateral and elevational directions is 11.4 and 5 mm, respectively. A new concept of a flexible printed circuit board was also developed to limit the size of the TRUS-PA probe to less than 15 mm. From the performance evaluation, it was found that the developed array with a field-of-view of 134° has a center frequency of 6.75 MHz, a −6-dB fractional bandwidth of 66%, and a crosstalk of less than −45 dB. In the tissue-mimicking phantom test andex vivoexperiments, the miniaturized convex array proved to be capable of providing combined US and PA images with acceptable imaging quality in spite of its small size. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) has garnered considerable attention as an attractive treatment tool for cancer due to precisely selective treatment and minimal side effects. The primary challenge of PTT, which hinders its widespread application, is the limited therapeutic depth. This limitation arises from optical scattering in biological tissues, causing inadequate heat distribution within the deep tissue. To overcome this challenge, ultrasound‐assisted PTT (ULTRA‐PTT) is proposed that leverages the temporary formation of gas bubbles induced by ultrasound within the light propagation path. These bubbles act as optical clearing agents, effectively reducing optical scattering in biological tissues. To facilitate ULTRA‐PTT, a dedicated handpiece consisting of a ring‐shaped ultrasound transducer and a laser delivery module is developed. In‐vivo experiments show that ULTRA‐PTT statistically outperforms conventional PTT in melanoma treatment, mostly due to its ability to deliver sufficient laser energy to deep‐seated cancer cells. These findings underscore the potential of ULTRA‐PTT to expand the clinical applications of PTT beyond local tumors occurring in superficial tissue. [ABSTRACT FROM AUTHOR]

Abstract: In an ultrasound image-guided High Intensity Focused Ultrasound (HIFU) surgery, reflected HIFU waves received by an imaging transducer should be suppressed for real-time simultaneous imaging and therapy. In this paper, we investigate the feasibility of pulse compression scheme combined with notch filtering in order to minimize these HIFU interference signals. A chirp signal modulated by the Dolph–Chebyshev window with 3–9MHz frequency sweep range is used for B-mode imaging and 4MHz continuous wave is used for HIFU. The second order infinite impulse response notch filters are employed to suppress reflected HIFU waves whose center frequencies are 4MHz and 8MHz. The prototype integrated HIFU/imaging transducer that composed of three rectangular elements with a spherically con-focused aperture was fabricated. The center element has the ability to transmit and receive 6MHz imaging signals and two outer elements are only used for transmitting 4MHz continuous HIFU wave. When the chirp signal and 4MHz HIFU wave are simultaneously transmitted to the target, the reflected chirp signals mixed with 4MHz and 8MHz HIFU waves are detected by the imaging transducer. After the application of notch filtering with pulse compression process, HIFU interference waves in this mixed signal are significantly reduced while maintaining original imaging signal. In the single scanline test using a strong reflector, the amplitude of the reflected HIFU wave is reduced to −45dB. In vitro test, with a sliced porcine muscle shows that the speckle pattern of the restored B-mode image is close to that of the original image. These preliminary results demonstrate the potential for the pulse compression scheme with notch filtering to achieve real-time ultrasound image-guided HIFU surgery. [Copyright &y& Elsevier]

Abstract: Coded tissue harmonic imaging with pulse inversion (CTHI-PI) based on a linear chirp signal can improve the signal-to-noise ratio with minimizing the peak range sidelobe level (PRSL), which is the main advantage over CTHI with bandpass filtering (CTHI-BF). However, the CTHI-PI technique could suffer from motion artifacts due to decreasing frame rate caused by two firings of opposite phase signals for each scanline. In this paper, a new CTHI method based on a nonlinear chirp signal (CTHI-NC) is presented, which can improve the separation of fundamental and harmonic components without sacrificing frame rate. The nonlinear chirp signal is designed to minimize the PRSL value by optimizing its frequency sweep rate and time duration. The performance of the CTHI-NC method was evaluated by measuring the PRSL and mainlobe width after compression. From the in vitro experiments, the CTHI-NC provided the PRSL of −40.6dB and the mainlobe width of 2.1μs for the transmit quadratic nonlinear chirp signal with the center frequency of 2.1MHz, the fractional bandwidth at −6dB of 0.6 and the time duration of 15μs. These results indicate that the proposed method could be used for improving frame rates in CTHI while providing comparable image quality to CTHI-PI. [ABSTRACT FROM AUTHOR]

Abstract: An acoustic guidance method for pedicle screw placement during spine fixation surgery was recently investigated, with a view toward preventing complications such as injury to the spinal cord, thecal sac, and spinal nerve roots due to screw misplacement. The method relies upon the change in the ultrasound amplitude reflected at different sites—from the outer posterior cortex, through the pedicle, and towards the distal ventral cortex. The amplitude change was empirically observed through in vitro measurement of ultrasound amplitude at the different sites by inserting a 2.5-MHz single element transducer into a vertebral body through insertion pathway created by an advancing screw. This paper provides a theoretical and experimental rationale behind these empirical findings and distance-dependent correlation coefficients between amplitude and bone mineral density within the vertebral body, which approached 97%. [ABSTRACT FROM AUTHOR]

Abstract: Background context: In pedicle screw fixation surgery, rigid instruments are inserted into a vertebral body. When the instruments are misdirected within the pedicle or advanced too far beyond it, perforations of the inner or outer cortex can cause damage to the spinal nerve roots and spinal cord. These complications can occur despite the use of imaging modalities, such as radiographs, fluoroscopy, and computerized axial tomography (CAT) scans. A-Mode ultrasound (US), a nonionizing modality, merits study for its possible use in such a type of surgery. Purpose: The purpose of the study was to determine the utility of A-mode US during pedicle screw placement, to characterize the approach to the marrow-cortex interface, and to obtain the signature profiles of cortex perforations. Study design: A-Mode data were generated on insertion of a forward-viewing transducer (FVT) and a side-viewing transducer (SVT) to successively greater drilled depths along the insertion pathway. A-Mode broadband US backscatter (BUB) pedicle screw emulation experiments were conducted with transducers inserted into drilled sheep vertebral bodies. BUB amplitude patterns were observed and analyzed. Descriptive statistics were used. Methods: In vitro acoustic experiments on vertebral bodies in a water bath were performed with two 1-MHz unfocused transducers to measure sound speed, broadband US attenuation, and backscatter coefficients. Micro-CAT scan three-dimensional (3-D) images of 10 disarticulated vertebral bodies were obtained pre- and postdrilling done in 5-mm depth increments with a flat-bottom drill. BUB patterns were noted of transducers inserted through rostral outer cortex, through the pedicle, and advanced to the ventral marrow-cortex interface. 2.5-MHz FVT and SVT were co-advanced in successive 5-mm increments along the insertion pathway, with BUBs measured at each point and the echoes composited into a single figure. Deliberate perforations of ventral cortex were made. Results: Evident patterns or measures indicating the proximity of the ventral marrow-cortex interface were: 1) marrow BUB values increasing in amplitude over three distal peaks in most FVT cases (7 out of 10) and SVT cases (9 out of 10); 2) BUB ratio of marrow-cortex interface to the smallest marrow value greater than 2, in all FVT cases (10 out of 10) with FVT mean of 4.00±1.82 (2.25–8.33); and 3) a ratio of distal BUB value to starting cortex BUB in the 0. 82 to 1.62 range (mean, 0.98±0.30) in 80% of FVT cases. Ventral FVT perforations resulted in a major drop in the BUB value. Conclusions: The increase in the BUB amplitudes in the distal insertion pathway suggests that, at least with a 2.5-MHz transducer, an approximate 1.5-cm US window exists in most cases, by which close approach of the ventral marrow-cortex interface could be anticipated. Other ratios may serve as stop criteria to prevent further drilling. A precipitous drop in BUB amplitude may be an indication of a cortex perforation. [Copyright &y& Elsevier]

Abstract: This paper proposes a frequency compounding method to reduce speckle interferences, where a concentric annular type high-frequency dual element transducer is used to broaden the bandwidth of an imaging system. In frequency compounding methods, frequency division is carried out to obtain sub-band images containing uncorrelated speckles, which sacrifices axial resolution. Therefore, frequency compounding often deteriorates the target-detecting capability, quantified by the total signal-to-noise ratio (SNR), when the speckle’s SNR (SSNR) is not improved as much as the degraded axial resolution. However, this could be avoided if the effective bandwidth required for frequency compounding is increased. The primary goal of the proposed approach, hence, is to improve SSNR by a factor of two under the condition where axial resolution is degraded by a factor of less than two, which indicates the total SNR improvement to higher than 40% compared to that of an original image. Since the method here employs a dual element transducer operating at 20 and 40MHz, the effective bandwidth necessary for frequency compounding becomes broadened. By dividing each spectrum of RF samples from both elements into two sub-bands, this method eventually enables four sets of the sub-band samples to contain uncorrelated speckles. This causes the axial resolution to be reduced by a factor of as low as 1.85, which means that this method would improve total SNR by at least 47%. An in vitro experiment on an excised pig eye was performed to validate the proposed approach, and the results showed that the SSNR was improved from 2.081±0.365 in the original image to 4.206±0.635 in the final compounding image. [Copyright &y& Elsevier]

Abstract: Electrochemical supercapacitive behaviour of polyaniline nanostructures, i.e., nanorods and nanospheres fabricated on aniline-primed conducting indium–tin oxide substrate via electroless surface polymerization using ammonium persulfate as initiator and selenious acid as efficient dopant is investigated. The self-assembled monolayer of urea derivative in presence of 3-(triethoxysilyl)-propyl isocyanate and aniline plays role of aniline-primed substrate. Polyaniline electrode composed of nanorods of excess surface area responsible for large redox reactions has shown 592Fg−1 specific capacitance which is significantly greater than closely compact polyaniline nanospheres, i.e., 214Fg−1. [Copyright &y& Elsevier]

Abstract: This paper presents a high-speed digital scan converter (DSC) capable of providing more than 400 images per second, which is necessary to examine the activities of the mouse heart whose rate is 5–10 beats per second. To achieve the desired high-speed performance in cost-effective manner, the DSC developed adopts a linear interpolation algorithm in which two nearest samples to each object pixel of a monitor are selected and only angular interpolation is performed. Through computer simulation with the Field II program, its accuracy was investigated by comparing it to that of bilinear interpolation known as the best algorithm in terms of accuracy and processing speed. The simulation results show that the linear interpolation algorithm is capable of providing an acceptable image quality, which means that the difference of the root mean square error (RMSE) values of the linear and bilinear interpolation algorithms is below 1%, if the sample rate of the envelope samples is at least four times higher than the Nyquist rate for the baseband component of echo signals. The designed DSC was implemented with a single FPGA (Stratix EP1S60F1020C6, Altera Corporation, San Jose, CA) on a DSC board that is a part of a high-speed ultrasound imaging system developed. The temporal and spatial resolutions of the implemented DSC were evaluated by examining its maximum processing time with a time stamp indicating when an image is completely formed and wire phantom testing, respectively. The experimental results show that the implemented DSC is capable of providing images at the rate of 400 images per second with negligible processing error. [Copyright &y& Elsevier]

Intravascular ultrasound (IVUS) is a valuable imaging modality for the diagnosis of atherosclerosis. It provides useful clinical information, such as lumen size, vessel wall thickness, and plaque composition, by providing a cross-sectional vascular image. For several decades, IVUS has made remarkable progress in improving the accuracy of diagnosing cardiovascular disease that remains the leading cause of death globally. As the quality of IVUS images mainly depends on the performance of the IVUS transducer, various IVUS transducers have been developed. Therefore, in this review, recently developed mechanically rotating IVUS transducers, especially ones exploiting piezoelectric ceramics or single crystals, are discussed. In addition, this review addresses the history and technical challenges in the development of IVUS transducers and the prospects of next-generation IVUS transducers. [ABSTRACT FROM AUTHOR]

PURPOSE. To evaluate differences in corneal responseto daily wear (DW) of soft contact lens (CL) wear with different CL solutionsand to assess the ability of in vivo confocal microscopy (CM) andtear lactate dehydrogenase (LDH) measurement to detect such differences inNZW rabbits. METHODS. Daily treatment of lenses consisted of a rub and rinse cleaning,then overnight soak in one of five solutions: Sauflon All in One (ALL), CompoundA (CoA), OPTI-FREE[sup ® ] Rinsing, Disinfecting, and Storage Solution(OPT), ReNu[sup ®]Multipurpose Solution (REN), and UNISOL[sup ®] Saline Solution (UNI). Rabbits (4/test group) wore 71% H[sub 2] O/type4 soft lenses approximately 7 hours daily. On days 0, 1, 3 and7, slit lamp examination, tear LDH measurement, and in vivo CM wereperformed after removal of lenses. Using in vivo CM, epithelial thickness,epithelial cell area, and stromal thickness were measured, both centrallyand peripherally. RESULTS. Epithelial thickness in ALL, CoA, and UNI-treated eyes showeda significant decrease of 15.6%, 13.3%, and 10.6% (p < 0.05 in all groups),centrally, while CoA, OPT, and UNI showed a significant decrease of 9.3%,7.1%, and 4.4% (p < 0.05 in all groups), peripherally. ALL showed a significant9.5% (p < 0.05) decrease of central cell area, while CoA showed a significant21.5% (p < 0.01) decrease peripherally. UNI demonstrated a significant3.2% (p < 0.05) decrease in central stromal thickness. ALL, CoA, and UNIshowed a significant increase in LDH level of 152.1%, 192.1%, and 308.2% (p< 0.05 in all groups) at day 3, respectively, but values declined at day7. Significant changes in basal epithelial morphology were also observed withCoA on day 7 on in vivo CM. CONCLUSIONS. Overall, lens care solutions in combination with CL wear mayinteract to cause increased epithelial desquamation leading to decreased surfacecell area and epithelial thickness. The clinical significance of these changeswill require further investiga... [ABSTRACT FROM AUTHOR]

Complete blockage of a coronary artery, called chronic total occlusion (CTO), frequently occurs due to atherosclerosis. To reopen the obstructed blood vessels with a stent, guidewire crossing is performed with the help of angiography that can provide the location of CTO lesions and the image of guidewire tip. Since angiography is incapable of imaging inside a CTO lesion, the surgeons are blind during guidewire crossing. For this reason, the success rate of guidewire crossing relies upon the proficiency of the surgeon, which is considerably reduced from 69.0% to 32.5% if extensive calcification, not penetrated by a guidewire, exists in CTO lesions. In this paper, a recently developed 40-MHz forward-looking intravascular ultrasound (FL–IVUS) transducer to visualize calcification within CTO lesions is reported. This transducer consists of a single element angled aperture and a guidewire passage. The aperture is spherically deformed to have a focal length of 3 mm in order to improve spatial resolution of FL–IVUS images. The angle between the beam direction and the axis of rotation is designed to be 30° to effectively visualize calcification within a CTO lesion as well as the blood vessel wall. The experimental results demonstrated that the developed FL–IVUS transducer facilitates visualization of calcification within CTO lesions and makes it possible to help the surgeon make decisions about whether to push the guidewire in order to cross the lesion or to change the surgical procedure. [ABSTRACT FROM AUTHOR]

Precise sentinel lymph node (SLN) identification is crucial not only for accurate diagnosis of micro-metastases at an early stage of cancer progression but also for reducing the number of SLN biopsies (SLNB) to minimize their severe side effects. Furthermore, it is desirable that an SLNB guidance should be as safe as possible in routine clinical use. Although there are currently various SLNB guidance methods for pre-operative or intra-operative assessment, none are ideal. We propose a real-time SLNB guidance method using contrast-enhanced tri-modal images (i.e., ultrasound, photoacoustic, and fluorescence) acquired by a recently developed hand-held tri-modal probe. The major advantage of tri-modal imaging is demonstrated here through an in vivo study of the technically-difficult case of nodal obstruction that frequently leads to false-negative results in patients. The results in a tumor model in rabbits and normal controls showed that tri-modal imaging is capable of clearly identifying obstructed SLNs and of indicating their metastatic involvement. Based on these findings, we propose an SLNB protocol to help surgeons take full advantage of the complementary information obtained from tri-modal imaging, including for pre-operative localization, intra-operative biopsy guidance and post-operative analysis. [ABSTRACT FROM AUTHOR]

In intravascular ultrasound (IVUS) imaging, a transducer is inserted into a blood vessel and rotated to obtain image data. For this purpose, the transducer aperture is typically less than 0.5 mm in diameter, which causes natural focusing to occur in the imaging depth ranging from 1 to 5 mm. Due to the small aperture, however, it is not viable to conduct geometric focusing in order to enhance the spatial resolution of IVUS images. Furthermore, this hampers narrowing the slice thickness of a cross-sectional scan plane in the imaging depth, which leads to lowering spatial and contrast resolutions of IVUS images. To solve this problem, we propose an oblong-shaped-focused transducer for IVUS imaging. Unlike the conventional IVUS transducers with either a circular or a square flat aperture, the proposed transducer has an oblong aperture of which long side is positioned along a blood vessel. This unique configuration makes it possible to conduct geometric focusing at a desired depth in the elevation direction. In this study, furthermore, it is demonstrated that a spherically shaped aperture in both lateral and elevation directions also improves lateral resolution, compared to the conventional flat aperture. To ascertain this, the conventional and the proposed IVUS transducers were designed and fabricated to evaluate and to compare their imaging performances through wire phantom and tissue-mimicking phantom experiments. For the proposed 50-MHz IVUS transducer, a PZT piece of 0.5 × 1.0 mm2 was spherically shaped for elevation focus at 3 mm by using the conventional press-focusing technique whereas the conventional one has a flat aperture of 0.5 × 0.5 mm2. The experimental results demonstrated that the proposed IVUS transducer is capable of improving spatial and contrast resolutions of IVUS images. [ABSTRACT FROM AUTHOR]

An electrical impedance matching (EIM) network is proposed to achieve the broad bandwidth of a high frequency ultrasound transducer and to improve the signal-to-noise ratio (SNR) of an ultrasound image. The proposed EIM network is based on a general filter structure, i.e., either low-pass filter (LPF) or high-pass filter (HPF) structure composing a capacitor and an inductor. Either filter type can be selected depending on the spectral characteristics of a transducer. The prominent advantage of the proposed method is the capability to broaden the spectrum of a transducer by means of modifying its original spectrum. The values of the electronic components are computed with the measured electrical impedances of a transducer and an imaging system. In this paper, the EIM between a custom-made 50 MHz ultrasound needle transducer and a commercial pulser/receiver system was conducted to verify the characteristics and performance of the proposed method. The experimental results demonstrated that the proposed EIM network is capable of achieving the best performance of the transducer, i.e., broad bandwidth and high SNR that are desirable for the high quality of high frequency ultrasound images. [ABSTRACT FROM AUTHOR]

Objective: Two-dimensional (2D) photoacoustic (PA) imaging based on array transducers provide high spatial resolution in the lateral direction by adopting receive dynamic focusing. However, the quality of PA image is often deteriorated by poor elevational resolution which is achieved by an acoustic lens. To overcome this limitation, we present a three-dimensional (3D) image reconstruction method using a commercial one-dimensional (1D) array transducer. Methods: In the method, the elevational resolution is improved by applying synthetic aperture focusing (SAF) technique along the elevational direction. For this, a commercially available 1D array transducer with an acoustic lens is modeled and appropriate synthetic focusing delay that can minimize the effect of the acoustic lens is derived by mathematical analysis. Results: From the simulation and experiment results, it was demonstrated that the proposed method can enhance the image quality of PA imaging, i.e., elevational resolution and signal-to-noise ratio (SNR). Conclusion: 3D PA images with improved elevational resolution were achieved using a clinical 1D array transducer. Significance: The presented method may be useful for clinical application such as detecting microcalcification, imaging of tumor vasculature and guidance of biopsy in real time. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HAP, Ca10(PO4)6(OH)2) nanoparticles with controlled materials properties have been synthesized through a two-step hydrothermal aging method to investigate fibronectin (Fn) adsorption. Two distinct populations of HAP nanoparticles have been generated: HAP1 particles had smaller size, plate-like shape, lower crystallinity, and more negative potential than HAP2 particles. We then developed two-dimensional platforms containing HAP and Fn and analyzed both the amount and the conformation of Fn via Förster resonance energy transfer (FRET) at various HAP concentrations. Our FRET analysis reveals that larger amounts of more compact Fn molecules were adsorbed onto HAP1 than onto HAP2 particles. Additionally, our data show that the amount of compact Fn adsorbed increased with increasing HAP concentration due to the formation of nanoparticle agglomerates. We propose that both the surface chemistry of single nanoparticles and the size and morphology of HAP agglomerates play significant roles in the interaction of Fn with HAP. Collectively, our findings suggest that the HAP-induced conformational changes of Fn, a critical mechanotransducer protein involved in the communication of cells with their environment, will ultimately affect downstream cellular behaviors. These results have important implications for our understanding of organic-inorganic interactions in physiological and pathological biomineralization processes such as HAP-related inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Effective receive beamforming in medical ultrasound imaging is important for enhancing spatial and contrast resolution. In current ultrasound receive beamforming, a constant sound speed (e.g., 1540m/s) is assumed. However, the variations of sound speed in soft tissues could introduce phase distortions, leading to degradation in spatial and contrast resolution. This degradation becomes even more severe in imaging fatty tissues (e.g., breast) and with obese patients. In this paper, a mean sound speed estimation method where phase variance of radio-frequency channel data in the region of interest is evaluated is presented for improving spatial and contrast resolution. The proposed estimation method was validated by the Field II simulation and the tissue mimicking phantom experiments. In the simulation, the sound speed of the medium was set to 1450m/s and the proposed method was capable of capturing this value correctly. From the phantom experiments, the −18-dB lateral resolution of the point target at 50mm obtained with the estimated mean sound speed was improved by a factor of 1.3, i.e., from 3.9mm to 2.9mm. The proposed estimation method also provides an improvement of 0.4 in the contrast-to-noise ratio, i.e., from 2.4 to 2.8. These results indicate that the proposed mean sound speed estimation method could enhance the spatial and contrast resolution in the medical ultrasound imaging systems. [Copyright &y& Elsevier]

Photoacoustic (PA) imaging is used widely in cancer diagnosis. However, the availability of PA agents has not made great progress due to the limitations of the one currently in use, porphyrin. Porphyrin–Micelle (PM), developed by synthesizing porphyrin and PEG-3.5k, confirmed the amplification of the PA agent signal, and added binding affinity in an LNCaP model by attaching prostate-specific membrane antigen PSMA. Compared to the previously used porphyrin, a superior signal was confirmed, and the potential of PMP was confirmed when it showed a signal superior to that of hemoglobin at the same concentration. In addition, in the in vivo mouse experiment, it was confirmed that the signal in the LNCaP xenograft model was stronger than that in the PC-3 xenograft model, and the PMP signal was about three times higher than that of PM and porphyrin. [ABSTRACT FROM AUTHOR]

As a molecular imaging modality, photoacoustic (PA) imaging has been in the spotlight because it can provide an optical contrast image of physiological information and a relatively deep imaging depth. However, its sensitivity is limited despite the use of exogenous contrast agents due to the background PA signals generated from nontargeted absorbers, such as blood and boundaries between different biological tissues. In addition, clutter artifacts generated in both in-plane and out-of-plane imaging region degrade the sensitivity of PA imaging. We propose a method to eliminate the nontargeted PA signals. For this study, we used a dual-modal ultrasound (US)-PA contrast agent that is capable of generating both the backscattered US and PA signals in response to the transmitted US and irradiated light, respectively. The US images of the contrast agents are used to construct a masking image that contains the location information about the target site and is applied to the PA image acquired after contrast agent injection. In vitro and in vivo experimental results demonstrated that the masking image constructed using the US images makes it possible to completely remove nontargeted PA signals. The proposed method can be used to enhance the clear visualization of the target area in PA images. [ABSTRACT FROM AUTHOR]

Accumulation of surficial tidal mud was observed in Muan Bay, Korea, to examine seasonal sedimentary cycles typical of semienclosed bays in contrast with open coast in the southeastern Yellow Sea. One-year monitoring of accumulation rates on the tidal flats indicates that patterns of deposition/erosion can be diverse according to both physiographic setting and seasons. During winter, tidal flats undergo slight deposition to moderate erosion depending on localities. In summer, however, the tidal flats are all consistently subject to stronger erosion. Meteorological data suggest that the erosional effect on the tidal flat might come from heavy rainfall during flooding seasons and possibly typhoon. The enduring rainfall could cause the exposed surface of the tidal flat to be sufficiently weakened for tidal currents alone to strip surficial mud off. [Copyright &y& Elsevier]

• SAF and CFW have been used for enhanced resolution of ultrasound imaging. • We ascertained the effectiveness of SAF and CFW for intravascular ultrasound (IVUS) imaging. • From the results, it was found that SAF is not effective for IVUS imaging. • A focused transducer without SAF and CFW may be the best choice for enhanced resolution. Synthetic aperture focusing (SAF) and coherence factor weighting (CFW) have been used to improve the lateral resolution of ultrasound images. Although the two methods are effective for array-based ultrasound imaging, many researchers have also employed the methods for single-element-based imaging including intravascular ultrasound (IVUS) imaging. For single-element-based imaging, CFW is generally calculated from the scanlines obtained by SAF and applied to the scanline obtained after coherent summation of the SAF delayed scanlines, which is called a SAF-CFW method. In the paper, a theoretical model was derived to explore the effectiveness of SAF and CFW for single-element-based imaging, and the model was used to explain that SAF is not effective for IVUS imaging in terms of enhancing the spatial resolution, although it has the advantage of improving a contrast-to-noise ratio (CNR). This means that the SAF-CFW method is not optimal for improving the spatial resolution of IVUS imaging. In contrast, it was found in simulations and experiments that applying CFW to the target scanline itself is beneficial for the spatial resolution rather than a coherent summed scanline for IVUS SAF imaging, but CNR was not as good as SAF and SAF-CFW. As a result of both simulation and experimentation, it could be concluded that focused IVUS transducers without the application of those methods may be more advantageous to improve the spatial and contrast resolution simultaneously, considering the system complexity in the implementation of such imaging methods. [ABSTRACT FROM AUTHOR]

Exosomes, which are released from all cells and take part in cell-to-cell communication, have been utilized as drug delivery vehicles in many recent studies. Immunotherapy is an emerging technology which uses patients' innate immune systems. In immunotherapy, immune cells are stimulated through antibodies, the other immune cells and genetic modifications for the purposes of, for instance, cancer therapy. In this study, tumor-derived re-assembled exosome (R-Exo) was simultaneously utilized as both a drug delivery carrier and an immunostimulatory agent. A chlorin e6 photosensitizer was loaded into tumor-derived exosomes during exosomal re-assembly. After this modification, R-Exo retains its original average size and has the same membrane proteins, which allows for targeting of tumor cells. Chlorin e6-loaded R-Exo (Ce6-R-Exo) can be visualized by photoacoustic imaging and can efficiently generate reactive oxygen species inside tumor cells under laser irradiation. In addition, Ce6-R-Exo increased the release of cytokines from immune cells, which indicates that these modified exosomes can be used as an immunotherapeutic agent. In conclusion, we developed a novel strategy that enables photoacoustic imaging-guided photodynamic and immune-combination therapy for the treatment of cancer with tumor-derived Ce6-R-Exo. Image 1 [ABSTRACT FROM AUTHOR]

We developed a forward-looking (FL) multimodal endoscopic system that offers color, spectral classified, high-frequency ultrasound (HFUS) B-mode, and integrated backscattering coefficient (IBC) images for tumor detection in situ. Examination of tumor distributions from the surface of the colon to deeper inside is essential for determining a treatment plan of cancer. For example, the submucosal invasion depth of tumors in addition to the tumor distributions on the colon surface is used as an indicator of whether the endoscopic dissection would be operated. Thus, we devised the FL multimodal endoscopic system to offer information on the tumor distribution from the surface to deep tissue with high accuracy. This system was evaluated with bilayer gelatin phantoms which have different properties at each layer of the phantom in a lateral direction. After evaluating the system with phantoms, it was employed to characterize forty human colon tissues excised from cancer patients. The proposed system could allow us to obtain highly resolved chemical, anatomical, and macro-molecular information on excised colon tissues including tumors, thus enhancing the detection of tumor distributions from the surface to deep tissue. These results suggest that the FL multimodal endoscopic system could be an innovative screening instrument for quantitative tumor characterization. [ABSTRACT FROM AUTHOR]

Bioresorbable vascular scaffold (BVS) has recently been spotlighted for its unique characteristics of absorbing into blood vessels and eventually disappearing. Although intravascular ultrasound (IVUS) is the most common guiding tool for stent deployment, the echogenicity of BVS struts has changed as the center of stent lumen and scanning rotation is not concentric, which may cause a critical erroneous measurement in practice. This study investigated the physical conditions for dimming the stent brightness in IVUS images using a finite-difference method (FDM) to numerically solve acoustic wave propagation through nonhomogeneous medium. The dimmed brightness is caused by an angled rectangular cross section of a strut and its similar acoustic impedance with water. Imaging frequency is not a major cause. However, the angle between the acoustic beam and the BVS surface is the major cause of the dimmed brightness. As a solution, an approach using a frequency compounding method with signal polarity comparator was proposed to recover the reduced brightness without sacrificing spatial resolutions. Based on the simulation study, the signal level from BVS can be attenuated down by 17 dB when the angle between the acoustic beamline and the surface of BVS is more than 45°. With the proposed frequency compounding approach, the reduced signal can be recovered by 6 dB. In the experimental BVS IVUS imaging, strut brightness was reduced by 18 dB with an angled strut position and recovered by 5 dB with the proposed frequency compounding method. A pig coronary was imaged to demonstrate the performance of the proposed method. [ABSTRACT FROM AUTHOR]

Objective: Interventional ultrasound imaging is a prerequisite for guiding implants and treatment within the hearts and blood vessels. Due to limitations on the catheter's diameter, interventional ultrasonic transducers have side-looking structures although forward-looking imaging may provide more intuitive and real time guidance in treating diseased sites ahead of catheters. To address the issue, a magnetically actuated forward-looking interventional ultrasound imaging device is implemented for the first time. Methods: A forward-looking catheter containing a 1 mm ring type focused 35 MHz ultrasound transducer and a micro magnet, was fabricated. For imaging, the transducer was placed at the center of four electromagnetic coils positioned on four sides of a squared acrylic housing. By modifying the magnetic field, the catheter tip could be remotely translated for sector scanning. Results: The scanning angle could reach up to 3° in 1 Hz with 15 mT, while wider angles of 5° could be achieved with a higher magnetic field of 25 mT for ex-vivo imaging. The position of the transducer could be detected by monitoring the motion with a CCD camera, mimicking clinical X-ray imaging. In the wire target and tissue mimicking phantom studies, the measured hole size, spatial resolution and distance between wires by the proposed system were comparable with the values from a linear scanner. Multi-frame real time data acquisition was demonstrated via ex-vivo imaging on a pig's coronary artery. Conclusion/Significance: The feasibility of magnetically actuated forward-looking interventional ultrasound imaging was demonstrated. The remote-controlled scanning method may allow to simplify the structures of forward-looking interventional ultrasound imaging catheters. [ABSTRACT FROM AUTHOR]

• Ultrasound therapy requires real-time monitoring during treatment. • The use of focused ultrasound (FUS) transducers for the purpose is limited due to their inability to provide high quality of images. • The proposed coded excitation and Wiener deconvolution can enhance the resolution, SNR, and CNR of images acquired by FUS transducers. • The performance of the proposed method was confirmed by imaging experiments. To enhance the effectiveness and safety of focused ultrasound (FUS) therapy, ultrasound image-based guidance and treatment monitoring are crucial. However, the use of FUS transducers for both therapy and imaging is impractical due to their low spatial resolution, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). To address this issue, we propose a new method that significantly improve the quality of images obtained by a FUS transducer. The proposed method employs coded excitation to enhance SNR and Wiener deconvolution to solve the problem of low axial resolution resulting from the narrow spectral bandwidth of FUS transducers. Specifically, the method eliminates the impulse response of a FUS transducer from received ultrasound signals using Wiener deconvolution, and pulse compression is performed using a mismatched filter. Simulation and commercial phantom experiments confirmed that the proposed method significantly improves the quality of images acquired by the FUS transducer. The −6 dB axial resolution was improved 1.27 mm to 0.37 mm that was similar to the resolution achieved by the imaging transducer, i.e., 0.33 mm. SNR and CNR also increased from 16.5 dB and 0.69 to 29.1 dB and 3.03, respectively, that were also similar to those by the imaging transducer (27.8 dB and 3.16). Based on the results, we believe that the proposed method has great potential to enhance the clinical utility of FUS transducers in ultrasound image-guided therapy. [ABSTRACT FROM AUTHOR]

A noncontact single-beam acoustic trapping technique has proven to be a promising tool for cell manipulation and characterization that provide essential knowledge for a variety of biomedical applications. Here, we investigated cell characteristics as to whether the calcium responses of suspended breast cancer cells to different acoustic trapping forces are related to their invasiveness. For this, we combined a single-beam acoustic trapping system with a 30-MHz press-focused lithium niobate ultrasound transducer and an epifluorescence microscope. Using the system, intracellular calcium changes of suspended MDA-MB-231 (highly invasive) and MCF-7 (weakly invasive) cells were monitored while trapping the cells at different acoustic pressures. The results showed that a single suspended breast cancer cell isolated by the acoustic microbeam behaved differently on the calcium elevation in response to changes in acoustic trapping force, depending on its invasiveness. In particular, the MDA-MB-231 cells exhibited higher calcium elevation than MCF-7 cells when each cell was trapped at low acoustic pressure. Based on these results, we believe that the single-beam acoustic trapping technique has high potential as an alternative tool for determining the degree of invasiveness of suspended breast cancer cells. [ABSTRACT FROM AUTHOR]

Tissue harmonic imaging (THI), an essential mode of commercial ultrasound imaging scanners, can provide images with high spatial and contrast resolutions. For THI, the frequency spectrum of a transducer is generally divided for the transmission of fundamental signal and the reception of its second harmonic. Therefore, it is difficult to use the THI mode for intravascular ultrasound (IVUS) imaging because typical IVUS transducers have a narrow −6-dB fractional bandwidth of about 50%. Due to its small aperture (about 0.5 mm) and the strength of IVUS being too weak, it is difficult to construct a high-quality tissue harmonic image. In this paper, we report a recently developed dual-frequency oblong-shaped-focused IVUS transducer for high-quality intravascular THI; the transducer consists of three elements arranged side by side in the horizontal (i.e., elevation) direction. The two outer elements with a center frequency of 35 MHz are responsible for ultrasound transmission and the center element has a center frequency of 70 MHz for the reception of the second-harmonic signals. All three elements have a spherical shape with a radius of 3 mm to efficiently generate harmonics in the region of interest. This configuration of the developed IVUS transducer was determined to facilitate high-quality THI, which was based on the results of Field II simulation and finite-element analysis. The images of wires and a tissue-mimicking phantom indicated that the tissue harmonic images produced by the developed transducer have not only a high spatial resolution but also a deep imaging depth, compared to the 35- and 70-MHz fundamental images. [ABSTRACT FROM AUTHOR]

Photoacoustic (PA) imaging detects acoustic signals generated by thermal expansion of a light-excited tissue or contrast agents. PA signal amplitude and image quality directly depend on the light fluence at the target depth. With conventional PA imaging systems, approximately 30% energy of incident light at the near-infrared region would be lost due to reflection on the skin surface. Such light loss directly leads to a reduction of PA signal and image quality. A new light delivery scheme that collects and redistributes reflected light energy was recently suggested, which is called the light catcher. In our previous study, proof of concept using a finite-element simulation model was shown and a laboratory-built prototype of the light catcher was applied on tissue-mimicking phantoms. In this paper, we present an elaborate prototype of a high-frequency PA probe with the light catcher fabricated using 3-D printing technology, which is conformal to a subcutaneous tumor in mice. The in vivo usefulness of the developed prototype was evaluated in a mouse tumor model. Equipped with the light catcher, PA signal amplitude from the clinical photosensitizer injected into the mouse tumor was enhanced by 33.7%, which is approximately equivalent to the percent light loss due to reflection on the skin. [ABSTRACT FROM PUBLISHER]

The superharmonic imaging of tissue has the potential for high spatial and contrast resolutions, compared to the fundamental and second harmonic imaging. For this technique, the spectral bandwidth of an ultrasound transducer is divided for transmission of ultrasound and reception of its superharmonics (i.e., higher than the second harmonic). Due to the spectral division for the transmission and reception, transmitted ultrasound energy is not sufficient to induce superharmonics in media without using contrast agents, and it is difficult that a transducer has a −6 dB fractional bandwidth of higher than 100%. For the superharmonic imaging of tissue, thus, multi-frequency array transducers are the best choice if available; transmit and receive elements are separate and have different center frequencies. However, the construction of a multi-frequency transducer for intravascular ultrasound (IVUS) imaging is particularly demanding because of its small size of less than 1 mm. Here, we report a recently developed dual-element focused IVUS transducer for the third harmonic imaging of tissue, which consists of a 35-MHz element for ultrasound transmission and a 105-MHz element for third harmonic reception. For high quality third harmonic imaging, both elements were fabricated to have the same focus at 2.5 mm. The results of tissue mimicking phantom tests demonstrated that the third harmonic images produced by the developed transducer had higher spatial resolution and deeper imaging depth than the fundamental images. [ABSTRACT FROM AUTHOR]

Biomedical imaging-guided cancer therapy should have capabilities of both accurate tumor diagnosis and high therapeutic efficacy for the personalized treatment. Various biomedical imaging-guided cancer therapies are currently being investigated to overcome current limitations that include low sensitivity of diagnosis and poor drug delivery to the tumor site. Here, we report the development of a multifunctional theranostic contrast agent demonstrating high sensitive photoacoustic and ultrasound imaging and effective local delivery of anticancer drug to a tumor site. A microbubble (porphyrin-MB) was developed using phospholipid–porphyrin conjugates to enhance ultrasound and photoacoustic signal intensities simultaneously. Paclitaxel-loaded human serum albumin nanoparticles (PTX-HSA-NPs) were then conjugated onto the surface of the microbubble. The developed PTX-HSA-NPs conjugated porphyrin-MB (porphyrin-MB-NPs) provided sensitive, dual modal images of a tumor at 700 nm optimal laser wavelength for photoacoustic imaging and 5–14 MHz operating frequency for the ultrasound imaging. In addition, porphyrin-MB-NPs efficiently suppressed tumor growth by ultrasound exposure. Exposure to the focused ultrasound triggered the collapse of porphyrin-MB-NPs, resulting in the local release of PTX-HSA-NPs and enhanced penetration into the tumor site. The increased preferential accumulation and penetration of PTX-HSA-NPs suppressed tumor growth 10-fold more than without exposure to ultrasound. In conclusion, the developed porphyrin-MB-NPs establish a new paradigm in simultaneous bi-functional ultrasound/photoacoustic imaging diagnosis and locally triggered release of nanomedicine and enhanced chemotherapy efficiency. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging is the latest promising diagnostic modality that has various advantages such as high spatial resolution, deep penetration depth, and use of non-ionizing radiation. It also employs a non-invasive imaging technique and optically functionalized imaging. The goal of this study was to develop a nanomedicine for simultaneous cancer therapy and diagnosis based on photoacoustic imaging. Human serum albumin nanoparticles loaded with melanin and paclitaxel (HMP-NPs) were developed using the desolvation technique. The photoacoustic-based diagnostic and chemotherapeutic properties of HMP-NPs were evaluated through in vitro and in vivo experiments. The size and zeta potential of the HMP-NPs were found to be 192.8 ± 21.11 nm and − 22.2 ± 4.39 mV, respectively. In in vitro experiments, HMP-NPs produced increased photoacoustic signal intensity because of the loaded melanin and decreased cellular viability because of the encapsulated paclitaxel, compared to the free human serum albumin nanoparticles (the control). In vivo experiments showed that the HMP-NPs efficiently accumulated inside the tumor, resulting in the enhanced photoacoustic signal intensity in the tumor site, compared to the normal tissues. The in vivo chemotherapy study demonstrated that HMP-NPs had the capability to treat cancer for an extended period. In conclusion, HMP-NPs were simultaneously capable of photoacoustic diagnostic and chemotherapy against cancer. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the diagnostic utility of PAI at detecting thyroid microcalcifications at 700 nm laser wavelengths. Methods: This study included 36 resected samples in 18 patients. To evaluate the PA manifestation of microcalcifications in PAI, gray level histogram and co-occurrence matrix (COM) texture parameters were extracted from the 3 fixed ROI US and PA images, respectively, per sample. We compared the textural parameters obtained from specimen PAIs between samples with punctate microcalcifications on specimen radiography and those without microcalcifications. Results: On specimen US, the mean value (2748.4±862.5) of samples with microcalcifications on specimen radiography was higher than that (1961.9±780.2) of those without microcalcifications (P = 0.007). However, there were no significant differences in textural parameters obtained from specimen PAIs between samples with punctate microcalcifications on specimen radiography and those without when applying both the mean value of the three slices of thyroid specimens and the value of the thyroid specimen slice which had the highest value of the mean values in specimen US. Conclusion: PAI did not show significant PA contrast on thyroid microcalcifications indicating that the experimental setup and protocols should be enhanced, e.g., method of complete blood rejection from ex vivo specimens, the multi-wavelength spectroscopic PA imaging method which can solely extract the PA signal from microcalcifications even with high spectral interferences, or PA imaging with narrower slice thickness using 2-dimensional array transducer, etc. [ABSTRACT FROM AUTHOR]

Background: We presented the photoacoustic imaging (PAI) tool and to evaluate whether microcalcifications in breast tissue can be detected on photoacoustic (PA) images. Methods: We collected 21 cores containing microcalcifications (n = 11, microcalcification group) and none (n = 10, control group) in stereotactic or ultrasound (US) guided 8-gauge vacuum-assisted biopsies. Photoacoustic (PA) images were acquired through ex vivo experiments by transmitting laser pulses with two different wavelengths (700 nm and 800 nm). The presence of microcalcifications in PA images were blindly assessed by two radiologists and compared with specimen mammography. A ratio of the signal amplitude occurring at 700 nm to that occurring at 800 nm was calculated for each PA focus and was called the PAI ratio. Results: Based on the change of PA signal amplitude between 700 nm and 800 nm, 10 out of 11 specimens containing microcalcifications and 8 out of 10 specimens without calcifications were correctly identified on blind review; the sensitivity, specificity, accuracy, positive predictive and negative predictive values of our blind review were 90.91%, 80.0%, 85.71%, 83.33% and 88.89%. The PAI ratio in the microcalcification group was significantly higher than that in the control group (the median PAI ratio, 2.46 versus 1.11, respectively, P = .001). On subgroup analysis in the microcalcification group, neither malignant diagnosis nor the number or size of calcification-foci was proven to contribute to PAI ratios. Conclusion: Breast microcalcifications generated distinguishable PA signals unlike breast tissue without calcifications. So, PAI, a non-ionizing and non-invasive hybrid imaging technique, can be an alternative in overcoming the limitations of conventional US imaging. [ABSTRACT FROM AUTHOR]

A combined transrectal ultrasound and photoacoustic (TRUS–PA) imaging probe was developed for the clear visualization of morphological changes and microvasculature distribution in the prostate, as this is required for accurate diagnosis and biopsy. The probe consisted of a miniaturized 128-element 7 MHz convex array transducer with 134.5° field-of-view (FOV), a bifurcated optical fiber bundle, and two optical lenses. The design goal was to make the size of the TRUS–PA probe similar to that of general TRUS probes (i.e., about 20 mm), for the convenience of the patients. New flexible printed circuit board (FPCB), acoustic structure, and optical lens were developed to meet the requirement of the probe size, as well as to realize a high-performance TRUS–PA probe. In visual assessment, the PA signals obtained with the optical lens were 2.98 times higher than those without the lens. Moreover, the in vivo experiment with the xenograft BALB/c (Albino, Immunodeficient Inbred Strain) mouse model showed that TRUS–PA probe was able to acquire the entire PA image of the mouse tight behind the porcine intestine about 25 mm depth. From the ex vivo and in vivo experimental results, it can be concluded that the developed TRUS–PA probe is capable of improving PA image quality, even though the TRUS–PA probe has a cross-section size and an FOV comparable to those of general TRUS probes. [ABSTRACT FROM AUTHOR]