Enhanced Chemodynamic Therapy Mediated by a Tumor-Specific Catalyst in Synergy with Mitophagy Inhibition Improves the Efficacy for Endometrial Cancer.

Chemodynamic therapy (CDT) relies on the tumor microenvironment (e.g., high H2 O2 level) responsive Fenton-like reactions to produce hydroxyl radicals (·OH) against tumors. However, endogenous H2 O2 is insufficient for effective chemodynamic responses. An NAD(P)H: quinone oxidoreductase 1 (NQO1)high catalase (CAT)low therapeutic window for the use of NQO1 bioactive drug ß-lapachone (ß-Lap) is first identified in endometrial cancer (EC). Accompanied by NADH depletion, NQO1 catalyzes ß-Lap to produce excess H2 O2 and initiate oxidative stress, which selectively suppress NQO1high EC cell proliferation, induce DNA double-strand breaks, and promote apoptosis. Moreover, shRNA-mediated NQO1 knockdown or dicoumarol rescues NQO1high EC cells from ß-Lap-induced cytotoxicity. Arginine-glycine-aspartic acid (RGD)-functionalized iron-based metal-organic frameworks (MOF(Fe)) further promote the conversion of the accumulated H2 O2 into highly oxidative ·OH, which in turn, exacerbates the oxidative damage to RGD-positive target cells. Furthermore, mitophagy inhibition by Mdivi-1 blocks a powerful antioxidant defense approach, ultimately ensuring the anti-tumor efficacy of stepwise-amplified reactive oxygen species signals. The tumor growth inhibition rate (TGI) is about 85.92%. However, the TGI of MOF(Fe)-based synergistic antitumor therapy decreases to only 50.46% in NQO1-deficient KLE tumors. Tumor-specific chemotherapy and CDT-triggered therapeutic modality present unprecedented therapeutic benefits in treating NQO1high EC.

Effect of geometric parameters of electrodes on skin heating for the design of non-ablative radiofrequency device.

BACKGROUND: Non-ablative radiofrequency (RF) has been widely used in clinical and at-home cosmetics devices. RF electrode geometry can influence the heat distribution in the tissue. This study analyzes the influence of geometric parameters of the electrode on the heat distribution in the layered tissue. MATERIALS & METHODS: The finite element simulation of the electrothermal coupling field was performed to obtain the three-dimensional (3D) temperature distribution of the four-layer tissue. The electrode geometric parameters including the inter-electrode spacing (5-12 mm), width (1-3 mm), length (3-10 mm), shapes (bar, dot and circle), and the coupling gel's electrical conductivity (0.2-1.5 S/m) were simulated. The maximum temperature at 2 mm depth (T-2 mm ) and the temperature difference (Tdiff ) between the maximum skin surface temperature and T-2 mm were obtained to evaluate the effectiveness and safety. RESULTS: The effect of geometric parameters on the effectiveness and safety was mixed. The maximum T-2 mm occurred with the 5 mm inter-electrode spacing, 3 mm width, 10 mm length, the circle-shaped electrode, and the 1.5 S/m coupling gel's electrical conductivity. The ratio of inter-electrode spacing to width at around four can achieve rapid temperature rise and skin surface temperature protection. The electrode shape influenced the area of temperature rise in the tissue's cross-section. The coupling gel's electrical conductivity should be close to that of the skin to avoid energy accumulation on the skin surface. CONCLUSION: The electrode's geometric parameters affect the effectiveness and safety of the RF product. This study has provided the simulation procedure for the electrode design.

[Measurement of Phase-controlled Characteristics of HIFU Based on Infrared Thermal Imaging].

Phase-Controlled high intensity focused ultrasound 3D temperature distribution is the key indicator for measuring the efficiency of HIFU transducer. Considerable progress has been achieved in the use of infrared (IR) imaging techniques for qualitative mapping of acoustic and thermal field of high intensity focused ultrasound (HIFU) transducers. This article proposes a method to measure phased-controlled characteristics of HIFU based on infrared thermal imaging and establishes a whole measurement system to make the method more quantitative and reliable. The result shows that the proposed measurement system is able to measure pHIFU characteristics rapidly and precisely, which will be of great significance in standardizing the measurement of pHIFU acoustic field.

[Research on Shielding of Emboli with the Phase-Controlled Ultrasound].

The postoperative neurological complications is associated with intraoperative cerebral emboli, which results from extracorporeal circulation and operation. It can effectively reduce the incidence of neurological complications with ultrasonic radiation. In fluids, a particle will change it's motion trail when it is acted by the radiation force generated by the ultrasound. This article mainly discuss how to shielding emboli with ultrasound. The equipment can transmit phased ultrasonic signals, which is designed on a FPGA development board. The board can generate a square wave, which is converted into a sine wave through a power amplifier. In addition, the control software has been developed on Qt development environment. The result indicates it's feasible to shielding emboli with ultrasonic radiation force. This article builds a strong foundation for the future research.

[Research on Choosing Position for Measurement of Magnetically Induced Displacement Force on Medical Devices].

Metal implants will be affected by force in the magnetic resonance environment, this paper's experiment measured all the spatial position of the magnetic field, combining with computer, found out the limit conditional position in the space available in the magnetic resonance environment. For devices below saturation, the location of maximum deflection is at the point where the multiply value of the magnitude of the magnetic field and the magnitude of the spatial gradient of the magnetic field is maximum. Above the magnetic saturation point, the maximum deflection will occur at the location where the magnitude of the magnetic field is maximum.

[Research on Choosing Position for Measurement of Magnetically Induced Displacement Force on Medical Devices].

Metal implants will be affected by force in the magnetic resonance environment, this paper's experiment measured all the spatial position of the magnetic field, combining with computer, found out the limit conditional position in the space available in the magnetic resonance environment. For devices below saturation, the location of maximum deflection is at the point where the multiply value of the magnitude of the magnetic field and the magnitude of the spatial gradient of the magnetic field is maximum. Above the magnetic saturation point, the maximum deflection will occur at the location where the magnitude of the magnetic field is maximum.

[A focused sound field measurement system by LabVIEW].

In this paper, according to the requirement of the focused sound field measurement, a focused sound field measurement system was established based on the LabVIEW virtual instrument platform. The system can automatically search the focus position of the sound field, and adjust the scanning path according to the size of the focal region. Three-dimensional sound field scanning time reduced from 888 hours in uniform step to 9.25 hours in variable step. The efficiency of the focused sound field measurement was improved. There is a certain deviation between measurement results and theoretical calculation results. Focal plane--6 dB width difference rate was 3.691%, the beam axis--6 dB length differences rate was 12.937%.

Sensitivity improvement of subharmonic-based pressure measurement using phospholipid-coated monodisperse microbubbles.

The use of the subharmonic signal from microbubbles exposed to ultrasound is a promising safe and cost-effective approach for the non-invasive measurement of blood pressure. Achieving a high sensitivity of the subharmonic amplitude to the ambient overpressure is crucial for clinical applications. However, currently used microbubbles have a wide size distribution and diverse shell properties. This causes uncertainty in the response of the subharmonic amplitude to changes in ambient pressure, which limits the sensitivity. The aim of this study was to use monodisperse microbubbles to improve the sensitivity of subharmonic-based pressure measurements. With the same shell materials and gas core, we used a flow-focusing microfluidic chip and a mechanical agitation method to fabricate monodisperse (∼2.45-µm mean radius and 4.7 % polydisperse index) and polydisperse microbubbles (∼1.51-µm mean radius and 48.4 % polydisperse index), respectively. We varied the ultrasound parameters (i.e., the frequency, peak negative pressure (PNP) and pulse length), and found that there was an optimal excitation frequency (2.8 MHz) for achieving maximal subharmonic emission for monodisperse microbubbles, but not for polydisperse microbubbles. Three distinct regimes (occurrence, growth, and saturation) were identified in the response of the subharmonic amplitude to increasing PNP for both monodisperse and polydisperse microbubbles. For the polydisperse microbubbles, the subharmonic amplitude decreased either monotonically or non-monotonically with ambient overpressure, depending on the PNP. By contrast, for the monodisperse microbubbles, there was only a monotonic decrease at all PNPs. The maximum sensitivity (1.18 dB/kPa, R2 = 0.97) of the subharmonic amplitude to ambient overpressure for the monodisperse microbubbles was ∼6.5 times higher than that for the polydisperse microbubbles (0.18 dB/kPa, R2 = 0.88). These results show that monodisperse microbubbles can achieve a more consistent response of the subharmonic signal to changes in ambient overpressure and greatly improve the measurement sensitivity.

Transcostal high-intensity focused ultrasound treatment using phased array with geometric correction.

In the high-intensity focused ultrasound treatment of liver tumors, ultrasound propagation is affected by the rib cage. Because of the diffraction and absorption of the bone, the sound distribution at the focal plane is altered, and more importantly, overheating on the rib surface might occur. To overcome these problems, a geometric correction method is applied to turn off the elements blocked by the ribs. The potential of steering the focus of the phased-array along the propagation direction to improve the transcostal treatment was investigated by simulations and experiments using different rib models and transducers. The ultrasound propagation through the ribs was computed by a hybrid method including the Rayleigh-Sommerfeld integral, k-space method, and angular spectrum method. A modified correction method was proposed to adjust the output of elements based on their relative area in the projected "shadow" of the ribs. The simulation results showed that an increase in the specific absorption rate gain up to 300% was obtained by varying the focal length although the optimal value varied in each situation. Therefore, acoustic simulation is required for each clinical case to determine a satisfactory treatment plan.

[Temperature distribution based on Monte Carlo method of optical transmission in tissues of laser ablation].

Monte Carlo method was used for calculation of finite-diameter laser distribution in tissues through convolution operation. Photo-thermal ablation model was set up on the basis of Pennes bioheat equation, and tissue temperature distribution was simulated by using finite element method by ANSYS through the model. The simulation result is helpful for clinical application of laser.

[Perfluoropentane droplets enhanced HIFU therapeutic effect].

A small HIFU system was used to investigate the phase-shift droplet vaporization in vivo and its effect on thermal absorption in tissue-mimicking phantoms. The experiments demonstrated that droplets could be vaporized to bubbles in vivo by the small HIFU system and the volume of bubbles could increase by tens of times. With appropriate droplets concentration, lesion volume produced by HIFU could be increased significantly under the same HIFU parameter.

A Three-dimensional Simulation Based on Radiofrequency Electrothermal Coupling fields for Skin Rejuvenation.

Radiofrequency (RF) current is used as an effective non-ablative method for skin rejuvenation. However, mixed results have been reported using different home-use RF devices. In order to evaluate the safety and effectiveness of home-use RF devices, this study has provided a three-dimensional (3D) simulation procedure based on the electrothermal coupling model for home-use RF devices. Firstly, the tissue geometric model with the setting electrode shapes was established and then imported into the simulation software. Secondly, electrical and thermal boundary conditions with excitation voltages were loaded to the corresponding components. In addition, the items of 3D temperatures at all locations and key temperatures of the tissue were assessed. The results have shown the temperature distributions of four commercial RF products, respectively. This 3D RF electrothermal coupling simulation can be conducted quickly and effectively to obtain the temperature and electric distribution of the home-use RF devices at different using periods, which is also useful for the design of home-use RF devices.Clinical Relevance- This study provides a simple and effective simulation procedure for device developers to evaluate the home-use RF devices when designing products. This simulation is also helpful for customer decision-making and performance evaluation considering different devices.

Reciprocal assistance of intravascular imaging in three-dimensional stent reconstruction: Using cross-modal translation based on disentanglement representation.

BACKGROUND: Accurate and efficient 3-dimension (3D) reconstruction of coronary stents in intravascular imaging of optical coherence tomography (OCT) or intravascular ultrasound (IVUS) is important for optimization of complex percutaneous coronary interventions (PCI). Deep learning has been used to address this technical challenge. However, manual annotation of stent is strenuous, especially for IVUS images. To this end, we aim to explore whether the OCT and IVUS images can assist each other in stent 3D reconstruction when one of them is lack of labeled dataset. METHODS: We firstly performed cross-modal translation between OCT and IVUS images, where disentangled representation was employed to generate synthetic images with good stent consistency. The reciprocal assistance of OCT and IVUS in stent 3D reconstruction was then conducted by applying unsupervised and semi-supervised learning with the aid of synthetic images. Stent consistency in synthetic images and reciprocal effectiveness in stent 3D reconstruction were quantitatively assessed by F1-Score (FS) on two datasets: OCT-High Definition IVUS (HD IVUS) and OCT-Conventional IVUS (IVUS). RESULTS: The employment of disentangled representation achieved higher stent consistency in synthetic images (OCT to HD IVUS: FS=0.789 vs 0.684; HD IVUS to OCT: FS=0.766 vs 0.682; OCT to IVUS: FS=0.806 vs 0.664; IVUS to OCT: FS=0.724 vs 0.673). For stent 3D reconstruction, the assistance from synthetic images significantly promoted unsupervised adaptation across modalities (OCT to HD IVUS: FS=0.776 vs 0.109; HD IVUS to OCT: FS=0.826 vs 0.125; OCT to IVUS: FS=0.782 vs 0.068; IVUS to OCT: FS=0.815 vs 0.123), and improved performance in semi-supervised learning, especially when only limited labeled data was available. CONCLUSION: The intravascular images of OCT and IVUS can provide reciprocal assistance to each other in stent 3D reconstruction by cross-modal translation, where the stent consistency in synthetic images was maintained by disentangled representation.

Effects of different parameters in the fast scanning method for HIFU treatment.

PURPOSE: High-intensity focused ultrasound is a promising method for the noninvasive treatment of benign and malignant tumors. This study analyzes the effects of scanning path, applied power, and geometric characteristics of the transducer on ablation using fast scanning method, a new scanning method that uses high-intensity focused ultrasound at different blood perfusion levels. METHODS: Two transducers, six scanning paths, and three focal patterns were used to examine the ablation results of the fast scanning method using power densities from 1.35 × 10(7) W∕m(3) to 4.5 × 10(7) W∕m(3) and blood perfusion rates from 2 × 10(-3) ml∕ml∕s to 16 × 10(-3) ml∕ml∕s. The Pennes equation was solved using the finite-difference time-domain method to simulate the heating procedure. RESULTS: Based on the results of the fast-scanning method, the different scanning paths exhibited small effect on the total treatment time supported by both simulation and least-square fit. Similar-sized lesions can result from the five different repeated paths, whereas a random path may lead to relative large fluctuations in ablation volume because of asymmetry of the lesions. Higher power levels increase the lesion volume and decrease the treatment time required for ablating a target area using the fast scanning method, whereas increased blood perfusion has the opposite effect on ablation volume and treatment time. A symmetric lesion can be produced through fast scanning method using a 65-element and a 90-element transducer. However, lesion production using the same operation scheme differs between the two transducers. CONCLUSIONS: Unlike traditional scanning methods, fast scanning method produces a planned lesion regardless of scanning path, as long as the path consists of repeated subsequences. This attribute makes fast scanning method an easy-operation scheme that produces relatively large symmetric lesions in homogeneous tissues. Applied power is the most important factor; however, high blood perfusion levels can limit or even hinder the full ablation of the target area. Therefore, tissue perfusion and transducer type should be given special attention to ensure the success and safety of ablation treatment.

[P-HIFU phased signal generator with highly precise timing function].

This article add mode control module to the phased-array using digital sampling technology which achieved a phase accuracy of 3.75 degrees, making phase, phased signal duration, interval for continuous signal and repeat times pre-configured before the out put of phased signal, to realize the precise timing of phased signal. Experiments indicate that the output of phased signal modulated by mode control can reach the timing precision of 0.48 micros and will not affect the original phase control function t. In addition it can realize intermittent therapy mode which can reduce the injury of non-focal areas caused by ultrasound energy.

[The control method design of thermal treatment system via fuzzy logic].

A novel system is proposed to control the liquid nitrogen cooling and radio frequency heating of tissue to achieve effective thermal ablation in the treatment using fuzzy logic controller and fuzzy logic PID type controller separately. Results of ex-vivo pig liver experiments demonstrate that this system is useful and could p control the desired treatment procedure.

Parameter effects on arterial vessel sonicated by high-intensity focused ultrasound: anex vivovascular phantom study.

Objective.This study is aimed to explore the effects of vascular and sonication parameters onex vivovessel sonicated by high-intensity focused ultrasound.Approach.The vascular phantom embedding the polyolefin tube orex vivovessel was sonicated. The vascular phantom with 1.6 and 3.2 mm tubes was sonicated at three acoustic powers (2.0, 3.5, 5.3 W). The occlusion level of post-sonication tubes was evaluated using ultrasound imaging. The vascular phantom with theex vivoabdominal aorta of rabbit for three flow rates (0, 5, 10 cm s-1) was sonicated at two acoustic powers (3.5 and 5.3 W). Different distances between focus and posterior wall (2, 4, 6 mm) and cooling times (0 and 10 s) were also evaluated. The diameter of the sonicated vessel was measured by B-mode imaging and microscopic photography. Histological examination was performed for the sonicated vessels.Main results.For the 5 cm s-1flow rate, the contraction index of vascular diameter (Dc) with 5.3 W and 10 s cooling time at 2 mm distance was 39 ± 9% (n = 9). With the same parameters except for 0 cm s-1flow rate, theDcwas increased to 45 ± 7% (n = 4). At 3.5 W, theDcwith 5 cm s-1flow rate was 23 ± 15% (n = 4). The distance and cooling time influenced the lesion along the vessel wall.Significance.This study has demonstrated the flow rate and acoustic power have the great impact on the vessel contraction. Besides, the larger lesion covering the vessel wall would promote the vessel contraction. And thein vivovalidation is required in the future study.

Spontaneous formation and characterization of silica mesoporous crystal spheres with reverse multiply twinned polyhedral hollows.

A crystal is an object with translational symmetry. Basic research into and production of new materials necessitates the preparation of crystals of a particular morphology and with well-defined crystal defects. In this work, we found novel silica mesoporous crystal spheres with polyhedral hollows (icosahedral, such as those observed for proteins of virus capsids, decahedral, Wulff polyhedral, etc.) formed by the reverse multiply twinned bicontinuous double diamond mesostructure. Vesicles with a low-curvature lamellar structure were first formed by the self-assembly of amphiphilic carboxylic acid molecules in the presence of a nonionic surfactant and then underwent a structural transformation process that gave a reverse multiply twinned mesoporous shell while maintaining the hollow shape. These polyhedral hollow crystals showed an enhanced contrast of backscattering signatures relative to the incident acoustic signals and thus could be used as a potential contrast agent in medical ultrasonography with drug loadings in the mesopores.

[Calculation of parameters and accurate control with real-time compensator in drive system of pulsatile blood pump].

This article introduces a new method using the servo motor which is controlled by ARM microcontroller to provide power for a pulsatile blood pump to beat. This method is featured with straightforward structure, accurate control, excellent timeliness, stable performance and small noise. And it can adjust the rate of beat, the rate of flow and the compression ratio according to actual demand.

Ultrasound-Guided High-Intensity Focused Ultrasound for Devascularization of Uterine Fibroid: A Feasibility Study.

This study aimed to establish the feasibility of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for devascularization of uterine fibroids. Ultrasound color Doppler flow imaging (CDFI) and B-mode imaging were used to target fibroid vascularity. The vessels were covered and ablated by high-intensity focused ultrasound spots. In this study, 42 fibroids with a volume of 66.98 ± 4.00 cm3 were treated. No blood flow was detected by post-treatment CDFI in 40 fibroids. The 6-mo non-perfusion volume rate was 75.23% ± 34.77% (n = 40). The mean shrinkage in fibroid volume was 38.20% and 43.89%, respectively, at 1 and 6 mo after treatment (p < 0.001). The uterine fibroid symptom and quality of life scores were reduced by 9.43% at 1 mo and 26.66% at 6-mo after treatment (p < 0.001). No serious adverse event was observed. This study demonstrates the feasibility of USgHIFU-induced fibroid devascularization, and more studies are required for the evaluation of safety and efficacy.