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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

Transrectal ultrasonography-guided transperineal bilateral seminal vesicle puncture and continuous irrigation for the treatment of intractable hematospermia

Hematospermia is a rare condition, but often causes frustration. The reason for this frustration is that theexact incidence of hematospermia remains unknown and its cause is difficult to determine.^1 Many reports in the past decades have focused on the etiology of hematospermia.^2 Hematospermia is treated initially by administration of antibiotics, coagulants, and sex steroid hormones. However, some cases may prove resistant to this therapy and the condition may continue. For some intractable and agnogenic cases, the therapeutic strategy mentioned above is not very effective. Recently, we treated 63 such nonresponsive patients by direct continuous antibiotic irrigation into the bilateral seminal vesicles through puncture under transrectal ultrasonography （TRUS） guidance.

Hepatocellular carcinoma clinical update: Current standards and therapeutic strategies

Hepatocellular carcinoma(HCC)accounts for the vast majority of primary hepatic malignancies.The overall incidence of this disease has always been significant,but in recent years it has continued to rise,now making HCC one of the leading causes of cancer deaths worldwide.Fortunately,research into the mechanisms of carcinogenesis and treatment options for this disease has also been progressing rapidly.Although the future for new insights and therapies appears more promising than ever,it also remains important to understand both the nature of HCC and the current state-of-the-art for treating affected patients.Although surgery is often considered to be a first choice,many patients present with extensive disease and are therefore not operative candidates.Fortunately,significant clinical advances over the last decade have contributed a number of new or improved treatment options.Many of these treatments require expertise from a variety of different clinical subspecialties.Indeed,managing patients with HCC has rapidly become a multi-modality,multi-disciplinary endeavor in which the details of each in-dividual’s circumstance can greatly impact outcomes,and strategies can be quite nuanced.The purpose of this review is to provide a perspective on the disease itself,the patients who become afflicted,the spectrum of currently available treatment options,and the strategies for their optimal implementation.Such knowledge can be critically important as new data become available on the research front.