Effect of high intensity ultrasound on the allergenicity of shrimp

The tropomyosin fraction of shrimp proteins is potentially responsible for allergic reaction in individuals with genetic predisposition to allergy. However, there are no efficient and safe methods to reduce its allergenicity. High intensity ultrasound is known to change the structure of proteins. This study is aimed at assessing high intensity ultmsound＇s effect on the allergenicity of shrimp allergen. Shrimp and purified shrimp allergen were treated with high intensity ultrasound for 30-180 min. Extracts of treated samples were analyzed by enzyme-linked immunosorbent assay （ELISA） with pool serum of shrimp allergy patients and polyclonal anti-allergen antibodies and by immunoblotting after polyacrylamide gel electrophoresis. Shrimp treated with high intensity ultrasound showed a decrease in allergenicity measured with ELISA. A linear relationship between the immune response induced by treated shrimp allergen and the applied treatment time was observed. The decrease in allergenicity was confirmed by immunoblot assays with shrimp allergic patients serum. Allergenicity of shrimp allergen extracted from treated shrimp was higher than that of purified shrimp allergen with the same treatment time. Gel-filtration HPLC was applied for analysis of shrimp allergen after treatment with high intensity ultrasound. Some fractions were appeared with increasing treatment time. The results suggested that high intensity ultrasound could be used to reduce the allergenicity of shrimp.

Complications of high intensity focused ultrasound in patients with recurrent and metastatic abdominal tumors

AIM： To analyze the local and systemic complications of high intensity focused ultrasound （HIFU） for patients with recurrent and metastatic abdominal tumors. METHODS： From Aug 2001 to Aug 2004, 17 patients with recurrent and metastatic abdominal tumors were enrolled in this study. Real-time sonography was taken, and vital signs, liver and kidney function, skin burns, local reactions, and systemic effects were observed and recored before, during, and after HIFU. CT and MR/were also taken before and after HIFU. RESULTS： All 17 patients had skin burns and pain in the treatment region; the next common complication was neurapraxia of the stomach and intestines to variable degrees. The other local and systemic complications were relatively rare. Severe complications were present in two patients; one developed a superior mesenteric artery infarction resulting in necrosis of the entire small intestines, and the other one suffered from a perforation in terminal ileum due to HIFU treatment. CONCLUSION： Although HIFU is a one of noninvasive treatments for the recurrent and metastatic abdominal tumors, there are still some common and severe complications which need serious consideration.

Low intensity ultrasound-induced apoptosis in human gastric carcinoma cells

AIM： To investigate the low intensity ultrasound （US）- induced apoptosis in human gastric carcinoma cells and its potential mechanism and to suggest a new therapeutic approach to gastric carcinoma. METHODS： Human SGC-7901 gastric carcinoma cells were cultured in vitro and irradiated by low intensity US for 10 min at different intensities with different incubation times after irradiation. Morphologic changes were examined under microscope with trypan blue staining and then the percentage of early apoptotic cells was detected by flow cytometry （FCM） with double staining of fiuorescein isothiocyanate （FITC）- Annexin V/propidium iodide （PI）. Two-dimensional electrophoresis （2DE） was used to get the protein profile and some proteins differently expressed after US irradiation were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS）. Functional analysis was performed to investigate the mechanism of US-induced cell apoptosis. RESULTS： The percentage of apoptotic cells increased about 10% after US irradiation （12.0 W/cm^2, 12 h culture）, The percentage of early apoptosis and secondary necrosis in the US-irradiated cells increased with the increased US intensity. Moreover, apoptotic cells increased with the increased culture time after US irradiation and reached its maximum at about 12 h.Several new proteins appeared after US irradiation and were up or down regulated more than 2 times. Some heat shock proteins （HSPs） were found to be associated with the signal process simulating the apoptosis of cells. CONCLUSION： Low intensity US could induce apoptosis in human gastric carcinoma cells. US-induced apoptosis is related to US intensity/culture time. US-induced apoptosis may be caspases-dependent and endoplasmic reticulum （ER） stress-triggered apoptosis may also contribute to it. Proteomic experimental system is useful in finding the protein alteration in carcinoma cells after US irradiation, helping to develop a new cancer therapy.

High intensity focused ultrasound: A noninvasive therapy for locally advanced pancreatic cancer

The noninvasive ablation of pancreatic cancer with high intensity focused ultrasound(HIFU) energy is received increasingly widespread interest. With rapidly temperature rise to cytotoxic levels within the focal volume of ultrasound beams, HIFU can selectively ablate a targeted lesion of the pancreas without any damage to surrounding or overlying tissues. Preliminary studies suggest that this approach is technical safe and feasible, and can be used alone or in combination with systemic chemotherapy for the treatment of patients with locally advanced pancreatic cancer. It can effectively alleviate cancer-related abdominal pain, and may confer an additional survival benefit with few significant complications. This review provides a brief overview of HIFU, describes current clinical applications, summarizes characteristics of continuous and pulsed HIFU, and discusses future applications and challenges in the treatment of pancreatic cancer.

Enhancing excess sludge aerobic digestion with low intensity ultrasound

In order to enhance the efficiency of aerobic digestion, the excess sludge was irradiated by low intensity ultrasound at a frequency of 28 kHz and acoustic intensity of 0.53 W/cm^2. The results show that the sludge stabilization without ultrasonic treatment can be achieved after 17 d of digestion, whereas the digestion time of ultrasonic groups can be cut by 3-7 d. During the same digestion elapsing, in ultrasonic groups the total volatile suspended solid removal rate is higher than that in the control group. The kinetics of aerobic digestion of excess sludge with ultrasound can also be described with first-order reaction.

Non-thermal ablation of rabbit liver VX2 tumor by pulsed high intensity focused ultrasound with ultrasound contrast agent:Pathological characteristics

AIM： To investigate the pathological characteristics of non-thermal damage induced by pulsed high intensity focused ultrasound （PHIFU） combined with ultrasound contrast agent （UCA）, SonoVue （Bracco SpA, Milan, Italy） in rabbit liver VX2 tumor. METHODS： Liver VX2 tumor models were established in 20 rabbits, which were divided randomly into PHIFU combined with ultrasound contrast agent group （PHIFU ＋ UCA group） and sham group. In the PHIFU ＋ UCA group, 0.2 mL of SonoVue was injected intravenously into the tumor, followed by ultrasound exposure of Isp 5900 W/cm^2. The rabbits were sacrificed one day after ultrasound exposure. Specimens of the exposed tumor tissues were obtained and observed pathologically under light microscope and transmission electron microscope. The remaining tumor tissues were sent for 2,3,5-Triphenyltetrazolium chloride （TTC） staining. RESULTS： Before Trc staining, tumor tissues in both the sham and the PHIFU ＋ UCA groups resembled gray fish meat, After TIC staining, the tumor tissues were uniformly stained red, with a clear boundary between tumor tissue and normal tissue, Histological examination showed signs of tumor cell injury in PHIFU ＋ UCA group, with cytoplasmic vacuoles of various sizes, chromatin margination and karyopyknosis. Electron microscopic examination revealed tumor cell volume reduction, karyopyknosis, chromatin margination, intercellular space widening, the presence of high electro＇n-density apoptotic bodies and vacuoles in cytoplasm. CONCLUSION： The non-thermal effects of PHIFU combined with UCA can be used to ablate rabbit liver VX2 tumors.

Osteogenic Effect of Low Intensity Pulsed Ultrasound on Rat Adipose-derived Stem Cells in vitro

The osteogenic in vitro effect of low intensity pulsed ultrasound (LIPUS) on SD rat adi-pose-derived stem cells (ADSCs) was investigated.Rat ADSCs underwent LIPUS (intensity=100 mW/cm2) or sham exposure for 8 min per treatment once everyday in vitro,and then the alkaline phos-phatase (ALP) activity and mineralized nodule formation were assessed to evaluate the osteogenic effect of LIPUS on ADSCs.To further explore the underlying mechanism,the osteogenic-related gene mRNA expression was determined by using reverse transcriptase-polymerase chain reaction (RT-PCR) at 1st,3rd,5th,7th day after exposure repectively.Westen blot was used to evaluate the protein expression levels of two osteogenic differentiation associated genes at 7th and 14th day repectively.It was found that ALP activity was increased after LIPUS exposure and LIPUS resulted in mineralized nodule formation of ADSCs in vitro.LIPUS-treated ADSCs displayed higher mRNA expression levels of runt-related transcription factor 2 (Runx2),osteocalcin (OCN),ALP and bone sialoprotein (BSP) genes than con-trols,and the protein levels of Runx2 and BSP were also increased.The results suggested that LIPUS may induce the osteogenic differentiation of ADSCs in vitro.

Sonablate-500^(TM) Transrectal High-intensity Focused Ultrasound (HIFU) for Benign Prostatic Hyperplasia Patients

To evaluate the safety and efficacy of transrectal high-intensity focused ultrasound （HIFU） in the treatment of benign prostatic hyperplasia （BPH）, serial studies were conducted in 150 BPH patients before and 30 min, 1, 2, 6 and 12 month（s） after Sonablate-500TM HIFU treatment. A silicon-coated indwelling 16F latex catheter was placed during the determination of the therapy zone. Preoperative and postoperative evaluations were made by using the international prostate symptom score （IPSS）, quality of life （QOL）, uroflowmetric findings and transrectal ultrasound, and incidence of complications. The cystourethrography was done in 23 patients within 1 year postoperatively. The results showed that after HIFU treatment, IPSS and QOL scores were significantly decreased at 1, 2, 6 and 12 month（s） （P〈0.01）. Maximum urine flow rate （6.0 to 17.2 mL/s, P〈0.01）, PVR （75.0 to 30.3, P〈0.01） and prostatic volume （65.0 to 38.1 mL, P〈0.05） were significantly improved 12 months after the operation. Recurrent urinary retention （17=2） and urethrorectal fistula （n=1） occurred at the 15th postoperative day. The duration of the HIFU prostate ablation was 25-90 min. The mean time for an indwelling catheter was 3-19 days. These data demonstrate that treatment of BPH with Sonab- late-500TM HIFU is safe and effective.

Identification of denatured and normal biological tissues based on compressed sensing and refined composite multi-scale fuzzy entropy during high intensity focused ultrasound treatment

In high intensity focused ultrasound(HIFU)treatment,it is crucial to accurately identify denatured and normal biological tissues.In this paper,a novel method based on compressed sensing(CS)and refined composite multi-scale fuzzy entropy(RCMFE)is proposed.First,CS is used to denoise the HIFU echo signals.Then the multi-scale fuzzy entropy(MFE)and RCMFE of the denoised HIFU echo signals are calculated.This study analyzed 90 cases of HIFU echo signals,including 45 cases in normal status and 45 cases in denatured status,and the results show that although both MFE and RCMFE can be used to identify denatured tissues,the intra-class distance of RCMFE on each scale factor is smaller than MFE,and the inter-class distance is larger than MFE.Compared with MFE,RCMFE can calculate the complexity of the signal more accurately and improve the stability,compactness,and separability.When RCMFE is selected as the characteristic parameter,the RCMFE difference between denatured and normal biological tissues is more evident than that of MFE,which helps doctors evaluate the treatment effect more accurately.When the scale factor is selected as 16,the best distinguishing effect can be obtained.

Role of acoustic interface layer during high intensity focused ultrasound therapeutics

After interface layer was simulated by the magnetic nano-particles in the egg white phantom, high intensity focused ultrasound （HIFU） at the same dosage was introduced to radiate the phantom in different depths to blow the acoustic interface layer to mimic ＂point＂ exposure. The results showed that the volumes of biological focal region （BFR） were enlarged when the acoustic focal region （AFR） is close with interface layer. This meant that the magnetic nano-particles enhanced the therapeutic efficiency of HIFU. When the distance of the AFR from the interface layer was 10 mm, the size and shape of the BFR were similar with those of the control group, but a larger lesion at the interface, which was harmful for treatment, was observed. When the distance of the AFR to the interface layer increased to 30 mm, the size and shape of the BFR were also similar to those of the control group. When the thickness of the interface layer diminished, the utility of enhancement decreased. Continuous increase of the safe area for treatment and decrease of the utility of enhancement were observed along with the abatement of the thickness of the interface layer

Experimental Study on Low Intensity Ultrasound and Tissue Engineering to Repair Segmental Bone Defects

In order to evaluate the efficacy of low intensity ultrasound and tissue engineering technique to repair segmental bone defects, the rabbit models of 1.5-cm long rabbit radial segmental osteoperiosteum defects were established and randomly divided into 2 groups. All defects were implanted with the composite of calcium phosphate cement and bone mesenchymal stem cells, and ad- ditionally those in experimental group were subjected to low intensity ultrasound exposure, while those in control group to sham exposure. The animals were killed on the postoperative week 4, 8 and 12 respectively, and specimens were harvested. By using radiography and the methods of biomechanics, histomorphology and bone density detection, new bone formation and material degradation were observed. The results showed that with the prolongation of time after operation, serum alkaline phosphatase （AKP） levels in both groups were gradually increased, especially in experimental group, reached the peak at 6th week （experimental group： 1,26 mmol/L; control group： 0.58 mmol/L）, suggesting the new bone formation in both two group, but the amount of new bone formation was greater and bone repairing capacity stronger in experimental group than in control group. On the 4th week in experimental group, chondrocytes differentiated into woven bone, and on the 12th week, remodeling of new lamellar bone and absorption of the composite material were observed. The mechanical strength of composite material and new born density in experimental group were significantly higher than in control group, indicating that low intensity ultrasound could not only effectively increase the formation of new bone, but also accelerate the calcification of new bone. It was concluded that low intensity ultrasound could evidently accelerate the healing of bone defects repaired by bone tissue engineering.

Analgesic effect of high intensity focused ultrasound in patients with advanced pancreatic cancer

Objective： The aim of this study was to evaluate the analgesic effect of high intensity focused ultrasound （HIFU） in patients with advanced pancreatic cancer. Methods： A total of 106 patients with advanced pancreatic cancer accompanied by abdominal pain were treated by HIFU. Pain intensities and quantities of morphine consumption before and after treatment were observed and compared. Results： The average pain intensities before treatment, and at d3, d7 after treatment were 5.80 ±2.14, 2.73 ± 2.68, 2.45 ± 2.43 respectively （P 〈 0.01）. Fifty-nine cases （55.7%） got to extremely effective, and 29 cases （27.4%） effective. Total efficient rate was 83.0 %. The average quantities of morphine consumption before and after treatment in the patients with grade III pain were 114.9 ± 132.5 rag, 16.8 ± 39.7 mg each person everyday respectively （P 〈 0.01）. Conclusion： HIFU can relieve pain suffered by patients with pancreatic cancer effectively. It is a new adjuvant treatment for pancreatic cancer pain.

High intensity focused ultrasound in combination with chemotherapy by the regime of PFC: a clinical study for advanced gastric carcinoma

Objective： To evaluate the recent curative efficacy and security of High intensity focused ultrasound （HIFU） in combination with chemotherapy（PFC） in patients with advanced gastric carcinoma. Method： Sixty patients with measurable advanced gastric carcinoma, proved pathologically, were divided into Group A and Group B. Group A： Patients were treated by HIFU（FEP-BY01） in combination with chemotherapy（PFC, paclitaxel, cisplatin and 5-fluorouracil）. Group B： Patients were treated with the single regime of PFC. Results： All cases could be evaluated, ha group A, 5 patients achieved complete response, 17 patients achieved partial response,and a response rate was 73.3%. The stable disease（SD） and the inefficiency all were 13.3% （4/30） respectively, and msurvival time（MST） was 13.9 months. In group B, 2 patients achieved complete response, 14 patients achieved partial response, and a response rate was 53.3%. The stable disease（SD） was 23.3%（7/30）. The inefficiency all were 23.3%（7/30） respectively, and median survival time was 9.6 months. There was significant difference between two groups MST（ P 〈 0.05）. Major toxicities included bone marrow depression, nausea, vomiting and alopecia, without significant differences between two groups（ P 〉 0.05）. Conclusion： This study shows that HIFU in combination with chemotherapy（PFC） was a new efficent and secure therapy for the patients with advanced gastric carcinoma. It was observed that the MST was prolonged. Prospective trials should be warranted to determine the result.

Low intensity ultrasound stimulates biological activity of aerobic activated sludge

This work aims to explore a procedure to improve biological wastewater treatment efficiency using low inten-sity ultrasound.The aerobic activated sludge from a munici-pal wastewater treatment plant was used as the experimental material.Oxygen uptake rate(OUR)of the activated sludge(AS)was determined to indicate the changes of AS activity stimulated by ultrasound at 35 kHz for 0-40 min with ultrasonic intensities of 0-1.2 W/cm^(2).The highest OUR was observed at the ultrasonic intensity of 0.3 W/cm^(2) and an irradiation period of 10 min;more than 15%increase was achieved immediately after sonication.More significantly,the AS activity stimulated by ultrasound could last 24 h after sonication,and the AS activity achieved its peak value within 8 h after sonication,or nearly 100%higher than the initial level after sonication.Therefore,to improve the wastewater treatment efficiency of bioreactors,ultrasound with an intensity of 0.3 W/cm^(2) could be employed to irradiate a part of the AS in the bioreactor for 10 min every 8 h.

Simulation of thermal field induced by concave spherical transducer in multi-layer media

High intensity focused ultrasound(HIFU)therapy is an effective method in clinical treatment of tumors,in order to explore the bio-heat conduction mechanism of in multi-layer media by concave spherical transducer,temperature field induced by this kind of transducer in multi-layer media will be simulated through solving Pennes equation with finite difference method,and the influence of initial sound pressure,absorption coefficient,and thickness of different layers of biological tissue as well as thermal conductivity parameter on sound focus and temperature distribution will be analyzed,respectively.The results show that the temperature in focus area increases faster while the initial sound pressure and thermal conductivity increase.The absorption coefficient is smaller,the ultrasound intensity in the focus area is bigger,and the size of the focus area is increasing.When the thicknesses of different layers of tissue change,the focus position changes slightly,but the sound intensity of the focus area will change obviously.The temperature in focus area will rise quickly before reaching a threshold,and then the temperature will keep in the threshold range.

Versatile nanocomposite augments high-intensity focused ultrasound for high-efficacy sonodynamic therapy of glioma

High-intensity focused ultrasound(HIFU),with inherent advantages of improved ultrasonic depth and low off-target damage,holds the promising capability for glioma treatment,but the relatively long therapeutic time and potential physical complications may hamper its clinical application.Herein,a bovine serum albumin(BSA)-based nanoplatform with in situ growth of MnO_(2) was synthesized,and Protoporphyrin IX(PpIX)was further anchored to obtain a versatile PpIX@MnO_(2)@BSA nanoplatform(denoted as BMP).By employing HIFU as the exogenous irradiation source,a high-efficacy sonodynamic therapy(SDT)is developed,in which the excited BMP enables the production of tumoricidal reactive oxygen species(ROS).The inherent tumor microenvironment(TME)-responsive property of MnO_(2) endows BMP with specific T1-weighted magnetic resonance imaging(MRI)by releasing Mn2+,and the simultaneously generated O_(2) facilitates hypoxia alleviation as well as ^(1)O_(2) generation.Compared with HIFU therapy alone,suppression of glioma growth and improved survival benefits are achieved through the designed TMEresponsive nanocomposite under HIFU exposure.The high-efficacy SDT strategy combining BMP and HIFU demonstrated favorable TME-responsive T1-weighted MRI,hypoxic environment alleviation,and anti-tumor capability,providing a perspective paradigm for MRI-guided glioma treatment.

Radiation force on absorbing targets and power measurements of a high intensity focused ultrasound (HIFU) source

Based on the analytic expressions for the radiated field of a circular concave piston given by Hasegawa et al.,an integral for calculation of the radiation force on a plane absorbing target in a spherically focused field is derived.A general relation between acoustic power P and normal radiation force Fn is obtained under the condition of kr 1.Numerical computation is carried out by using the symbolic computation program for practically focused sources and absorbing circular targets.The results show that,for a given source,there is a range of target positions where the radiation force is independent of the target's position under the assumption that the contribution of the acoustic field behind the target to the radiation force can be neglected.The experiments are carried out and confirm that there is a range of target positions where the measured radiation force is basically independent of the target's position even at high acoustic power (up to 700 W).It is believed that when the radiation force method is used to measure the acoustic power radiated from a focused source,the size of the target must be selected in such a way that no observable sound can be found in the region behind the target.

Cardiac ablation by transesophageal high intensity focused ultrasound

Cardiac ablation is an important modality of invasive therapy in modem cardiology, especially in the treatment of arrhythmias, as well as other diseases such as hypertrophic obstructive cardiomyopathy （HOCM）. Since Huang et alI used radiofrequency （RF） to ablate canine atrial ventricular junction, RF has developed into the leading energy source in catheter ablation of arrhythmias. However, there are several limitations associated with RF ablation, one of which is that it requires good contact and the depth of the lesion formed is usually limited. Thus, it is often very difficult to ablate arrhythmias originated at the epicardium with a routine endocardial RF delivery.

A New Full Bridge High Intensity Focused Ultrasound Power System with Harmonic Cancellation

The feasibility of a new full bridge high intensity focused ultrasound(HIFU) amplifier system with harmonic cancellation is evaluated in this study. Harmonic cancellation technique is applied to these power amplifiers, which can eliminate the 3rd harmonic and all even harmonics. Since this technique requires two channels of phase signal to control one channel of power amplifier, the signal generator is required to double its output. The transducer array proposed in this study has 100 elements. So we choose an FPGA chip to generate 200 driving signals, and each channel has a phase resolution of 2ns, less than 1°. The phase signal from the FPGA meets the requirement of driving the power amplifiers. The output waveform of one channel of power amplifier(voltage across the transducer) is evaluated, and shows fewer harmonic components.

Harnessing macrophages in thermal and non-thermal ablative therapies for urologic cancers-Potential for immunotherapy

Prostate and bladder cancers are one of the cancers occurring worldwide.In addition to radical surgery,the past decade has also focused on targeted therapy of overexpressed cancer proteins that are lethal and critical for cancer cell survival.However,targeted therapy cannot adapt for changing of cancer molecular characteristics and,ultimately,a clone that bypasses the targeted therapy emerges.This can be overcome by immunotherapy.New studies on ablative therapy of cancers show presence of immunomodulatory effect in these modalities.Tumor ablation prime the immune system for further destruction of persistent primary tumor in addition to destruction of concurrent metastatic disease and also reduce recurrence.Ablative therapies can achieve a state of increased antigenicity.Its combination with a novel macrophage targeted therapy may enhance immune priming,trafficking,and/or effector phases;thereby improving clinical outcomes.Tumor associated macrophages or M2 phenotype are now known to mediate this immunosuppressive pro-tumorigenic effect.Alteration of macrophage differentiation may enhance tumor destruction of ablative therapy.This breakthrough in immunotherapy opens up arenas for further robust clinical trials on combinatorial therapies.In the present review,we aim to elucidate the major aspects of immune stimulatory minimal invasive approaches by combining with macrophage directed pathways.