Cavitation erosion on different metallic materials under high hydrostatic pressure evaluated with the spatially confined sonoluminescence.

Cavitation erosion is a general phenomenon in the fields of aviation, navigation, hydraulic machinery, and so on, causing great damage to fluid machinery. With the vast requirements in deep ocean applications, it is urgent to study the mechanism of cavitation erosion and the cavitation erosion resistance of different materials under high hydrostatic pressure to predict and avoid the effect of cavitation erosion. In this work, the spatially confined cavitation bubble cloud associated with Gaussian-like intensity distribution sonoluminescence (SL) was produced by a spherically focused ultrasound transducer with two opening ends near metallic plates under different hydrostatic pressures (0.1, 3, 6, and 10 MPa). The cavitation erosion effects on copper, 17-4PH stainless steel and tungsten plates were studied. Through coupling analysis towards the SL intensity distribution, the macro/micro morphology of cavitation erosion, and the physical parameters of different metallic materials (hardness, yield strength, and melting point), it is found that with increasing hydrostatic pressure, the erosion effect is intensified, the depth of cavitation pits increases, the phenomenon of melting can be observed on materials with relatively low melting points, and the cavitation erosion experienced an evolution process from high-temperature creep to fracture. This work has also established a method for the evaluation of materials' cavitation erosion resistance with measurable SL intensity distribution, which is promising to promote the designing and selection of anti-cavitation materials in deep-sea applications.

Prediction of non-perfusion volume ratio for uterine fibroids treated with ultrasound-guided high-intensity focused ultrasound based on MRI radiomics combined with clinical parameters.

BACKGROUND: Prediction of non-perfusion volume ratio (NPVR) is critical in selecting patients with uterine fibroids who will potentially benefit from ultrasound-guided high-intensity focused ultrasound (HIFU) treatment, as it reduces the risk of treatment failure. The purpose of this study is to construct an optimal model for predicting NPVR based on T2-weighted magnetic resonance imaging (T2MRI) radiomics features combined with clinical parameters by machine learning. MATERIALS AND METHODS: This retrospective study was conducted among 223 patients diagnosed with uterine fibroids from two centers. The patients from one center were allocated to a training cohort (n = 122) and an internal test cohort (n = 46), and the data from the other center (n = 55) was used as an external test cohort. The least absolute shrinkage and selection operator (LASSO) algorithm was employed for feature selection in the training cohort. The support vector machine (SVM) was adopted to construct a radiomics model, a clinical model, and a radiomics-clinical model for NPVR prediction, respectively. The area under the curve (AUC) and the decision curve analysis (DCA) were performed to evaluate the predictive validity and the clinical usefulness of the model, respectively. RESULTS: A total of 851 radiomic features were extracted from T2MRI, of which seven radiomics features were screened for NPVR prediction-related radiomics features. The radiomics-clinical model combining radiomics features and clinical parameters showed the best predictive performance in both the internal (AUC = 0.824, 95% CI 0.693-0.954) and external (AUC = 0.773, 95% CI 0.647-0.902) test cohorts, and the DCA also suggested the radiomics-clinical model had the highest net benefit. CONCLUSIONS: The radiomics-clinical model could be applied to the NPVR prediction of patients with uterine fibroids treated by HIFU to provide an objective and effective method for selecting potential patients who would benefit from the treatment mostly.

Surface modifications of biomaterials in different applied fields.

Biomaterial implantation into the human body plays a key role in the medical field and biological applications. Increasing the life expectancy of biomaterial implants, reducing the rejection reaction inside the human body and reducing the risk of infection are the problems in this field that need to be solved urgently. The surface modification of biomaterials can change the original physical, chemical and biological properties and improve the function of materials. This review focuses on the application of surface modification techniques in various fields of biomaterials reported in the past few years. The surface modification techniques include film and coating synthesis, covalent grafting, self-assembled monolayers (SAMs), plasma surface modification and other strategies. First, a brief introduction to these surface modification techniques for biomaterials is given. Subsequently, the review focuses on how these techniques change the properties of biomaterials, and evaluates the effects of modification on the cytocompatibility, antibacterial, antifouling and surface hydrophobic properties of biomaterials. In addition, the implications for the design of biomaterials with different functions are discussed. Finally, based on this review, it is expected that the biomaterials have development prospects in the medical field.

A Theragnostic HIFU Transducer and System for Inherently Registered Imaging and Therapy.

OBJECTIVE: One big challenge with high intensity focused ultrasound (HIFU) is the difficulty in accurate prediction of focal location due to the complex wave propagation in heterogeneous medium even with imaging guidance. This study aims to overcome this by combining therapy and imaging guidance with one single HIFU transducer using the vibro-acoustography (VA) strategy. METHODS: Based on the VA imaging method, a HIFU transducer consisting of 8 transmitting elements was proposed for therapy planning, treatment and evaluation. Inherent registration between the therapy and imaging created unique spatial consistence in HIFU transducer's focal region in the above three procedures. Performance of this imaging modality was first evaluated through in-vitro phantoms. In-vitro and ex-vivo experiments were then designed to demonstrate the proposed dual-mode system's ability in conducting accurate thermal ablation. RESULTS: Point spread function of the HIFU-converted imaging system had a full wave half maximum of about 1.2 mm in both directions at a transmitting frequency of 1.2 MHz, which outperformed the conventional ultrasound imaging (3.15 MHz) in in-vitro situation. Image contrast was also tested on the in-vitro phantom. Various geometric patterns could be accurately 'burned out' on the testing objects by the proposed system both in vitro and ex vivo. CONCLUSION: Implementation of imaging and therapy with one HIFU transducer in this manner is feasible and it has potential as a novel strategy for addressing the long-standing problem in the HIFU therapy, possibly pushing this non-invasive technique forward towards wider clinical applications.

Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy.

BACKGROUND: High-intensity focused ultrasound (HIFU) has shown considerable promise in treating solid tumors, but its ultrasonic energy is easily attenuated, resulting in insufficient energy accumulation in the target area. Moreover, HIFU ablation alone may inevitably lead to the presence of residual tumors, which may cause tumor recurrence and metastasis. Here, we describe a synergistic regimen combining HIFU facilitation with immunomodulation based on a novel oxygen-carrying biomimetic perfluorocarbon nanoparticle (M@P-SOP) to stimulate immunogenic cell death in tumor cells while alleviating immune suppression tumor microenvironment. METHODS: M@P-SOP was prepared by double emulsion and film extrusion method. The anticancer and antimetastatic effects of M@P-SOP were evaluated on a preclinical transplanted 4T1 tumor model by combining HIFU and immunotherapy. Flow cytometry and immunofluorescence were used to clarify the potential mechanism of HIFU+M@P-SOP and their role in anti-programmed death ligand-1 (PD-L1) therapy. RESULTS: Guided by photoacoustic/MR/ultrasound (US) multimodal imaging, M@P-SOP was abundantly enriched in tumor, which greatly enhanced HIFU's killing of tumor tissue in situ, induced stronger tumor immunogenic cell death, stimulated dendritic cell maturation and activated CD8+ T cells. At the same time, M@P-SOP released oxygen to alleviate the tumor hypoxic environment, repolarizing the protumor M2-type macrophages into antitumor M1-type. With concurrent anti-PD-L1 treatment, the antitumor immune response was further amplified to the whole body, and the growth of mimic distant tumor was effectively suppressed. CONCLUSIONS: Our findings offer a highly promising HIFU synergist for effectively ameliorating acoustic and hypoxia environment, eventually inhibiting tumor growth and metastasis by stimulating host's antitumor immunity under HIFU ablation, especially in synergizing with PD-L1 antibody immunotherapy.

Magnetic resonance imaging parameter-based machine learning for prognosis prediction of high-intensity focused ultrasound ablation of uterine fibroids.

Objectives: To develop and apply magnetic resonance imaging (MRI) parameter-based machine learning (ML) models to predict non-perfused volume (NPV) reduction and residual regrowth of uterine fibroids after high-intensity focused ultrasound (HIFU) ablation.Methods: MRI data of 573 uterine fibroids in 410 women who underwent HIFU ablation from the Chongqing Haifu Hospital (training set, N = 405) and the First Affiliated Hospital of Chongqing Medical University (testing set, N = 168) were retrospectively analyzed. Fourteen MRI parameters were screened for important predictors using the Boruta algorithm. Multiple ML models were constructed to predict NPV reduction and residual fibroid regrowth in a median of 203.0 (interquartile range: 122.5-367.5) days. Furthermore, optimal models were used to plot prognostic prediction curves.Results: Fourteen features, including postoperative NPV, indicated predictive ability for NPV reduction. Based on the 10-fold cross-validation, the best average performance of multilayer perceptron achieved with R2 was 0.907. In the testing set, the best model was linear regression (R2 =0.851). Ten features, including the maximum thickness of residual fibroids, revealed predictive power for residual fibroid regrowth. Random forest model achieved the best performance with an average area under the curve (AUC) of 0.904 (95% confidence interval (CI), 0.869-0.939), which was maintained in the testing set with an AUC of 0.891 (95% CI, 0.850-0.929).Conclusions: ML models based on MRI parameters can be used for prognostic prediction of uterine fibroids after HIFU ablation. They can potentially serve as a new method for learning more about ablated fibroids.

Quantitative evaluation of the microjet velocity and cavitation erosion on a copper plate produced by a spherical cavity focused transducer at the high hydrostatic pressure.

Cavitation erosion at the high hydrostatic pressure causes the equipment to operate abnormally for the huge economic losses. Few methods can quantitatively evaluate the cavitation erosion intensity. In order to solve this problem, the cavitation erosion on a copper plate was carried out in a spherical cavity focused transducer system at the hydrostatic pressure of 3, 6, and 10 MPa. Meanwhile, the corresponding cavitation threshold, the initial bubble radius, and the microjet velocity in the ultrasonic field are theoretically analyzed to determine the dimension and velocity of microjet based on the following hypotheses: (1) the influence of the coalescence on the bubble collapse is ignored; (2) the dimension of the microjet is equal to the largest bubble size without the influence of gravity and buoyancy. Using the Westervelt equation for the nonlinear wave propagation and the Johnson-Cook material constitutive model for the high strain rate, a microjet impact model of the multi-bubble cavitation was constructed. In addition, through the analogy with the indentation test, an inversion model was proposed to calculate the microjet velocity and the cavitation erosion intensity. The microjet geometric model was constructed from the dimension and velocity of the microjet. The continuous microjet impact was proposed according to the equivalent impact momentum and solved by the finite element method. The relative errors of the pit depth are 4.02%, 3.34%, and 1.84% at the hydrostatic pressure of 3, 6, and 10 MPa, respectively, and the relative error in the evolution of pit morphology is 7.33% at 10 MPa, which verified the reliability of the proposed models. Experimental and simulation results show that the higher the hydrostatic pressure, the greater the pit depth, pit diameter, the pit-to-microjet diameter ratio, and the cavitation erosion intensity, but the smaller the pit diameter-to-depth ratio. The cavitation erosion intensity becomes significant with the ongoing ultrasonic exposure. In addition, a comparison of the cavitation pit morphology in the microjet pulsed and continuous impact modes shows that the continuous impact mode is effective without the elastic deformation caused by the residual stress. Using the cavitation pit morphology at the different hydrostatic pressures, the microjet velocity can be estimated successfully and accurately in a certain range, whose corresponding errors at the lower and upper limit are 5.98% and 0.11% at 3 MPa, 6.62% and 9.14% at 6 MPa, 6.54% and 5.42% at 10 MPa, respectively. Our proposed models are valid only when the cavitation pit diameter-to-depth ratio is close to 1. Altogether, the cavitation erosion induced by multi-bubble collapses in the focal region of a focused transducer could be evaluated both experimentally and numerically. Using the cavitation pit morphology and the inversion model, the microjet velocity in a certain range could be estimated successfully with satisfactory accuracy.

Potential Application of Low-Intensity Focused Ultrasound in Rapidly Relieving Delayed-Onset Muscle Soreness Induced by High-Intensity Exercise.

OBJECTIVES: To evaluate the efficacy of low-intensity focused ultrasound (LIFU) treatment on rapid relief of delayed-onset muscle soreness (DOMS) triggered by high-intensity exercise. METHODS: A total of 16 healthy male college students were randomly divided into two groups: the LIFU group (n = 8) and the Sham group (n = 8). After the exercise protocol, the LIFU group received treatment, which parameters included that the power output was 2.5 W/cm2 , the frequency was 1 MHz, and the treating time was 20 minutes. The Sham group was treated with LIFU without energy output. Visual analog scale was used to evaluate the level of DOMS in every participant. The activities of plasma creatine kinase, lactate dehydrogenase, and the plasma concentration were measured by spectrophotometry. Tumor necrosis factor-α and interleukin-6 of serum were analyzed by enzyme-linked immunosorbent assay. RESULTS: The visual analog scale of quadriceps femoris and/or calf muscles in the LIFU group decreased significantly at 24 hours (P < 0.01) and 48 hours (P < .01) after the exercise protocol. Both the accumulation of lactic acid (P < .01) in muscle and the activity of lactate dehydrogenase (P < .01) reduced immediately after LIFU treatment. The activities of tumor necrosis factor-α and interleukin-6 24 hours lowered in the LIFU group (P < .01). CONCLUSIONS: LIFU treatment could relieve muscle soreness rapidly and effectively in the early stages of DOMS. The application of LIFU may provide a potential strategy for clinical treatment for DOMS.

Acoustic Beam Mapping for Guiding HIFU Therapy In Vivo Using Sub-Therapeutic Sound Pulse and Passive Beamforming.

OBJECTIVE: Although HIFU has been successfully applied in various clinical applications in the past two decades for the ablation of many types of tumors, one bottleneck in its wider applications is the lack of a reliable and affordable strategy to guide the therapy. This study aims at estimating the therapeutic beam path at the pre-treatment stage to guide the therapeutic procedure. METHODS: An incident beam mapping technique using passive beamforming was proposed based on a clinical HIFU system and an ultrasound imaging research system. An optimization model was created to map the cross-like beam pattern by maximizing the total energy within the mapped area. This beam mapping technique was validated by comparing the estimated focal region with the HIFU-induced actual focal region (damaged region) through simulation, in-vitro, ex-vivo and in-vivo experiments. RESULTS: The results of this study showed that the proposed technique was, to a large extent, tolerant of sound speed inhomogeneities, being able to estimate the focal location with errors of 0.15 mm and 0.93 mm under in-vitro and ex-vivo situations respectively, and slightly over 1 mm under the in-vivo situation. It should be noted that the corresponding errors were 6.8 mm, 3.2 mm, and 9.9 mm respectively when the conventional geometrical method was used. CONCLUSION: This beam mapping technique can be very helpful in guiding the HIFU therapy and can be easily applied in clinical environments with an ultrasound-guided HIFU system. SIGNIFICANCE: The technique is safe and can potentially be adapted to other ultrasound-related beam manipulating applications.

Effects of sub-atmospheric pressure and dissolved oxygen concentration on lesions generated in ex vivo tissues by high intensity focused ultrasound.

BACKGROUND: Acoustic cavitation plays an important role in the medical treatment using high-intensity focused ultrasound (HIFU), but unnecessarily strong cavitation also could deform the morphology and enlarge the size of lesions. It is known that the increase of ambient hydrostatic pressure (Pstat) can control the acoustic cavitation. But the question of how the decrease of Pstat and dissolved oxygen concentration (DOC) influence the strength of cavitation has not been thoroughly answered. In this study, we aimed to investigate the relationship among the Pstat, DOC and the strength of cavitation. METHODS: Ex vivo bovine liver tissues were immersed in degassed water with different DOC of 1.0 mg/L, 1.5 mg/L and 2.0 mg/L. Ultrasound (US) of 1 MHz and the spatial and temporal average intensity (Isata) of 6500 W/cm2 was used to expose two groups of in vitro bovine livers for 2 s; one group was under atmospheric pressure (Pstat = 1 bar) and the other was under sub-atmospheric pressure (Pstat = 0.1 bar). Acoustic cavitation was detected by a passive cavitation detector (PCD) during the exposure process. Echo signals at the focal zone of HIFU were monitored by B-mode ultrasound imaging before and after exposure. The difference between two pressure groups was tested using paired sample t-test. The difference among different DOC groups was evaluated by one-way analysis of variance (ANOVA). RESULTS: The results demonstrated a significant difference of broadband acoustic emissions from the cavitation bubbles, echo signals on B-mode image, morphology of lesions under various conditions of ambient pressure and DOC. The lesion volume in tissue was increased with the increase of ambient pressure and DOC. CONCLUSION: Cavitation could be suppressed through sub-atmospheric pressure and low DOC level in liver tissue, which could provide a method of controlling cavitation in HIFU treatment to avoid unpredictable lesions.

Study on fracture of tungsten wire induced by acoustic cavitation at different hydrostatic pressures and driving electric powers.

The near-solid wall multi-bubble cavitation is an extremely complex phenomenon, and cavitation has strong erosiveness. The melting point (about 3410 °C) of tungsten is highest among all pure metals, and its hardness is also very high (its yield strength is greater than 1 GPa). What would happen to pure tungsten wire under extreme conditions caused by collapsing cavitation bubbles at high hydrostatic pressure? In this paper, we have studied the fracture process of pure tungsten wire with diameter of 0.2 mm mounted at the focus of a standing acoustic wave produced by a spherical cavity transducer with two open ends placed in a near spherical pressure container, and also studied the macro and micro morphological characteristics of the fracture and the surface damage at different fracture stages of tungsten wire under various hydrostatic pressures and driving electric powers. The results have shown that the fracture time of tungsten wire is inversely proportional to avitation intensity with hydrostatic pressure and driving electric power, the higher the acoustic pressure caused by higher electric power, the shorter the fracture time. The possible fracture mechanisms of tungsten wire in this situation we found mainly contributed to asymmetrically bubbles collapse near the surface of tungsten wire, leading to tearing the surface apart; consequently cracks along the radial and axial directions of a tungsten wire extend simultaneously, classified as trans-granular fracture and inter-granular fracture, respectively. With the increase of cavitation intensity, the cracks tend to extend more radially and the axial crack propagation path becomes shorter, that is, mainly for trans-granular fracture; with the decrease of cavitation intensity, intergranular fracture becomes more obvious. When the hydrostatic pressure was 10 MPa and the driving electric power was 2 kW, the fibers became softener due to the fracture of the tungsten wire. The fracture caused by acoustic cavitation was different from conventional mechanical fracture, such as tensile, shear, fatigue fracture, on macro and micro morphology.

HIFUNet: Multi-Class Segmentation of Uterine Regions From MR Images Using Global Convolutional Networks for HIFU Surgery Planning.

Accurate segmentation of uterus, uterine fibroids, and spine from MR images is crucial for high intensity focused ultrasound (HIFU) therapy but remains still difficult to achieve because of 1) the large shape and size variations among individuals, 2) the low contrast between adjacent organs and tissues, and 3) the unknown number of uterine fibroids. To tackle this problem, in this paper, we propose a large kernel Encoder-Decoder Network based on a 2D segmentation model. The use of this large kernel can capture multi-scale contexts by enlarging the valid receptive field. In addition, a deep multiple atrous convolution block is also employed to enlarge the receptive field and extract denser feature maps. Our approach is compared to both conventional and other deep learning methods and the experimental results conducted on a large dataset show its effectiveness.

Ghrelin combined with sodium tanshinone IIA sulfonate pretreatment reduces apoptosis and fractalkine expression induced by high-dose glucose in human umbilical vein endothelial cells.

BACKGROUND: To explore the regulatory role of ghrelin combined with sodium tanshinone IIA sulfonate (STS) pretreatment in cell apoptosis and fractalkine (FKN) expression of human umbilical vein endothelial cells (HUVECs) induced with high-dose glucose. METHODS: HUVECs were assigned into control group, high-dose glucose group (HG group), high-dose glucose with ghrelin group (Gr+HG group), and high-dose glucose companied with ghrelin and STS group (Gr+STS+HG group). The apoptosis of HUVECs was determined by Hoechst 33258 straining and flow cytometry (FCM). Nitric oxide (NO) level was measured by total NO assay kit. The mRNA and protein levels of ß-catenin, p-GSK-3ß and FKN were accessed by Western blot and real-time quantitative polymerase chain reaction (RT-qPCR), respectively. RESULTS: High-dose glucose significantly accelerated apoptosis in HUVECs. The apoptotic rate was lower in Gr+HG group and much lower in Gr+STS+HG group than control group. NO level was significantly reduced in the HG group, which was partly inhibited in Gr+HG group and obviously increased in Gr+STS+HG group than controls. In addition, mRNA levels of GSK-3ß and FKN in HUVECs decreased in Gr+HG group, which was more obviously decreased in Gr+STS+HG group. However, ghrelin treatment upregulated ß-catenin and p-GSK-3ß (Ser9), but downregulated FKN during high-dose glucose treatment, which was more obvious in Gr+STS+HG group. CONCLUSIONS: Pretreatment of ghrelin combined with STS reduces the apoptosis rate of HUVECs induced by high glucose environment and inhibits the expression of FKN via ß-catenin/Wnt signaling pathway.

Enzyme-Catalytic Self-Triggered Release of Drugs from a Nanosystem for Efficient Delivery to Nuclei of Tumor Cells.

Stimulus-responsive drug delivery nanosystems (DDSs) are of great significance in improving cancer therapy for intelligent control over drug release. However, among them, many DDSs are unable to realize rapid and sufficient drug release because most internal stimulants might be consumed during the release process. To address the plight, an abundant supply of stimulants is highly desirable. Herein, a core crosslinked pullulan-di-(4,1-hydroxybenzylene)diselenide nanosystem, which could generate abundant exogenous-stimulant reactive oxygen species (ROS) via tumor-specific NAD(P)H:quinone oxidoreductase-1 (NQO1) catalysis, was constructed by the encapsulation of ß-lapachone. The enzyme-catalytic-generated ROS induced self-triggered cascade amplification release of loaded doxorubicin (DOX) in the tumor cells, thus achieving efficient delivery of DOX to the nuclei of tumor cells by breaking the diselenide bond of the nanosystem. As a result, the antitumor effect of this nanosystem was significantly improved in the HepG2 xenograft model. In general, this study offers a new paradigm for utilizing the interaction between the loaded agent and carrier in the tumor cells to obtain self-triggered drug release in the design of DDSs for enhanced cancer therapy.

Cardiovascular risk of sitagliptin in treating patients with type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus (T2DM) have a very high risk of cardiovascular related events, and reducing complications is an important evaluation criterion of efficacy and safety of hypoglycemic drugs. Previous studies have shown that the dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP4i), such as sitagliptin, might reduce the incidence of major cardiovascular events (MACEs). However, the safety and efficacy of sitagliptin remains controversial, especially the safety for cardiovascular related events. Here, a systematic review was conducted to assess the cardiovascular safety of sitagliptin in T2DM patients. The literature research dating up to October 2018 was performed in the electronic database. The clinical trials about sitagliptin for T2DM patients were included. Two reviewers independently screened literature according to the inclusion and exclusion criteria. The primary outcome was the MACE, and the secondary outcome was all-cause mortality. Finally, 32 clinical trials composed of 16082 T2DM patients were included in this meta-analysis. The results showed that: there was no significant difference between sitagliptin group and the control group on MACE (odds ratio (OR) = 0.85, 95% confidence intervals (CIs) = 0.63-1.15), myocardial infarction (MI) (OR = 0.66, 95% CI = 0.38-1.16), stroke (OR = 0.83, 95% CI = 0.44-1.54) and mortality (OR = 0.52, 95% CI = 0.26-1.07). These results demonstrated that sitagliptin did not increase the risk of cardiovascular events in patients with T2DM.

Reasons for different therapeutic effects of high-intensity focused ultrasound ablation on excised uterine fibroids with different signal intensities on T2-weighted MRI: a study of histopathological characteristics.

OBJECTIVE: The objective of this study was to explore the correlations between the therapeutic effect of high intensity focused ultrasound (HIFU) and histopathological characteristics of excised uterine fibroids with different signal intensities as visualized on T2-weighted magnetic resonance imaging (MRI). METHODS: We collected 47 specimens of uterine fibroids after surgical resection and classified them into four groups according to preoperative T2-weighted MRI hypo-intense, isointense, heterogeneous intense and homogeneous hyper-intense. Then, specimens in each group were irradiated by HIFU with the same parameters and the necrotic tissue volume was calculated. The smooth muscle cell (SMC) count and collagen fiber content were quantitatively measured and compared between different groups. We analyzed the correlation between the necrotic tissue volume and SMC count and the collagen fiber content. RESULTS: Necrotic tissue volume gradually decreased from the hypo-intense group to the homogeneous hyper-intense group (p = .008). The SMC count from the hypo-intense group to the homogeneous hyper-intense group was 215.6 ± 59.3, 237.0(89.5), 232.3 ± 72.5 and 330.5 ± 30.9, respectively; collagen fiber content was 0.65 ± 0.07, 0.64 ± 0.10, 0.53 ± 0.11 and 0.41 ± 0.06, respectively. Comparison among the four groups showed that SMC count progressively increased (p = .001) but collagen fiber content progressively decreased (p = .000) from the hypo-intense group to the homogeneous hyper-intense group. Correlation analysis showed that necrotic tissue volume was negatively correlated with SMC count (R = -0.488, p=.013) but positively correlated with collagen fiber content (R = 0.534, p = .005). CONCLUSIONS: Differences in histopathological characteristics may be one of the reasons for different therapeutic effects of HIFU ablation on uterine fibroids with different signal intensities on T2-weighted MRI.

Fast MR thermometry using an echo-shifted sequence with simultaneous multi-slice imaging.

PURPOSE: Real-time monitoring is important for the safety and effectiveness of high-intensity focused ultrasound (HIFU) therapy. Magnetic resonance imaging is the preferred imaging modality for HIFU monitoring, with its unique capability of temperature imaging. For real-time temperature imaging, higher temporal resolution and larger spatial coverage are needed. In this study, a sequence based on the echo-shifted RF-spoiled gradient echo (GRE) with simultaneous multi-slice (SMS) imaging was designed for fast temperature imaging. METHODS: A phantom experiment was conducted to evaluate the accuracy of the echo-shifted sequence using a fluorescent fiber thermometer as reference. The temperature uncertainty of the echo-shifted sequence was compared with the traditional GRE sequence at room temperature through the ex vivo porcine muscle. Finally, the ex vivo porcine liver tissue experiment using HIFU heating was performed to demonstrate that the spatial coverage was increased without decreasing temporal resolution. RESULTS: The echo-shifted sequence had a better temperature uncertainty performance compared with the traditional GRE sequence with the same temporal resolution. The ex vivo heating experiment confirmed that by combining the SMS technique and echo-shifted sequence, the spatial coverage was increased without decreasing the temporal resolution while maintaining high temperature measurement precision. CONCLUSION: The proposed technique was validated as an effective real-time method for monitoring HIFU therapy.

Ultrasound-enhanced delivery of doxorubicin/all-trans retinoic acid-loaded nanodiamonds into tumors.

AIM: To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy. MATERIALS & METHODS: A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs. RESULTS: The distribution of DOX/ATRA-NDs in the tumor tissues increased threefold when ultrasound was applied at 1 MHz and 0.6 W/cm2. Comparing with unmodified chemotherapeutics, the combined therapy induced more tumor cells apoptosis and greater tumor growth inhibition in both liver and breast tumor models. CONCLUSION: DOX-ATRA-NDs demonstrate great potential in clinical applications.

Effects of different hydrostatic pressure on lesions in ex vivo bovine livers induced by high intensity focused ultrasound.

It is well-known that acoustic cavitation associated with the high intensity focused ultrasound (HIFU) treatment often would change the morphology and size of lesions in its treatment. In most studies reported in literature, high ambient hydrostatic pressure was used to suppress the cavitation completely. Investigation of the effects by varying the ambient hydrostatic pressure (Pstat) is still lacking. In this paper, the effects of HIFU on lesions in ex vivo bovine liver specimens under various Pstat are systematically investigated. A 1MHz HIFU transducer, with an aperture diameter of 70mm and a focal length of 55mm, was used to generate two groups US exposure of different acoustic intensities and exposure time (6095W/cm2×8s and 9752W/cm2×5s), while keeping the same acoustic energies per unit area (48760J/cm2). The peak acoustic negative pressures (p-) of the two groups were p1-=9.58MPa and p2-=10.82MPa, respectively, with the difference pd-=p2--p1-=1.24MPa. A passive cavitation detection (PCD) was used to monitor the ultrasonic cavitation signal during exposure of the two groups. The US exposures were done under the following ambient hydrostatic pressures, Pstat: atmospheric pressure, 0.5MPa, 1.0MPa, 1.5MPa, 2.0MPa, 2.5MPa and3.0MPa, respectively. The result of PCD showed that there was a statistically significant increase above background noise level in broadband emissions at dose of 9752W/cm2×5s, but not at dose of 6095W/cm2×8s under atmospheric pressure; i.e., the acoustic cavitation took place for p2- but not for p1- when under atmospheric pressure. The results also showed that there was no statistically difference of the morphology and size of lesions for 6095W/cm2×8s exposure under the aforementioned different ambient hydrostatic pressures. But the lesions generated at 9752W/cm2×5s exposure under Pstat=atmospheric pressure, 0.5MPa, 1.0MPa (all of them are less than pd-), were larger than those under 1.5MPa, 2.0MPa, 2.5MPa and 3.0MPa (all of them are over than pd-) which were consistence with 6095W/cm2×8s group. It was concluded that when Pstat>pd-, the acoustic cavitation was suppressed and prompted that there was no need to elevate Pstat higher than p- to suppress the acoustic cavitation in tissue, just need Pstat higher than pd-.

High intensity focused ultrasound inhibits melanoma cell migration and metastasis through attenuating microRNA-21-mediated PTEN suppression.

High intensity focused ultrasound (HIFU) technology is becoming a potential noninvasive treatment for solid tumor. To explore whether HIFU can be applied to treat melanoma and its metastasis, we investigated the effect of HIFU on murine melanoma model. While there was little influence on cell survival, viability or apoptosis, HIFU exposure suppressed melanoma cell migration in vitro and metastasis in vivo. The expression of microRNA-21(miR-21) was down-regulated and PTEN expression was up-regulated in response to HIFU exposure, which was in concomitant with the reduction of AKT activity. Furthermore, ectopic miR-21 expression suppressed this effect of HIFU. These results demonstrate that HIFU exposure can inhibit AKT-mediated melanoma metastasis via miR-21 inhibition to restore PTEN expression. Therefore, targeting the miR-21/PTEN/AKT pathway might be a novel strategy of HIFU in treatment of melanoma.