Microbubble detection on ultrasound imaging by utilizing phase patterned waves.

OBJECTIVE: Super-resolution ultrasonography (SR-US) offers the advantage of visualization of intricate microvasculature, which is crucial for disease diagnosis. Mapping of microvessels is possible by localizing microbubbles that act as contrast agents and tracking their location. However, there are limitations such as the low detectability of microbubbles and the utilization of a diluted concentration of microbubbles, leading to the extension of the acquisition time. We aim to enhance the detectability of microbubbles to reduce the acquisition time of acoustic data necessary for mapping the microvessels. Approach: We propose utilizing phase patterned waves (PPWs) characterized by spatially patterned phase distributions in the incident beam to achieve this. In contrast to conventional ultrasound irradiation methods, this irradiation method alters bubble interactions, enhancing the oscillation response of microbubbles and generating more significant scattered waves from specific microbubbles. This enhances the detectability of microbubbles, thereby enabling the detection of microbubbles that were undetectable by the conventional method. The objective is to maximize the overall detection of bubbles by utilizing ultrasound imaging with additional PPWs, including the conventional method. In this paper, we apply PPWs to ultrasound imaging simulations considering bubble-bubble interactions to elucidate the characteristics of PPWs, and demonstrate their efficacy by employing PPWs on microbubbles fixed in a phantom by the experiment. Main results: By utilizing two types of PPWs in addition to the conventional ultrasound irradiation method, we confirmed the detection of up to 93.3% more microbubbles compared to those detected using the conventional method alone. Significance: Ultrasound imaging using additional PPWs made it possible to increase the number of detected microbubbles, which is expected to improve the efficiency of bubble detection.

Batch Fine Magnetic Pattern Transfer Method on Permanent Magnets Using Coercivity Change during Heating for Magnetic MEMS.

In magnetic microelectromechanical systems (MEMSs), permanent magnets in the form of a thick film or thin plate are used for structural and manufacturing purposes. However, the geometric shape induces a strong self-demagnetization field during thickness-direction magnetization, limiting the surface magnetic flux density and output power. The magnets must be segmented or magnetized in a fine and multi-pole manner to weaken the self-demagnetization field. Few studies have been performed on fine multi-pole magnetization techniques that can generate a higher surface magnetic flux density than segmented magnets and are suitable for mass production. This paper proposes a batch fine multi-pole magnetic pattern transfer (MPT) method for the magnets of MEMS devices. The proposed method uses two master magnets with identical magnetic patterns to sandwich a target magnet. Subsequently, the coercivity of the target magnet is reduced via heating, and the master magnet's magnetic pattern is transferred to the target magnet. Stripe, checkerboard, and concentric circle patterns with a pole pitch of 0.3 mm are magnetized on the NdFeB master magnets N38EH with high intrinsic coercivity via laser-assisted heating magnetization. The MPT yields the highest surface magnetic flux density at 160 °C, reaching 39.7-66.1% of the ideal magnetization pattern on the NdFeB target magnet N35.

Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility.

BACKGROUND: High-Mobility Group Box 1 (HMGB1) and HMGB2 are chromatin-associated proteins that belong to the HMG protein family, and are involved in the regulation of DNA transcription during cell differentiation, proliferation and regeneration in various tissues. However, the role of HMGB2 in ovarian folliculogenesis is largely unknown. METHODS: We investigated the functional role of HMGB1 and HMGB2 in ovarian folliculogenesis and fertilization using C57BL/6 wild type (WT) and HMGB2-knockout (KO) mice. Ovarian tissues were obtained from WT and HMGB2-KO mice at postnatal days 0, 3, 7, and 2, 6 months of age, then performed immunohistochemistry, qPCR and Western blotting analyses. Oocyte fertilization capability was examined by natural breeding and in vitro fertilization experiments. RESULTS: In HMGB2-KO mice, ovary weight was decreased due to reduced numbers of oocytes and follicles. Natural breeding and in vitro fertilization results indicated that HMGB2-KO mice are subfertile, but not sterile. Immunohistochemistry showed that oocytes expressed HMGB2, but not HMGB1, in neonatal and adult WT ovaries. Interestingly, in HMGB2-KO ovaries, a compensatory increase in HMGB1 was found in oocyte nuclei of neonatal and 2-month-old mice; however, this was lost at 6 months of age. CONCLUSIONS: The depletion of HMGB2 led to alterations in ovarian morphology and function, suggesting that HMGB2 plays an essential role in ovarian development, folliculogenesis and fertilization.

A Disposable Electromagnetic Bi-Directional Micropump Utilizing a Rotating Multi-Pole Ring Magnetic Coupling.

Electromagnetic bi-directional micropumps (EMBM) are indispensable for the development of portable devices which enable fluid transportation in forward and reverse directions. However, the high disposal cost of rare-earth magnets attached to the fluidic part and the low pump density due to multiple motors limit their practical application in disposable multi-channel microfluidic applications such as droplet-based oscillatory-flow (DBOF) rapid PCR amplification. Therefore, this paper presented a low-cost, disposable, high-pump-density EMBM. To reduce the disposal cost, we separated the magnets from the disposable fluidic part and used cylindrical holes to store and guide the magnet, which resulted in the ability to reuse all the magnets. To increase the pump density, we used the combination of one motor and one multi-pole ring magnet to drive several channels simultaneously. A proof-of-concept prototype with a pump density of 0.28 cm-2 was fabricated and experimentally evaluated. The fabricated micropump exhibited a maximum flow rate of 0.86 mL/min and a maximum backpressure of 0.5 kPa at a resonant frequency around 50 Hz. The developed multi-channel micropump with reusable magnets is highly beneficial to the development of low-cost and high-throughput rapid PCR amplification microchips and therefore can have a significant impact on timely infectious disease recognition and intervention.

Number concentration dependence of ultrasonic disruption ratio of diameter-sorted microcapsules.

The use of ultrasound to destroy microcapsules in microbubble-assisted drug delivery systems (DDS) is of great interest. In the present study, the disruption ratios of capsule clusters were measured by observing and experimentally analyzing microcapsules with polymer shells undergoing disruption by ultrasound. The microcapsules were dispersed in a planar microchamber filled with a gelatin gel and sonicated using 1 MHz focused ultrasound. Different capsule populations were obtained using a filtration technique to modify and control the capsule sizes. The disruption ratio as a function of the concentration of capsules was obtained through image processing of the recorded photomicrographs. We found that the disruption ratio for each population exponentially decreases as the particle number concentration (PNC) increases. The maximum disruption ratio of the diameter-sorted capsules was larger than that of polydispersed capsules. Particularly, for resonant capsule populations, the ratio was more than twice that of polydispersed capsules. Furthermore, the maximum disruption ratio occurred at higher concentrations as the mean particle diameter of the capsule cluster decreased.

Crucial role of high-mobility group box 2 in mouse ovarian follicular development through estrogen receptor beta.

High-mobility group box 2 (HMGB2) is a chromatin-associated protein that is an important regulator of gene transcription, recombination, and repair processes. The functional importance of HMGB2 has been reported in various organs, including the testis, heart, and cartilage. However, its role in the ovary is largely unknown. In this study, ovary tissues from wild-type (WT) and HMGB2-knock-out (KO) mice were examined by histopathological staining and immunohistochemistry. The ovary size and weight were significantly lower in HMGB2-KO mice than in age-matched WT littermates. Histopathological analysis revealed ovarian atrophy and progressive fibrosis in 10-month-old HMGB2-KO mouse ovaries. Compared to age-matched WT mice, the numbers of oocytes and developing follicles were significantly decreased at 2 months of age and were completely depleted at 10 months of age in HMGB2-KO mice. Immunohistochemistry revealed the expression of HMGB2 in the granulosa cells of developing follicles, oocytes, some corpora lutea, and stromal cells. Importantly, HMGB2-positive cells were co-localized with estrogen receptor beta (ERß), but not ERα. Estrogen response element-binding activity was demonstrated by southwestern histochemistry, and it was decreased in HMGB2-KO mouse ovaries. Cell proliferation activity was also decreased in HMGB2-KO mouse ovaries in parallel with the decreased folliculogenesis. These results indicated that the depletion of HMGB2 induced ovarian atrophy that was characterized by a decreased ovarian size and weight, progressive fibrosis, as well as decreased oocytes and folliculogenesis. In conclusion, we demonstrated the crucial role of HMGB2 in mouse ovarian folliculogenesis through ERß expression.

Depletion of high-mobility group box 2 causes seminiferous tubule atrophy via aberrant expression of androgen and estrogen receptors in mouse testis†.

High-mobility group box 2, a chromatin-associated protein that interacts with deoxyribonucleic acid, is implicated in multiple biological processes, including gene transcription, replication, and repair. High-mobility group box 2 is expressed in several tissues, including the testis; however, its functional role is largely unknown. Here, we elucidated the role of high-mobility group box 2 in spermatogenesis. Paraffin-embedded testicular tissues were obtained from 8-week-old and 1-year-old wild-type and knock-out mice. Testis weight and number of seminiferous tubules were decreased, whereas atrophic tubules were increased in high-mobility group box 2-depleted mice. Immunohistochemistry revealed that atrophic tubules contained Sertoli cells, but not germ cells. Moreover, decreased cell proliferation and increased apoptosis were demonstrated in high-mobility group box 2-depleted mouse testis. To elucidate the cause of tubule atrophy, we examined the expression of androgen and estrogen receptors, and the results indicated aberrant expression of androgen receptor and estrogen receptor alpha in Sertoli and Leydig cells. Southwestern histochemistry detected decreased estrogen response element-binding sites in high-mobility group box 2-depleted mouse testis. High-mobility group box 1, which has highly similar structure and function as high-mobility group box 2, was examined by immunohistochemistry and western blotting, which indicated increased expression in testis. These findings indicate a compensatory increase in high-mobility group box 1 expression in high-mobility group box 2 knock-out mouse testis. In summary, depletion of high-mobility group box 2 induced aberrant expression of androgen receptor and estrogen receptor alpha, leading to decreased germ cell proliferation and increased apoptosis which resulted in focal seminiferous tubule atrophy.

Experiment and modeling of translational dynamics of an oscillating bubble cluster in a stationary sound field.

Translational motion of an oscillating bubble cluster under sound irradiation is studied experimentally and is modeled in the framework of the classical approach of Bjerknes. An experimental technique is proposed to observe bubble cluster formation and its translational dynamics interacting with wall boundaries due to the secondary Bjerknes force. The translational motion observed in the experiment is modeled by extending the classical theory of Bjerknes on a single bubble; a bubble cluster is treated as a single bubble. The extended Bjerknes theory is shown to allow us to predict the overall trajectory of the cluster translating toward a wall of finite acoustic impedance by tuning acoustic energy loss at the wall. The drag force turns out to be unimportant for the translation of a millimeter-sized cluster that we observed.

Nonlinear normal modes and localization in two bubble oscillators.

We investigated a bifurcation structure of coupled nonlinear oscillation of two spherical gas bubbles subject to a stationary sound field by means of nonlinear modal analysis. The goal of this paper is to describe an energy localization phenomenon of coupled two-bubble oscillators, resulting from symmetry-breaking bifurcation of the steady-state oscillation. Approximate asymptotic solutions of nonlinear normal modes (NNMs) and steady state oscillation are obtained based on the method of multiple scales. It is found that localized oscillation arises in a neighborhood of the localized normal modes. The analytical solutions of the amplitude and the phase shift of the steady-state oscillation are compared to numerical results and found to be in good agreement within the limit of small-amplitude oscillation. For larger amplitude oscillation, a bifurcation diagram of the localized solution as a function of the driving frequency and the separation distance between the bubbles is provided in the presence of the thermal damping. The numerical results show that the localized oscillation can occur for a fairly typical parameter range used in practical experiments and simulations in the early literatures.