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.

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.

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.

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.

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.

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.

Enhancing of Nanocatalyst-Driven Chemodynaminc Therapy for Endometrial Cancer Cells Through Inhibition of PINK1/Parkin-Mediated Mitophagy.

PURPOSE: Iron-based nanomaterials have recently been developed as excellent and potent Fenton reagents to reactive oxygen species (ROS) during chemodynamic therapy (CDT). The performance of the materials, however, can be impaired by the intrinsic antioxidant defense mechanism in organisms, such as autophagy. METHODS: The nanoscale metal-organic frameworks (nMOFs), nMIL-100 (Fe), were exploited and characterized. Also, the Fenton-like catalytic characteristics, anti-endometrial cancer (EC) effects and potential mechanisms of nMIL-100 (Fe) nanoparticles were investigated in vitro. RESULTS: The synthesized nMIL-100 (Fe) nanocatalyst catalyzed hydroxyl radicals (·OH) production in the presence of hydrogen peroxide (H2O2) and simultaneously depleted intracellular glutathione (GSH). Combining with H2O2, nMIL-100 (Fe) nanoparticles exhibited enhanced cytotoxicity for EC cells, especially for progesterone treatment-insensitive KLE cells, probably due to relatively lower expression of the catalase gene. The accumulated ·OH initiated PTEN induced putative kinase 1 (PINK1)/E3 ubiquitin-protein ligase Parkin-mediated cytoprotective mitophagy in turn to partially rescue ·OH-induced cell apoptosis. Furthermore, both pretreatments of EC cells with siRNA-mediated Parkin knockdown and Mdivi-1 (a mitophagy inhibitor) addition were sufficient to ensure nMIL-100 (Fe) synergizing with H2O2-induced oxidative damages. CONCLUSION: These results suggest that the degree of mitophagy should be taken into consideration to optimize therapeutic efficiency when developing ROS based-CDT for EC cancer therapies. Therefore, a nMIL-100 (Fe)-guided, elevated ROS and overwhelmed mitophagy-mediated therapeutic strategy may have greater promise for EC therapy compared with current treatment modalities.

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.

Fusion of Multiple-angles Intraoperative US Images and Pretreatment MR Images for USgHIFU Treatment of Uterine Fibroid: Retrospective Evaluation Based on Clinical Dataset.

High-intensity focused ultrasound (HIFU) has been widely used for treatment of uterine fibroids. However, due to the limited resolution of ultrasound image in deep organs, the guidance of ultrasound-guided HIFU (USgHIFU) treatment greatly depends on clinicians' experience in US image. To address this issue, fusion of intraoperative US images and pretreatment MR images has been proposed. Contour segmentation and multiple-angles 2D US images combination are performed to obtain 3D points along the contour of uterus. Iterative closest point (ICP) algorithm based on prior knowledge is used to register these point sets. MR and US images of six treated patients are used for evaluation. The mean distance error (MDE) of our algorithm is 1.71±0.59 mm, and the average running time is 0.18 s. The results have verified the feasibility of fusion of MR images and US images for USgHIFU guidance. In addition, this method may be also potential for post-ablation evaluation with follow-up MR images.

Automatic stent reconstruction in optical coherence tomography based on a deep convolutional model.

Intravascular optical coherence tomography (IVOCT) can accurately assess stent apposition and expansion, thus enabling the optimisation of a stenting procedure to minimize the risk of device failure. This paper presents a deep convolutional based model for automatic detection and segmentation of stent struts. The input of pseudo-3D images aggregated the information from adjacent frames to refine the probability of strut detection. In addition, multi-scale shortcut connections were implemented to minimize the loss of spatial resolution and refine the segmentation of strut contours. After training, the model was independently tested in 21,363 cross-sectional images from 170 IVOCT image pullbacks. The proposed model obtained excellent segmentation (0.907 Dice and 0.838 Jaccard) and detection metrics (0.943 precision, 0.940 recall and 0.936 F1-score), significantly better than conventional features-based algorithms. This performance was robust and homogenous among IVOCT pullbacks with different sources of acquisition (clinical centres, imaging operators, type of stent, time of acquisition and challenging scenarios). In addition, excellent agreement between the model and a commercialized software was observed in the quantification of clinically relevant parameters. In conclusion, the deep-convolutional model can accurately detect stent struts in IVOCT images, thus enabling the fully-automatic quantification of stent parameters in an extremely short time. It might facilitate the application of quantitative IVOCT analysis in real-world clinical scenarios.

Evaluating Targeting Accuracy in the Focal Plane for an Ultrasound-guided High-intensity Focused Ultrasound Phased-array System.

Phased arrays are increasingly used as high-intensity focused ultrasound (HIFU) transducers in the existing extracorporeal ultrasound-guided HIFU (USgHIFU) systems. The HIFU transducers in such systems are usually spherical in shape with a central hole where a US imaging probe is mounted and can be rotated. The image on the plane of treatment can be reconstructed through the image sequence acquired during the rotation of the probe. Therefore, the treatment plan can be made on the reconstructed images. In order to evaluate the targeting accuracy in the focal plane of such systems, the protocol of a method using a bovine muscle and marker-embedded phantom is described. In the phantom, four solid balls at the corners of a square resin model serve as the reference markers in the reconstructed image. The target should be moved so that both its center and the center of the square model can coincide according to their relative positions in the reconstructed image. Swine muscle with a thickness of about 30 mm is placed above the phantom to mimic the beam path in clinical settings. After sonication, the treatment plane in the phantom is scanned and the boundary of the associated lesion is extracted from the scanned image. The targeting accuracy can be evaluated by measuring the distance between the centers of target and lesion, as well as three derivative parameters. This method cannot only evaluate the targeting accuracy of the target consisting of multiple focal spots rather than a single focal spot in a clinically relevant beam path of the USgHIFU phased-array system, but it can be also used in the preclinical evaluation or regular maintenance of USgHIFU systems configured with phased-array or self-focused HIFU transducer.

[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%.

[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.

New treatment strategy of cryosurgery and temperature control.

Cryosurgery, recommended as an effective method for tumor treatment, has been widely used in clinics. However, it might lead to a high probability of tumor recurrence due to incomplete tumor damage. The treatment protocol for cryosurgery is essential to achieve the desired therapeutic effects. In this study, a new temperature fluctuation treatment method was proposed, and the fuzzy control method based on piecewise adjustment was developed for temperature control during the treatment. Ex vivo rat liver experiments were conducted and histopathology analysis used to study the therapeutic effects of the new treatment method.

[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.

Quantitative assessment of acoustic intensity in the focused ultrasound field using hydrophone and infrared imaging.

With the popularity of ultrasound therapy in clinics, characterization of the acoustic field is important not only to the tolerability and efficiency of ablation, but also for treatment planning. A quantitative method was introduced to assess the intensity distribution of a focused ultrasound beam using a hydrophone and an infrared camera with no prior knowledge of the acoustic and thermal parameters of the absorber or the configuration of the array elements. This method was evaluated in both theoretical simulations and experimental measurements. A three-layer model was developed to calculate the acoustic field in the absorber, the absorbed acoustic energy during the sonication and the consequent temperature elevation. Experiments were carried out to measure the acoustic pressure with the hydrophone and the temperature elevation with the infrared camera. The percentage differences between the derived results and the simulation are <4.1% for on-axis intensity and <21.1% for -6-dB beam width at heating times up to 360 ms in the focal region of three phased-array ultrasound transducers using two different absorbers. The proposed method is an easy, quick and reliable approach to calibrating focused ultrasound transducers with satisfactory accuracy.