Exercise improves the outcome of anticancer treatment with ultrasound-hyperthermia-enhanced nanochemotherapy and autophagy inhibitor.

It has been shown that exercise has a direct impact on tumor growth along with functional improvement. Previous studies have shown that exercise decreases the risk of cancer recurrence across various types of cancer. It was indicated that exercise stimulates the immune system to fight cancer. Previous study demonstrated that pulsed-wave ultrasound hyperthermia (pUH) combined with PEGylated liposomal doxorubicin (PLD) and chloroquine (CQ) inhibits 4T1 tumors growth and delays their recurrence. In this study, we investigated if the combinatorial treatment with high-intensity interval training (HIIT) combined with pUH-enhanced PLD delivery and CQ improved the outcome. The mouse experiment composed of three groups, HIIT+PLD+pUH+CQ group, PLD+pUH+CQ group, and the control group. HIIT+PLD+pUH+CQ group received 6 weeks of HIIT (15 min per day, 5 days per week) before 4T1 tumor implantation. Seven days later, they received therapy with PLD (10 mg/kg) + pUH (3 MHz, 50% duty cycle, 0.65 W/cm2, 15min) + CQ (50 mg/kg daily). Results showed that HIIT+PLD+pUH+CQ significantly reduced the tumor volumes and brought about longer survival of tumor-bearing mice than PLD+pUH+CQ did. Blood cell components were analyzed and showed that neutrophil and reticulocytes decreased while lymphocytes increased after exercise.

Effectiveness of external respiratory surrogates for in vivo liver motion estimation.

PURPOSE: Due to low frame rate of MRI and high radiation damage from fluoroscopy and CT, liver motion estimation using external respiratory surrogate signals seems to be a better approach to track liver motion in real-time for liver tumor treatments in radiotherapy and thermotherapy. This work proposes a liver motion estimation method based on external respiratory surrogate signals. Animal experiments are also conducted to investigate related issues, such as the sensor arrangement, multisensor fusion, and the effective time period. METHODS: Liver motion and abdominal motion are both induced by respiration and are proved to be highly correlated. Contrary to the difficult direct measurement of the liver motion, the abdominal motion can be easily accessed. Based on this idea, our study is split into the model-fitting stage and the motion estimation stage. In the first stage, the correlation between the surrogates and the liver motion is studied and established via linear regression method. In the second stage, the liver motion is estimated by the surrogate signals with the correlation model. Animal experiments on cases of single surrogate signal, multisurrogate signals, and long-term surrogate signals are conducted and discussed to verify the practical use of this approach. RESULTS: The results show that the best single sensor location is at the middle of the upper abdomen, while multisurrogate models are generally better than the single ones. The estimation error is reduced from 0.6 mm for the single surrogate models to 0.4 mm for the multisurrogate models. The long-term validity of the estimation models is quite satisfactory within the period of 10 min with the estimation error less than 1.4 mm. CONCLUSIONS: External respiratory surrogate signals from the abdomen motion produces good performance for liver motion estimation in real-time. Multisurrogate signals enhance estimation accuracy, and the estimation model can maintain its accuracy for at least 10 min. This approach can be used in practical applications such as the liver tumor treatment in radiotherapy and thermotherapy.

Enhancement of focused ultrasound with microbubbles on the treatments of anticancer nanodrug in mouse tumors.

Ultrasound sonication with microbubbles (MBs) has the potential to enhance the delivery of nanoparticles into the sonicated tumors. In this study, we investigated the feasibility of focused ultrasound (FUS) sonication with MBs to improve nanodrug delivery and tumor treatment. Tumor-bearing mice were first injected with MBs (SonoVue) intravenously, were then sonicated at the tumors with FUS sonication, and were finally injected with the PEGylated liposomal doxorubicin (DOX). The accumulation of DOX in tumors with time, the tumor growth responses for initial treated tumor size and DOX dosage, and the response for an additional sonication after DOX injection were studied. The results demonstrate that FUS sonication with MBs can significantly enhance DOX accumulation in the sonicated tumor at 24 hours after treatment. A significant hindrance to tumor growth is achieved for a small tumor with a low dose, whereas large tumors require a higher dose.

Large-Volume Focused-Ultrasound Mild Hyperthermia for Improving Blood-Brain Tumor Barrier Permeability Application.

Mild hyperthermia can locally enhance permeability of the blood-tumor barrier in brain tumors, improving delivery of antitumor nanodrugs. However, a clinical transcranial focused ultrasound (FUS) system does not provide this modality yet. The study aimed at the development of the transcranial FUS technique dedicated for large-volume mild hyperthermia in the brain. Acoustic pressure, multiple-foci, temperature and thermal dose induced by FUS were simulated in the brain through the skull. A 1-MHz, 114-element, spherical helmet transducer was fabricated to verify large-volume hyperthermia in the phantom. The simulated results showed that two foci were simultaneously formed at (2, 0, 0) and (-2, 0, 0) and at (0, 2, 0) and (0, -2, 0), using the phases of focusing pattern 1 and the phases of focusing pattern 2, respectively. Switching two focusing patterns at 5 Hz produced a hyperthermic zone with an ellipsoid of 7 mm × 6 mm × 11 mm in the brain and the temperature was 41-45 °C in the ellipsoid as the maximum intensity was 150 W/cm2 and sonication time was 3 min. The phased array driven by switching two mode phases generated a 41 °C-contour region of 10 ± 1 mm × 8 ± 2 mm × 13 ± 2 mm in the phantom after 3-min sonication. Therefore, we have demonstrated our developed FUS technique for large-volume mild hyperthermia.

A feasibility study of wireless inductively coupled surface coil for MR-guided high-intensity focused ultrasound ablation of rodents on clinical MRI systems.

Recently, to conduct preclinical imaging research on clinical MRI systems has become an attractive alternative to researchers due to its wide availability, cost, and translational application to clinical human studies when compared to dedicated small animal, high-field preclinical MRI. However, insufficient signal-to-noise ratio (SNR) significantly degrades the applicability of those applications which require high SNR, e.g. magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) treatment. This study introduces a wireless inductively coupled surface (WICS) coil design used on a clinical 3 T MRI system for MRgHIFU ablation. To evaluate the SNR improvement and temperature accuracy of WICS coil, the ex vivo experiments were performed on the pork tenderloins (n = 7) and the hind legs of deceased Sprague-Dawley rats (n = 5). To demonstrate the feasibility, the in vivo experiments were performed on the hind leg of Sprague-Dawley rat (n = 1). For all experiments, temperature measurements were performed before and during HIFU ablation. Temperature curves with and without WICS coil were compared to evaluate the temperature precision in ex vivo experiments. The use of WICS coil improves the temperature accuracy from 0.85 to 0.14 °C, demonstrating the feasibility of performing small animal MRgHIFU experiments using clinical 3 T MRI system with WICS coil.

Detecting blood-brain barrier disruption within minimal hemorrhage following transcranial focused ultrasound: a correlation study with contrast-enhanced MRI.

Focused ultrasound combined with an intravascular ultrasound contrast agent can induce transient disruption of the blood-brain barrier, and the blood-brain barrier disruption can be detected by contrast-enhanced MRI. There is, however, no study investigating the ability of various MR methods to detect focused ultrasound-induced blood-brain barrier disruption within minimal hemorrhage. Sonication was applied to 15 rat brains with four different doses of ultrasound contrast agent (0, 10, 30, or 50 µL/kg), and contrast-enhanced T1-weighted spin echo, gradient echo images, and longitudinal relaxation rate mapping along with effective transverse relaxation time-weighted and susceptibility-weighted images were acquired. Volume-of-interest-based and threshold-based analyses were performed to quantify the contrast enhancement, which was then correlated with the ultrasound contrast agent dose and with the amount of Evans blue extravasation. Both effective transverse relaxation time-weighted and susceptibility-weighted images did not detect histology-proved intracranial hemorrhage at 10 µL/kg, but MRI failed to detect mild intracranial hemorrhage at 30 µL/kg. All tested sequences showed detectable contrast enhancement increasing with ultrasound contrast agent dose. In correlating with Evans blue extravasation, the gradient echo sequence was slightly better than the spin echo sequence and was comparable to longitudinal relaxation rate mapping. In conclusion, both gradient echo and spin echo sequences were all reliable in indicating the degree of focused ultrasound-induced blood-brain barrier disruption within minimal hemorrhage.

Anatomical Phase Extraction (APE) Method: A Novel Method to Correct Detrimental Effects of Tissue-Inhomogeneity in Referenceless MR Thermometry-Preliminary Ex Vivo Investigation.

PURPOSE: We present a novel background tissue phase removing method, called anatomical phase extraction (APE), and to investigate the accuracy of temperature estimation and capability of reducing background artifacts compared with the conventional referenceless methods. METHODS: Susceptibility variance was acquired by subtracting pretreatment baseline images taken at different locations (nine pretreatment baselines are acquired and called φ 1 to φ 9). The susceptibility phase data φ S was obtained using the Wiener deconvolution algorithm. The background phase data φ T was isolated by subtracting φ S from the whole phase data. Finally, φ T was subtracted from the whole phase data before applying the referenceless method. As a proof of concept, the proposed APE method was performed on ex vivo pork tenderloin and compared with other two referenceless temperature estimation approaches, including reweighted ℓ1 referenceless (RW- ℓ1) and ℓ2 referenceless methods. The proposed APE method was performed with four different baselines combination, namely, (φ 1, φ 5, φ 2, φ 4), (φ 3, φ 5, φ 2, φ 6), (φ 7, φ 5, φ 8, φ 4), and (φ 9, φ 5, φ 8, φ 6), and called APE experiment 1 to 4, respectively. The multibaseline method was used as a standard reference. The mean absolute error (MAE) and two-sample t-test analysis in temperature estimation of three regions of interest (ROI) between the multibaseline method and the other three methods, i.e., APE, RW- ℓ1, and ℓ2, were calculated and compared. RESULTS: Our results show that the mean temperature errors of the APE method-experiment 1, APE method-experiment 2, APE method-experiment 3, APE method-experiment 4, and RW- ℓ1 and ℓ2 referenceless method are 1.02°C, 1.04°C, 1.00°C, 1.00°C, 4.75°C, and 13.65°C, respectively. The MAEs of the RW- ℓ1 and ℓ2 referenceless methods were higher than that of APE method. The APE method showed no significant difference (p > 0.05), compared with the multibaseline method. CONCLUSION: The present work demonstrates the use of the APE method on referenceless MR thermometry to improve the accuracy of temperature estimation during MRI guided high-intensity focused ultrasound for ablation treatment.

Pulse sequence and timing of contrast-enhanced MRI for assessing blood-brain barrier disruption after transcranial focused ultrasound in the presence of hemorrhage.

PURPOSE: To optimize the timing of contrast-enhanced magnetic resonance imaging (MRI) that best indicates blood-brain barrier (BBB) disruption induced by focused ultrasound (FUS) along with an ultrasound contrast agent (UCA) and to verify that the contrast-enhanced spin-echo MRI sequence can indicate the degree and location of BBB disruption in the presence of hemorrhage better than a gradient-echo sequence. MATERIALS AND METHODS: Sonication was applied to 12 rat brains with four different doses of UCA to cause variable degrees of hemorrhage. Two imaging sequences were performed to acquire T1-weighted (T1W) images at two time-points after the administration of a T1-shortening contrast agent. The contrast enhancement at the sonicated regions was quantified and correlated against Evans blue (EB) staining. RESULTS: The spin-echo T1W images at 10 minutes post-contrast enhancement showed the best correlation with EB staining in both quantity of EB extravasation (r = 0.812; P < 0.01) and spatial distribution (r = 0.528, P < 0.01). This capability was more robust than the gradient-echo sequence. CONCLUSION: Our results suggest that contrast-enhanced T1W spin-echo sequence acquired in the early phase post-contrast enhancement should be considered to monitor the degree and location of BBB disruption under the possibility of hemorrhage induced by FUS.

Combination Therapy of Pulsed-Wave Ultrasound Hyperthermia and Immunostimulant OK-432 Enhances Systemic Antitumor Immunity for Cancer Treatment.

PURPOSE: In this study, we hypothesized that systemic antitumor immunity might be enhanced by combining pulsed-wave ultrasound hyperthermia (pUSHT) with OK-432 and that the induced antitumor immunity could confer protection against tumorigenesis. These hypotheses were tested in bilateral and rechallenged tumor models. METHODS AND MATERIALS: Bilateral and rechallenged tumor models were applied in the studies. In the bilateral tumor model, BALB/c mice were inoculated in both flanks with CT26-luc tumor cells. The tumors in the right flank were treated with 4 courses of pUSHT with or without OK-432. In the rechallenged tumor model, tumor cells were implanted into the right flank. Once formed, the tumors were treated with pUSHT with OK-432, followed by surgical resection. New tumor cells were then implanted into the contralateral flank. The antitumor response was evaluated via infiltrated immune cells and the severity of necrosis/apoptosis in tumors. RESULTS: In the bilateral tumor model, the tumor growth rate and growth activity of both treated (100% reduction) and untreated tumors (90.5% reduction) were significantly inhibited with the combination treatment compared with the sham control group, and the systemic antitumor effect was prolonged. The survival rate was significantly enhanced (sham control, 8 days; OK plus pUSHT, >20 days). IFNγ+ CD4 (treated tumor, 8.6-fold; untreated tumor, 4-fold), IFNγ+ CD8 (treated tumor, 6.7-fold; untreated tumor, 2.6-fold), and T cell and NK cell (treated tumor, 4-fold; untreated tumor, 2.5-fold) infiltration was increased in the combination group compared with the control group. In the rechallenged tumor model, new tumors failed to form with the combination treatment. CONCLUSION: This experimental study combining pUSHT and OK-432 explored a new therapeutic strategy for controlling colon cancer metastasis. The results show that the combination treatment may produce an effective antitumor immune response.

A sequence-based hybrid predictor for identifying conformationally ambivalent regions in proteins.

BACKGROUND: Proteins are dynamic macromolecules which may undergo conformational transitions upon changes in environment. As it has been observed in laboratories that protein flexibility is correlated to essential biological functions, scientists have been designing various types of predictors for identifying structurally flexible regions in proteins. In this respect, there are two major categories of predictors. One category of predictors attempts to identify conformationally flexible regions through analysis of protein tertiary structures. Another category of predictors works completely based on analysis of the polypeptide sequences. As the availability of protein tertiary structures is generally limited, the design of predictors that work completely based on sequence information is crucial for advances of molecular biology research. RESULTS: In this article, we propose a novel approach to design a sequence-based predictor for identifying conformationally ambivalent regions in proteins. The novelty in the design stems from incorporating two classifiers based on two distinctive supervised learning algorithms that provide complementary prediction powers. Experimental results show that the overall performance delivered by the hybrid predictor proposed in this article is superior to the performance delivered by the existing predictors. Furthermore, the case study presented in this article demonstrates that the proposed hybrid predictor is capable of providing the biologists with valuable clues about the functional sites in a protein chain. The proposed hybrid predictor provides the users with two optional modes, namely, the high-sensitivity mode and the high-specificity mode. The experimental results with an independent testing data set show that the proposed hybrid predictor is capable of delivering sensitivity of 0.710 and specificity of 0.608 under the high-sensitivity mode, while delivering sensitivity of 0.451 and specificity of 0.787 under the high-specificity mode. CONCLUSION: Though experimental results show that the hybrid approach designed to exploit the complementary prediction powers of distinctive supervised learning algorithms works more effectively than conventional approaches, there exists a large room for further improvement with respect to the achieved performance. In this respect, it is of interest to investigate the effects of exploiting additional physiochemical properties that are related to conformational ambivalence. Furthermore, it is of interest to investigate the effects of incorporating lately-developed machine learning approaches, e.g. the random forest design and the multi-stage design. As conformational transition plays a key role in carrying out several essential types of biological functions, the design of more advanced predictors for identifying conformationally ambivalent regions in proteins deserves our continuous attention.

Time dependency of ultrasound-facilitated gene transfection.

BACKGROUND: The use of ultrasound (US)-facilitated gene therapy is increasing rapidly as a result of its high specificity and non-invasiveness. However, the acoustic parameters that produce the most efficient transfection have not been established. The present study investigated the effects of time parameters [including pulsing strategy (on- and off-times), exposure duration, pore opening time and expression duration] of US-facilitated gene transfection. METHODS: Cervical cancer cells (HeLa cells) cultured with pCMViLUC plasmids were exposed to 1-MHz pulsed US, and gene transfection efficiency and cell viability were assessed. The ability of in vivo transfection by ultrasound using different pulsing strategy was also evaluated. RESULTS: For a constant total exposure time, the transfection was always better for a longer on-time (on-off ratio = 1, or 50% duty cycle) than a shorter one (ratio = 0.1, 9% duty cycle), whether performed in vitro or in vivo. However, for a fixed on-time, there was a strong inverse correlation between transfection efficiency and off-time (r(2) = 0.89). Multiple regression analysis showed that the on-time, off-time and on-off ratio are all independent variables for US-facilitated gene transfection. Furthermore, transfection increased with the total exposure time, but plateaued for long exposure times. More than half of the opened pores closed within 15 s after the cessation of US exposure. The half-life of the transfected DNA was 7.43 days. CONCLUSIONS: Time is an important determinant of US-facilitated gene transfection. Methods for increasing the transfected number of plasmids, such as increasing the concentration of plasmids or the duration of pore opening, will be critical for future research and clinical applications.

Differences in gene expression between sonoporation in tumor and in muscle.

BACKGROUND: Ultrasound (US) is a novel and effective tool for the local delivery of genes into target tissues. US can temporarily change the permeability of a cell membrane and thus enhance the delivery of naked DNA into cells. In the present study, the efficiencies of gene expression mediated by US delivery in orthotopic liver tumor, subcutaneous tumor and muscle tissue were evaluated by changing the contrast agent concentrations and US exposure durations. METHODS: Plasmid DNA coding for luciferase, interleukin-12 or enhanced green fluorescence protein was mixed with SonoVue and injected intratumorally or intramuscularly. The injection sites were then exposed to US (20% duty cycle and 0.4 W/cm(2) intensity). RESULTS: The results obtained showed that the optimal condition was 50% SonoVue for tumors and 30% for muscle, with 10 min of US exposure. The expression levels of the transfected DNAs were in the order: muscle > subcutaneous tumor > orthotopic liver tumor. CONCLUSIONS: The present study indicates that muscle tissue is a good target site for producing large amounts of gene products for the purpose of gene therapy.

Identification of CpG methylation of the SNRPN gene by methylation-specific multiplex PCR.

In this article, we show that methylation-specific multiplex PCR (MS-multiplex PCR) is a sensitive and specific single assay for detecting CpG methylation status as well as copy number aberrations. We used MS-multiplex PCR to simultaneously amplify three sequences: the 3' ends of the SNRPN gene (for unmethylated sequences), the KRITI gene (as internal control), and the promoter of the SNRPN gene containing CpG islands (for methylated sequences) after digestion with a methylation-sensitive restriction enzyme (HhaI). We established this duplex assay for the analysis of 38 individuals with Prader-Willi syndrome, 2 individuals with Angelman syndrome, and 28 unaffected individuals. By comparing the copy number of the three regions, the methylation status and the copy number changes can be easily distinguished by MS-multiplex PCR without the need of bisulfite treatment of the DNA. The data showed that MS-multiplex PCR allows for the estimation of the methylation level by comparing the copy number aberrations of unknown samples to the standards with a known methylated status. The in-house-designed MS-multiplex PCR protocol is a relatively simple, cost-effective, and highly reproducible approach as a significant strategy in clinical applications for epigenetics in a routine laboratory.

Pulsed-wave Ultrasound Hyperthermia Enhanced Nanodrug Delivery Combined with Chloroquine Exerts Effective Antitumor Response and Postpones Recurrence.

Autophagy is found to serve as a surviving mechanism for cancer cells. Inhibiting autophagy has been considered as an adjuvant anti-cancer strategy. In this study, we investigated the anti-tumor effect of combining pulsed-wave ultrasound hyperthermia (pUH) enhanced PEGylated liposomal doxorubicin (PLD) delivery with an autophagy inhibitor chloroquine (CQ). BALB/c mice bearing subcutaneous 4T1 tumor received intravenous injection of PLD (10 mg/kg) plus 15-minute on-tumor pUH on Day 5 after tumor implantation and were then fed with CQ (50 mg/kg daily) thereafter. Prolonged suppression of tumor growth was attained with PLD + pUH + CQ treatment, whereas in PLD + pUH group tumors quickly recurred after an initial inhibition. Treatment with CQ monotherapy had no benefit compared to the control group. Immunohistochemical staining and Western blotting showed that autophagy of cancer cells was blocked for the mice receiving CQ. It indicates that PLD + pUH + CQ is a promising strategy to treat cancer for a long-term inhibition.

Acetic-Acid Plasma-Polymerization on Polymeric Substrates for Biomedical Application.

: Cold plasma is an emerging technology offering many potential applications for regenerative medicine or tissue engineering. This study focused on the characterization of the carboxylic acid functional groups deposited on polymeric substrates using a plasma polymerization process with an acetic acid precursor. The acetic acid precursor contains oxygen and hydrocarbon that, when introduced to a plasma state, forms the polylactide-like film on the substrates. In this study, polymeric substrates were modified by depositing acetic acid plasma film on the surface to improve hydrophilic quality and biocompatibility. The experimental results that of electron spectroscopy for chemical analysis (ESCA) to show for acetic acid film, three peaks corresponding to the C-C group (285.0 eV), C-O group (286.6 eV), and C=O group (288.7 eV) were observed. The resulting of those indicated that appropriate acetic acid plasma treatment could increase the polar components on the surface of substrates to improve the hydrophilicity. In addition, in vitro cell culture studies showed that the embryonic stem (ES) cell adhesion on the acetic acid plasma-treated polymeric substrates is better than the untreated. Such acetic acid film performance makes it become a promising candidate as the surface coating layer on polymeric substrates for biomedical application.

Comparison of the mismatch-specific endonuclease method and denaturing high-performance liquid chromatography for the identification of HBB gene mutations.

BACKGROUND: Beta-thalassemia is a common autosomal recessive hereditary disease in the Meditertanean, Asia and African areas. Over 600 mutations have been described in the beta-globin (HBB), of which more than 200 are associated with a beta-thalassemia phenotype. RESULTS: We used two highly-specific mutation screening methods, mismatch-specific endonuclease and denaturing high-performance liquid chromatography, to identify mutations in the HBB gene. The sensitivity and specificity of these two methods were compared. We successfully distinguished mutations in the HBB gene by the mismatch-specific endonuclease method without need for further assay. This technique had 100% sensitivity and specificity for the study sample. CONCLUSION: Compared to the DHPLC approach, the mismatch-specific endonuclease method allows mutational screening of a large number of samples because of its speed, sensitivity and adaptability to semi-automated systems. These findings demonstrate the feasibility of using the mismatch-specific endonuclease method as a tool for mutation screening.

Genotyping of the G1138A mutation of the FGFR3 gene in patients with achondroplasia using high-resolution melting analysis.

OBJECTIVES: The fibroblast growth factor receptor 3 gene (FGFR3) plays a critical role in cartilage growth-plate differentiation and bony development. It has been shown that 97% of patients with achondroplasia have a G to A transition mutation at position 1138 (c.1138 G>A) of codon 380 of the FGFR3 gene. DESIGN AND METHODS: Exon 8 of the FGFR3 gene was analyzed in 40 patients with achondroplasia, as well as in 50 control individuals for the presence of the c.1138G>A variant using melting curve analysis with a high-resolution melting instrument (HR-1). RESULTS: The high-resolution melting curve analysis successfully genotyped the c.1138G>A mutation in exon 8 of the FGFR3 gene in all 40 patients with achondroplasia without the need of further assays. The technique had a sensitivity and specificity of 100%. CONCLUSION: High-resolution melting analysis is a simple, rapid, and sensitive one tube assay for genotyping the FGFR3 gene. The technique is a low cost high-throughput FGFR3 screening assay.

Split-focused ultrasound transducer with multidirectional heating for breast tumor thermal surgery.

This study investigated the feasibility of using a split-focused ultrasound transducer to perform thermal surgery on breast tumors, based on a multidirectional heating scheme. The transducer is a square section of a sphere with a radius of 10 cm. The transducer was tilted such that its acoustic beam was 45 degrees relative to the rib surface, and its focal zone was arranged by a shift of 6 mm away from the center of the planning target volume. The multifocus switching technique was employed to enhance the heating efficiency. When a single transducer was used, the transducer sonicated from a certain position for a given duration, and then rotated sequentially to continue the heating. Computer simulations and in vitro phantom experiments have been studied for this heating system. Both simulation and experimental results demonstrated that the system based on a multidirectional heating scheme is capable of generating a proper thermal lesion within 8 min. Meanwhile, from the simulation results, the rib heating was effectively alleviated by tilting the transducer to induce the total reflection at the muscle/bone interface. While using multiple ultrasound transducers, an appropriate arrangement was designed to have the same configuration of acoustic beams as is used for a single-transducer strategy. The simulation results from the four-transducer strategy indicated that the heating results could be further improved. This study revealed that it is very promising to have an appropriate arrangement of a single split-focused ultrasound transducer with mechanical rotation, or to have multiple split-focused transducers that use multidirectional heating for breast tumor thermal therapy.

Quantitative evaluation of the use of microbubbles with transcranial focused ultrasound on blood-brain-barrier disruption.

It has been shown that focused ultrasound (FUS) can disrupt the blood-brain barrier (BBB) noninvasively and reversibly at target locations when applied in the presence of ultrasound contrast agent (UCA). In this study, the dose-dependent effects of UCA on BBB disruption were investigated in the brains of 16 male Wistar rats sonicated by 1.0-MHz transcranial FUS, with the UCA present at four doses. The BBB disruption was evaluated quantitatively based on the extravasation of Evans blue (EB). The amount of EB extravasation in the brain increased with the quantity of UCA injected into the femoral vein prior to sonication. Moreover, the use of a suitable dose of UCA resulted in the BBB disruption being concentrated in the focal region instead of the entire brain. Our results indicate that injecting an appropriate quantity of UCA effectively increases and localizes the BBB disruption induced by transcranial FUS sonications.

Plasma Deposition and UV Light Induced Surface Grafting Polymerization of NIPAAm on Stainless Steel for Enhancing Corrosion Resistance and Its Drug Delivery Property.

When stainless steel is implanted in human bodies, the corrosion resistance and biocompatibility must be considered. In this study, first, a protective organic silicone film was coated on the surface of stainless steel by a plasma deposition technique with a precursor of hexamethyldisilazane (HMDSZ). Then, ultraviolet (UV) light-induced graft polymerization of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) in different molar ratios were applied onto the organic silicone film in order to immobilize thermos-/pH-sensitive composite hydrogels on the surface. The thermo-/pH-sensitive composite hydrogels were tested at pH values of 4, 7.4 and 10 of a phosphate buffer saline (PBS) solution at a fixed temperature of 37 °C to observe the swelling ratio and drug delivery properties of caffeine which served as a drug delivery substance. According to the results of Fourier Transformation Infrared (FTIR) spectra and a potential polarization dynamic test, the silicone thin film formed by plasma deposition not only improved the adhesion ability between the substrate and hydrogels but also exhibited a high corrosion resistance. Furthermore, the composite hydrogels have an excellent release ratio of up to 90% of the absorbed amount after 8h at a pH of 10. In addition, the results of potential polarization dynamic tests showed that the corrosion resistance of stainless steel could be improved by the HMDSZ plasma deposition.