High intensity focused ultrasound (HIFU) in tumor therapy.

PubMed

Sequeiros, Roberto Blanco; Joronen, Kirsi; Komar, Gaber; Koskinen, Seppo K

HIFU (high intensity focused ultrasound) is a method in which high-frequency ultrasound is focused on a tissue in order to achieve a thermal effect and the subsequent percutaneously ablation, or tissue modulation. HIFU is non-invasive and results in an immediate tissue destruction effect corresponding to surgery, either percutaneously or through body cavities. HIFU can be utilized in the treatment of both benign and malignant tumors. In neurological diseases, focused HIFU can be used in the treatment of disorders of the basal ganglia.

Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor.

PubMed

Ravikumar, Vinod K; Parker, Jonathon J; Hornbeck, Traci S; Santini, Veronica E; Pauly, Kim Butts; Wintermark, Max; Ghanouni, Pejman; Stein, Sherman C; Halpern, Casey H

2017-08-01

Essential tremor remains a very common yet medically refractory condition. A recent phase 3 study demonstrated that magnetic resonance-guided focused ultrasound thalamotomy significantly improved upper limb tremor. The objectives of this study were to assess this novel therapy's cost-effectiveness compared with existing procedural options. Literature searches of magnetic resonance-guided focused ultrasound thalamotomy, DBS, and stereotactic radiosurgery for essential tremor were performed. Pre- and postoperative tremor-related disability scores were collected from 32 studies involving 83 magnetic resonance-guided focused ultrasound thalamotomies, 615 DBSs, and 260 stereotactic radiosurgery cases. Utility, defined as quality of life and derived from percent change in functional disability, was calculated; Medicare reimbursement was employed as a proxy for societal cost. Medicare reimbursement rates are not established for magnetic resonance-guided focused ultrasound thalamotomy for essential tremor; therefore, reimbursements were estimated to be approximately equivalent to stereotactic radiosurgery to assess a cost threshold. A decision analysis model was constructed to examine the most cost-effective option for essential tremor, implementing meta-analytic techniques. Magnetic resonance-guided focused ultrasound thalamotomy resulted in significantly higher utility scores compared with DBS (P < 0.001) or stereotactic radiosurgery (P < 0.001). Projected costs of magnetic resonance-guided focused ultrasound thalamotomy were significantly less than DBS (P < 0.001), but not significantly different from radiosurgery. Magnetic resonance-guided focused ultrasound thalamotomy is cost-effective for tremor compared with DBS and stereotactic radiosurgery and more effective than both. Even if longer follow-up finds changes in effectiveness or costs, focused ultrasound thalamotomy will likely remain competitive with both alternatives. © 2017 International Parkinson and Movement

MO-AB-210-03: Workshop [Advancements in high intensity focused ultrasound

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Z.

The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrationsmore » with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant

MO-AB-210-00: Diagnostic Ultrasound Imaging Quality Control and High Intensity Focused Ultrasound Therapy Hands-On Workshop

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrationsmore » with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant

High-intensity focused ultrasound: advances in technology and experimental trials support enhanced utility of focused ultrasound surgery in oncology

PubMed Central

Malietzis, G; Monzon, L; Hand, J; Wasan, H; Leen, E; Abel, M; Muhammad, A; Abel, P

2013-01-01

High-intensity focused ultrasound (HIFU) is a rapidly maturing technology with diverse clinical applications. In the field of oncology, the use of HIFU to non-invasively cause tissue necrosis in a defined target, a technique known as focused ultrasound surgery (FUS), has considerable potential for tumour ablation. In this article, we outline the development and underlying principles of HIFU, overview the limitations and commercially available equipment for FUS, then summarise some of the recent technological advances and experimental clinical trials that we predict will have a positive impact on extending the role of FUS in cancer therapy. PMID:23403455

Ultrasound-mediated Optical Imaging and Focusing in Scattering Media

NASA Astrophysics Data System (ADS)

Suzuki, Yuta

photorefractive materials as the phase-conjugate mirrors. By using a large-area photorefractive polymer as the phase-conjugate mirror, we boosted the focused optical energy by ~40 times over the output of a previously used photorefractive Bi 12SiO20 crystal. Furthermore, using both a photorefractive polymer and a Bi12SiO20 crystal as the phase-conjugate mirrors, we show direct visualization and dynamic control of TRUE focus, and demonstrate fluorescence imaging in a thick turbid medium. The last part of this dissertation describes improvements in the scanning speed of a TRUE focus, using digital phase-conjugate mirrors in both transmission and reflection modes. By employing a multiplex recording of ultrasonically encoded wavefronts in transmission mode, we have accelerated the generation of multiple TRUE foci, using frequency sweeping of both ultrasound and light. With this technique, we obtained a 2-D image of a fluorescent target centered inside a turbid sample having a thickness of 2.4 lt'. Also, by gradually moving the focal position in reflection mode, we show that the TRUE focal intensity is improved, and can be continuously scanned to image fluorescent targets in a shorter time.

The effect of blood acceleration on the ultrasound power Doppler spectrum

NASA Astrophysics Data System (ADS)

Matchenko, O. S.; Barannik, E. A.

2017-09-01

The purpose of the present work was to study the influence of blood acceleration and time window length on the power Doppler spectrum for Gaussian ultrasound beams. The work has been carried out on the basis of continuum model of the ultrasound scattering from inhomogeneities in fluid flow. Correlation function of fluctuations has been considered for uniformly accelerated scatterers, and the resulting power Doppler spectra have been calculated. It is shown that within the initial phase of systole uniformly accelerated slow blood flow in pulmonary artery and aorta tends to make the correlation function about 4.89 and 7.83 times wider, respectively, than the sensitivity function of typical probing system. Given peak flow velocities, the sensitivity function becomes, vice versa, about 4.34 and 3.84 times wider, respectively, then the correlation function. In these limiting cases, the resulting spectra can be considered as Gaussian. The optimal time window duration decreases with increasing acceleration of blood flow and equals to 11.62 and 7.54 ms for pulmonary artery and aorta, respectively. The width of the resulting power Doppler spectrum is shown to be defined mostly by the wave vector of the incident field, the duration of signal and the acceleration of scatterers in the case of low flow velocities. In the opposite case geometrical properties of probing field and the average velocity itself are more essential. In the sense of signal-noise ratio, the optimal duration of time window can be found. Abovementioned results may contribute to the improved techniques of Doppler ultrasound diagnostics of cardiovascular system.

Technical characterization of an ultrasound source for noninvasive thermoablation by high-intensity focused ultrasound.

PubMed

Köhrmann, K U; Michel, M S; Steidler, A; Marlinghaus, E; Kraut, O; Alken, P

2002-08-01

To develop a generator for high-intensity focused ultrasound (HIFU, a method of delivering ultrasonic energy with resultant heat and tissue destruction to a tight focus at a selected depth within the body), designed for extracorporeal coupling to allow various parenchymal organs to be treated. The ultrasound generated by a cylindrical piezo-ceramic element is focused at a depth of 10 cm using a parabolic reflector with a diameter of 10 cm. A diagnostic B-mode ultrasonographic transducer is integrated into the source to allow the focus to be located in the target area. The field distribution of the sound pressure was measured in degassed water using a needle hydrophone. An ultrasound-force balance was used to determine the acoustic power. These measurements allowed the spatially averaged sound intensity to be calculated. The morphology and extent of tissue necrosis induced by HIFU was examined on an ex-vivo kidney model. The two-dimensional field distribution resulted in an approximately ellipsoidal focus of 32 x 4 mm (- 6 dB). The spatially maximum averaged sound intensity was 8591 W/cm2 at an electrical power of 400 W. The lesion caused to the ex-vivo kidney at this maximum generator power with a pulse duration of 2 s was a clearly delineated ellipsoidal coagulation necrosis up to 8.8 x 2.3 mm (length x width) and with central liquefied necrosis of 7.9 x 1.9 mm. This newly developed ultrasound generator with a focal length of 10 cm can induce clear necrosis in parenchymal tissue. Because of its specific configuration and the available power range of the ultrasound generator, there is potential for therapeutic noninvasive ablation of tissue deep within a patient's body.

Development of ultrasound focusing discrete array for air-coupled ultrasound generation

NASA Astrophysics Data System (ADS)

Korobov, Alexander I.; Izosimova, Maria Y.; Toschov, Sergey A.

2010-01-01

The technique and results of synthesis of ultrasound focusing discrete arrays for air-coupled ultrasound generation are presented. One of the arrays is an antenna 22 cm in diameter. It consists of 60 transmitters of Murata Company. The resonant frequency of each transmitter is 40 kHz, diameter is 16 mm. The transmitters were placed in first four Fresnel zones. Each of the zones was emitting with anti-phases. Position data and pressure field in focus were calculated using Rayleigh integral. Parameters of made array were measured using method of air-coupled vibrometry with laser scanning vibrometer. Measured parameters (operating frequency is 40 ± 1 kHz, focal distance is 308 mm, size of focal spot is 16.3 mm, and pressure in focus is about 150 dB) are in good agreement with calculated data. The examples of use of designed arrays for noncontact non-destructive diagnostics of some structural materials are reported. Work supported by RFBR.

Combinational light emitting diode-high frequency focused ultrasound treatment for HeLa cell.

PubMed

Choe, Se-Woon; Park, Kitae; Park, Chulwoo; Ryu, Jaemyung; Choi, Hojong

2017-12-01

Light sources such as laser and light emitting diode or ultrasound devices have been widely used for cancer therapy and regenerative medicines, since they are more cost-effective and less harmful than radiation therapy, chemotherapy or magnetic treatment. Compared to laser and low intensity ultrasound techniques, light emitting diode and high frequency focused ultrasound shows enhanced therapeutic effects, especially for small tumors. We propose combinational light emitting diode-high frequency focused ultrasound treatment for human cervical cancer HeLa cells. Individual red, green, and blue light emitting diode light only, high frequency focused ultrasound only, or light emitting diode light combined with high frequency focused ultrasound treatments were applied in order to characterize the responses of HeLa cells. Cell density exposed by blue light emitting diode light combined with high frequency focused ultrasound (2.19 ± 0.58%) was much lower than that of cells exposed by red and green light emitting diode lights (81.71 ± 9.92% and 61.81 ± 4.09%), blue light emitting diode light (11.19 ± 2.51%) or high frequency focused ultrasound only (9.72 ± 1.04%). We believe that the proposed combinational blue light emitting diode-high frequency focused ultrasound treatment could have therapeutic benefits to alleviate cancer cell proliferation.

[Focused ultrasound therapy: current status and potential applications in neurosurgery].

PubMed

Dervishi, E; Aubry, J-F; Delattre, J-Y; Boch, A-L

2013-12-01

High Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At the focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. In fact, this approach has been tested in a number of clinical studies for the treatment of several tumors, primarily the prostate, uterine, breast, bone, liver, kidney and pancreas. For transcranial brain therapy, the skull bone is a major limitation, however, new adaptive techniques of phase correction for focusing ultrasound through the skull have recently been implemented by research systems, paving the way for HIFU therapy to become an interesting alternative to brain surgery and radiotherapy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Numerical simulations of clinical focused ultrasound functional neurosurgery

NASA Astrophysics Data System (ADS)

Pulkkinen, Aki; Werner, Beat; Martin, Ernst; Hynynen, Kullervo

2014-04-01

A computational model utilizing grid and finite difference methods were developed to simulate focused ultrasound functional neurosurgery interventions. The model couples the propagation of ultrasound in fluids (soft tissues) and solids (skull) with acoustic and visco-elastic wave equations. The computational model was applied to simulate clinical focused ultrasound functional neurosurgery treatments performed in patients suffering from therapy resistant chronic neuropathic pain. Datasets of five patients were used to derive the treatment geometry. Eight sonications performed in the treatments were then simulated with the developed model. Computations were performed by driving the simulated phased array ultrasound transducer with the acoustic parameters used in the treatments. Resulting focal temperatures and size of the thermal foci were compared quantitatively, in addition to qualitative inspection of the simulated pressure and temperature fields. This study found that the computational model and the simulation parameters predicted an average of 24 ± 13% lower focal temperature elevations than observed in the treatments. The size of the simulated thermal focus was found to be 40 ± 13% smaller in the anterior-posterior direction and 22 ± 14% smaller in the inferior-superior direction than in the treatments. The location of the simulated thermal focus was off from the prescribed target by 0.3 ± 0.1 mm, while the peak focal temperature elevation observed in the measurements was off by 1.6 ± 0.6 mm. Although the results of the simulations suggest that there could be some inaccuracies in either the tissue parameters used, or in the simulation methods, the simulations were able to predict the focal spot locations and temperature elevations adequately for initial treatment planning performed to assess, for example, the feasibility of sonication. The accuracy of the simulations could be improved if more precise ultrasound tissue properties (especially of the

A cMUT probe for ultrasound-guided focused ultrasound targeted therapy.

PubMed

Gross, Dominique; Coutier, Caroline; Legros, Mathieu; Bouakaz, Ayache; Certon, Dominique

2015-06-01

Ultrasound-mediated targeted therapy represents a promising strategy in the arsenal of modern therapy. Capacitive micromachined ultrasonic transducer (cMUT) technology could overcome some difficulties encountered by traditional piezoelectric transducers. In this study, we report on the design, fabrication, and characterization of an ultrasound-guided focused ultrasound (USgFUS) cMUT probe dedicated to preclinical evaluation of targeted therapy (hyperthermia, thermosensitive liposomes activation, and sonoporation) at low frequency (1 MHz) with simultaneous ultrasonic imaging and guidance (15 to 20 MHz). The probe embeds two types of cMUT arrays to perform the modalities of targeted therapy and imaging respectively. The wafer-bonding process flow employed for the manufacturing of the cMUTs is reported. One of its main features is the possibility of implementing two different gap heights on the same wafer. All the design and characterization steps of the devices are described and discussed, starting from the array design up to the first in vitro measurements: optical (microscopy) and electrical (impedance) measurements, arrays' electroacoustic responses, focused pressure field mapping (maximum peak-to-peak pressure = 2.5 MPa), and the first B-scan image of a wire-target phantom.

WE-G-12A-01: High Intensity Focused Ultrasound Surgery and Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farahani, K; O'Neill, B

More and more emphasis is being made on alternatives to invasive surgery and the use of ionizing radiation to treat various diseases including cancer. Novel screening, diagnosis, treatment and monitoring of response to treatment are also hot areas of research and new clinical technologies. Ultrasound(US) has gained traction in all of the aforementioned areas of focus. Especially with recent advances in the use of ultrasound to noninvasively treat various diseases/organ systems. This session will focus on covering MR-guided focused ultrasound and the state of the art clinical applications, and the second speaker will survey the more cutting edge technologies e.g.more » Focused Ultrasound (FUS) mediated drug delivery, principles of cavitation and US guided FUS. Learning Objectives: Fundamental physics and physical limitations of US interaction with tissue and nanoparticles The alteration of tissue transport using focused ultrasound US control of nanoparticle drug carriers for targeted release The basic principles of MRI-guided focused ultrasound (MRgFUS) surgery and therapy the current state of the art clinical applications of MRgFUS requirements for quality assurance and treatment planning.« less

High-Intensity Focused Ultrasound Therapy: an Overview for Radiologists

PubMed Central

Kim, Young-sun; Choi, Min Joo; Lim, Hyo Keun; Choi, Dongil

2008-01-01

High-intensity focused ultrasound therapy is a novel, emerging, therapeutic modality that uses ultrasound waves, propagated through tissue media, as carriers of energy. This completely non-invasive technology has great potential for tumor ablation as well as hemostasis, thrombolysis and targeted drug/gene delivery. However, the application of this technology still has many drawbacks. It is expected that current obstacles to implementation will be resolved in the near future. In this review, we provide an overview of high-intensity focused ultrasound therapy from the basic physics to recent clinical studies with an interventional radiologist's perspective for the purpose of improving the general understanding of this cutting-edge technology as well as speculating on future developments. PMID:18682666

Nonlinear absorption in biological tissue for high intensity focused ultrasound.

PubMed

Liu, Xiaozhou; Li, Junlun; Gong, Xiufen; Zhang, Dong

2006-12-22

In recent years the propagation of the high intensity focused ultrasound (HIFU) in biological tissue is an interesting area due to its potential applications in non-invasive treatment of disease. The base principle of these applications is the heat effect generated by ultrasound absorption. In order to control therapeutic efficiency, it is important to evaluate the heat generation in biological tissue irradiated by ultrasound. In his paper, based on the Khokhlov-Zabolotkaya-Kuznetsov (KZK) equation in frequency-domain, the numerical simulations of nonlinear absorption in biological tissues for high intensity focused ultrasound are performed. We find that ultrasound thermal transfer effect will be enhanced with the increasing of initial acoustic intensity due to the high harmonic generation. The concept of extra absorption factor is introduced to describe nonlinear absorption in biological tissue for HIFU. The theoretical results show that the heat deposition induced by the nonlinear theory can be nearly two times as large as that predicated by linear theory. Then, the influence of the diffraction effect on the position of the focus in HIFU is investigated. It is shown that the sound focus moves toward the transducer compared with the geometry focus because of the diffraction of the sound wave. The position of the maximum heat deposition is shifted to the geometry focus with the increase of initial acoustic intensity because the high harmonics are less diffraction. Finally, the temperature in the porcine fat tissue changing with the time is predicated by Pennes' equation and the experimental results verify the nonlinear theoretical prediction.

Externally Delivered Focused Ultrasound for Renal Denervation.

PubMed

Neuzil, Petr; Ormiston, John; Brinton, Todd J; Starek, Zdenek; Esler, Murray; Dawood, Omar; Anderson, Thomas L; Gertner, Michael; Whitbourne, Rob; Schmieder, Roland E

2016-06-27

The aim of this study was to assess clinical safety and efficacy outcomes of renal denervation executed by an externally delivered, completely noninvasive focused therapeutic ultrasound device. Renal denervation has emerged as a potential treatment approach for resistant hypertension. Sixty-nine subjects received renal denervation with externally delivered focused ultrasound via the Kona Medical Surround Sound System. This approach was investigated across 3 consecutive studies to optimize targeting, tracking, and dosing. In the third study, treatments were performed in a completely noninvasive way using duplex ultrasound image guidance to target the therapy. Short- and long-term safety and efficacy were evaluated through use of clinical assessments, magnetic resonance imaging scans prior to and 3 and 24 weeks after renal denervation, and, in cases in which a targeting catheter was used to facilitate targeting, fluoroscopic angiography with contrast. All patients tolerated renal denervation using externally delivered focused ultrasound. Office blood pressure (BP) decreased by 24.6 ± 27.6/9.0 ± 15.0 mm Hg (from baseline BP of 180.0 ± 18.5/97.7 ± 13.7 mm Hg) in 69 patients after 6 months and 23.8 ± 24.1/10.3 ± 13.1 mm Hg in 64 patients with complete 1-year follow-up. The response rate (BP decrease >10 mm Hg) was 75% after 6 months and 77% after 1 year. The most common adverse event was post-treatment back pain, which was reported in 32 of 69 patients and resolved within 72 h in most cases. No intervention-related adverse events involving motor or sensory deficits were reported. Renal function was not altered, and vascular safety was established by magnetic resonance imaging (all patients), fluoroscopic angiography (n = 48), and optical coherence tomography (n = 5). Using externally delivered focused ultrasound and noninvasive duplex ultrasound, image-guided targeting was associated with substantial BP reduction without any major safety signals. Further

Portable ultrasound in disaster triage: a focused review.

PubMed

Wydo, S M; Seamon, M J; Melanson, S W; Thomas, P; Bahner, D P; Stawicki, S P

2016-04-01

Ultrasound technology has become ubiquitous in modern medicine. Its applications span the assessment of life-threatening trauma or hemodynamic conditions, to elective procedures such as image-guided peripheral nerve blocks. Sonographers have utilized ultrasound techniques in the pre-hospital setting, emergency departments, operating rooms, intensive care units, outpatient clinics, as well as during mass casualty and disaster management. Currently available ultrasound devices are more affordable, portable, and feature user-friendly interfaces, making them well suited for use in the demanding situation of a mass casualty incident (MCI) or disaster triage. We have reviewed the existing literature regarding the application of sonology in MCI and disaster scenarios, focusing on the most promising and practical ultrasound-based paradigms applicable in these settings.

High Intensity Focused Ultrasound (HIFU) Based Thrombolysis Using Multiple Frequency Excitations

NASA Astrophysics Data System (ADS)

Suo, Dingjie

High intensity focused ultrasound (HIFU) based thrombolysis has emerged as a promising drug-free approach for ischemic stroke treatment. The large amount of acoustic power required by this approach, however, poses a critical challenge to the future clinical translation because of the potential thermal damages. In this dissertation, multi-frequency acoustic waves at MHz range (near 1.5 MHz) were first introduced as HIFU excitations to reduce the required treatment power as well as the treatment time. It was found that dual-frequency thrombolysis efficiency was statistically better than that of single-frequency, under the same acoustic power and excitation condition. Microbubbles (MBs) combined with dual-frequency focused ultrasound (DFFU) for thrombolysis in vitro was then proposed to further reduce the power required. MBs are widely used in therapeutic ultrasound thrombolysis due to the nonlinear characteristics of their harmonic responses, coalescence and cavitation effects, which could further enhance efficiency. It was shown in this study that MBs, with sufficient concentration, could significantly lower the power threshold for thrombolysis for both DFFU and single-frequency focused ultrasound (SFFU). MBs mediated DFFU thrombolysis were then studied with a flow system that mimicked the blood flow in the artery of the brain. It was found that the cavitation threshold of a DFFU excitation yielded a lower level than that of a SFFU excitation. All the experimental results indicated that multi-frequency ultrasound could improve the thrombolysis efficiency. However, this was not well established numerically. Hence, a numerical investigation on the inertial cavitation threshold of MBs under multifrequency ultrasound irradiation was then investigated to confirm the benefit of using multi-frequency ultrasound for various applications. The main contribution and findings of this dissertation are as follows: 1) For the HIFU along study, when varying the acoustic power while

Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability.

PubMed

Mooney, Skyler J; Shah, Kairavi; Yeung, Sharon; Burgess, Alison; Aubert, Isabelle; Hynynen, Kullervo

2016-01-01

Transcranial focused ultrasound technology used to transiently open the blood-brain barrier, is capable of stimulating hippocampal neurogenesis; however, it is not yet known what aspects of the treatment are necessary for enhanced neurogenesis to occur. The present study set out to determine whether the opening of blood-brain barrier, the specific pressure amplitudes of focused ultrasound, and/or the intravenous administration of microbubbles (phospholipid microspheres) are necessary for the enhancement of neurogenesis. Specifically, mice were exposed to burst (10ms, 1Hz burst repetition frequency) focused ultrasound at the frequency of 1.68MHz and with 0.39, 0.78, 1.56 and 3.0MPa pressure amplitudes. These treatments were also conducted with or without microbubbles, at 0.39 + 0.78MPa or 1.56 + 3.0MPa, respectively. Only focused ultrasound at the ~0.78 MPa pressure amplitude with microbubbles promoted hippocampal neurogenesis and was associated with an increase in blood-brain barrier permeability. These results suggest that focused ultrasound -mediated neurogenesis is dependent upon the opening of the blood-brain barrier.

High Intensity Focused Ultrasound Monitoring using Harmonic Motion Imaging for Focused Ultrasound (HMIFU) under boiling or slow denaturation conditions

PubMed Central

Hou, Gary Y.; Marquet, Fabrice; Wang, Shutao; Apostolakis, Iason-Zacharias; Konofagou, Elisa E.

2015-01-01

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a recently developed High-Intensity Focused Ultrasound (HIFU) treatment monitoring method that utilizes an amplitude-modulated therapeutic ultrasound beam to induce an oscillatory radiation force at the HIFU focus and estimates the focal tissue displacement to monitor the HIFU thermal treatment. In this study, the performance of HMIFU under acoustic, thermal and mechanical effects were investigated. The performance of HMIFU was assessed in ex vivo canine liver specimens (n=13) under slow denaturation or boiling regimes. Passive Cavitation Detector (PCD) was used to assess the acoustic cavitation activity while a bare-wire thermocouple was used to monitor the focal temperature change. During lesioning with slow denaturation, high quality displacements (correlation coefficient above 0.97) were observed under minimum cavitation noise, indicating tissue the initial-softening-then-stiffening property change. During HIFU with boiling, HMIFU monitored a consistent change in lesion-to-background displacement contrast (0.46±0.37) despite the presence of strong cavitation noise due to boiling during lesion formation. Therefore, HMIFU effectively monitored softening-then-stiffening during lesioning under slow denaturation, and detected lesioning under boiling with a distinct change in displacement contrast under boiling in the presence of cavitation. In conclusion, HMIFU was shown effective in HIFU monitoring and lesioning identification without being significantly affected by cavitation noise. PMID:26168177

Feasibility of a focused ultrasound training programme for medical undergraduate students.

PubMed

Wong, Ivan; Jayatilleke, Thilina; Kendall, Richard; Atkinson, Paul

2011-03-01

Although ultrasound is a core skill for many clinical specialties, UK medical schools are not currently required to teach this skill. The College of Emergency Medicine (CEM) has championed the use of ultrasound to answer focused clinical questions in emergency settings. We have designed and piloted an ultrasound training course for undergraduate medical students addressing one important indication: ultrasound assessment of the abdominal aorta. Fourteen clinical students, who had no prior experience of using ultrasound, received focused ultrasound training in the form of didactic instruction, a short bedside practical workshop and self-directed learning over a 20-day period. At the end of this period, the students were assessed by a structured viva and an observed structured clinical examination (OSCE) used for accreditation by the CEM. The primary endpoint was the number of students who passed the assessment. The secondary endpoint was the accuracy of the students' anatomical measurements. Thirteen of the 14 (93%) students completed the training and assessment. Eight of the 13 (62%) students passed both the viva and OSCE, and were deemed to have achieved the CEM standard. The measurements by the competent students were not statistically different from those of experienced practitioners. We have shown for the first time that it is feasible to train inexperienced undergraduate students to scan the abdominal aorta to a professional standard using a focused training course. It is time for the medical education community to address whether focused ultrasound training should accompany traditional clinical skills, such as using a stethoscope, in UK medical school curricula. © Blackwell Publishing Ltd 2011.

High intensity focused ultrasound (HIFU).

PubMed

Barkin, Jack

2011-04-01

Curative treatments for localized prostate cancer, from least invasive to most invasive, include brachytherapy, cryosurgery, three-dimensional conformal radiation therapy, external beam radiation therapy, and radical prostatectomy. A patient with localized, low risk or intermediate risk prostate cancer who is diagnosed at an early age and receives one of these treatments has only an approximately 50% chance of maintaining an undetectable prostate-specific antigen (PSA) level, good spontaneous erections, and total continence by 5 years after treatment. This article discusses transrectal high intensity focused ultrasound (HIFU) treatment of localized prostate cancer using the Sonablate 500 (Focus Surgery, Indianapolis, IN, USA) device, which the author has adopted in favor of the Ablatherm (EDAP, TMS S. A., Lyons, France) device, the other HIFU device approved for use in Canada. Characteristics of the ideal prostate cancer include stage T1-T2b, less than 40 cc in size, and with an anterior-posterior dimension of up to 35 mm high. The anterior zone of the prostate is treated before the posterior zone. The procedure involves 2 to 3 second bursts of ultrasound energy, followed by 3 second cooling cycles. In each treatment lesion, the physician achieves a temperature of 100 C at the focal point. The device allows for real-time visualization of tissue response following the delivery of ultrasound energy. HIFU is a minimally invasive, outpatient treatment for localized prostate cancer that provides similar short term and medium term cure rates and considerably less morbidity and side effects than other treatments. Although the effectiveness of HIFU has not yet been demonstrated in large, long term studies, this treatment option should be discussed with patients who have just been diagnosed with low risk or intermediate risk prostate cancer and desire aggressive, noninvasive, curative therapy, with potentially a lower incidence of side effects compared to conventional

Low-intensity focused ultrasound mediated localized drug delivery for liver tumors in rabbits.

PubMed

Gong, Yuping; Wang, Zhigang; Dong, Guifang; Sun, Yang; Wang, Xi; Rong, Yue; Li, Maoping; Wang, Dong; Ran, Haitao

2016-09-01

To explore the antitumor effects of low-intensity focused ultrasound (LIFU) mediated localized drug delivery of adriamycin-microbubble-PLGA nanoparticle complexes on rabbits VX2 liver tumor. ADM-NMCs were prepared by covalent linking of ADM-PLGA nanoparticles (ADM-NPs) to the shell of the microbubbles. A fixed water bag filled with microbubbles was subjected to LIFU and non-focused ultrasound respectively, and the ultrasound images of which were recorded before and after ultrasonication. A total of 54 VX2 liver tumor-burdened rabbits were divided into six groups randomly, including control, ADM-NPs combined with LIFU, microbubbles combined with LIFU, ADM-NPs and microbubbles combined with LIFU, ADM-NMCs combined with LIFU and ADM-NMCs combined with Non-FUS. The tumor volume and volume inhibition rate (VIR) of tumor progression were calculated and compared. Apoptotic cells were labeled by terminal deoxyuridine nick end. Proliferating cell nuclear antigen was detected by immunohistochemistry. The median survival time of the animals were recorded and compared. ADM-NMCs were successfully prepared with an average diameter of 1721 nm. The highest VIR and apoptotic index (AI) were found in the group of ADM-NMCs combined with LIFU while the lowest proliferating index (PI) was simultaneously observed in this group. The median survival time of the rabbits in the ADM-NMCs combined with LIFU group was the longest (71days) among all groups. ADM-NMCs combined with LIFU could inhibit the rabbits VX2 liver tumor progress by delaying the tumor proliferation and accelerating apoptosis, which presents a novel process for liver tumor targeting chemotherapy.

Manipulation of Microbubble Clusters Using Focused Ultrasound

NASA Astrophysics Data System (ADS)

Matsuzaki, Hironobu; Osaki, Taichi; Kawaguchi, Kei; Unga, Johan; Ichiyanagi, Mitsuhisa; Azuma, Takashi; Suzuki, Ryo; Maruyama, Kazuo; Takagi, Shu

2017-11-01

In recent years, microbubbles (MBs) are expected to be utilized for the ultrasound drug delivery system (DDS). For the MB-DDS, it is important to establish a method of controlling bubbles and bubble clusters using ultrasound field. The objective of this study is to clarify behaviors of bubble clusters with various physical conditions. MBs in the ultrasound field are subjected to the primary Bjerknes force. The force traps MBs at the focal region of the focused ultrasound field. The trapped MBs form a bubble cluster at the region. A bubble cluster continues growing with absorbing surrounding bubbles until it reaches a maximum size beyond which it disappears from the focal region. In the present study, two kinds of MBs are used for the experiment. One is Sonazoid with average diameter of 2.6 um and resonant frequency of 5 MHz. The other is developed by Teikyo Univ., with average diameter of 1.5 um and presumed resonant frequency of 4 MHz. The bubble cluster's behaviors are analyzed using the high-speed camera. Sonazoid clusters have larger critical size than the other in every frequency, and its cluster size is inversely proportional to the ultrasound frequency, while Teikyo-bubble clusters have different tendency. These results are discussed in the presentation.

Improved heating efficiency with High-Intensity Focused Ultrasound using a new ultrasound source excitation.

PubMed

Bigelow, Timothy A

2009-01-01

High-Intensity Focused Ultrasound (HIFU) is quickly becoming one of the best methods to thermally ablate tissue noninvasively. Unlike RF or Laser ablation, the tissue can be destroyed without inserting any probes into the body minimizing the risk of secondary complications such as infections. In this study, the heating efficiency of HIFU sources is improved by altering the excitation of the ultrasound source to take advantage of nonlinear propagation. For ultrasound, the phase velocity of the ultrasound wave depends on the amplitude of the wave resulting in the generation of higher harmonics. These higher harmonics are more efficiently converted into heat in the body due to the frequency dependence of the ultrasound absorption in tissue. In our study, the generation of the higher harmonics by nonlinear propagation is enhanced by transmitting an ultrasound wave with both the fundamental and a higher harmonic component included. Computer simulations demonstrated up to a 300% increase in temperature increase compared to transmitting at only the fundamental for the same acoustic power transmitted by the source.

Numerical Study on Focusing of Ultrasounds in Microbubble-enhanced HIFU

NASA Astrophysics Data System (ADS)

Matsumoto, Yoichiro; Okita, Kohei; Takagi, Shu

2011-11-01

The injection of microbubbles into the target tissue enhances tissue heating in High-Intensity Focused Ultrasound therapy, via inertial cavitation. The control of the inertial cavitation is required to achieve the efficient tissue ablation. Microbubbles between a transducer and a target disturb the ultrasound propagation depending on the conditions. A method to clear such microbubbles has been proposed by Kajiyama et al. [Physics Procedia 3 (2010) 305-314]. In the method, the irradiation of intense ultrasounds with a burst waveform fragmentize microbubbles in the pathways before the irradiation of ultrasounds for tissue heating. The vitro experiment using a gel containing microbubbles has showed that the method enables to heat the target correctly by controlling the microbubble distribution. Following the experiment, we simulate the focusing of ultrasounds through a mixture containing microbubbles with considering the size and number density distributions in space. The numerical simulation shows that the movement of the heating region from the transducer side to the target by controlling the microbubble distributions. The numerical results elucidate well the experimental ones.

Non-thermal High-intensity Focused Ultrasound for Breast Cancer Therapy

DTIC Science & Technology

2012-07-01

AD ________________ Award Number: W81XWH-11-1-0341 TITLE: Non-thermal high-intensity focused ultrasound for breast cancer therapy PRINCIPAL...30 Jun 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Non-thermal high-intensity focused ultrasound for breast cancer therapy 5b. GRANT NUMBER W81XWH...the in vivo animal experiments. However, the tasks planned for the animal studies were not completed due to the delayed approval of the animal

Particle Accelerator Focus Automation

NASA Astrophysics Data System (ADS)

Lopes, José; Rocha, Jorge; Redondo, Luís; Cruz, João

2017-08-01

The Laboratório de Aceleradores e Tecnologias de Radiação (LATR) at the Campus Tecnológico e Nuclear, of Instituto Superior Técnico (IST) has a horizontal electrostatic particle accelerator based on the Van de Graaff machine which is used for research in the area of material characterization. This machine produces alfa (He+) and proton (H+) beams of some μA currents up to 2 MeV/q energies. Beam focusing is obtained using a cylindrical lens of the Einzel type, assembled near the high voltage terminal. This paper describes the developed system that automatically focuses the ion beam, using a personal computer running the LabVIEW software, a multifunction input/output board and signal conditioning circuits. The focusing procedure consists of a scanning method to find the lens bias voltage which maximizes the beam current measured on a beam stopper target, which is used as feedback for the scanning cycle. This system, as part of a wider start up and shut down automation system built for this particle accelerator, brings great advantages to the operation of the accelerator by turning it faster and easier to operate, requiring less human presence, and adding the possibility of total remote control in safe conditions.

Tissue ablation accelerated by peripheral scanning mode with high-intensity focused ultrasound: a study on isolated porcine liver perfusion.

PubMed

Bu, Rui; Yin, Li; Yang, Han; Wang, Qi; Wu, Feng; Zou, Jian Zhong

2013-08-01

The aims of this study were to investigate the feasibility of accelerated tissue ablation using a peripheral scanning mode with high-intensity focused ultrasound (HIFU) and to explore the effect of flow rate on total energy consumption of the target tissues. Using a model of isolated porcine liver perfusion via the portal vein and hepatic artery, we conducted a scanning protocol along the periphery of the target tissues using linear-scanned HIFU to carefully adjust the varying focal depth, generator power, scanning velocity and line-by-line interval over the entire ablation range. Porcine livers were divided into four ablation groups: group 1, n = 12, with dual-vessel perfusion; group 2, n = 11, with portal vein perfusion alone; group 3, n = 10, with hepatic artery perfusion alone; and group 4, n = 11, control group with no-flow perfusion. The samples were cut open consecutively at a thickness of 3 mm, and the actual ablation ranges were calculated along the periphery of the target tissues after triphenyl tetrazolium chloride staining. Total energy consumption was calculated as the sum of the energy requirements at various focal depths in each group. On the basis of the pre-supposed scanning protocol, the peripheral region of the target tissue formed a complete coagulation necrosis barrier in each group with varying dose combinations, and the volume of the peripheral necrotic area did not differ significantly among the four groups (p > 0.05). Furthermore, total energy consumption in each group significantly decreased with the corresponding decrease in flow rate (p < 0.01). This study revealed that the complete peripheral necrosis barrier within the target tissues can defined using linear-scanned HIFU in an isolated porcine liver perfusion model. Additionally, the flow rate in the major hepatic vessels may play an important role in the use of the peripheral ablation mode, and this novel mode of ablation may enhance the therapeutic efficacy and tolerability of the

Neurosurgical Applications of High-Intensity Focused Ultrasound with Magnetic Resonance Thermometry.

PubMed

Colen, Rivka R; Sahnoune, Iman; Weinberg, Jeffrey S

2017-10-01

Magnetic resonance guided focused ultrasound surgery (MRgFUS) has potential noninvasive effects on targeted tissue. MRgFUS integrates MRI and focused ultrasound surgery (FUS) into a single platform. MRI enables visualization of the target tissue and monitors ultrasound-induced effects in near real-time during FUS treatment. MRgFUS may serve as an adjunct or replace invasive surgery and radiotherapy for specific conditions. Its thermal effects ablate tumors in locations involved in movement disorders and essential tremors. Its nonthermal effects increase blood-brain barrier permeability to enhance delivery of therapeutics and other molecules. Copyright © 2017 Elsevier Inc. All rights reserved.

Acoustic Droplet Vaporization for Enhancement of Thermal Ablation by High Intensity Focused Ultrasound

PubMed Central

Zhang, Man; Fabiilli, Mario L.; Haworth, Kevin J.; Padilla, Frederic; Swanson, Scott D.; Kripfgans, Oliver D.; Carson, Paul L.; Fowlkes, J. Brian

2011-01-01

Rationale and Objectives Acoustic droplet vaporization (ADV) shows promise for spatial control and acceleration of thermal lesion production. Our hypothesis was that microbubbles generated by ADV could enhance high intensity focused ultrasound (HIFU) thermal ablation by controlling and increasing local energy absorption. Materials and Methods Thermal lesions were produced in tissue-mimicking phantoms using focused ultrasound (1.44 MHz) with a focal intensity of 4000 W·cm-2 in degassed water at 37°C. The average lesion volume was measured by visible change in optical opacity and by T2-weighted MRI. In addition, in vivo HIFU lesions were generated in a canine liver before and after an intravenous injection of droplets with a similar acoustic setup. Results Thermal lesions were seven-fold larger in phantoms containing droplets (3×105 droplets/mL) compared to phantoms without droplets. The mean lesion volume with a 2 s HIFU exposure in droplet-containing phantoms was comparable to that made by a 5 s exposure in phantoms without droplets. In the in vivo study, the average lesion volumes without and with droplets were 0.017 ± 0.006 cm3 (n = 4, 5 s exposure) and 0.265 ± 0.005 cm3 (n = 3, 5 s exposure), respectively – a factor of 15 difference. The shape of ADV bubbles imaged with B-mode ultrasound was very similar to the actual lesion shape as measured optically and by MRI. Conclusion ADV bubbles may facilitate clinical HIFU ablation by reducing treatment time or requisite in situ total acoustic power, and provide ultrasonic imaging feedback of the thermal therapy. PMID:21703883

Impact of Focused Ultrasound-enhanced Drug Delivery on Survival in Rats with Glioma

NASA Astrophysics Data System (ADS)

Treat, Lisa Hsu; Zhang, Yongzhi; McDannold, Nathan; Hynynen, Kullervo

2009-04-01

Malignancies of the brain remain difficult to treat with chemotherapy because the selective permeability of the blood-brain barrier (BBB) blocks many potent agents from reaching their target. Previous studies have illustrated the feasibility of drug and antibody delivery across the BBB using MRI-guided focused ultrasound. In this study, we investigated the impact of focused ultrasound-enhanced delivery of doxorubicin on survival in rats with aggressive glioma. Sprague-Dawley rats were implanted with 9 L gliosarcoma cells in the brain. Eight days after implantation, each rat received one of the following: (1) no treatment (control), (2) a single treatment with microbubble-enhanced MRI-guided focused ultrasound (FUS only), (3) a single treatment with i.v. liposomal doxorubicin (DOX only), or (4) a single treatment with microbubble-enhanced MRI-guided focused ultrasound and concurrent i.v. injections of liposomal doxorubicin (FUS+DOX). The survival time from implantation to death or euthanasia was recorded. We observed a modest but significant increase in median survival time in rats treated with combined MRI-guided focused ultrasound chemotherapy, compared to chemotherapy alone (p<0.001). There was no significant improvement in survival between those who received stand-alone chemotherapy and those who did not receive any treatment (p>0.10). Our study demonstrates for the first time a therapeutic benefit achieved with ultrasound-enhanced drug delivery across the blood-brain barrier. This confirmation of efficacy in an in vivo tumor model indicates that targeted drug delivery using MRI-guided focused ultrasound has the potential to have a major impact on the treatment of patients with brain tumors and other neurological disorders.

Clinical Application of High-intensity Focused Ultrasound in Cancer Therapy

PubMed Central

Hsiao, Yi-Hsuan; Kuo, Shou-Jen; Tsai, Horng-Der; Chou, Ming-Chih; Yeh, Guang-Perng

2016-01-01

The treatment of cancer is an important issue in both developing and developed countries. Clinical use of ultrasound in cancer is not only for the diagnosis but also for the treatment. Focused ultrasound surgery (FUS) is a noninvasive technique. By using the combination of high-intensity focused ultrasound (HIFU) and imaging method, FUS has the potential to ablate tumor lesions precisely. The main mechanisms of HIFU ablation involve mechanical and thermal effects. Recent advances in HIFU have increased its popularity. Some promising results were achieved in managing various malignancies, including pancreas, prostate, liver, kidney, breast and bone. Other applications include brain tumor ablation and disruption of the blood-brain barrier. We aim at briefly outlining the clinical utility of FUS as a noninvasive technique for a variety of types of cancer treatment. PMID:26918034

Focused ultrasound as a tool to input sensory information to humans (Review)

NASA Astrophysics Data System (ADS)

Gavrilov, L. R.; Tsirulnikov, E. M.

2012-01-01

This review is devoted to the analysis of studies and implementations related to the use of focused ultrasound for functional effects on neuroreceptor structures. Special attention was paid to the stimulation of neuroreceptor structures in order to input sensory information to humans. This branch of medical and physiological acoustics appeared in Russia in the early 1970s and was being efficiently developed up to the late 1980s. Then, due to lack of financial support, only individual researchers remained at this field and, as a result, we have no full- fledged theoretical research and practical implementations in this area yet. Many promising possibilities of using functional effects of focused ultrasound in medicine and physiology have remained unimplemented for a long time. However, new interesting ideas and approaches have appeared in recent years. Very recently, very questionable projects have been reported related to the use of ultrasound for targeted functional effects on the human brain performed in some laboratories. In this review, the stages of the development of scientific research devoted to the functional effects of focused ultrasound are described. By activating the neuroreceptor structures of the skin by means pulses of focused ultrasound, one can cause all the sensations perceived by human beings through the skin in everyday life, such as tactile sensations, thermal (heat and cold), tickling, itching, and various types of pain. Stimulation of the ear labyrinth of humans with normal hearing using amplitude-modulated ultrasound causes auditory sensations corresponding to an audio modulating signal (pure tones, music, speech, etc.). Activation of neuroreceptor structures by means of focused ultrasound is used for the diagnosis of various neurological and skin diseases, as well as hearing disorders. It has been shown that the activation is related to the mechanical action of ultrasound, for example, by the radiation force, as well as to the direct

MR techniques for guiding high-intensity focused ultrasound (HIFU) treatments.

PubMed

Kuroda, Kagayaki

2018-02-01

To make full use of the ability of magnetic resonance (MR) to guide high-intensity focused ultrasound (HIFU) treatment, effort has been made to improve techniques for thermometry, motion tracking, and sound beam visualization. For monitoring rapid temperature elevation with proton resonance frequency (PRF) shift, data acquisition and processing can be accelerated with parallel imaging and/or sparse sampling in conjunction with appropriate signal processing methods. Thermometry should be robust against tissue motion, motion-induced magnetic field variation, and susceptibility change. Thus, multibaseline, referenceless, or hybrid techniques have become important. In cases with adipose or bony tissues, for which PRF shift cannot be used, thermometry with relaxation times or signal intensity may be utilized. Motion tracking is crucial not only for thermometry but also for targeting the focus of an ultrasound in moving organs such as the liver, kidney, or heart. Various techniques for motion tracking, such as those based on an anatomical image atlas with optical-flow displacement detection, a navigator echo to seize the diaphragm position, and/or rapid imaging to track vessel positions, have been proposed. Techniques for avoiding the ribcage and near-field heating have also been examined. MR acoustic radiation force imaging (MR-ARFI) is an alternative to thermometry that can identify the location and shape of the focal spot and sound beam path. This technique could be useful for treating heterogeneous tissue regions or performing transcranial therapy. All of these developments, which will be discussed further in this review, expand the applicability of HIFU treatments to a variety of clinical targets while maintaining safety and precision. 2 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:316-331. © 2017 International Society for Magnetic Resonance in Medicine.

Focused ultrasound thermal therapy system with ultrasound image guidance and temperature measurement feedback.

PubMed

Lin, Kao-Han; Young, Sun-Yi; Hsu, Ming-Chuan; Chan, Hsu; Chen, Yung-Yaw; Lin, Win-Li

2008-01-01

In this study, we developed a focused ultrasound (FUS) thermal therapy system with ultrasound image guidance and thermocouple temperature measurement feedback. Hydraulic position devices and computer-controlled servo motors were used to move the FUS transducer to the desired location with the measurement of actual movement by linear scale. The entire system integrated automatic position devices, FUS transducer, power amplifier, ultrasound image system, and thermocouple temperature measurement into a graphical user interface. For the treatment procedure, a thermocouple was implanted into a targeted treatment region in a tissue-mimicking phantom under ultrasound image guidance, and then the acoustic interference pattern formed by image ultrasound beam and low-power FUS beam was employed as image guidance to move the FUS transducer to have its focal zone coincident with the thermocouple tip. The thermocouple temperature rise was used to determine the sonication duration for a suitable thermal lesion as a high power was turned on and ultrasound image was used to capture the thermal lesion formation. For a multiple lesion formation, the FUS transducer was moved under the acoustic interference guidance to a new location and then it sonicated with the same power level and duration. This system was evaluated and the results showed that it could perform two-dimensional motion control to do a two-dimensional thermal therapy with a small localization error 0.5 mm. Through the user interface, the FUS transducer could be moved to heat the target region with the guidance of ultrasound image and acoustic interference pattern. The preliminary phantom experimental results demonstrated that the system could achieve the desired treatment plan satisfactorily.

PRESAGE® as a new calibration method for high intensity focused ultrasound therapy

NASA Astrophysics Data System (ADS)

Costa, M.; McErlean, C.; Rivens, I.; Adamovics, J.; Leach, M. O.; ter Haar, G.; Doran, S. J.

2015-01-01

High Intensity Focused ultrasound (HIFU) is a non-invasive cancer therapy that makes use of the mainly thermal effects of ultrasound to destroy tissue. In order to achieve reliable treatment planning, it is necessary to characterise the ultrasound source (transducer) and to understand how the wave propagates in tissue and the energy deposition in the focal region. This novel exploratory study investigated how HIFU affects PRESAGE®, an optical phantom used for radiotherapy dosimetry, which is potentially a rapid method of calibrating the transducer. Samples, of two different formulations, were exposed to focused ultrasound and imaged using Optical Computed Tomography. First results showed that, PRESAGE® changes colour on ultrasound exposure (darker green regions were observed) with the alterations being related to the acoustic power and sample composition. Future work will involve quantification of these alterations and understanding how to relate them to the mechanisms of action of HIFU.

A numerical study on the oblique focus in MR-guided transcranial focused ultrasound

NASA Astrophysics Data System (ADS)

Hughes, Alec; Huang, Yuexi; Pulkkinen, Aki; Schwartz, Michael L.; Lozano, Andres M.; Hynynen, Kullervo

2016-11-01

Recent clinical data showing thermal lesions from treatments of essential tremor using MR-guided transcranial focused ultrasound shows that in many cases the focus is oblique to the main axis of the phased array. The potential for this obliquity to extend the focus into lateral regions of the brain has led to speculation as to the cause of the oblique focus, and whether it is possible to realign the focus. Numerical simulations were performed on clinical export data to analyze the causes of the oblique focus and determine methods for its correction. It was found that the focal obliquity could be replicated with the numerical simulations to within 23.2+/- {{13.6}\\circ} of the clinical cases. It was then found that a major cause of the focal obliquity was the presence of sidelobes, caused by an unequal deposition of power from the different transducer elements in the array at the focus. In addition, it was found that a 65% reduction in focal obliquity was possible using phase and amplitude corrections. Potential drawbacks include the higher levels of skull heating required when modifying the distribution of power among the transducer elements, and the difficulty at present in obtaining ideal phase corrections from CT information alone. These techniques for the reduction of focal obliquity can be applied to other applications of transcranial focused ultrasound involving lower total energy deposition, such as blood-brain barrier opening, where the issue of skull heating is minimal.

Focused ultrasound: concept for automated transcutaneous control of hemorrhage in austere settings.

PubMed

Kucewicz, John C; Bailey, Michael R; Kaczkowski, Peter J; Carter, Stephen J

2009-04-01

High intensity focused ultrasound (HIFU) is being developed for a range of clinical applications. Of particular interest to NASA and the military is the use of HIFU for traumatic injuries because HIFU has the unique ability to transcutaneously stop bleeding. Automation of this technology would make possible its use in remote, austere settings by personnel not specialized in medical ultrasound. Here a system to automatically detect and target bleeding is tested and reported. The system uses Doppler ultrasound images from a clinical ultrasound scanner for bleeding detection and hardware for HIFU therapy. The system was tested using a moving string to simulate blood flow and targeting was visualized by Schlieren imaging to show the focusing of the HIFU acoustic waves. When instructed by the operator, a Doppler ultrasound image is acquired and processed to detect and localize the moving string, and the focus of the HIFU array is electronically adjusted to target the string. Precise and accurate targeting was verified in the Schlieren images. An automated system to detect and target simulated bleeding has been built and tested. The system could be combined with existing algorithms to detect, target, and treat clinical bleeding.

High-intensity focused ultrasound ablation for treatment of hepatocellular carcinoma and hypersplenism: preliminary study.

PubMed

Zhu, Jing; Zhu, Hui; Mei, Zhechuan; Jin, Chengbing; Ran, Lifeng; Zhou, Kun; Yang, Wei; Zhang, Lian; She, Chaokun

2013-10-01

The purpose of this work was to preliminarily investigate the efficacy and safety of high-intensity focused ultrasound treatment of hepatocellular carcinoma and hypersplenism. Nine patients with hepatocellular carcinoma complicated by hypersplenism (5 male and 4 female; median age, 56 years; range, 51-66 years) were treated with ultrasound-guided high-intensity focused ultrasound. Complications were recorded. Laboratory examination and magnetic resonance imaging were used to evaluate the efficacy. After high-intensity focused ultrasound treatment, mean spleen ablation ± SD of 28.76% ± 6.1% was discovered; meanwhile, the white blood cell count, platelet count, and liver function of the patients were substantially improved during the follow-up period. In addition, symptoms such as epistaxis and gingival bleeding were ameliorated or even eliminated, and the quality of life was improved. Follow-up imaging showed a nonperfused volume in the spleen and an absence of a tumor blood supply at the treated lesions in the liver. For the first time to our knowledge, high-intensity focused ultrasound ablation was used to treat hepatocellular carcinoma complicated by hypersplenism. High-intensity focused ultrasound may be an effective and safe alternative for treatment of hepatocellular carcinoma complicated by hypersplenism, but further studies are necessary to clarify the mechanisms.

Intensity dependence of focused ultrasound lesion position

NASA Astrophysics Data System (ADS)

Meaney, Paul M.; Cahill, Mark D.; ter Haar, Gail R.

1998-04-01

Knowledge of the spatial distribution of intensity loss from an ultrasonic beam is critical to predicting lesion formation in focused ultrasound surgery. To date most models have used linear propagation models to predict the intensity profiles needed to compute the temporally varying temperature distributions. These can be used to compute thermal dose contours that can in turn be used to predict the extent of thermal damage. However, these simulations fail to adequately describe the abnormal lesion formation behavior observed for in vitro experiments in cases where the transducer drive levels are varied over a wide range. For these experiments, the extent of thermal damage has been observed to move significantly closer to the transducer with increasing transducer drive levels than would be predicted using linear propagation models. The simulations described herein, utilize the KZK (Khokhlov-Zabolotskaya-Kuznetsov) nonlinear propagation model with the parabolic approximation for highly focused ultrasound waves, to demonstrate that the positions of the peak intensity and the lesion do indeed move closer to the transducer. This illustrates that for accurate modeling of heating during FUS, nonlinear effects must be considered.

Distribution of temperature elevation caused by moving high-intensity focused ultrasound transducer

NASA Astrophysics Data System (ADS)

Kim, Jungsoon; Jung, Jihee; Kim, Moojoon; Ha, Kanglyeol; Lee, Eunghwa; Lee, Ilkwon

2015-07-01

Ultrasonic thermal treatment for dermatology has been developed using a small high-intensity focused ultrasound (HIFU) transducer. The transducer moves horizontally at a constant while it emits focused ultrasound because the treatment needs a high-temperature area in skin tissue over a wide range of depths. In this paper, a tissue-mimicking phantom made of carrageenan and a thermochromic film were adopted to examine the temperature distribution in the phantom noninvasively when the focused ultrasound was irradiated from the moving transducer. The dependence of the high-temperature area on the irradiated acoustic energy and on the movement interval of the HIFU was analyzed experimentally. The results will be useful in ensuring safety and estimating the remedial value of the treatment.

A Novel Approach to Regeneration of Bone: Using Focused Ultrasound for the Spatiotemporal Patterning of Angiogenic and Osteogenic Factors

DTIC Science & Technology

2012-04-01

approach uses high intensity focused ultrasound ( HIFU ) and heat shock/ligand-dependent gene switches. Focused ultrasound generates localized...vasculature and bone. The approach uses high intensity focused ultrasound ( HIFU ) and heat shock/ligand-dependent gene switches. Focused ultrasound ...regeneration. Biomedical applications of high intensity focused ultrasound ( HIFU ) have revolved primarily around the mechanical and thermal ablation of

MRI-guided focused ultrasound surgery in musculoskeletal diseases: the hot topics

PubMed Central

Napoli, Alessandro; Sacconi, Beatrice; Battista, Giuseppe; Guglielmi, Giuseppe; Catalano, Carlo; Albisinni, Ugo

2016-01-01

MRI-guided focused ultrasound surgery (MRgFUS) is a minimally invasive treatment guided by the most sophisticated imaging tool available in today's clinical practice. Both the imaging and therapeutic sides of the equipment are based on non-ionizing energy. This technique is a very promising option as potential treatment for several pathologies, including musculoskeletal (MSK) disorders. Apart from clinical applications, MRgFUS technology is the result of long, heavy and cumulative efforts exploring the effects of ultrasound on biological tissues and function, the generation of focused ultrasound and treatment monitoring by MRI. The aim of this article is to give an updated overview on a “new” interventional technique and on its applications for MSK and allied sciences. PMID:26607640

Factors affecting tumor ablation during high intensity focused ultrasound treatment.

PubMed

Hassanuddin, Aizan; Choi, Jun-Ho; Seo, Dong-Wan; Ryu, Choong Heon; Kim, Su-Hui; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

2014-07-01

High intensity focused ultrasound (HIFU) utilizes a targeted extracorporeal focused ultrasound beam to ablate neoplastic pancreatic tissue. We used an in vitro model to examine the effects of bone, metallic stents, plastic stents, metal plates, and cyst-like lesions on HIFU treatment. HIFU was delivered to the phantom models implanted with foreign bodies, and the location, shape, and size of the ablated zones were evaluated. Bone and metallic plates reflected the ultrasound beam, shifting the ablation zone from the focal zone to the prefocal area. In the phantoms containing metal stent, plastic stent, and cyst, most of the ablative energy was reflected to the prefocal area by the surface, with the remainder penetrating through the phantom. The area of the ablated margins was significantly larger in size and volume than the intended focal ablation zone. During HIFU therapy, artificial or anatomical barriers could affect the direction of the ultrasound beams, shifting the ablation zone from the focal area to a prefocal site with a larger than expected ablation zone. These factors should be considered prior to HIFU treatment for pancreatic tumors because they could limit ablation success, in addition to causing complications.

Non-Thermal High-Intensity Focused Ultrasound for Breast Cancer Therapy

DTIC Science & Technology

2013-07-01

ultrasound for breast cancer therapy PRINCIPAL INVESTIGATOR: Chang Ming (Charlie) Ma, Ph.D...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Non-thermal high-intensity focused ultrasound for breast cancer therapy 5b. GRANT NUMBER W81XWH-11-1-0341...treatment systems for small animal models. Advanced imaging systems will be required to determine the gross tumor volume, to plan the HIFU treatment, to

Focused ultrasound and microbubbles for enhanced extravasation.

PubMed

Böhmer, M R; Chlon, C H T; Raju, B I; Chin, C T; Shevchenko, T; Klibanov, A L

2010-11-20

The permeability of blood vessels for albumin can be altered by using ultrasound and polymer or lipid-shelled microbubbles. The region in which the microbubbles were destroyed with focused ultrasound was quantified in gel phantoms as a function of pressure, number of cycles and type of microbubble. At 2MPa the destruction took place in a fairly wide area for a lipid-shelled agent, while for polymer-shelled agents at this setting, distinct destruction spots with a radius of only 1mm were obtained. When microbubbles with a thicker shell were used, the pressure above which the bubbles were destroyed shifts to higher values. In vivo both lipid and polymer microbubbles increased the extravasation of the albumin binding dye Evans Blue, especially in muscle leading to about 6-8% of the injected dose to extravasate per gram muscle tissue 30 min after start of the treatment, while no Evans Blue could be detected in muscle in the absence of microbubbles. Variation in the time between ultrasound treatment and Evans Blue injection, demonstrated that the time window for promoting extravasation is at least an hour at the settings used. In MC38 tumors, extravasation already occurred without ultrasound and only a trend towards enhancement with about a factor of 2 could be established with a maximum percentage injected dose per gram of 3%. Ultrasound mediated microbubble destruction especially enhances the extravasation in the highly vascularized outer part of the MC38 tumor and adjacent muscle and would, therefore, be most useful for release of, for instance, anti-angiogenic drugs. Copyright © 2010 Elsevier B.V. All rights reserved.

Optimizing sonication protocols for transthoracic focused ultrasound surgery

NASA Astrophysics Data System (ADS)

Gao, J.; Volovick, A.; Cao, R.; Nabi, G.; Cochran, S.; Melzer, A.; Huang, Z.

2012-11-01

During transthoracic focused ultrasound surgery (TFUS), the intervening ribs absorb and reflect the majority of the ultrasound energy excited by an acoustic source, resulting in pain, bone injuries and insufficient energy delivered to the target organs of liver, kidney, and pancreas. Localized hot spots may also exist at the interfaces between the ribs and soft tissue and in the highly absorptive regions such as the skin and connective tissue. The aims of this study were to clarify the effects of focal beam distortion and frequency-dependent rib heating in TFUS and to propose possible techniques to reduce the side-effects of rib heating and increase ultrasound efficacy. Frequency-dependent heating at the target and the ribs were estimated using finite element analysis (PZFlex, Weidlinger Associates Inc, USA) along with experimental verification on a range of different phantoms. The ratio of ultrasonic power density at the target and the ribs, the time-varying spatial distribution of temperature, and the ablated focus of each sonication were taken as key indicators to determine the optimal operating frequency. Comparison with a patient specific model was also made. TFUS seems to be useful to treat tumours that are small and near the surface of the abdominal organs. For targets deep inside these organs, severe attenuation of energy occurs, suggesting that purely ultrasound thermal ablation with advanced heating patterns will have limited effects in improving the treatment efficacy. Results demonstrate that the optimal ultrasound frequency is around 0.8 MHz for the configurations considered, but this may shift to higher frequencies with changes in the axial and lateral positions of the tumours relative to the ribs. To date, we have elucidated the most important effects and correlated these with idealised anatomical geometry. The changes in frequency and other techniques such as selection of excited element patterns in FUS arrays had some effect. However, more advanced

Sonochemiluminescence observation of lipid- and polymer-shelled ultrasound contrast agents in 1.2 MHz focused ultrasound field.

PubMed

Qiao, Yangzi; Cao, Hua; Zhang, Shusheng; Yin, Hui; Wan, Mingxi

2013-01-01

Ultrasound contrast agents (UCAs) are frequently added into the focused ultrasound field as cavitation nuclei to enhance the therapeutic efficiency. Since their presence will distort the pressure field and make the process unpredictable, comprehension of their behaviors especially the active zone spatial distribution is an important part of better monitoring and using of UCAs. As shell materials can strongly alter the acoustic behavior of UCAs, two different shells coated UCAs, lipid-shelled and polymer-shelled UCAs, in a 1.2 MHz focused ultrasound field were studied by the Sonochemiluminescence (SCL) method and compared. The SCL spatial distribution of lipid-shelled group differed from that of polymer-shelled group. The shell material and the character of focused ultrasound field work together to the SCL distribution, causing the lipid-shelled group to have a maximum SCL intensity in pre-focal region at lower input power than that of polymer-shelled group, and a brighter SCL intensity in post-focal region at high input power. The SCL inactive area of these two groups both increased with the input power. The general behavior of the UCAs can be studied by both the average SCL intensity and the backscatter signals. As polymer-shelled UCAs are more resistant to acoustic pressure, they had a higher destruction power and showed less reactivation than lipid-shelled ones. Copyright © 2012 Elsevier B.V. All rights reserved.

Time-dependent change of blood flow in the prostate treated with high-intensity focused ultrasound.

PubMed

Shoji, Sunao; Tonooka, Akiko; Hashimoto, Akio; Nakamoto, Masahiko; Tomonaga, Tetsuro; Nakano, Mayura; Sato, Haruhiro; Terachi, Toshiro; Koike, Junki; Uchida, Toyoaki

2014-09-01

Avascular areas on contrast-enhanced magnetic resonance imaging have been considered to be areas of localized prostate cancer successfully treated by high-intensity focused ultrasound. However, the optimal timing of magnetic resonance imaging has not been discussed. The thermal effect of high-intensity focused ultrasound is degraded by regional prostatic blood flow. Conversely, the mechanical effect of high-intensity focused ultrasound (cavitation) is not affected by blood flow, and can induce vessel damage. In this series, the longitudinal change of blood flow on contrast-enhanced magnetic resonance imaging was observed from postoperative day 1 to postoperative day 14 in 10 patients treated with high-intensity focused ultrasound. The median rates of increase in the non-enhanced volume of the whole gland, transition zone and peripheral zone from postoperative day 1 to postoperative day 14 were 36%, 39%, and 34%, respectively. In another pathological analysis of the prostate tissue of 17 patients immediately after high-intensity focused ultrasound without neoadjuvant hormonal therapy, we observed diffuse coagulative degeneration and partial non-coagulative prostate tissue around arteries with vascular endothelial cell detachment. These observations on contrast-enhanced magnetic resonance imaging support a time-dependent change of the blood flow in the prostate treated with high-intensity focused ultrasound. Additionally, our pathological findings support the longitudinal changes of these magnetic resonance imaging findings. Further large-scale studies will investigate the most appropriate timing of contrast-enhanced magnetic resonance imaging for evaluation of the effectiveness of high-intensity focused ultrasound for localized prostate cancer. © 2014 The Japanese Urological Association.

Review of MRI positioning devices for guiding focused ultrasound systems.

PubMed

Yiallouras, C; Damianou, C

2015-06-01

This article contains a review of positioning devices that are currently used in the area of magnetic resonance imaging (MRI) guided focused ultrasound surgery (MRgFUS). The paper includes an extensive review of literature published since the first prototype system was invented in 1991. The technology has grown into a fast developing area with application to any organ accessible to ultrasound. The initial design operated using hydraulic principles, while the latest technology incorporates piezoelectric motors. Although, in the beginning there were fears regarding MRI safety, during recent years, the deployment of MR-safe positioning devices in FUS has become routine. Many of these positioning devices are now undergoing testing in clinical trials. Existing MRgFUS systems have been utilized mostly in oncology (fibroids, brain, liver, kidney, bone, pancreas, eye, thyroid, and prostate). It is anticipated that, in the near future, there will be a positioning device for every organ that is accessible by focused ultrasound. Copyright © 2014 John Wiley & Sons, Ltd.

Hot topics in biomedical ultrasound: ultrasound therapy and its integration with ultrasonic imaging

NASA Astrophysics Data System (ADS)

Everbach, E. Carr

2005-09-01

Since the development of biomedical ultrasound imaging from sonar after WWII, there has been a clear divide between ultrasonic imaging and ultrasound therapy. While imaging techniques are designed to cause as little change as possible in the tissues through which ultrasound propagates, ultrasound therapy typically relies upon heating or acoustic cavitation to produce a desirable therapeutic effect. Concerns over the increasingly high acoustic outputs of diagnostic ultrasound scanners prompted the adoption of the Mechanical Index (MI) and Thermal Index (TI) in the early 1990s. Therapeutic applications of ultrasound, meanwhile, have evolved from deep tissue heating in sports medicine to include targeted drug delivery, tumor and plaque ablation, cauterization via high intensity focused ultrasound (HIFU), and accelerated dissolution of blood clots. The integration of ultrasonic imaging and therapy in one device is just beginning, but the promise of improved patient outcomes is balanced by regulatory and practical impediments.

MR-guided focused ultrasound: a potentially disruptive technology.

PubMed

Bradley, William G

2009-07-01

A disruptive technology is a technological innovation that overturns the existing dominant technologies in a market. Magnetic resonance (MR)-guided focused ultrasound (MRgFUS) is a noninvasive procedure based on the combination of real-time MR anatomic guidance, MR thermometry, and high-intensity focused ultrasound. Several hundred transducer elements become convergent at a point under MR guidance, leading to heating and coagulation necrosis. Outside the focal point, there is no significant heating. There is no need to break the skin for procedures in the body or to perform a craniotomy for procedures in the brain. This lack of invasiveness is what makes MRgFUS so disruptive compared with surgery. At present, MRgFUS has been used for the ablation of uterine fibroids, breast tumors, painful bony metastases, and liver tumors. In the brain, it has been used for the ablation of glioblastomas and for functional neurosurgery. Phantom and animal studies suggest future applications for prostate cancer and acute stroke treatment.

MR-guided focused ultrasound robot for performing experiments on large animals

NASA Astrophysics Data System (ADS)

Mylonas, N.; Damianou, C.

2011-09-01

Introduction: In this paper an experimental MRI-guided focused ultrasound robot for large animals is presented. Materials and methods: A single element spherically focused transducer of 4 cm diameter, focusing at 10 cm and operating at 1 MHz was used. A positioning device was developed in order to scan the ultrasound transducer for performing MR-guided focused ultrasound experiments in large animals such as pig, sheep and dog. The positioning device incorporates only MRI compatible materials such as piezoelectric motors, Acrylonitrile Butadiene Styrene (ABS) plastic, brass screws, and brass pulleys. The system is manufactured automatically using a rapid prototyping system. Results: The system was tested successfully in a number of animals for various tasks (creation of single lesions, creation of overlapping lesions, and MR compatibility). Conclusions: A simple, cost effective, portable positioning device has been developed which can be used in virtually any clinical MRI scanner since it can be sited on the scanner's table. The propagation of HIFU can be via a lateral or superior-inferior approach. This system has the potential to be marketed as a cost effective solution for performing experiments in small and large animals.

A long arm for ultrasound: a combined robotic focused ultrasound setup for magnetic resonance-guided focused ultrasound surgery.

PubMed

Krafft, Axel J; Jenne, Jürgen W; Maier, Florian; Stafford, R Jason; Huber, Peter E; Semmler, Wolfhard; Bock, Michael

2010-05-01

Focused ultrasound surgery (FUS) is a highly precise noninvasive procedure to ablate pathogenic tissue. FUS therapy is often combined with magnetic resonance (MR) imaging as MR imaging offers excellent target identification and allows for continuous monitoring of FUS induced temperature changes. As the dimensions of the ultrasound (US) focus are typically much smaller than the targeted volume, multiple sonications and focus repositioning are interleaved to scan the focus over the target volume. Focal scanning can be achieved electronically by using phased-array US transducers or mechanically by using dedicated mechanical actuators. In this study, the authors propose and evaluate the precision of a combined robotic FUS setup to overcome some of the limitations of the existing MRgFUS systems. Such systems are typically integrated into the patient table of the MR scanner and thus only provide an application of the US wave within a limited spatial range from below the patient. The fully MR-compatible robotic assistance system InnoMotion (InnoMedic GmbH, Herxheim, Germany) was originally designed for MR-guided interventions with needles. It offers five pneumatically driven degrees of freedom and can be moved over a wide range within the bore of the magnet. In this work, the robotic system was combined with a fixed-focus US transducer (frequency: 1.7 MHz; focal length: 68 mm, and numerical aperture: 0.44) that was integrated into a dedicated, in-house developed treatment unit for FUS application. A series of MR-guided focal scanning procedures was performed in a polyacrylamide-egg white gel phantom to assess the positioning accuracy of the combined FUS setup. In animal experiments with a 3-month-old domestic pig, the system's potential and suitability for MRgFUS was tested. In phantom experiments, a total targeting precision of about 3 mm was found, which is comparable to that of the existing MRgFUS systems. Focus positioning could be performed within a few seconds

Combined Ultrasound and MR Imaging to Guide Focused Ultrasound Therapies in the Brain

PubMed Central

Arvanitis, Costas D.; Livingstone, Margaret S.; McDannold, Nathan

2013-01-01

Purpose Several emerging therapies with potential for use in the brain harness effects produced by acoustic cavitation – the interaction between ultrasound and microbubbles either generated during sonication or introduced into the vasculature. Systems developed for transcranial MRI-guided focused ultrasound (MRgFUS) thermal ablation can enable their clinical translation, but methods for real-time monitoring and control are currently lacking. Acoustic emissions produced during sonication can provide information about the location, strength, and type of the microbubble oscillations within the ultrasound field, and they can be mapped in real-time using passive imaging approaches. Here, we tested whether such mapping can be achieved transcranially within a clinical brain MRgFUS system. Materials and Methods We integrated an ultrasound imaging array into the hemisphere transducer of the MRgFUS device. Passive cavitation maps were obtained during sonications combined with a circulating microbubble agent at 20 targets in the cingulate cortex in three macaques. The maps were compared with MRI-evident tissue effects. Results The system successfully mapped microbubble activity during both stable and inertial cavitation, which was correlated with MRI-evident transient blood-brain barrier disruption and vascular damage, respectively. The location of this activity was coincident with the resulting tissue changes within the expected resolution limits of the system. Conclusion While preliminary, these data clearly demonstrate, for the first time, that is possible to construct maps of stable and inertial cavitation transcranially, in a large animal model, and under clinically relevant conditions. Further, these results suggest that this hybrid ultrasound/MRI approach can provide comprehensive guidance for targeted drug delivery via blood-brain barrier disruption and other emerging ultrasound treatments, facilitating their clinical translation. We anticipate it will also prove to

Combined ultrasound and MR imaging to guide focused ultrasound therapies in the brain

NASA Astrophysics Data System (ADS)

Arvanitis, Costas D.; Livingstone, Margaret S.; McDannold, Nathan

2013-07-01

Several emerging therapies with potential for use in the brain, harness effects produced by acoustic cavitation—the interaction between ultrasound and microbubbles either generated during sonication or introduced into the vasculature. Systems developed for transcranial MRI-guided focused ultrasound (MRgFUS) thermal ablation can enable their clinical translation, but methods for real-time monitoring and control are currently lacking. Acoustic emissions produced during sonication can provide information about the location, strength and type of the microbubble oscillations within the ultrasound field, and they can be mapped in real-time using passive imaging approaches. Here, we tested whether such mapping can be achieved transcranially within a clinical brain MRgFUS system. We integrated an ultrasound imaging array into the hemisphere transducer of the MRgFUS device. Passive cavitation maps were obtained during sonications combined with a circulating microbubble agent at 20 targets in the cingulate cortex in three macaques. The maps were compared with MRI-evident tissue effects. The system successfully mapped microbubble activity during both stable and inertial cavitation, which was correlated with MRI-evident transient blood-brain barrier disruption and vascular damage, respectively. The location of this activity was coincident with the resulting tissue changes within the expected resolution limits of the system. While preliminary, these data clearly demonstrate, for the first time, that it is possible to construct maps of stable and inertial cavitation transcranially, in a large animal model, and under clinically relevant conditions. Further, these results suggest that this hybrid ultrasound/MRI approach can provide comprehensive guidance for targeted drug delivery via blood-brain barrier disruption and other emerging ultrasound treatments, facilitating their clinical translation. We anticipate that it will also prove to be an important research tool that will

Pubic Bone Osteomyelitis after Salvage High-Intensity Focused Ultrasound for Prostate Cancer

PubMed Central

Robison, Christopher M.; Gor, Ronak A.; Metro, Michael J.

2014-01-01

High-intensity focused ultrasound can be used for the primary treatment of prostate cancer and biochemical recurrence after radical prostatectomy or radiation. Complications of high-intensity focused ultrasound include urinary retention, urethral stenosis, stress incontinence, urinary tract infections, dysuria, impotence, and rarely, rectourethral or rectovesicular fistula. We describe a patient presenting with urinary retention, urinary tract infections and intermittent stress incontinence, later found to be associated with pubic bone osteomyelitis stemming from a prostatopubic fistula. PMID:24917777

High Intensity Focused Ultrasound Tumor Therapy System and Its Application

NASA Astrophysics Data System (ADS)

Sun, Fucheng; He, Ye; Li, Rui

2007-05-01

At the end of last century, a High Intensity Focused Ultrasound (HIFU) tumor therapy system was successfully developed and manufactured in China, which has been already applied to clinical therapy. This article aims to discuss the HIFU therapy system and its application. Detailed research includes the following: power amplifiers for high-power ultrasound, ultrasound transducers with large apertures, accurate 3-D mechanical drives, a software control system (both high-voltage control and low-voltage control), and the B-mode ultrasonic diagnostic equipment used for treatment monitoring. Research on the dosage of ultrasound required for tumour therapy in multiple human cases has made it possible to relate a dosage formula, presented in this paper, to other significant parameters such as the volume of thermal tumor solidification, the acoustic intensity (I), and the ultrasound emission time (tn). Moreover, the HIFU therapy system can be applied to the clinical treatment of both benign and malignant tumors in the pelvic and abdominal cavity, such as uterine fibroids, liver cancer and pancreatic carcinoma.

Gaussian representation of high-intensity focused ultrasound beams.

PubMed

Soneson, Joshua E; Myers, Matthew R

2007-11-01

A method for fast numerical simulation of high-intensity focused ultrasound beams is derived. The method is based on the frequency-domain representation of the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation, and assumes for each harmonic a Gaussian transverse pressure distribution at all distances from the transducer face. The beamwidths of the harmonics are constrained to vary inversely with the square root of the harmonic number, and as such this method may be viewed as an extension of a quasilinear approximation. The technique is capable of determining pressure or intensity fields of moderately nonlinear high-intensity focused ultrasound beams in water or biological tissue, usually requiring less than a minute of computer time on a modern workstation. Moreover, this method is particularly well suited to high-gain simulations since, unlike traditional finite-difference methods, it is not subject to resolution limitations in the transverse direction. Results are shown to be in reasonable agreement with numerical solutions of the full KZK equation in both tissue and water for moderately nonlinear beams.

Microlens array for focusing airborne ultrasound using heated wire grid

NASA Astrophysics Data System (ADS)

Cai, Liang-Wu; Sánchez-Dehesa, José

2007-10-01

This letter reports on the focusing of airborne ultrasound by a simple grid of heated wires. The focusing is analogous to that of an array of optical microlenses. The focusing pattern is determined by the spacing between wires, and the focusing areas are tightly confined with a great "depth of field." Such acoustical microlens arrays have great potentials for shaping beams produced by ultrasonic transducers, in applications such as ultrasonic cleaning and nondestructive testing.

Interaction of high intensity focused ultrasound with biological materials

NASA Technical Reports Server (NTRS)

Bar-Cohen, Y.; Mal, A.; Feng, F.; Kabo, M.; Wang, J.

2002-01-01

This work is motivated by the possible medical application of focused ultrasound in minimally invasive treatment of a variety of disorders including those associated with soft tissue or disk element disruption in the vicinity of the spine causing impingement on the spinal cord.

Feasibility of MRI-guided Focused Ultrasound as Organ-Sparing Treatment for Testicular Cancer

NASA Astrophysics Data System (ADS)

Staruch, Robert; Curiel, Laura; Chopra, Rajiv; Hynynen, Kullervo

2009-04-01

High cure rates for testicular cancer have prompted interest in organ-sparing surgery for patients with bilateral disease or single testis. Focused ultrasound (FUS) ablation could offer a noninvasive approach to organ-sparing surgery. The objective of this study was to determine the feasibility of using MR thermometry to guide organ-sparing focused ultrasound surgery in the testis. The testes of anesthetized rabbits were sonicated in several discrete locations using a single-element focused transducer operating at 2.787MHz. Focal heating was visualized with MR thermometry, using a measured PRF thermal coefficient of -0.0089±0.0003 ppm/° C. Sonications at 3.5-14 acoustic watts applied for 30 seconds produced maximum temperature elevations of 10-80° C, with coagulation verified by histology. Coagulation of precise volumes in the testicle is feasible with MRI-guided focused ultrasound. Variability in peak temperature for given sonication parameters suggests the need for online temperature feedback control.

Microbubble mediated dual-frequency high intensity focused ultrasound thrombolysis: An In vitro study

NASA Astrophysics Data System (ADS)

Suo, Dingjie; Jin, Zhiyang; Jiang, Xiaoning; Dayton, Paul A.; Jing, Yun

2017-01-01

High intensity focused ultrasound (HIFU) has recently emerged as a promising alternative approach for thrombolysis. However, the high acoustic energy required by HIFU could elicit thermal damage bioeffects, impeding the clinical translation of this technique. This paper investigates the use of dual-frequency focused ultrasound (DFFU) mediated by microbubbles (MBs) to minimize the acoustic power required for thrombolysis in vitro. It was found that MBs, with sufficient concentration, could significantly lower the power threshold for thrombolysis for both DFFU and single-frequency focused ultrasound (SFFU). In addition, SFFU needs about 96%-156% higher energy to achieve the same thrombolysis efficiency as that of DFFU. The thrombolysis efficiency is also found to increase with the duty cycle. The measured cavitation signals reveal that the enhanced inertial cavitation is likely responsible for the improved thrombolysis under DFFU and MBs.

Magnetic resonance guided high-intensity focused ultrasound ablation of musculoskeletal tumors

PubMed Central

Avedian, Raffi S.; Gold, Garry; Ghanouni, Pejman; Pauly, Kim Butts

2015-01-01

This article reviews the fundamental principles and clinical experimental uses of magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) ablation of musculoskeletal tumors. MRgHIFU is a noninvasive treatment modality that takes advantage of the ability of magnetic resonance to measure tissue temperature and uses this technology to guide high-intensity focused ultrasound waves to a specific focus within the human body that results in heat generation and complete thermal necrosis of the targeted tissue. Adjacent normal tissues are spared because of the accurate delivery of thermal energy, as well as, local blood perfusion that provides a cooling effect. MRgHIFU is approved by the Food and Drug Administration for the treatment of uterine fibroids and is used on an experimental basis to treat breast, prostate, liver, bone, and brain tumors. PMID:26120376

Using Power Ultrasound to Accelerate Food Freezing Processes: Effects on Freezing Efficiency and Food Microstructure.

PubMed

Zhang, Peizhi; Zhu, Zhiwei; Sun, Da-Wen

2018-05-31

Freezing is an effective way of food preservation. However, traditional freezing methods have the disadvantages of low freezing efficiency and generation of large ice crystals, leading to possible damage of food quality. Power ultrasound assisted freezing as a novel technique can effectively reduce the adverse effects during freezing process. This paper gives an overview on recent researches of power ultrasound technique to accelerate the food freezing processes and illustrates the main principles of power ultrasound assisted freezing. The effects of power ultrasound on liquid food, model solid food as well as fruit and vegetables are discussed, respectively, from the aspects of increasing freezing rate and improving microstructure. It is shown that ultrasound assisted freezing can effectively improve the freezing efficiency and promote the formation of small and evenly distributed ice crystals, resulting in better food quality. Different inherent properties of food samples affect the effectiveness of ultrasound application and optimum ultrasound parameters depend on the nature of the samples. The application of ultrasound to the food industry is more likely on certain types of food products and more efforts are still needed to realize the industrial translation of laboratory results.

Thrombolysis using multi-frequency high intensity focused ultrasound at MHz range: an in vitro study

NASA Astrophysics Data System (ADS)

Suo, Dingjie; Guo, Sijia; Lin, Weili; Jiang, Xiaoning; Jing, Yun

2015-09-01

High intensity focused ultrasound (HIFU) based thrombolysis has emerged as a promising drug-free treatment approach for ischemic stroke. The large amount of acoustic power required by this approach, however, poses a critical challenge to the future clinical translation. In this study, multi-frequency acoustic waves at MHz range (near 1.5 MHz) were introduced as HIFU excitations to reduce the required power for treatment as well as the treatment time. In vitro bovine blood clots weighing around 150 mg were treated by single-frequency and multi-frequency HIFU. The pulse length was 2 ms for all experiments except the ones where the duty cycle was changed. It was found that dual-frequency thrombolysis efficiency was statistically better than single-frequency under the same acoustic power and excitation condition. When varying the acoustic power but fixing the duty cycle at 5%, it was found that dual-frequency ultrasound can save almost 30% power in order to achieve the same thrombolysis efficiency. In the experiment where the duty cycle was increased from 0.5% to 10%, it was shown that dual-frequency ultrasound can achieve the same thrombolysis efficiency with only half of the duty cycle of single-frequency. Dual-frequency ultrasound could also accelerate the thrombolysis by a factor of 2-4 as demonstrated in this study. No significant differences were found between dual-frequencies with different frequency differences (0.025, 0.05, and 0.1 MHz) and between dual-frequency and triple-frequency. The measured cavitation doses of dual-frequency and triple-frequency excitations were at about the same level but both were significantly higher than that of single-frequency.

Focused Ultrasound Surgery in Oncology: Overview and Principles

PubMed Central

McDannold, Nathan J.; Hynynen, Kullervo; Jolesz, Ferenc A.

2011-01-01

Focused ultrasound surgery (FUS) is a noninvasive image-guided therapy and an alternative to surgical interventions. It presents an opportunity to revolutionize cancer therapy and to affect or change drug delivery of therapeutic agents in new focally targeted ways. In this article the background, principles, technical devices, and clinical cancer applications of image-guided FUS are reviewed. © RSNA, 2011 PMID:21436096

Standardized Six-Step Approach to the Performance of the Focused Basic Obstetric Ultrasound Examination.

PubMed

Abuhamad, Alfred; Zhao, Yili; Abuhamad, Sharon; Sinkovskaya, Elena; Rao, Rashmi; Kanaan, Camille; Platt, Lawrence

2016-01-01

This study aims to validate the feasibility and accuracy of a new standardized six-step approach to the performance of the focused basic obstetric ultrasound examination, and compare the new approach to the regular approach performed in the scheduled obstetric ultrasound examination. A new standardized six-step approach to the performance of the focused basic obstetric ultrasound examination, to evaluate fetal presentation, fetal cardiac activity, presence of multiple pregnancy, placental localization, amniotic fluid volume evaluation, and biometric measurements, was prospectively performed on 100 pregnant women between 18(+0) and 27(+6) weeks of gestation and another 100 pregnant women between 28(+0) and 36(+6) weeks of gestation. The agreement of findings for each of the six steps of the standardized six-step approach was evaluated against the regular approach. In all ultrasound examinations performed, substantial to perfect agreement (Kappa value between 0.64 and 1.00) was observed between the new standardized six-step approach and the regular approach. The new standardized six-step approach to the focused basic obstetric ultrasound examination can be performed successfully and accurately between 18(+0) and 36(+6) weeks of gestation. This standardized approach can be of significant benefit to limited resource settings and in point of care obstetric ultrasound applications. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Thrombus resolution and hemodynamic recovery using ultrasound-accelerated thrombolysis in acute pulmonary embolism.

PubMed

Kennedy, Robert J; Kenney, Hai H; Dunfee, Brian L

2013-06-01

To evaluate retrospectively the safety profile and clinical success of ultrasound-accelerated thrombolysis for acute pulmonary embolism (PE) with a standard lytic infusion protocol. A retrospective study was performed at a single center treating patients with acute PE between October 2009 and April 2012. On diagnosis of submassive or massive PE by pulmonary computed tomography angiography or ventilation/perfusion scan, all patients received anticoagulation and treatment using the EkoSonic endovascular system (EKOS Corporation, Bothell, Washington). The ultrasound-accelerated thrombolytic infusion catheters were placed into the affected pulmonary arteries to facilitate administration of recombinant tissue plasminogen activator at 0.5-1.0mg/h/catheter. Treatment of 60 patients (35 men, 25 women; age 61 y±16; 53 bilateral PE; 48 submassive PE) resulted in complete thrombus clearance (≥90%) in 57% and near-complete (50%-90%) clearance in 41% of patients after infusion of 35.1 mg±11.1 of recombinant tissue plasminogen activator over 19.6 hours±6.0. Measurements before and after treatment showed a decrease in pulmonary artery pressure (47 mm Hg±15 to 38 mm Hg±12 [systolic], P<.001) and Miller score (25±3 to 17±6, P<.001). There were 57 patients who survived to discharge. All three patients who died in the hospital presented with massive PE. On 90-day follow-up, 56 patients (93%) were alive. The current study demonstrates effectiveness and safety of ultrasound-accelerated thrombolysis in patients with acute PE with a large thrombus burden. Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.

Transcranial MR-Guided Focused Ultrasound: A Review of the Technology and Neuro Applications

PubMed Central

Ghanouni, Pejman; Pauly, Kim Butts; Elias, W. Jeff; Henderson, Jaimie; Sheehan, Jason; Monteith, Stephen; Wintermark, Max

2015-01-01

MR guided focused ultrasound is a new, minimally invasive method of targeted tissue thermal ablation that may be of use to treat central neuropathic pain, essential tremor, Parkinson tremor, and brain tumors. The system has also been used to temporarily disrupt the blood-brain barrier to allow targeted drug delivery to brain tumors. This article reviews the physical principles of MR guided focused ultrasound and discusses current and potential applications of this exciting technology. PMID:26102394

An Electro-Optic Spatial Light Modulator for Thermoelastic Generation of Programmably Focused Ultrasound.

DTIC Science & Technology

1984-12-01

The concept proposed is an electro - optic technique that would make it possible to spatially modulate a high power pulsed laser beam to thermoelastically induce focused ultrasound in a test material. Being a purely electro - optic device, the modulator, and therefore the depth at which the acoustic focus occurs, can be programmed electronically at electronic speeds. If successful, it would become possible to scan ultrasound continuously in three dimensions within the component or structure under test. (Author)

An electro-optic spatial light modulator for thermoelastic generation of programmably focused ultrasound

NASA Astrophysics Data System (ADS)

1984-12-01

The concept proposed is an electro-optic technique that would make it possible to spatially modulate a high power pulsed laser beam to thermoelastically induce focused ultrasound in a test material. Being a purely electro-optic device, the modulator, and therefore the depth at which the acoustic focus occurs, can be programmed electronically at electronic speeds. If successful, it would become possible to scan ultrasound continuously in three dimensions within the component or structure under test.

Pulsed-focusing recirculating linacs for muon acceleration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Rolland

2014-12-31

Since the muon has a short lifetime, fast acceleration is essential for high-energy applications such as muon colliders, Higgs factories, or neutrino factories. The best one can do is to make a linear accelerator with the highest possible accelerating gradient to make the accelerating time as short as possible. However, the cost of such a single linear accelerator is prohibitively large due to expensive power sources, cavities, tunnels, and related infrastructure. As was demonstrated in the Thomas Jefferson Accelerator Facility (Jefferson Lab) Continuous Electron Beam Accelerator Facility (CEBAF), an elegant solution to reduce cost is to use magnetic return arcsmore » to recirculate the beam through the accelerating RF cavities many times, where they gain energy on each pass. In such a Recirculating Linear Accelerator (RLA), the magnetic focusing strength diminishes as the beam energy increases in a conventional linac that has constant strength quadrupoles. After some number of passes the focusing strength is insufficient to keep the beam from going unstable and being lost. In this project, the use of fast pulsed quadrupoles in the linac sections was considered for stronger focusing as a function of time to allow more successive passes of a muon beam in a recirculating linear accelerator. In one simulation, it was shown that the number of passes could be increased from 8 to 12 using pulsed magnet designs that have been developed and tested. This could reduce the cost of linac sections of a muon RLA by 8/12, where more improvement is still possible. The expense of a greater number of passes and corresponding number of return arcs was also addressed in this project by exploring the use of ramped or FFAG-style magnets in the return arcs. A better solution, invented in this project, is to use combined-function dipole-quadrupole magnets to simultaneously transport two beams of different energies through one magnet string to reduce costs of return arcs by almost a

TU-B-210-00: MR-Guided Focused Ultrasound Therapy in Oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advancedmore » techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, “MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue”, will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, “MRI guided High Intensity Focused Ultrasound – Advanced Approaches for Ablation and Hyperthermia”, will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. Learning Objectives: Learn background on devices and techniques for MR guided HIFU for cancer therapy Understand issues and current status of clinical MRg HIFU Understand strategies for compensating for organ movement during MRgHIFU Understand strategies for strategies for delivering hyperthermia with MRgHIFU CM - research collaboration with Philips.« less

Vaginal Pessary for Uterine Repositioning During High-Intensity Focused Ultrasound Ablation of Uterine Leiomyomas

PubMed Central

Pulanic, Tajana Klepac; Venkatesan, Aradhana M.; Segars, James; Sokka, Sham; Wood, Bradford J.; Stratton, Pamela

2015-01-01

In order to ensure safe magnetic resonance-guided high-intensity focused ultrasound ablation of uterine leiomyomas, ultrasound beam path should be free of intervening scar and bowel. Pre-treatment magnetic resonance imaging of a 9cm long and 7.7cm wide leiomyomatous uterus in a 39-year-old woman with menorrhagia and abdominopelvic pain initially demonstrated a focused ultrasound treatment path without bowel between the uterus and abdominal wall. On the day of ablation, however, multiple loops of bowel were observed in the ultrasound beam path by magnetic resonance imaging. Uterine repositioning was accomplished with a 76 mm donut vaginal pessary which anteverted the fundus and successfully displaced bowel. A vaginal pessary may aid in repositioning an axial or retroverted uterus to enable ablation of uterine leiomyomas. PMID:26584482

Vaginal Pessary for Uterine Repositioning during High-Intensity Focused Ultrasound Ablation of Uterine Leiomyomas.

PubMed

Klepac Pulanic, Tajana; Venkatesan, Aradhana M; Segars, James; Sokka, Sham; Wood, Bradford J; Stratton, Pamela

2016-01-01

In order to ensure safe magnetic resonance-guided, high-intensity focused, ultrasound ablation of uterine leiomyomas, the ultrasound beam path should be free of intervening scar and bowel. Pre-treatment MRI of a 9-cm long and 7.7-cm wide leiomyomatous uterus in a 39-year-old woman with menorrhagia and abdominopelvic pain initially demonstrated a focused ultrasound treatment path without a bowel between the uterus and the abdominal wall. On the day of ablation, however, multiple loops of bowel were observed in the ultrasound beam path by MRI. Uterine repositioning was accomplished with a 76-mm donut vaginal pessary, which anteverted the fundus and successfully displaced the bowel. A vaginal pessary may aid in repositioning an axial or retroverted uterus to enable ablation of uterine leiomyomas. © 2015 S. Karger AG, Basel.

Driving Circuitry for Focused Ultrasound Noninvasive Surgery and Drug Delivery Applications

PubMed Central

El-Desouki, Munir M.; Hynynen, Kullervo

2011-01-01

Recent works on focused ultrasound (FUS) have shown great promise for cancer therapy. Researchers are continuously trying to improve system performance, which is resulting in an increased complexity that is more apparent when using multi-element phased array systems. This has led to significant efforts to reduce system size and cost by relying on system integration. Although ideas from other fields such as microwave antenna phased arrays can be adopted in FUS, the application requirements differ significantly since the frequency range used in FUS is much lower. In this paper, we review recent efforts to design efficient power monitoring, phase shifting and output driving techniques used specifically for high intensity focused ultrasound (HIFU). PMID:22346589

Driving circuitry for focused ultrasound noninvasive surgery and drug delivery applications.

PubMed

El-Desouki, Munir M; Hynynen, Kullervo

2011-01-01

Recent works on focused ultrasound (FUS) have shown great promise for cancer therapy. Researchers are continuously trying to improve system performance, which is resulting in an increased complexity that is more apparent when using multi-element phased array systems. This has led to significant efforts to reduce system size and cost by relying on system integration. Although ideas from other fields such as microwave antenna phased arrays can be adopted in FUS, the application requirements differ significantly since the frequency range used in FUS is much lower. In this paper, we review recent efforts to design efficient power monitoring, phase shifting and output driving techniques used specifically for high intensity focused ultrasound (HIFU).

FOCUS SPLITTING ASSOCIATED WITH PROPAGATION OF FOCUSED ULTRASOUND THROUGH THE RIB CAGE

PubMed Central

Khokhlova, V. A.; Bobkova, S. M.; Gavrilov, L. R.

2011-01-01

The effect of focus splitting after propagation of focused ultrasound through a rib cage is investigated theoretically. It is shown that the mechanism of this effect is caused by the interference of waves from two or more spatially separated sources, such as intercostal spaces. Analytical estimates of the parameters of splitting are obtained, i.e., the number of foci, their amplitudes, diameter, and the distance between them, depending on the transducer parameters, as well as the dimensions of the rib cage and position of ribs relative to the radiator. Various configurations of the relative positioning of ribs and radiator are considered; it is shown which of them are the most effective for real surgical operations. PMID:21607120

Magnetic Resonance-Guided High-Intensity Focused Ultrasound Ablation of Osteoid Osteoma: A Case Series Report.

PubMed

Rovella, Marcello S; Martins, Guilherme L P; Cavalcanti, Conrado F A; Bor-Seng-Shu, Edson; Camargo, Olavo P; Cerri, Giovanni G; Menezes, Marcos R

2016-04-01

Osteoid osteoma is painful benign tumor. The aim of this study was to report our initial experience using magnetic resonance-guided focused ultrasound to treat osteoid osteomas. This retrospective single-center study included four patients treated with magnetic resonance-guided focused ultrasound. They presented with severe pain with reduced quality of life and a poor response to clinical treatment. The pre- and post-treatment evaluation comprised computed tomography and magnetic resonance imaging and focused on quality of life and the impact of pain on daily activities. After treatment, three patients had complete pain resolution with no recurrence. One patient had a recurrence of symptoms after 2 wk and underwent a new successful treatment with increased energy levels. On average, 13 sonications were administered (8-18 sonications/treatment) with an average energy of 2,003 J (range: 1,063-3,522 J). Magnetic resonance-guided focused ultrasound appears to be a feasible, tolerable and effective treatment in selected patients with osteoid osteomas. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

MRI monitoring of focused ultrasound sonications near metallic hardware.

PubMed

Weber, Hans; Ghanouni, Pejman; Pascal-Tenorio, Aurea; Pauly, Kim Butts; Hargreaves, Brian A

2018-07-01

To explore the temperature-induced signal change in two-dimensional multi-spectral imaging (2DMSI) for fast thermometry near metallic hardware to enable MR-guided focused ultrasound surgery (MRgFUS) in patients with implanted metallic hardware. 2DMSI was optimized for temperature sensitivity and applied to monitor focus ultrasound surgery (FUS) sonications near metallic hardware in phantoms and ex vivo porcine muscle tissue. Further, we evaluated its temperature sensitivity for in vivo muscle in patients without metallic hardware. In addition, we performed a comparison of temperature sensitivity between 2DMSI and conventional proton-resonance-frequency-shift (PRFS) thermometry at different distances from metal devices and different signal-to-noise ratios (SNR). 2DMSI thermometry enabled visualization of short ultrasound sonications near metallic hardware. Calibration using in vivo muscle yielded a constant temperature sensitivity for temperatures below 43 °C. For an off-resonance coverage of ± 6 kHz, we achieved a temperature sensitivity of 1.45%/K, resulting in a minimum detectable temperature change of ∼2.5 K for an SNR of 100 with a temporal resolution of 6 s per frame. The proposed 2DMSI thermometry has the potential to allow MR-guided FUS treatments of patients with metallic hardware and therefore expand its reach to a larger patient population. Magn Reson Med 80:259-271, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Non-invasive peripheral nerve stimulation via focused ultrasound in vivo

NASA Astrophysics Data System (ADS)

Downs, Matthew E.; Lee, Stephen A.; Yang, Georgiana; Kim, Seaok; Wang, Qi; Konofagou, Elisa E.

2018-02-01

Focused ultrasound (FUS) has been employed on a wide range of clinical applications to safely and non-invasively achieve desired effects that have previously required invasive and lengthy procedures with conventional methods. Conventional electrical neuromodulation therapies that are applied to the peripheral nervous system (PNS) are invasive and/or non-specific. Recently, focused ultrasound has demonstrated the ability to modulate the central nervous system and ex vivo peripheral neurons. Here, for the first time, noninvasive stimulation of the sciatic nerve eliciting a physiological response in vivo is demonstrated with FUS. FUS was applied on the sciatic nerve in mice with simultaneous electromyography (EMG) on the tibialis anterior muscle. EMG signals were detected during or directly after ultrasound stimulation along with observable muscle contraction of the hind limb. Transecting the sciatic nerve downstream of FUS stimulation eliminated EMG activity during FUS stimulation. Peak-to-peak EMG response amplitudes and latency were found to be comparable to conventional electrical stimulation methods. Histology along with behavioral and thermal testing did not indicate damage to the nerve or surrounding regions. The findings presented herein demonstrate that FUS can serve as a targeted, safe and non-invasive alternative to conventional peripheral nervous system stimulation to treat peripheral neuropathic diseases in the clinic.

Numerical evaluation of the skull for human neuromodulation with transcranial focused ultrasound

NASA Astrophysics Data System (ADS)

Mueller, Jerel K.; Ai, Leo; Bansal, Priya; Legon, Wynn

2017-12-01

Objective. Transcranial focused ultrasound is an emerging field for human non-invasive neuromodulation, but its dosing in humans is difficult to know due to the skull. The objective of the present study was to establish modeling methods based on medical images to assess skull differences between individuals on the wave propagation of ultrasound. Approach. Computational models of transcranial focused ultrasound were constructed using CT and MR scans to solve for intracranial pressure. We explored the effect of including the skull base in models, different transducer placements on the head, and differences between 250 kHz or 500 kHz acoustic frequency for both female and male models. We further tested these features using linear, nonlinear, and elastic simulations. To better understand inter-subject skull thickness and composition effects we evaluated the intracranial pressure maps between twelve individuals at two different skull sites. Main results. Nonlinear acoustic simulations resulted in virtually identical intracranial pressure maps with linear acoustic simulations. Elastic simulations showed a difference in max pressures and full width half maximum volumes of 15% at most. Ultrasound at an acoustic frequency of 250 kHz resulted in the creation of more prominent intracranial standing waves compared to 500 kHz. Finally, across twelve model human skulls, a significant linear relationship to characterize intracranial pressure maps was not found. Significance. Despite its appeal, an inherent problem with the use of a noninvasive transcranial ultrasound method is the difficulty of knowing intracranial effects because of the skull. Here we develop detailed computational models derived from medical images of individuals to simulate the propagation of neuromodulatory ultrasound across the skull and solve for intracranial pressure maps. These methods allow for a much better understanding of the intracranial effects of ultrasound for an individual in order to

Shape-based ultrasound tomography using a Born model with application to high intensity focused ultrasound therapy.

PubMed

Ulker Karbeyaz, Başak; Miller, Eric L; Cleveland, Robin O

2008-05-01

A shaped-based ultrasound tomography method is proposed to reconstruct ellipsoidal objects using a linearized scattering model. The method is motivated by the desire to detect the presence of lesions created by high intensity focused ultrasound (HIFU) in applications of cancer therapy. The computational size and limited view nature of the relevant three-dimensional inverse problem renders impractical the use of traditional pixel-based reconstruction methods. However, by employing a shape-based parametrization it is only necessary to estimate a small number of unknowns describing the geometry of the lesion, in this paper assumed to be ellipsoidal. The details of the shape-based nonlinear inversion method are provided. Results obtained from a commercial ultrasound scanner and a tissue phantom containing a HIFU-like lesion demonstrate the feasibility of the approach where a 20 mm x 5 mm x 6 mm ellipsoidal inclusion was detected with an accuracy of around 5%.

Apparatus, systems, and methods for ultrasound synthetic aperature focusing

DOEpatents

Schuster, George J.; Crawford, Susan L.; Doctor, Steven R.; Harris, Robert V.

2005-04-12

One form of the present invention is a technique for interrogating a sample with ultrasound which includes: generating ultrasonic energy data corresponding to a volume of a sample and performing a synthetic aperture focusing technique on the ultrasonic energy data. The synthetic aperture focusing technique includes: defining a number of hyperbolic surfaces which extend through the volume at different depths and a corresponding number of multiple element accumulation vectors, performing a focused element calculation procedure for a group of vectors which are representative of the interior of a designated aperture, performing another focused element calculation procedure for vectors corresponding to the boundary of the aperture, and providing an image corresponding to features of the sample in accordance with the synthetic aperture focusing technique.

FOCUSING OF HIGH POWER ULTRASOUND BEAMS AND LIMITING VALUES OF SHOCK WAVE PARAMETERS

PubMed Central

Bessonova, O.V.; Khokhlova, V.A.; Bailey, M.R.; Canney, M.S.; Crum, L.A.

2009-01-01

In this work, the influence of nonlinear and diffraction effects on amplification factors of focused ultrasound systems is investigated. The limiting values of acoustic field parameters obtained by focusing of high power ultrasound are studied. The Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation was used for the numerical modeling. Solutions for the nonlinear acoustic field were obtained at output levels corresponding to both pre- and post- shock formation conditions in the focal area of the beam in a weakly dissipative medium. Numerical solutions were compared with experimental data as well as with known analytic predictions. PMID:20161349

FOCUSING OF HIGH POWER ULTRASOUND BEAMS AND LIMITING VALUES OF SHOCK WAVE PARAMETERS.

PubMed

Bessonova, O V; Khokhlova, V A; Bailey, M R; Canney, M S; Crum, L A

2009-07-21

In this work, the influence of nonlinear and diffraction effects on amplification factors of focused ultrasound systems is investigated. The limiting values of acoustic field parameters obtained by focusing of high power ultrasound are studied. The Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation was used for the numerical modeling. Solutions for the nonlinear acoustic field were obtained at output levels corresponding to both pre- and post- shock formation conditions in the focal area of the beam in a weakly dissipative medium. Numerical solutions were compared with experimental data as well as with known analytic predictions.

Focusing of high power ultrasound beams and limiting values of shock wave parameters

NASA Astrophysics Data System (ADS)

Bessonova, O. V.; Khokhlova, V. A.; Bailey, M. R.; Canney, M. S.; Crum, L. A.

2009-10-01

In this work, the influence of nonlinear and diffraction effects on amplification factors of focused ultrasound systems is investigated. The limiting values of acoustic field parameters obtained by focusing of high power ultrasound are studied. The Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation was used for the numerical modeling. Solutions for the nonlinear acoustic field were obtained at output levels corresponding to both pre- and post-shock formation conditions in the focal area of the beam in a weakly dissipative medium. Numerical solutions were compared with experimental data as well as with known analytic predictions.

Phospholipid Capped Mesoporous Nanoparticles for Targeted High Intensity Focused Ultrasound Ablation.

PubMed

Yildirim, Adem; Chattaraj, Rajarshi; Blum, Nicholas T; Shi, Dennis; Kumar, Kaushlendra; Goodwin, Andrew P

2017-09-01

The mechanical effects of cavitation can be effective for therapy but difficult to control, thus potentially leading to off-target side effects in patients. While administration of ultrasound active agents such as fluorocarbon microbubbles and nanodroplets can locally enhance the effects of high intensity focused ultrasound (HIFU), it has been challenging to prepare ultrasound active agents that are small and stable enough to accumulate in tumors and internalize into cancer cells. Here, this paper reports the synthesis of 100 nm nanoparticle ultrasound agents based on phospholipid-coated, mesoporous, hydrophobically functionalized silica nanoparticles that can internalize into cancer cells and remain acoustically active. The ultrasound agents produce bubbles when subjected to short HIFU pulses (≈6 µs) with peak negative pressure as low as ≈7 MPa and at particle concentrations down to 12.5 µg mL -1 (7 × 10 9 particles mL -1 ). Importantly, ultrasound agents are effectively uptaken by cancer cells without cytotoxic effects, but HIFU insonation causes destruction of the cells by the acoustically generated bubbles, as demonstrated by (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and lactate dehydrogenase assays and flow cytometry. Finally, it is showed that the HIFU dose required to effectively eliminate cancer cells in the presence of ultrasound agents causes only a small temperature increase of ≈3.5 °C. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Laser-Induced Focused Ultrasound for Cavitation Treatment: Toward High-Precision Invisible Sonic Scalpel.

PubMed

Lee, Taehwa; Luo, Wei; Li, Qiaochu; Demirci, Hakan; Guo, L Jay

2017-10-01

Beyond the implementation of the photoacoustic effect to photoacoustic imaging and laser ultrasonics, this study demonstrates a novel application of the photoacoustic effect for high-precision cavitation treatment of tissue using laser-induced focused ultrasound. The focused ultrasound is generated by pulsed optical excitation of an efficient photoacoustic film coated on a concave surface, and its amplitude is high enough to produce controllable microcavitation within the focal region (lateral focus <100 µm). Such microcavitation is used to cut or ablate soft tissue in a highly precise manner. This work demonstrates precise cutting of tissue-mimicking gels as well as accurate ablation of gels and animal eye tissues. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reproducibility of Ultrasound-Guided High Intensity Focused Ultrasound (HIFU) Thermal Lesions in Minimally-Invasive Brain Surgery

NASA Astrophysics Data System (ADS)

Zahedi, Sulmaz

This study aims to prove the feasibility of using Ultrasound-Guided High Intensity Focused Ultrasound (USg-HIFU) to create thermal lesions in neurosurgical applications, allowing for precise ablation of brain tissue, while simultaneously providing real time imaging. To test the feasibility of the system, an optically transparent HIFU compatible tissue-mimicking phantom model was produced. USg-HIFU was then used for ablation of the phantom, with and without targets. Finally, ex vivo lamb brain tissue was imaged and ablated using the USg-HIFU system. Real-time ultrasound images and videos obtained throughout the ablation process showing clear lesion formation at the focal point of the HIFU transducer. Post-ablation gross and histopathology examinations were conducted to verify thermal and mechanical damage in the ex vivo lamb brain tissue. Finally, thermocouple readings were obtained, and HIFU field computer simulations were conducted to verify findings. Results of the study concluded reproducibility of USg-HIFU thermal lesions for neurosurgical applications.

Photoacoustic micro-imaging of focused ultrasound induced blood-brain-barrier opening in a rat model

NASA Astrophysics Data System (ADS)

Wang, Po-Hsun; Hsu, Po-Hung; Liu, Hao-Li; Wang, Churng-Ren Chris; Li, Meng-Lin

2010-02-01

Blood brain barrier (BBB) prevents most of the drug from transmitting into the brain tissue and decreases the treatment performance for brain disease. One of the methods to overcome the difficulty of drug delivery is to locally increase the permeability of BBB with high-intensity focused ultrasound. In this study, we have investigated the feasibility of photoacoustic microscopy of focused-ultrasound induced BBB opening in a rat model in vivo with gold nanorods (AuNRs) as a contrast agent. This study takes advantage of the strong near-infrared absorption of AuNRs and their extravasation tendency from BBB opening foci due to their nano-scale size. Before the experiments, craniotomy was performed on rats to provide a path for focused ultrasound beam. Localized BBB opening at the depth of about 3 mm from left cortex of rat brains was achieved by delivering 1.5 MHz focused ultrasound energy into brain tissue in the presence of microbubbles. PEGylated AuNRs with a peak optical absorption at ~800 nm were then intravenously administered. Pre-scan prior to BBB disruption and AuNR injection was taken to mark the signal background. After injection, the distribution of AuNRs in rat brains was monitored up to 2 hours. Experimental results show that imaging AuNRs reveals BBB disruption area in left brains while there are no changes observed in the right brains. From our results, photoacoustic imaging plus AuNRs shows the promise as a novel monitoring strategy in identifying the location and variation of focused-ultrasound BBB-opening in a rat model.

High-intensity focused ultrasound in the treatment of breast tumours.

PubMed

Peek, Mirjam C L; Wu, Feng

2018-01-01

High-intensity focused ultrasound (HIFU) is a minimally invasive technique that has been used for the treatment of both benign and malignant tumours. With HIFU, an ultrasound (US) beam propagates through soft tissue as a high-frequency pressure wave. The US beam is focused at a small target volume, and due to the energy building up at this site, the temperature rises, causing coagulative necrosis and protein denaturation within a few seconds. HIFU is capable of providing a completely non-invasive treatment without causing damage to the directly adjacent tissues. HIFU can be either guided by US or magnetic resonance imaging (MRI). Guided imaging is used to plan the treatment, detect any movement during the treatment and monitor response in real-time. This review describes the history of HIFU, the HIFU technique, available devices and gives an overview of the published literature in the treatment of benign and malignant breast tumours with HIFU.

A new sensitizer DVDMS combined with multiple focused ultrasound treatments: an effective antitumor strategy

NASA Astrophysics Data System (ADS)

Xiong, Wenli; Wang, Pan; Hu, Jianmin; Jia, Yali; Wu, Lijie; Chen, Xiyang; Liu, Quanhong; Wang, Xiaobing

2015-12-01

Sonodynamic therapy (SDT) was developed as a promising noninvasive approach. The present study investigated the antitumor effect of a new sensitizer (sinoporphyrin sodium, referred to as DVDMS) combined with multiple ultrasound treatments on sarcoma 180 both in vitro and in vivo. The combined treatment significantly suppressed cell viability, potentiated apoptosis, and markedly inhibited angiogenesis in vivo. In vivo, the tumor weight inhibition ratio reached 89.82% fifteen days after three sonication treatments plus DVDMS. This effect was stronger than one ultrasound alone (32.56%) and than one round of sonication plus DVDMS (59.33%). DVDMS combined with multiple focused ultrasound treatments initiated tumor tissue destruction, induced cancer cell apoptosis, inhibited tumor angiogenesis, suppressed cancer cell proliferation, and decreased VEGF and PCNA expression levels. Moreover, the treatment did not show obvious signs of side effects or induce a drop in body weight. These results indicated that DVDMS combined with multiple focused ultrasounds may be a promising strategy against solid tumor.

Radio frequency focused interdigital linear accelerator

DOEpatents

Swenson, Donald A.; Starling, W. Joel

2006-08-29

An interdigital (Wideroe) linear accelerator employing drift tubes, and associated support stems that couple to both the longitudinal and support stem electromagnetic fields of the linac, creating rf quadrupole fields along the axis of the linac to provide transverse focusing for the particle beam. Each drift tube comprises two separate electrodes operating at different electrical potentials as determined by cavity rf fields. Each electrode supports two fingers, pointing towards the opposite end of the drift tube, forming a four-finger geometry that produces an rf quadrupole field distribution along its axis. The fundamental periodicity of the structure is equal to one half of the particle wavelength .beta..lamda., where .beta. is the particle velocity in units of the velocity of light and .lamda. is the free space wavelength of the rf. Particles are accelerated in the gaps between drift tubes. The particle beam is focused in regions inside the drift tubes.

Electron Beam Focusing in the Linear Accelerator (linac)

NASA Astrophysics Data System (ADS)

Jauregui, Luis

2015-10-01

To produce consistent data with an electron accelerator, it is critical to have a well-focused beam. To keep the beam focused, quadrupoles (quads) are employed. Quads are magnets, which focus the beam in one direction (x or y) and defocus in the other. When two or more quads are used in series, a net focusing effect is achieved in both vertical and horizontal directions. At start up there is a 5% calibration error in the linac at Thomas Jefferson National Accelerator Facility. This means that the momentum of particles passing through the quads isn't always what is expected, which affects the focusing of the beam. The objective is to find exactly how sensitive the focusing in the linac is to this 5% error. A linac was simulated, which contained 290 RF Cavities with random electric fields (to simulate the 5% calibration error), and a total momentum kick of 1090 MeV. National Science Foundation, Department of Energy, Jefferson Lab, Old Dominion University.

Targeted disruption of the blood brain barrier with focused ultrasound: association with cavitation activity

NASA Astrophysics Data System (ADS)

McDannold, N.; Vykhodtseva, N.; Hynynen, K.

2006-02-01

Acoustic emission was monitored during focused ultrasound exposures in conjunction with an ultrasound contrast agent (Optison®) in order to determine if cavitation activity is associated with the induction of blood-brain barrier disruption (BBBD). Thirty-four locations were sonicated (frequency: 260 kHz) at targets 10 mm deep in rabbit brain (N = 9). The sonications were applied at peak pressure amplitudes ranging from 0.11 to 0.57 MPa (burst length: 10 ms; repetition frequency of 1 Hz; duration: 20 s). Acoustic emission was recorded with a focused passive cavitation detector. This emission was recorded at each location during sonications with and without Optison®. Detectable wideband acoustic emission was observed only at 0.40 and 0.57 MPa. BBBD was observed in contrast MRI after sonication at 0.29-0.57 MPa. The appearance of small regions of extravasated erythrocytes appeared to be associated with this wideband emission signal. The results thus suggest that BBBD resulting from focused ultrasound pulses in the presence of Optison® can occur without indicators for inertial cavitation in vivo, wideband emission and extravasation. If inertial cavitation is not responsible for the BBBD, other ultrasound/microbubble interactions are likely the source. A significant increase in the emission signal due to Optison® at the second and third harmonics of the ultrasound driving frequency was found to correlate with BBBD and might be useful as an online method to indicate when the disruption occurs.

Localization of focused-ultrasound beams in a tissue phantom, using remote thermocouple arrays.

PubMed

Hariharan, Prasanna; Dibaji, Seyed Ahmad Reza; Banerjee, Rupak K; Nagaraja, Srinidhi; Myers, Matthew R

2014-12-01

In focused-ultrasound procedures such as vessel cauterization or clot lysis, targeting accuracy is critical. To investigate the targeting accuracy of the focused-ultrasound systems, tissue phantoms embedded with thermocouples can be employed. This paper describes a method that utilizes an array of thermocouples to localize the focused ultrasound beam. All of the thermocouples are located away from the beam, so that thermocouple artifacts and sensor interference are minimized. Beam propagation and temperature rise in the phantom are simulated numerically, and an optimization routine calculates the beam location that produces the best agreement between the numerical temperature values and those measured with thermocouples. The accuracy of the method was examined as a function of the array characteristics, including the number of thermocouples in the array and their orientation. For exposures with a 3.3-MHz source, the remote-thermocouple technique was able to predict the focal position to within 0.06 mm. Once the focal location is determined using the localization method, temperatures at desired locations (including the focus) can be estimated from remote thermocouple measurements by curve fitting an analytical solution to the heat equation. Temperature increases in the focal plane were predicted to within 5% agreement with measured values using this method.

Ejection of small droplet from microplate using focused ultrasound

NASA Astrophysics Data System (ADS)

Tanaka, Hiroki; Mizuno, Yosuke; Nakamura, Kentaro

2017-08-01

We discussed an ultrasonic system for single-droplet ejection from a microplate, which is one of the basic and important procedures in the noncontact handling of droplets in air. In this system, a 1.5 MHz concave transducer located below the microplate is used for chasing the liquid surface through a pulse echo method, and also for the ejection of a 1 µL single droplet by the burst of focused ultrasound. We investigated the relationship between the droplet ejection characteristics, the distance from the transducer to the surface of liquid, the material property, and the excitation condition of the focused ultrasonic transducer. It was verified that the optimal position of the transducer was off the focal point of sound pressure by ±1 mm, because the sound intensity had to be controlled to eject a single droplet. Subsequently, we confirmed experimentally that the ejected droplet volume linearly depended on the surface tension of the liquid, and that the droplet volume and ejection velocity were determined by the Webber number, Reynolds number, and Ohnesolge number. In addition, by optimizing the duration of the burst ultrasound, the droplet volume and ejection velocity were controlled.

Blood coagulation using High Intensity Focused Ultrasound (HIFU)

NASA Astrophysics Data System (ADS)

Nguyen, Phuc V.; Oh, Junghwan; Kang, Hyun Wook

2014-03-01

High Intensity Focused Ultrasound (HIFU) technology provides a feasible method of achieving thermal coagulation during surgical procedures. One of the potential clinical benefits of HIFU can induce immediate hemostasis without suturing. The objective of this study was to investigate the efficiency of a HIFU system for blood coagulation on severe vascular injury. ngHIFU treatment was implemented immediately after bleeding in artery. The ultrasound probe was made of piezoelectric material, generating a central frequency of 2.0 MHz as well as an ellipsoidal focal spot of 2 mm in lateral dimension and 10 mm in axial dimension. Acoustic coagulation was employed on a perfused chicken artery model in vitro. A surgical incision (1 to 2 mm long) was made with a scapel on the arterial wall, and heparinized autologous blood was made to leak out from the incision with a syringe pump. A total of 5 femoral artery incisions was treated with the HIFU beam. The intensity of 4500 W/cm2 at the focus was applied for all treatments. Complete hemostasis was achieved in all treatments, along with the treatment times of 25 to 50 seconds. The estimated intraoperative blood loss was from 2 to 5 mL. The proposed HIFU system may provide an effective method for immediate blood coagulation for arteries and veins in clinical applications.

A simulation model for predicting the temperature during the application of MR-guided focused ultrasound for stroke treatment using pulsed ultrasound

NASA Astrophysics Data System (ADS)

Hadjisavvas, V.; Damianou, C.

2011-09-01

In this paper a simulation model for predicting the temperature during the application of MR-guided focused ultrasound for stroke treatment using pulsed ultrasound is presented. A single element spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating at either 0.5 MHz or 1 MHz was considered. The power field was estimated using the KZK model. The temperature was estimated using the bioheat equation. The goal was to extract the acoustic parameters (power, pulse duration, duty factor and pulse repetition frequency) that maintain a temperature increase of less than 1 °C during the application of a pulse ultrasound protocol. It was found that the temperature change increases linearly with duty factor. The higher the power, the lower the duty factor needed to keep the temperature change to the safe limit of 1 °C. The higher the frequency the lower the duty factor needed to keep the temperature change to the safe limit of 1 °C. Finally, the deeper the target, the higher the duty factor needed to keep the temperature change to the safe limit of 1 °C. The simulation model was tested in brain tissue during the application of pulse ultrasound and the measured temperature was in close agreement with the simulated temperature. This simulation model is considered to be very useful tool for providing acoustic parameters (frequency, power, duty factor, pulse repetition frequency) during the application of pulsed ultrasound at various depths in tissue so that a safe temperature is maintained during the treatment. This model could be tested soon during stroke clinical trials.

Pulsed focused ultrasound-induced displacements in confined in vitro blood clots.

PubMed

Wright, Cameron C; Hynynen, Kullervo; Goertz, David E

2012-03-01

Ultrasound has been shown to potentiate the effects of tissue plasminogen activator to improve clot lysis in a range of in vitro and in vivo studies as well as in clinical trials. One possible mechanism of action is acoustic radiation force-induced clot displacements. In this study, we investigate the temporal and spatial dynamics of clot displacements and strain initiated by focused ultrasound pulses. Displacements were produced by a 1.51 MHz f-number 1 transducer over a range of acoustic powers (1-85 W) in clots constrained within an agar vessel phantom channel. Displacements were tracked during and after a 5.45 ms therapy pulse using a 20 MHz high-frequency ultrasound imaging probe. Peak thrombus displacements were found to be linear as a function of acoustic power up to 60 W before leveling off near 128 μm for the highest transmit powers. The time to peak displacement and recovery time of blood clots was largely independent of acoustic powers with measured values near 2 ms. A linear relationship between peak axial strain and transmit power was observed, reaching a peak value of 11% at 35 W. The peak strain occurred ~0.75 mm from the focal zone for all powers investigated in both lateral and axial directions. These results indicate that substantial displacements can be induced by focused ultrasound in confined blood clots, and that the spatial and temporal displacement patterns are complex and highly dependent on exposure conditions, which has implications for future work investigating their link to clot lysis and for developing approaches to exploit these effects.

Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment.

PubMed

Liu, Hao-Li; Hua, Mu-Yi; Chen, Pin-Yuan; Chu, Po-Chun; Pan, Chia-Hsin; Yang, Hung-Wei; Huang, Chiung-Yin; Wang, Jiun-Jie; Yen, Tzu-Chen; Wei, Kuo-Chen

2010-05-01

To demonstrate the feasibility of using focused ultrasound to enhance delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas in rats with induced tumors and determine if such an approach increases treatment efficacy. All animal experiments were approved by the animal committee and adhered to the experimental animal care guidelines. A 400-kHz focused ultrasound generator was used to transcranially disrupt the blood-brain barrier (BBB) in rat brains by delivering burst-tone ultrasound energy in the presence of microbubbles. The process was monitored in vivo by using magnetic resonance (MR) imaging. Cultured C6 glioma cells implanted in Sprague-Dawley rats were used as the tumor model. BCNU (13.5 mg/kg) was administered intravenously and its concentration in brains was quantified by using high-performance liquid chromatography. MR imaging was used to evaluate the effect of treatments longitudinally, including analysis of tumor progression and animal survival, and brain tissues were histologically examined. Methods including the two-tailed unpaired t test and the Mantel-Cox test were used for statistical analyses, with a significance level of .05. Focused ultrasound significantly enhanced the penetration of BCNU through the BBB in normal (by 340%) and tumor-implanted (by 202%) brains without causing hemorrhaging. Treatment of tumor-implanted rats with focused ultrasound alone had no beneficial effect on tumor progression or on animal survival up to 60 days. Administration of BCNU only transiently controlled tumor progression; nevertheless, relative to untreated controls, animal survival was improved by treatment with BCNU alone (increase in median survival time [IST(median)], 15.7%, P = .023). Treatment with focused ultrasound before BCNU administration controlled tumor progression (day 31: 0.05 cm(3) + or - 0.1 [standard deviation] vs 0.28 cm(3) + or - 0.1) and improved animal survival relative to untreated controls (IST(median), 85.9%, P = .0015

Compact and tunable focusing device for plasma wakefield acceleration

NASA Astrophysics Data System (ADS)

Pompili, R.; Anania, M. P.; Chiadroni, E.; Cianchi, A.; Ferrario, M.; Lollo, V.; Notargiacomo, A.; Picardi, L.; Ronsivalle, C.; Rosenzweig, J. B.; Shpakov, V.; Vannozzi, A.

2018-03-01

Plasma wakefield acceleration, either driven by ultra-short laser pulses or electron bunches, represents one of the most promising techniques able to overcome the limits of conventional RF technology and allows the development of compact accelerators. In the particle beam-driven scenario, ultra-short bunches with tiny spot sizes are required to enhance the accelerating gradient and preserve the emittance and energy spread of the accelerated bunch. To achieve such tight transverse beam sizes, a focusing system with short focal length is mandatory. Here we discuss the development of a compact and tunable system consisting of three small-bore permanent-magnet quadrupoles with 520 T/m field gradient. The device has been designed in view of the plasma acceleration experiments planned at the SPARC_LAB test-facility. Being the field gradient fixed, the focusing is adjusted by tuning the relative position of the three magnets with nanometer resolution. Details about its magnetic design, beam-dynamics simulations, and preliminary results are examined in the paper.

MRI-Guided Focused Ultrasound as a New Method of Drug Delivery

PubMed Central

Thanou, M.; Gedroyc, W.

2013-01-01

Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS-) mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery. PMID:23738076

Effect of controlled offset of focal position in cavitation-enhanced high-intensity focused ultrasound treatment

NASA Astrophysics Data System (ADS)

Goto, Kota; Takagi, Ryo; Miyashita, Takuya; Jimbo, Hayato; Yoshizawa, Shin; Umemura, Shin-ichiro

2015-07-01

High-intensity focused ultrasound (HIFU) is a noninvasive treatment for tumors such as cancer. In this method, ultrasound is generated outside the body and focused to the target tissue. Therefore, physical and mental stresses on the patient are minimal. A drawback of the HIFU treatment is a long treatment time for a large tumor due to the small therapeutic volume by a single exposure. Enhancing the heating effect of ultrasound by cavitation bubbles may solve this problem. However, this is rather difficult because cavitation clouds tend to be formed backward from the focal point while ultrasonic intensity for heating is centered at the focal point. In this study, the focal points of the trigger pulses to generate cavitation were offset forward from those of the heating ultrasound to match the cavitation clouds with the heating patterns. Results suggest that the controlled offset of focal points makes the thermal coagulation more predictable.

High-Intensity Focused Ultrasound (HIFU) in Localized Prostate Cancer Treatment.

PubMed

Alkhorayef, Mohammed; Mahmoud, Mustafa Z; Alzimami, Khalid S; Sulieman, Abdelmoneim; Fagiri, Maram A

2015-01-01

High-intensity focused ultrasound (HIFU) applies high-intensity focused ultrasound energy to locally heat and destroy diseased or damaged tissue through ablation. This study intended to review HIFU to explain the fundamentals of HIFU, evaluate the evidence concerning the role of HIFU in the treatment of prostate cancer (PC), review the technologies used to perform HIFU and the published clinical literature regarding the procedure as a primary treatment for PC. Studies addressing HIFU in localized PC were identified in a search of internet scientific databases. The analysis of outcomes was limited to journal articles written in English and published between 2000 and 2013. HIFU is a non-invasive approach that uses a precisely delivered ultrasound energy to achieve tumor cell necrosis without radiation or surgical excision. In current urological oncology, HIFU is used clinically in the treatment of PC. Clinical research on HIFU therapy for localized PC began in the 1990s, and the majority of PC patients were treated with the Ablatherm device. HIFU treatment for localized PC can be considered as an alternative minimally invasive therapeutic modality for patients who are not candidates for radical prostatectomy. Patients with lower pre-HIFU PSA level and favourable pathologic Gleason score seem to present better oncologic outcomes. Future advances in technology and safety will undoubtedly expand the HIFU role in this indication as more of patient series are published, with a longer follow-up period.

High-Intensity Focused Ultrasound (HIFU) in Localized Prostate Cancer Treatment

PubMed Central

Alkhorayef, Mohammed; Mahmoud, Mustafa Z.; Alzimami, Khalid S.; Sulieman, Abdelmoneim; Fagiri, Maram A.

2015-01-01

Summary Background High-intensity focused ultrasound (HIFU) applies high-intensity focused ultrasound energy to locally heat and destroy diseased or damaged tissue through ablation. This study intended to review HIFU to explain the fundamentals of HIFU, evaluate the evidence concerning the role of HIFU in the treatment of prostate cancer (PC), review the technologies used to perform HIFU and the published clinical literature regarding the procedure as a primary treatment for PC. Material/Methods Studies addressing HIFU in localized PC were identified in a search of internet scientific databases. The analysis of outcomes was limited to journal articles written in English and published between 2000 and 2013. Results HIFU is a non-invasive approach that uses a precisely delivered ultrasound energy to achieve tumor cell necrosis without radiation or surgical excision. In current urological oncology, HIFU is used clinically in the treatment of PC. Clinical research on HIFU therapy for localized PC began in the 1990s, and the majority of PC patients were treated with the Ablatherm device. Conclusions HIFU treatment for localized PC can be considered as an alternative minimally invasive therapeutic modality for patients who are not candidates for radical prostatectomy. Patients with lower pre-HIFU PSA level and favourable pathologic Gleason score seem to present better oncologic outcomes. Future advances in technology and safety will undoubtedly expand the HIFU role in this indication as more of patient series are published, with a longer follow-up period. PMID:25806099

Phase-shift nano-emulsions induced cavitation and ablation during high intensity focused ultrasound exposure

NASA Astrophysics Data System (ADS)

Qiao, Yangzi; Yin, Hui; Chang, Nan; Wan, Mingxi

2017-03-01

Phase-shift Nano-emulsions (PSNEs) with a small initial diameter in nanoscale have the potential to leak out of the blood vessels and to accumulate at target point of tissue. At desired location, PSNEs can undergo acoustic droplet vaporization (ADV) process, change into gas bubbles and enhance focused ultrasound efficiency. The aim of this work was to provide spatial and temporal information on PSNE induced cavitation and ablation effects during pulsed high intensity focused ultrasound (HIFU) exposure. The PSNEs were composed of perfluorohaxane (PFH) and bovine serum albumin (BSA), and then uniformly distributed in a transparent polyacrylamide phantom. The Sonoluminescence (SL) method was employed to visualize the cavitation distribution and formation process of PSNEs induced cavitation. For the phantom which was used for ablation observation, heat sensitive BSA was added. When the temperature generated by ultrasound exposure was high enough to denature BSA, the transparent phantom would turn out white lesions. The shape of the lesion and the formation process were compared with those of cavitation. Each of the pulse contained 12 cycles for a duration of 10 µs. And the duty cycle changed from 1:10 to 1:40. The total "on" time of HIFU was 2s. PSNE can evidently accelerate cavitation emitting bright SL in pre-focal region. The cavitation was generated layer by layer towards the transducer. The formed bubble wall can block acoustic waves transmitting to the distal end. And the lesion appeared to be separated into two parts. One in pre-focal region stemmed from one point and grew quickly toward the transducer. The other in focal region was formed by merging some small white dots, and grew much slower. The influence of duty cycle has also been examined. The lower duty cycle with longer pulse-off time would generate more intense cavitation, however, smaller lesion. Bubble cloud gradually developed within phantom would greatly influence the cavitation and ablation

[The effect of focused ultrasound on the physicochemical properties of Sarcoma 180 cell membrane].

PubMed

Li, Tao; Hao, Qiao; Wang, Xiaobing; Liu, Quanhong

2009-10-01

This study was amied to detect the changes in the cell membrane of Sarcoma 180 (S180) cells induced by focused ultrasound and to probe the underlying mechanism. The viability of tumor cells was examined at various intensities and different treatment times by ultrasound at the frequency of 2.2MHz. Flow cytometry and fluorescence microscopy were used to detect the loading of fluorescein isothiocyanate dextran (FD500) which signifies the change of membrane permeability. The results showed that after the cells were treated by ultrasound, especially when irradiated for 60s, the number of fluorescent cell, which represented the transient change of membrane permeabilization with cell survival, increased significantly. Then the damage of cell membrane was evaluated by the measurement of lactate dehydrogenase (LDH) release which became more severe as the radiation time was increasing. The generation of lipid peroxidation was estimated using the Thibabituric Acid (TBA) method after irradiation. The results reveal that the instant cell damage effects induced by ultrasound may be related to the improved membrane lipid peroxidation levels post-treatment. The physicochemical properties of S180 cell membrane were changed by focused ultrasound. The findings also imply an exposure time-dependent pattern and suggest that the lipid peroxidation produced by acoustic cavitation may play important roles in these actions.

Multiple high-intensity focused ultrasound probes for kidney-tissue ablation.

PubMed

Häcker, Axel; Chauhan, Sunita; Peters, Kristina; Hildenbrand, Ralf; Marlinghaus, Ernst; Alken, Peter; Michel, Maurice Stephan

2005-10-01

To investigate kidney-tissue ablation by high-intensity focused ultrasound (HIFU) using multiple and single probes. Ultrasound beams (1.75 MHz) produced by a piezoceramic element (focal distance 80 mm) were focused at the center of renal parenchyma. One of the three probes (mounted on a jig) could also be used for comparison with a single probe at comparable power ratings. Lesion dimensions were examined in perfused and unperfused ex vivo porcine kidneys at different power levels (40, 60, and 80 W) and treatment times (4, 6, and 8 seconds). At identical power levels, the lesions induced by multiple probes were larger than those induced by a single probe. Lesion size increased with increasing pulse duration and generator power. The sizes and shapes of the lesions were predictably repeatable in all samples. Lesions in perfused kidneys were smaller than those in unperfused kidneys. Ex vivo, kidney-tissue ablation by means of multiple HIFU probes offers significant advantages over single HIFU probes in respect of lesion size and formation. These advantages need to be confirmed by tests in vivo at higher energy levels.

An ultrasound wearable system for the monitoring and acceleration of fracture healing in long bones.

PubMed

Protopappas, Vasilios C; Baga, Dina A; Fotiadis, Dimitrios I; Likas, Aristidis C; Papachristos, Athanasios A; Malizos, Konstantinos N

2005-09-01

An ultrasound wearable system for remote monitoring and acceleration of the healing process in fractured long bones is presented. The so-called USBone system consists of a pair of ultrasound transducers, implanted into the fracture region, a wearable device and a centralized unit. The wearable device is responsible to carry out ultrasound measurements using the axial-transmission technique and initiate therapy sessions of low-intensity pulsed ultrasound. The acquired measurements and other data are wirelessly transferred from the patient-site to the centralized unit, which is located in a clinical setting. The evaluation of the system on an animal tibial osteotomy model is also presented. A dataset was constructed for monitoring purposes consisting of serial ultrasound measurements, follow-up radiographs, quantitative computed tomography-based densitometry and biomechanical data. The animal study demonstrated the ability of the system to collect ultrasound measurements in an effective and reliable fashion and participating orthopaedic surgeons accepted the system for future clinical application. Analysis of the acquired measurements showed that the pattern of evolution of the ultrasound velocity through healing bones over the postoperative period monitors a dynamic healing process. Furthermore, the ultrasound velocity of radiographically healed bones returns to 80% of the intact bone value, whereas the correlation coefficient of the velocity with the material and mechanical properties of the healing bone ranges from 0.699 to 0.814. The USBone system constitutes the first telemedicine system for the out-hospital management of patients sustained open fractures and treated with external fixation devices.

Creating Brain Lesions by Low Intensity Focused Ultrasound with Microbubbles: A Rat Study at Half MHz

PubMed Central

Huang, Yuexi; Vykhodtseva, Natalia I.; Hynynen, Kullervo

2014-01-01

Low intensity focused ultrasound was applied with microbubbles (Definity, 0.02 mL/kg) to produce brain lesions in 50 rats at 558 kHz. Burst sonications (burst length: 10 ms; pulse repetition frequency: 1 Hz; total exposure: 5 min; acoustic powers: 0.47-1.3W) generated ischemic or hemorrhagic lesions at the focal volume revealed by both MR imaging and histology. Shorter burst (2 ms) or shorter sonication time (1 min) reduced the probability of lesion production. Longer pulses (200ms, 500ms and continuous wave) caused significant near-field damages. Using microbubbles with focused ultrasound significantly reduced the acoustic power levels, therefore avoided skull heating issues and potentially can extend the treatable volume of transcranial focused ultrasound to the brain tissues close to the skull. PMID:23743099

Pulsed ultrasounds accelerate healing of rib fractures in an experimental animal model: an effective new thoracic therapy?

PubMed

Santana-Rodríguez, Norberto; Clavo, Bernardino; Fernández-Pérez, Leandro; Rivero, José C; Travieso, María M; Fiuza, María D; Villar, Jesús; García-Castellano, José M; Hernández-Pérez, Octavio; Déniz, Antonio

2011-05-01

Rib fractures are a frequent traumatic injury associated with a relatively high morbidity. Currently, the treatment of rib fractures is symptomatic. Since it has been reported that pulsed ultrasounds accelerates repair of limb fractures, we hypothesized that the application of pulsed ultrasounds will modify the course of healing in an animal model of rib fracture. We studied 136 male Sprague-Dawley rats. Animals were randomly assigned to different groups of doses (none, 50, 100, and 250 mW/cm(2) of intensity for 3 minutes per day) and durations (2, 10, 20, and 28 days) of treatment with pulsed ultrasounds. In every subgroup, we analyzed radiologic and histologic changes in the bone callus. In addition, we examined changes in gene expression of relevant genes involved in wound repair in both control and treated animals. Histologic and radiologic consolidation was significantly increased by pulsed ultrasound treatment when applied for more than 10 days. The application of 50 mW/cm(2) was the most effective dose. Only the 100 and 250 mW/cm(2) doses were able to significantly increase messenger RNA expression of insulin-like growth factor 1, suppressor of cytokine signaling-2 and -3, and vascular endothelial growth factor and decrease monocyte chemoattractant protein-1 and collagen type II-alpha 1. Our findings indicate that pulsed ultrasound accelerates the consolidation of rib fractures. This study is the first to show that pulsed ultrasound promotes the healing of rib fractures. From a translational point of view, this easy, cheap technique could serve as an effective new therapeutic modality in patients with rib fractures. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Robotic active positioning for magnetic resonance-guided high-intensity focused ultrasound

NASA Astrophysics Data System (ADS)

Xiao, Xu; Huang, Zhihong; Volovick, Alexander; Melzer, Andreas

2012-11-01

Magnetic resonance (MR) guided High-intensity focused ultrasound (HIFU) is a noninvasive method producing thermal necrosis and cavitation at the position of tumors with high accuracy. Because the typical size of the high-intensity focused ultrasound focus are much smaller than the targeted tumor or other tissues, multiple sonications and focus repositioning become necessary for HIFU treatment. In order to reach a much wider range, manual repositioning or using MR compatible mechanical actuators could be used. The repositioning technique is a time consuming procedure because it needs a series of MR imaging to detect the transducer and markers preplaced on the mechanical devices. We combined an active tracking technique into the MR guided HIFU system. In this work, the robotic system used is the MR-compatible robotics from InnoMotion{trade mark, serif} (IBSMM, Engineering spol. s r.o. / Ltd, Czech) which is originally designed for MR-guided needle biopsy. The precision and positioning speed of the combined robotic HIFU system are evaluated in this study. Compared to the existing MR guided HIFU systems, the combined robotic system with active tracking techniques provides a potential that allows the HIFU treatment to operate in a larger spatial range and with a faster speed.

Combined passive acoustic mapping and magnetic resonance thermometry for monitoring phase-shift nanoemulsion enhanced focused ultrasound therapy

NASA Astrophysics Data System (ADS)

Crake, Calum; Meral, F. Can; Burgess, Mark T.; Papademetriou, Iason T.; McDannold, Nathan J.; Porter, Tyrone M.

2017-08-01

Focused ultrasound (FUS) has the potential to enable precise, image-guided noninvasive surgery for the treatment of cancer in which tumors are identified and destroyed in a single integrated procedure. However, success of the method in highly vascular organs has been limited due to heat losses to perfusion, requiring development of techniques to locally enhance energy absorption and heating. In addition, FUS procedures are conventionally monitored using MRI, which provides excellent anatomical images and can map temperature, but is not capable of capturing the full gamut of available data such as the acoustic emissions generated during this inherently acoustically-driven procedure. Here, we employed phase-shift nanoemulsions (PSNE) embedded in tissue phantoms to promote cavitation and hence temperature rise induced by FUS. In addition, we incorporated passive acoustic mapping (PAM) alongside simultaneous MR thermometry in order to visualize both acoustic emissions and temperature rise, within the bore of a full scale clinical MRI scanner. Focal cavitation of PSNE could be resolved using PAM and resulted in accelerated heating and increased the maximum elevated temperature measured via MR thermometry compared to experiments without nanoemulsions. Over time, the simultaneously acquired acoustic and temperature maps show translation of the focus of activity towards the FUS transducer, and the magnitude of the increase in cavitation and focal shift both increased with nanoemulsion concentration. PAM results were well correlated with MRI thermometry and demonstrated greater sensitivity, with the ability to detect cavitation before enhanced heating was observed. The results suggest that PSNE could be beneficial for enhancement of thermal focused ultrasound therapies and that PAM could be a critical tool for monitoring this process.

Transcostal high-intensity focused ultrasound treatment using phased array with geometric correction.

PubMed

Qiao, Shan; Shen, Guofeng; Bai, Jingfeng; Chen, Yazhu

2013-08-01

In the high-intensity focused ultrasound treatment of liver tumors, ultrasound propagation is affected by the rib cage. Because of the diffraction and absorption of the bone, the sound distribution at the focal plane is altered, and more importantly, overheating on the rib surface might occur. To overcome these problems, a geometric correction method is applied to turn off the elements blocked by the ribs. The potential of steering the focus of the phased-array along the propagation direction to improve the transcostal treatment was investigated by simulations and experiments using different rib models and transducers. The ultrasound propagation through the ribs was computed by a hybrid method including the Rayleigh-Sommerfeld integral, k-space method, and angular spectrum method. A modified correction method was proposed to adjust the output of elements based on their relative area in the projected "shadow" of the ribs. The simulation results showed that an increase in the specific absorption rate gain up to 300% was obtained by varying the focal length although the optimal value varied in each situation. Therefore, acoustic simulation is required for each clinical case to determine a satisfactory treatment plan.

Weakening Pin Bone Attachment in Fish Fillets Using High-Intensity Focused Ultrasound.

PubMed

Skjelvareid, Martin H; Stormo, Svein Kristian; Þórarinsdóttir, Kristín Anna; Heia, Karsten

2017-09-18

High Intensity Focused Ultrasound (HIFU) can be used for the localized heating of biological tissue through the conversion of sound waves into heat. Although originally developed for human medicine, HIFU may also be used to weaken the attachment of pin bones in fish fillets to enable easier removal of such bones. This was shown in the present study, where a series of experiments were performed on HIFU phantoms and fillets of cod and salmon. In thin objects such as fish fillets, the heat is mainly dissipated at the surfaces. However, bones inside the fillet absorb ultrasound energy more efficiently than the surrounding tissue, resulting in a "self-focusing" heating of the bones. Salmon skin was found to effectively block the ultrasound, resulting in a significantly lower heating effect in fillets with skin. Cod skin partly blocked the ultrasound, but only to a small degree, enabling HIFU treatment through the skin. The treatment of fillets to reduce the pin bone attachment yielded an average reduction in the required pulling force by 50% in cod fillets with skin, with little muscle denaturation, and 72% in skinned fillets, with significant muscle denaturation. Salmon fillets were treated from the muscle side of the fillet to circumvent the need for penetration through skin. The treatment resulted in a 30% reduction in the peak pulling force and 10% reduction in the total pulling work, with a slight denaturation of the fillet surface.

High-Frequency Focused Water-Coupled Ultrasound Used for Three-Dimensional Surface Depression Profiling

NASA Technical Reports Server (NTRS)

Roth, Don J.; Whalen, Mike F.; Hendricks, J. Lynne; Bodis, James R.

2001-01-01

To interface with other solids, many surfaces are engineered via methods such as plating, coating, and machining to produce a functional surface ensuring successful end products. In addition, subsurface properties such as hardness, residual stress, deformation, chemical composition, and microstructure are often linked to surface characteristics. Surface topography, therefore, contains the signatures of the surface and possibly links to volumetric properties, and as a result serves as a vital link between surface design, manufacturing, and performance. Hence, surface topography can be used to diagnose, monitor, and control fabrication methods. At the NASA Glenn Research Center, the measurement of surface topography is important in developing high-temperature structural materials and for profiling the surface changes of materials during microgravity combustion experiments. A prior study demonstrated that focused air-coupled ultrasound at 1 MHz could profile surfaces with a 25-m depth resolution and a 400-m lateral resolution over a 1.4-mm depth range. In this work, we address the question of whether higher frequency focused water-coupled ultrasound can improve on these specifications. To this end, we employed 10- and 25-MHz focused ultrasonic transducers in the water-coupled mode. The surface profile results seen in this investigation for 25-MHz water-coupled ultrasound, in comparison to those for 1-MHz air-coupled ultrasound, represent an 8 times improvement in depth resolution (3 vs. 25 m seen in practice), an improvement of at least 2 times in lateral resolution (180 vs. 400 m calculated and observed in practice), and an improvement in vertical depth range of 4 times (calculated).

Real-Time Monitoring Of Regional Tissue Elasticity During FUS Focused Ultrasound Therapy Using Harmonic Motion Imaging

NASA Astrophysics Data System (ADS)

Maleke, Caroline; Pernot, Mathieu; Konofagou, Elisa

2006-05-01

The feasibility of the Harmonic Motion Imaging (HMI) technique for simultaneous monitoring and generation of focused ultrasound therapy using two separate focused ultrasound transducer elements has previously been shown. In this study, a new HMI technique is described that images tissue displacement induced by a harmonic radiation force induced using a single focused ultrasound element. First, wave propagation simulation models were used to compare the use of a single Amplitude-Modulated (AM) focused beam versus two overlapping focused beams as previously implemented for HMI. Simulation results indicated that, unlike in the two-beam configuration, the AM beam produced a consistent, stable focus for the applied harmonic radiation force. The AM beam thus offered the unique advantage of sustaining the application of the spatially-invariant radiation force. Experiments were then performed on gelatin gel phantoms and tissue in vitro bovine liver. The radiation force was generated by a 4.68 MHz focused transducer using a low-frequency Amplitude-Modulated (AM) RF-signal. RF data were acquired at 7.5 MHz with a PRF of 6.5 kHz and displacements were estimated using a 1D cross-correlation algorithm on successive RF signals. Furthermore, taking advantage of the real-time capability of our method, the change in the elastic properties was monitored during focused ultrasound (FUS) ablation of tissue in vitro bovine liver. Based on the harmonic displacements, their temperature-dependence, and the calculated acoustic radiation force, the change in the relative, regional stiffness could be monitored during heating and ablation, both using the displacement amplitude and the resulting phase shift change of the displacement relative to the radiation force temporal profile. In conclusion, the feasibility of using an AM radiation force for HMI for simultaneous monitoring and treatment during ultrasound therapy was demonstrated in phantoms and tissues in vitro. Further study of this

In vitro characterization of perfluorocarbon droplets for focused ultrasound therapy

NASA Astrophysics Data System (ADS)

Schad, Kelly C.; Hynynen, Kullervo

2010-09-01

Focused ultrasound therapy can be enhanced with microbubbles by thermal and cavitation effects. However, localization of treatment is difficult as bioeffects can occur outside of the target region. Spatial control of bubbles can be achieved by ultrasound-induced conversion of liquid perfluorocarbon droplets to gas bubbles. This study was undertaken to determine the acoustic parameters for bubble production by droplet conversion and how it depends on the acoustic conditions and droplet physical parameters. Lipid-encapsulated droplets containing dodecafluoropentane were manufactured with sizes ranging from 1.9 to 7.2 µm in diameter and diluted to a concentration of 8 × 106 droplets mL-1. The droplets were sonicated in vitro with a focused ultrasound transducer and varying frequency and exposure under flow conditions through an acoustically transparent vessel. The sonications were 10 ms in duration at frequencies of 0.578, 1.736 and 2.855 MHz. The pressure threshold for droplet conversion was measured with an active transducer operating in pulse-echo mode and simultaneous measurements of broadband acoustic emissions were performed with passive acoustic detection. The results show that droplets cannot be converted at low frequency without broadband emissions occurring. However, the pressure threshold for droplet conversion decreased with increasing frequency, exposure and droplet size. The pressure threshold for broadband emissions was independent of the droplet size and was 2.9, 4.4 and 5.3 MPa for 0.578, 1736 and 2.855 MHz, respectively. In summary, we have demonstrated that droplet conversion is feasible for clinically relevant sized droplets and acoustic exposures.

In vitro characterization of perfluorocarbon droplets for focused ultrasound therapy.

PubMed

Schad, Kelly C; Hynynen, Kullervo

2010-09-07

Focused ultrasound therapy can be enhanced with microbubbles by thermal and cavitation effects. However, localization of treatment is difficult as bioeffects can occur outside of the target region. Spatial control of bubbles can be achieved by ultrasound-induced conversion of liquid perfluorocarbon droplets to gas bubbles. This study was undertaken to determine the acoustic parameters for bubble production by droplet conversion and how it depends on the acoustic conditions and droplet physical parameters. Lipid-encapsulated droplets containing dodecafluoropentane were manufactured with sizes ranging from 1.9 to 7.2 microm in diameter and diluted to a concentration of 8 x 10(6) droplets mL(-1). The droplets were sonicated in vitro with a focused ultrasound transducer and varying frequency and exposure under flow conditions through an acoustically transparent vessel. The sonications were 10 ms in duration at frequencies of 0.578, 1.736 and 2.855 MHz. The pressure threshold for droplet conversion was measured with an active transducer operating in pulse-echo mode and simultaneous measurements of broadband acoustic emissions were performed with passive acoustic detection. The results show that droplets cannot be converted at low frequency without broadband emissions occurring. However, the pressure threshold for droplet conversion decreased with increasing frequency, exposure and droplet size. The pressure threshold for broadband emissions was independent of the droplet size and was 2.9, 4.4 and 5.3 MPa for 0.578, 1736 and 2.855 MHz, respectively. In summary, we have demonstrated that droplet conversion is feasible for clinically relevant sized droplets and acoustic exposures.

Computational exploration of wave propagation and heating from transcranial focused ultrasound for neuromodulation

NASA Astrophysics Data System (ADS)

Mueller, Jerel K.; Ai, Leo; Bansal, Priya; Legon, Wynn

2016-10-01

Objective. While ultrasound is largely established for use in diagnostic imaging, its application for neuromodulation is relatively new and crudely understood. The objective of the present study was to investigate the effects of tissue properties and geometry on the wave propagation and heating in the context of transcranial neuromodulation. Approach. A computational model of transcranial-focused ultrasound was constructed and validated against empirical data. The models were then incrementally extended to investigate a number of issues related to the use of ultrasound for neuromodulation, including the effect on wave propagation of variations in geometry of skull and gyral anatomy as well as the effect of multiple tissue and media layers, including scalp, skull, CSF, and gray/white matter. In addition, a sensitivity analysis was run to characterize the influence of acoustic properties of intracranial tissues. Finally, the heating associated with ultrasonic stimulation waveforms designed for neuromodulation was modeled. Main results. The wave propagation of a transcranially focused ultrasound beam is significantly influenced by the cranial domain. The half maximum acoustic beam intensity profiles are insensitive overall to small changes in material properties, though the inclusion of sulci in models results in greater peak intensity values compared to a model without sulci (1%-30% greater). Finally, heating using currently employed stimulation parameters in humans is highest in bone (0.16 °C) and is negligible in brain (4.27 × 10-3 °C) for a 0.5 s exposure. Significance. Ultrasound for noninvasive neuromodulation holds great promise and appeal for its non-invasiveness, high spatial resolution and deep focal lengths. Here we show gross brain anatomy and biological material properties to have limited effect on ultrasound wave propagation and to result in safe heating levels in the skull and brain.

Computational exploration of wave propagation and heating from transcranial focused ultrasound for neuromodulation.

PubMed

Mueller, Jerel K; Ai, Leo; Bansal, Priya; Legon, Wynn

2016-10-01

While ultrasound is largely established for use in diagnostic imaging, its application for neuromodulation is relatively new and crudely understood. The objective of the present study was to investigate the effects of tissue properties and geometry on the wave propagation and heating in the context of transcranial neuromodulation. A computational model of transcranial-focused ultrasound was constructed and validated against empirical data. The models were then incrementally extended to investigate a number of issues related to the use of ultrasound for neuromodulation, including the effect on wave propagation of variations in geometry of skull and gyral anatomy as well as the effect of multiple tissue and media layers, including scalp, skull, CSF, and gray/white matter. In addition, a sensitivity analysis was run to characterize the influence of acoustic properties of intracranial tissues. Finally, the heating associated with ultrasonic stimulation waveforms designed for neuromodulation was modeled. The wave propagation of a transcranially focused ultrasound beam is significantly influenced by the cranial domain. The half maximum acoustic beam intensity profiles are insensitive overall to small changes in material properties, though the inclusion of sulci in models results in greater peak intensity values compared to a model without sulci (1%-30% greater). Finally, heating using currently employed stimulation parameters in humans is highest in bone (0.16 °C) and is negligible in brain (4.27 × 10(-3) °C) for a 0.5 s exposure. Ultrasound for noninvasive neuromodulation holds great promise and appeal for its non-invasiveness, high spatial resolution and deep focal lengths. Here we show gross brain anatomy and biological material properties to have limited effect on ultrasound wave propagation and to result in safe heating levels in the skull and brain.

MR-guided adaptive focusing of ultrasound

PubMed Central

Larrat, Benoît; Pernot, Mathieu; Montaldo, Gabriel; Fink, Mathias; Tanter, Mickaël

2010-01-01

Adaptive focusing of ultrasonic waves under the guidance of a Magnetic Resonance (MR) system is demonstrated for medical applications. This technique is based on the maximization of the ultrasonic wave intensity at one targeted point in space. The wave intensity is indirectly estimated from the local tissue displacement induced at the chosen focus by the acoustic radiation force of ultrasonic beams. Coded ultrasonic waves are transmitted by an ultrasonic array and an MRI scanner is used to measure the resulting local displacements through a motion sensitive MR sequence. After the transmission of a set of spatially encoded ultrasonic waves, a non iterative inversion process is employed to accurately estimate the spatial-temporal aberration induced by the propagation medium and to maximize the acoustical intensity at the target. Both programmable and physical aberrating layers introducing strong distortions (up to 2π radians) were recovered within acceptable errors (<0.8 rad). This non invasive technique is shown to accurately correct phase aberrations in a phantom gel with negligible heat deposition and limited acquisition time. These refocusing performances demonstrate a major potential in the field of MR-Guided Ultrasound Therapy in particular for transcranial brain HIFU. PMID:20704061

Application of MR-guided focused pulsed ultrasound for destroying clots in vitro using thrombolytic drugs

NASA Astrophysics Data System (ADS)

Hadjisavvas, V.; Ioannides, K.; Damianou, C.

2011-09-01

In this paper an MR-guided focused pulsed ultrasound system for the treatment of stroke using thrombolytic drugs in a model in vitro is presented. A single element spherically focused transducer of 5 cm diameter; focusing at 10 cm and operating at 0.5 MHz or 1 MHz was used. The transducer was mounted in an MR compatible robot. The artery was modelled using a silicone tube. Tissue was modelled using polyaclylimide gel. Coagulated blood was used to model thrombus. A thermocouple was placed in the thrombus in order to measure the thrombus temperature. The effect of power, beam, and frequency was investigated. The goal was to maintain a temperature increase of less than 1 °C during the application of pulse ultrasound (called safe temperature). With the application of ultrasound alone there was no notable destruction of the thrombus. With the combination of ultrasound and thrombolytic drugs destruction occurred after 60 mins of pulse exposure (PRF = 1 s, duty factor = 10%, and with thrombus placed at 1 cm deep in the tissue). This simple in vitro model was proven very successful for evaluating MRgFUS as a modality for treating stroke. In the future we plan to apply this treatment protocol in live animals and humans.

Optimization of real-time acoustical and mechanical monitoring of high intensity focused ultrasound (HIFU) treatment using harmonic motion imaging for high focused ultrasound (HMIFU).

PubMed

Hou, Gary Y; Marquet, Fabrice; Wang, Shutao; Konofagou, Elisa E

2013-01-01

Harmonic Motion Imaging (HMI) for Focused Ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in silica, in vitro and in vivo. Its principle is based on emission of an Amplitude-modulated therapeutic ultrasound beam utilizing a therapeutic transducer to induce an oscillatory radiation force while tracking the focal tissue mechanical response during the HIFU treatment using a confocally-aligned diagnostic transducer. In order to translate towards the clinical implementation of HMIFU, a complete assessment study is required in order to investigate the optimal radiation force threshold for reliable monitoring the local tissue mechanical property changes, i.e., the estimation HMIFU displacement under thermal, acoustical, and mechanical effects within focal medium (i.e., boiling, cavitation, and nonlinearity) using biological specimen. In this study, HMIFU technique is applied on HIFU treatment monitoring on freshly excised ex vivo canine liver specimens. In order to perform the multi-characteristic assessment, the diagnostic transducer was operated as either a pulse-echo imager or Passive Cavitation Detector (PCD) to assess the acoustic and mechanical response, while a bare-wire thermocouple was used to monitor the focal temperature change. As the acoustic power of HIFU treatment was ranged from 2.3 to 11.4 W, robust HMI displacement was observed across the entire range. Moreover, an optimized range for high quality displacement monitoring was found to be between 3.6 to 5.2W, where displacement showed an increase followed by significant decrease, indicating a stiffening of focal medium due to thermal lesion formation, while the correlation coefficient was maintained above 0.95.

A collimated focused ultrasound beam of high acoustic transmission and minimum diffraction achieved by using a lens with subwavelength structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Zhou; Tu, Juan; Cheng, Jianchun

An acoustic focusing lens incorporated with periodically aligned subwavelength grooves corrugated on its spherical surface has been developed. It is demonstrated theoretically and experimentally that acoustic focusing achieved by using the lens can suppress the relative side-lobe amplitudes, enhance the focal gain, and minimize the shifting of the focus. Use of the lens coupled with a planar ultrasound transducer can generate an ultrasound beam with enhanced acoustic transmission and collimation effect, which offers the capability of improving the safety, efficiency, and accuracy of targeted surgery implemented by high intensity focused ultrasound.

High-intensity focused ultrasound in obstetrics and gynecology: the birth of a new era of noninvasive surgery?

PubMed

Griffiths, A; terHaar, G; Rivens, I; Giussani, D; Lees, C

2012-12-01

Although ultrasound is an essential investigative modality in obstetrics and gynecology, the potential for therapeutic high-intensity focused ultrasound (HIFU) (also referred to as focused ultrasound surgery, FUS) to offer an alternative to invasive surgery is less well known. The ability of HIFU to create discrete regions of tissue necrosis only in precisely targeted positions by careful placement of the focus, without the need for any surgical intervention, has made HIFU of interest to those seeking noninvasive alternatives to conventional abdominal surgery. This article reviews the current experimental and clinical experience with HIFU in obstetrics and gynecology, and outlines potential future applications in fetal medicine and the challenges faced in their development. © Georg Thieme Verlag KG Stuttgart · New York.

An Rf Focused Interdigital Ion Accelerating Structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swenson, D.A.

2003-08-26

An Rf Focused Interdigital (RFI) ion accelerating structure will be described. It represents an effective combination of the Wideroee (or interdigital) linac structure, used for many low frequency, heavy ion applications, and the rf electric quadrupole focusing used in the RFQ and RFD linac structures. As in the RFD linac structure, rf focusing is introduced into the RFI linac structure by configuring the drift tubes as two independent pieces operating at different electrical potentials as determined by the rf fields of the linac structure. Each piece (or electrode) of the RFI drift tube supports two fingers pointed inwards towards themore » opposite end of the drift tube forming a four-finger geometry that produces an rf quadrupole field along the axis of the linac for focusing the beam. However, because of the differences in the rf field configuration along the axis, the scheme for introducing rf focusing into the interdigital linac structure is quite different from that adopted for the RFD linac structure. The RFI linac structure promises to have significant size, efficiency, performance, and cost advantages over existing linac structures for the acceleration of low energy ion beams of all masses (light to heavy). These advantages will be reviewed. A 'cold model' of this new linac structure has been fabricated and the results of rf cavity measurements on this cold model will be presented.« less

Analytical estimation of ultrasound properties, thermal diffusivity, and perfusion using magnetic resonance-guided focused ultrasound temperature data

PubMed Central

Dillon, C R; Borasi, G; Payne, A

2016-01-01

For thermal modeling to play a significant role in treatment planning, monitoring, and control of magnetic resonance-guided focused ultrasound (MRgFUS) thermal therapies, accurate knowledge of ultrasound and thermal properties is essential. This study develops a new analytical solution for the temperature change observed in MRgFUS which can be used with experimental MR temperature data to provide estimates of the ultrasound initial heating rate, Gaussian beam variance, tissue thermal diffusivity, and Pennes perfusion parameter. Simulations demonstrate that this technique provides accurate and robust property estimates that are independent of the beam size, thermal diffusivity, and perfusion levels in the presence of realistic MR noise. The technique is also demonstrated in vivo using MRgFUS heating data in rabbit back muscle. Errors in property estimates are kept less than 5% by applying a third order Taylor series approximation of the perfusion term and ensuring the ratio of the fitting time (the duration of experimental data utilized for optimization) to the perfusion time constant remains less than one. PMID:26741344

Acoustic characterization of Thiel liver for magnetic resonance-guided focused ultrasound treatment.

PubMed

Karakitsios, Ioannis; Joy, Joyce; Mihcin, Senay; Melzer, Andreas

2017-04-01

The purpose of this work was to measure the essential acoustic parameters, i.e., acoustic impedance, reflection coefficient, attenuation coefficient, of Thiel embalmed human and animal liver. The Thiel embalmed tissue can be a promising, pre-clinical model to study liver treatment with Magnetic Resonance-guided Focused Ultrasound (MRgFUS). Using a single-element transducer and the contact pulse-echo method, the acoustic parameters, i.e., acoustic impedance, reflection coefficient and attenuation coefficient of Thiel embalmed human and animal liver were measured. The Thiel embalmed livers had higher impedance, similar reflection and lower attenuation compared to the fresh tissue. Embalming liver with Thiel fluid affects its acoustic properties. During MRgFUS sonication of a Thiel organ, more focused ultrasound (FUS) will be backscattered by the organ, and higher acoustic powers are required to reach coagulation levels (temperatures >56 °C).

Ultrasound window-modulated compounding Nakagami imaging: Resolution improvement and computational acceleration for liver characterization.

PubMed

Ma, Hsiang-Yang; Lin, Ying-Hsiu; Wang, Chiao-Yin; Chen, Chiung-Nien; Ho, Ming-Chih; Tsui, Po-Hsiang

2016-08-01

Ultrasound Nakagami imaging is an attractive method for visualizing changes in envelope statistics. Window-modulated compounding (WMC) Nakagami imaging was reported to improve image smoothness. The sliding window technique is typically used for constructing ultrasound parametric and Nakagami images. Using a large window overlap ratio may improve the WMC Nakagami image resolution but reduces computational efficiency. Therefore, the objectives of this study include: (i) exploring the effects of the window overlap ratio on the resolution and smoothness of WMC Nakagami images; (ii) proposing a fast algorithm that is based on the convolution operator (FACO) to accelerate WMC Nakagami imaging. Computer simulations and preliminary clinical tests on liver fibrosis samples (n=48) were performed to validate the FACO-based WMC Nakagami imaging. The results demonstrated that the width of the autocorrelation function and the parameter distribution of the WMC Nakagami image reduce with the increase in the window overlap ratio. One-pixel shifting (i.e., sliding the window on the image data in steps of one pixel for parametric imaging) as the maximum overlap ratio significantly improves the WMC Nakagami image quality. Concurrently, the proposed FACO method combined with a computational platform that optimizes the matrix computation can accelerate WMC Nakagami imaging, allowing the detection of liver fibrosis-induced changes in envelope statistics. FACO-accelerated WMC Nakagami imaging is a new-generation Nakagami imaging technique with an improved image quality and fast computation. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative ultrasound imaging for monitoring in situ high-intensity focused ultrasound exposure.

PubMed

Ghoshal, Goutam; Kemmerer, Jeremy P; Karunakaran, Chandra; Abuhabsah, Rami; Miller, Rita J; Sarwate, Sandhya; Oelze, Michael L

2014-10-01

Quantitative ultrasound (QUS) imaging is hypothesized to map temperature elevations induced in tissue with high spatial and temporal resolution. To test this hypothesis, QUS techniques were examined to monitor high-intensity focused ultrasound (HIFU) exposure of tissue. In situ experiments were conducted on mammary adenocarcinoma tumors grown in rats and lesions were formed using a HIFU system. A thermocouple was inserted into the tumor to provide estimates of temperature at one location. Backscattered time-domain waveforms from the tissue during exposure were recorded using a clinical ultrasonic imaging system. Backscatter coefficients were estimated using a reference phantom technique. Two parameters were estimated from the backscatter coefficient (effective scatterer diameter (ESD) and effective acoustic concentration (EAC). The changes in the average parameters in the regions corresponding to the HIFU focus over time were correlated to the temperature readings from the thermocouple. The changes in the EAC parameter were consistently correlated to temperature during both heating and cooling of the tumors. The changes in the ESD did not have a consistent trend with temperature. The mean ESD and EAC before exposure were 120 ± 16 μm and 32 ± 3 dB/cm3, respectively, and changed to 144 ± 9 μm and 51 ± 7 dB/cm3, respectively, just before the last HIFU pulse was delivered to the tissue. After the tissue cooled down to 37 °C, the mean ESD and EAC were 126 ± 8 μm and 35 ± 4 dB/cm3, respectively. Peak temperature in the range of 50-60 °C was recorded by a thermocouple placed just behind the tumor. These results suggest that QUS techniques have the potential to be used for non-invasive monitoring of HIFU exposure. © The Author(s) 2014.

High-intensity focused ultrasound (HIFU) array system for image-guided ablative therapy (IGAT)

NASA Astrophysics Data System (ADS)

Kaczkowski, Peter J.; Keilman, George W.; Cunitz, Bryan W.; Martin, Roy W.; Vaezy, Shahram; Crum, Lawrence A.

2003-06-01

Recent interest in using High Intensity Focused Ultrasound (HIFU) for surgical applications such as hemostasis and tissue necrosis has stimulated the development of image-guided systems for non-invasive HIFU therapy. Seeking an all-ultrasound therapeutic modality, we have developed a clinical HIFU system comprising an integrated applicator that permits precisely registered HIFU therapy delivery and high quality ultrasound imaging using two separate arrays, a multi-channel signal generator and RF amplifier system, and a software program that provides the clinician with a graphical overlay of the ultrasound image and therapeutic protocol controls. Electronic phasing of a 32 element 2 MHz HIFU annular array allows adjusting the focus within the range of about 4 to 12 cm from the face. A central opening in the HIFU transducer permits mounting a commercial medical imaging scanhead (ATL P7-4) that is held in place within a special housing. This mechanical fixture ensures precise coaxial registration between the HIFU transducer and the image plane of the imaging probe. Recent enhancements include development of an acoustic lens using numerical simulations for use with a 5-element array. Our image-guided therapy system is very flexible and enables exploration of a variety of new HIFU therapy delivery and monitoring approaches in the search for safe, effective, and efficient treatment protocols.

Magnetic resonance-guided focused ultrasound surgery for treatment of painful osseous metastases

NASA Astrophysics Data System (ADS)

Hurwitz, Mark; Machtinger, Ronit; Fennessy, Fiona

2011-03-01

Magnetic resonance guided focused ultrasound surgery (MRgFUS) is an emerging technology that can non-invasively heat and ablate targeted tissue utilizing ultrasound energy. Use of MR imaging for treatment guidance provides several key advantages over more widely used ultrasound guidance for focused ultrasound ablation. MR allows for precise targeting, detailed beam path visualization, real time non-invasive temperature measurement, and treatment feedback to ensure therapeutic goals are achieved. In the realm of oncology, management of painful bone metastases is a common and daunting clinical problem. The Insightec ExAblate System has been shown in phase I/II trials for treatment of bone metastases to have an excellent safety profile and high rates of pain response. An international multi-center phase III trial for patients with painful bone metastases or multiple myeloma who are not candidates for radiation therapy is currently open. Patients are randomized 3:1 to MRgFUS or sham treatment with crossover to study treatment allowed for sham failures. The primary study endpoint is assessment of pain control over 3 months following treatment. In addition safety, quality of life, cost effectiveness analysis, and patient perceived clinical benefit are also being assessed. Details of the MRgFUS system, technical and clinical therapeutic parameters, use of real time non-invasive MR thermometry, and examples of patient treatments with use of MRgFUS to treat bone metastases will be discussed. New directions in use of MRgFUS including an update on development of a new mobile applicator and integration of MRgFUS in multimodality oncologic care will also be presented.

MRI-Guided Focused Ultrasound Surgery

PubMed Central

Jolesz, Ferenc A.

2014-01-01

MRI-guided focused ultrasound (MRgFUS) surgery is a noninvasive thermal ablation method that uses magnetic resonance imaging (MRI) for target definition, treatment planning, and closed-loop control of energy deposition. Integrating FUS and MRI as a therapy delivery system allows us to localize, target, and monitor in real time, and thus to ablate targeted tissue without damaging normal structures. This precision makes MRgFUS an attractive alternative to surgical resection or radiation therapy of benign and malignant tumors. Already approved for the treatment of uterine fibroids, MRgFUS is in ongoing clinical trials for the treatment of breast, liver, prostate, and brain cancer and for the palliation of pain in bone metastasis. In addition to thermal ablation, FUS, with or without the use of microbubbles, can temporarily change vascular or cell membrane permeability and release or activate various compounds for targeted drug delivery or gene therapy. A disruptive technology, MRgFUS provides new therapeutic approaches and may cause major changes in patient management and several medical disciplines. PMID:19630579

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

PubMed

Yu, Ying; Shen, Guofeng; Zhou, Yufeng; Bai, Jingfeng; Chen, Yazhu

2013-11-01

With the popularity of ultrasound therapy in clinics, characterization of the acoustic field is important not only to the tolerability and efficiency of ablation, but also for treatment planning. A quantitative method was introduced to assess the intensity distribution of a focused ultrasound beam using a hydrophone and an infrared camera with no prior knowledge of the acoustic and thermal parameters of the absorber or the configuration of the array elements. This method was evaluated in both theoretical simulations and experimental measurements. A three-layer model was developed to calculate the acoustic field in the absorber, the absorbed acoustic energy during the sonication and the consequent temperature elevation. Experiments were carried out to measure the acoustic pressure with the hydrophone and the temperature elevation with the infrared camera. The percentage differences between the derived results and the simulation are <4.1% for on-axis intensity and <21.1% for -6-dB beam width at heating times up to 360 ms in the focal region of three phased-array ultrasound transducers using two different absorbers. The proposed method is an easy, quick and reliable approach to calibrating focused ultrasound transducers with satisfactory accuracy. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

MR-Guided Pulsed High-Intensity Focused Ultrasound Enhancement of Gene Therapy Combined With Androgen Deprivation and Radiotherapy for Prostate Cancer Treatment

DTIC Science & Technology

2009-09-01

first statement of work is to determine if high intensity focused ultrasound ( HIFU ) increases the cellular uptake of AS-MDM2, AS-bcl-2 and AS-PKA...Drug Delivery in Prostate Tumor in vivo Using MR Guided Focused Ultrasound (MRg HIFU ). WC, IFMBE Proceedings 25: pp341-344, 2009 6...pharmaceutical agents in the treatment target. In the model system proposed, pulsed high intensity focused ultrasound ( HIFU ) is hypothesized to improve

Integrated ultrasound and magnetic resonance imaging for simultaneous temperature and cavitation monitoring during focused ultrasound therapies

PubMed Central

Arvanitis, Costas D.; McDannold, Nathan

2013-01-01

Purpose: Ultrasound can be used to noninvasively produce different bioeffects via viscous heating, acoustic cavitation, or their combination, and these effects can be exploited to develop a wide range of therapies for cancer and other disorders. In order to accurately localize and control these different effects, imaging methods are desired that can map both temperature changes and cavitation activity. To address these needs, the authors integrated an ultrasound imaging array into an MRI-guided focused ultrasound (MRgFUS) system to simultaneously visualize thermal and mechanical effects via passive acoustic mapping (PAM) and MR temperature imaging (MRTI), respectively. Methods: The system was tested with an MRgFUS system developed for transcranial sonication for brain tumor ablation in experiments with a tissue mimicking phantom and a phantom-filled ex vivo macaque skull. In experiments on cavitation-enhanced heating, 10 s continuous wave sonications were applied at increasing power levels (30–110 W) until broadband acoustic emissions (a signature for inertial cavitation) were evident. The presence or lack of signal in the PAM, as well as its magnitude and location, were compared to the focal heating in the MRTI. Additional experiments compared PAM with standard B-mode ultrasound imaging and tested the feasibility of the system to map cavitation activity produced during low-power (5 W) burst sonications in a channel filled with a microbubble ultrasound contrast agent. Results: When inertial cavitation was evident, localized activity was present in PAM and a marked increase in heating was observed in MRTI. The location of the cavitation activity and heating agreed on average after registration of the two imaging modalities; the distance between the maximum cavitation activity and focal heating was −3.4 ± 2.1 mm and −0.1 ± 3.3 mm in the axial and transverse ultrasound array directions, respectively. Distortions and other MRI issues introduced small

Integrated ultrasound and magnetic resonance imaging for simultaneous temperature and cavitation monitoring during focused ultrasound therapies.

PubMed

Arvanitis, Costas D; McDannold, Nathan

2013-11-01

Ultrasound can be used to noninvasively produce different bioeffects via viscous heating, acoustic cavitation, or their combination, and these effects can be exploited to develop a wide range of therapies for cancer and other disorders. In order to accurately localize and control these different effects, imaging methods are desired that can map both temperature changes and cavitation activity. To address these needs, the authors integrated an ultrasound imaging array into an MRI-guided focused ultrasound (MRgFUS) system to simultaneously visualize thermal and mechanical effects via passive acoustic mapping (PAM) and MR temperature imaging (MRTI), respectively. The system was tested with an MRgFUS system developed for transcranial sonication for brain tumor ablation in experiments with a tissue mimicking phantom and a phantom-filled ex vivo macaque skull. In experiments on cavitation-enhanced heating, 10 s continuous wave sonications were applied at increasing power levels (30-110 W) until broadband acoustic emissions (a signature for inertial cavitation) were evident. The presence or lack of signal in the PAM, as well as its magnitude and location, were compared to the focal heating in the MRTI. Additional experiments compared PAM with standard B-mode ultrasound imaging and tested the feasibility of the system to map cavitation activity produced during low-power (5 W) burst sonications in a channel filled with a microbubble ultrasound contrast agent. When inertial cavitation was evident, localized activity was present in PAM and a marked increase in heating was observed in MRTI. The location of the cavitation activity and heating agreed on average after registration of the two imaging modalities; the distance between the maximum cavitation activity and focal heating was -3.4 ± 2.1 mm and -0.1 ± 3.3 mm in the axial and transverse ultrasound array directions, respectively. Distortions and other MRI issues introduced small uncertainties in the PAM�

Laser-enhanced thermal effect of moderate intensity focused ultrasound on bio-tissues

NASA Astrophysics Data System (ADS)

Zhao, JinYu; Zhang, ShuYi; Shui, XiuJi; Fan, Li

2017-09-01

For avoiding extra-damage to healthy tissues surrounding the focal point during high intensity focused ultrasound (HIFU) treatment in medical therapy, to reduce the ultrasonic intensity outside the focal point is expected. Thus, the heating processes induced by moderate intensity focused ultrasound (MIFU) and enhanced by combined irradiation of laser pulses for bio-tissues are studied in details. For fresh bio-tissues, the enhanced thermal effects by pulsed laser combined with MIFU irradiation are observed experimentally. To explore the mechanisms of these effects, several tissue-mimicking materials composed of agar mixed with graphite powders are prepared and studied for comparison, but the laser-enhanced thermal effects in these mimicking materials are much less than that in the fresh bio-tissues. Therefore, it is suggested that the laser-enhanced thermal effects may be mainly attributed to bio-activities and related photo-bio-chemical effects of fresh tissues.

Controlled tissue emulsification produced by high intensity focused ultrasound shock waves and millisecond boiling

PubMed Central

Khokhlova, Tatiana D.; Canney, Michael S.; Khokhlova, Vera A.; Sapozhnikov, Oleg A.; Crum, Lawrence A.; Bailey, Michael R.

2011-01-01

In high intensity focused ultrasound (HIFU) applications, tissue may be thermally necrosed by heating, emulsified by cavitation, or, as was recently discovered, emulsified using repetitive millisecond boiling caused by shock wave heating. Here, this last approach was further investigated. Experiments were performed in transparent gels and ex vivo bovine heart tissue using 1, 2, and 3 MHz focused transducers and different pulsing schemes in which the pressure, duty factor, and pulse duration were varied. A previously developed derating procedure to determine in situ shock amplitudes and the time-to-boil was refined. Treatments were monitored using B-mode ultrasound. Both inertial cavitation and boiling were observed during exposures, but emulsification occurred only when shocks and boiling were present. Emulsified lesions without thermal denaturation were produced with shock amplitudes sufficient to induce boiling in less than 20 ms, duty factors of less than 0.02, and pulse lengths shorter than 30 ms. Higher duty factors or longer pulses produced varying degrees of thermal denaturation combined with mechanical emulsification. Larger lesions were obtained using lower ultrasound frequencies. The results show that shock wave heating and millisecond boiling is an effective and reliable way to emulsify tissue while monitoring the treatment with ultrasound. PMID:22088025

Using High Frequency Focused Water-Coupled Ultrasound for 3-D Surface Depression Profiling

NASA Technical Reports Server (NTRS)

Roth, Don J.; Whalen, Mike F.; Hendricks, J. Lynne; Bodis, James R.

1999-01-01

Surface topography is an important variable in the performance of many industrial components and is normally measured with diamond-tip profilometry over a small area or using optical scattering methods for larger area measurement. A prior study was performed demonstrating that focused air-coupled ultrasound at 1 MHz was capable of profiling surfaces with 25 micron depth resolution and 400 micron lateral resolution over a 1.4 mm depth range. In this article, the question of whether higher-frequency focused water-coupled ultrasound can improve on these specifications is addressed. 10 and 25 MHz focused ultrasonic transducers were employed in the water-coupled mode. Time-of-flight images of the sample surface were acquired and converted to depth / surface profile images using the simple relation (d = V*t/2) between distance (d), time-of-flight (t), and the velocity of sound in water (V). Results are compared for the two frequencies used and with those from the 1 MHz air-coupled configuration.

Treatment of Parkinson's disease in rats by Nrf2 transfection using MRI-guided focused ultrasound delivery of nanomicrobubbles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Long, Ling; Cai, Xiaodong; Guo, Ruomi

Parkinson's disease (PD) is a very common neurological disorder. However, effective therapy is lacking. Although the blood-brain-barrier (BBB) protects the brain, it prevents the delivery of about 90% of drugs and nucleotides into the brain, thereby hindering the development of gene therapy for PD. Magnetic resonance imaging (MRI)-guided focused ultrasound delivery of microbubbles enhances the delivery of gene therapy vectors across the BBB and improves transfection efficiency. In the present study, we delivered nuclear factor E2-related factor 2 (Nrf2, NFE2L2) contained in nanomicrobubbles into the substantia nigra of PD rats by MRI-guided focused ultrasound, and we examined the effect ofmore » Nrf2 over-expression in this animal model of PD. The rat model of PD was established by injecting 6-OHDA in the right substantia nigra stereotactically. Plasmids (pDC315 or pDC315/Nrf2) were loaded onto nanomicrobubbles, and then injected through the tail vein with the assistance of MRI-guided focused ultrasound. MRI-guided focused ultrasound delivery of nanomicrobubbles increased gene transfection efficiency. Furthermore, Nrf2 gene transfection reduced reactive oxygen species levels, thereby protecting neurons in the target region. - Highlights: • MRI-guided focused ultrasound enhances gene transfection into the brain of rats. • Increased Nrf2 expression protects neurons in the rat model of PD. • Nrf2 protects neurons in PD by inhibiting ROS production.« less

A scanned focused ultrasound device for hyperthermia: numerical simulation and prototype implementation

NASA Astrophysics Data System (ADS)

Meaney, Paul M.; Raynolds, Timothy; Geimer, Shireen D.; Potwin, Lincoln; Paulsen, Keith D.

2004-07-01

We are developing a scanned focused ultrasound system for hyperthermia treatment of breast cancer. Focused ultrasound has significant potential as a therapy delivery device because it can focus sufficient heating energy below the skin surface with minimal damage to intervening tissue. However, as a practical therapy system, the focal zone is generally quite small and requires either electronic (in the case of a phased array system) or mechanical steering (for a fixed bowl transducer) to cover a therapeutically useful area. We have devised a simple automated steering system consisting of a focused bowl transducer supported by three vertically movable rods which are connected to computer controlled linear actuators. This scheme is particularly attractive for breast cancer hyperthermia where the support rods can be fed through the base of a liquid coupling tank to treat tumors within the breast while coupled to our noninvasive microwave thermal imaging system. A MATLAB routine has been developed for controlling the rod motion such that the beam focal point scans a horizontal spiral and the subsequent heating zone is cylindrical. In coordination with this effort, a 3D finite element thermal model has been developed to evaluate the temperature distributions from the scanned focused heating. In this way, scanning protocols can be optimized to deliver the most uniform temperature rise to the desired location.

Noninvasive thermal ablation of hepatocellular carcinoma by using magnetic resonance imaging-guided focused ultrasound.

PubMed

Jolesz, Ferenc A; Hynynen, Kullervo; McDannold, Nathan; Freundlich, David; Kopelman, Doron

2004-11-01

A number of minimally invasive methods have been tested for the thermal ablation of liver tumors as an alternative to surgical resection. The use of focused ultrasound transducers to ablate deep tumors offers the first completely noninvasive alternative to these techniques. By increasing the flexibility of this technology with modern phased-array transducer design and by combining it with magnetic resonance imaging for targeting and online guidance, a powerful tool results with the potential to offer treatment to a larger population of patients, to reduce trauma to the patient, and to reduce the cost of treatment. In this article, we review previous work with focused ultrasound in the liver and recent experimental results with magnetic resonance imaging guidance.

Ultrasonic atomization of tissue and its role in tissue fractionation by high intensity focused ultrasound

PubMed Central

Simon, Julianna C.; Sapozhnikov, Oleg A.; Khokhlova, Vera A.; Wang, Yak-Nam; Crum, Lawrence A.; Bailey, Michael R.

2012-01-01

Atomization and fountain formation is a well-known phenomenon that occurs when a focused ultrasound wave in liquid encounters an air interface. High intensity focused ultrasound (HIFU) has been shown to fractionate tissue into submicron-size fragments in a process termed boiling histotripsy, wherein the focused ultrasound wave superheats the tissue at the focus, producing a millimetre-size boiling or vapour bubble in several milliseconds. Yet the question of how this millimetre-size boiling bubble creates submicron-size tissue fragments remains. The hypothesis of this work is that tissue can behave as a liquid such that it forms a fountain and atomization within the vapour bubble produced in boiling histotripsy. We describe an experiment, in which a 2-MHz HIFU transducer (maximum in situ intensity of 24,000 W/cm2) was aligned with an air-tissue interface meant to simulate the boiling bubble. Atomization and fountain formation were observed with high-speed photography and resulted in tissue erosion. Histological examination of the atomized tissue showed whole and fragmented cells and nuclei. Air-liquid interfaces were also filmed. Our conclusion was that HIFU can fountain and atomize tissue. Although this process does not entirely mimic what was observed in liquids, it does explain many aspects of tissue fractionation in boiling histotripsy. PMID:23159812

Integrated medical school ultrasound: development of an ultrasound vertical curriculum.

PubMed

Bahner, David P; Adkins, Eric J; Hughes, Daralee; Barrie, Michael; Boulger, Creagh T; Royall, Nelson A

2013-07-02

Physician-performed focused ultrasonography is a rapidly growing field with numerous clinical applications. Focused ultrasound is a clinically useful tool with relevant applications across most specialties. Ultrasound technology has outpaced the education, necessitating an early introduction to the technology within the medical education system. There are many challenges to integrating ultrasound into medical education including identifying appropriately trained faculty, access to adequate resources, and appropriate integration into existing medical education curricula. As focused ultrasonography increasingly penetrates academic and community practices, access to ultrasound equipment and trained faculty is improving. However, there has remained the major challenge of determining at which level is integrating ultrasound training within the medical training paradigm most appropriate. The Ohio State University College of Medicine has developed a novel vertical curriculum for focused ultrasonography which is concordant with the 4-year medical school curriculum. Given current evidenced-based practices, a curriculum was developed which provides medical students an exposure in focused ultrasonography. The curriculum utilizes focused ultrasonography as a teaching aid for students to gain a more thorough understanding of basic and clinical science within the medical school curriculum. The objectives of the course are to develop student understanding in indications for use, acquisition of images, interpretation of an ultrasound examination, and appropriate decision-making of ultrasound findings. Preliminary data indicate that a vertical ultrasound curriculum is a feasible and effective means of teaching focused ultrasonography. The foreseeable limitations include faculty skill level and training, initial cost of equipment, and incorporating additional information into an already saturated medical school curriculum. Focused ultrasonography is an evolving concept in medicine

Echocardiographic assessment with right ventricular function improvement following ultrasound-accelerated catheter-directed thrombolytic therapy in submassive pulmonary embolism.

PubMed

Doheny, Charles; Gonzalez, Lorena; Duchman, Stanley M; Varon, Joseph; Bechara, Carlos F; Cheung, Mathew; Lin, Peter H

2018-06-01

Introduction The objective of this study was to evaluate the efficacy of ultrasound-accelerated catheter-directed thrombolytic therapy in patients with submassive pulmonary embolism. Methods Clinical records of 46 patients with submassive pulmonary embolism who underwent ultrasound-accelerated catheter-directed pulmonary thrombolysis using tissue plasminogen activator, from 2007 to 2017, were analyzed. All patients experienced clinical symptoms with computed tomography evidence of pulmonary thrombus burden. Right ventricular dysfunction was present in all patients by echocardiographic finding of right ventricle-to-left ventricle ratio > 0.9. Treatment outcome, procedural complications, right ventricular pressures, and thrombus clearance were evaluated. Follow-up evaluation included echocardiographic assessment of right ventricle-to-left ventricle ratio at one month, six months, and one year. Results Technical success was achieved in all patients ( n = 46, 100%). Our patients received an average of 18.4 ± 4.7 mg of tissue plasminogen activator using ultrasound-accelerated thrombolytic catheter with an average infusion time of 16.5± 5.4 h. Clinical success was achieved in all patients (100%). Significant reduction of mean pulmonary artery pressure occurred following the treatment, which decreased from 36 ± 8 to 21 ± 5 mmHg ( p < 0.001). There were no major bleeding complications. All-cause mortality at 30 days was 0%. No patient developed recurrent pulmonary embolism during follow-up. During the follow-up period, 43 patients (93%) showed improvement of right ventricular dysfunction based on echocardiographic assessment. The right ventricle-to-left ventricle ratio decreased from 1.32 ± 0.18 to 0.91 ± 0.13 at the time of hospital discharge ( p < 0.01). The right ventricular function remained improved at 6 months and 12 months of follow-up, as right ventricle-to-left ventricle ratio were 0.92 ± 0.14 ( p < 0.01) and 0

Towards deep brain monitoring with superficial EEG sensors plus neuromodulatory focused ultrasound

PubMed Central

Darvas, F; Mehić, E; Caler, CJ; Ojemann, JG; Mourad, PD

2017-01-01

Noninvasive recordings of electrophysiological activity have limited anatomical specificity and depth. We hypothesized that spatially tagging a small volume of brain with a unique electroencephalogram (EEG) signal induced by pulsed focused ultrasound (pFU) could overcome those limitations. As a first step towards testing this hypothesis, we applied transcranial ultrasound (2 MHz, 200 microsecond-long pulses applied at 1050 Hz for one second at a spatial peak temporal average intensity of 1.4 W/cm2) to the brains of anesthetized rats while simultaneously recording EEG signals. We observed a significant 1050 Hz electrophysiological signal only when ultrasound was applied to living brain. Moreover, amplitude demodulation of the EEG signal at 1050 Hz yielded measurement of gamma band (>30 Hz) brain activity consistent with direct measurements of that activity. These results represent preliminary support for use of pFU as a spatial tagging mechanism for non-invasive EEG-based mapping of deep brain activity with high spatial resolution. PMID:27181686

Advances of high intensity focused ultrasound (HIFU) for pancreatic cancer.

PubMed

Xiaoping, Li; Leizhen, Zheng

2013-11-01

High intensity focused ultrasound (HIFU) is a novel therapeutic modality. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumours, including pancreatic cancer. Preliminary studies suggest that HIFU may be useful for the palliative therapy of cancer-related pain in patients with unresectable pancreatic cancer. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges.

Clinical factors analysis of curative effect of focused ultrasound treatment for non neoplastic epithelial disorders of vulva.

PubMed

Sun, Xin; Xue, Min; Deng, Xinliang; Wan, Yajun

2010-09-01

To explore the related factors to influence the curative effect of focused ultrasound treatment for non neoplastic epithelial disorders of vulva. A total of 382 patients with non neoplastic epithelial disorders of vulva were included in this study and treated by focused ultrasound. During and after the treatment, the symptoms and physical signs of the subjects were observed, and the efficacy was evaluated. We analyzed the relation between pathologic type, age, course, area, or itch degree and curative effect. Symptoms of all patients were relieved, and appearance and color of the vulva became normal after the ultrasound treatment, with a total effective rate of 99.74%. The cure ratios of patients with different pathologic types, ages, courses, areas, and itch degrees were significantly different (χ(2)=9.58, P<0.01; χ(2)=22.385, P<0.01; χ(2)=32.260, P<0.01; χ(2)=57.99,P<0.01; χ(2)=42.13,P<0.01, respectively). Focused ultrasound treatment is safe and effective for the nonneoplastic epithelial disorders of the vulva and the efficacy is associated with the pathologic type, age, course, area, and itch degree.

Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound.

PubMed

Bazan-Peregrino, Miriam; Rifai, Bassel; Carlisle, Robert C; Choi, James; Arvanitis, Costas D; Seymour, Leonard W; Coussios, Constantin C

2013-07-10

Oncolytic viruses (OV) and ultrasound-enhanced drug delivery are powerful novel technologies. OV selectively self-amplify and kill cancer cells but their clinical use has been restricted by limited delivery from the bloodstream into the tumor. Ultrasound has been previously exploited for targeted release of OV in vivo, but its use to induce cavitation, microbubble oscillations, for enhanced OV tumor extravasation and delivery has not been previously reported. By identifying and optimizing the underlying physical mechanism, this work demonstrates that focused ultrasound significantly enhances the delivery and biodistribution of systemically administered OV co-injected with microbubbles. Up to a fiftyfold increase in tumor transgene expression was achieved, without any observable tissue damage. Ultrasound exposure parameters were optimized as a function of tumor reperfusion time to sustain inertial cavitation, a type of microbubble activity, throughout the exposure. Passive detection of acoustic emissions during treatment confirmed inertial cavitation as the mechanism responsible for enhanced delivery and enabled real-time monitoring of successful viral delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

Microbubble gas volume: A unifying dose parameter in blood-brain barrier opening by focused ultrasound.

PubMed

Song, Kang-Ho; Fan, Alexander C; Hinkle, Joshua J; Newman, Joshua; Borden, Mark A; Harvey, Brandon K

2017-01-01

Focused ultrasound with microbubbles is being developed to transiently, locally and noninvasively open the blood-brain barrier (BBB) for improved pharmaceutical delivery. Prior work has demonstrated that, for a given concentration dose, microbubble size affects both the intravascular circulation persistence and extent of BBB opening. When matched to gas volume dose, however, the circulation half-life was found to be independent of microbubble size. In order to determine whether this holds true for BBB opening as well, we independently measured the effects of microbubble size (2 vs. 6 µm diameter) and concentration, covering a range of overlapping gas volume doses (1-40 µL/kg). We first demonstrated precise targeting and a linear dose-response of Evans Blue dye extravasation to the rat striatum for a set of constant microbubble and ultrasound parameters. We found that dye extravasation increased linearly with gas volume dose, with data points from both microbubble sizes collapsing to a single line. A linear trend was observed for both the initial sonication (R 2 =0.90) and a second sonication on the contralateral side (R 2 =0.68). Based on these results, we conclude that microbubble gas volume dose, not size, determines the extent of BBB opening by focused ultrasound (1 MHz, ~0.5 MPa at the focus). This result may simplify planning for focused ultrasound treatments by constraining the protocol to a single microbubble parameter - gas volume dose - which gives equivalent results for varying size distributions. Finally, using optimal parameters determined for Evan Blue, we demonstrated gene delivery and expression using a viral vector, dsAAV1-CMV-EGFP, one week after BBB disruption, which allowed us to qualitatively evaluate neuronal health.

[Effect of low-dose focused ultrasound pre-irradiation versus microbubbles for enhancing high-intensity focused ultrasound ablation of VX2 hepatic tumor in rabbits].

PubMed

Zhang, Yi; Yang, Chao; Zou, Jian-Zhong; Chen, Fei; Ou, Xia; Zou, Hai-Rong; Wang, Yan

2016-10-20

To compare the effect of low-dose focused ultrasound pre-irradiation and microbubbles for enhancing the ablation effect of high intensity focused ultrasound (HIFU) on VX 2 hepatic tumor in rabbits. Fifty-five rabbits bearing VX 2 hepatic tumor were randomly divided into low-dose pre-irradiation + HIFU ablation group, microbubbles+HIFU ablation group, and HIFU ablation group for corresponding treatments. The pathological changes in the tumors after low-dose irradiation, time for HIFU ablation, tumor volume with coagulative necrosis, energy efficiency factor (EEF), pathological changes in the ablated tumor, and sound channel of HIFU ablation were observed. Tumor cell edema, vacuolar changes in the cytoplasm and tumor interstitial vascular congestion were observed 24 h after low-dose pre-irradiation. The ablation time were significantly shorter, coagulative necrosis volume was larger, and EEF was lower in low-dose irradiation + HIFU ablation group and microbubbles+HIFU ablation group than in simple HIFU ablation group (P<0.05), but the differences between the former two groups were not significant. The effectiveness and stability of the synergistic effect of low-dose pre-irradiation were inferior to microbubbles, but the former ensured a better safety of the sound channel. Low-dose irradiation has comparable synergistic effect in HIFU with microbubbles with such advantages as non-invasiveness, high concentration and good safety, and can be a potentially new method to enhance the efficiency of HIFU.

Transvaginal 3D Image-Guided High Intensity Focused Ultrasound Array

NASA Astrophysics Data System (ADS)

Held, Robert; Nguyen, Thuc Nghi; Vaezy, Shahram

2005-03-01

The goal of this project is to develop a transvaginal image-guided High Intensity Focused Ultrasound (HIFU) device using piezocomposite HIFU array technology, and commercially-available ultrasound imaging. Potential applications include treatment of uterine fibroids and abnormal uterine bleeding. The HIFU transducer was an annular phased array, with a focal length range of 30-60 mm, an elliptically-shaped aperture of 35×60 mm, and an operating frequency of 3 MHz. A pillow-shaped bag with water circulation will be used for coupling the HIFU energy into the tissue. An intra-cavity imaging probe (C9-5, Philips) was integrated with the HIFU array such that the focal axis of the HIFU transducer was within the image plane. The entire device will be covered by a gel-filled condom when inserted in the vaginal cavity. To control it, software packages were developed in the LabView programming environment. An imaging algorithm processed the ultrasound image to remove noise patterns due to the HIFU signal. The device will be equipped with a three-dimensional tracking system, using a six-degrees-of-freedom articulating arm. Necrotic lesions were produced in a tissue-mimicking phantom and a turkey breast sample for all focal lengths. Various HIFU doses allow various necrotic lesion shapes, including thin ellipsoidal, spherical, wide cylindrical, and teardrop-shaped. Software control of the device allows multiple foci to be activated sequentially for desired lesion patterns. Ultrasound imaging synchronization can be achieved using hardware signals obtained from the imaging system, or software signals determined empirically for various imaging probes. The image-guided HIFU device will provide a valuable tool in visualization of uterine fibroid tumors for the purposes of planning and subsequent HIFU treatment of the tumor, all in a 3D environment. The control system allows for various lesions of different shapes to be optimally positioned in the tumor to cover the entire tumor

Simulation Studies of the Dielectric Grating as an Accelerating and Focusing Structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soong, Ken; Peralta, E.A.; Byer, R.L.

A grating-based design is a promising candidate for a laser-driven dielectric accelerator. Through simulations, we show the merits of a readily fabricated grating structure as an accelerating component. Additionally, we show that with a small design perturbation, the accelerating component can be converted into a focusing structure. The understanding of these two components is critical in the successful development of any complete accelerator. The concept of accelerating electrons with the tremendous electric fields found in lasers has been proposed for decades. However, until recently the realization of such an accelerator was not technologically feasible. Recent advances in the semiconductor industry,more » as well as advances in laser technology, have now made laser-driven dielectric accelerators imminent. The grating-based accelerator is one proposed design for a dielectric laser-driven accelerator. This design, which was introduced by Plettner, consists of a pair of opposing transparent binary gratings, illustrated in Fig. 1. The teeth of the gratings serve as a phase mask, ensuring a phase synchronicity between the electromagnetic field and the moving particles. The current grating accelerator design has the drive laser incident perpendicular to the substrate, which poses a laser-structure alignment complication. The next iteration of grating structure fabrication seeks to monolithically create an array of grating structures by etching the grating's vacuum channel into a fused silica wafer. With this method it is possible to have the drive laser confined to the plane of the wafer, thus ensuring alignment of the laser-and-structure, the two grating halves, and subsequent accelerator components. There has been previous work using 2-dimensional finite difference time domain (2D-FDTD) calculations to evaluate the performance of the grating accelerator structure. However, this work approximates the grating as an infinite structure and does not accurately model a

Transverse acoustic trapping using a Gaussian focused ultrasound

PubMed Central

Lee, Jungwoo; Teh, Shia-Yen; Lee, Abraham; Kim, Hyung Ham; Lee, Changyang; Shung, K. Kirk

2009-01-01

The optical tweezer has become a popular device to manipulate particles in nanometer scales, and to study the underlying principles of many cellular or molecular interactions. Theoretical analysis was previously carried out at the authors’ laboratory, to show that similar acoustic trapping of microparticles may be possible with a single beam ultrasound. This paper experimentally presents the transverse trapping of 125 μm lipid droplets under an acoustically transparent mylar film, which is an intermediate step toward achieving acoustic tweezers in 3D. Despite the lack of axial trapping capability in the current experimental arrangement, it was found that a 30 MHz focused beam could be used to laterally direct the droplets towards the focus. The spatial range within which acoustic traps may guide droplet motion was in the range of hundreds of micrometers, much greater than that of optical traps. This suggests that this acoustic device may offer an alternative for manipulating microparticles in a wider spatial range. PMID:20045590

Modes of elastic plates and shells in water driven by modulated radiation pressure of focused ultrasound

NASA Astrophysics Data System (ADS)

Marston, Philip L.; Daniel, Timothy D.; Abawi, Ahmad T.; Kirsteins, Ivars

2015-11-01

The modulated radiation pressure (MRP) of ultrasound has been used for decades to selectively excite low frequency modes associated with surface tension of fluid objects in water. Much less is known about the excitation of low frequency modes of less compliant metallic objects. Here we use MRP of focused ultrasound to excite resonant flexural vibrations of a circular metal plate in water. The source transducer was driven with a double-sideband suppressed carrier voltage as in. The response of the target (detected with a hydrophone) was at twice the modulation frequency and proportional to the square of the drive voltage. Since the radiation pressure of focused beams is spatially localized, mode shapes could be identified by scanning the source along the target while measuring the target's response. Additional measurements were done with an open-ended water-filled copper circular cylindrical shell in which resonant frequencies and mode shapes were also identified. These experiments show how focused ultrasound can be used to identify low-frequency modes of elastic objects without direct contact. Supported by ONR.

Real-time Monitoring of High Intensity Focused Ultrasound (HIFU) Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound (HMIFU).

PubMed

Grondin, Julien; Payen, Thomas; Wang, Shutao; Konofagou, Elisa E

2015-11-03

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a technique that can perform and monitor high-intensity focused ultrasound (HIFU) ablation. An oscillatory motion is generated at the focus of a 93-element and 4.5 MHz center frequency HIFU transducer by applying a 25 Hz amplitude-modulated signal using a function generator. A 64-element and 2.5 MHz imaging transducer with 68kPa peak pressure is confocally placed at the center of the HIFU transducer to acquire the radio-frequency (RF) channel data. In this protocol, real-time monitoring of thermal ablation using HIFU with an acoustic power of 7 W on canine livers in vitro is described. HIFU treatment is applied on the tissue during 2 min and the ablated region is imaged in real-time using diverging or plane wave imaging up to 1,000 frames/second. The matrix of RF channel data is multiplied by a sparse matrix for image reconstruction. The reconstructed field of view is of 90° for diverging wave and 20 mm for plane wave imaging and the data are sampled at 80 MHz. The reconstruction is performed on a Graphical Processing Unit (GPU) in order to image in real-time at a 4.5 display frame rate. 1-D normalized cross-correlation of the reconstructed RF data is used to estimate axial displacements in the focal region. The magnitude of the peak-to-peak displacement at the focal depth decreases during the thermal ablation which denotes stiffening of the tissue due to the formation of a lesion. The displacement signal-to-noise ratio (SNRd) at the focal area for plane wave was 1.4 times higher than for diverging wave showing that plane wave imaging appears to produce better displacement maps quality for HMIFU than diverging wave imaging.

Real-time Monitoring of High Intensity Focused Ultrasound (HIFU) Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound (HMIFU)

PubMed Central

Grondin, Julien; Payen, Thomas; Wang, Shutao; Konofagou, Elisa E.

2015-01-01

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a technique that can perform and monitor high-intensity focused ultrasound (HIFU) ablation. An oscillatory motion is generated at the focus of a 93-element and 4.5 MHz center frequency HIFU transducer by applying a 25 Hz amplitude-modulated signal using a function generator. A 64-element and 2.5 MHz imaging transducer with 68kPa peak pressure is confocally placed at the center of the HIFU transducer to acquire the radio-frequency (RF) channel data. In this protocol, real-time monitoring of thermal ablation using HIFU with an acoustic power of 7 W on canine livers in vitro is described. HIFU treatment is applied on the tissue during 2 min and the ablated region is imaged in real-time using diverging or plane wave imaging up to 1,000 frames/second. The matrix of RF channel data is multiplied by a sparse matrix for image reconstruction. The reconstructed field of view is of 90° for diverging wave and 20 mm for plane wave imaging and the data are sampled at 80 MHz. The reconstruction is performed on a Graphical Processing Unit (GPU) in order to image in real-time at a 4.5 display frame rate. 1-D normalized cross-correlation of the reconstructed RF data is used to estimate axial displacements in the focal region. The magnitude of the peak-to-peak displacement at the focal depth decreases during the thermal ablation which denotes stiffening of the tissue due to the formation of a lesion. The displacement signal-to-noise ratio (SNRd) at the focal area for plane wave was 1.4 times higher than for diverging wave showing that plane wave imaging appears to produce better displacement maps quality for HMIFU than diverging wave imaging. PMID:26556647

Characterization of Different Microbubbles in Assisting Focused Ultrasound-Induced Blood-Brain Barrier Opening

NASA Astrophysics Data System (ADS)

Wu, Sheng-Kai; Chu, Po-Chun; Chai, Wen-Yen; Kang, Shih-Tsung; Tsai, Chih-Hung; Fan, Ching-Hsiang; Yeh, Chih-Kuang; Liu, Hao-Li

2017-04-01

Microbubbles (MBs) serve as a critical catalyst to amplify local cavitation in CNS capillary lumen to facilitate focused ultrasound (FUS) to transiently open the blood-brain barrier (BBB). However, limited understanding is available regarding the effect of different microbubbles to induce BBB opening. The aim of this study is to characterize different MBs on their effect in FUS-induced BBB opening. Three MBs, SonoVue, Definity, and USphere, were tested, with 0.4-MHz FUS exposure at 0.62-1.38 of mechanical index (MI) on rats. Evans blue, dynamic contrast-enhanced (DCE) MRI and small-animal ultrasound imaging were used as surrogates to allow molecule-penetrated quantification, BBB-opened observation, and MBs circulation/persistence. Cavitation activity was measured via the passive cavitation detection (PCD) setup to correlate with the exposure level and the histological effect. Under given and identical MB concentrations, the three MBs induced similar and equivalent BBB-opening effects and persistence. In addition, a treatment paradigm by adapting exposure time is proposed to compensate MB decay to retain the persistence of BBB-opening efficiency in multiple FUS exposures. The results potentially improve understanding of the equivalence among MBs in focused ultrasound CNS drug delivery, and provide an effective strategy for securing persistence in this treatment modality.

Novel Non-invasive Treatment With High-intensity Focused Ultrasound (HIFU).

PubMed

Marinova, M; Rauch, M; Schild, H H; Strunk, H M

2016-02-01

Ultrasound is not only used for diagnostic purposes but it also can be applied therapeutically so far that nowadays high-intensity focused ultrasound (HIFU) even represents a novel non-invasive treatment modality for various solid tumors. HIFU works by causing selectively deep tissue destruction of target lesions within the body without harming adjacent and overlying structures. In this article, we present an overview on both the mode of action and requirements for a HIFU treatment as well as on the safety and the current status of indications and possible applications with regard to benign and malignant gynecological diseases. Based on numerous studies and original articles, HIFU proved to be an effective and low-risk treatment option particularly for uterine fibroids and adenomyosis, but it also seems to be effective for breast fibroadenomas or even for breast cancer in special cases and other rare entities. © Georg Thieme Verlag KG Stuttgart · New York.

Localized Harmonic Motion Imaging for Focused Ultrasound Surgery Targeting

PubMed Central

Curiel, Laura; Hynynen, Kullervo

2011-01-01

Recently, an in vivo real-time ultrasound-based monitoring technique that uses localized harmonic motion (LHM) to detect changes in tissues during focused ultrasound surgery (FUS) has been proposed to control the exposure. This technique can potentially be used as well for targeting imaging. In the present study we evaluated the potential of using LHM to detect changes in stiffness and the feasibility of using it for imaging purposes in phantoms and in vivo tumor detection. A single-element FUS transducer (80 mm focal length, 100 mm diameter, 1.485 MHz) was used for inducing a localized harmonic motion and a separate ultrasound diagnostic transducer excited by a pulser/receiver (5 kHz PRF, 5 MHz) was used to track motion. The motion was estimated using cross-correlation techniques on the acquired RF signal. Silicon phantom studies were performed in order to determine the size of inclusion that was possible to detect using this technique. Inclusions were discerned from the surroundings as a reduction on LHM amplitude and it was possible to depict inclusions as small as 4 mm. The amplitude of the induced LHM was always lower at the inclusions as compared with the one obtained at the surroundings. Ten New Zealand rabbits had VX2 tumors implanted on their thighs and LHM was induced and measured at the tumor region. Tumors (as small as 10 mm in length and 4 mm in width) were discerned from the surroundings as a reduction on LHM amplitude. PMID:21683514

Endogenous Catalytic Generation of O2 Bubbles for In Situ Ultrasound-Guided High Intensity Focused Ultrasound Ablation.

PubMed

Liu, Tianzhi; Zhang, Nan; Wang, Zhigang; Wu, Meiying; Chen, Yu; Ma, Ming; Chen, Hangrong; Shi, Jianlin

2017-09-26

High intensity focused ultrasound (HIFU) surgery generally suffers from poor precision and low efficiency in clinical application, especially for cancer therapy. Herein, a multiscale hybrid catalytic nanoreactor (catalase@MONs, abbreviated as C@M) has been developed as a tumor-sensitive contrast and synergistic agent (C&SA) for ultrasound-guided HIFU cancer surgery, by integrating dendritic-structured mesoporous organosilica nanoparticles (MONs) and catalase immobilized in the large open pore channels of MONs. Such a hybrid nanoreactor exhibited sensitive catalytic activity toward H 2 O 2 , facilitating the continuous O 2 gas generation in a relatively mild manner even if incubated with 10 μM H 2 O 2 , which finally led to enhanced ablation in the tissue-mimicking PAA gel model after HIFU exposure mainly resulting from intensified cavitation effect. The C@M nanoparticles could be accumulated within the H 2 O 2 -enriched tumor region through enhanced permeability and retention effect, enabling durable contrast enhancement of ultrasound imaging, and highly efficient tumor ablation under relatively low power of HIFU exposure in vivo. Very different from the traditional perfluorocarbon-based C&SA, such an on-demand catalytic nanoreactor could realize the accurate positioning of tumor without HIFU prestimulation and efficient HIFU ablation with a much safer power output, which is highly desired in clinical HIFU application.

High-intensity focused ultrasound sonothrombolysis: the use of perfluorocarbon droplets to achieve clot lysis at reduced acoustic power.

PubMed

Pajek, Daniel; Burgess, Alison; Huang, Yuexi; Hynynen, Kullervo

2014-09-01

The purpose of this study was to evaluate use of intravascular perfluorocarbon droplets to reduce the sonication power required to achieve clot lysis with high-intensity focused ultrasound. High-intensity focused ultrasound with droplets was initially applied to blood clots in an in vitro flow apparatus, and inertial cavitation thresholds were determined. An embolic model for ischemic stroke was used to illustrate the feasibility of this technique in vivo. Recanalization with intravascular droplets was achieved in vivo at 24 ± 5% of the sonication power without droplets. Recanalization occurred in 71% of rabbits that received 1-ms pulsed sonications during continuous intravascular droplet infusion (p = 0.041 vs controls). Preliminary experiments indicated that damage was confined to the ultrasonic focus, suggesting that tolerable treatments would be possible with a more tightly focused hemispheric array that allows the whole focus to be placed inside of the main arteries in the human brain. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Acceleration and focusing of plasma flows

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griswold, Martin Elias

The acceleration of flowing plasmas is a fundamental problem that is useful in a wide variety of technological applications. We consider the problem from the perspective of plasma propulsion. Gridded ion thrusters and Hall thrusters are the most commonly used devices to create flowing plasma for space propulsion, but both suffer from fundamental limitations. Gridded ion sources create good quality beams in terms of energy spread and spatial divergence, but the Child-Langmuir law in the non-neutral acceleration region limits the maximum achievable current density. Hall thrusters avoid this limitation by accelerating ions in quasi-neutral plasma but, as a result, producemore » plumes with high spatial divergence and large energy spread. In addition the more complicated magnetized plasma in the Hall Thruster produces oscillations that can reduce the efficiency of the thruster by increasing electron transport to the anode. We present investigations of three techniques to address the fundamental limitations on the performance of each thruster. First, we propose a method to increase the time-averaged current density (and thus thrust density) produced by a gridded ion source above the Child-Langmuir limit by introducing time-varying boundary conditions. Next, we use an electrostatic plasma lens to focus the Hall thruster plume, and finally we develop a technique to suppress a prominent oscillation that degrades the performance of Hall thrusters. The technique to loosen the constraints on current density from gridded ion thrusters actually applies much more broadly to any space charge limited flow. We investigate the technique with a numerical simulation and by proving a theoretical upper bound. While we ultimately conclude that the approach is not suitable for space propulsion, our results proved useful in another area, providing a benchmark for research into the spontaneously time-dependent current that arises in microdiodes. Next, we experimentally demonstrate a novel

Optimal conditions for tissue perforation using high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

Mochizuki, Takashi; Kihara, Taizo; Ogawa, Kouji; Tanabe, Ryoko; Yosizawa, Shin; Umemura, Shin-ichiro; Kakimoto, Takashi; Yamashita, Hiromasa; Chiba, Toshio

2012-10-01

To perforate tissue lying deep part in body, a large size transducer was assembled by combining four spherical-shaped transducers, and the optimal conditions for tissue perforation have studied using ventricle muscle of chicken as a target. The ex vivo experiments showed that ventricle muscle was successfully perforated both when it was exposed to High Intensity Focused Ultrasound (HIFU) directly and when it was exposed to HIFU through atrial muscle layer. Moreover, it was shown that calculated acoustic power distributions are well similar to the perforation patterns, and that the acoustic energy distributes very complexly near the focus. Lastly, perforation on the living rabbit bladder wall was demonstrated as a preliminary in vivo experiment.

Compare ultrasound-mediated heating and cavitation between flowing polymer- and lipid-shelled microbubbles during focused ultrasound exposures.

PubMed

Zhang, Siyuan; Zong, Yujin; Wan, Mingxi; Yu, Xiaojun; Fu, Quanyou; Ding, Ting; Zhou, Fanyu; Wang, Supin

2012-06-01

This paper compares the efficiency of flowing polymer- and lipid-shelled microbubbles (MBs) in the heating and cavitation during focused ultrasound exposures. Temperature and cavitation activity were simultaneously measured as the two types of shelled MBs and saline flowing through a 3 mm diameter vessel in the phantom with varying flow velocities (0-20 cm/s) at different acoustic power levels (0.6-20 W) with each exposure for 5 s. Temperature and cavitation for the lipid-shelled MBs were higher than those for the polymer-shelled MBs. Temperature rise decreased with increasing flow velocities for the two types of shelled MBs and saline at acoustic power 1.5 W. At acoustic power 11.1 W, temperature rise increased with increasing flow velocities for the lipid-shelled MBs. For the polymer-shelled MBs, the temperature rise increased with increasing flow velocities from 3-15 cm/s and decreased at 20 cm/s. Cavitation increased with increasing flow velocity for the two shelled MBs and there were no significant changes of cavitation with increasing flow velocities for saline. These results suggested that lipid-shelled MBs may have a greater efficiency than polymer-shelled MBs in heating and cavitation during focused ultrasound exposures.

Hyperthermia in bone generated with MR imaging-controlled focused ultrasound: control strategies and drug delivery.

PubMed

Staruch, Robert; Chopra, Rajiv; Hynynen, Kullervo

2012-04-01

To evaluate the feasibility of achieving image-guided drug delivery in bone by using magnetic resonance (MR) imaging-controlled focused ultrasound hyperthermia and temperature-sensitive liposomes. Experiments were approved by the institutional animal care committee. Hyperthermia (43°C, 20 minutes) was generated in 10-mm-diameter regions at a muscle-bone interface in nine rabbit thighs by using focused ultrasound under closed-loop temperature control with MR thermometry. Thermosensitive liposomal doxorubicin was administered systemically during heating. Heating uniformity and drug delivery were evaluated for control strategies with the temperature control image centered 10 mm (four rabbits) or 0 mm (five rabbits) from the bone. Simulations estimated temperature elevations in bone. Drug delivery was quantified by using the fluorescence of doxorubicin extracted from bone marrow and muscle and was compared between treated and untreated thighs by using the one-sided Wilcoxon signed rank test. With ultrasound focus and MR temperature control plane 0 mm and 10 mm from the bone interface, average target region temperatures were 43.1°C and 43.3°C, respectively; numerically estimated bone temperatures were 46.8°C and 78.1°C. The 10-mm offset resulted in thermal ablation; numerically estimated muscle temperature was 66.1°C at the bone interface. Significant increases in doxorubicin concentration occurred in heated versus unheated marrow (8.2-fold, P = .002) and muscle (16.8-fold, P = .002). Enhancement occurred for 0- and 10-mm offsets, which suggests localized drug delivery in bone is possible with both hyperthermia and thermal ablation. MR imaging-controlled focused ultrasound can achieve localized hyperthermia in bone for image-guided drug delivery in bone with temperature-sensitive drug carriers. © RSNA, 2012.

Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: a pilot study.

PubMed

Martínez-Fernández, Raul; Rodríguez-Rojas, Rafael; Del Álamo, Marta; Hernández-Fernández, Frida; Pineda-Pardo, Jose A; Dileone, Michele; Alonso-Frech, Fernando; Foffani, Guglielmo; Obeso, Ignacio; Gasca-Salas, Carmen; de Luis-Pastor, Esther; Vela, Lydia; Obeso, José A

2018-01-01

Ablative neurosurgery has been used to treat Parkinson's disease for many decades. MRI-guided focused ultrasound allows focal lesions to be made in deep brain structures without skull incision. We investigated the safety and preliminary efficacy of unilateral subthalamotomy by focused ultrasound in Parkinson's disease. This prospective, open-label pilot study was done at CINAC (Centro Integral de Neurociencias), University Hospital HM Puerta del Sur in Madrid, Spain. Eligible participants had Parkinson's disease with markedly asymmetric parkinsonism. Patients with severe dyskinesia, history of stereotactic surgery or brain haemorrhage, a diagnosis of an unstable cardiac or psychiatric disease, or a skull density ratio of 0·3 or less were excluded. Enrolled patients underwent focused ultrasound unilateral subthalamotomy. The subthalamic nucleus was targeted by means of brain images acquired with a 3-Tesla MRI apparatus. Several sonications above the definitive ablation temperature of 55°C were delivered and adjusted according to clinical response. The primary outcomes were safety and a change in the motor status of the treated hemibody as assessed with part III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) in both off-medication and on-medication states at 6 months. Adverse events were monitored up to 48 h after treatment and at scheduled clinic visits at 1, 3, and 6 months after treatment. The study is registered with ClinicalTrials.gov, number NCT02912871. Between April 26 and June 14, 2016, ten patients with markedly asymmetric parkinsonism that was poorly controlled pharmacologically were enrolled for focused ultrasound unilateral subthalamotomy. By 6 months follow-up, 38 incidents of adverse events had been recorded, none of which were serious or severe. Seven adverse events were present at 6 months. Three of these adverse events were directly related to subthalamotomy: off-medication dyskinesia in the treated arm

High-intensity focused ultrasound combined with hysteroscopic resection to treat retained placenta accreta.

PubMed

Lee, Jae-Seong; Hong, Gi-Youn; Park, Byung-Joon; Hwang, Hyejin; Kim, Rayon; Kim, Tae-Eung

2016-09-01

We present a case of retained placenta accreta treated by high-intensity focused ultrasound (HIFU) ablation followed by hysteroscopic resection. The patient was diagnosed as submucosal myoma based on ultrasonography in local clinic. Pathologic examination of several pieces of tumor mass from the hysteroscopic procedure revealed necrotic chorionic villi with calcification. HIFU was performed using an ultrasound-guided HIFU tumor therapeutic system. The ultrasound machine had been used for real-time monitoring of the HIFU procedure. After HIFU treatment, no additional vaginal bleeding or complications were observed. A hysteroscopic resection was performed to remove ablated placental tissue 7 days later. No abnormal vaginal bleeding or discharge was seen after the procedure. The patient was stable postoperatively. We proposed HIFU and applied additional hysteroscopic resection for a safe and effective method for treating retained placenta accreta to prevent complications from the remaining placental tissue and to improve fertility options.

Monitoring of tissue heating with medium intensity focused ultrasound via four dimensional optoacoustic tomography

NASA Astrophysics Data System (ADS)

Oyaga Landa, Francisco Javier; Ronda Penacoba, Silvia; Deán-Ben, Xosé Luís.; Montero de Espinosa, Francisco; Razansky, Daniel

2018-02-01

Medium intensity focused ultrasound (MIFU) holds promise in important clinical applications. Generally, the aim in MIFU is to stimulate physiological mechanisms that reinforce healing responses, avoiding reaching temperatures that can cause permanent tissue damage. The outcome of interventions is then strongly affected by the temperature distribution in the treated region, and accurate monitoring represents a significant clinical need. In this work, we showcase the capacities of 4D optoacoustic imaging to monitor tissue heating during MIFU. The proposed method allows localizing the ultrasound focus, estimating the peak temperature and measuring the size of the heat-affected volume. Calibration experiments in a tissue-mimicking phantom demonstrate that the optoacoustically-estimated temperature accurately matches thermocouple readings. The good performance of the suggested approach in real tissues is further showcased in experiments with bovine muscle samples.

Short- and long-term efficacy of focused ultrasound therapy for non-neoplastic epithelial disorders of the vulva.

PubMed

Wu, C; Zou, M; Xiong, Y; Wang, L; Chen, H; Fan, Y; Li, C

2017-08-01

To investigate the short- and long-term efficacy and influential factors of focused ultrasound for the treatment of non-neoplastic epithelial disorders of the vulva (NNEDV). A retrospective observational study. A gynaecologic department in a single centre in China. Patients with NNEDV were included in this study: 85 patients were diagnosed with lichen simplex chronicus (LSC), 44 patients with vulva lichen sclerosus (VLS), and seven patients with lichen planus (LP). A total of 136 eligible patients with NNEDV were treated with focused ultrasound. After the treatment, based on changes in the degree of symptom severity and local skin signs (lesion size, skin colour and elasticity) before and after treatment, the treatment effectiveness for each patient was assessed. We further analysed the relations among pathologic type, age, course and curative rate. Statistical analysis was performed using the Chi-square (McNemar) test. Improvement in the symptoms and physical signs and the predictive factors. Symptom relief was observed in all patients. The appearance and colour of the vulva returned to normal after the ultrasound treatment. Complete remission (CR) occurred in 68 of 136 (50%) patients (41 patients with LSC and 12 patients with VLS). The response rate was 93.38% (127/136). Seven patients who had a poor response to the first session of treatment were treated again with ultrasound therapy and a good response was observed. No severe complications were observed. There was no significant difference in treatment results among the different pathological types (P > 0.05). However, the course of the disease and the age of the patients were related to the treatment results (P < 0.05). NNEDV can be treated with focused ultrasound effectively and safely. The course of the disease and the age of the patients may be predictive factors. Patients with non-neoplastic epithelial disorders of the vulva can be safely and effectively treated with focused ultrasound. No significant

A modeling-based assessment of acousto-optic sensing for monitoring high-intensity focused ultrasound lesion formation

NASA Astrophysics Data System (ADS)

Adams, Matthew Tyler

Real-time acousto-optic (AO) sensing---a dual-wave modality that combines ultrasound with diffuse light to probe the optical properties of turbid media---has been demonstrated to non-invasively detect changes in ex vivo tissue optical properties during high-intensity focused ultrasound (HIFU) exposure. The AO signal indicates the onset of lesion formation and predicts resulting lesion volumes. Although proof-of-concept experiments have been successful, many of the underlying parameters and mechanisms affecting thermally induced optical property changes and the AO detectability of HIFU lesion formation are not well understood. In thesis, a numerical simulation was developed to model the AO sensing process and capture the relevant acoustic, thermal, and optical transport processes. The simulation required data that described how optical properties changed with heating. Experiments were carried out where excised chicken breast was exposed to thermal bath heating and changes in the optical absorption and scattering spectra (500 nm--1100 nm) were measured using a scanning spectrophotometer and an integrating sphere assembly. Results showed that the standard thermal dose model currently used for guiding HIFU treatments needs to be adjusted to describe thermally induced optical property changes. To model the entire AO process, coupled models were used for ultrasound propagation, tissue heating, and diffusive light transport. The angular spectrum method was used to model the acoustic field from the HIFU source. Spatial-temporal temperature elevations induced by the absorption of ultrasound were modeled using a finite-difference time-domain solution to the Pennes bioheat equation. The thermal dose model was then used to determine optical properties based on the temperature history. The diffuse optical field in the tissue was then calculated using a GPU-accelerated Monte Carlo algorithm, which accounted for light-sound interactions and AO signal detection. The simulation was

Electrostatic quadrupole focused particle accelerating assembly with laminar flow beam

DOEpatents

Maschke, A.W.

1984-04-16

A charged particle accelerating assembly provided with a predetermined ratio of parametric structural characteristics and with related operating voltages applied to each of its linearly spaced focusing and accelerating quadrupoles, thereby to maintain a particle beam traversing the electrostatic fields of the quadrupoles in the assembly in an essentially laminar flow through the assembly.

Electrostatic quadrupole focused particle accelerating assembly with laminar flow beam

DOEpatents

Maschke, Alfred W.

1985-01-01

A charged particle accelerating assembly provided with a predetermined ratio of parametric structural characteristics and with related operating voltages applied to each of its linearly spaced focusing and accelerating quadrupoles, thereby to maintain a particle beam traversing the electrostatic fields of the quadrupoles in the assembly in an essentially laminar flow throughout the assembly.

Effect of polarization and focusing on laser pulse driven auto-resonant particle acceleration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sagar, Vikram; Sengupta, Sudip; Kaw, Predhiman

2014-04-15

The effect of laser polarization and focusing is theoretically studied on the final energy gain of a particle in the Auto-resonant acceleration scheme using a finite duration laser pulse with Gaussian shaped temporal envelope. The exact expressions for dynamical variables viz. position, momentum, and energy are obtained by analytically solving the relativistic equation of motion describing particle dynamics in the combined field of an elliptically polarized finite duration pulse and homogeneous static axial magnetic field. From the solutions, it is shown that for a given set of laser parameters viz. intensity and pulse length along with static magnetic field, themore » energy gain by a positively charged particle is maximum for a right circularly polarized laser pulse. Further, a new scheme is proposed for particle acceleration by subjecting it to the combined field of a focused finite duration laser pulse and static axial magnetic field. In this scheme, the particle is initially accelerated by the focused laser field, which drives the non-resonant particle to second stage of acceleration by cyclotron Auto-resonance. The new scheme is found to be efficient over two individual schemes, i.e., auto-resonant acceleration and direct acceleration by focused laser field, as significant particle acceleration can be achieved at one order lesser values of static axial magnetic field and laser intensity.« less

Electron acceleration by a focused laser pulse in a static magnetic field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang Shihua; Wu Fengmin; Zhao Xianghao

2007-12-15

The model given by K. P. Singh [Phys. Rev. E 69, 056410 (2004)] for vacuum laser acceleration in a static magnetic field is revisited by including the effects of diffraction and the longitudinal electric field of a focused laser beam. Compared with a similar model without a static magnetic field, a simulation shows that electrons can gain much more net energy in this model even using the fifth-order corrected equations for the field of a focused laser beam. The acceleration mechanism and the acceleration efficiency are also investigated.

Contrast-enhanced ultrasound evaluation of pancreatic cancer xenografts in nude mice after irradiation with sub-threshold focused ultrasound for tumor ablation

PubMed Central

Wang, Rui; Guo, Qian; Chen, Yi Ni; Hu, Bing; Jiang, Li Xin

2017-01-01

We evaluated the efficacy of contrast-enhanced ultrasound for assessing tumors after irradiation with sub-threshold focused ultrasound (FUS) ablation in pancreatic cancer xenografts in nude mice. Thirty tumor-bearing nude mice were divided into three groups: Group A received sham irradiation, Group B received a moderate-acoustic energy dose (sub-threshold), and Group C received a high-acoustic energy dose. In Group B, B-mode ultrasound (US), color Doppler US, and dynamic contrast-enhanced ultrasound (DCE-US) studies were conducted before and after irradiation. After irradiation, tumor growth was inhibited in Group B, and the tumors shrank in Group C. In Group A, the tumor sizes were unchanged. In Group B, contrast-enhanced ultrasound (CEUS) images showed a rapid rush of contrast agent into and out of tumors before irradiation. After irradiation, CEUS revealed contrast agent perfusion only at the tumor periphery and irregular, un-perfused volumes of contrast agent within the tumors. DCE-US perfusion parameters, including peak intensity (PI) and area under the curve (AUC), had decreased 24 hours after irradiation. PI and AUC were increased 48 hours and 2weeks after irradiation. Time to peak (TP) and sharpness were increased 24 hours after irradiation. TP decreased at 48 hours and 2 weeks after irradiation. CEUS is thus an effective method for early evaluation after irradiation with sub-threshold FUS. PMID:28402267

The efficacy of a combination non-thermal focused ultrasound and radiofrequency device for noninvasive body contouring in Asians.

PubMed

Shek, Samantha Y N; Yeung, Chi K; Chan, Johnny C Y; Chan, Henry H L

2016-02-01

Several studies have been published on the first generation non-thermal focused ultrasound with an average improvement of 0-3.95 cm reported. We aim to investigate the efficacy of the second-generation non-thermal focused ultrasound device with a combined radiofrequency hand piece. With the addition of radiofrequency energy, the temperature of the adipose tissue is raised before focused ultrasound is applied. This facilitates the mechanical disruption of fat cells by focused ultrasound. Twenty subjects were recruited and underwent three treatments biweekly. Caliper reading, abdominal circumference, and standardized photographs were taken with the Vectra(®) system at all visits. We aim to have the subjects stand and hold the same position and the photograph taken after exhalation. Caliper and circumference measurements carry uncertainty. It is impossible to eliminate all uncertainties but can be improved by having the same trained physician assistant perform the measurement at the same site and taking an average of three readings. Pain score and satisfaction were recorded by means of the visual analogue scale. The efficacy is defined by a statistically significant improvement in circumferential improvement based on intention-to-treat analysis. Seventeen subjects completed the treatment schedule. Abdominal circumference showed statistically significant improvement at 2 weeks post-second treatment (P = 0.023) and almost all subsequent follow-ups. Caliper readings were statistically significant at 2 weeks post-second treatment (P = 0.013) and almost all follow-ups. The mean pain score reported was 2.3 on the visual analog scale and 6% were unsatisfied with the overall treatments. Six incidents of wheal formation appeared immediately after treatment all of which subsided spontaneously within several hours. The combination non-thermal focused ultrasound and radiofrequency device is effective for improving body contour in Asians. © 2015 Wiley Periodicals, Inc.

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound

PubMed Central

2014-01-01

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation of target tissues. While this emerging modality is increasingly used for the treatment of various types of extracranial soft tissue tumors, it has only recently been acknowledged as a modality for noninvasive neurosurgery. MRgFUS has been particularly successful for functional neurosurgery, whereas its clinical application for tumor neurosurgery has been delayed for various technical and procedural reasons. Here, we report the case of a 63-year-old patient presenting with a centrally located recurrent glioblastoma who was included in our ongoing clinical phase I study aimed at evaluating the feasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying 25 high-power sonications under MR imaging guidance, partial tumor ablation could be achieved without provoking neurological deficits or other adverse effects in the patient. This proves, for the first time, the feasibility of using transcranial MR-guided focused ultrasound to safely ablate substantial volumes of brain tumor tissue. PMID:25671132

Temperature distributions in tissues during local hyperthermia by stationary or steered beams of unfocused or focused ultrasound.

PubMed Central

Lele, P. P.; Parker, K. J.

1982-01-01

Temperature distributions resulting from insonation with stationary or steered beams of unfocused or focused ultrasound were measured in tissue-equivalent phantom, beef muscle in vitro, dog muscle mass, and transplanted murine tumours in vivo. Arrays of 4 to 6 thermocouples stepped through the volume of interest under computer control were used to measure the steady-state temperatures at 600 to 800 locations in both in vitro and in vivo experiments. The results were confirmed in spontaneous tumours in dog patients using fewer multi-thermocouple probes. Plane wave ultrasound was found to result in spatially non-uniform hyperthermia even in superficial tumours. The region of maximum temperature rise was small in extent and was situated at a depth which varied in the different models from 0.5 to 1.0 cm. Neither its location nor its extent could be varied by spatial manipulations of the transducer or by changing the insonation parameters except the ultrasonic frequency. A second region of hyperthermia was produced at depth by reflective heating if an ultrasonically reflective target, such as bone or air-containing tissue, was located below the target tissue. On the other hand, using available steered, focused ultrasound techniques, tumours (whether situated superficially or at depth) could be heated to a uniform, controllable temperature without undesirable temperature elevation in surrounding normal tissues. The use of steered, focused ultrasound permits deposition of energy to be tailored to the specific needs of each individual tumour. The small size of the focal region enables heating of tumours even when located near ultrasound reflecting targets. PMID:6950746

Hyperechogenicity during high intensity focused ultrasound (HIFU)

NASA Astrophysics Data System (ADS)

Crum, Lawrence; Bailey, Michael; Rabkin, Brian; Khokhlova, Vera; Vaezy, Shahram

2005-09-01

Ultrasound guidance of HIFU therapy is attractive because of its portability, low cost, real-time image processing, simple integration with HIFU instruments, and the extensive availability of diagnostic ultrasound; however, the use of ultrasound visualization for the guidance and monitoring of HIFU therapy often relies on the appearance of a hyperechoic region in the ultrasound image. It is often assumed that the formation of a hyperechoic region at the HIFU treatment site results from bubble activity generated during HIFU exposure. However, it has been determined that this region can be generated with relatively short bursts of HIFU (on the order of 30 ms), bursts so short that negligible temperature elevations are expected to occur. In examining the histology associated with these hyperechoes, there is little evidence of traditional cavitation damage; rather, it appears as if there are many bubbles generated within the individuals cells, suggesting a thermal mechanism. Thermocouple measurements of the temperature elevation were inaccurate due to the short insonation period, but showed only a few-degree temperature rise. These anomalous results will be presented, along with additional data on HIFU hyperechogenicity, and a hypothesis given for the phenomenological origins of this effect. [Work supported in part by the NSBRI, U.S. Army, and the NIH.

Spatial and temporal observation of phase-shift nano-emulsions assisted cavitation and ablation during focused ultrasound exposure.

PubMed

Qiao, Yangzi; Zong, Yujin; Yin, Hui; Chang, Nan; Li, Zhaopeng; Wan, Mingxi

2014-09-01

Phase-shift nano-emulsions (PSNEs) with a small initial diameter in nanoscale have the potential to leak out of the blood vessels and to accumulate at the target point of tissue. At desired location, PSNEs can undergo acoustic droplet vaporization (ADV) process, change into gas bubbles and enhance focused ultrasound efficiency. The threshold of droplet vaporization and influence of acoustic parameters have always been research hotspots in order to spatially control the potential of bioeffects and optimize experimental conditions. However, when the pressure is much higher than PSNEs' vaporization threshold, there were little reports on their cavitation and thermal effects. In this study, PSNEs induced cavitation and ablation effects during pulsed high-intensity focused ultrasound (HIFU) exposure were investigated, including the spatial and temporal information and the influence of acoustic parameters. Two kinds of tissue-mimicking phantoms with uniform PSNEs were prepared because of their optical transparency. The Sonoluminescence (SL) method was employed to visualize the cavitation activities. And the ablation process was observed as the heat deposition could produce white lesion. Precisely controlled HIFU cavitation and ablation can be realized at a relatively low input power. But when the input power was high, PSNEs can accelerate cavitation and ablation in pre-focal region. The cavitation happened layer by layer advancing the transducer. While the lesion appeared to be separated into two parts, one in pre-focal region stemmed from one point and grew quickly, the other in focal region grew much more slowly. The influence of duty cycle has also been examined. Longer pulse off time would cause heat transfer to the surrounding media, and generate smaller lesion. On the other hand, this would give outer layer bubbles enough time to dissolve, and inner bubbles can undergo violent collapse and emit bright light. Copyright © 2014 Elsevier B.V. All rights reserved.

Robotically assisted velocity-sensitive triggered focused ultrasound surgery

NASA Astrophysics Data System (ADS)

Maier, Florian; Brunner, Alexander; Jenne, Jürgen W.; Krafft, Axel J.; Semmler, Wolfhard; Bock, Michael

2012-11-01

Magnetic Resonance (MR) guided Focused Ultrasound Surgery (FUS) of abdominal organs is challenging due to breathing motion and limited patient access in the MR environment. In this work, an experimental robotically assisted FUS setup was combined with a MR-based navigator technique to realize motion-compensated sonications and online temperature imaging. Experiments were carried out in a static phantom, during periodic manual motion of the phantom without triggering, and with triggering to evaluate the triggering method. In contrast to the non-triggered sonication, the results of the triggered sonication show a confined symmetric temperature distribution. In conclusion, the velocity sensitive navigator can be employed for triggered FUS to compensate for periodic motion. Combined with the robotic FUS setup, flexible treatment of abdominal targets might be realized.

Elasticity mapping of tissue mimicking phantoms by remote palpation with a focused ultrasound beam and intensity autocorrelation measurements

NASA Astrophysics Data System (ADS)

Usha Devi, C.; Bharat Chandran, R. S.; Vasu, R. M.; Sood, A. K.

2007-05-01

We use a focused ultrasound beam to load a region of interest (ROI) in a tissue-mimicking phantom and read out the vibration amplitude of phantom particles from the modulation depth in the intensity autocorrelation of a coherent light beam that intercepted the ROI. The modulation depth, which is also affected by the local light absorption coefficient, which is employed in ultrasound assisted optical tomography, to read out absorption coefficient is greatly influenced by the vibration amplitude, depends to a great extend on local elasticity. We scan a plane in an elastography phantom with an inhomogeneous inclusion, in elasticity with the focused ultrasound and from the measured modulation depth variation create a qualitative map of the elasticity variation in the interrogated plane.

An Investigation of High Intensity Focused Ultrasound Thrombolysis

NASA Astrophysics Data System (ADS)

Wright, Cameron; Hynynen, Kullervo; Goertz, David

2011-09-01

Investigations into high intensity focused ultrasound (HIFU) thrombolysis in vitro and in vivo in a rabbit femoral artery thrombus model were performed. A 1.51 MHz focused transducer was used to treat clots with pulse lengths of 1-10 ms, acoustic powers of 1-300 W and exposure durations of 5-20 s. Our measurements indicate the creation of acoustic radiation force induced clot displacements are insufficient to mechanically fractionate clots, despite reaching displacements >100 μm. Only under the presence of inertial cavitation was HIFU able to disrupt clots. Cavitation thresholds of 160 W in vitro and 215 W in vivo were observed. In vitro, clots insonified at powers above the cavitation threshold eroded regions up to 2.5× the transducer beam width. Successful recanalization in vivo occurred in 5/20 cases for 1ms pulses at powers >215 W. 10 ms pulses created high incidences of symptomatic bleeding while 1 ms pulses did not. These results demonstrate treatment feasibility in vivo, although further work is required to understand the influence of different acoustic parameters on treatment outcome.

Microbubbles in Ultrasound-Triggered Drug and Gene Delivery

PubMed Central

Hernot, Sophie; Klibanov, Alexander L.

2008-01-01

Ultrasound contrast agents, in the form of gas-filled microbubbles, are becoming popular in perfusion monitoring; they are employed as molecular imaging agents. Microbubbles are manufactured from biocompatible materials, they can be injected intravenously, and some are approved for clinical use. Microbubbles can be destroyed by ultrasound irradiation. This destruction phenomenon can be applied to targeted drug delivery and enhancement of drug action. The ultrasonic field can be focused at the target tissues and organs; thus, selectivity of the treatment can be improved, reducing undesirable side effects. Microbubbles enhance ultrasound energy deposition in the tissues and serve as cavitation nuclei, increasing intracellular drug delivery. DNA delivery and successful tissue transfection is observed in the areas of the body where ultrasound is applied after intravascular administration of microbubbles and plasmid DNA. Accelerated blood clot dissolution in the areas of insonation by cooperative action of thrombolytic agents and microbubbles is demonstrated in several clinical trials. PMID:18486268

Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound

PubMed Central

Cao, Yang; Chen, Yuli; Yu, Tao; Guo, Yuan; Liu, Fengqiu; Yao, Yuanzhi; Li, Pan; Wang, Dong; Wang, Zhigang; Chen, Yu; Ran, Haitao

2018-01-01

Background: As one of the most effective triggers with high tissue-penetrating capability and non-invasive feature, ultrasound shows great potential for controlling the drug release and enhancing the chemotherapeutic efficacy. In this study, we report, for the first time, construction of a phase-changeable drug-delivery nanosystem with programmable low-intensity focused ultrasound (LIFU) that could trigger drug-release and significantly enhance anticancer drug delivery. Methods: Liquid-gas phase-changeable perfluorocarbon (perfluoropentane) and an anticancer drug (doxorubicin) were simultaneously encapsulated in two kinds of nanodroplets. By triggering LIFU, the nanodroplets could be converted into microbubbles locally in tumor tissues for acoustic imaging and the loaded anticancer drug (doxorubicin) was released after the microbubble collapse. Based on the acoustic property of shell materials, such as shell stiffness, two types of nanodroplets (lipid-based nanodroplets and PLGA-based nanodroplets) were activated by different acoustic pressure levels. Ultrasound irradiation duration and power of LIFU were tested and selected to monitor and control the drug release from nanodroplets. Various ultrasound energies were introduced to induce the phase transition and microbubble collapse of nanodroplets in vitro (3 W/3 min for lipid nanodroplets; 8 W/3 min for PLGA nanodroplets). Results: We detected three steps in the drug-releasing profiles exhibiting the programmable patterns. Importantly, the intratumoral accumulation and distribution of the drug with LIFU exposure were significantly enhanced, and tumor proliferation was substantially inhibited. Co-delivery of two drug-loaded nanodroplets could overcome the physical barriers of tumor tissues during chemotherapy. Conclusion: Our study provides a new strategy for the efficient ultrasound-triggered chemotherapy by nanocarriers with programmable LIFU capable of achieving the on-demand drug release. PMID:29507623

High-Intensity Focused Ultrasound: Current Status for Image-Guided Therapy

PubMed Central

Copelan, Alexander; Hartman, Jason; Chehab, Monzer; Venkatesan, Aradhana M.

2015-01-01

Image-guided high-intensity focused ultrasound (HIFU) is an innovative therapeutic technology, permitting extracorporeal or endocavitary delivery of targeted thermal ablation while minimizing injury to the surrounding structures. While ultrasound-guided HIFU was the original image-guided system, MR-guided HIFU has many inherent advantages, including superior depiction of anatomic detail and superb real-time thermometry during thermoablation sessions, and it has recently demonstrated promising results in the treatment of both benign and malignant tumors. HIFU has been employed in the management of prostate cancer, hepatocellular carcinoma, uterine leiomyomas, and breast tumors, and has been associated with success in limited studies for palliative pain management in pancreatic cancer and bone tumors. Nonthermal HIFU bioeffects, including immune system modulation and targeted drug/gene therapy, are currently being explored in the preclinical realm, with an emphasis on leveraging these therapeutic effects in the care of the oncology patient. Although still in its early stages, the wide spectrum of therapeutic capabilities of HIFU offers great potential in the field of image-guided oncologic therapy. PMID:26622104

Localised drug release using MRI-controlled focused ultrasound hyperthermia.

PubMed

Staruch, Robert; Chopra, Rajiv; Hynynen, Kullervo

2011-01-01

Thermosensitive liposomes provide a mechanism for triggering the local release of anticancer drugs, but this technology requires precise temperature control in targeted regions with minimal heating of surrounding tissue. The objective of this study was to evaluate the feasibility of using MRI-controlled focused ultrasound (FUS) and thermosensitive liposomes to achieve thermally mediated localised drug delivery in vivo. Results are reported from ten rabbits, where a FUS beam was scanned in a circular trajectory to heat 10-15 mm diameter regions in normal thigh to 43°C for 20-30 min. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive liposomal doxorubicin was infused intravenously during hyperthermia. Unabsorbed liposomes were flushed from the vasculature by saline perfusion 2 h later, and tissue samples were harvested from heated and unheated thigh regions. The fluorescence intensity of the homogenised samples was used to calculate the concentration of doxorubicin in tissue. Closed-loop control of FUS heating using MRI thermometry achieved temperature distributions with mean, T90 and T10 of 42.9°C, 41.0°C and 44.8°C, respectively, over a period of 20 min. Doxorubicin concentrations were significantly higher in tissues sampled from heated than unheated regions of normal thigh muscle (8.3 versus 0.5 ng/mg, mean per-animal difference = 7.8 ng/mg, P < 0.05, Wilcoxon matched pairs signed rank test). The results show the potential of MRI-controlled focused ultrasound hyperthermia for enhanced local drug delivery with temperature-sensitive drug carriers.

Dense plasma focus (DPF) accelerated non radio isotopic radiological source

DOEpatents

Rusnak, Brian; Tang, Vincent

2017-01-31

A non-radio-isotopic radiological source using a dense plasma focus (DPF) to produce an intense z-pinch plasma from a gas, such as helium, and which accelerates charged particles, such as generated from the gas or injected from an external source, into a target positioned along an acceleration axis and of a type known to emit ionizing radiation when impinged by the type of accelerated charged particles. In a preferred embodiment, helium gas is used to produce a DPF-accelerated He2+ ion beam to a beryllium target, to produce neutron emission having a similar energy spectrum as a radio-isotopic AmBe neutron source. Furthermore, multiple DPFs may be stacked to provide staged acceleration of charged particles for enhancing energy, tunability, and control of the source.

A NEW METHOD FOR THE GENERATION AND USE OF FOCUSED ULTRASOUND IN EXPERIMENTAL BIOLOGY

PubMed Central

Lynn, John G.; Zwemer, Raymund L.; Chick, Arthur J.; Miller, August E.

1942-01-01

1. An efficient generator of focused ultrasound has been designed, built, and successfully operated. 2. The generator has been used to produce focal heating in the centers of paraffin blocks, and in a similar manner, focal areas of destruction were obtained deep in fresh liver tissue with minimal effects at the surface and no effects on the intervening tissue. 3. In animals, focused ultrasound of high intensity produced local cerebral changes as inferred from behavior disabilities and as demonstrated at autopsy. This local brain effect was achieved through intervening scalp, skull, and meninges. The resulting behavior disabilities disappeared in from 2 to 16 hours. 4. To date, it has not been possible to produce such brain changes without incidental injury to the skin and subcutaneous tissue lying at the base of the cone of radiation. 5. Improvements in generation and application of the focused supersonic beam are suggested whereby it should be possible to increase still further the focal effects in the brain, with a corresponding decrease or elimination of complicating surface injury. PMID:19873337

Nonthermal ablation in the rat brain using focused ultrasound and an ultrasound contrast agent: long-term effects

PubMed Central

McDannold, Nathan; Zhang, Yongzhi; Vykhodtseva, Natalia

2016-01-01

OBJECTIVE Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently under investigation as a less invasive alternative to radiosurgery and resection. A major limitation of the method is that its use is currently restricted to centrally located brain targets. The combination of FUS and a microbubble-based ultrasound contrast agent greatly reduces the ultrasound exposure level needed to ablate brain tissue and could be an effective means to increase the “treatment envelope” for FUS in the brain. This method, however, ablates tissue through a different mechanism: destruction of the microvasculature. It is not known whether nonthermal FUS ablation in substantial volumes of tissue can safely be performed without unexpected effects. The authors investigated this question by ablating volumes in the brains of normal rats. METHODS Overlapping sonications were performed in rats (n = 15) to ablate a volume in 1 hemisphere per animal. The sonications (10-msec bursts at 1 Hz for 60 seconds; peak negative pressure 0.8 MPa) were combined with the ultrasound contrast agent Optison (100 μl/kg). The rats were followed with MRI for 4–9 weeks after FUS, and the brains were examined with histological methods. RESULTS Two weeks after sonication and later, the lesions appeared as cyst-like areas in T2-weighted MR images that were stable over time. Histological examination demonstrated well-defined lesions consisting of a cyst-like cavity that remained lined by astrocytic tissue. Some white matter structures within the sonicated area were partially intact. CONCLUSIONS The results of this study indicate that nonthermal FUS ablation can be used to safely ablate tissue volumes in the brain without unexpected delayed effects. The findings are encouraging for the use of this ablation method in the brain. PMID:26848919

High-intensity focused ultrasound ablation of thyroid nodules: first human feasibility study.

PubMed

Esnault, Olivier; Franc, Brigitte; Ménégaux, Fabrice; Rouxel, Agnès; De Kerviler, Eric; Bourrier, Pierre; Lacoste, François; Chapelon, Jean-Yves; Leenhardt, Laurence

2011-09-01

Thyroid surgery is common, but complications may occur. High-intensity focused ultrasound (HIFU) is a minimally invasive alternative to surgery. We hypothesized that an optimized HIFU device could be safe and effective for ablating benign thyroid nodules without affecting neighboring structures. In this open, single-center feasibility study, 25 patients were treated with HIFU with real-time ultrasound imaging 2 weeks before a scheduled thyroidectomy for multinodular goiter. Thyroid ultrasonography imaging, thyroid function, were evaluated before and after treatment. Adverse events were carefully recorded. Each patient received HIFU for one thyroid nodule, solid or mixed, with mean diameter ≥8 mm, and no suspicion of malignancy. The HIFU device was progressively adjusted with stepwise testing. The energy level for ablation ranged from 35 to 94 J/pulse for different groups of patients. One pathologist examined all removed thyroids. Three patients discontinued treatment due to pain or skin microblister. Among the remaining 22 patients, 16 showed significant changes by ultrasound. Macroscopic and histological examinations showed that all lesions were confined to the targeted nodule without affecting neighboring structures. At pathological analysis, the extent of nodule destruction ranged from 2% to 80%. Five out of 22 patients had over 20% pathological lesions unmistakably attributed to HIFU. Seventeen cases had putative lesions including nonspecific necrosis, hemorrhage, nodule detachment, cavitations, and cysts. Among these 17 cases, 12 had both ultrasound changes and cavitation at histology that may be expected for an HIFU effect. In the last three patients ablated at the highest energy level, significant ultrasound changes and complete coagulative necrosis were observed in 80%, 78%, and 58% of the targeted area, respectively. There were no major complications of ablation. This study showed the potential efficacy of HIFU for human thyroid nodule ablation

Low-pressure pulsed focused ultrasound with microbubbles promotes an anticancer immunological response.

PubMed

Liu, Hao-Li; Hsieh, Han-Yi; Lu, Li-An; Kang, Chiao-Wen; Wu, Ming-Fang; Lin, Chun-Yen

2012-11-11

High-intensity focused-ultrasound (HIFU) has been successfully employed for thermal ablation of tumors in clinical settings. Continuous- or pulsed-mode HIFU may also induce a host antitumor immune response, mainly through expansion of antigen-presenting cells in response to increased cellular debris and through increased macrophage activation/infiltration. Here we demonstrated that another form of focused ultrasound delivery, using low-pressure, pulsed-mode exposure in the presence of microbubbles (MBs), may also trigger an antitumor immunological response and inhibit tumor growth. A total of 280 tumor-bearing animals were subjected to sonographically-guided FUS. Implanted tumors were exposed to low-pressure FUS (0.6 to 1.4 MPa) with MBs to increase the permeability of tumor microvasculature. Tumor progression was suppressed by both 0.6 and 1.4-MPa MB-enhanced FUS exposures. We observed a transient increase in infiltration of non-T regulatory (non-Treg) tumor infiltrating lymphocytes (TILs) and continual infiltration of CD8+ cytotoxic T-lymphocytes (CTL). The ratio of CD8+/Treg increased significantly and tumor growth was inhibited. Our findings suggest that low-pressure FUS exposure with MBs may constitute a useful tool for triggering an anticancer immune response, for potential cancer immunotherapy.

THE MECHANISM OF LESION FORMATION BY FOCUSED ULTRASOUND ABLATION CATHETER FOR TREATMENT OF ATRIAL FIBRILLATION

PubMed Central

Sinelnikov, Y.D.; Fjield, T.; Sapozhnikov, O.A.

2009-01-01

The application of therapeutic ultrasound for the treatment of atrial fibrillation (AF) is investigated. The results of theoretical and experimental investigation of ultrasound ablation catheter are presented. The major components of the catheter are the high power cylindrical piezoelectric element and parabolic balloon reflector. Thermal elevation in the ostia of pulmonary veins is achieved by focusing the ultrasound beam in shape of a torus that transverses the myocardial tissue. High intensity ultrasound heating in the focal zone results in a lesion surrounding the pulmonary veins that creates an electrical conduction blocks and relief from AF symptoms. The success of the ablation procedure largely depends on the correct choice of reflector geometry and ultrasonic power. We present a theoretical model of the catheter’s acoustic field and bioheat transfer modeling of cardiac lesions. The application of an empirically derived relation between lesion formation and acoustic power is shown to correlate with the experimental data. Developed control methods combine the knowledge of theoretical acoustics and the thermal lesion formation simulations with experiment and thereby establish rigorous dosimetry that contributes to a safe and effective ultrasound ablation procedure. PMID:20161431

Weakening Pin Bone Attachment in Fish Fillets Using High-Intensity Focused Ultrasound

PubMed Central

Stormo, Svein Kristian; Þórarinsdóttir, Kristín Anna; Heia, Karsten

2017-01-01

High Intensity Focused Ultrasound (HIFU) can be used for the localized heating of biological tissue through the conversion of sound waves into heat. Although originally developed for human medicine, HIFU may also be used to weaken the attachment of pin bones in fish fillets to enable easier removal of such bones. This was shown in the present study, where a series of experiments were performed on HIFU phantoms and fillets of cod and salmon. In thin objects such as fish fillets, the heat is mainly dissipated at the surfaces. However, bones inside the fillet absorb ultrasound energy more efficiently than the surrounding tissue, resulting in a “self-focusing” heating of the bones. Salmon skin was found to effectively block the ultrasound, resulting in a significantly lower heating effect in fillets with skin. Cod skin partly blocked the ultrasound, but only to a small degree, enabling HIFU treatment through the skin. The treatment of fillets to reduce the pin bone attachment yielded an average reduction in the required pulling force by 50% in cod fillets with skin, with little muscle denaturation, and 72% in skinned fillets, with significant muscle denaturation. Salmon fillets were treated from the muscle side of the fillet to circumvent the need for penetration through skin. The treatment resulted in a 30% reduction in the peak pulling force and 10% reduction in the total pulling work, with a slight denaturation of the fillet surface. PMID:28926968

Safety of ultrasound-guided high-intensity focused ultrasound ablation for diffuse adenomyosis: A retrospective cohort study.

PubMed

Feng, Yujie; Hu, Liang; Chen, Wenzhi; Zhang, Rong; Wang, Xi; Chen, Jinyun

2017-05-01

To evaluate the safety of ultrasound-guided high-intensity focused ultrasound (HIFU) ablation for patients with diffuse adenomyosis. This was a retrospective cohort study. The data was collected from 417 symptomatic adenomyosis patients who underwent ultrasound-guided HIFU between January 2012 and December 2015 at 1st Affiliated Hospital of Chongqing Medical University, Chongqing, China. Among them were 260 patients with diffuse adenomyosis (Group D) and 157 patients with focal adenomyosis (Group F). All patients underwent contrast-enhanced magnetic resonance imaging (MRI) one week before and the day after HIFU treatment. Successful treatment with HIFU was measured by the non-perfused volume ratio (NPVR). Intraprocedural and postprocedural adverse effects and complications were recorded to assess the safety of the procedure. Patients were followed-up for three months post-treatment. Complications were given a grade A through F according to the SIR Standards. All patients successfully completed the procedure, non-perfused regions appeared in 415 (99.5%) patients. The non-perfused volume ratio (NPVR) of Group D was significantly lower than that of Group F (P<0.05). During the procedure, the odds ratio of skin-burning pain was 1.7 (OR=1.617, 95% CI: 1.103-2.532), when comparing Group D with Group F, while the odds ratio of inguinal pain was equal to 2.0 (OR=2.038, 95% CI: 1.161-3.580), when Group F was compared to Group D. 97 patients (23.3%) received nominal therapy due to complications ([Society of interventional radiology, SIR]-B grade), among them, there were 62 cases (23.8%) in Group D and 35 cases (22.3%) in Group F. No significant difference was found between the two groups (P>0.05) and neither of the reported complications of SIR-C-SIR-F occurred within the two groups. Based on our results, ultrasound-guided HIFU is safe for the treatment of diffuse adenomyosis, and controlling the ablation zone is crucial to ensure patients' safety. Copyright © 2016 Elsevier

Accurate acoustic power measurement for low-intensity focused ultrasound using focal axial vibration velocity

NASA Astrophysics Data System (ADS)

Tao, Chenyang; Guo, Gepu; Ma, Qingyu; Tu, Juan; Zhang, Dong; Hu, Jimin

2017-07-01

Low-intensity focused ultrasound is a form of therapy that can have reversible acoustothermal effects on biological tissue, depending on the exposure parameters. The acoustic power (AP) should be chosen with caution for the sake of safety. To recover the energy of counteracted radial vibrations at the focal point, an accurate AP measurement method using the focal axial vibration velocity (FAVV) is proposed in explicit formulae and is demonstrated experimentally using a laser vibrometer. The experimental APs for two transducers agree well with theoretical calculations and numerical simulations, showing that AP is proportional to the square of the FAVV, with a fixed power gain determined by the physical parameters of the transducers. The favorable results suggest that the FAVV can be used as a valuable parameter for non-contact AP measurement, providing a new strategy for accurate power control for low-intensity focused ultrasound in biomedical engineering.

Development of a Tissue-Mimicking Phantom for Evaluating the Focusing Performance of High Intensity Focused Ultrasound

NASA Astrophysics Data System (ADS)

Zongyu, Jing; Faqi, Li; Jiangzhong, Zou; Zhibiao, Wang

2006-05-01

Objectives: To develop a tissue mimicking phantom which can be used to evaluate the focusing performance of the HIFU transducer, and the phantom should has the same acoustic characteristic and thermotics characteristic as the biological tissue. Materials and methods: The tissue mimicking phantom was made from water, gelatin, fresh biologic tissue Its ultrasonic parameters (attenuation coefficient) of the phantom was measured by the method of radiation pressure, and thermotics parameters of the phantom, including thermal conductivity, specific heat/fusion point et al were tested under the Measurement meter. The HIFU biological effect of the phantom was evaluated under the Model JC focused ultrasound tumor therapeutic system, developed and produced by Chongqing HIFU Technology Co. Ltd (working frequency: 0.7MHz; acoustic power: 200W; focal distance: 135mm; Acoustic focal region: 3×3×25 cubic mm). Results: The self-made phantom is sable, has smooth and glossy appearance, well-distributed construction, and good elasticity. We measured the followed values for acoustic and thermal properties: density 1049±2 kg/m3; attenuation 0.532±0.017 dB/cm (0.8 MHz), 0.612±0.021 dB/cm (1.0 MHz); thermal conductivity 0.76±0.08 W/m/-°C; specific heat 3653±143 J/kg-°C; fusion point154±8°C. The BFR induced in the phantom after HIFU exposure was stable in its size and appearance. Conclusion: We produced and improved one tissue mimicking phantom successfully which had semblable ultrasound and thermphysical properties like the soft tissue, and can replace the bovine liver to investigate the HIFU biological effect and to detect the focusing performance of the HIFU energy transducer. The research was supported by Chongqing University of Medical Science (CX200320).

Trans-cranial opening of the blood-brain barrier in targeted regions using a stereotaxic brain atlas and focused ultrasound energy.

PubMed

Bing, Chenchen; Ladouceur-Wodzak, Michelle; Wanner, Clinton R; Shelton, John M; Richardson, James A; Chopra, Rajiv

2014-01-01

The blood-brain barrier (BBB) protects the brain by preventing the entry of large molecules; this poses a major obstacle for the delivery of drugs to the brain. A novel technique using focused ultrasound (FUS) energy combined with microbubble contrast agents has been widely used for non-invasive trans-cranial BBB opening. Traditionally, FUS research is conducted with magnetic resonance imaging (MRI) guidance, which is expensive and poses physical limitations due to the magnetic field. A system that could allow researchers to test brain therapies without MR intervention could facilitate and accelerate translational research. In this study, we present a novel FUS system that uses a custom-built FUS generator mounted on a motorized stereotaxic apparatus with embedded brain atlas to locally open the BBB in rodents. The system was initially characterized using a tissue-mimicking phantom. Rodent studies were also performed to evaluate whether non-invasive, localized BBB opening could be achieved using brain atlas-based targeting. Brains were exposed to pulsed focused ultrasound energy at 1.06 MHz in rats and 3.23 MHz in mice, with the focal pressure estimated to be 0.5-0.6 MPa through the skull. BBB opening was confirmed in gross tissue sections by the presence of Evans blue leakage in the exposed region of the brain and by histological assessment. The targeting accuracy of the stereotaxic system was better than 0.5 mm in the tissue-mimicking phantom. Reproducible localized BBB opening was verified with Evans blue dye leakage in 32/33 rats and had a targeting accuracy of ±0.3 mm. The use of higher frequency exposures in mice enabled a similar precision of localized BBB opening as was observed with the low frequency in the rat model. With this dedicated small-animal motorized stereotaxic-FUS system, we achieved accurate targeting of focused ultrasound exposures in the brain for non-invasive opening of the BBB. This system can be used as an alternative to MR

Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU) in Treatment of Symptomatic Uterine Myomas

PubMed Central

Filipowska, Justyna; Łoziński, Tomasz

2014-01-01

Summary Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) is a noninvasive technique for ablation therapy for uterine myomas, where focused ultrasound energy beam generates localized high temperature in the selected area and coagulates chosen tissue, leaving the skin and tissues in between unharmed. Magnetic resonance imaging enables accurate targeting for HIFU as well as temperature monitoring during treatment. MR guidance with 3D anatomical imaging provides reference data for treatment planning, while real-time temperature monitoring aids in controlling ablation process. This review provides basic information regarding methodology, clinical indications for this kind of treatment, expected outcome and patient management during MR-HIFU procedure. The aim of this work is to introduce a new, noninvasive treatment method for uterine leiomyomas and to present a comparison with other currently used methods. PMID:25469176

Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU) in Treatment of Symptomatic Uterine Myomas.

PubMed

Filipowska, Justyna; Loziński, Tomasz

2014-01-01

Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) is a noninvasive technique for ablation therapy for uterine myomas, where focused ultrasound energy beam generates localized high temperature in the selected area and coagulates chosen tissue, leaving the skin and tissues in between unharmed. Magnetic resonance imaging enables accurate targeting for HIFU as well as temperature monitoring during treatment. MR guidance with 3D anatomical imaging provides reference data for treatment planning, while real-time temperature monitoring aids in controlling ablation process. This review provides basic information regarding methodology, clinical indications for this kind of treatment, expected outcome and patient management during MR-HIFU procedure. The aim of this work is to introduce a new, noninvasive treatment method for uterine leiomyomas and to present a comparison with other currently used methods.

Trans-cranial focused ultrasound without hair shaving: feasibility study in an ex vivo cadaver model

PubMed Central

2013-01-01

In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound procedure, current practice is to shave the patient’s head on treatment day. Here we present an initial attempt to evaluate the feasibility of trans-cranial focused ultrasound in an unshaved, ex vivo human head model. A human skull filled with tissue-mimicking phantom and covered with a wig made of human hair was sonicated using 220- and 710-kHz head transducers to evaluate the feasibility of acoustic energy transfer. Heating at the focal point was measured by MR proton resonance shift thermometry. Results showed that the hair had a negligible effect on focal spot thermal rise at 220 kHz and a 17% drop in temperature elevation when using 710 kHz. PMID:25512865

[MR-guided focused ultrasound. Current and future applications].

PubMed

Trumm, C G; Napoli, A; Peller, M; Clevert, D-A; Stahl, R; Reiser, M; Matzko, M

2013-03-01

High-intensity focused ultrasound (synonyms FUS and HIFU) under magnetic resonance imaging (MRI) guidance (synonyms MRgFUS and MR-HIFU) is a completely non-invasive technology for accurate thermal ablation of a target tissue while neighboring tissues and organs are preserved. The combination of FUS with MRI for planning, (near) real-time monitoring and outcome assessment of treatment markedly enhances the safety of the procedure. The MRgFUS procedure is clinically established in particular for the treatment of symptomatic uterine fibroids, followed by palliative ablation of painful bone metastases. Furthermore, promising results have been shown for the treatment of adenomyosis, malignant tumors of the prostate, breast and liver and for various intracranial applications, such as thermal ablation of brain tumors, functional neurosurgery and transient disruption of the blood-brain barrier.

High Intensity Focused Ultrasound: A Novel Model of Mild Traumatic Brain Injury

DTIC Science & Technology

2013-11-07

RE, Melo B, Christensen B, Ngo L-A, Monette G, Bradbury C. 2008. Measuring premorbid IQ in traumatic brain injury: An examination of the validity of...High Intensity Focused Ultrasound: A Novel Model of Mild Traumatic Brain Injury by Brendan J. Finton Thesis...Mild Traumatic Brain Injury" is appropriately acknowledged and, beyond brief excerpts, is with the permission of the copyright owner. Brendan J

A Multicenter Controlled Study to Evaluate Multiple Treatments With Nonthermal Focused Ultrasound for Noninvasive Fat Reduction.

PubMed

Coleman, William P; Coleman, William; Weiss, Robert A; Kenkel, Jeffrey M; Ad-El, Dean D; Amir, Ruthie

2017-01-01

Demand for nonsurgical esthetic body procedures has led to the development of noninvasive techniques for reducing localized subcutaneous adipose tissue. This study assessed multiple treatments with nonthermal focused ultrasound for noninvasive abdominal treatment of excess fat deposits. Subjects were randomly assigned to Group 1 for a 4-week control phase before undergoing 3 abdominal fat reduction treatments, at 2-week intervals, or to Group 2 for immediate treatment. Weight, abdominal circumference, tolerability to treatment, subject satisfaction, and adverse events were recorded. Weight remained stable in the 126 participants. Mean reduction in midline circumference was 2.5 ± 2.1 cm in the Group 1 and 3.5 ± 2.7 cm in the Group 2 at Week 22. The effect of multiple treatments was cumulative with a steady decrease in abdominal circumferences during the study. Erythema was observed in 28% of treatments but was mild and transient in nature. Subjects tolerated the treatments well and were satisfied with treatment outcome. The study demonstrated the efficacy and safety of multiple nonthermal focused ultrasound treatments of excess abdominal fat deposits. Although the remodeling effect is minor compared with traditional surgical procedures, successive focused ultrasound treatments significantly reduced treatment area circumference, while avoiding invasive techniques and their associated disadvantages.

Using passive cavitation images to classify high-intensity focused ultrasound lesions.

PubMed

Haworth, Kevin J; Salgaonkar, Vasant A; Corregan, Nicholas M; Holland, Christy K; Mast, T Douglas

2015-09-01

Passive cavitation imaging provides spatially resolved monitoring of cavitation emissions. However, the diffraction limit of a linear imaging array results in relatively poor range resolution. Poor range resolution has limited prior analyses of the spatial specificity and sensitivity of passive cavitation imaging in predicting thermal lesion formation. In this study, this limitation is overcome by orienting a linear array orthogonal to the high-intensity focused ultrasound propagation direction and performing passive imaging. Fourteen lesions were formed in ex vivo bovine liver samples as a result of 1.1-MHz continuous-wave ultrasound exposure. The lesions were classified as focal, "tadpole" or pre-focal based on their shape and location. Passive cavitation images were beamformed from emissions at the fundamental, harmonic, ultraharmonic and inharmonic frequencies with an established algorithm. Using the area under a receiver operating characteristic curve (AUROC), fundamental, harmonic and ultraharmonic emissions were found to be significant predictors of lesion formation for all lesion types. For both harmonic and ultraharmonic emissions, pre-focal lesions were classified most successfully (AUROC values of 0.87 and 0.88, respectively), followed by tadpole lesions (AUROC values of 0.77 and 0.64, respectively) and focal lesions (AUROC values of 0.65 and 0.60, respectively). Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Transmural ultrasound imaging of thermal lesion and action potential changes in perfused canine cardiac wedge preparations by high intensity focused ultrasound ablation.

PubMed

Wu, Ziqi; Gudur, Madhu S R; Deng, Cheri X

2013-01-01

Intra-procedural imaging is important for guiding cardiac arrhythmia ablation. It is difficult to obtain intra-procedural correlation of thermal lesion formation with action potential (AP) changes in the transmural plane during ablation. This study tested parametric ultrasound imaging for transmural imaging of lesion and AP changes in high intensity focused ultrasound (HIFU) ablation using coronary perfused canine ventricular wedge preparations (n = 13). The preparations were paced from epi/endocardial surfaces and subjected to HIFU application (3.5 MHz, 11 Hz pulse-repetition-frequency, 70% duty cycle, duration 4 s, 3500 W/cm(2)), during which simultaneous optical mapping (1 kframes/s) using di-4-ANEPPS and ultrasound imaging (30 MHz) of the same transmural surface of the wedge were performed. Spatiotemporally correlated AP measurements and ultrasound imaging allowed quantification of the reduction of AP amplitude (APA), shortening of AP duration at 50% repolarization, AP triangulation, decrease of optical AP rise, and change of conduction velocity along tissue depth direction within and surrounding HIFU lesions. The threshold of irreversible change in APA correlating to lesions was determined to be 43 ± 1% with a receiver operating characteristic (ROC) area under curve (AUC) of 0.96 ± 0.01 (n = 13). Ultrasound imaging parameters such as integrated backscatter, Rayleigh (α) and log-normal (σ) parameters, cumulative extrema of σ were tested, with the cumulative extrema of σ performing the best in detecting lesion (ROC AUC 0.89 ± 0.01, n = 13) and change of APA (ROC AUC 0.79 ± 0.03, n = 13). In conclusion, characteristic tissue and AP changes in HIFU ablation were identified and spatiotemporally correlated using optical mapping and ultrasound imaging. Parametric ultrasound imaging using cumulative extrema of σ can detect HIFU lesion and APA reduction.

Transmural Ultrasound Imaging of Thermal Lesion and Action Potential Changes in Perfused Canine Cardiac Wedge Preparations by High Intensity Focused Ultrasound Ablation

PubMed Central

Wu, Ziqi; Gudur, Madhu S. R.; Deng, Cheri X.

2013-01-01

Intra-procedural imaging is important for guiding cardiac arrhythmia ablation. It is difficult to obtain intra-procedural correlation of thermal lesion formation with action potential (AP) changes in the transmural plane during ablation. This study tested parametric ultrasound imaging for transmural imaging of lesion and AP changes in high intensity focused ultrasound (HIFU) ablation using coronary perfused canine ventricular wedge preparations (n = 13). The preparations were paced from epi/endocardial surfaces and subjected to HIFU application (3.5 MHz, 11 Hz pulse-repetition-frequency, 70% duty cycle, duration 4 s, 3500 W/cm2), during which simultaneous optical mapping (1 kframes/s) using di-4-ANEPPS and ultrasound imaging (30 MHz) of the same transmural surface of the wedge were performed. Spatiotemporally correlated AP measurements and ultrasound imaging allowed quantification of the reduction of AP amplitude (APA), shortening of AP duration at 50% repolarization, AP triangulation, decrease of optical AP rise, and change of conduction velocity along tissue depth direction within and surrounding HIFU lesions. The threshold of irreversible change in APA correlating to lesions was determined to be 43±1% with a receiver operating characteristic (ROC) area under curve (AUC) of 0.96±0.01 (n = 13). Ultrasound imaging parameters such as integrated backscatter, Rayleigh (α) and log-normal (σ) parameters, cumulative extrema of σ were tested, with the cumulative extrema of σ performing the best in detecting lesion (ROC AUC 0.89±0.01, n = 13) and change of APA (ROC AUC 0.79±0.03, n = 13). In conclusion, characteristic tissue and AP changes in HIFU ablation were identified and spatiotemporally correlated using optical mapping and ultrasound imaging. Parametric ultrasound imaging using cumulative extrema of σ can detect HIFU lesion and APA reduction. PMID:24349337

Realtime control of multiple-focus phased array heating patterns based on noninvasive ultrasound thermography.

PubMed

Casper, Andrew; Liu, Dalong; Ebbini, Emad S

2012-01-01

A system for the realtime generation and control of multiple-focus ultrasound phased-array heating patterns is presented. The system employs a 1-MHz, 64-element array and driving electronics capable of fine spatial and temporal control of the heating pattern. The driver is integrated with a realtime 2-D temperature imaging system implemented on a commercial scanner. The coordinates of the temperature control points are defined on B-mode guidance images from the scanner, together with the temperature set points and controller parameters. The temperature at each point is controlled by an independent proportional, integral, and derivative controller that determines the focal intensity at that point. Optimal multiple-focus synthesis is applied to generate the desired heating pattern at the control points. The controller dynamically reallocates the power available among the foci from the shared power supply upon reaching the desired temperature at each control point. Furthermore, anti-windup compensation is implemented at each control point to improve the system dynamics. In vitro experiments in tissue-mimicking phantom demonstrate the robustness of the controllers for short (2-5 s) and longer multiple-focus high-intensity focused ultrasound exposures. Thermocouple measurements in the vicinity of the control points confirm the dynamics of the temperature variations obtained through noninvasive feedback. © 2011 IEEE

PULSED FOCUSED ULTRASOUND TREATMENT OF MUSCLE MITIGATES PARALYSIS-INDUCED BONE LOSS IN THE ADJACENT BONE: A STUDY IN A MOUSE MODEL

PubMed Central

Poliachik, Sandra L.; Khokhlova, Tatiana D.; Wang, Yak-Nam; Simon, Julianna C.; Bailey, Michael R.

2015-01-01

Bone loss can result from bed rest, space flight, spinal cord injury or age-related hormonal changes. Current bone loss mitigation techniques include pharmaceutical interventions, exercise, pulsed ultrasound targeted to bone and whole body vibration. In this study, we attempted to mitigate paralysis-induced bone loss by applying focused ultrasound to the midbelly of a paralyzed muscle. We employed a mouse model of disuse that uses onabotulinumtoxinA-induced paralysis, which causes rapid bone loss in 5 d. A focused 2 MHz transducer applied pulsed exposures with pulse repetition frequency mimicking that of motor neuron firing during walking (80 Hz), standing (20 Hz), or the standard pulsed ultrasound frequency used in fracture healing (1 kHz). Exposures were applied daily to calf muscle for 4 consecutive d. Trabecular bone changes were characterized using micro-computed tomography. Our results indicated that application of certain focused pulsed ultrasound parameters was able to mitigate some of the paralysis-induced bone loss. PMID:24857416

Optimizing MR imaging-guided navigation for focused ultrasound interventions in the brain

NASA Astrophysics Data System (ADS)

Werner, B.; Martin, E.; Bauer, R.; O'Gorman, R.

2017-03-01

MR imaging during transcranial MR imaging-guided Focused Ultrasound surgery (tcMRIgFUS) is challenging due to the complex ultrasound transducer setup and the water bolus used for acoustic coupling. Achievable image quality in the tcMRIgFUS setup using the standard body coil is significantly inferior to current neuroradiologic standards. As a consequence, MR image guidance for precise navigation in functional neurosurgical interventions using tcMRIgFUS is basically limited to the acquisition of MR coordinates of salient landmarks such as the anterior and posterior commissure for aligning a stereotactic atlas. Here, we show how improved MR image quality provided by a custom built MR coil and optimized MR imaging sequences can support imaging-guided navigation for functional tcMRIgFUS neurosurgery by visualizing anatomical landmarks that can be integrated into the navigation process to accommodate for patient specific anatomy.

Lysis of Chlamydomonas reinhardtii by high-intensity focused ultrasound as a function of exposure time.

PubMed

Bigelow, Timothy A; Xu, Jin; Stessman, Dan J; Yao, Linxing; Spalding, Martin H; Wang, Tong

2014-05-01

Efficient lysis of microalgae for lipid extraction is an important concern when processing biofuels. Historically, ultrasound frequencies in the range of 10-40 kHz have been utilized for this task. However, greater efficiencies might be achievable if higher frequencies could be used. In our study, we evaluated the potential of using 1.1 MHz ultrasound to lyse microalgae for biofuel production while using Chlamydomonas reinhardtii as a model organism. The ultrasound was generated using a spherically focused transducer with a focal length of 6.34 cm and an active diameter of 6.36 cm driven by 20 cycle sine-wave tone bursts at a pulse repetition frequency of 2 kHz (3.6% duty cycle). The time-average acoustic power output was 26.2 W while the spatial-peak-pulse-average intensity (ISPPA) for each tone burst was 41 kW/cm(2). The peak compressional and rarefactional pressures at the focus were 102 and 17 MPa, respectively. The exposure time was varied for the different cases in the experiments from 5s to 9 min and cell lysis was assessed by quantifying the percentage of protein and chlorophyll release into the supernate as well as the lipid extractability. Free radical generation and lipid oxidation for the different ultrasound exposures were also determined. We found that there was a statistically significant increase in lipid extractability for all of the exposures compared to the control. The longer exposures also completely fragmented the cells releasing almost all of the protein and chlorophyll into the supernate. The cavitation activity did not significantly increase lipid oxidation while there was a minor trend of increased free radical production with increased ultrasound exposure. Copyright © 2013 Elsevier B.V. All rights reserved.

Oblong-Shaped-Focused Transducers for Intravascular Ultrasound Imaging.

PubMed

Lee, Junsu; Jang, Jihun; Chang, Jin Ho

2017-03-01

In intravascular ultrasound (IVUS) imaging, a transducer is inserted into a blood vessel and rotated to obtain image data. For this purpose, the transducer aperture is typically less than 0.5 mm in diameter, which causes natural focusing to occur in the imaging depth ranging from 1 to 5 mm. Due to the small aperture, however, it is not viable to conduct geometric focusing in order to enhance the spatial resolution of IVUS images. Furthermore, this hampers narrowing the slice thickness of a cross-sectional scan plane in the imaging depth, which leads to lowering spatial and contrast resolutions of IVUS images. To solve this problem, we propose an oblong-shaped-focused transducer for IVUS imaging. Unlike the conventional IVUS transducers with either a circular or a square flat aperture, the proposed transducer has an oblong aperture of which long side is positioned along a blood vessel. This unique configuration makes it possible to conduct geometric focusing at a desired depth in the elevation direction. In this study, furthermore, it is demonstrated that a spherically shaped aperture in both lateral and elevation directions also improves lateral resolution, compared to the conventional flat aperture. To ascertain this, the conventional and the proposed IVUS transducers were designed and fabricated to evaluate and to compare their imaging performances through wire phantom and tissue-mimicking phantom experiments. For the proposed 50-MHz IVUS transducer, a PZT piece of 0.5 × 1.0 mm 2 was spherically shaped for elevation focus at 3 mm by using the conventional press-focusing technique whereas the conventional one has a flat aperture of 0.5 × 0.5 mm 2 . The experimental results demonstrated that the proposed IVUS transducer is capable of improving spatial and contrast resolutions of IVUS images.

Potential mechanism in sonodynamic therapy and focused ultrasound induced apoptosis in sarcoma 180 cells in vitro.

PubMed

Tang, Wei; Liu, Quanhong; Wang, Xiaobing; Wang, Pan; Zhang, Jing; Cao, Bing

2009-12-01

Sonodynamic therapy employs a combination of ultrasound and a sonosensitizer to enhance the cytotoxic effect of ultrasound and promote apoptosis. However, the mechanism underlying the synergistic effect of ultrasound and hematoporphyrin is still unclear. In this study, we investigated mechanism of the induction of apoptosis by sonodynamic therapy in Sarcoma 180 cells. The cell suspension was treated by 1.75-MHz focused continuous ultrasound at an acoustic power (I(SATA)) of 1.4+/-0.07 W/cm(2) for 3 min in the absence or presence of 20 microg/ml hematoporphyrin. The proportion of apoptotic cells was determined by flow cytometry. We then analyzed the reactive oxygen species generation and localization by confocal microscopy. Western blotting and reverse transcriptase-polymerase chain reaction were used to analyze the expression of caspase-8, caspase-9, poly(ADP)-ribose polymerase, and nuclear factor-kappaB. The findings of our study indicate that ultrasound treatment induced the activation of nuclear factor-kappaB as an early stress response. When cells were pretreated with hematoporphyrin, the initial response to the therapy was the formation of (1)O(2) in the mitochondria. Our results primarily demonstrate that the mechanisms of induction of apoptosis by ultrasound and hematoporphyrin-sonodynamic therapies are very different. Our findings can provide a basis for explaining the synergistic effect of ultrasound and hematoporphyrin.

Intensification of the impact of high-intensity focused ultrasound (HIFU) with special spatiotemporal modulation

NASA Astrophysics Data System (ADS)

Gusev, V. A.; Rudenko, O. V.

2013-01-01

The principle of forming a special form of powerful acoustic signals is proposed, which makes it possible to ensure precise spatiotemporal beam focusing. The introduction of a transverse-coordinate-dependent local wave frequency is suggested, due to which the equality of the formation lengths of a discontinuity for all rays is achieved. This thereby ensures an increase in nonlinear absorption; as a result, the temperature and radiation action of focused ultrasound on the medium increase.

Arbitrary shaped, liquid filled reverberators with non-resonant transducers for broadband focusing of ultrasound using Time Reversed Acoustics.

PubMed

Sarvazyan, A; Fillinger, L

2009-03-01

The ability to generate short focused ultrasonic pulses with duration on the order of one period of carrier frequency depends on the bandwidth of the transmitter as the pulse duration is inversely proportional to the bandwidth. Conventional focusing arrays used for focusing ultrasound have limited bandwidth due to the resonant nature of the piezoelements generating ultrasound. Theoretically it is possible to build a broadband phased array composed of "non-resonant" elements: wedge-shaped or flat-concave piezotransducers, though there are numerous technical difficulties in designing arrays with hundreds of elements of complex shape. This task is much easier to realize in an alternative technique of ultrasound focusing based on the principles of Time Reversed Acoustics (TRA) because in TRA systems, effective focusing can be achieved with just a few, or even one, transducers. The goal of this study is to demonstrate the possibility of broadband focusing of ultrasonic waves using a TRA system with non-resonant transducers and to explore the factors affecting the performance of such a system. A new type of TRA reverberators, such as water-filled thin-wall plastic vessels, which can be used with the submersible piezotransducers fixed internally in the reverberator, are proposed and tested. The experiments are conducted in a water tank with the walls and bottom covered by a sound absorbing lining. A needle hydrophone mounted on a 3D positioning system is used as a beacon for the TRA focusing and then for measuring the spatial distribution of the focused ultrasound field. The bandwidth and spatial distribution of the signal focused by the TRA system using a single channel with the resonant versus non-resonant transducers have been analyzed. Two types of non-resonant transducers were tested: a flat-concave transducer with a diameter of 30 mm, and a thickness varying from 2 mm in the center to 11 mm at the edge, and a specially designed submersible transducer having an

MR-guided focused ultrasound surgery, present and future

PubMed Central

Schlesinger, David; Benedict, Stanley; Diederich, Chris; Gedroyc, Wladyslaw; Klibanov, Alexander; Larner, James

2013-01-01

MR-guided focused ultrasound surgery (MRgFUS) is a quickly developing technology with potential applications across a spectrum of indications traditionally within the domain of radiation oncology. Especially for applications where focal treatment is the preferred technique (for example, radiosurgery), MRgFUS has the potential to be a disruptive technology that could shift traditional patterns of care. While currently cleared in the United States for the noninvasive treatment of uterine fibroids and bone metastases, a wide range of clinical trials are currently underway, and the number of publications describing advances in MRgFUS is increasing. However, for MRgFUS to make the transition from a research curiosity to a clinical standard of care, a variety of challenges, technical, financial, clinical, and practical, must be overcome. This installment of the Vision 20/20 series examines the current status of MRgFUS, focusing on the hurdles the technology faces before it can cross over from a research technique to a standard fixture in the clinic. It then reviews current and near-term technical developments which may overcome these hurdles and allow MRgFUS to break through into clinical practice. PMID:23927296

MR-guided adaptive focusing of therapeutic ultrasound beams in the human head

PubMed Central

Marsac, Laurent; Chauvet, Dorian; Larrat, Benoît; Pernot, Mathieu; Robert, B.; Fink, Mathias; Boch, Anne-Laure; Aubry, Jean-François; Tanter, Mickaël

2012-01-01

Purpose This study aims to demonstrate, using human cadavers the feasibility of energy-based adaptive focusing of ultrasonic waves using Magnetic Resonance Acoustic Radiation Force Imaging (MR-ARFI) in the framework of non-invasive transcranial High Intensity Focused Ultrasound (HIFU) therapy. Methods Energy-based adaptive focusing techniques were recently proposed in order to achieve aberration correction. We evaluate this method on a clinical brain HIFU system composed of 512 ultrasonic elements positioned inside a full body 1.5 T clinical Magnetic Resonance (MR) imaging system. Cadaver heads were mounted onto a clinical Leksell stereotactic frame. The ultrasonic wave intensity at the chosen location was indirectly estimated by the MR system measuring the local tissue displacement induced by the acoustic radiation force of the ultrasound (US) beams. For aberration correction, a set of spatially encoded ultrasonic waves was transmitted from the ultrasonic array and the resulting local displacements were estimated with the MR-ARFI sequence for each emitted beam. A non-iterative inversion process was then performed in order to estimate the spatial phase aberrations induced by the cadaver skull. The procedure was first evaluated and optimized in a calf brain using a numerical aberrator mimicking human skull aberrations. The full method was then demonstrated using a fresh human cadaver head. Results The corrected beam resulting from the direct inversion process was found to focus at the targeted location with an acoustic intensity 2.2 times higher than the conventional non corrected beam. In addition, this corrected beam was found to give an acoustic intensity 1.5 times higher than the focusing pattern obtained with an aberration correction using transcranial acoustic simulation based on X-ray computed tomography (CT) scans. Conclusion The proposed technique achieved near optimal focusing in an intact human head for the first time. These findings confirm the strong

Noninvasive transcranial stimulation of rat abducens nerve by focused ultrasound.

PubMed

Kim, Hyungmin; Taghados, Seyed Javid; Fischer, Krisztina; Maeng, Lee-So; Park, Shinsuk; Yoo, Seung-Schik

2012-09-01

Nonpharmacologic and nonsurgical transcranial modulation of the nerve function may provide new opportunities in evaluation and treatment of cranial nerve diseases. This study investigates the possibility of using low-intensity transcranial focused ultrasound (FUS) to selectively stimulate the rat abducens nerve located above the base of the skull. FUS (frequencies of 350 kHz and 650 kHz) operating in a pulsed mode was applied to the abducens nerve of Sprague-Dawley rats under stereotactic guidance. The abductive eyeball movement ipsilateral to the side of sonication was observed at 350 kHz, using the 0.36-msec tone burst duration (TBD), 1.5-kHz pulse repetition frequency (PRF), and the overall sonication duration of 200 msec. Histologic and behavioral monitoring showed no signs of disruption in the blood brain barrier (BBB), as well as no damage to the nerves and adjacent brain tissue resulting from the sonication. As a novel functional neuro-modulatory modality, the pulsed application of FUS has potential for diagnostic and therapeutic applications in diseases of the peripheral nervous system. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Ultrasound-Guided Transesophageal High-Intensity Focused Ultrasound Cardiac Ablation in a Beating Heart: A Pilot Feasibility Study in Pigs.

PubMed

Bessiere, Francis; N'djin, W Apoutou; Colas, Elodie Constanciel; Chavrier, Françoise; Greillier, Paul; Chapelon, Jean Yves; Chevalier, Philippe; Lafon, Cyril

2016-08-01

Catheter ablation for the treatment of arrhythmia is associated with significant complications and often-repeated procedures. Consequently, a less invasive and more efficient technique is required. Because high-intensity focused ultrasound (HIFU) enables the generation of precise thermal ablations in deep-seated tissues without harming the tissues in the propagation path, it has the potential to be used as a new ablation technique. A system capable of delivering HIFU into the heart by a transesophageal route using ultrasound (US) imaging guidance was developed and tested in vivo in six male pigs. HIFU exposures were performed on atria and ventricles. At the time of autopsy, visual inspection identified thermal lesions in the targeted areas in three of the animals. These lesions were confirmed by histologic analysis (mean size: 5.5 mm(2) × 11 mm(2)). No esophageal thermal injury was observed. One animal presented with bradycardia due to an atrio-ventricular block, which provides real-time confirmation of an interaction between HIFU and the electrical circuits of the heart. Thus, US-guided HIFU has the potential to minimally invasively create myocardial lesions without an intra-cardiac device. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Pathological, Oncologic and Functional Outcomes of a Prospective Registry of Salvage High Intensity Focused Ultrasound Ablation for Radiorecurrent Prostate Cancer.

PubMed

Siddiqui, Khurram M; Billia, Michele; Arifin, Andrew; Li, Fan; Violette, Philippe; Chin, Joseph L

2017-01-01

In this prospective registry we prospectively assessed the oncologic, functional and safety outcomes of salvage high intensity focused ultrasound for radiorecurrent prostate cancer. A total of 81 men were prospectively recruited and evaluated at regular scheduled study visits to 6 months after high intensity focused ultrasound and thereafter as per standard of care. Transrectal ultrasound guided biopsy was performed at 6 months. The primary end point was absence or histological persistence of disease at 6-month biopsy. Secondary end points included quality of life, biochemical recurrence-free survival, overall survival, cancer specific survival and progression to androgen deprivation therapy. Survival analysis was performed according to the Kaplan-Meier method and multivariate analysis was performed using the log rank (Mantel-Cox) test. Mean ± SD prostate specific antigen before high intensity focused ultrasound was 4.06 ± 2.88 ng/ml. At 6 months 63 men underwent biopsy, of whom 22 (35%) had residual disease. At a mean followup of 53.5 ± 31.6 months median biochemical recurrence-free survival was 63 months. The 5-year overall and cancer specific survival rates were 88% and 94.4%, respectively. Nadir prostate specific antigen less than 0.5 ng/ml was a significant predictor of biochemical recurrence-free survival (p=0.014, 95% CI 1.22-5.87). I-PSS significantly increased (p <0.001) while IIEF-5 scores decreased and the SF-36 score did not change significantly. The rate of rectal fistulization and severe incontinence was 3.7% each. A total of 223 complications were recorded in the 180 days after high intensity focused ultrasound (Clavien-Dindo grade 1-195, grade II-20, grade III-7, grade IVa-1). Salvage high intensity focused ultrasound appears to be a viable treatment option for radiorecurrent prostate cancer, with acceptable morbidity. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Focused ultrasound transducer spatial peak intensity estimation: a comparison of methods

NASA Astrophysics Data System (ADS)

Civale, John; Rivens, Ian; Shaw, Adam; ter Haar, Gail

2018-03-01

Characterisation of the spatial peak intensity at the focus of high intensity focused ultrasound transducers is difficult because of the risk of damage to hydrophone sensors at the high focal pressures generated. Hill et al (1994 Ultrasound Med. Biol. 20 259-69) provided a simple equation for estimating spatial-peak intensity for solid spherical bowl transducers using measured acoustic power and focal beamwidth. This paper demonstrates theoretically and experimentally that this expression is only strictly valid for spherical bowl transducers without a central (imaging) aperture. A hole in the centre of the transducer results in over-estimation of the peak intensity. Improved strategies for determining focal peak intensity from a measurement of total acoustic power are proposed. Four methods are compared: (i) a solid spherical bowl approximation (after Hill et al 1994 Ultrasound Med. Biol. 20 259-69), (ii) a numerical method derived from theory, (iii) a method using measured sidelobe to focal peak pressure ratio, and (iv) a method for measuring the focal power fraction (FPF) experimentally. Spatial-peak intensities were estimated for 8 transducers at three drive powers levels: low (approximately 1 W), moderate (~10 W) and high (20-70 W). The calculated intensities were compared with those derived from focal peak pressure measurements made using a calibrated hydrophone. The FPF measurement method was found to provide focal peak intensity estimates that agreed most closely (within 15%) with the hydrophone measurements, followed by the pressure ratio method (within 20%). The numerical method was found to consistently over-estimate focal peak intensity (+40% on average), however, for transducers with a central hole it was more accurate than using the solid bowl assumption (+70% over-estimation). In conclusion, the ability to make use of an automated beam plotting system, and a hydrophone with good spatial resolution, greatly facilitates characterisation of the FPF, and

A novel transcutaneous, non-focused ultrasound energy delivering device is able to induce subcutaneous adipose tissue destruction in an animal model.

PubMed

Levi, Assi; Amitai, Dan Ben; Lapidoth, Moshe

2017-01-01

The understanding that adipocytes are greatly influenced by thermal changes combined with the advancement of non-invasive ultrasound technologies have led to the application of ultrasound as an energy source to induce thermal fat destruction. While application of high intensity focused, ultrasound energy have been widely explored, there is far less information regarding the effects of non-focused ultrasound on adipose tissue. The purpose of this study was to characterize the effects of a novel transcutaneous, multi-elements, non-focused ultrasound energy regimen in an animal model, as a proof-of-concept of its potential to treat non-invasive subcutaneous benign tumors. The non-invasive transcutaneous ultrasound system prototype (LUMENIS, Ltd., Yoqneam, Israel) was applied to thermally induce adipocytes' death. During treatment, the ultrasound energy was transmitted into the subcutaneous adipose tissue (SAT) of 12 domestic adult female pigs. Two modes of operation (long and short), which differ in both the acoustic energy applied to the tissue and in their time durations (i.e., differ in their power settings), were used in this study. Efficacy and safety assessments included: Temperature measurement of skin and subcutaneous adipose tissue (SAT) visual inspection and ultrasound imaging of the thermally affected areas, histopathological assessment of tissue samples using hematoxylin & eosin, and Masson's trichrome stains and in situ cell death detection kit for apoptosis assessment. The long and short treatment modes led to a 13.2°C and 17.8°C rise from baseline, respectively, in the SAT, whereas skin surface temperature was practically unaffected. Visual, ultrasonographic, and histopathological evaluation of the treated area showed SAT ablation. No treatment-related changes were observed in the epidermis, dermis subcutaneous muscle and nerves, or in livers and kidneys of treated animals. Additionally, no significant changes from baseline in blood- and urine

Long-term outcomes following high intensity focused ultrasound ablation for atrial fibrillation.

PubMed

Davies, Edward J; Bazerbashi, Samer; Asopa, Sanjay; Haywood, Guy; Dalrymple-Hay, Malcolm

2014-01-01

The aim of this study is to assess the safety and efficacy of the Epicor high intensity focused ultrasound (St. Jude, Inc.®, Minneapolis, MN, USA) system using seven-day ambulatory electrocardiogram (ECG) monitoring over a two-year follow-up period. One hundred and ten patients undergoing ablation were included from a single center between January 2006 and December 2009. Rhythm was assessed using seven-day ambulatory ECG or permanent pacemaker interrogation. Seventeen patients were lost to follow-up, seven through death. Results were reported according to atrial fibrillation (AF) class preoperatively: paroxysmal, persistent, and long-standing persistent (LSP). Forty-nine percent of patients remained in sinus rhythm at greater than two years. The percentage of patients in sinus rhythm according to preoperative AF class were 81% (paroxysmal AF), 56% (persistent AF), and 18% (long-standing AF). The class of AF prior to surgery, left atrium size, and body mass index determined the long-term outcome. There were no procedure-related complications. We conclude that high intensity focused ultrasound ablation for atrial fibrillation using the Epicor system is safe and effective for surgical patients with paroxysmal AF. The persistent and LSP AF results suggest that alternative ablation strategies should be considered for these patients. © 2013 Wiley Periodicals, Inc.

A multi-element high intensity focused ultrasound transducer: Design, fabrication, and testing

NASA Astrophysics Data System (ADS)

Vaezy, Shahram; Held, Robert; Miller, Blake; Fleury, Gerard

2004-05-01

The goal of this project is to develop an intra-cavity image-guided high intensity focused ultrasound (HIFU) device using piezocomposite technology and commercially available ultrasound imaging. The HIFU array, manufactured by Imasonic Corporation, is an 11-element annular phased array, with a focal length range of 30-60 mm, and operating frequency of 3 MHz (bandwidth of 1 MHz). The imaging probe (C9-5, Philips) is configured such that the focal axis of the HIFU beam was within the image plane. The array includes six complete central rings and five side-truncated peripheral rings, all with the natural radius of curvature of 50 mm. Impedance of all elements is approximately 50 ohms (10% accuracy for real and imaginary parts). Cross coupling between adjacent elements is less than, -40 dB. High power measurements showed more than 75% efficiency, at surface intensity of 2.66 W/cm2. Schlieren imaging showed effective focusing at all focal lengths (30-60 mm). The image-guided HIFU device requires water or hydrogel coupling, and possibly water cooling. The results of the full characterization for lesion formation in tissue-mimicking phantoms and biological tissues will be presented. Possible applications include uterine fibroids, abnormal uterine bleeding, and intraoperative hemostasis of occult hemorrhage.

MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits.

PubMed

McDannold, Nathan; Vykhodtseva, Natalia; Raymond, Scott; Jolesz, Ferenc A; Hynynen, Kullervo

2005-11-01

Focused ultrasound offers a method to disrupt the blood-brain barrier (BBB) noninvasively and reversibly at targeted locations. The purpose of this study was to test the safety of this method by searching for ischemia and apoptosis in areas with BBB disruption induced by pulsed ultrasound in the presence of preformed gas bubbles and by looking for delayed effects up to one month after sonication. Pulsed ultrasound exposures (sonications) were performed in the brains of 24 rabbits under monitoring by magnetic resonance imaging (MRI) (ultrasound: frequency = 1.63 MHz, burst length = 100 ms, PRF = 1 Hz, duration = 20 s, pressure amplitude 0.7 to 1.0 MPa). Before sonication, an ultrasound contrast agent (Optison, GE Healthcare, Milwaukee, WI, USA) was injected IV. BBB disruption was confirmed with contrast-enhanced MR images. Whole brain histologic examination was performed using haematoxylin and eosin staining for general histology, vanadium acid fuchsin-toluidine blue staining for ischemic neurons and TUNEL staining for apoptosis. The main effects observed were tiny regions of extravasated red blood cells scattered around the sonicated locations, indicating affected capillaries. Despite these vasculature effects, only a few cells in some of the sonicated areas showed evidence for apoptosis or ischemia. No ischemic or apoptotic regions were detected that would indicate a compromised blood supply was induced by the sonications. No delayed effects were observed either by MRI or histology up to 4 wk after sonication. Ultrasound-induced BBB disruption is possible without inducing substantial vascular damage that would result in ischemic or apoptotic death to neurons. These findings indicate that this method is safe for targeted drug delivery, at least when compared with the currently available invasive methods.

Modes of targets in water excited and identified using radiation pressure of modulated focused ultrasound

NASA Astrophysics Data System (ADS)

Daniel, Timothy; Fortuner, Auberry; Abawi, Ahmad; Kirsteins, Ivars; Marston, Philip

2016-11-01

The modulated radiation pressure (MRP) of ultrasound has been widely used to selectively excite low frequency modes of fluid objects. We previously used MRP to excite less compliant metallic object in water including the low frequency modes of a circular metal plate in water. A larger focused ultrasonic transducer allows us to drive modes of larger more-realistic targets. In our experiments solid targets are suspended by strings or supported on sand and the modulated ultrasound is focused on the target's surface. Target sound emissions were recorded and a laser vibrometer was used to measure the surface velocity of the target to give the magnitude of the target response. The source transducer was driven with a doublesideband suppressed carrier voltage as in. By varying the modulation frequency and monitoring target response, resonant frequencies can be measured and compared to finite element models. We also demonstrate the radiation torque of a focused first-order acoustic vortex beam associated with power absorption in the Stokes layer adjacent to a sphere. Funded by ONR.

Multi-parametric monitoring of high intensity focused ultrasound (HIFU) treatment using harmonic motion imaging for focused ultrasound (HMIFU)

NASA Astrophysics Data System (ADS)

Hou, Gary Y.; Marquet, Fabrice; Wang, Shutao; Konofagou, Elisa

2012-11-01

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in vitro and in vivo. Here, a multi-parametric study is performed to investigate both elastic and acoustics-independent viscoelastic tissue changes using the Harmonic Motion Imaging (HMI) displacement, axial compressive strain and relative phase-shift during high energy HIFU where tissue boiling occurs. Forty three (n=18) thermal lesions were formed in ex vivo canine liver specimens. Two dimensional (2D) transverse HMI displacement maps were also obtained before and after lesion formation. The same method was repeated in 10-, 20-and 30-s HIFU durations at three different acoustic powers of 8, 10, and 11W. For the 10-, 20-, and 30-s treatment cases, a steady decrease in the displacement (-8.67±4.80, -14.44±7.77, 24.03±12.11μm), compressive strain -0.16±0.06, -0.71±0.30, -0.68±0.36 %, and phase shift +1.80±6.80, -15.80±9.44, -18.62±13.14 ° were obtained, respectively, indicating overall increase of relative stiffness and decrease of the viscosity-to-stiffness ratio during heating. After treatment, 2D HMI displacement images of the thermal lesions showed an increased lesion-to-background contrast of 1.34±0.19, 1.98±0.30, 2.26±0.80 and lesion size of 40.95±8.06, 47.6±4.87, and 52.23±2.19 mm2, respectively, which was validated again with pathology 25.17±6.99, 42.17±1.77, 47.17±3.10 mm2. Additionally, studies also investigated the performance of mutli-parametric monitoring under the influence of boiling and attenuation change due to tissue boiling, where discrepancies were found such as deteriorated displacement SNR and reversed lesion-to-background displacement contrast with indication on possible increase in attenuation and tissue gelatification or pulverization. Despite the challenge of the boiling mechanism, the relative phase shift served as consist biomechanical tissue

Ultrasound and polar homogeneous reactions.

PubMed

Tuulmets, A

1997-04-01

The effect of ultrasound on the rates of homogeneous heterolytic reactions not switched to a free radical pathway can be explained by the perturbation of the molecular organization of or the solvation in the reacting system. A quantitative analysis of the sonochemical acceleration on the basis of the microreactor concept was carried out. It was found that (1) the Diels-Alder reaction cannot be accelerated by ultrasound except when SET or free radical processes are promoted, (2) the rectified diffusion during cavitation cannot be responsible for the acceleration of reactions, and (3) the sonochemical acceleration of polar homogeneous reactions takes place in the bulk reaction medium. This implies the presence of a 'sound-field' sonochemistry besides the 'hot-spot' sonochemistry. The occurrence of a sonochemical deceleration effect can be predicted.

Open-source, small-animal magnetic resonance-guided focused ultrasound system.

PubMed

Poorman, Megan E; Chaplin, Vandiver L; Wilkens, Ken; Dockery, Mary D; Giorgio, Todd D; Grissom, William A; Caskey, Charles F

2016-01-01

MR-guided focused ultrasound or high-intensity focused ultrasound (MRgFUS/MRgHIFU) is a non-invasive therapeutic modality with many potential applications in areas such as cancer therapy, drug delivery, and blood-brain barrier opening. However, the large financial costs involved in developing preclinical MRgFUS systems represent a barrier to research groups interested in developing new techniques and applications. We aim to mitigate these challenges by detailing a validated, open-source preclinical MRgFUS system capable of delivering thermal and mechanical FUS in a quantifiable and repeatable manner under real-time MRI guidance. A hardware and software package was developed that includes closed-loop feedback controlled thermometry code and CAD drawings for a therapy table designed for a preclinical MRI scanner. For thermal treatments, the modular software uses a proportional integral derivative controller to maintain a precise focal temperature rise in the target given input from MR phase images obtained concurrently. The software computes the required voltage output and transmits it to a FUS transducer that is embedded in the delivery table within the magnet bore. The delivery table holds the FUS transducer, a small animal and its monitoring equipment, and a transmit/receive RF coil. The transducer is coupled to the animal via a water bath and is translatable in two dimensions from outside the magnet. The transducer is driven by a waveform generator and amplifier controlled by real-time software in Matlab. MR acoustic radiation force imaging is also implemented to confirm the position of the focus for mechanical and thermal treatments. The system was validated in tissue-mimicking phantoms and in vivo during murine tumor hyperthermia treatments. Sonications were successfully controlled over a range of temperatures and thermal doses for up to 20 min with minimal temperature overshoot. MR thermometry was validated with an optical temperature probe, and focus

High Intensity Focused Ultrasound Ablation of Pancreatic Neuroendocrine Tumours: Report of Two Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orgera, Gianluigi, E-mail: gianluigi.orgera@ieo.it; Krokidis, Miltiadis; Monfardini, Lorenzo

2011-04-15

We describe the use of ultrasound-guided high-intensity focused ultrasound (HIFU) for ablation of two pancreatic neuroendocrine tumours (NETs; insulinomas) in two inoperable young female patients. Both suffered from episodes of severe nightly hypoglycemia that was not efficiently controlled by medical treatment. After HIFU ablation, local disease control and symptom relief were achieved without postinterventional complications. The patients remained free of symptoms during 9-month follow-up. The lesions appeared to be decreased in volume, and there was decreased enhancing pattern in the multidetector computed tomography control (MDCT). HIFU is likely to be a valid alternative for symptoms control in patients with pancreaticmore » NETs. However, currently the procedure should be reserved for inoperable patients for whom symptoms cannot be controlled by medical therapy.« less

High-Intensity Focused Ultrasound (HIFU) in Uterine Fibroid Treatment: Review Study.

PubMed

Mahmoud, Mustafa Z; Alkhorayef, Mohammed; Alzimami, Khalid S; Aljuhani, Manal Saud; Sulieman, Abdelmoneim

2014-01-01

High-intensity focused ultrasound (HIFU) is a highly precise medical procedure used locally to heat and destroy diseased tissue through ablation. This study intended to review HIFU in uterine fibroid therapy, to evaluate the role of HIFU in the therapy of leiomyomas as well as to review the actual clinical activities in this field including efficacy and safety measures beside the published clinical literature. An inclusive literature review was carried out in order to review the scientific foundation, and how it resulted in the development of extracorporeal distinct devices. Studies addressing HIFU in leiomyomas were identified from a search of the Internet scientific databases. The analysis of literature was limited to journal articles written in English and published between 2000 and 2013. In current gynecologic oncology, HIFU is used clinically in the treatment of leiomyomas. Clinical research on HIFU therapy for leiomyomas began in the 1990s, and the majority of patients with leiomyomas were treated predominantly with HIFUNIT 9000 and prototype single focus ultrasound devices. HIFU is a non-invasive and highly effective standard treatment with a large indication range for all sizes of leiomyomas, associated with high efficacy, low operative morbidity and no systemic side effects. Uterine fibroid treatment using HIFU was effective and safe in treating symptomatic uterine fibroids. Few studies are available in the literature regarding uterine artery embolization (UAE). HIFU provides an excellent option to treat uterine fibroids.

High-Intensity Focused Ultrasound (HIFU) in Uterine Fibroid Treatment: Review Study

PubMed Central

Mahmoud, Mustafa Z.; Alkhorayef, Mohammed; Alzimami, Khalid S.; Aljuhani, Manal Saud; Sulieman, Abdelmoneim

2014-01-01

Summary Background High-intensity focused ultrasound (HIFU) is a highly precise medical procedure used locally to heat and destroy diseased tissue through ablation. This study intended to review HIFU in uterine fibroid therapy, to evaluate the role of HIFU in the therapy of leiomyomas as well as to review the actual clinical activities in this field including efficacy and safety measures beside the published clinical literature. Material/Methods An inclusive literature review was carried out in order to review the scientific foundation, and how it resulted in the development of extracorporeal distinct devices. Studies addressing HIFU in leiomyomas were identified from a search of the Internet scientific databases. The analysis of literature was limited to journal articles written in English and published between 2000 and 2013. Results In current gynecologic oncology, HIFU is used clinically in the treatment of leiomyomas. Clinical research on HIFU therapy for leiomyomas began in the 1990s, and the majority of patients with leiomyomas were treated predominantly with HIFUNIT 9000 and prototype single focus ultrasound devices. HIFU is a non-invasive and highly effective standard treatment with a large indication range for all sizes of leiomyomas, associated with high efficacy, low operative morbidity and no systemic side effects. Conclusions Uterine fibroid treatment using HIFU was effective and safe in treating symptomatic uterine fibroids. Few studies are available in the literature regarding uterine artery embolization (UAE). HIFU provides an excellent option to treat uterine fibroids. PMID:25371765

High-intensity-focused-ultrasound (HIFU) induced homeostasis and tissue ablation

NASA Astrophysics Data System (ADS)

Chauhan, Sunita; Michel, M. S.; Alken, Peter; Kohrmann, K. U.; Haecker, Axel

2003-06-01

At high intensity levels, ultrasound energy focused into remote tissue targets in human body has shown to produce thermal necrosis in circumscribed regions with sub-millimeter accuracy. The non-invasive modality known as HIFU has enormous potential for thermal ablation of cancers/tumors of the human body without any adverse effects in the surrounding normal tissue. In this paper, empirical results for parametric assessment and interdependence of several exposure variables are presented for producing thermal necrosis as well as hemostasis. Multiple HIFU transducers in selective spatial configuration have been deployed using a suitably designed experiemntal harness, with and without motorized jig scanning. The pre-planning and on-line procedure for treatment and specified instrumentation is described. Custom designed 25mm aperture HIFU probes resonating at 2 MHz focused at 64 and 80 mm are used. Results have been obtained in ex-vivo animal tissue and in vitro biological phantoms for hemostasis.

Morphometric analysis of high-intensity focused ultrasound-induced lipolysis on cadaveric abdominal and thigh skin.

PubMed

Lee, Sugun; Kim, Hee-Jin; Park, Hyun Jun; Kim, Hyoung Moon; Lee, So Hyun; Cho, Sung Bin

2017-07-01

Non-focused ultrasound and high-intensity focused ultrasound (HIFU) devices induce lipolysis by generating acoustic cavitation and coagulation necrosis in targeted tissues. We aimed to investigate the morphometric characteristics of immediate tissue reactions induced by 2 MHz, 13-mm focused HIFU via two-dimensional ultrasound images and histologic evaluation of cadaveric skin from the abdomen and thigh. Acoustic fields of a 2 MHz, 38-mm HIFU transducer were characterized by reconstruction of the fields using acoustic intensity measurement. Additionally, abdominal and thigh tissues from a fresh cadaver were treated with a HIFU device for a single, two, and three pulses at the pulse energy of 130 J/cm 2 and a penetration depth of 13 mm. Acoustic intensity measurement revealed characteristic focal zones of significant thermal injury at the depth of 38 mm. In both the abdomen and thigh tissue, round to oval ablative thermal injury zones (TIZs) were visualized in subcutaneous fat layers upon treatment with a single pulse of HIFU treatment. Two to three HIFU pulses generated larger and more remarkable ablative zones throughout subcutaneous fat layers. Finally, experimental treatment in a tumescent infiltration-like setting induced larger HIFU-induced TIZs of an oval or columnar shape, compared to non-tumescent settings. Although neither acoustic intensity measurement nor cadaveric tissue exactly reflects in vivo HIFU-induced reactions in human tissue, we believe that our data will help guide further in vivo studies in investigating the therapeutic efficacy and safety of HIFU-induced lipolysis.

High-Frequency Ultrasound M-mode Imaging for Identifying Lesion and Bubble Activity during High-Intensity Focused Ultrasound Ablation

PubMed Central

Kumon, R. E.; Gudur, M. S. R.; Zhou, Y.; Deng, C. X.

2012-01-01

Effective real-time monitoring of high-intensity focused ultrasound (HIFU) ablation is important for application of HIFU technology in interventional electrophysiology. This study investigated rapid, high-frequency M-mode ultrasound imaging for monitoring spatiotemporal changes during HIFU application. HIFU (4.33 MHz, 1 kHz PRF, 50% duty cycle, 1 s, 2600 – 6100 W/cm2) was applied to ex-vivo porcine cardiac tissue specimens with a confocally and perpendicularly aligned high-frequency imaging system (Visualsonics Vevo 770, 55 MHz center frequency). Radiofrequency (RF) data from M-mode imaging (1 kHz PRF, 2 s × 7 mm) was acquired before, during, and after HIFU treatment (n = 12). Among several strategies, the temporal maximum integrated backscatter with a threshold of +12 dB change showed the best results for identifying final lesion width (receiver-operating characteristic curve area 0.91 ± 0.04, accuracy 85 ± 8%, as compared to macroscopic images of lesions). A criterion based on a line-to-line decorrelation coefficient is proposed for identification of transient gas bodies. PMID:22341055

Physiological Motion and Registration of Abnormalities in Liver During Focused Ultrasound Surgery

NASA Astrophysics Data System (ADS)

Chauhan, Sunita; Rh, Abhilash

Continuous deformation and dislocation of soft tissues in the abdominal and thoracic region presents a major issue for effective targeting of all non-invasive ablative modalities such as radiotherapy/surgery and Focused Ultrasound Surgery. Most significant among these is the movement of the target organs due to physiological processes such as respiration. The movement is found to be most significant for liver and kidneys. We studied movement and compensation strategies with the aim to implement them during ultrasound ablation using our robotic system for targeted FUS dose delivery. The motion pattern of the liver can be assumed to be in a single plane as it closely follows the movement of the diaphragm. However, the movement of kidneys is three dimensional and follows complicated patterns. Kidney motion is highly subject specific and has poor repeatability. In our research, we quantify the relation of liver movement and the breathing pattern so as to achieve real-time movement compensation using a prediction-correlation approach.

Quantitative Magnetic Resonance Thermometry and Its Use with MR-Guided Focused Ultrasound

NASA Astrophysics Data System (ADS)

Pauly, Kim

2014-03-01

Focused ultrasound (FUS) uses a large area array, typically outside the body, that is geometrically or electronically focused to a point deep in the body. Such focusing provides amplification of the ultrasound intensity, thereby allowing heating of tissue to the point of coagulation at the focus, without damage to the intervening tissue. Guidance of FUS treatments deep in the body can be done quantitatively with magnetic resonance (MR) thermometry, termed MRgFUS. The physics behind MR thermometry lie in the changes in hydrogen bonding with temperature. As tissue temperature rises, hydrogen bonds break, allowing the return of the electron cloud to shield water protons, reducing the magnetic field seen by the protons, and the resonant frequency. The change in resonant frequency is -0.01 ppm per degree C and is the same for all aqueous tissues. The result of the shift in proton resonant frequency is seen in the phase of gradient echo images. Subtraction of the phase of images acquired before and during heating allows the removal of background phase from other sources, yielding quantitative temperature maps. Temperature standard deviations less than 1 degree C are readily achievable and thermal dose maps are easily calculated. Thermal dose is found from a conversion of the whole temperature-time curve to an equivalent number of minutes at 43 degrees C. A thermal dose of 240 minutes is often taken as the threshold for tissue damage. MR thermometry is complicated by the motion of the target tissue and/or motion of other organs such as occurs during respiration. More sophisticated algorithms than the simple baseline subtraction take advantage of the facts that motion can be repetitive (in the case of respiratory motion) and/or the fact that the focal region in MRgFUS is small, allowing for extraction of the heat from the phase profile without subtraction of a background phase.

High intensity focused ultrasound surgery (HIFU) of the brain: A historical perspective, with modern applications

PubMed Central

Jagannathan, Jay; Sanghvi, Narendra K; Crum, Lawrence A; Yen, Chun-Po; Medel, Ricky; Dumont, Aaron S; Sheehan, Jason P; Steiner, Ladislau; Jolesz, Ferenc; Kassell, Neal F

2014-01-01

The field of MRI-guided high intensity focused ultrasound surgery (MRgFUS) is a rapidly evolving one with many potential applications in neurosurgery. This is the first of three articles on MRgFUS, this paper focuses on the historical development of the technology and it's potential applications to modern neurosurgery. The evolution of MRgFUS has occurred in parallel with modern neurological surgery and the two seemingly distinct disciplines share many of the same pioneering figures. Early studies on focused ultrasound treatment in the 1940's and 1950's demonstrated the ability to perform precise lesioning in the human brain, with a favorable risk-benefit profile. However, the need for a craniotomy, as well as lack of sophisticated imaging technology resulted in limited growth of HIFU for neurosurgery. More recently, technological advances, have permitted the combination of HIFU along with MRI guidance to provide an opportunity to effectively treat a variety of CNS disorders. Although challenges remain, HIFU-mediated neurosurgery may offer the ability to target and treat CNS conditions that were previously extremely difficult to perform. The remaining two articles in this series will focus on the physical principles of modern MRgFUS as well as current and future avenues for investigation. PMID:19190451

Singular value decomposition of received ultrasound signal to separate tissue, blood flow, and cavitation signals

NASA Astrophysics Data System (ADS)

Ikeda, Hayato; Nagaoka, Ryo; Lafond, Maxime; Yoshizawa, Shin; Iwasaki, Ryosuke; Maeda, Moe; Umemura, Shin-ichiro; Saijo, Yoshifumi

2018-07-01

High-intensity focused ultrasound is a noninvasive treatment applied by externally irradiating ultrasound to the body to coagulate the target tissue thermally. Recently, it has been proposed as a noninvasive treatment for vascular occlusion to replace conventional invasive treatments. Cavitation bubbles generated by the focused ultrasound can accelerate the effect of thermal coagulation. However, the tissues surrounding the target may be damaged by cavitation bubbles generated outside the treatment area. Conventional methods based on Doppler analysis only in the time domain are not suitable for monitoring blood flow in the presence of cavitation. In this study, we proposed a novel filtering method based on the differences in spatiotemporal characteristics, to separate tissue, blood flow, and cavitation by employing singular value decomposition. Signals from cavitation and blood flow were extracted automatically using spatial and temporal covariance matrices.

Phase-shift perfluorocarbon agents enhance high intensity focused ultrasound thermal delivery with reduced near-field heating

PubMed Central

Phillips, Linsey C.; Puett, Connor; Sheeran, Paul S.; Dayton, Paul A.; Wilson Miller, G.; Matsunaga, Terry O.

2013-01-01

Ultrasound contrast agents are known to enhance high intensity focused ultrasound (HIFU) ablation, but these perfluorocarbon microbubbles are limited to the vasculature, have a short half-life in vivo, and may result in unintended heating away from the target site. Herein, a nano-sized (100–300 nm), dual perfluorocarbon (decafluorobutane/dodecafluoropentane) droplet that is stable, is sufficiently small to extravasate, and is convertible to micron-sized bubbles upon acoustic activation was investigated. Microbubbles and nanodroplets were incorporated into tissue-mimicking acrylamide-albumin phantoms. Microbubbles or nanodroplets at 0.1 × 106 per cm3 resulted in mean lesion volumes of 80.4 ± 33.1 mm3 and 52.8 ± 14.2 mm3 (mean ± s.e.), respectively, after 20 s of continuous 1 MHz HIFU at a peak negative pressure of 4 MPa, compared to a lesion volume of 1.0 ± 0.8 mm3 in agent-free control phantoms. Magnetic resonance thermometry mapping during HIFU confirmed undesired surface heating in phantoms containing microbubbles, whereas heating occurred at the acoustic focus of phantoms containing the nanodroplets. Maximal change in temperature at the target site was enhanced by 16.9% and 37.0% by microbubbles and nanodroplets, respectively. This perfluorocarbon nanodroplet has the potential to reduce the time to ablate tumors by one-third during focused ultrasound surgery while also safely enhancing thermal deposition at the target site. PMID:23927187

Self focusing in a spatially modulated electrostatic field particle accelerator

NASA Astrophysics Data System (ADS)

Russman, F.; Marini, S.; Peter, E.; de Oliveira, G. I.; Rizzato, F. B.

2018-02-01

In the present analysis, we study the action of a three-dimensional (3D) modulated electrostatic wave over a charged particle. Meanwhile, the particle's velocity is smaller than the phase-velocity of the carrier, and the particle could be reflected by the potential or could pass through the potential with no significant change in the longitudinal velocity—and its dynamics could be described by a ponderomotive approximation. Otherwise, the particle is trapped by the potential and it is accelerated towards the speed of light, independently of the initial particle's phase—in this case, the ponderomotive approximation is no longer valid. During the acceleration process, numerical simulations show the particle is focused, simultaneously. These results suggest the accelerator proposed here is promising.

New piezocrystal material in the development of a 96-element array transducer for MR-guided focused ultrasound surgery

NASA Astrophysics Data System (ADS)

Qiu, Zhen; Habeshaw, Roderick; Fortine, Julien; Huang, Zhihong; Démoré, Christine; Cochran, Sandy

2012-11-01

Piezocrystal materials have been recognized as having better performance than piezoelectric ceramics, and have thus been widely adopted in ultrasound imaging arrays. Although their behaviour is susceptible to temperature and pressure, their large electromechanical coupling coefficients and other excellent piezoelectric properties also offer the potential for further improvements in the efficiency of therapeutic ultrasound transducers. Furthermore, new piezocrystals with modified compositions have been developed recently to increase their tolerance to temperature and pressure. In this work, a prototype of faceted bowl transducer was designed and manufactured as a proof of concept to explore practical issues associated with adoption of piezocrystals for magnetic resonance imaging guided focused ultrasound surgery.

Magnetic resonance-guided shielding of prefocal acoustic obstacles in focused ultrasound therapy: application to intercostal ablation in liver.

PubMed

Salomir, Rares; Petrusca, Lorena; Auboiroux, Vincent; Muller, Arnaud; Vargas, Maria-Isabel; Morel, Denis R; Goget, Thomas; Breguet, Romain; Terraz, Sylvain; Hopple, Jerry; Montet, Xavier; Becker, Christoph D; Viallon, Magalie

2013-06-01

The treatment of liver cancer is a major public health issue because the liver is a frequent site for both primary and secondary tumors. Rib heating represents a major obstacle for the application of extracorporeal focused ultrasound to liver ablation. Magnetic resonance (MR)-guided external shielding of acoustic obstacles (eg, the ribs) was investigated here to avoid unwanted prefocal energy deposition in the pathway of the focused ultrasound beam. Ex vivo and in vivo (7 female sheep) experiments were performed in this study. Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) was performed using a randomized 256-element phased-array transducer (f∼1 MHz) and a 3-T whole-body clinical MR scanner. A physical mask was inserted in the prefocal beam pathway, external to the body, to block the energy normally targeted on the ribs. The effectiveness of the reflecting material was investigated by characterizing the efficacy of high-intensity focused ultrasound beam reflection and scattering on its surface using Schlieren interferometry. Before high-intensity focused ultrasound sonication, the alignment of the protectors with the conical projections of the ribs was required and achieved in multiple steps using the embedded graphical tools of the MR scanner. Multiplanar near real-time MR thermometry (proton resonance frequency shift method) enabled the simultaneous visualization of the local temperature increase at the focal point and around the exposed ribs. The beam defocusing due to the shielding was evaluated from the MR acoustic radiation force impulse imaging data. Both MR thermometry (performed with hard absorber positioned behind a full-aperture blocking shield) and Schlieren interferometry indicated a very good energy barrier of the shielding material. The specific temperature contrast between rib surface (spatial average) and focus, calculated at the end point of the MRgHIFU sonication, with protectors vs no protectors, indicated an important

High-intensity focused ultrasound for potential treatment of polycystic ovary syndrome: toward a noninvasive surgery.

PubMed

Shehata, Islam A; Ballard, John R; Casper, Andrew J; Hennings, Leah J; Cressman, Erik; Ebbini, Emad S

2014-02-01

To investigate the feasibility of using high-intensity focused ultrasound (HIFU), under dual-mode ultrasound arrays (DMUAs) guidance, to induce localized thermal damage inside ovaries without damage to the ovarian surface. Laboratory feasibility study. University-based laboratory. Ex vivo canine and bovine ovaries. DMUA-guided HIFU. Detection of ovarian damage by ultrasound imaging, gross pathology, and histology. It is feasible to induce localized thermal damage inside ovaries without damage to the ovarian surface. DMUA provided sensitive imaging feedback regarding the anatomy of the treated ovaries and the ablation process. Different ablation protocols were tested, and thermal damage within the treated ovaries was histologically characterized. The absence of damage to the ovarian surface may eliminate many of the complications linked to current laparoscopic ovarian drilling (LOD) techniques. HIFU may be used as a less traumatic tool to perform LOD. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A boundary condition to the Khokhlov-Zabolotskaya equation for modeling strongly focused nonlinear ultrasound fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosnitskiy, P., E-mail: pavrosni@yandex.ru; Yuldashev, P., E-mail: petr@acs366.phys.msu.ru; Khokhlova, V., E-mail: vera@acs366.phys.msu.ru

2015-10-28

An equivalent source model was proposed as a boundary condition to the nonlinear parabolic Khokhlov-Zabolotskaya (KZ) equation to simulate high intensity focused ultrasound (HIFU) fields generated by medical ultrasound transducers with the shape of a spherical shell. The boundary condition was set in the initial plane; the aperture, the focal distance, and the initial pressure of the source were chosen based on the best match of the axial pressure amplitude and phase distributions in the Rayleigh integral analytic solution for a spherical transducer and the linear parabolic approximation solution for the equivalent source. Analytic expressions for the equivalent source parametersmore » were derived. It was shown that the proposed approach allowed us to transfer the boundary condition from the spherical surface to the plane and to achieve a very good match between the linear field solutions of the parabolic and full diffraction models even for highly focused sources with F-number less than unity. The proposed method can be further used to expand the capabilities of the KZ nonlinear parabolic equation for efficient modeling of HIFU fields generated by strongly focused sources.« less

[Basics of emergency ultrasound].

PubMed

Schellhaas, S; Breitkreutz, R

2012-09-05

Focused ultrasound is a key methodology of critical care medicine. By referencing few ultrasound differential diagnosis, it is possible to identifying in real-time the reason of the critical state of a patient. Therefore typical focused ultrasound protocols were developed. The well known Focused Assessment with Sonography for trauma (FAST) was incorporated into the Advanced Trauma Life Support (ATLS) for shock room. Focused echocardiographic evaluation in life support (FEEL) has been designed to be conformed with the universal Advanced Life Support (ALS) algorithm and to identify treatable conditions such as acute right ventricular pressure overload in pulmonary embolism, hypovolemia, or pericardial effusion/tamponade. Using lung ultrasound one can differentiate pulmonary edema, pleural effusion or pneumothorax.

Electron dynamics in a plasma focus. [electron acceleration

NASA Technical Reports Server (NTRS)

Hohl, F.; Gary, S. P.; Winters, P. A.

1977-01-01

Results are presented of a numerical integration of the three-dimensional relativistic equations of motion of electrons subject to given electric and magnetic fields deduced from experiments. Fields due to two different models are investigated. For the first model, the fields are those due to a circular distribution of axial current filaments. As the current filaments collapse toward the axis, large azimuthal magnetic and axial electric fields are induced. These fields effectively heat the electrons to a temperature of approximately 8 keV and accelerate electrons within the radius of the filaments to high axial velocities. Similar results are obtained for the current-reduction phase of focus formation. For the second model, the fields are those due to a uniform current distribution. Both the current-reduction and the compression phases were studied. These is little heating or acceleration of electrons during the compression phase because the electrons are tied to the magnetic field. However, during the current-reduction phase, electrons near the axis are accelerated toward the center electrode and reach energies of 100 keV. A criterion is obtained which limits the runaway electron current to about 400 A.

Functional Assay of Cancer Cell Invasion Potential Based on Mechanotransduction of Focused Ultrasound.

PubMed

Weitz, Andrew C; Lee, Nan Sook; Yoon, Chi Woo; Bonyad, Adrineh; Goo, Kyo Suk; Kim, Seaok; Moon, Sunho; Jung, Hayong; Zhou, Qifa; Chow, Robert H; Shung, K Kirk

2017-01-01

Cancer cells undergo a number of biophysical changes as they transform from an indolent to an aggressive state. These changes, which include altered mechanical and electrical properties, can reveal important diagnostic information about disease status. Here, we introduce a high-throughput, functional technique for assessing cancer cell invasion potential, which works by probing for the mechanically excitable phenotype exhibited by invasive cancer cells. Cells are labeled with fluorescent calcium dye and imaged during stimulation with low-intensity focused ultrasound, a non-contact mechanical stimulus. We show that cells located at the focus of the stimulus exhibit calcium elevation for invasive prostate (PC-3 and DU-145) and bladder (T24/83) cancer cell lines, but not for non-invasive cell lines (BPH-1, PNT1A, and RT112/84). In invasive cells, ultrasound stimulation initiates a calcium wave that propagates from the cells at the transducer focus to other cells, over distances greater than 1 mm. We demonstrate that this wave is mediated by extracellular signaling molecules and can be abolished through inhibition of transient receptor potential channels and inositol trisphosphate receptors, implicating these proteins in the mechanotransduction process. If validated clinically, our technology could provide a means to assess tumor invasion potential in cytology specimens, which is not currently possible. It may therefore have applications in diseases such as bladder cancer, where cytologic diagnosis of tumor invasion could improve clinical decision-making.

Functional Assay of Cancer Cell Invasion Potential Based on Mechanotransduction of Focused Ultrasound

PubMed Central

Weitz, Andrew C.; Lee, Nan Sook; Yoon, Chi Woo; Bonyad, Adrineh; Goo, Kyo Suk; Kim, Seaok; Moon, Sunho; Jung, Hayong; Zhou, Qifa; Chow, Robert H.; Shung, K. Kirk

2017-01-01

Cancer cells undergo a number of biophysical changes as they transform from an indolent to an aggressive state. These changes, which include altered mechanical and electrical properties, can reveal important diagnostic information about disease status. Here, we introduce a high-throughput, functional technique for assessing cancer cell invasion potential, which works by probing for the mechanically excitable phenotype exhibited by invasive cancer cells. Cells are labeled with fluorescent calcium dye and imaged during stimulation with low-intensity focused ultrasound, a non-contact mechanical stimulus. We show that cells located at the focus of the stimulus exhibit calcium elevation for invasive prostate (PC-3 and DU-145) and bladder (T24/83) cancer cell lines, but not for non-invasive cell lines (BPH-1, PNT1A, and RT112/84). In invasive cells, ultrasound stimulation initiates a calcium wave that propagates from the cells at the transducer focus to other cells, over distances greater than 1 mm. We demonstrate that this wave is mediated by extracellular signaling molecules and can be abolished through inhibition of transient receptor potential channels and inositol trisphosphate receptors, implicating these proteins in the mechanotransduction process. If validated clinically, our technology could provide a means to assess tumor invasion potential in cytology specimens, which is not currently possible. It may therefore have applications in diseases such as bladder cancer, where cytologic diagnosis of tumor invasion could improve clinical decision-making. PMID:28824873

76 FR 43119 - Medical Devices; General and Plastic Surgery Devices; Classification of the Focused Ultrasound...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

... and it is identified as a device using focused ultrasound to produce localized, mechanical motion... labeling includes warnings related to patient reaction in terms of pain and information to user in terms of observable skin reactions that are known to be precursors to the potential thermal adverse effects...

Design and Characterization of Dual-Curvature 1.5-Dimensional High-Intensity Focused Ultrasound Phased-Array Transducer

PubMed Central

Chen, Gin-Shin; Lin, Che-Yu; Jeong, Jong Seob; Cannata, Jonathan M.; Lin, Win-Li; Chang, Hsu; Shung, K. Kirk

2013-01-01

A dual-curvature focused ultrasound phased-array transducer with a symmetric control has been developed for noninvasive ablative treatment of tumors. The 1.5-D array was constructed in-house and the electro-acoustic conversion efficiency was measured to be approximately 65%. In vitro experiments demonstrated that the array uses 256 independent elements to achieve 2-D wide-range high-intensity electronic focusing. PMID:22293745

Multi-resolution simulation of focused ultrasound propagation through ovine skull from a single-element transducer

NASA Astrophysics Data System (ADS)

Yoon, Kyungho; Lee, Wonhye; Croce, Phillip; Cammalleri, Amanda; Yoo, Seung-Schik

2018-05-01

Transcranial focused ultrasound (tFUS) is emerging as a non-invasive brain stimulation modality. Complicated interactions between acoustic pressure waves and osseous tissue introduce many challenges in the accurate targeting of an acoustic focus through the cranium. Image-guidance accompanied by a numerical simulation is desired to predict the intracranial acoustic propagation through the skull; however, such simulations typically demand heavy computation, which warrants an expedited processing method to provide on-site feedback for the user in guiding the acoustic focus to a particular brain region. In this paper, we present a multi-resolution simulation method based on the finite-difference time-domain formulation to model the transcranial propagation of acoustic waves from a single-element transducer (250 kHz). The multi-resolution approach improved computational efficiency by providing the flexibility in adjusting the spatial resolution. The simulation was also accelerated by utilizing parallelized computation through the graphic processing unit. To evaluate the accuracy of the method, we measured the actual acoustic fields through ex vivo sheep skulls with different sonication incident angles. The measured acoustic fields were compared to the simulation results in terms of focal location, dimensions, and pressure levels. The computational efficiency of the presented method was also assessed by comparing simulation speeds at various combinations of resolution grid settings. The multi-resolution grids consisting of 0.5 and 1.0 mm resolutions gave acceptable accuracy (under 3 mm in terms of focal position and dimension, less than 5% difference in peak pressure ratio) with a speed compatible with semi real-time user feedback (within 30 s). The proposed multi-resolution approach may serve as a novel tool for simulation-based guidance for tFUS applications.

Multi-resolution simulation of focused ultrasound propagation through ovine skull from a single-element transducer.

PubMed

Yoon, Kyungho; Lee, Wonhye; Croce, Phillip; Cammalleri, Amanda; Yoo, Seung-Schik

2018-05-10

Transcranial focused ultrasound (tFUS) is emerging as a non-invasive brain stimulation modality. Complicated interactions between acoustic pressure waves and osseous tissue introduce many challenges in the accurate targeting of an acoustic focus through the cranium. Image-guidance accompanied by a numerical simulation is desired to predict the intracranial acoustic propagation through the skull; however, such simulations typically demand heavy computation, which warrants an expedited processing method to provide on-site feedback for the user in guiding the acoustic focus to a particular brain region. In this paper, we present a multi-resolution simulation method based on the finite-difference time-domain formulation to model the transcranial propagation of acoustic waves from a single-element transducer (250 kHz). The multi-resolution approach improved computational efficiency by providing the flexibility in adjusting the spatial resolution. The simulation was also accelerated by utilizing parallelized computation through the graphic processing unit. To evaluate the accuracy of the method, we measured the actual acoustic fields through ex vivo sheep skulls with different sonication incident angles. The measured acoustic fields were compared to the simulation results in terms of focal location, dimensions, and pressure levels. The computational efficiency of the presented method was also assessed by comparing simulation speeds at various combinations of resolution grid settings. The multi-resolution grids consisting of 0.5 and 1.0 mm resolutions gave acceptable accuracy (under 3 mm in terms of focal position and dimension, less than 5% difference in peak pressure ratio) with a speed compatible with semi real-time user feedback (within 30 s). The proposed multi-resolution approach may serve as a novel tool for simulation-based guidance for tFUS applications.

Fluorescent microscope system to monitor real-time interactions between focused ultrasound, echogenic drug delivery vehicles, and live cell membranes.

PubMed

Ibsen, Stuart; Benchimol, Michael; Esener, Sadik

2013-01-01

Rapid development in the field of ultrasound triggered drug delivery has made it essential to study the real-time interaction between the membranes of live cells and the membranes of echogenic delivery vehicles under exposure to focused ultrasound. The objective of this work was to design an analysis system that combined fluorescent imagining, high speed videography, and definable pulse sequences of focused ultrasound to allow for real time observations of both cell and vehicle membranes. Documenting the behavior of the membranes themselves has not previously been possible due to limitations with existing optical systems used to understand the basic physics of microbubble/ultrasound interaction and the basic interaction between microbubbles and cells. The performance of this new system to monitor membrane behavior was demonstrated by documenting the modes of vehicle fragmentation at different ultrasound intensity levels. At 1.5MPa the membranes were shown to completely fragment while at intensities below 1MPa the membranes pop open and slowly unfold. The interaction between these vehicles and cell membranes was also documented by the removal of fluorescent particles from the surfaces of live cells out to 20μm from the microbubble location. The fluid flow created by microstreaming around ensonated microbubbles was documented at video recording speeds from 60 to 18,000 frames per second. This information about membrane behavior allows the chemical and physical properties of the drug delivery vehicle to be designed along with the ultrasound pulse sequence to cause the most efficient drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

Fluorescent Microscope System to Monitor Real-Time Interactions between Focused Ultrasound, Echogenic Drug Delivery Vehicles, and Live Cell Membranes

PubMed Central

Ibsen, Stuart; Benchimol, Michael; Esener, Sadik

2012-01-01

Rapid development in the field of ultrasound triggered drug delivery has made it essential to study the real-time interaction between the membranes of live cells and the membranes of echogenic delivery vehicles under exposure to focused ultrasound. The objective of this work was to design an analysis system that combined fluorescent imagining, high speed videography, and definable pulse sequences of focused ultrasound to allow for real time observations of both cell and vehicle membranes. Documenting the behavior of the membranes themselves has not previously been possible due to limitations with existing optical systems used to understand the basic physics of microbubble/ultrasound interaction and the basic interaction between microbubbles and cells. The performance of this new system to monitor membrane behavior was demonstrated by documenting the modes of vehicle fragmentation at different ultrasound intensity levels. At 1.5 MPa the membranes were shown to completely fragment while at intensities below 1 MPa there is a popping and slow unfolding. The interaction between these vehicles and cell membranes was also documented by the removal of fluorescent particles from the surfaces of live cells out to 20 μm from the microbubble location. The fluid flow created by microstreaming around ensonated microbubbles was documented at video recording speeds from 60 to 18,000 frames per second. This information about membrane behavior allows the chemical and physical properties of the drug delivery vehicle to be designed along with the ultrasound pulse sequence to cause the most efficient drug delivery. PMID:22749476

Use of high-intensity focused ultrasound in the treatment of both benign and malignant prostatic disease

NASA Astrophysics Data System (ADS)

Kernen, Kenneth M.; Miles, Brian J.

2000-05-01

Prostate cancer, the most common malignancy in men in the United States, accounts for more than 29% of all male cancers diagnosed and 13% of all cancer deaths. This translates into approximately 200,000 men diagnosed and 37,000 men who will die from the disease this year in this country. A significant number of patients ultimately choose external beam radiation or interstitial radioactive implants (brachytherapy) combined with external beam radiotherapy as their primary treatment. Approximately 25 - 35% of external beam irradiation patients and 20 - 30% of interstitial implants combined with external beam radiotherapy will fail within 10 years. The treatment options for patients with localized radiorecurrent disease include watchful waiting, endocrine therapy, salvage radiotherapy, and salvage radical prostatectomy, cryotherapy and now high intensity focused ultrasound therapy (HIFU). Although some studies regarding watchful waiting demonstrated comparable results to formal treatment for early prostate cancer, other studies have shown metastatic and mortality rates that are significantly higher, and that radiorecurrent patients would have even greater rates of metastasis and progression to death. Prostate cancer cure by means of endocrine therapy is highly unlikely and its role is still one of palliation with a side effect profile which includes hot flashes, osteoporosis, fatigue, loss of muscle mass, anemia, loss of libido and potency. The role of salvage radiotherapy may offer local control, however long term efficacy has yet to be determined. In a recent series, only 50% of the patients were controlled for a mean of four years with salvage radiotherapy. Salvage prostatectomy has the advantage of providing excellent local control and even a cure if the cancer is confined to the prostate or within the surrounding periprostatic tissue. Historically, salvage prostatectomy is technically demanding and fraught with higher complications. In one large series

Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound.

PubMed

Kobus, Thiele; Vykhodtseva, Natalia; Pilatou, Magdalini; Zhang, Yongzhi; McDannold, Nathan

2016-02-01

The purpose of this study was to investigate the effects on the brain of multiple sessions of blood-brain barrier (BBB) disruption using focused ultrasound (FUS) in combination with micro-bubbles over a range of acoustic exposure levels. Six weekly sessions of FUS, using acoustical pressures between 0.66 and 0.80 MPa, were performed under magnetic resonance guidance. The success and degree of BBB disruption was estimated by signal enhancement of post-contrast T1-weighted imaging of the treated area. Histopathological analysis was performed after the last treatment. The consequences of repeated BBB disruption varied from no indications of vascular damage to signs of micro-hemorrhages, macrophage infiltration, micro-scar formations and cystic cavities. The signal enhancement on the contrast-enhanced T1-weighted imaging had limited value for predicting small-vessel damage. T2-weighted imaging corresponded well with the effects on histopathology and could be used to study treatment effects over time. This study demonstrates that repeated BBB disruption by FUS can be performed with no or limited damage to the brain tissue. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior.

PubMed

Burgess, Alison; Dubey, Sonam; Yeung, Sharon; Hough, Olivia; Eterman, Naomi; Aubert, Isabelle; Hynynen, Kullervo

2014-12-01

To validate whether repeated magnetic resonance (MR) imaging-guided focused ultrasound treatments targeted to the hippocampus, a brain structure relevant for Alzheimer disease ( AD Alzheimer disease ), could modulate pathologic abnormalities, plasticity, and behavior in a mouse model. All animal procedures were approved by the Animal Care Committee and are in accordance with the Canadian Council on Animal Care. Seven-month-old transgenic (TgCRND8) (Tg) mice and their nontransgenic (non-Tg) littermates were entered in the study. Mice were treated weekly with MR imaging-guided focused ultrasound in the bilateral hippocampus (1.68 MHz, 10-msec bursts, 1-Hz burst repetition frequency, 120-second total duration). After 1 month, spatial memory was tested in the Y maze with the novel arm prior to sacrifice and immunohistochemical analysis. The data were compared by using unpaired t tests and analysis of variance with Tukey post hoc analysis. Untreated Tg mice spent 61% less time than untreated non-Tg mice exploring the novel arm of the Y maze because of spatial memory impairments (P < .05). Following MR imaging-guided focused ultrasound, Tg mice spent 99% more time exploring the novel arm, performing as well as their non-Tg littermates. Changes in behavior were correlated with a reduction of the number and size of amyloid plaques in the MR imaging-guided focused ultrasound-treated animals (P < .01). Further, after MR imaging-guided focused ultrasound treatment, there was a 250% increase in the number of newborn neurons in the hippocampus (P < .01). The newborn neurons had longer dendrites and more arborization after MR imaging-guided focused ultrasound, as well (P < .01). Repeated MR imaging-guided focused ultrasound treatments led to spatial memory improvement in a Tg mouse model of AD Alzheimer disease . The behavior changes may be mediated by decreased amyloid pathologic abnormalities and increased neuronal plasticity. © RSNA, 2014.

Transcranial focused ultrasound stimulation of human primary visual cortex

NASA Astrophysics Data System (ADS)

Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik

2016-09-01

Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

Noninvasive body sculpting technologies with an emphasis on high-intensity focused ultrasound.

PubMed

Jewell, Mark L; Solish, Nowell J; Desilets, Charles S

2011-10-01

Body-sculpting procedures are becoming increasingly popular in the United States. Although surgical lipoplasty remains the most common body sculpting procedure, a demand exists for noninvasive alternatives capable of reducing focal adiposity without the risks of adverse events (AEs) associated with invasive excisional body-sculpting procedures. This report describes the mechanism of action, efficacy, safety, and tolerability of cryolipolysis, radiofrequency ablation, low-level external laser therapy, injection lipolysis, low-intensity nonthermal ultrasound, and high-intensity focused ultrasound (HIFU), with an emphasis on thermal HIFU. The articles cited were identified via a PubMed search, with additional article citations identified by manual searching of the reference lists of articles identified through the literature search. Each of the noninvasive treatments reviewed can be administered on an outpatient basis. These treatments generally have fewer complications than lipoplasty and require little or no anesthesia or analgesia. However, HIFU is the only treatment that can produce significant results in a single treatment, and only radiofrequency, low-level laser therapy, and cryolipolysis have been approved for use in the United States. Early clinical data on HIFU support its efficacy and safety for body sculpting. In contrast, radiofrequency, laser therapy, and injection lipolysis have been associated with significant AEs. The published literature suggests that noninvasive body-sculpting techniques such as radiofrequency ablation, cryolipolysis, external low-level lasers, laser ablation, nonthermal ultrasound, and HIFU may be appropriate options for nonobese patients requiring modest reduction of adipose tissue.

Displacement analysis of diagnostic ultrasound backscatter: A methodology for characterizing, modeling, and monitoring high intensity focused ultrasound therapy

PubMed Central

Speyer, Gavriel; Kaczkowski, Peter J.; Brayman, Andrew A.; Crum, Lawrence A.

2010-01-01

Accurate monitoring of high intensity focused ultrasound (HIFU) therapy is critical for widespread clinical use. Pulse-echo diagnostic ultrasound (DU) is known to exhibit temperature sensitivity through relative changes in time-of-flight between two sets of radio frequency (RF) backscatter measurements, one acquired before and one after therapy. These relative displacements, combined with knowledge of the exposure protocol, material properties, heat transfer, and measurement noise statistics, provide a natural framework for estimating the administered heating, and thereby therapy. The proposed method, termed displacement analysis, identifies the relative displacements using linearly independent displacement patterns, or modes, each induced by a particular time-varying heating applied during the exposure interval. These heating modes are themselves linearly independent. This relationship implies that a linear combination of displacement modes aligning the DU measurements is the response to an identical linear combination of heating modes, providing the heating estimate. Furthermore, the accuracy of coefficient estimates in this approximation is determined a priori, characterizing heating, thermal dose, and temperature estimates for any given protocol. Predicted performance is validated using simulations and experiments in alginate gel phantoms. Evidence for a spatially distributed interaction between temperature and time-of-flight changes is presented. PMID:20649206

Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery.

PubMed

Feshitan, Jameel A; Vlachos, Fotis; Sirsi, Shashank R; Konofagou, Elisa E; Borden, Mark A

2012-01-01

We have synthesized a biomaterial consisting of Gd(III) ions chelated to lipid-coated, size-selected microbubbles for utility in both magnetic resonance and ultrasound imaging. The macrocyclic ligand DOTA-NHS was bound to PE headgroups on the lipid shell of pre-synthesized microbubbles. Gd(III) was then chelated to DOTA on the microbubble shell. The reaction temperature was optimized to increase the rate of Gd(III) chelation while maintaining microbubble stability. ICP-OES analysis of the microbubbles determined a surface density of 7.5 × 10(5) ± 3.0 × 10(5) Gd(III)/μm(2) after chelation at 50 °C. The Gd(III)-bound microbubbles were found to be echogenic in vivo during high-frequency ultrasound imaging of the mouse kidney. The Gd(III)-bound microbubbles also were characterized by magnetic resonance imaging (MRI) at 9.4 T by a spin-echo technique and, surprisingly, both the longitudinal and transverse proton relaxation rates were found to be roughly equal to that of no-Gd(III) control microbubbles and saline. However, the relaxation rates increased significantly, and in a dose-dependent manner, after sonication was used to fragment the Gd(III)-bound microbubbles into non-gas-containing lipid bilayer remnants. The longitudinal (r(1)) and transverse (r(2)) molar relaxivities were 4.0 ± 0.4 and 120 ± 18 mM(-1)s(-1), respectively, based on Gd(III) content. The Gd(III)-bound microbubbles may find application in the measurement of cavitation events during MRI-guided focused ultrasound therapy and to track the biodistribution of shell remnants. Copyright © 2011 Elsevier Ltd. All rights reserved.

Localized Ablation of Thyroid Tissue by High-Intensity Focused Ultrasound: an Alternative to Surgery?

NASA Astrophysics Data System (ADS)

Esnault, Olivier; Franc, Brigitte; Chapelon, Jean-Yves; Lacoste, Francois

2006-05-01

PURPOSE: The aim of this study was to evaluate the feasibility of using a High-intensity focused ultrasound (HIFU) device to obtain a localised destruction of the thyroid with no damage to adjacent tissues. MATERIALS AND METHODS: The ewe model was used because its thyroid gland is easily accessible with ultrasound. The animals were anaesthetised with 10 mg / kg IV injection of Penthothal. The HIFU pulses were generated by a 3-MHz spherical transducer under ultrasound guidance. Macroscopic and microscopic tissue lesions were identified after formalin fixation of the anterior part of the ewe's neck. RESULTS: After determining the optimal instrument settings to obtain localized thyroid ablation, the repeatability of the method was evaluated using a HIFU prototype designed specifically for human use: in 13 ewes (26 treated lobes), an average of 20 (range: 14-27) ultrasound pulses (pulse duration: 3 s) per lobe covering a mean volume of 0.5 cm3 (range: 0.3-0.7 cm3) were delivered. The ewes were sacrificed 2-5 weeks after treatment delivery. No damage to the nerves, trachea, esophagus or muscle was observed. Only 3 ewes suffered superficial skin burns. The desired thyroid lesions were obtained in 25/26 treated lobes, as demonstrated by fibrotic tissues, which replaced necrotic areas. CONCLUSION: These results obtained in the ewe model show that thyroid lesions of defined volume can be induced safely and suggest that the HIFU device is now ready for human trials.

Quantitative assessment of cerebral glucose metabolic rates after blood-brain barrier disruption induced by focused ultrasound using FDG-MicroPET.

PubMed

Yang, Feng-Yi; Chang, Wen-Yuan; Chen, Jyh-Cheng; Lee, Lin-Chien; Hung, Yi-Shun

2014-04-15

The goal of this study was to evaluate the pharmacokinetics of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the expression of glucose transporter 1 (GLUT1) protein after blood-brain barrier (BBB) disruption of normal rat brains by focused ultrasound (FUS). After delivery of an intravenous bolus of ~37 MBq (1 mCi) (18)F-FDG, dynamic positron emission tomography scans were performed on rats with normal brains and those whose BBBs had been disrupted by FUS. Arterial blood sampling was collected throughout the scanning procedure. A 2-tissue compartmental model was used to estimate (18)F-FDG kinetic parameters in brain tissues. The rate constants Ki, K1, and k3 were assumed to characterize the uptake, transport, and hexokinase activity, respectively, of (18)F-FDG. The uptake of (18)F-FDG in brains significantly decreased immediately after the blood-brain barrier was disrupted. At the same time, the derived values of Ki, K1, and k3 for the sonicated brains were significantly lower than those for the control brains. In agreement with the reduction in glucose, Western blot analyses confirmed that focused ultrasound exposure significantly reduced the expression of GLUT1 protein in the brains. Furthermore, the effect of focused ultrasound on glucose uptake was transient and reversible 24h after sonication. Our results indicate that focused ultrasound may inhibit GLUT1 expression to decrease the glucose uptake in brain tissue during the period of BBB disruption. Copyright © 2013 Elsevier Inc. All rights reserved.

[Control parameters for high-intensity focused ultrasound (HIFU) for tissue ablation in the ex-vivo kidney].

PubMed

Köhrmann, K U; Michel, M S; Steidler, A; Marlinghaus, E H; Kraut, O; Alken, P

2002-01-01

Therapeutic application of contactless thermoablation by high-intensity focused ultrasound (HIFU) demands precise physical definition of focal size and determination of control parameters. Our objective was to define the focal expansion of a new ultrasound generator and to evaluate the extent of tissue ablation under variable generator parameters in an ex vivo model. Axial and transversal distribution of ultrasound intensity in the area of the focal point was calculated by needle hydrophone. The extent of tissue necrosis after focused ultrasound was assessed in an ex vivo porcine kidney model applying generator power up to 400 Watt and pulse duration up to 8 s. The measurement of field distribution revealed a physical focal size of 32 x 4 mm. Sharp demarcation between coagulation necrosis and intact tissue was observed in our tissue model. Lesion size was kept under control by variation of both generator power and impulse duration. At a constant impulse duration of 2 s, generator power of 100 W remained below the threshold doses for induction of a reproducible lesion. An increase in power up to 200 W and 400 W, respectively, induced lesions with diameters up to 11.2 x 3 mm. Constant total energy (generator power x impulse duration) led to a larger lesion size under higher generator power. It is possible to induce sharply demarcated, reproducible thermonecrosis, which can be regulated by generator power and impulse duration, by means of a cylindrical piezo element with a paraboloid reflector at a focal distance of 10 cm. The variation of generator power was an especially suitable control parameter for the inducement of a defined lesion size.

Registration of surface structures using airborne focused ultrasound.

PubMed

Sundström, N; Börjesson, P O; Holmer, N G; Olsson, L; Persson, H W

1991-01-01

A low-cost measuring system, based on a personal computer combined with standard equipment for complex measurements and signal processing, has been assembled. Such a system increases the possibilities for small hospitals and clinics to finance advanced measuring equipment. A description of equipment developed for airborne ultrasound together with a personal computer-based system for fast data acquisition and processing is given. Two air-adapted ultrasound transducers with high lateral resolution have been developed. Furthermore, a few results for fast and accurate estimation of signal arrival time are presented. The theoretical estimation models developed are applied to skin surface profile registrations.

High-intensity focused ultrasound ablation around the tubing.

PubMed

Siu, Jun Yang; Liu, Chenhui; Zhou, Yufeng

2017-01-01

High-intensity focused ultrasound (HIFU) has been emerging as an effective and noninvasive modality in cancer treatment with very promising clinical results. However, a small vessel in the focal region could be ruptured, which is an important concern for the safety of HIFU ablation. In this study, lesion formation in the polyacrylamide gel phantom embedded with different tubing (inner diameters of 0.76 mm and 3 mm) at varied flow speeds (17-339 cm/s) by HIFU ablation was photographically recorded. Produced lesions have decreased length (~30%) but slightly increased width (~6%) in comparison to that without the embedded tubing. Meanwhile, bubble activities during the exposures were measured by passive cavitation detection (PCD) at the varied pulse repetition frequency (PRF, 10-30 Hz) and duty cycle (DC, 10%-20%) of the HIFU bursts. High DC and low flow speed were found to produce stronger bubble cavitation whereas no significant influence of the PRF. In addition, high-speed photography illustrated that the rupture of tubing was produced consistently after the first HIFU burst within 20 ms and then multiple bubbles would penetrate into the intraluminal space of tubing through the rupture site by the acoustic radiation force. Alignment of HIFU focus to the anterior surface, middle, and posterior surface of tubing led to different characteristics of vessel rupture and bubble introduction. In summary, HIFU-induced vessel rupture is possible as shown in this phantom study; produced lesion sizes and shapes are dependent on the focus alignment to the tubing, flow speed, and tubing properties; and bubble cavitation and the formation liquid jet may be one of the major mechanisms of tubing rupture as shown in the high-speed photography.

High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI).

PubMed

Han, Yang; Hou, Gary Yi; Wang, Shutao; Konofagou, Elisa

2015-08-07

Several ultrasound-based imaging modalities have been proposed for image guidance and monitoring of high-intensity focused ultrasound (HIFU) treatment. However, accurate localization and characterization of the effective region of treatment (focal spot) remain important obstacles in the clinical implementation of HIFU ablation. Harmonic motion imaging for focused ultrasound (HMIFU) is a HIFU monitoring technique that utilizes radiation-force-induced localized oscillatory displacement. HMIFU has been shown to correctly identify the formation and extent of HIFU thermal ablation lesions. However a significant problem remains in identifying the location of the HIFU focus, which is necessary for treatment planning. In this study, the induced displacement was employed to localize the HIFU focal spot inside the tissue prior to treatment. Feasibility was shown with two separate systems. The 1D HMIFU system consisted of a HIFU transducer emitting an amplitude-modulated HIFU beam for mechanical excitation and a confocal single-element, pulse-echo transducer for simultaneous RF acquisition. The 2D HIFU system consists of a HIFU phased array, and a co-axial imaging phased array for simultaneous imaging. Initial feasibility was first performed on tissue-mimicking gelatin phantoms and the focal zone was defined as the region corresponding to the -3dB full width at half maximum of the HMI displacement. Using the same parameters, in vitro experiments were performed in canine liver specimens to compare the defined focal zone with the lesion. In vitro measurements showed good agreement between the HMI predicted focal zone and the induced HIFU lesion location. HMIFU was experimentally shown to be capable of predicting and tracking the focal region in both phantoms and in vitro tissues. The accuracy of focal spot localization was evaluated by comparing with the lesion location in post-ablative tissues, with a R(2) = 0.821 at p < 0.002 in the 2D HMI system. We demonstrated the

High Intensity Focused Ultrasound (HIFU) Focal Spot Localization Using Harmonic Motion Imaging (HMI)

PubMed Central

Han, Yang; Hou, Gary Yi; Wang, Shutao; Konofagou, Elisa

2015-01-01

Several ultrasound-based imaging modalities have been proposed for image guidance and monitoring of High-Intensity Focused Ultrasound (HIFU) treatment. However, accurate localization and characterization of the effective region of treatment (focal spot) remain important obstacles in the clinical implementation of HIFU ablation. Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a HIFU monitoring technique that utilizes radiation-force-induced localized oscillatory displacement. HMIFU has been shown to correctly identify the formation and extent of HIFU thermal ablation lesions. However a significant problem remains in identifying the location of the HIFU focus, which is necessary for treatment planning. In this study, the induced displacement was employed to localize the HIFU focal spot inside the tissue prior to treatment. Feasibility was shown with two separate systems. The 1D HMIFU system consisted of a HIFU transducer emitting an amplitude-modulated HIFU beam for mechanical excitation and a confocal single-element, pulse-echo transducer for simultaneous RF acquisition. The 2D HIFU system consists of a HIFU phased array, and a co-axial imaging phased array for simultaneous imaging. Initial feasibility was first performed on tissue-mimicking gelatin phantoms and the focal zone was defined as the region corresponding to the −3 dB full width at half maximum of the HMI displacement. Using the same parameters, in vitro experiments were performed in canine liver specimens to compare the defined focal zone with the lesion. In vitro measurements showed good agreement between the HMI predicted focal zone and the induced HIFU lesion location. HMIFU was experimentally shown to be capable of predicting and tracking the focal region in both phantoms and in vitro tissues. The accuracy of focal spot localization was evaluated by comparing with the lesion location in post-ablative tissues, with a R2 = 0.821 at p<0.002 in the 2D HMI system. We demonstrated the

High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI)

NASA Astrophysics Data System (ADS)

Han, Yang; Hou, Gary Yi; Wang, Shutao; Konofagou, Elisa

2015-08-01

Several ultrasound-based imaging modalities have been proposed for image guidance and monitoring of high-intensity focused ultrasound (HIFU) treatment. However, accurate localization and characterization of the effective region of treatment (focal spot) remain important obstacles in the clinical implementation of HIFU ablation. Harmonic motion imaging for focused ultrasound (HMIFU) is a HIFU monitoring technique that utilizes radiation-force-induced localized oscillatory displacement. HMIFU has been shown to correctly identify the formation and extent of HIFU thermal ablation lesions. However a significant problem remains in identifying the location of the HIFU focus, which is necessary for treatment planning. In this study, the induced displacement was employed to localize the HIFU focal spot inside the tissue prior to treatment. Feasibility was shown with two separate systems. The 1D HMIFU system consisted of a HIFU transducer emitting an amplitude-modulated HIFU beam for mechanical excitation and a confocal single-element, pulse-echo transducer for simultaneous RF acquisition. The 2D HIFU system consists of a HIFU phased array, and a co-axial imaging phased array for simultaneous imaging. Initial feasibility was first performed on tissue-mimicking gelatin phantoms and the focal zone was defined as the region corresponding to the  -3dB full width at half maximum of the HMI displacement. Using the same parameters, in vitro experiments were performed in canine liver specimens to compare the defined focal zone with the lesion. In vitro measurements showed good agreement between the HMI predicted focal zone and the induced HIFU lesion location. HMIFU was experimentally shown to be capable of predicting and tracking the focal region in both phantoms and in vitro tissues. The accuracy of focal spot localization was evaluated by comparing with the lesion location in post-ablative tissues, with a R2 = 0.821 at p  <  0.002 in the 2D HMI system. We demonstrated

High-intensity focused ultrasound ablation for diffuse uterine leiomyomatosis: A case report.

PubMed

Chen, Li; Xiao, Xiao; Wang, Qingling; Wu, Can; Zou, Min; Xiong, Yu

2015-11-01

Diffuse uterine leiomyomatosis (DUL) is a rare and unique type of uterine leiomyoma which affects women of reproductive age. While treatments like medication, uterine artery embolization (UAE) and hysteroscopic myomectomy show some effectiveness, hysterectomy is currently the only known treatment capable of eliminating the symptoms of this disease. This case report demonstrates that high intensity focused ultrasound (HIFU) ablation may offer these patients a new treatment strategy that could control the symptoms of DUL and spare the uterus from hysterectomy. Copyright © 2015 Elsevier B.V. All rights reserved.

Investigation of Ion Beam Production and Acceleration Using Linear Electron Beams and a Pulse Powered Plasma Focus.

DTIC Science & Technology

1984-03-01

POWERED PLASMA FOCUS Contract No. AFOSR-83-0145 PROGRESS REPORT For the Period April 1, 1983 through March 31, 1984 Submitted to Air Force Office of...AND ACCELERATION USING LINEAR ELECTRON BEAMS AND A PULSE POWERED PLASMA FOCUS Contract No. AFOSR-83-0145 PROGRESS REPORT For the Period April 1, 1983...Acceleration Using Linear Electron Beams and a Pulse Powered Plasma Focus " 01 €,G APRIL 1, 1983 THROUGH MRCH 31, 1984 A. Collective Acceleration and Related

Monitoring high-intensity focused ultrasound (HIFU) therapy using radio frequency ultrasound backscatter to quantify heating

NASA Astrophysics Data System (ADS)

Kaczkowski, Peter J.; Anand, Ajay

2005-09-01

The spatial distribution and temporal history of tissue temperature is an essential indicator of thermal therapy progress, and treatment safety and efficacy. Magnetic resonance methods provide the gold standard noninvasive measurement of temperature but are costly and cumbersome compared to the therapy itself. We have been developing the use of ultrasound backscattering for real-time temperature estimation; ultrasonic methods have been limited to relatively low temperature rise, primarily due to lack of sensitivity at protein denaturation temperatures (50-70°C). Through validation experiments on gel phantoms and ex vivo tissue we show that temperature rise can be accurately mapped throughout the therapeutic temperature range using a new BioHeat Transfer Equation (BHTE) model-constrained inverse approach. Speckle-free temperature and thermal dose maps are generated using the ultrasound calibrated model over the imaged region throughout therapy delivery and post-treatment cooling periods. Results of turkey breast tissue experiments are presented for static HIFU exposures, in which the ultrasound calibrated BHTE temperature maps are shown to be very accurate (within a degree) using independent thermocouple measurements. This new temperature monitoring method may speed clinical adoption of ultrasound-guided HIFU therapy. [Work supported by Army MRMC.

Reduced clot debris size using standing waves formed via high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

Guo, Shifang; Du, Xuan; Wang, Xin; Lu, Shukuan; Shi, Aiwei; Xu, Shanshan; Bouakaz, Ayache; Wan, Mingxi

2017-09-01

The feasibility of utilizing high intensity focused ultrasound (HIFU) to induce thrombolysis has been demonstrated previously. However, clinical concerns still remain related to the clot debris produced via fragmentation of the original clot potentially being too large and hence occluding downstream vessels, causing hazardous emboli. This study investigates the use of standing wave fields formed via HIFU to disintegrate the thrombus while achieving a reduced clot debris size in vitro. The results showed that the average diameter of the clot debris calculated by volume percentage was smaller in the standing wave mode than in the travelling wave mode at identical ultrasound thrombolysis settings. Furthermore, the inertial cavitation dose was shown to be lower in the standing wave mode, while the estimated cavitation bubble size distribution was similar in both modes. These results show that a reduction of the clot debris size with standing waves may be attributed to the particle trapping of the acoustic potential well which contributed to particle fragmentation.

Miniaturized high-intensity focused ultrasound device in patients with glaucoma: a clinical pilot study.

PubMed

Aptel, Florent; Charrel, Thomas; Lafon, Cyril; Romano, Fabrice; Chapelon, Jean-Yves; Blumen-Ohana, Esther; Nordmann, Jean-Philippe; Denis, Philippe

2011-11-11

To evaluate the relative safety and potential efficacy of high-intensity focused ultrasound cyclocoagulation by a miniaturized annular device containing six piezoceramic transducers in patients with refractory glaucoma. This was a three-center prospective interventional pilot study. Twelve eyes of 12 patients with refractory glaucoma were insonified using a ring-shaped probe containing six miniaturized high-frequency transducers operating at 21 MHz. Ultrasound biomicroscopy (UBM) and a complete ophthalmic examination were performed before the procedure and at 1 day, 1 week, 1 month, and 3 months after the procedure. Additional visits were performed 6 and 12 months after the procedure. Intraocular pressure was significantly reduced (P < 0.01) from a mean preoperative value of 37.9 ± 10.7 mm Hg to a mean postoperative value of 27.3 ± 12.4, 25.2 ± 11.3, 25.2 ± 7.7, 24.8 ± 9.8, and 26.3 ± 5.1 mm Hg at 1 day, 1 week, 1 month, 3 months, and 6 months, respectively, and to a mean value of 24.7 ± 8.5 at the last follow-up visit. No major intraoperative or postoperative complications occurred. Minor postoperative corneal complications developed in four patients with previous corneal abnormalities: superficial punctate keratitis (n = 3) and central superficial corneal ulceration (n = 1). UBM showed cystic involution of the ciliary body in 9 of the 12 eyes and a suprachoroidal fluid space in 8 of the 12 eyes. Ultrasonic circular cyclocoagulation using high-intensity focused ultrasound delivered by a circular miniaturized device containing six piezoceramic transducers seems to be an effective and well-tolerated method to reduce intraocular pressure in patients with refractory glaucoma.

Noninvasive and Targeted Drug Delivery to the Brain Using Focused Ultrasound

PubMed Central

2013-01-01

Brain diseases are notoriously difficult to treat due to the presence of the blood-brain barrier (BBB). Here, we review the development of focused ultrasound (FUS) as a noninvasive method for BBB disruption, aiding in drug delivery to the brain. FUS can be applied through the skull to a targeted region in the brain. When combined with microbubbles, FUS causes localized and reversible disruption of the BBB. The cellular mechanisms of BBB disruption are presented. Several therapeutic agents have been delivered to the brain resulting in significant improvements in pathology in models of glioblastoma and Alzheimer’s disease. The requirements for clinical translation of FUS will be discussed. PMID:23379618

Localized delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat brain using focused ultrasound.

PubMed

Mulik, Rohit S; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R

2016-03-01

Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2 × more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Localized Delivery of Low-Density Lipoprotein Docosahexaenoic Acid Nanoparticles to the Rat Brain using Focused Ultrasound

PubMed Central

Mulik, Rohit S.; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R.

2016-01-01

Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2× more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain. PMID:26790145

High-intensity focused ultrasound for the treatment of solid tumor: Chinese clinical experience

NASA Astrophysics Data System (ADS)

Takeuchi, Akira; Zhang, Hong; Sun, Kun; Hasumura, Hiromi; Liu, Botao; Fu, Yurui; Yang, Zaocheng

2006-05-01

As a non-invasive modality, high-intensity focused ultrasound (HIFU) therapy has been received an interest for the treatment of solid tumor. There are some makers of HIFU for the equipment in China. The Sonic CZ901 is developed from the Mianyang stream that has a great advantage for guiding by color Doppler ultrasound imaging. For the research about possibility of this equipment, we evaluate the clinical usefulness to the solid tumor of HIFU treatment at Wujing general hospital in Beijing. We elucidate the result in 28 cases with benign and malignant tumor (Uterine myoma:16, Benign prostatic hypertrophy:5, Benign breast tumor:2, Breast cancer:1, Retroperitoneal tumor:1, Pheochromocytoma:1, Liver cancer: 2) . After 14˜90days, all cases show the reduction of tumor size (Max.3.2cm, Min.1.6cm, :Mean 2.2cm reduced), and the blood flow of tumor completely reduced in 7/23, partially reduced in16/23. Clinical symptoms disappeared in 7, clearly improved in 14, improved in 7. All treatments had no adverse event except for two cases of liver cancer. They felt an abdominal pain that controllable by medicine and it improved within 6hours. It is concluded that HIFU with guide by ultrasound imaging is very safe, painless and effective as the anti-tumor treatment.

Focused ultrasound treatment of abscesses induced by methicillin resistant Staphylococcus aureus: Feasibility study in a mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rieck, Birgit; Bates, David; Pichardo, Samuel, E-mail: spichard@lakeheadu.ca, E-mail: lcuriel@lakeheadu.ca

Purpose: To study the therapeutic effect of focused ultrasound on abscesses induced by methicillin-resistantStaphylococcus aureus (MRSA). MRSA is a major nosocomial pathogen where immunocompromised patients are prone to develop infections that are less and less responsive to regular treatments. Because of its capability to induce a rise of temperature at a very precise location, the use of focused ultrasound represents a considerable opportunity for therapy of localized MRSA-related infections. Methods: 50μl of MRSA strain USA400 bacteria suspension at a concentration of 1.32 ± 0.5 × 10{sup 5} colony forming units (cfu)/μl was injected subcutaneously in the left flank of BALB/cmore » mice. An abscess of 6 ± 2 mm in diameter formed after 48 h. A transducer operating at 3 MHz with a focal length of 50 mm and diameter of 32 mm was used to treat the abscess. The focal point was positioned 2 mm under the skin at the abscess center. Forty-eight hours after injection four ultrasound exposures of 9 s each were applied to each abscess under magnetic resonance imaging guidance. Each exposure was followed by a 1 min pause. These parameters were based on preliminary experiments to ensure repetitive accurate heating of the abscess. Real-time estimation of change of temperature was done using water-proton resonance frequency and a communication toolbox (matMRI) developed inhouse. Three experimental groups of animals each were tested: control, moderate temperature (MT), and high temperature (HT). MT and HT groups reached, respectively, 52.3 ± 5.1 and 63.8 ± 7.5 °C at the end of exposure. Effectiveness of the treatment was assessed by evaluating the bacteria amount of the treated abscess 1 and 4 days after treatment. Myeloperoxidase (MPO) assay evaluating the neutrophil amount was performed to assess the local neutrophil recruitment and the white blood cell count was used to evaluate the systemic inflammatory response after focused ultrasound treatment. Results

Investigation of Plasma Focus in Coaxial Accelerator with Pre-Ionization of Gas,

DTIC Science & Technology

appears that when the accelerating current beyond the end of the central electrodes has sufficiently high levels a plasma focus is formed which is...obtained from an investigation of the main properties of the plasma focus in a system with a pre-ionized gas, achieved by means of an inductive electrical field.

Update on Clinical MR-guided Focused Ultrasound Applications

PubMed Central

McDannold, Nathan

2015-01-01

SYNOPSIS Focused ultrasound (FUS) can be used to thermally ablate tissue. The performance of FUS under magnetic resonance (MR) guidance enables aiming the focus at the target, accurate treatment planning, real-time temperature mapping, and evaluation of the treatment. This review updates several clinical applications of MR-guided FUS. MR-guided FUS has a CE mark and FDA approval for thermal ablation for uterine fibroids and bone metastases related pain management. Thousands of uterine fibroid patients have successfully been treated with minor side effects. Technical improvements, increased experience, and the use of a screening MRI examination should further improve treatment outcome. When used for bone metastases and other bone diseases, thermal ablation leads to pain relief due to denervation, and debulking of the tumor. The use of a hemi-spherical multi-element transducer and phase corrections have enabled application of FUS through the skull. Transcranial MR-guided FUS has received CE certification for ablation of deep, central locations in the brain such as the thalamus. Thermal ablation of specific parts of the thalamus can result in relief of the symptoms in neurological disorders such as essential tremor, Parkinson’s, and neuropathic pain. No CE mark or FDA approval has been obtained as yet for treatment of prostate cancer or breast cancer, but several approaches have been proposed and clinical trials should show the potential of MR-guided FUS for these and other applications. PMID:26499282

A DERATING METHOD FOR THERAPEUTIC APPLICATIONS OF HIGH INTENSITY FOCUSED ULTRASOUND

PubMed Central

Bessonova, O.V.; Khokhlova, V.A.; Canney, M.S.; Bailey, M.R.; Crum, L.A.

2010-01-01

Current methods of determining high intensity focused ultrasound (HIFU) fields in tissue rely on extrapolation of measurements in water assuming linear wave propagation both in water and in tissue. Neglecting nonlinear propagation effects in the derating process can result in significant errors. In this work, a new method based on scaling the source amplitude is introduced to estimate focal parameters of nonlinear HIFU fields in tissue. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK-type equation and are compared to those simulated for propagation in water. Focal waveforms, peak pressures, and intensities are calculated over a wide range of source outputs and linear focusing gains. Our modeling indicates, that for the high gain sources which are typically used in therapeutic medical applications, the focal field parameters derated with our method agree well with numerical simulation in tissue. The feasibility of the derating method is demonstrated experimentally in excised bovine liver tissue. PMID:20582159

A derating method for therapeutic applications of high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

Bessonova, O. V.; Khokhlova, V. A.; Canney, M. S.; Bailey, M. R.; Crum, L. A.

2010-05-01

Current methods of determining high intensity focused ultrasound (HIFU) fields in tissue rely on extrapolation of measurements in water assuming linear wave propagation both in water and in tissue. Neglecting nonlinear propagation effects in the derating process can result in significant errors. A new method based on scaling the source amplitude is introduced to estimate focal parameters of nonlinear HIFU fields in tissue. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK-type equation and are compared to those simulated for propagation in water. Focal wave-forms, peak pressures, and intensities are calculated over a wide range of source outputs and linear focusing gains. Our modeling indicates, that for the high gain sources which are typically used in therapeutic medical applications, the focal field parameters derated with our method agree well with numerical simulation in tissue. The feasibility of the derating method is demonstrated experimentally in excised bovine liver tissue.

A DERATING METHOD FOR THERAPEUTIC APPLICATIONS OF HIGH INTENSITY FOCUSED ULTRASOUND.

PubMed

Bessonova, O V; Khokhlova, V A; Canney, M S; Bailey, M R; Crum, L A

2010-01-01

Current methods of determining high intensity focused ultrasound (HIFU) fields in tissue rely on extrapolation of measurements in water assuming linear wave propagation both in water and in tissue. Neglecting nonlinear propagation effects in the derating process can result in significant errors. In this work, a new method based on scaling the source amplitude is introduced to estimate focal parameters of nonlinear HIFU fields in tissue. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK-type equation and are compared to those simulated for propagation in water. Focal waveforms, peak pressures, and intensities are calculated over a wide range of source outputs and linear focusing gains. Our modeling indicates, that for the high gain sources which are typically used in therapeutic medical applications, the focal field parameters derated with our method agree well with numerical simulation in tissue. The feasibility of the derating method is demonstrated experimentally in excised bovine liver tissue.

High-intensity focused ultrasound ablation around the tubing

PubMed Central

Siu, Jun Yang; Liu, Chenhui

2017-01-01

High-intensity focused ultrasound (HIFU) has been emerging as an effective and noninvasive modality in cancer treatment with very promising clinical results. However, a small vessel in the focal region could be ruptured, which is an important concern for the safety of HIFU ablation. In this study, lesion formation in the polyacrylamide gel phantom embedded with different tubing (inner diameters of 0.76 mm and 3 mm) at varied flow speeds (17–339 cm/s) by HIFU ablation was photographically recorded. Produced lesions have decreased length (~30%) but slightly increased width (~6%) in comparison to that without the embedded tubing. Meanwhile, bubble activities during the exposures were measured by passive cavitation detection (PCD) at the varied pulse repetition frequency (PRF, 10–30 Hz) and duty cycle (DC, 10%-20%) of the HIFU bursts. High DC and low flow speed were found to produce stronger bubble cavitation whereas no significant influence of the PRF. In addition, high-speed photography illustrated that the rupture of tubing was produced consistently after the first HIFU burst within 20 ms and then multiple bubbles would penetrate into the intraluminal space of tubing through the rupture site by the acoustic radiation force. Alignment of HIFU focus to the anterior surface, middle, and posterior surface of tubing led to different characteristics of vessel rupture and bubble introduction. In summary, HIFU-induced vessel rupture is possible as shown in this phantom study; produced lesion sizes and shapes are dependent on the focus alignment to the tubing, flow speed, and tubing properties; and bubble cavitation and the formation liquid jet may be one of the major mechanisms of tubing rupture as shown in the high-speed photography. PMID:29161293

High-intensity focused ultrasound treatment in patients with refractory glaucoma.

PubMed

Giannaccare, Giuseppe; Vagge, A; Gizzi, C; Bagnis, A; Sebastiani, S; Del Noce, C; Fresina, M; Traverso, C E; Campos, E C

2017-03-01

To assess the safety and efficacy of ultrasound coagulation of the ciliary body in refractory glaucoma. This prospective multicenter interventional study was conducted in two Italian university-affiliated glaucoma centers: St. Orsola-Malpighi Teaching Hospital (Bologna, Italy) and University Eye Clinic of Genoa (Genoa, Italy). The main inclusion criterion was the diagnosis of glaucoma with a baseline intraocular pressure (IOP) ≥ 21 mmHg while on maximum topical and systemic medical hypotensive treatment. The EyeOP1 device (Eye Tech Care, Rillieux-la-Pape, France), which was employed in the study, uses miniaturized transducers to produce high-intensity focused ultrasound (HIFU). Treatment consisted of the sequential activation of each transducer lasting 4 s (group 1), 6 s (group 2) or 8 s (group 3). Hypotensive medications were interrupted after surgery and then prescribed only if postoperative IOP was ≥ 21 mmHg during follow-up visits. Patients were assessed before and 1, 7, 14, 30, 90 and 180 days after the procedure. Primary outcomes were the mean IOP reduction in the overall population and in groups 1, 2 and 3, and the rates of complete success, qualified success and failure. Thirty eyes (16 open-angle, 10 angle-closure and 4 neovascular glaucoma) of 30 patients were included. The mean preoperative IOP was 30.1 ± 10.5 mmHg. Twenty-nine patients completed the entire study follow-up; one patient exited from the study 3 months after HIFU and underwent trabeculectomy. At days 1 and 180, the mean IOP was significantly reduced (18.4 ± 7.2 and 20.2 ± 6.2 mmHg, respectively; all p < 0.0001). Group 3 patients (8-s ultrasound exposure time) showed a greater IOP reduction than the other two groups (-16.2 ± 8.3 for group 3 vs. -8.8 ± 6.6 for group 2 and -3.7 ± 6.5 for group 1; p = 0.02 and p < 0.001, respectively). Qualified and complete success was achieved in 23.3 and 46.7% of patients, respectively; treatment

Beam trapping in high-current cyclic accelerators with strong-focusing fields. Memorandum report, January-December 1984

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sprangle, P.; Kapetanakos, C.A.

1985-03-06

In cyclic induction accelerators, the energy of the particles increases slowly in synchronism with the vertical (betatron) magnetic field. As a consequence of the slow acceleration, the charged particles must be confined by the weak-focusing magnetic field over long periods of time, and thus field errors, instabilities, and radiation losses can impose limitations on the acceleration process. These limitations can be substantially relaxed if the acceleration were to occur rapidly, say over a few microseconds. An appropriate name for such an accelerator is REBA-TRON (Rapid Electron Beam Accelerator). This paper considers a possible mechanism which could trap a high currentmore » electron beam in the strong focusing magnetic fields of the rebatron. We investigate a possible mechanism for trapping an intense relativistic electron beam confined by strong focusing fields. In our model the electron beam is assumed to be injected into torsatron fields off axis, near the chamber walls. The finite resistivity of the walls results in a drag force on the beam centroid which may cause the beam to spiral inward towards the axis of the chamber. We have analyzed this mechanism and obtained decay rates for the inward spiraling beam motion.« less

Time-reversal transcranial ultrasound beam focusing using a k-space method

PubMed Central

Jing, Yun; Meral, F. Can; Clement, Greg. T.

2012-01-01

This paper proposes the use of a k-space method to obtain the correction for transcranial ultrasound beam focusing. Mirroring past approaches, A synthetic point source at the focal point is numerically excited, and propagated through the skull, using acoustic properties acquired from registered computed tomograpy of the skull being studied. The received data outside the skull contains the correction information and can be phase conjugated (time reversed) and then physically generated to achieve a tight focusing inside the skull, by assuming quasi-plane transmission where shear waves are not present or their contribution can be neglected. Compared with the conventional finite-difference time-domain method for wave propagation simulation, it will be shown that the k-space method is significantly more accurate even for a relatively coarse spatial resolution, leading to a dramatically reduced computation time. Both numerical simulations and experiments conducted on an ex vivo human skull demonstrate that, precise focusing can be realized using the k-space method with a spatial resolution as low as only 2.56 grid points per wavelength, thus allowing treatment planning computation on the order of minutes. PMID:22290477

Current and Future Clinical Applications of High-Intensity Focused Ultrasound (HIFU) for Pancreatic Cancer.

PubMed

Jang, Hyun Joo; Lee, Jae-Young; Lee, Don-Haeng; Kim, Won-Hong; Hwang, Joo Ha

2010-09-01

High-intensity focused ultrasound (HIFU) is a novel therapeutic modality that permits noninvasive treatment of various benign and malignant solid tumors, including prostatic cancer, uterine fibroids, hepatic tumors, renal tumors, breast cancers, and pancreatic cancers. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumors, including pancreatic cancer. The results of nonrandomized studies of HIFU therapy in patients with pancreatic cancer have suggested that HIFU treatment can effectively alleviate cancer-related pain without any significant complications. This noninvasive method of delivering ultrasound energy into the body has recently been evolving from a method for purely thermal ablation to harnessing the mechanical effects of HIFU to induce a systemic immune response and to enhance targeted drug delivery. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges.

Current and Future Clinical Applications of High-Intensity Focused Ultrasound (HIFU) for Pancreatic Cancer

PubMed Central

Jang, Hyun Joo; Lee, Jae-Young; Lee, Don-Haeng; Kim, Won-Hong

2010-01-01

High-intensity focused ultrasound (HIFU) is a novel therapeutic modality that permits noninvasive treatment of various benign and malignant solid tumors, including prostatic cancer, uterine fibroids, hepatic tumors, renal tumors, breast cancers, and pancreatic cancers. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumors, including pancreatic cancer. The results of nonrandomized studies of HIFU therapy in patients with pancreatic cancer have suggested that HIFU treatment can effectively alleviate cancer-related pain without any significant complications. This noninvasive method of delivering ultrasound energy into the body has recently been evolving from a method for purely thermal ablation to harnessing the mechanical effects of HIFU to induce a systemic immune response and to enhance targeted drug delivery. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges. PMID:21103296

High-intensity focused ultrasound (HIFU) for adenomyosis: Two-year follow-up results.

PubMed

Shui, Lian; Mao, Shihua; Wu, Qingrong; Huang, Guohua; Wang, Jian; Zhang, Ruitao; Li, Kequan; He, Jia; Zhang, Lian

2015-11-01

To evaluate the long-term improvement of clinical symptoms of adenomyosis after treatment with ultrasound-guided high intensity focused ultrasound (USgHIFU). From January 2010 to December 2011, 350 patients with adenomyosis were treated with USgHIFU. Among the 350 patients, 224 of them completed the two years follow-up. The patients were followed up at 3 months, 1 year, and 2 years after HIFU treatment. Adverse effects and complications were recorded. All patients completed HIFU ablation without severe postoperative complications. 203 of the 224 patients who showed varying degrees of dysmenorrhea before treatment had the symptom scores decreased significantly after treatment (P<0.001). The relief rate was 84.7%, 84.7%, and 82.3%, respectively at 3 months, 1 year, and 2 years after treatment. The menstrual volume in 109 patients with menorrhagia was significantly improved after treatment (P<0.001) with a relief rate of 79.8%, 80.7%, and 78.9%, respectively at 3 months, 1 year, and 2 years after HIFU treatment. With its ability to sustain long-term clinical improvements, HIFU is a safe and effective treatment for adenomyosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Multi-parametric monitoring and assessment of high-intensity focused ultrasound (HIFU) boiling by harmonic motion imaging for focused ultrasound (HMIFU): an ex vivo feasibility study

NASA Astrophysics Data System (ADS)

Hou, Gary Y.; Marquet, Fabrice; Wang, Shutao; Konofagou, Elisa E.

2014-03-01

Harmonic motion imaging for focused ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in vitro and in vivo. Here, a multi-parametric study is performed to investigate both elastic and acoustics-independent viscoelastic tissue changes using the Harmonic Motion Imaging (HMI) displacement, axial compressive strain and change in relative phase shift during high energy HIFU treatment with tissue boiling. Forty three (n = 43) thermal lesions were formed in ex vivo canine liver specimens (n = 28). Two-dimensional (2D) transverse HMI displacement maps were also obtained before and after lesion formation. The same method was repeated in 10 s, 20 s and 30 s HIFU durations at three different acoustic powers of 8, 10, and 11 W, which were selected and verified as treatment parameters capable of inducing boiling using both thermocouple and passive cavitation detection (PCD) measurements. Although a steady decrease in the displacement, compressive strain, and relative change in the focal phase shift (Δϕ) were obtained in numerous cases, indicating an overall increase in relative stiffness, the study outcomes also showed that during boiling, a reverse lesion-to-background displacement contrast was detected, indicating potential change in tissue absorption, geometrical change and/or, mechanical gelatification or pulverization. Following treatment, corresponding 2D HMI displacement images of the thermal lesions also mapped consistent discrepancy in the lesion-to-background displacement contrast. Despite the expectedly chaotic changes in acoustic properties with boiling, the relative change in phase shift showed a consistent decrease, indicating its robustness to monitor biomechanical properties independent of the acoustic property changes throughout the HIFU treatment. In addition, the 2D HMI displacement images confirmed and indicated the increase in the thermal lesion size with

Multi-parametric monitoring and assessment of High Intensity Focused Ultrasound (HIFU) boiling by Harmonic Motion Imaging for Focused Ultrasound (HMIFU): An ex vivo feasibility study

PubMed Central

Hou, Gary Y.; Marquet, Fabrice; Wang, Shutao; Konofagou, Elisa E.

2014-01-01

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in vitro and in vivo. Here, a multi-parametric study is performed to investigate both elastic and acoustics-independent viscoelastic tissue changes using the Harmonic Motion Imaging (HMI) displacement, axial compressive strain and change in relative phase-shift during high energy HIFU treatment with tissue boiling. Forty three (n=43) thermal lesions were formed in ex vivo canine liver specimens (n=28). Two dimensional (2D) transverse HMI displacement maps were also obtained before and after lesion formation. The same method was repeated in 10-s, 20-s and 30-s HIFU durations at three different acoustic powers of 8, 10, and 11W, which were selected and verified as treatment parameters capable of inducing boiling using both thermocouple and Passive Cavitation Detection (PCD) measurements. Although a steady decrease in the displacement, compressive strain, and relative change in the focal phase shift (Δφ) were obtained in numerous cases, indicating an overall increase in relative stiffness, the study outcomes also showed that during boiling, a reverse lesion-to-background displacement contrast was detected, indicating potential change in tissue absorption, geometrical change and/or, mechanical gelatification or pulverization. Following treatment, corresponding 2D HMI displacement images of the thermal lesions also mapped consistent discrepancy in the lesion-to-background displacement contrast. Despite unpredictable changes in acoustic properties with boiling, the relative change in phase shift showed a consistent decrease, indicating its robustness to monitor biomechanical properties independent of the acoustic property change throughout the HIFU treatment. In addition, the 2D HMI displacement images confirmed and indicated the increase in the thermal lesion size with treatment duration

Multi-parametric monitoring and assessment of high-intensity focused ultrasound (HIFU) boiling by harmonic motion imaging for focused ultrasound (HMIFU): an ex vivo feasibility study.

PubMed

Hou, Gary Y; Marquet, Fabrice; Wang, Shutao; Konofagou, Elisa E

2014-03-07

Harmonic motion imaging for focused ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in vitro and in vivo. Here, a multi-parametric study is performed to investigate both elastic and acoustics-independent viscoelastic tissue changes using the Harmonic Motion Imaging (HMI) displacement, axial compressive strain and change in relative phase shift during high energy HIFU treatment with tissue boiling. Forty three (n = 43) thermal lesions were formed in ex vivo canine liver specimens (n = 28). Two-dimensional (2D) transverse HMI displacement maps were also obtained before and after lesion formation. The same method was repeated in 10 s, 20 s and 30 s HIFU durations at three different acoustic powers of 8, 10, and 11 W, which were selected and verified as treatment parameters capable of inducing boiling using both thermocouple and passive cavitation detection (PCD) measurements. Although a steady decrease in the displacement, compressive strain, and relative change in the focal phase shift (Δϕ) were obtained in numerous cases, indicating an overall increase in relative stiffness, the study outcomes also showed that during boiling, a reverse lesion-to-background displacement contrast was detected, indicating potential change in tissue absorption, geometrical change and/or, mechanical gelatification or pulverization. Following treatment, corresponding 2D HMI displacement images of the thermal lesions also mapped consistent discrepancy in the lesion-to-background displacement contrast. Despite the expectedly chaotic changes in acoustic properties with boiling, the relative change in phase shift showed a consistent decrease, indicating its robustness to monitor biomechanical properties independent of the acoustic property changes throughout the HIFU treatment. In addition, the 2D HMI displacement images confirmed and indicated the increase in the thermal lesion size with

Enhanced target normal sheath acceleration based on the laser relativistic self-focusing

NASA Astrophysics Data System (ADS)

Zou, D. B.; Zhuo, H. B.; Yang, X. H.; Shao, F. Q.; Ma, Y. Y.; Yu, T. P.; Wu, H. C.; Yin, Y.; Ge, Z. Y.; Li, X. H.

2014-06-01

The enhanced target normal sheath acceleration of ions in laser target interaction via the laser relativistic self-focusing effect is investigated by theoretical analysis and particle-in-cell simulations. The temperature of the hot electrons in the underdense plasma is greatly increased due to the occurrence of resonant absorption, while the electron-betatron-oscillation frequency is close to its witnessed laser frequency [Pukhov et al., Phys. Plasma 6, 2847 (1999)]. While these hot electrons penetrate through the backside solid target, a stronger sheath electric field at the rear surface of the target is induced, which can accelerate the protons to a higher energy. It is also shown that the optimum length of the underdense plasma is approximately equal to the self-focusing distance.

Processing ultrasound backscatter to monitor high-intensity focused ultrasound (HIFU) therapy

NASA Astrophysics Data System (ADS)

Kaczkowski, Peter J.; Anand, Ajay; Bailey, Michael R.

2005-09-01

The development of new noninvasive surgical methods such as HIFU for the treatment of cancer and internal bleeding requires simultaneous development of new sensing approaches to guide, monitor, and assess the therapy. Ultrasound imaging using echo amplitude has long been used to map tissue morphology for diagnostic interpretation by the clinician. New quantitative ultrasonic methods that rely on amplitude and phase processing for tissue characterization are being developed for monitoring of ablative therapy. We have been developing the use of full wave ultrasound backscattering for real-time temperature estimation, and to image changes in tissue backscatter spectrum as therapy progresses. Both approaches rely on differential processing of the backscatter signal in time, and precise measurement of phase differences. Noise and artifacts from motion and nonstationary speckle statistics are addressed by constraining inversions for tissue parameters with physical models. We present results of HIFU experiments with static point and scanned HIFU exposures in which temperature rise can be accurately mapped using a new heat transfer equation (HTE) model-constrained inverse approach. We also present results of a recently developed spectral imaging method that elucidates microbubble-mediated nonlinearity not visible as a change in backscatter amplitude. [Work supported by Army MRMC.

A semi-analytical model of a time reversal cavity for high-amplitude focused ultrasound applications

NASA Astrophysics Data System (ADS)

Robin, J.; Tanter, M.; Pernot, M.

2017-09-01

Time reversal cavities (TRC) have been proposed as an efficient approach for 3D ultrasound therapy. They allow the precise spatio-temporal focusing of high-power ultrasound pulses within a large region of interest with a low number of transducers. Leaky TRCs are usually built by placing a multiple scattering medium, such as a random rod forest, in a reverberating cavity, and the final peak pressure gain of the device only depends on the temporal length of its impulse response. Such multiple scattering in a reverberating cavity is a complex phenomenon, and optimisation of the device’s gain is usually a cumbersome process, mostly empirical, and requiring numerical simulations with extremely long computation times. In this paper, we present a semi-analytical model for the fast optimisation of a TRC. This model decouples ultrasound propagation in an empty cavity and multiple scattering in a multiple scattering medium. It was validated numerically and experimentally using a 2D-TRC and numerically using a 3D-TRC. Finally, the model was used to determine rapidly the optimal parameters of the 3D-TRC which had been confirmed by numerical simulations.

Annular phased-array high-intensity focused ultrasound device for image-guided therapy of uterine fibroids.

PubMed

Held, Robert Thomas; Zderic, Vesna; Nguyen, Thuc Nghi; Vaezy, Shahram

2006-02-01

An ultrasound (US), image-guided high-intensity focused ultrasound (HIFU) device was developed for noninvasive ablation of uterine fibroids. The HIFU device was an annular phased array, with a focal depth range of 30-60 mm, a natural focus of 50 mm, and a resonant frequency of 3 MHz. The in-house control software was developed to operate the HIFU electronics drive system for inducing tissue coagulation at different distances from the array. A novel imaging algorithm was developed to minimize the HIFU-induced noise in the US images. The device was able to produce lesions in bovine serum albumin-embedded polyacrylamide gels and excised pig liver. The lesions could be seen on the US images as hyperechoic regions. Depths ranging from 30 to 60 mm were sonicated at acoustic intensities of 4100 and 6100 W/cm2 for 15 s each, with the latter producing average lesion volumes at least 63% larger than the former. Tissue sonication patterns that began distal to the transducer produced longer lesions than those that began proximally. The variation in lesion dimensions indicates the possible development of HIFU protocols that increase HIFU throughput and shorten tumor treatment times.

In vivo photoacoustics and high frequency ultrasound imaging of mechanical high intensity focused ultrasound (HIFU) ablation.

PubMed

Daoudi, Khalid; Hoogenboom, Martijn; den Brok, Martijn; Eikelenboom, Dylan; Adema, Gosse J; Fütterer, Jürgen J; de Korte, Chris L

2017-04-01

The thermal effect of high intensity focused ultrasound (HIFU) has been clinically exploited over a decade, while the mechanical HIFU is still largely confined to laboratory investigations. This is in part due to the lack of adequate imaging techniques to better understand the in-vivo pathological and immunological effects caused by the mechanical treatment. In this work, we explore the use of high frequency ultrasound (US) and photoacoustics (PA) as a potential tool to evaluate the effect of mechanical ablation in-vivo , e.g. boiling histotripsy. Two mice bearing a neuroblastoma tumor in the right leg were ablated using an MRI-HIFU system conceived for small animals and monitored using MRI thermometry. High frequency US and PA imaging were performed before and after the HIFU treatment. Afterwards, the tumor was resected for further assessment and evaluation of the ablated region using histopathology. High frequency US imaging revealed the presence of liquefied regions in the treated area together with fragmentized tissue which appeared with different reflecting proprieties compared to the surrounding tissue. Photoacoustic imaging on the other hand revealed the presence of deoxygenated blood within the tumor after the ablation due to the destruction of blood vessel network while color Doppler imaging confirmed the blood vessel network destruction within the tumor. The treated area and the presence of red blood cells detected by photoacoustics were further confirmed by the histopathology. This feasibility study demonstrates the potential of high frequency US and PA approach for assessing in-vivo the effect of mechanical HIFU tumor ablation.

In vivo photoacoustics and high frequency ultrasound imaging of mechanical high intensity focused ultrasound (HIFU) ablation

PubMed Central

Daoudi, Khalid; Hoogenboom, Martijn; den Brok, Martijn; Eikelenboom, Dylan; Adema, Gosse J.; Fütterer, Jürgen J.; de Korte, Chris L.

2017-01-01

The thermal effect of high intensity focused ultrasound (HIFU) has been clinically exploited over a decade, while the mechanical HIFU is still largely confined to laboratory investigations. This is in part due to the lack of adequate imaging techniques to better understand the in-vivo pathological and immunological effects caused by the mechanical treatment. In this work, we explore the use of high frequency ultrasound (US) and photoacoustics (PA) as a potential tool to evaluate the effect of mechanical ablation in-vivo, e.g. boiling histotripsy. Two mice bearing a neuroblastoma tumor in the right leg were ablated using an MRI-HIFU system conceived for small animals and monitored using MRI thermometry. High frequency US and PA imaging were performed before and after the HIFU treatment. Afterwards, the tumor was resected for further assessment and evaluation of the ablated region using histopathology. High frequency US imaging revealed the presence of liquefied regions in the treated area together with fragmentized tissue which appeared with different reflecting proprieties compared to the surrounding tissue. Photoacoustic imaging on the other hand revealed the presence of deoxygenated blood within the tumor after the ablation due to the destruction of blood vessel network while color Doppler imaging confirmed the blood vessel network destruction within the tumor. The treated area and the presence of red blood cells detected by photoacoustics were further confirmed by the histopathology. This feasibility study demonstrates the potential of high frequency US and PA approach for assessing in-vivo the effect of mechanical HIFU tumor ablation. PMID:28736668

Ultrasound-Accelerated, Catheter-Directed Thrombolysis for Inferior Vena Cava Thrombosis After an Orthotopic Liver Transplant

PubMed Central

Latchana, Nicholas; Dowell, Joshua D.; Taani, Jamal Al; Michaels, Anthony; Elkhammas, Elmadhi; Black, Sylvester M.

2015-01-01

Inferior vena cava thrombosis is a rare occurrence after an orthotopic liver transplant that is associated with a high rate of retransplant and mortality. There is no consensus regarding the optimal therapeutic strategy. Surgical management, including thrombectomy with revision of the cavocaval anastomosis, has been described. With the use of endovascular therapies, several minimally invasive approaches are available that are effective and avoid the high morbidity associated with reoperative surgery. We describe our successful experience using an approach after a liver transplant in which the inferior vena cava thrombosis in a patient presenting with acute renal failure, anorexia, weight loss, and fatigue using an ultrasound-accelerated, catheter-directed thrombolysis platform in conjunction with systemic anticoagulation. PMID:24918871

Dual-frequency focused ultrasound using optoacoustic and piezoelectric transmitters for single-pulsed free-field cavitation in water

NASA Astrophysics Data System (ADS)

Baac, Hyoung Won; Lee, Taehwa; Ok, Jong G.; Hall, Timothy; Jay Guo, L.

2013-12-01

Pulsed ultrasonic cavitation is a promising modality for non-contact targeted therapy, enabling mechanical ablation of the tissue. We demonstrate a spatio-temporal superposition approach of two ultrasound pulses (high and low frequencies) producing a tight cavitation zone of 100 μm in water, which is an-order-of-magnitudes smaller than those obtained by the existing high-amplitude transducers. Particularly, laser-generated focused ultrasound (LGFU) was employed for the high-frequency operation (15 MHz). As demonstrated, LGFU plays a primary role to define the cavitation zone. The generation rate of cavitation bubbles could be dramatically increased up to 4.1% (cf. 0.06% without the superposition) with moderated threshold requirement.

Deep tissue penetration of nanoparticles using pulsed-high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

You, Dong Gil; Yoon, Hong Yeol; Jeon, Sangmin; Um, Wooram; Son, Sejin; Park, Jae Hyung; Kwon, Ick Chan; Kim, Kwangmeyung

2017-11-01

Recently, ultrasound (US)-based drug delivery strategies have received attention to improve enhanced permeation and retention (EPR) effect-based passive targeting efficiency of nanoparticles in vitro and in vivo conditions. Among the US treatment techniques, pulsed-high intensity focused ultrasound (pHIFU) have specialized for improving tissue penetration of various macromolecules and nanoparticles without irreversible tissue damages. In this study, we have demonstrated that pHIFU could be utilized to improve tissue penetration of fluorescent dye-labeled glycol chitosan nanoparticles (FCNPs) in femoral tissue of mice. pHIFU could improve blood flow of the targeted-blood vessel in femoral tissue. In addition, tissue penetration of FCNPs was specifically increased 5.7-, 8- and 9.3-folds than that of non-treated (0 W pHIFU) femoral tissue, when the femoral tissue was treated with 10, 20 and 50 W of pHIFU, respectively. However, tissue penetration of FCNPs was significantly reduced after 3 h post-pHIFU treatment (50 W). Because overdose (50 W) of pHIFU led to irreversible tissue damages, including the edema and chapped red blood cells. These overall results support that pHIFU treatment can enhance the extravasation and tissue penetration of FCNPs as well as induce irreversible tissue damages. We expect that our results can provide advantages to optimize pHIFU-mediated delivery strategy of nanoparticles for further clinical applications.

Robotized High Intensity Focused Ultrasound (HIFU) system for treatment of mobile organs using motion tracking by ultrasound imaging: An in vitro study.

PubMed

Chanel, Laure-Anais; Nageotte, Florent; Vappou, Jonathan; Luo, Jianwen; Cuvillon, Loic; de Mathelin, Michel

2015-01-01

High Intensity Focused Ultrasound (HIFU) therapy is a very promising method for ablation of solid tumors. However, intra-abdominal organ motion, principally due to breathing, is a substantial limitation that results in incorrect tumor targeting. The objective of this work is to develop an all-in-one robotized HIFU system that can compensate motion in real-time during HIFU treatment. To this end, an ultrasound visual servoing scheme working at 20 Hz was designed. It relies on the motion estimation by using a fast ultrasonic speckle tracking algorithm and on the use of an interleaved imaging/HIFU sonication sequence for avoiding ultrasonic wave interferences. The robotized HIFU system was tested on a sample of chicken breast undergoing a vertical sinusoidal motion at 0.25 Hz. Sonications with and without motion compensation were performed in order to assess the effect of motion compensation on thermal lesions induced by HIFU. Motion was reduced by more than 80% thanks to this ultrasonic visual servoing system.

Characterization of different bubble formulations for blood-brain barrier opening using a focused ultrasound system with acoustic feedback control.

PubMed

Bing, Chenchen; Hong, Yu; Hernandez, Christopher; Rich, Megan; Cheng, Bingbing; Munaweera, Imalka; Szczepanski, Debra; Xi, Yin; Bolding, Mark; Exner, Agata; Chopra, Rajiv

2018-05-22

Focused ultrasound combined with bubble-based agents serves as a non-invasive way to open the blood-brain barrier (BBB). Passive acoustic detection was well studied recently to monitor the acoustic emissions induced by the bubbles under ultrasound energy, but the ability to perform reliable BBB opening with a real-time feedback control algorithm has not been fully evaluated. This study focuses on characterizing the acoustic emissions of different types of bubbles: Optison, Definity, and a custom-made nanobubble. Their performance on reliable BBB opening under real-time feedback control based on acoustic detection was evaluated both in-vitro and in-vivo. The experiments were conducted using a 0.5 MHz focused ultrasound transducer with in-vivo focal pressure ranges from 0.1-0.7 MPa. Successful feedback control was achieved with all three agents when combining with infusion injection. Localized opening was confirmed with Evans blue dye leakage. Microscopic images were acquired to review the opening effects. Under similar total gas volume, nanobubble showed a more reliable opening effect compared to Optison and Definity (p < 0.05). The conclusions obtained from this study confirm the possibilities of performing stable opening using a feedback control algorithm combined with infusion injection. It also opens another potential research area of BBB opening using sub-micron bubbles.

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging

NASA Astrophysics Data System (ADS)

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-01

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×109 MBs ml-1 using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C3F8) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd3+ ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T1-weighted turbo-spin-echo sequence MR imaging. Heavy T2*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T1-, T2- and T2*-weighted MR images. The r1 and r2 relaxivities for Gd-DTPA were 7.69 and 21.35 s-1mM-1, respectively, indicating that the MBs represent a positive contrast agent in T1-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging.

PubMed

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-07

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10(9) MBs ml(-1) using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C(3)F(8)) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd(3+) ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T(1)-weighted turbo-spin-echo sequence MR imaging. Heavy T(2)*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T(1)-, T(2)- and T(2)*-weighted MR images. The r(1) and r(2) relaxivities for Gd-DTPA were 7.69 and 21.35 s(-1)mM(-1), respectively, indicating that the MBs represent a positive contrast agent in T(1)-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual

Low-Pressure Burst-Mode Focused Ultrasound Wave Reconstruction and Mapping for Blood-Brain Barrier Opening: A Preclinical Examination

PubMed Central

Xia, Jingjing; Tsui, Po-Hsiang; Liu, Hao-Li

2016-01-01

Burst-mode focused ultrasound (FUS) exposure has been shown to induce transient blood-brain barrier (BBB) opening for potential CNS drug delivery. FUS-BBB opening requires imaging guidance during the intervention, yet current imaging technology only enables postoperative outcome confirmation. In this study, we propose an approach to visualize short-burst low-pressure focal beam distribution that allows to be applied in FUS-BBB opening intervention on small animals. A backscattered acoustic-wave reconstruction method based on synchronization among focused ultrasound emission, diagnostic ultrasound receiving and passively beamformed processing were developed. We observed that focal beam could be successfully visualized for in vitro FUS exposure with 0.5–2 MHz without involvement of microbubbles. The detectable level of FUS exposure was 0.467 MPa in pressure and 0.05 ms in burst length. The signal intensity (SI) of the reconstructions was linearly correlated with the FUS exposure level both in-vitro (r2 = 0.9878) and in-vivo (r2 = 0.9943), and SI level of the reconstructed focal beam also correlated with the success and level of BBB-opening. The proposed approach provides a feasible way to perform real-time and closed-loop control of FUS-based brain drug delivery. PMID:27295608

Low-Pressure Burst-Mode Focused Ultrasound Wave Reconstruction and Mapping for Blood-Brain Barrier Opening: A Preclinical Examination

NASA Astrophysics Data System (ADS)

Xia, Jingjing; Tsui, Po-Hsiang; Liu, Hao-Li

2016-06-01

Burst-mode focused ultrasound (FUS) exposure has been shown to induce transient blood-brain barrier (BBB) opening for potential CNS drug delivery. FUS-BBB opening requires imaging guidance during the intervention, yet current imaging technology only enables postoperative outcome confirmation. In this study, we propose an approach to visualize short-burst low-pressure focal beam distribution that allows to be applied in FUS-BBB opening intervention on small animals. A backscattered acoustic-wave reconstruction method based on synchronization among focused ultrasound emission, diagnostic ultrasound receiving and passively beamformed processing were developed. We observed that focal beam could be successfully visualized for in vitro FUS exposure with 0.5-2 MHz without involvement of microbubbles. The detectable level of FUS exposure was 0.467 MPa in pressure and 0.05 ms in burst length. The signal intensity (SI) of the reconstructions was linearly correlated with the FUS exposure level both in-vitro (r2 = 0.9878) and in-vivo (r2 = 0.9943), and SI level of the reconstructed focal beam also correlated with the success and level of BBB-opening. The proposed approach provides a feasible way to perform real-time and closed-loop control of FUS-based brain drug delivery.

Radio Frequency Ultrasound Time Series Signal Analysis to Evaluate High-intensity Focused Ultrasound Lesion Formation Status in Tissue.

PubMed

Mobasheri, Saeedeh; Behnam, Hamid; Rangraz, Parisa; Tavakkoli, Jahan

2016-01-01

High-intensity focused ultrasound (HIFU) is a novel treatment modality used by scientists and clinicians in the recent decades. This modality has had a great and significant success as a noninvasive surgery technique applicable in tissue ablation therapy and cancer treatment. In this study, radio frequency (RF) ultrasound signals were acquired and registered in three stages of before, during, and after HIFU exposures. Different features of RF time series signals including the sum of amplitude spectrum in the four quarters of the frequency range, the slope, and intercept of the best-fit line to the entire power spectrum and the Shannon entropy were utilized to distinguish between the HIFU-induced thermal lesion and the normal tissue. We also examined the RF data, frame by frame to identify exposure effects on the formation and characteristics of a HIFU thermal lesion at different time steps throughout the treatment. The results obtained showed that the spectrum frequency quarters and the slope and intercept of the best fit line to the entire power spectrum both increased two times during the HIFU exposures. The Shannon entropy, however, decreased after the exposures. In conclusion, different characteristics of RF time series signal possess promising features that can be used to characterize ablated and nonablated tissues and to distinguish them from each other in a quasi-quantitative fashion.

Focal point determination in magnetic resonance-guided focused ultrasound using tracking coils.

PubMed

Svedin, Bryant T; Beck, Michael J; Hadley, J Rock; Merrill, Robb; de Bever, Joshua T; Bolster, Bradley D; Payne, Allison; Parker, Dennis L

2017-06-01

To develop a method for rapid prediction of the geometric focus location in MR coordinates of a focused ultrasound (US) transducer with arbitrary position and orientation without sonicating. Three small tracker coil circuits were designed, constructed, attached to the transducer housing of a breast-specific MR-guided focused US (MRgFUS) system with 5 degrees of freedom, and connected to receiver channel inputs of an MRI scanner. A one-dimensional sequence applied in three orthogonal directions determined the position of each tracker, which was then corrected for gradient nonlinearity. In a calibration step, low-level heating located the US focus in one transducer position orientation where the tracker positions were also known. Subsequent US focus locations were determined from the isometric transformation of the trackers. The accuracy of this method was verified by comparing the tracking coil predictions to thermal center of mass calculated using MR thermometry data acquired at 16 different transducer positions for MRgFUS sonications in a homogeneous gelatin phantom. The tracker coil predicted focus was an average distance of 2.1 ± 1.1 mm from the thermal center of mass. The one-dimensional locator sequence and prediction calculations took less than 1 s to perform. This technique accurately predicts the geometric focus for a transducer with arbitrary position and orientation without sonicating. Magn Reson Med 77:2424-2430, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Acceleration of low-energy ions at parallel shocks with a focused transport model

DOE PAGES

Zuo, Pingbing; Zhang, Ming; Rassoul, Hamid K.

2013-04-10

Here, we present a test particle simulation on the injection and acceleration of low-energy suprathermal particles by parallel shocks with a focused transport model. The focused transport equation contains all necessary physics of shock acceleration, but avoids the limitation of diffusive shock acceleration (DSA) that requires a small pitch angle anisotropy. This simulation verifies that the particles with speeds of a fraction of to a few times the shock speed can indeed be directly injected and accelerated into the DSA regime by parallel shocks. At higher energies starting from a few times the shock speed, the energy spectrum of acceleratedmore » particles is a power law with the same spectral index as the solution of standard DSA theory, although the particles are highly anisotropic in the upstream region. The intensity, however, is different from that predicted by DSA theory, indicating a different level of injection efficiency. It is found that the shock strength, the injection speed, and the intensity of an electric cross-shock potential (CSP) jump can affect the injection efficiency of the low-energy particles. A stronger shock has a higher injection efficiency. In addition, if the speed of injected particles is above a few times the shock speed, the produced power-law spectrum is consistent with the prediction of standard DSA theory in both its intensity and spectrum index with an injection efficiency of 1. CSP can increase the injection efficiency through direct particle reflection back upstream, but it has little effect on the energetic particle acceleration once the speed of injected particles is beyond a few times the shock speed. This test particle simulation proves that the focused transport theory is an extension of DSA theory with the capability of predicting the efficiency of particle injection.« less

Acoustic characterization of high intensity focused ultrasound fields: A combined measurement and modeling approach

PubMed Central

Canney, Michael S.; Bailey, Michael R.; Crum, Lawrence A.; Khokhlova, Vera A.; Sapozhnikov, Oleg A.

2008-01-01

Acoustic characterization of high intensity focused ultrasound (HIFU) fields is important both for the accurate prediction of ultrasound induced bioeffects in tissues and for the development of regulatory standards for clinical HIFU devices. In this paper, a method to determine HIFU field parameters at and around the focus is proposed. Nonlinear pressure waveforms were measured and modeled in water and in a tissue-mimicking gel phantom for a 2 MHz transducer with an aperture and focal length of 4.4 cm. Measurements were performed with a fiber optic probe hydrophone at intensity levels up to 24 000 W∕cm2. The inputs to a Khokhlov–Zabolotskaya–Kuznetsov-type numerical model were determined based on experimental low amplitude beam plots. Strongly asymmetric waveforms with peak positive pressures up to 80 MPa and peak negative pressures up to 15 MPa were obtained both numerically and experimentally. Numerical simulations and experimental measurements agreed well; however, when steep shocks were present in the waveform at focal intensity levels higher than 6000 W∕cm2, lower values of the peak positive pressure were observed in the measured waveforms. This underrepresentation was attributed mainly to the limited hydrophone bandwidth of 100 MHz. It is shown that a combination of measurements and modeling is necessary to enable accurate characterization of HIFU fields. PMID:19062878

An ex vivo feasibility experimental study on targeted cell surgery by high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

Wang, Zhi Biao; Wu, Junru; Fang, Liao Qiong; Wang, Hua; Li, Fa Qi; Tian, Yun Bo; Gong, Xiao Bo; Zhang, Hong; Zhang, Lian; Feng, Ruo

2012-10-01

High intensity focused ultrasound (HIFU) has become a new noninvasive surgical modality in medicine. A portion of tissue seated inside a patient's body may experience coagulative necrosis after a few seconds of insonification by high intensity focused ultrasound (US) generated by an extracorporeal focusing US transducer. The region of tissue affected by coagulative necrosis (CN) usually has an ellipsoidal shape when the thermal effect due to US absorption plays the dominant role. Its long and short axes are parallel and perpendicular to the US propagation direction respectively. It was shown by ex vivo experiments that the dimension of the short and long axes of the tissue which experiences CN can be as small as 50 μm and 250 μm respectively after one second exposure of US pulse (the spatial and pulse average acoustic power is on the order of tens of Watts and the local acoustic spatial and temporal pulse averaged intensity is on the order of 3 × 104 W/cm2) generated by a 1.6 MHz HIFU transducer of 12 cm diameter and 11 cm geometric focal length (f-number = 0.92). The numbers of cells which suffered CN were estimated to be on the order of 40. This result suggests that HIFU is able to interact with tens of cells at/near its focal zone while keeping the neighboring cells minimally affected, and thus the targeted cell surgery may be achievable.

Image-guided Navigation of Single-element Focused Ultrasound Transducer

PubMed Central

Kim, Hyungmin; Chiu, Alan; Park, Shinsuk; Yoo, Seung-Schik

2014-01-01

The spatial specificity and controllability of focused ultrasound (FUS), in addition to its ability to modify the excitability of neural tissue, allows for the selective and reversible neuromodulation of the brain function, with great potential in neurotherapeutics. Intra-operative magnetic resonance imaging (MRI) guidance (in short, MRg) has limitations due to its complicated examination logistics, such as fixation through skull screws to mount the stereotactic frame, simultaneous sonication in the MRI environment, and restrictions in choosing MR-compatible materials. In order to overcome these limitations, an image-guidance system based on optical tracking and pre-operative imaging data is developed, separating the imaging acquisition for guidance and sonication procedure for treatment. Techniques to define the local coordinates of the focal point of sonication are presented. First, mechanical calibration detects the concentric rotational motion of a rigid-body optical tracker, attached to a straight rod mimicking the sonication path, pivoted at the virtual FUS focus. The spatial error presented in the mechanical calibration was compensated further by MRI-based calibration, which estimates the spatial offset between the navigated focal point and the ground-truth location of the sonication focus obtained from a temperature-sensitive MR sequence. MRI-based calibration offered a significant decrease in spatial errors (1.9±0.8 mm; 57% reduction) compared to the mechanical calibration method alone (4.4±0.9 mm). Using the presented method, pulse-mode FUS was applied to the motor area of the rat brain, and successfully stimulated the motor cortex. The presented techniques can be readily adapted for the transcranial application of FUS to intact human brain. PMID:25232203

Ultrasound physics and instrumentation for pathologists.

PubMed

Lieu, David

2010-10-01

Interest in pathologist-performed ultrasound-guided fine-needle aspiration is increasing. Educational courses discuss clinical ultrasound and biopsy techniques but not ultrasound physics and instrumentation. To review modern ultrasound physics and instrumentation to help pathologists understand the basis of modern ultrasound. A review of recent literature and textbooks was performed. Ultrasound physics and instrumentation are the foundations of clinical ultrasound. The key physical principle is the piezoelectric effect. When stimulated by an electric current, certain crystals vibrate and produce ultrasound. A hand-held transducer converts electricity into ultrasound, transmits it into tissue, and listens for reflected ultrasound to return. The returning echoes are converted into electrical signals and used to create a 2-dimensional gray-scale image. Scanning at a high frequency improves axial resolution but has low tissue penetration. Electronic focusing moves the long-axis focus to depth of the object of interest and improves lateral resolution. The short-axis focus in 1-dimensional transducers is fixed, which results in poor elevational resolution away from the focal zone. Using multiple foci improves lateral resolution but degrades temporal resolution. The sonographer can adjust the dynamic range to change contrast and bring out subtle masses. Contrast resolution is limited by processing speed, monitor resolution, and gray-scale perception of the human eye. Ultrasound is an evolving field. New technologies include miniaturization, spatial compound imaging, tissue harmonics, and multidimensional transducers. Clinical cytopathologists who understand ultrasound physics, instrumentation, and clinical ultrasound are ready for the challenges of cytopathologist-performed ultrasound-guided fine-needle aspiration and core-needle biopsy in the 21st century.

High-intensity focused ultrasound for the treatment of fibroadenomata (HIFU-F) study.

PubMed

Peek, Mirjam C L; Ahmed, Muneer; Douek, Michael

2015-01-01

Breast fibroadenomata (FAD) are the most common benign lesions in women. For palpable lesions, there are currently three standard treatment options: reassurance (with or without follow-up), vacuum-assisted mammotomy (VAM) or surgical excision. High-intensity focused ultrasound (HIFU) ablation has been used in the treatment of FAD. The drawback of HIFU is its prolonged treatment duration. The aim of this trial is to evaluate circumferential HIFU treatment for the effective ablation of FAD with a reduced treatment time. Fifty patients (age ≥18 years) will be recruited with symptomatic FAD, visible on ultrasound (US, grade U2 benign). In patients ≥25 years, cytology or histology will be performed to confirm the diagnosis of a FAD. These patients will receive HIFU treatment using the US-guided Echopulse device (Theraclion Ltd., Malakoff, France) under local anaesthesia. An additional 50 patients will be recruited and contacted 6 months after discharge from the breast clinic. These patients will be offered an US scan to determine the change in size of their FAD. This natural change in size will be compared to the decrease in size after HIFU treatment. Secondary outcome measures include post-treatment complications, patient recorded outcome measures, mean treatment time and cost analysis. Current Controlled Trials: ISRCTN76622747.

Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles

NASA Astrophysics Data System (ADS)

Burgess, M. T.; Apostolakis, I.; Konofagou, E. E.

2018-03-01

Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum beamforming with absolute time delays. Since the axial image resolution is now dependent on the duration of the received acoustic cavitation emission, short pulses of FUS were used to limit its duration. Image sets were acquired at high-frame rates for calculation of power cavitation images analogous to power Doppler imaging. Power cavitation imaging displays the mean intensity of acoustic cavitation over time and was correlated with areas of acoustic cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS could constitute a standalone system that may not require MRI guidance during the procedure. The same technique can be used for other acoustic cavitation-based FUS therapies, for both safety and guidance.

Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles.

PubMed

Burgess, M T; Apostolakis, I; Konofagou, E E

2018-03-15

Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum beamforming with absolute time delays. Since the axial image resolution is now dependent on the duration of the received acoustic cavitation emission, short pulses of FUS were used to limit its duration. Image sets were acquired at high-frame rates for calculation of power cavitation images analogous to power Doppler imaging. Power cavitation imaging displays the mean intensity of acoustic cavitation over time and was correlated with areas of acoustic cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS could constitute a standalone system that may not require MRI guidance during the procedure. The same technique can be used for other acoustic cavitation-based FUS therapies, for both safety and guidance.

High-intensity focused ultrasound treatment of placenta accreta after vaginal delivery: a preliminary study.

PubMed

Bai, Y; Luo, X; Li, Q; Yin, N; Fu, X; Zhang, H; Qi, H

2016-04-01

To evaluate the safety and efficiency of high-intensity focused ultrasound (HIFU) in the treatment of placenta accreta after vaginal delivery. Enrolled into this study between September 2011 and September 2013 were 12 patients who had been diagnosed with placenta accreta following vaginal delivery and who had stable vital signs. All patients were treated using an ultrasound-guided HIFU treatment system. As indication of the effectiveness of the treatment we considered decreased vascular index on color Doppler imaging, decrease in size of residual placenta compared with pretreatment size on assessment by three-dimensional ultrasound with Virtual Organ Computer-aided Analysis, reduced signal intensity and degree of enhancement on magnetic resonance imaging and avoidance of hysterectomy following treatment. To assess the safety of HIFU treatment, we recorded side effects, hemorrhage, infection, sex steroid levels, return of menses and subsequent pregnancy. Patients were followed up in this preliminary study until December 2013. The 12 patients receiving HIFU treatment had an average postpartum hospital stay of 6.8 days and an average period of residual placental involution of 36.9 days. HIFU treatment did not apparently increase the risk of infection or hemorrhage and no patient required hysterectomy. In all patients menstruation recommenced after an average of 80.2 days, and sex steroid levels during the middle luteal phase of the second menstrual cycle were normal. Two patients became pregnant again during the follow-up period. This preliminary study suggests that ultrasound-guided HIFU is a safe and effective non-invasive method to treat placenta accreta patients after vaginal delivery who have stable vital signs and desire to preserve fertility. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Low-Energy Ions Injection and Acceleration at Oblique Shocks with Focused Transport Model

NASA Astrophysics Data System (ADS)

Zuo, P.; Zhang, M.; Feng, X. S.

2017-12-01

There is strong evidence that a small portion of suprathermal particles from hot coronal material or remnants of previous solar energetic particle (SEP) events serve as the source of large SEP events. Here we present a test particle simulation on the injection and acceleration of low-energy suprathermal particles by Laminar nonrelativistic oblique shocks in the framework of the focused transport theory, which is proved to contain all necessary physics of shock acceleration, but avoid the limitation of diffusive shock acceleration (DSA). We first characterize the role of cross-shock potential (CSP) on pickup ions (PUIs) acceleration. The CSP can affect the shape of the spectrum segment at lower energies, but it does not change the spectral index of the final power-law spectrum at high energies. It is found that a stronger CSP jump results in a dramatically improved injection efficiency. Our simulation results also show that the injection efficiency of PUIs is mass-dependent, which is lower for species with a higher mass. The injection efficiency as the function of Mach number, obliquity, injection speed, and shock strength is also calculated. It can be proved that the focused transport theory is an extension of DSA theory with the capability of predicting the efficiency of source particle injection.

MR-guided high-intensity focused ultrasound ablation of breast cancer with a dedicated breast platform.

PubMed

Merckel, Laura G; Bartels, Lambertus W; Köhler, Max O; van den Bongard, H J G Desirée; Deckers, Roel; Mali, Willem P Th M; Binkert, Christoph A; Moonen, Chrit T; Gilhuijs, Kenneth G A; van den Bosch, Maurice A A J

2013-04-01

Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.

Prediction of thermal coagulation from the instantaneous strain distribution induced by high-intensity focused ultrasound

NASA Astrophysics Data System (ADS)

Iwasaki, Ryosuke; Takagi, Ryo; Tomiyasu, Kentaro; Yoshizawa, Shin; Umemura, Shin-ichiro

2017-07-01

The targeting of the ultrasound beam and the prediction of thermal lesion formation in advance are the requirements for monitoring high-intensity focused ultrasound (HIFU) treatment with safety and reproducibility. To visualize the HIFU focal zone, we utilized an acoustic radiation force impulse (ARFI) imaging-based method. After inducing displacements inside tissues with pulsed HIFU called the push pulse exposure, the distribution of axial displacements started expanding and moving. To acquire RF data immediately after and during the HIFU push pulse exposure to improve prediction accuracy, we attempted methods using extrapolation estimation and applying HIFU noise elimination. The distributions going back in the time domain from the end of push pulse exposure are in good agreement with tissue coagulation at the center. The results suggest that the proposed focal zone visualization employing pulsed HIFU entailing the high-speed ARFI imaging method is useful for the prediction of thermal coagulation in advance.

Focused ultrasound-mediated drug delivery through the blood-brain barrier

PubMed Central

Burgess, Alison; Shah, Kairavi; Hough, Olivia; Hynynen, Kullervo

2015-01-01

Despite recent advances in blood-brain barrier (BBB) research, it remains a significant hurdle for the pharmaceutical treatment of brain diseases. Focused ultrasound (FUS) is one method to transiently increase permeability of the BBB to promote drug delivery to specific brain regions. An introduction to the BBB and a brief overview of the methods which can be used to circumvent the BBB to promote drug delivery is provided. In particular, we discuss the advantages and limitations of FUS technology and the efficacy of FUS-mediated drug delivery in models of disease. MRI for targeting and evaluating FUS treatments, combined with administration of microbubbles, allows for transient, reproducible BBB opening. The integration of a real-time acoustic feedback controller has improved treatment safety. Successful clinical translation of FUS has the potential to transform the treatment of brain disease worldwide without requiring the development of new pharmaceutical agents. PMID:25936845

Randomized sham-controlled trial to evaluate the safety and effectiveness of a high-intensity focused ultrasound device for noninvasive body sculpting.

PubMed

Jewell, Mark L; Baxter, Richard A; Cox, Sue Ellen; Donofrio, Lisa M; Dover, Jeffrey S; Glogau, Richard G; Kane, Michael A; Weiss, Robert A; Martin, Patrick; Schlessinger, Joel

2011-07-01

High-intensity focused ultrasound presents a noninvasive approach to body sculpting for nonobese patients. The purpose of this study was to evaluate the safety and effectiveness of a high-intensity focused ultrasound device for sculpting of the abdomen and flanks. Adults (aged 18 to 65 years) with subcutaneous abdominal fat greater than or equal to 2.5 cm thick who met screening criteria were randomized to receive high-intensity focused ultrasound treatment of the anterior abdomen and flanks at energy levels (a total of three passes each) of 47 J/cm (141 J/cm total), 59 J/cm (177 J/cm), or 0 J/cm (no energy applied, sham control). The primary endpoint was change from baseline waist circumference at the iliac crest level at posttreatment week 12. Subjective aesthetic assessments included the Global Aesthetic Improvement Scale and a patient satisfaction questionnaire. Safety assessments included adverse events, laboratory values, and physical examinations. For the primary endpoint, in the intent-to-treat population, statistical significance versus sham was achieved for the 59-J/cm (-2.44; p = 0.01) but not the 47-J/cm treatment group (-2.06 cm; p = 0.13). In a per-protocol population, statistical significance versus sham was achieved for both the 59-J/cm (-2.52 cm; p = 0.002) and the 47-J/cm treatment groups (-2.10 cm; p = 0.04). Investigator subjective measures of global aesthetic improvement and patient satisfaction also favored each active treatment versus sham. Adverse events included mild to moderate discomfort, bruising, and edema. Laboratory values and physical examinations were unremarkable. Treatment with this high-intensity focused ultrasound device reduced waist circumference and was generally well tolerated for noninvasive body sculpting. Reduction in waist circumference was statistically significant with both active treatments (per protocol). Therapeutic, II.(Figure is included in full-text article.).

Magnetic resonance imaging-guided focused ultrasound treatment of symptomatic uterine fibroids: impact of technology advancement on ablation volumes in 115 patients.

PubMed

Trumm, Christoph G; Stahl, Robert; Clevert, Dirk-André; Herzog, Peter; Mindjuk, Irene; Kornprobst, Sabine; Schwarz, Christina; Hoffmann, Ralf-Thorsten; Reiser, Maximilian F; Matzko, Matthias

2013-06-01

The aim of this study was to assess the impact of the advanced technology of the new ExAblate 2100 system (Insightec Ltd, Haifa, Israel) for magnetic resonance imaging (MRI)-guided focused ultrasound surgery on treatment outcomes in patients with symptomatic uterine fibroids, as measured by the nonperfused volume ratio. This is a retrospective analysis of 115 women (mean age, 42 years; range, 27-54 years) with symptomatic fibroids who consecutively underwent MRI-guided focused ultrasound treatment in a single center with the new generation ExAblate 2100 system from November 2010 to June 2011. Mean ± SD total volume and number of treated fibroids (per patient) were 89 ± 94 cm and 2.2 ± 1.7, respectively. Patient baseline characteristics were analyzed regarding their impact on the resulting nonperfused volume ratio. Magnetic resonance imaging-guided focused ultrasound treatment was technically successful in 115 of 123 patients (93.5%). In 8 patients, treatment was not possible because of bowel loops in the beam pathway that could not be mitigated (n = 6), patient movement (n = 1), and system malfunction (n = 1). Mean nonperfused volume ratio was 88% ± 15% (range, 38%-100%). Mean applied energy level was 5400 ± 1200 J, and mean number of sonications was 74 ± 27. No major complications occurred. Two cases of first-degree skin burn resolved within 1 week after the intervention. Of the baseline characteristics analyzed, only the planned treatment volume had a statistically significant impact on nonperfused volume ratio. With technological advancement, the outcome of MRI-guided focused ultrasound treatment in terms of the nonperfused volume ratio can be enhanced with a high safety profile, markedly exceeding results reported in previous clinical trials.

High-intensity focused ultrasound treatment in refractory glaucoma patients: results at 1 year of prospective clinical study.

PubMed

Melamed, Shlomo; Goldenfeld, Modi; Cotlear, Daniel; Skaat, Alon; Moroz, Iris

2015-01-01

To evaluate the safety and efficacy of the ultrasonic circular cyclo-coagulation procedure using high-intensity focused ultrasound by a miniaturized annular device containing 6 piezoceramic transducers in patients with refractory glaucoma. This was a prospective interventional noncomparative study of 20 eyes of 20 patients with refractory glaucoma. All eyes were treated with 6 activated transducers operating at 21 MHz. Ultrasound biomicroscopy and a complete ophthalmic examination were performed before the procedure and at 1 day, 1 week, and 1, 3, 6, and 12 months after the procedure. Primary outcomes were surgical success (defined as intraocular pressure (IOP) reduction from baseline ≥20% and IOP >5 mm Hg) at the last follow-up visit. Secondary outcomes were mean IOP at each follow-up visit compared to baseline, medication use, complications, and re-interventions. Intraocular pressure was significantly reduced (p<0.01) from a mean preoperative value of 36.4 ± 5.7 mm Hg to a mean postoperative value of 22.5 ± 10.3 mm Hg at 12 months. Four patients needed to be re-treated. The mean IOP reduction achieved was 38%. Surgical success was achieved in 13 of 20 eyes (65%). No major intraoperative or postoperative complications occurred. Ultrasonic circular cyclo-coagulation using high-intensity focused ultrasound delivered by a circular miniaturized device containing 6 piezoceramic transducers is an effective and well-tolerated method to reduce IOP in patients with refractory glaucoma.

MR compatible positioning device for guiding a focused ultrasound system for the treatment of brain deseases.

PubMed

Mylonas, N; Damianou, C

2014-03-01

A prototype magnetic resonance imaging (MRI)-compatible positioning device that navigates a high intensity focused ultrasound (HIFU) transducer is presented. The positioning device has three user-controlled degrees of freedom that allow access to brain targets using a lateral coupling approach. The positioning device can be used for the treatment of brain cancer (thermal mode ultrasound) or ischemic stroke (mechanical mode ultrasound). The positioning device incorporates only MRI compatible materials such as piezoelectric motors, ABS plastic, brass screws, and brass rack and pinion. The robot has the ability to accurately move the transducer thus creating overlapping lesions in rabbit brain in vivo. The registration and repeatability of the system was evaluated using tissues in vitro and gel phantom and was also tested in vivo in the brain of a rabbit. A simple, cost effective, portable positioning device has been developed which can be used in virtually any clinical MRI scanner since it can be placed on the table of the MRI scanner. This system can be used to treat in the future patients with brain cancer and ischemic stroke. Copyright © 2013 John Wiley & Sons, Ltd.

Combination of bubble liposomes and high-intensity focused ultrasound (HIFU) enhanced antitumor effect by tumor ablation.

PubMed

Hamano, Nobuhito; Negishi, Yoichi; Takatori, Kyohei; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo; Niidome, Takuro; Aramaki, Yukihiko

2014-01-01

Ultrasound (US) is used in the clinical setting not only for diagnosis but also for therapy. As a therapeutic US technique, high-intensity focused ultrasound (HIFU) can be applied to treat cancer in a clinical setting. Microbubbles increased temperature and improved the low therapeutic efficiency under HIFU; however, microbubbles have room for improvement in size, stability, and targeting ability. To solve these issues, we reported that "Bubble liposomes" (BLs) containing the US imaging gas (perfluoropropane gas) liposomes were suitable for ultrasound imaging and gene delivery. In this study, we examined whether BLs and HIFU could enhance the ablation area of the tumor and the antitumor effect. First, we histologically analyzed the tumor after BLs and HIFU. The ablation area of the treatment of BLs and HIFU was broader than that of HIFU alone. Next, we monitored the temperature of the tumor, and examined the antitumor effect. The temperature increase with BLs and HIFU treatment was faster and higher than that with HIFU alone. Moreover, treatment with BLs and HIFU enhanced the antitumor effect, which was better than with HIFU alone. Thus, the combination of BLs and HIFU could be efficacious for cancer therapy.

Ultrasound line-by-line scanning method of spatial-temporal active cavitation mapping for high-intensity focused ultrasound.

PubMed

Ding, Ting; Zhang, Siyuan; Fu, Quanyou; Xu, Zhian; Wan, Mingxi

2014-01-01

This paper presented an ultrasound line-by-line scanning method of spatial-temporal active cavitation mapping applicable in a liquid or liquid filled tissue cavities exposed by high-intensity focused ultrasound (HIFU). Scattered signals from cavitation bubbles were obtained in a scan line immediately after one HIFU exposure, and then there was a waiting time of 2 s long enough to make the liquid back to the original state. As this pattern extended, an image was built up by sequentially measuring a series of such lines. The acquisition of the beamformed radiofrequency (RF) signals for a scan line was synchronized with HIFU exposure. The duration of HIFU exposure, as well as the delay of the interrogating pulse relative to the moment while HIFU was turned off, could vary from microseconds to seconds. The feasibility of this method was demonstrated in tap-water and a tap-water filled cavity in the tissue-mimicking gelatin-agar phantom as capable of observing temporal evolutions of cavitation bubble cloud with temporal resolution of several microseconds, lateral and axial resolution of 0.50 mm and 0.29 mm respectively. The dissolution process of cavitation bubble cloud and spatial distribution affected by cavitation previously generated were also investigated. Although the application is limited by the requirement for a gassy fluid (e.g. tap water, etc.) that allows replenishment of nuclei between HIFU exposures, the technique may be a useful tool in spatial-temporal cavitation mapping for HIFU with high precision and resolution, providing a reference for clinical therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

Tuning the DARHT Axis-II linear induction accelerator focusing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ekdahl, Carl A.

2012-04-24

Flash radiography of large hydrodynamic experiments driven by high explosives is a well-known diagnostic technique in use at many laboratories, and the Dual-Axis Radiography for Hydrodynamic Testing (DARHT) facility at Los Alamos produces flash radiographs of large hydrodynamic experiments. Two linear induction accelerators (LIAs) make the bremsstrahlung radiographic source spots for orthogonal views of each test. The 2-kA, 20-MeV Axis-I LIA creates a single 60-ns radiography pulse. The 1.7-kA, 16.5-MeV Axis-II LIA creates up to four radiography pulses by kicking them out of a longer pulse that has a 1.6-{mu}s flattop. The Axis-II injector, LIA, kicker, and downstream transport (DST)more » to the bremsstrahlung converter are described. Adjusting the magnetic focusing and steering elements to optimize the electron-beam transport through an LIA is often called 'tuning.' As in all high-current LIAs, the focusing field is designed to be as close to that of the ideal continuous solenoid as physically possible. In ideal continuous solenoidal transport a smoothly varying beam size can easily be found for which radial forces balance, and the beam is said to be 'matched' to the focusing field. A 'mismatched' beam exhibits unwanted oscillations in size, which are a source of free energy that contributes to emittance growth. This is undesirable, because in the absence of beam-target effects, the radiographic spot size is proportional to the emittance. Tuning the Axis-II LIA is done in two steps. First, the solenoidal focusing elements are set to values designed to provide a matched beam with little or no envelope oscillations, and little or no beam-breakup (BBU) instability growth. Then, steering elements are adjusted to minimize the motion of the centroid of a well-centered beam at the LIA exit. This article only describes the design of the tune for the focusing solenoids. The DARHT Axis-II LIA was required to be re-tuned after installing an accelerator cell to replace a

Hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound in the treatment of a rabbit liver trauma model

PubMed Central

Zhao, Da-wei; Tian, Meng; Yang, Jian-zheng; Du, Peng; Bi, Jie; Zhu, Xinjian

2016-01-01

The aim of our study was to investigate the hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound treatment of liver trauma. Thirty rabbits with liver trauma were randomly divided into three groups—the microbubble-enhanced ultrasound (MEUS; further subdivided based on exposure intensity into MEUS1 [0.11 W/cm2], MEUS2 [0.55 W/cm2], and MEUS3 [1.1 W/cm2]), ultrasound without microbubbles (US), and microbubbles without ultrasound (MB) groups. The pre- and post-treatment bleeding weight and visual bleeding scores were evaluated. The serum liver enzyme concentrations as well as the blood perfusion level represented by mean peak contrast intensity (PI) ratio in the treatment area were analyzed. The hemostatic mechanism was evaluated by histological and transmission electron microscopic examination of liver tissue samples. The MEUS subgroups 1–3 (grade 0–1, grade 0–2, and grade 1–2, respectively) exhibited significantly lower post-treatment visual bleeding scores than the US and MB groups (both, grade 3–4; all, P < 0.05). Subgroups MEUS1 (0.346 ± 0.345 g) and MEUS2 (2.232 ± 2.256 g) exhibited significantly lower post-treatment bleeding weight than the US and MB groups (5.698 ± 1.938 and 5.688 ± 2.317 g, respectively; all, P < 0.05). Additionally, MEUS subgroups 1–3 exhibited significantly lower post-treatment blood perfusion levels (PI ratios, 0.64 ± 0.085, 0.73 ± 0.045, and 0.84 ± 0.034, respectively) than the US and MB groups (PI ratios, 1.00 ± 0.005 and 0.99 ± 0.005, respectively; all, P < 0.05). In the MEUS group, hepatic cells became edematous and compressed the hepatic sinus and associated blood vessels. However, the serum liver enzyme levels were not significantly altered. Microbubble-enhanced non-focused ultrasound does not significantly affect blood perfusion and liver function and can be used to induce rapid hemostasis in case of liver trauma. PMID:27633577

Electrophysiological changes correlated with temperature increases induced by high-intensity focused ultrasound ablation.

PubMed

Wu, Ziqi; Kumon, Ronald E; Laughner, Jacob I; Efimov, Igor R; Deng, Cheri X

2015-02-01

To gain better understanding of the detailed mechanisms of high-intensity focused ultrasound (HIFU) ablation for cardiac arrhythmias, we investigated how the cellular electrophysiological (EP) changes were correlated with temperature increases and thermal dose (cumulative equivalent minutes [CEM43]) during HIFU application using Langendorff-perfused rabbit hearts. Employing voltage-sensitive dye di-4-ANEPPS, we measured the EP and temperature during HIFU using simultaneous optical mapping and infrared imaging. Both action potential amplitude (APA) and action potential duration at 50% repolarization (APD50) decreased with temperature increases, and APD50 was more thermally sensitive than APA. EP and tissue changes were irreversible when HIFU-induced temperature increased above 52.3 ± 1.4°C and log10(CEM43) above 2.16 ± 0.51 (n = 5), but were reversible when temperature was below 50.1 ± 0.8°C and log10(CEM43) below -0.9 ± 0.3 (n = 9). EP and temperature/thermal dose changes were spatially correlated with HIFU-induced tissue necrosis surrounded by a transition zone. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

High-intensity focused ultrasound for ex vivo kidney tissue ablation: influence of generator power and pulse duration.

PubMed

Häcker, Axel; Köhrmann, Kai Uwe; Knoll, Thomas; Langbein, Sigrun; Steidler, Annette; Kraut, Oliver; Marlinghaus, Ernst; Alken, Peter; Michel, Maurice Stephan

2004-11-01

The therapeutic application of noninvasive tissue ablation by high-intensity focused ultrasound (HIFU) requires precise physical definition of the focal size and determination of control parameters. The objective of this study was to measure the extent of ex-vivo porcine kidney tissue ablation at variable generator parameters and to identify parameters to control lesion size. The ultrasound waves generated by a cylindrical piezoceramic element (1.04 MHz) were focused at a depth of 100 mm using a parabolic reflector (diameter 100 mm). A needle hydrophone was used to measure the field distribution of the sound pressure. The morphology and extent of tissue necrosis were examined at generator powers of up to 400 W (P(el)) and single pulse durations of as long as 8 seconds. The two-dimensional field distribution resulted in an approximately ellipsoidal focus of 32 x 4 mm (-6 dB). A sharp demarcation between coagulation necrosis and intact tissue was observed. Lesion size was controlled by both the variation of generator power and the pulse duration. At a constant pulse duration of 2 seconds, a generator power of 100 W remained below the threshold doses for inducing a reproducible lesion. An increase in power to as high as 400 W induced lesions with average dimensions of as much as 11.2 x 3 mm. At constant total energy (generator power x pulse duration), lesion size increased at higher generator power. This ultrasound generator can induce defined and reproducible necrosis in ex-vivo kidney tissue. Lesion size can be controlled by adjusting the generator power and pulse duration. Generator power, in particular, turned out to be a suitable control parameter for obtaining a lesion of a defined size.

Successful treatment of central venous catheter induced superior vena cava syndrome with ultrasound accelerated catheter-directed thrombolysis.

PubMed

Dumantepe, Mert; Tarhan, Arif; Ozler, Azmi

2013-06-01

Superior vena cava (SVC) syndrome results from obstruction of flow through the vessel either by external compression or thrombosis. External compression by intrathoracic neoplasms is the most common etiology, especially lung cancer and lymphoma. Thrombosis is becoming increasingly common due to the use of indwelling catheters and implantable central venous access devices. Most patients are unresponsive to anticoagulation alone which appears to be effective only in the mildest cases. However, recent advances in catheter-based interventions have led to the development of a variety of minimally invasive endovascular strategies to remove venous thrombus and accepted as an important first-line treatment given its high overall success rate and low morbidity as compared with medical and surgical treatments. Ultrasound accelerated catheter-directed thrombolysis (UACDT) has been developed to rapidly and completely resolve the existing thrombus. This technique integrates high frequency, low intensity ultrasound (US) with standard CDT in order to accelerate clot dissolution, reducing treatment time and the incidence of thrombolysis-related complications. An US wave enhances drug permeation through thrombus by disaggregating the fibrin matrix, exposing additional plasminogen receptor sites to the thrombolytic agent. The US energy affects thrombus in the entire venous segment, increasing the probability of complete thrombus clearing. We report the case of a 56-year-old man who presented with a 5 days history of SVC syndrome symptoms who had been receiving chemotherapy for colon cancer through a right subclavian vein port catheter. The patient successfully treated with UACDT with EkoSonic(®) Mach4e Endovascular device with an overnight infusion. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.

Primary malignant tumours of the bony pelvis: US-guided high intensity focused ultrasound ablation.

PubMed

Wang, Yang; Wang, Wei; Tang, Jie

2013-11-01

The aim of this review is to evaluate the value of ultrasound (US)-guided high intensity focused ultrasound (HIFU) ablation in the treatment of primary malignant tumours of the bony pelvis. Eleven patients with primary malignant tumours of the bony pelvis received US-guided HIFU ablation. The maximum tumour size ranged from 5.6 to 25.0 cm (median 10.5 cm). Treatment was curative in four patients and palliative in seven patients. During follow-up, the effectiveness of HIFU ablation was assessed by contrast-enhanced magnetic resonance (MR). Significant coagulative necrosis was obtained in all patients after scheduled HIFU ablations; the volume ablation ratio was 86.7% ± 12.5% (range 65-100%). Complete tumour necrosis was achieved in all patients receiving curative HIFU ablation. No major complications were encountered. No patients died of local tumour progression during follow-up. US-guided HIFU ablation may be a safe and effective minimally invasive technique for the local treatment of primary malignant tumours of the bony pelvis.

Conventional, ultrasound-assisted, and accelerated-solvent extractions of anthocyanins from purple sweet potatoes.

PubMed

Cai, Zhan; Qu, Ziqian; Lan, Yu; Zhao, Shujuan; Ma, Xiaohua; Wan, Qiang; Jing, Pu; Li, Pingfan

2016-04-15

Purple sweet potatoes (PSPs) are rich in anthocyanins. In this study, we investigated the extraction efficiency of anthocyanins from PSPs using conventional extraction (CE), ultrasound-assisted extraction (UAE), and accelerated-solvent extraction (ASE). Additionally, the effects of these extraction methods on antioxidant activity and anthocyanin composition of PSP extracts were evaluated. In order of decreasing extraction efficiency, the extraction methods were ASE>UAE>CE for anthocyanins (218-244 mg/100 g DW) and CE>UAE>ASE for total phenolics (631-955 mg/100 g DW) and flavonoids (28-40 mg/100 g DW). Antioxidant activities of PSP extracts were CE≈UAE>ASE for ORAC (766-1091 mg TE/100 g DW) and ASE>CE≈UAE for FRAP (1299-1705 mg TE/100 g DW). Twelve anthocyanins were identified. ASE extracts contained more diacyl anthocyanins and less nonacyl and monoacyl anthocyanins than CE and ASE extracts (P<0.05). Copyright © 2015 Elsevier Ltd. All rights reserved.

Design and validation of an MR-conditional robot for transcranial focused ultrasound surgery in infants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, Karl D., E-mail: karl.price@sickkids.ca

Purpose: Current treatment of intraventricular hemorrhage (IVH) involves cerebral shunt placement or an invasive brain surgery. Magnetic resonance-guided focused ultrasound (MRgFUS) applied to the brains of pediatric patients presents an opportunity to treat IVH in a noninvasive manner, termed “incision-less surgery.” Current clinical and research focused ultrasound systems lack the capability to perform neonatal transcranial surgeries due to either range of motion or dexterity requirements. A novel robotic system is proposed to position a focused ultrasound transducer accurately above the head of a neonatal patient inside an MRI machine to deliver the therapy. Methods: A clinical Philips Sonalleve MRgFUS systemmore » was expanded to perform transcranial treatment. A five degree-of-freedom MR-conditional robot was designed and manufactured using MR compatible materials. The robot electronics and control were integrated into existing Philips electronics and software interfaces. The user commands the position of the robot with a graphical user interface, and is presented with real-time MR imaging of the patient throughout the surgery. The robot is validated through a series of experiments that characterize accuracy, signal-to-noise ratio degeneration of an MR image as a result of the robot, MR imaging artifacts generated by the robot, and the robot’s ability to operate in a representative surgical environment inside an MR machine. Results: Experimental results show the robot responds reliably within an MR environment, has achieved 0.59 ± 0.25 mm accuracy, does not produce severe MR-imaging artifacts, has a workspace providing sufficient coverage of a neonatal brain, and can manipulate a 5 kg payload. A full system demonstration shows these characteristics apply in an application environment. Conclusions: This paper presents a comprehensive look at the process of designing and validating a new robot from concept to implementation for use in an MR environment

Intense focused ultrasound stimulation of the rotator cuff: evaluation of the source of pain in rotator cuff tears and tendinopathy.

PubMed

Gellhorn, Alfred C; Gillenwater, Cody; Mourad, Pierre D

2015-09-01

The objective of this preliminary study was to evaluate the ability of individual 0.1-s long pulses of intense focused ultrasound (iFU) emitted with a carrier frequency of 2 MHz to evoke diagnostic sensations when applied to patients whose shoulders have rotator cuff tears or tendinopathy. Patients were adults with painful shoulders and clinical and imaging findings consistent with rotator cuff disease. iFU stimulation of the shoulder was performed using B-mode ultrasound coupled with a focused ultrasound transducer that allowed image-guided delivery of precisely localized pulses of energy to different anatomic areas around the rotator cuff. The main outcome measure was iFU spatial average-temporal average intensity (I_SATA), and location required to elicit sensation. In control patients, iFU produced no sensation throughout the range of stimulation intensities (≤2000 W/cm(2) I_SATA). In patients with rotator cuff disease, iFU was able to induce sensation in the tendons of the rotator cuff, the subacromial bursa, and the subchondral bone in patients with chronic shoulder pain and rotator cuff disease, with an average ± standard deviation intensity equaling 680 ± 281 W/cm(2) I_SATA. This result suggests a primary role for these tissues in the pathogenesis of shoulder pain related to rotator cuff tendinopathy. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Novel ultrasound method to reposition kidney stones

PubMed Central

Shah, Anup; Owen, Neil R.; Lu, Wei; Cunitz, Bryan W.; Kaczkowski, Peter J.; Harper, Jonathan D.; Bailey, Michael R.; Crum, Lawrence A.

2011-01-01

The success of surgical management of lower pole stones is principally dependent on stone fragmentation and residual stone clearance. Choice of surgical method depends on stone size, yet all methods are subject to post-surgical complications resulting from residual stone fragments. Here we present a novel method and device to reposition kidney stones using ultrasound radiation force delivered by focused ultrasound and guided by ultrasound imaging. The device couples a commercial imaging array with a focused annular array transducer. Feasibility of repositioning stones was investigated by implanting artificial and human stones into a kidney-mimicking phantom that simulated a lower pole and collecting system. During experiment, stones were located by ultrasound imaging and repositioned by delivering short bursts of focused ultrasound. Stone motion was concurrently monitored by fluoroscopy, ultrasound imaging, and video photography, from which displacement and velocity were estimated. Stones were seen to move immediately after delivering focused ultrasound and successfully repositioned from the lower pole to the collecting system. Estimated velocities were on the order of 1 cm/s. This in vitro study demonstrates a promising modality to facilitate spontaneous clearance of kidney stones and increased clearance of residual stone fragments after surgical management. PMID:20967437

Effect of abdominal liposuction on sonographically guided high-intensity focused ultrasound ablation.

PubMed

Zhao, Wen-Peng; Chen, Jin-Yun; Chen, Wen-Zhi

2014-09-01

The aim of this study was to evaluate the effect of abdominal liposuction on sonographically guided high-intensity focused ultrasound (HIFU) ablation. A total of 10 women with uterine fibroids or adenomyosis who had received abdominal liposuction were analyzed after sonographically guided HIFU ablation. Of the 10 women, 6 had a diagnosis of uterine fibroids, and 4 had a diagnosis of uterine adenomyosis. All of them had a history of a horizontal-margin split-cesarean delivery. In addition, 26 women with a history of a single horizontal-margin split-cesarean delivery who had a diagnosis of uterine fibroids or adenomyosis but had not received liposuction were analyzed together as a control group. Of the 10 women, 1 woman with uterine fibroids developed local skin erythema after treatment; 1 women with uterine adenomyosis developed a skin burn after treatment; and the remaining women had obvious skin-burning pain during treatment. All women who had not received liposuction finished the treatment with no serious adverse events during or after treatment. The pain scores and incidence of skin-burning pain were significantly higher in the liposuction group than the control group (P= .021 and .038, respectively). Abdominal liposuction may increase the risk of skin burns during sonographically guided HIFU ablation. © 2014 by the American Institute of Ultrasound in Medicine.

Temperature distributions measurement of high intensity focused ultrasound using a thin-film thermocouple array and estimation of thermal error caused by viscous heating.

PubMed

Matsuki, Kosuke; Narumi, Ryuta; Azuma, Takashi; Yoshinaka, Kiyoshi; Sasaki, Akira; Okita, Kohei; Takagi, Shu; Matsumoto, Yoichiro

2013-01-01

To improve the throughput of high intensity focused ultrasound (HIFU) treatment, we have considered a focus switching method at two points. For this method, it is necessary to evaluate the thermal distribution under exposure to ultrasound. The thermal distribution was measured using a prototype thin-film thermocouple array, which has the advantage of minimizing the influence of the thermocouple on the acoustic and temperature fields. Focus switching was employed to enlarge the area of temperature increase and evaluate the proposed evaluation parameters with respect to safety and uniformity. The results indicate that focus switching can effectively expand the thermal lesion while maintaining a steep thermal boundary. In addition, the influence caused by the thin-film thermocouple array was estimated experimentally. This thermocouple was demonstrated to be an effective tool for the measurement of temperature distributions induced by HIFU.

Full Modeling of High-Intensity Focused Ultrasound and Thermal Heating in the Kidney Using Realistic Patient Models.

PubMed

Suomi, Visa; Jaros, Jiri; Treeby, Bradley; Cleveland, Robin O

2018-05-01

High-intensity focused ultrasound (HIFU) therapy can be used for noninvasive treatment of kidney (renal) cancer, but the clinical outcomes have been variable. In this study, the efficacy of renal HIFU therapy was studied using nonlinear acoustic and thermal simulations in three patients. The acoustic simulations were conducted with and without refraction in order to investigate its effect on the shape, size, and pressure distribution at the focus. The values for the attenuation, sound speed, perfusion, and thermal conductivity of the kidney were varied over the reported ranges to determine the effect of variability on heating. Furthermore, the phase aberration was studied in order to quantify the underlying phase shifts using a second-order polynomial function. The ultrasound field intensity was found to drop on average 11.1 dB with refraction and 6.4 dB without refraction. Reflection at tissue interfaces was found to result in a loss less than 0.1 dB. Focal point splitting due to refraction significantly reduced the heating efficacy. Of all the tissue parameters, perfusion was found to affect the heating the most. Small changes in temperature were seen with varying attenuation and thermal conductivity, but no visible changes were present with sound speed variations. The aberration study revealed an underlying trend in the spatial distribution of the phase shifts. The results show that the efficacy of HIFU therapy in the kidney could be improved with aberration correction. A method is proposed by which patient specific pretreatment calculations could be used to overcome the aberration and therefore make ultrasound treatment possible.

Disrupting the blood-brain barrier by focused ultrasound induces sterile inflammation.

PubMed

Kovacs, Zsofia I; Kim, Saejeong; Jikaria, Neekita; Qureshi, Farhan; Milo, Blerta; Lewis, Bobbi K; Bresler, Michele; Burks, Scott R; Frank, Joseph A

2017-01-03

MRI-guided pulsed focused ultrasound (pFUS) combined with systemic infusion of ultrasound contrast agent microbubbles (MB) causes localized blood-brain barrier (BBB) disruption that is currently being advocated for increasing drug or gene delivery in neurological diseases. The mechanical acoustic cavitation effects of opening the BBB by low-intensity pFUS+MB, as evidenced by contrast-enhanced MRI, resulted in an immediate damage-associated molecular pattern (DAMP) response including elevations in heat-shock protein 70, IL-1, IL-18, and TNFα indicative of a sterile inflammatory response (SIR) in the parenchyma. Concurrent with DAMP presentation, significant elevations in proinflammatory, antiinflammatory, and trophic factors along with neurotrophic and neurogenesis factors were detected; these elevations lasted 24 h. Transcriptomic analysis of sonicated brain supported the proteomic findings and indicated that the SIR was facilitated through the induction of the NFκB pathway. Histological evaluation demonstrated increased albumin in the parenchyma that cleared by 24 h along with TUNEL + neurons, activated astrocytes, microglia, and increased cell adhesion molecules in the vasculature. Infusion of fluorescent beads 3 d before pFUS+MB revealed the infiltration of CD68 + macrophages at 6 d postsonication, as is consistent with an innate immune response. pFUS+MB is being considered as part of a noninvasive adjuvant treatment for malignancy or neurodegenerative diseases. These results demonstrate that pFUS+MB induces an SIR compatible with ischemia or mild traumatic brain injury. Further investigation will be required before this approach can be widely implemented in clinical trials.

Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression

PubMed Central

Perna, Giampaolo; Iannone, Giuseppe; Alciati, Alessandra; Caldirola, Daniela

2016-01-01

Anxiety disorders (AnxDs) are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Aβ accumulation, and immune-inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed. PMID:26881136

High-frequency rapid B-mode ultrasound imaging for real-time monitoring of lesion formation and gas body activity during high-intensity focused ultrasound ablation.

PubMed

Gudur, Madhu Sudhan Reddy; Kumon, Ronald E; Zhou, Yun; Deng, Cheri X

2012-08-01

The goal of this study was to examine the ability of high-frame-rate, high-resolution imaging to monitor tissue necrosis and gas-body activities formed during high-intensity focused ultrasound (HIFU) application. Ex vivo porcine cardiac tissue specimens (n = 24) were treated with HIFU exposure (4.33 MHz, 77 to 130 Hz pulse repetition frequency (PRF), 25 to 50% duty cycle, 0.2 to 1 s, 2600 W/cm(2)). RF data from B-mode ultrasound imaging were obtained before, during, and after HIFU exposure at a frame rate ranging from 77 to 130 Hz using an ultrasound imaging system with a center frequency of 55 MHz. The time history of changes in the integrated backscatter (IBS), calibrated spectral parameters, and echo-decorrelation parameters of the RF data were assessed for lesion identification by comparison against gross sections. Temporal maximum IBS with +12 dB threshold achieved the best identification with a receiver-operating characteristic (ROC) curve area of 0.96. Frame-to-frame echo decorrelation identified and tracked transient gas-body activities. Macroscopic (millimeter-sized) cavities formed when the estimated initial expansion rate of gas bodies (rate of expansion in lateral-to-beam direction) crossed 0.8 mm/s. Together, these assessments provide a method for monitoring spatiotemporal evolution of lesion and gas-body activity and for predicting macroscopic cavity formation.

Feasibility study of high intensity focused ultrasound (HIFU) for the treatment of hydatid cysts of the liver.

PubMed

Imankulov, S B; Fedotovskikh, G V; Shaimardanova, G M; Yerlan, M; Zhampeisov, N K

2015-11-01

This study evaluates the feasibility of using high intensity focused ultrasound (HIFU) for the treatment of hydatid cysts of the liver. HIFU ablation was carried out in 62 patients with echinococcosis of the liver. The mean age of patients was 40.76±14.84 (range: 17-72 years). The effectiveness of the treatment was monitored in real-time by changes in the gray-scale, and by morphological studies, computed tomography, magnetic resonance imaging, and ultrasound. Criteria for evaluating the effectiveness of treatment in real time were outlines. Cytomorphological picture of destructive changes of parasitic elements was presented as well. Loss of embryonic elements of the parasite was observed at the subcellular level after HIFU-ablation and underlines the effectiveness of HIFU. Copyright © 2015. Published by Elsevier B.V.

Back-streaming ion emission and beam focusing on high power linear induction accelerator

NASA Astrophysics Data System (ADS)

Zhu, Jun; Chen, Nan; Yu, Haijun; Jiang, Xiaoguo; Wang, Yuan; Dai, Wenhua; Gao, Feng; Wang, Minhong; Li, Jin; Shi, Jinshui

2011-08-01

Ions released from target surfaces by impact of a high intensity and current electron beam can be accelerated and trapped in the beam potential, and further destroy the beam focus. By solving the 2D Poisson equation, we found that the charge neutralization factor of the ions to the beam under space charge limited condition is 1/3, which is large enough to disrupt the spot size. Therefore, the ion emission at the target in a single-pulse beam/target system must be source limited. Experimental results on the time-resolved beam profile measurement have also proven that. A new focus scheme is proposed in this paper to focus the beam to a small spot size with the existence of back-streaming ions. We found that the focal spot will move upstream as the charge neutralization factor increases. By comparing the theoretical and experimental focal length of the Dragon-I accelerator (20 MeV, 2.5 kA, 60 ns flattop), we found that the average neutralization factor is about 5% in the beam/target system.

Nanobiotechnology promotes noninvasive high-intensity focused ultrasound cancer surgery.

PubMed

Chen, Yu; Chen, Hangrong; Shi, Jianlin

2015-01-07

The successful cancer eradication in a noninvasive manner is the ultimate objective in the fight against cancer. As a "bloodless scalpel," high-intensity focused ultrasound (HIFU) is regarded as one of the most promising and representative noninvasive therapeutic modalities for cancer surgery. However, large-scale clinical applications of HIFU are still in their infancy because of critical efficiency and safety issues which remain to be solved. Fortunately, recently developed nanobiotechnology provides an alternative efficient approach to improve such important issues in HIFU, especially for cancer therapy. This Research News presents the very recent exciting progresses on the elaborate design and fabrication of organic, inorganic, and organic/inorganic hybrid nanoparticles for enhancing the HIFU ablation efficiency against tumor tissues. It is highly expected that this Research News can arouse more extensive research enthusiasm on the development of functional nanomaterials for highly efficient HIFU-based synergistic therapy, which will give a promising noninvasive therapeutic modality for the successful cancer therapy with minimal damage to surrounding normal tissues, due to the noninvasive and site-specific therapeutic features of HIFU. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multifunctional pulse generator for high-intensity focused ultrasound system

NASA Astrophysics Data System (ADS)

Tamano, Satoshi; Yoshizawa, Shin; Umemura, Shin-Ichiro

2017-07-01

High-intensity focused ultrasound (HIFU) can achieve high spatial resolution for the treatment of diseases. A major technical challenge in implementing a HIFU therapeutic system is to generate high-voltage high-current signals for effectively exciting a multichannel HIFU transducer at high efficiencies. In this paper, we present the development of a multifunctional multichannel generator/driver. The generator can produce a long burst as well as an extremely high-voltage short pulse of pseudosinusoidal waves (trigger HIFU) and second-harmonic superimposed waves for HIFU transmission. The transmission timing, waveform, and frequency can be controlled using a field-programmable gate array (FPGA) via a universal serial bus (USB) microcontroller. The hardware is implemented in a compact printed circuit board. The test results of trigger HIFU reveal that the power consumption and the temperature rise of metal-oxide semiconductor field-effect transistors were reduced by 19.9% and 38.2 °C, respectively, from the previous design. The highly flexible performance of the novel generator/driver is demonstrated in the generation of second-harmonic superimposed waves, which is useful for cavitation-enhanced HIFU treatment, although the previous design exhibited difficulty in generating it.

Expulsion of Fibroids to the Endometrial Cavity after Magnetic Resonance Imaging-guided High Intensity Focused Ultrasound Surgery (MRgFUS) Treatment of Intramural Uterine Fibroids

PubMed Central

Jeong, Jae-Hyeok; Hong, Gil Pyo; Kim, Yu-Ri; Hong, Da Gyo; Ha, Jae-Eun; Yeom, Jung In; Kim, Eun-Jeong; Kim, Hyung-Il

2016-01-01

Objectives This report seeks to introduce some cases of the patients who received magnetic resonance imaging (MRI)-guided high intensity focused ultrasound (HIFU) surgery (MRgFUS)-based intramural uterine fibroids treatment where the post-MRgFUS intramural uterine fibroids decreased in its volume and protruded towards the endometrial cavity to be expelled by hysteroscopy. Methods Of the 157 patients who had received MRgFUS treatment in the Obstetrics and Gynecology of the Hospital from March, 2015 to February, 2016; this study examined 6 of the cases where, after high intensity focused ultrasound treatment, intramural uterine fibroids protruded towards the endometrial cavity to be removed by hysteroscopic myomectomy. The high intensity focused ultrasound utilized in the cases were Philips Achieva 1.5 Tesla MR (Philips Healthcare, Best, The Netherlands) and Sonalleve HIFU system. Results The volume of fibroids ranged from 26.0 cm3 to 199.5 cm3, averaging 95.6 cm3. The major axis length ranged from 4.0 cm to 8.2 cm, averaging 6.3 cm. Fibroid location in all of the patients was in intramural uterine before treatment but after the high intensity focused ultrasound treatment, the fibroids were observed to protrude towards the endometrial cavity in at least Day 5 or up to Day 73 to allow hysteroscopic myomectomy. Conclusions In some cases, after an intramural uterine fibroid is treated with MRgFUS, fibroid volume is decreased and the fibroid protrudes towards the endometrial cavity. In this case, hysteroscopic myomectomy can be a useful solution. PMID:28119893

Acoustic Droplet Vaporization for the Enhancement of Ultrasound Thermal Therapy.

PubMed

Zhang, Man; Fabiilli, Mario; Carson, Paul; Padilla, Frederic; Swanson, Scott; Kripfgans, Oliver; Fowlkes, Brian

2010-10-11

Acoustic droplet vaporization (ADV) is an ultrasound method for converting biocompatible microdroplets into microbubbles. The objective is to demonstrate that ADV bubbles can enhance high intensity focused ultrasound (HIFU) therapy by controlling and increasing energy absorption at the focus. Thermal phantoms were made with or without droplets. Compound lesions were formed in the phantoms by 5-second exposures with 5-second delays. Center to center spacing of individual lesions was 5.5 mm in either a linear pattern or a spiral pattern. Prior to the HIFU, 10 cycle tone bursts with 0.25% duty cycle were used to vaporize the droplets, forming an "acoustic trench" within 30 seconds. The transducer was then focused in the middle of the back bubble wall to form thermal lesions in the trench. All lesions were imaged optically and with 2T MRI. With the use of ADV and the acoustic trench, a uniform thermal ablation volume of 15 cm(3) was achieved in 4 minutes; without ADV only less than 15% of this volume was filled. The commonly seen tadpole shape characteristic of bubble-enhanced HIFU lesions was not evident with the acoustic trench. In conclusion, ADV shows promise for the spatial control and dramatic acceleration of thermal lesion production by HIFU.

Defect detection around rebars in concrete using focused ultrasound and reverse time migration.

PubMed

Beniwal, Surendra; Ganguli, Abhijit

2015-09-01

Experimental and numerical investigations have been performed to assess the feasibility of damage detection around rebars in concrete using focused ultrasound and a Reverse Time Migration (RTM) based subsurface imaging algorithm. Since concrete is heterogeneous, an unfocused ultrasonic field will be randomly scattered by the aggregates, thereby masking information about damage(s). A focused ultrasonic field, on the other hand, increases the possibility of detection of an anomaly due to enhanced amplitude of the incident field in the focal region. Further, the RTM based reconstruction using scattered focused field data is capable of creating clear images of the inspected region of interest. Since scattering of a focused field by a damaged rebar differs qualitatively from that of an undamaged rebar, distinct images of damaged and undamaged situations are obtained in the RTM generated images. This is demonstrated with both numerical and experimental investigations. The total scattered field, acquired on the surface of the concrete medium, is used as input for the RTM algorithm to generate the subsurface image that helps to identify the damage. The proposed technique, therefore, has some advantage since knowledge about the undamaged scenario for the concrete medium is not necessary to assess its integrity. Copyright © 2015 Elsevier B.V. All rights reserved.

Blood-Brain Barrier: Real-time Feedback-controlled Focused Ultrasound Disruption by Using an Acoustic Emissions–based Controller

PubMed Central

Hynynen, Kullervo

2012-01-01

Purpose: To determine if focused ultrasound disruption of the blood-brain barrier (BBB) can be safely controlled by using real-time modulation of treatment pressures on the basis of acoustic emissions from the exposed microbubbles. Materials and Methods: All experiments were performed with the approval of the institutional animal care committee. Transcranial focused ultrasound (551.5 kHz, 10-msec bursts, 2-Hz pulse repetition frequency, 2 minute sonication) in conjunction with circulating microbubbles was applied in 86 locations in 27 rats to disrupt the BBB. Acoustic emissions captured during each burst by using a wideband polyvinylidene fluoride hydrophone were analyzed for spectral content and used to adjust treatment pressures. Pressures were increased incrementally after each burst until ultraharmonic emissions were detected, at which point the pressure was reduced to a percentage of the pressure required to induce the ultraharmonics and was maintained for the remainder of the sonication. Disruption was evaluated at contrast material–enhanced T1-weighted magnetic resonance (MR) imaging. Mean enhancement was calculated by averaging the signal intensity at the focus over a 3 × 3-pixel region of interest and comparing it with that in nonsonicated tissue. Histologic analysis was performed to determine the extent of damage to the tissue. Statistical analysis was performed by using Student t tests. Results: For sonications resulting in BBB disruption, the mean peak pressure was 0.28 MPa ± 0.05 (standard deviation) (range, 0.18–0.40 MPa). By using the control algorithm, a linear relationship was found between the scaling level and the mean enhancement on T1-weighted MR images after contrast agent injection. At a 50% scaling level, mean enhancement of 19.6% ± 1.7 (standard error of the mean) was achieved without inducing damage. At higher scaling levels, histologic analysis revealed gross tissue damage, while at a 50% scaling level, no damage was observed at

Editorial: Focus on Laser- and Beam-Driven Plasma Accelerators

NASA Astrophysics Data System (ADS)

Joshi, Chan; Malka, Victor

2010-04-01

The ability of short but intense laser pulses to generate high-energy electrons and ions from gaseous and solid targets has been well known since the early days of the laser fusion program. However, during the past decade there has been an explosion of experimental and theoretical activity in this area of laser-matter interaction, driven by the prospect of realizing table-top plasma accelerators for research, medical and industrial uses, and also relatively small and inexpensive plasma accelerators for high-energy physics at the frontier of particle physics. In this focus issue on laser- and beam-driven plasma accelerators, the latest advances in this field are described. Focus on Laser- and Beam-Driven Plasma Accelerators Contents Slow wave plasma structures for direct electron acceleration B D Layer, J P Palastro, A G York, T M Antonsen and H M Milchberg Cold injection for electron wakefield acceleration X Davoine, A Beck, A Lifschitz, V Malka and E Lefebvre Enhanced proton flux in the MeV range by defocused laser irradiation J S Green, D C Carroll, C Brenner, B Dromey, P S Foster, S Kar, Y T Li, K Markey, P McKenna, D Neely, A P L Robinson, M J V Streeter, M Tolley, C-G Wahlström, M H Xu and M Zepf Dose-dependent biological damage of tumour cells by laser-accelerated proton beams S D Kraft, C Richter, K Zeil, M Baumann, E Beyreuther, S Bock, M Bussmann, T E Cowan, Y Dammene, W Enghardt, U Helbig, L Karsch, T Kluge, L Laschinsky, E Lessmann, J Metzkes, D Naumburger, R Sauerbrey, M. Scḧrer, M Sobiella, J Woithe, U Schramm and J Pawelke The optimum plasma density for plasma wakefield excitation in the blowout regime W Lu, W An, M Zhou, C Joshi, C Huang and W B Mori Plasma wakefield acceleration experiments at FACET M J Hogan, T O Raubenheimer, A Seryi, P Muggli, T Katsouleas, C Huang, W Lu, W An, K A Marsh, W B Mori, C E Clayton and C Joshi Electron trapping and acceleration on a downward density ramp: a two-stage approach R M G M Trines, R Bingham, Z Najmudin

Gold nanoparticle nucleated cavitation for enhanced high intensity focused ultrasound therapy

NASA Astrophysics Data System (ADS)

McLaughlan, J. R.; Cowell, D. M. J.; Freear, S.

2018-01-01

High intensity focused ultrasound (HIFU) or focused ultrasound surgery is a non-invasive technique for the treatment of cancerous tissue, which is limited by difficulties in getting real-time feedback on treatment progress and long treatment durations. The formation and activity of acoustic cavitation, specifically inertial cavitation, during HIFU exposures has been demonstrated to enhance heating rates. However, without the introduction of external nuclei its formation an activity can be unpredictable, and potentially counter-productive. In this study, a combination of pulse laser illumination (839 nm), HIFU exposures (3.3 MHz) and plasmonic gold nanorods (AuNR) was demonstrated as a new approach for the guidance and enhancement of HIFU treatments. For imaging, short duration HIFU pulses (10 μs) demonstrated broadband acoustic emissions from AuNR nucleated cavitation with a signal-to-noise ranging from 5-35 dB for peak negative pressures between 1.19-3.19  ±  0.01 MPa. In the absence of either AuNR or laser illumination these emissions were either not present or lower in magnitude (e.g. 5 dB for 3.19 MPa). Continuous wave (CW) HIFU exposures for 15 s, were then used to generate thermal lesions for peak negative pressures from 0.2-2.71  ±  0.01 MPa at a fluence of 3.4 mJ cm-2 . Inertial cavitation dose (ICD) was monitored during all CW exposures, where exposures combined with both laser illumination and AuNRs resulted in the highest level of detectable emissions. This parameter was integrated over the entire exposure to give a metric to compare with measured thermal lesion area, where it was found that a minimum total ICD of 1.5 × 103 a.u. was correlated with the formation of thermal lesions in gel phantoms. Furthermore, lesion area (mm2) was increased for equivalent exposures without either AuNRs or laser illumination. Once combined with cancer targeting AuNRs this approach could allow for the future theranostic use of HIFU, such as

Electron Acceleration by Beating of Two Intense Cross-Focused Hollow Gaussian Laser Beams in Plasma

NASA Astrophysics Data System (ADS)

Mahmoud, Saleh T.; Gauniyal, Rakhi; Ahmad, Nafis; Rawat, Priyanka; Purohit, Gunjan

2018-01-01

This paper presents propagation of two cross-focused intense hollow Gaussian laser beams (HGBs) in collisionless plasma and its effect on the generation of electron plasma wave (EPW) and electron acceleration process, when relativistic and ponderomotive nonlinearities are simultaneously operative. Nonlinear differential equations have been set up for beamwidth of laser beams, power of generated EPW, and energy gain by electrons using WKB and paraxial approximations. Numerical simulations have been carried out to investigate the effect of typical laser-plasma parameters on the focusing of laser beams in plasmas and further its effect on power of excited EPW and acceleration of electrons. It is observed that focusing of two laser beams in plasma increases for higher order of hollow Gaussian beams, which significantly enhanced the power of generated EPW and energy gain. The amplitude of EPW and energy gain by electrons is found to enhance with an increase in the intensity of laser beams and plasma density. This study will be useful to plasma beat wave accelerator and in other applications requiring multiple laser beams. Supported by United Arab Emirates University for Financial under Grant No. UPAR (2014)-31S164

High intensity focused ultrasound vs. cryotherapy as primary treatment for prostate cancer

PubMed Central

Ranjan, Pratyush; Saurabh, Gyan; Bansal, Rahul; Gupta, Amit

2008-01-01

Prostate cancer is one of the most commonly diagnosed cancers. Here, we will be discussing two upcoming techniques for its management. One is cryotherapy which has returned from oblivion after nearly 150 years armed with latest technology and looking as if its full potential has been recognized now. On the other hand is high intensity focused ultrasound (HIFU), the application of ultrasound to this field is relatively new and hence a lot of excitement and hope. We searched MEDLINE (PubMed 1942-2005), reference lists of retrieved articles, urology textbooks and our own data looking for studies comparing cryotherapy and HIFU. From 81 titles or abstracts, two independent reviewers identified 50 as potentially relevant. Disagreement was resolved by discussion involving the third reviewer and we finally identified 45 articles. Full reports of 45 articles were retrieved and final selection was made by the same two independent reviewers using the same criteria as for the initial selection. Data were extracted and methodological qualities of selected studies were reviewed by two independent reviewers. Qualitative analysis and synthesis were done. Treatment options depend upon the age of patient, grade of tumor and expectations out of treatment. Patient choice governs the treatment actually to be given. It is the selection of a patient for a particular treatment option that decides how favorable the outcome is going to be. Both these techniques are relatively new and they look promising but both lack long-term data to prove their efficacy. PMID:19468352

Thermal fixation of swine liver tissue after magnetic resonance-guided high-intensity focused ultrasound ablation.

PubMed

Courivaud, Frédéric; Kazaryan, Airazat M; Lund, Alice; Orszagh, Vivian C; Svindland, Aud; Marangos, Irina Pavlik; Halvorsen, Per Steinar; Jebsen, Peter; Fosse, Erik; Hol, Per Kristian; Edwin, Bjørn

2014-07-01

The aim of this study was to investigate experimental conditions for efficient and controlled in vivo liver tissue ablation by magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) in a swine model, with the ultimate goal of improving clinical treatment outcome. Histological changes were examined both acutely (four animals) and 1 wk after treatment (five animals). Effects of acoustic power and multiple sonication cycles were investigated. There was good correlation between target size and observed ablation size by thermal dose calculation, post-procedural MR imaging and histopathology, when temperature at the focal point was kept below 90°C. Structural histopathology investigations revealed tissue thermal fixation in ablated regions. In the presence of cavitation, mechanical tissue destruction occurred, resulting in an ablation larger than the target. Complete extra-corporeal MR-guided HIFU ablation in the liver is feasible using high acoustic power. Nearby large vessels were preserved, which makes MR-guided HIFU promising for the ablation of liver tumors adjacent to large veins. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

CAVITATION THRESHOLD OF MICROBUBBLES IN GEL TUNNELS BY FOCUSED ULTRASOUND

PubMed Central

Sassaroli, E.; Hynynen, K.

2007-01-01

The investigation of inertial cavitation in micro-tunnels has significant implications for the development of therapeutic applications of ultrasound such as ultrasound-mediated drug and gene delivery. The threshold for inertial cavitation was investigated using a passive cavitation detector with a center frequency of 1 MHz. Micro-tunnels of various diameters (90 to 800 μm) embedded in gel were fabricated and injected with a solution of Optison™ contrast agent of concentrations 1.2% and 0.2% diluted in water. An ultrasound pulse of duration 500 ms and center frequency 1.736 MHz was used to insonate the microbubbles. The acoustic pressure was increased at one second intervals until broadband noise emission was detected. The pressure threshold at which broadband noise emission was observed was found to be dependent on the diameter of the micro-tunnels, with an average increase of 1.2 to 1.5 between the smallest and the largest tunnels, depending on the microbubble concentration. The evaluation of inertial cavitation in gel tunnels rather than tubes provides a novel opportunity to investigate microbubble collapse in a situation that simulates in vivo blood vessels better than tubes with solid walls do. PMID:17590501

Control of treatment size in cavitation-enhanced high-intensity focused ultrasound using radio-frequency echo signals

NASA Astrophysics Data System (ADS)

Tomiyasu, Kentaro; Takagi, Ryo; Iwasaki, Ryosuke; Yoshizawa, Shin; Umemura, Shin-ichiro

2017-07-01

In high-intensity focused ultrasound (HIFU) treatment, controlling the ultrasound dose at each focal target spot is important because it is a problem that the length of the coagulated region in front of the focal point deviates owing to the differences in absorption in each focal target spot and attenuation in the intervening tissues. In this study, the detected changes in the power spectra of HIFU echoes were used by controlling the HIFU duration in the “trigger HIFU” sequence with the aim to increase coagulation size through the enhancement of the ultrasonic heating by the cavitation induced by the preceding extremely high intensity short “trigger” pulse. The result shows that this method can be used to detect boiling bubbles and the following generated cavitation bubbles at their early stage. By automatically stopping HIFU exposure immediately after detecting the bubbles, overheating was prevented and the deviation of the length of the coagulated region was reduced.

Animal and Clinical Studies for the Treatment of Liver Carcinomas with High-Intensity Focused Ultrasound (HIFU)

NASA Astrophysics Data System (ADS)

Fukuda, Hiroyuki; Yamaguchi, Taketo; Yukisawa, Seigo; Masuya, Yoshio; Sudo, Kentaro; Okabe, Shinichiro; Yoshikawa, Masaharu; Ebara, Masaaki; Saisho, Hiromitsu; Ohto, Masao; Shinozuka, Norihiro; Li, Fagi; Zhu, Hui; Jin, Chengbin; Wu, Feng; Wang, Zhi-Biao

2007-05-01

In the study carried out in goats, we used the JC200 focused ultrasound tumor therapeutic system (Chongqing Haifu Tech Co., Ltd, China). The therapeutic ultrasound energy is produced by a transducer with a focal length of 160mm, at a frequency of 0.8MHz. The animals (n=6) were divided into a control group (n=3) and an experimental group subjected to costectomy (n=3). Costectomy was performed 1 week before HIFU. There was no difference in the coagulation volume between the two groups. Skin burns accompanied with reddish color and focal edema were observed in two goats. There were no other complications. In the clinical study, HIFU was applied in patients with with ⩽ 3 lesions of liver carcinoma ⩽ 4cm in diameter. The complications and anti-tumor effects on liver carcinomas should be evaluated. Tumor ablation was complete in 5 of 6 patients. There were no complications such as skin burns and local pain. HIFU did not influence blood chemical findings.

Plasma development in the accelerator of a 2-kJ focus discharge.

PubMed

Fischer, H; Haering, K H

1979-07-01

Optical image structures from early breakdown ( approximately 200 nsec) to focus formation (~1300 nsec) in 3 Torr hydrogen were studied by means of 2 image converter shutters having 50-nsec and 10-nsec exposure. Space charge limited cathode spots at the outer electrode (OE)-spoke-shaped positive columns across the gap-and an extended electron cloud along the center electrode (CE) determine the current flow during early breakdown. Ionization increases exponentially within the center gap plasma. This is separated from the CE by a pattern of anode drop filaments. Filament structures grow into the z-axis accelerated current sheath, which in addition carries the early spoke pattern. The sheath appears homogeneous after leaving the accelerator exit.

Pediatric Sarcomas Are Targetable by MR-Guided High Intensity Focused Ultrasound (MR-HIFU): Anatomical Distribution and Radiological Characteristics.

PubMed

Shim, Jenny; Staruch, Robert M; Koral, Korgun; Xie, Xian-Jin; Chopra, Rajiv; Laetsch, Theodore W

2016-10-01

Despite intensive therapy, children with metastatic and recurrent sarcoma or neuroblastoma have a poor prognosis. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is a noninvasive technique allowing the delivery of targeted ultrasound energy under MR imaging guidance. MR-HIFU may be used to ablate tumors without ionizing radiation or target chemotherapy using hyperthermia. Here, we evaluated the anatomic locations of tumors to assess the technical feasibility of MR-HIFU therapy for children with solid tumors. Patients with sarcoma or neuroblastoma with available cross-sectional imaging were studied. Tumors were classified based on the location and surrounding structures within the ultrasound beam path as (i) not targetable, (ii) completely or partially targetable with the currently available MR-HIFU system, and (iii) potentially targetable if a respiratory motion compensation technique was used. Of the 121 patients with sarcoma and 61 patients with neuroblastoma, 64% and 25% of primary tumors were targetable at diagnosis, respectively. Less than 20% of metastases at diagnosis or relapse were targetable for both sarcoma and neuroblastoma. Most targetable lesions were located in extremities or in the pelvis. Respiratory motion compensation may increase the percentage of targetable tumors by 4% for sarcomas and 10% for neuroblastoma. Many pediatric sarcomas are localized at diagnosis and are targetable by current MR-HIFU technology. Some children with neuroblastoma have bony tumors targetable by MR-HIFU at relapse, but few newly diagnosed children with neuroblastoma have tumors amenable to MR-HIFU therapy. Clinical trials of MR-HIFU should focus on patients with anatomically targetable tumors. © 2016 Wiley Periodicals, Inc.

Tele-ultrasound and paramedics: real-time remote physician guidance of the Focused Assessment With Sonography for Trauma examination.

PubMed

Boniface, Keith S; Shokoohi, Hamid; Smith, E Reed; Scantlebury, Kari

2011-06-01

The aim of this study was to examine the capability of ultrasound-naïve paramedics to obtain interpretable Focused Assessment With Sonography for Trauma (FAST) images under the remote direction of emergency physicians (EPs). Paramedics without experience using ultrasound participated in a 20-minute lecture covering orientation to the ultrasound machine and the FAST examination. The paramedics subsequently performed FAST examinations on a model patient, whereas the EP remained in another room, out of visual contact. The EP communicated with the paramedic via radio, viewing video from the ultrasound machine on a monitor and directing the probe movements to obtain the views of the FAST examination. We examined the success rate, time to complete the examinations, and adequacy of images from the paramedics' first FAST examination. Fifty-one paramedics performed their first FAST examinations and were able to successfully complete 100% of the views of the FAST. The median time from probe placement to examination completion was 262 seconds (interquartile range, 206-343 seconds). The median time to complete right upper quadrant (RUQ) versus left upper quadrant (LUQ) views was 39 and 50 seconds, respectively. The time to complete the LUQ scan took significantly longer than the RUQ (P < .01). Paramedics completed cardiac and pelvic view in a median time of 42 and 25 seconds, respectively. The study demonstrated that paramedics with no prior ultrasound experience could obtain FAST images under remote guidance from experienced EPs in less than 5 minutes. Given rapidly evolving data transmission technology, this has applicability in battlefield, remote, and rural prehospital settings. Copyright © 2011 Elsevier Inc. All rights reserved.

In vivo feasibility of real-time monitoring of focused ultrasound surgery (FUS) using harmonic motion imaging (HMI).

PubMed

Maleke, Caroline; Konofagou, Elisa E

2010-01-01

In this study, the Harmonic Motion Imaging for Focused Ultrasound (HMIFU) technique is applied to monitor changes in mechanical properties of tissues during thermal therapy in a transgenic breast cancer mouse model in vivo. An HMIFU system, composed of a 4.5-MHz focused ultrasound (FUS) and a 3.3-MHz phased-array imaging transducer, was mechanically moved to image and ablate the entire tumor. The FUS transducer was driven by an amplitude-modulated (AM) signal at 15 Hz. The acoustic intensity ( I(spta)) was equal to 1050 W/cm(2) at the focus. A digital low-pass filter was used to filter out the spectrum of the FUS beam and its harmonics prior to displacement estimation. The resulting axial displacement was estimated using 1-D cross-correlation on the acquired RF signals. Results from two mice with eight lesions formed in each mouse (16 lesions total) showed that the average peak-to-peak displacement amplitude before and after lesion formation was respectively equal to 17.34 +/- 1.34 microm and 10.98 +/- 1.82 microm ( p < 0.001). Cell death was also confirmed by hematoxylin and eosin histology. HMI displacement can be used to monitor the relative tissue stiffness changes in real time during heating so that the treatment procedure can be performed in a time-efficient manner. The HMIFU system may, therefore, constitute a cost-efficient and reliable alternative for real-time monitoring of thermal ablation.

Preliminary ex vivo feasibility study on targeted cell surgery by high intensity focused ultrasound (HIFU).

PubMed

Wang, Zhi Biao; Wu, Junru; Fang, Liao Qiong; Wang, Hua; Li, Fa Qi; Tian, Yun Bo; Gong, Xiao Bo; Zhang, Hong; Zhang, Lian; Feng, Ruo

2011-04-01

High intensity focused ultrasound (HIFU) has become a new noninvasive surgical modality in medicine. A portion of tissue seated inside a patient's body may experience coagulative necrosis after a few seconds of insonification by high intensity focused ultrasound (US) generated by an extracorporeal focusing US transducer. The region of tissue affected by coagulative necrosis (CN) usually has an ellipsoidal shape when the thermal effect due to US absorption plays the dominant role. Its long and short axes are parallel and perpendicular to the US propagation direction respectively. It was shown by numerical computations using a nonlinear Gaussian beams model to describe the sound field in a focal zone and ex vivo experiments that the dimension of the short and long axes of the tissue which experiences CN can be as small as 50μm and 250μm respectively after one second exposure of US pulse (the spatial and pulse average acoustic power is on the order of tens of Watts and the local acoustic spatial and temporal pulse averaged intensity is on the order of 3×10(4)W/cm(2)) generated by a 1.6MHz HIFU transducer of 12cm diameter and 11cm geometric focal length (f-number=0.92). The concept of thermal dose of cumulative equivalent minutes was used to describe the possible tissue coagulative necrosis generated by HIFU. The numbers of cells which suffered CN were estimated to be on the order of 40. This result suggests that HIFU is able to interact with tens of cells at/near its focal zone while keeping the neighboring cells minimally affected, and thus the targeted cell surgery may be achievable. Copyright © 2010 Elsevier B.V. All rights reserved.

Growth inhibition in a brain metastasis model by antibody delivery using focused ultrasound-mediated blood-brain barrier disruption.

PubMed

Kobus, Thiele; Zervantonakis, Ioannis K; Zhang, Yongzhi; McDannold, Nathan J

2016-09-28

HER2-targeting antibodies (i.e. trastuzumab and pertuzumab) prolong survival in HER2-positive breast cancer patients with extracranial metastases. However, the response of brain metastases to these drugs is poor, and it is hypothesized that the blood-brain barrier (BBB) limits drug delivery to the brain. We investigated whether we could improve the response by temporary disruption of the BBB using focused ultrasound in combination with microbubbles. To study this, we inoculated 30 nude rats with HER2-positive cells derived from a brain metastasis of a breast cancer patient (MDA-MB-361). The animals were divided into three groups: a control-group that received no treatment; an antibody-only group that received six weekly treatments of trastuzumab and pertuzumab; and an ultrasound+antibody group that received trastuzumab and pertuzumab in combination with six weekly sessions of BBB disruption using focused ultrasound. In two animals, the leakiness of the tumors before disruption was evaluated using contrast-enhanced T1-weighted magnetic resonance imaging and found that the tumors were not leaky. The same technique was used to evaluate the effectiveness of BBB disruption, which was successful in all sessions. The tumor in the control animals grew exponentially with a growth constant of 0.042±0.011mm(3)/day. None of the antibody-only animals responded to the treatment and the growth constant was 0.033±0.009mm(3)/day during the treatment period. Four of the ten animals in the ultrasound+antibody-group showed a response to the treatment with an average growth constant of 0.010±0.007mm(3)/day, compared to a growth constant 0.043±0.013mm(3)/day for the six non-responders. After the treatment period, the tumors in all groups grew at similar rates. As the tumors were not leaky before BBB disruption and there were no responders in the antibody-only group, these results show that at least in some cases disruption of the BBB is necessary for a response to the antibodies in

Treatment of glaucoma with high intensity focused ultrasound.

PubMed

Aptel, Florent; Lafon, Cyril

2015-05-01

Glaucoma is a common disease mainly due to an increase in pressure inside the eye, leading to a progressive destruction of the optic nerve, potentially to blindness. Intraocular pressure (IOP) is the result of a balance between production of liquid that fills the eye--aqueous humour--and its resorption. All treatments for glaucoma aim to reduce IOP and can therefore have two mechanisms of action: reducing aqueous humour production by the partial destruction or medical inhibition of the ciliary body--the anatomical structure responsible for production of aqueous humour--or facilitating the evacuation of aqueous humour from the eye. Several physical methods can be used to destroy the ciliary body, e.g. laser, cryotherapy, microwave. All these methods have two major drawbacks: they are non-selective for the organ to be treated and they have an unpredictable dose–effect relationship. High intensity focused ultrasound (HIFU) can be used to coagulate the ciliary body and avoid these drawbacks. A commercially available device was marketed in the 1980s, but later abandoned, essentially for technical reasons. A smaller circular device using miniaturised transducers was recently developed and proposed for clinical practice. Experimental studies have shown selective coagulation necrosis of the treated ciliary body. The first three clinical trials in humans have shown that this device was well tolerated and allowed a significant, predictable and sustained reduction of IOP. The aim of this contribution is to present a summary of the work concerning the use of HIFU to treat glaucoma.

Focused ultrasound-mediated sonochemical internalization: an alternative to light-based therapies

NASA Astrophysics Data System (ADS)

Gonzales, Jonathan; Nair, Rohit Kumar; Madsen, Steen J.; Krasieva, Tatiana; Hirschberg, Henry

2016-07-01

Activation of sonosensitizers via focused ultrasound (FUS), i.e., sonodynamic therapy has been proposed as an extension to light-activated photodynamic therapy for the treatment of brain as well as other tumors. The use of FUS, as opposed to light, allows treatment to tumor sites buried deep within tissues as well as through the intact skull. We have examined ultrasonic activation of sonosensitizers together with the anticancer agent bleomycin (BLM), i.e., sonochemical internalization (SCI). SCI is a technique that utilizes FUS for the enhanced delivery of endo-lysosomal trapped macromolecules into the cell cytoplasm in a similar manner to light-based photochemical internalization. The released agent can, therefore, exert its full biological activity, in contrast to being degraded by lysosomal hydrolases. Our results indicate that, compared to drug or FUS treatment alone, FUS activation of the sonosensitizer AlPcS2a together with BLM significantly inhibits the ability of treated glioma cells to grow as three-dimensional tumor spheroids in vitro.

Usage of Magnetic Resonance Guided Focused Ultrasound Surgery (mrgfus) in Oncology

NASA Astrophysics Data System (ADS)

Bauer, Yair

2011-09-01

Magnetic resonance guided focused ultrasound surgery (MRgFUS) is a non-invasive incision-less surgical approach which limits the tissue destruction to the targeted tumor. Acoustic energy penetrates through intact skin and through the tissues surrounding the tumor without causing any significant bio-effects. Energy deposition takes place mainly at the focal spot where heat induced thermal coagulation of the targeted tissue is accomplished. Real time targeting and image guidance is provided by MRI tumor margin definition and real time thermometry provides closed loop feedback control of energy deposition. The patient lies in the MRI scanner throughout the treatment planning and treatment, and the physician conducts the treatment from the MRgFUS workstation in the adjacent MR control room. The ExAblate system for MRgFUS is commercially available in many countries for treatment of uterine fibroids. The system has also received CE and KFDA approval for pain palliation of bone metastases, and research of other oncologic applications is underway.

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

PubMed

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

2017-04-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: potential for targeting experimental brain tumors.

PubMed

Diaz, Roberto Jose; McVeigh, Patrick Z; O'Reilly, Meaghan A; Burrell, Kelly; Bebenek, Matthew; Smith, Christian; Etame, Arnold B; Zadeh, Gelareh; Hynynen, Kullervo; Wilson, Brian C; Rutka, James T

2014-07-01

Spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS) capability in the near-infrared range is an emerging molecular imaging technique. We used magnetic resonance image-guided transcranial focused ultrasound (TcMRgFUS) to reversibly disrupt the blood-brain barrier (BBB) adjacent to brain tumor margins in rats. Glioma cells were found to internalize SERS capable nanoparticles of 50nm or 120nm physical diameter. Surface coating with anti-epidermal growth factor receptor antibody or non-specific human immunoglobulin G, resulted in enhanced cell uptake of nanoparticles in-vitro compared to nanoparticles with methyl terminated 12-unit polyethylene glycol surface. BBB disruption permitted the delivery of SERS capable spherical 50 or 120nm gold nanoparticles to the tumor margins. Thus, nanoparticles with SERS imaging capability can be delivered across the BBB non-invasively using TcMRgFUS and have the potential to be used as optical tracking agents at the invasive front of malignant brain tumors. This study demonstrates the use of magnetic resonance image-guided transcranial focused ultrasound to open the BBB and enable spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS)-based molecular imaging for experimental tumor tracking. Copyright © 2014 Elsevier Inc. All rights reserved.

MR-guided pulsed high intensity focused ultrasound enhancement of docetaxel combined with radiotherapy for prostate cancer treatment

NASA Astrophysics Data System (ADS)

Mu, Zhaomei; Ma, C.-M.; Chen, Xiaoming; Cvetkovic, Dusica; Pollack, Alan; Chen, Lili

2012-01-01

The purpose of this study is to evaluate the efficacy of the enhancement of docetaxel by pulsed focused ultrasound (pFUS) in combination with radiotherapy (RT) for treatment of prostate cancer in vivo. LNCaP cells were grown in the prostates of male nude mice. When the tumors reached a designated volume by MRI, tumor bearing mice were randomly divided into seven groups (n = 5): (1) pFUS alone; (2) RT alone; (3) docetaxel alone; (4) docetaxel + pFUS (5) docetaxel + RT (6) docetaxel + pFUS + RT, and (7) control. MR-guided pFUS treatment was performed using a focused ultrasound treatment system (InSightec ExAblate 2000) with a 1.5T GE MR scanner. Animals were treated once with pFUS, docetaxel, RT or their combinations. Docetaxel was given by i.v. injection at 5 mg kg-1 before pFUS. RT was given 2 Gy after pFUS. Animals were euthanized 4 weeks after treatment. Tumor volumes were measured on MRI at 1 and 4 weeks post-treatment. Results showed that triple combination therapies of docetaxel, pFUS and RT provided the most significant tumor growth inhibition among all groups, which may have potential for the treatment of prostate cancer due to an improved therapeutic ratio.

Fast Lesion Mapping during HIFU Treatment Using Harmonic Motion Imaging guided Focused Ultrasound (HMIgFUS) In Vitro and In Vivo

PubMed Central

Han, Yang; Wang, Shutao; Payen, Thomas; Konofagou, Elisa

2017-01-01

The successful clinical application of High Intensity Focused Ultrasound (HIFU) ablation depends on reliable monitoring of the lesion formation. Harmonic Motion Imaging guided Focused Ultrasound (HMIgFUS) is an ultrasound-based elasticity imaging technique, which monitors HIFU ablation based on the stiffness change of the tissue instead of the echo intensity change in conventional B-mode monitoring, rendering it potentially more sensitive to lesion development. Our group has shown that predicting the lesion location based on the radiation force-excited region is feasible during HMIgFUS. In this study, the feasibility of a fast lesion mapping method is explored to directly monitor the lesion map during HIFU. The HMI lesion map was generated by subtracting the reference HMI image from the present HMI peak-to-peak displacement map to be streamed on the computer display. The dimensions of the HMIgFUS lesions were compared against gross pathology. Excellent agreement was found between the lesion depth (r2 = 0.81, slope = 0.90), width (r2 = 0.85, slope = 1.12) and area (r2 = 0.58, slope = 0.75). In vivo feasibility was assessed in a mouse with a pancreatic tumor. These findings demonstrate that HMIgFUS can successfully map thermal lesion and monitor lesion development in real time in vitro and in vivo. The HMIgFUS technique may therefore constitute a novel clinical tool for HIFU treatment monitoring. PMID:28323638

Thrombus resolution and right ventricular functional recovery using ultrasound-accelerated thrombolysis in acute massive and submassive pulmonary embolism.

PubMed

Ozcinar, Evren; Cakici, Mehmet; Dikmen Yaman, Nur; Baran, Cagdas; Aliyev, Anar; Inan, Bahadir; Durdu, Serkan; Akar, Ahmet R; Sirlak, Mustafa

2017-10-01

This study aims to evaluate the efficacy and safety of ultrasound-accelerated catheter-directed thrombolysis (UACDT) in the treatment of massive and submassive pulmonary embolism (PE). We conducted a prospective, observational cohort study of consequtive patients with massive or submassive PE treated with low-dose UACDT using EKOS EkoSonic® system at single center from May 2014 until April 2015. Overall, thirty-eight patients (median age, 64.5 years) were included. The primary safety outcomes were change in right ventricular (RV) to left ventricular (LV) diameter ratio within 24 hours of procedure initiation, at 1- and 6-month follow-up and major bleeding within 96 hours of the procedure initiation. BNP, troponin and D-dimer levels were also measured. The ultrasound-accelerated thrombolytic catheters were bilaterally placed in 25 (65.8%) patients. The median tissue plasminogen activator (tPA) dose for all patients in our study was 21.0 mg and the median infusion time was 15 hours. Measurements before and after treatment showed a decrease in pulmonary artery pressure. The median value of RV/LV diameter ratio decreased from 0.9 (0.7-1.1) at baseline to 0.7 (0-0.97) at 6-month follow-up (P=0.001) and pulmonary artery pressure from 61.4 ±16.7 to 37.2±9.1 mmHg (P=0.001). The median BNP level at baseline was 169 (29-721) pg/mL and 45.5 (0-328) pg/mL at 6 month follow-up (P=0.001). Of 38 patients with PE, one had intracranial hemorrage, one gastrointestinal bleeding and two developed puncture site bleeding. This prospective study provides alternative treatment option and an addition to the treatment algorithm for the management of pulmonary embolism.

Ultrasound accelerated Claisen Schmidt condensation: A green route to chalcones

NASA Astrophysics Data System (ADS)

Calvino, V.; Picallo, M.; López-Peinado, A. J.; Martín-Aranda, R. M.; Durán-Valle, C. J.

2006-06-01

Chalcones have been synthesized under sonochemical irradiation by Claisen-Schmidt condensation between benzaldehyde and acetophenone. Two basic activated carbons (Na and Cs-Norit) have been used as catalysts. The effect of the ultrasound activation has been studied. A substantial enhancing effect in the yield was observed when the carbon catalyst was activated under ultrasonic waves. This "green" method (combination of alkaline-doped carbon catalyst and ultrasound waves) has been applied to the synthesis of several chalcones with antibacterial properties achieving, in all cases, excellent activities and selectivities. A comparative study under non-sonic activation has showed that the yields are lower in silent conditions, indicating that the sonication exerts a positive effect on the activity of the catalyst. Cs-doped carbon is presented as the optimum catalyst, giving excellent activity for this type of condensation. Cs-Norit carbon catalyst can compete with the traditional NaOH/EtOH when the reaction is carried out under ultrasounds. The role of solvent in this reaction was studied with ethanol. High conversion was obtained in absence of solvent. The carbons were characterized by thermal analysis, nitrogen adsorption and X-ray photoelectron spectroscopy.

Focused ultrasound-mediated bbb disruption is associated with an increase in activation of AKT: experimental study in rats

PubMed Central

2010-01-01

Background The Blood Brain Barrier (BBB) maintains the homeostasis of central nervous system by preventing the free passage of macromolecules from the systemic circulation into the brain. This normal physiological function of the BBB presents a challenge for delivery of therapeutic compounds into the brain. Recent studies have shown that the application of focused ultrasound together with ultrasound contrast agent (microbubbles) temporarily increases the permeability of the BBB. This effect is associated with breakdown of tight junctions, the structures that regulate the paracellular permeability of the endothelial cell layer. The influence of this ultrasound effect on the activation of intracellular signaling proteins is currently not well understood. Therefore, the aim of this study was to investigate the activation of cell survival signaling molecules in response to ultrasound-mediated BBB opening; Methods The BBB was disrupted in two four-spot lines (1-1.5 mm spacing) along the right hemisphere of rat brain with ultrasound beams (0.3 MPa, 120 s, 10 ms bursts, repetition frequency = 1 Hz) in the presence Definity microbubbles. Contrast-enhanced MRI images were acquired to assess the extent of BBB opening upon which the animals were sacrificed and the brains removed and processed for biochemical and immunohistochemical analyses; Results Immunoblotting of sonicated brain lysates resolved by SDS-PAGE demonstrated an increase in phosphorylation of Akt and its downstream signaling molecule, GSK3β, while the phosphorylation of MAPK remained unchanged. The elevated levels of pAkt and pGSK3β are still evident after 24 hours post-sonication, a time point where the integrity of the BBB is known to be re-established. Furthermore, immunofluoresence staining localized this increase in pAkt and pGSK3β levels to neuronal cells flanking the region of the disrupted BBB; Conclusions Our data demonstrates that ultrasound-mediated BBB disruption causes an activation of the Akt

Magnetic Resonance Imaging-Guided Focused Ultrasound Surgery for the Treatment of Symptomatic Uterine Fibroids.

PubMed

Geraci, Laura; Napoli, Alessandro; Catalano, Carlo; Midiri, Massimo; Gagliardo, Cesare

2017-01-01

Uterine fibroids, the most common benign tumor in women of childbearing age, may cause symptoms including pelvic pain, menorrhagia, dysmenorrhea, pressure, urinary symptoms, and infertility. Various approaches are available to treat symptomatic uterine fibroids. Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) represents a recently introduced noninvasive safe and effective technique that can be performed without general anesthesia, in an outpatient setting. We review the principles of MRgFUS, describing patient selection criteria for the treatments performed at our center and we present a series of five selected patients with symptomatic uterine fibroids treated with this not yet widely known technique, showing its efficacy in symptom improvement and fibroid volume reduction.

Real-time control of focused ultrasound heating based on rapid MR thermometry.

PubMed

Vimeux, F C; De Zwart, J A; Palussiére, J; Fawaz, R; Delalande, C; Canioni, P; Grenier, N; Moonen, C T

1999-03-01

Real-time control of the heating procedure is essential for hyperthermia applications of focused ultrasound (FUS). The objective of this study is to demonstrate the feasibility of MRI-controlled FUS. An automatic control system was developed using a dedicated interface between the MR system control computer and the FUS wave generator. Two algorithms were used to regulate FUS power to maintain the focal point temperature at a desired level. Automatic control of FUS power level was demonstrated ex vivo at three target temperature levels (increase of 5 degrees C, 10 degrees C, and 30 degrees C above room temperature) during 30-minute hyperthermic periods. Preliminary in vivo results on rat leg muscle confirm that necrosis estimate, calculated on-line during FUS sonication, allows prediction of tissue damage. CONCLUSIONS. The feasibility of fully automatic FUS control based on MRI thermometry has been demonstrated.

Modelling the temperature evolution of bone under high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

ten Eikelder, H. M. M.; Bošnački, D.; Elevelt, A.; Donato, K.; Di Tullio, A.; Breuer, B. J. T.; van Wijk, J. H.; van Dijk, E. V. M.; Modena, D.; Yeo, S. Y.; Grüll, H.

2016-02-01

Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has been clinically shown to be effective for palliative pain management in patients suffering from skeletal metastasis. The underlying mechanism is supposed to be periosteal denervation caused by ablative temperatures reached through ultrasound heating of the cortex. The challenge is exact temperature control during sonication as MR-based thermometry approaches for bone tissue are currently not available. Thus, in contrast to the MR-HIFU ablation of soft tissue, a thermometry feedback to the HIFU is lacking, and the treatment of bone metastasis is entirely based on temperature information acquired in the soft tissue adjacent to the bone surface. However, heating of the adjacent tissue depends on the exact sonication protocol and requires extensive modelling to estimate the actual temperature of the cortex. Here we develop a computational model to calculate the spatial temperature evolution in bone and the adjacent tissue during sonication. First, a ray-tracing technique is used to compute the heat production in each spatial point serving as a source term for the second part, where the actual temperature is calculated as a function of space and time by solving the Pennes bio-heat equation. Importantly, our model includes shear waves that arise at the bone interface as well as all geometrical considerations of transducer and bone geometry. The model was compared with a theoretical approach based on the far field approximation and an MR-HIFU experiment using a bone phantom. Furthermore, we investigated the contribution of shear waves to the heat production and resulting temperatures in bone. The temperature evolution predicted by our model was in accordance with the far field approximation and agreed well with the experimental data obtained in phantoms. Our model allows the simulation of the HIFU treatments of bone metastasis in patients and can be extended to a planning tool prior to MR

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation of liver tumours.

PubMed

Wijlemans, J W; Bartels, L W; Deckers, R; Ries, M; Mali, W P Th M; Moonen, C T W; van den Bosch, M A A J

2012-09-28

Recent decades have seen a paradigm shift in the treatment of liver tumours from invasive surgical procedures to minimally invasive image-guided ablation techniques. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a novel, completely non-invasive ablation technique that has the potential to change the field of liver tumour ablation. The image guidance, using MR imaging and MR temperature mapping, provides excellent planning images and real-time temperature information during the ablation procedure. However, before clinical implementation of MR-HIFU for liver tumour ablation is feasible, several organ-specific challenges have to be addressed. In this review we discuss the MR-HIFU ablation technique, the liver-specific challenges for MR-HIFU tumour ablation, and the proposed solutions for clinical translation.

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation of liver tumours

PubMed Central

Bartels, L.W.; Deckers, R.; Ries, M.; Mali, W.P.Th.M.; Moonen, C.T.W.; van den Bosch, M.A.A.J.

2012-01-01

Abstract Recent decades have seen a paradigm shift in the treatment of liver tumours from invasive surgical procedures to minimally invasive image-guided ablation techniques. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a novel, completely non-invasive ablation technique that has the potential to change the field of liver tumour ablation. The image guidance, using MR imaging and MR temperature mapping, provides excellent planning images and real-time temperature information during the ablation procedure. However, before clinical implementation of MR-HIFU for liver tumour ablation is feasible, several organ-specific challenges have to be addressed. In this review we discuss the MR-HIFU ablation technique, the liver-specific challenges for MR-HIFU tumour ablation, and the proposed solutions for clinical translation. PMID:23022541

Longitudinal Ultrasound Education Track Curriculum Implemented Within an Emergency Medicine Residency Program.

PubMed

Boulger, Creagh; Adams, Daniel Z; Hughes, Daralee; Bahner, David P; King, Andrew

2017-06-01

Emergency Medicine residency programs offer ultrasound-focused curricula to address Accreditation Council for Graduate Medical Education (ACGME) milestones. Although some programs offer advanced clinical tracks in ultrasound, no standard curriculum exists. We sought to establish a well-defined ultrasound track curriculum to allow interested residents to develop advanced clinical skills and scholarship within this academic niche. The curriculum involves a greater number of clinical scans, ultrasound-focused scholarly and quality improvement projects, enhanced faculty-driven ultrasound focused didactics, and participation at a national ultrasound conference to receive certification. Successful ultrasound scholarly tracks can provide residents with the potential to obtain fellowships or competency beyond ACGME requirements. © 2017 by the American Institute of Ultrasound in Medicine.

Jet formation and shock wave emission during collapse of ultrasound-induced cavitation bubbles and their role in the therapeutic applications of high-intensity focused ultrasound.

PubMed

Brujan, E A; Ikeda, T; Matsumoto, Y

2005-10-21

The dynamics of inertial cavitation bubbles produced by short pulses of high-intensity focused ultrasound near a rigid boundary are studied to get a better understanding of the role of jet formation and shock wave emission during bubble collapse in the therapeutic applications of ultrasound. The bubble dynamics are investigated by high-speed photography with up to 2 million frames/s and acoustic measurements, as well as by numerical calculations. The significant parameter of this study is the dimensionless stand-off, gamma, which is defined as the distance of the bubble centre at its maximum expansion scaled by the maximum bubble radius. High-speed photography is applied to observe the bubble motion and the velocity of the liquid jet formed during bubble collapse. Hydrophone measurements are used to determine the pressure and the duration of the shock wave emitted during bubble rebound. Calculations yield the variation with time of the bubble wall, the maximum velocity and the kinetic energy of the re-entrant jet. The comparisons between experimental and numerical data are favourable with regard to both shape history and translational motion of the bubble. The acoustic energy constitutes the largest individual amount in the energy balance of bubble collapse. The ratio of the shock wave energy, measured at 10 mm from the emission centre, to the cavitation bubble energy was 1:2.4 at gamma = 1.55 and 1:3.5 at gamma = 1. At this distance, the shock wave pressure ranges from 0.122 MPa, at gamma = 1, to 0.162 MPa, at gamma = 1.55, and the temporal duration at the half maximum level is 87 ns. The maximum jet velocity ranges from 27 m s(-1), at gamma = 1, to 36 m s(-1), at gamma = 1.55. For gamma < 1.2, the re-entrant jet can generate an impact pressure on the nearby boundary larger than 50 MPa. We discuss the implications of the results for the therapeutic applications of high-intensity focused ultrasound.

Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction.

PubMed

Businelli, Caterina; de Wit, Charlotte; Visser, Gerard H A; Pistorius, Lourens R

2014-09-10

Abstract Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency. Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses. Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses. Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.

Harmonic motion imaging for focused ultrasound (HMIFU): a fully integrated technique for sonication and monitoring of thermal ablation in tissues.

PubMed

Maleke, C; Konofagou, E E

2008-03-21

FUS (focused ultrasound), or HIFU (high-intensity-focused ultrasound) therapy, a minimally or non-invasive procedure that uses ultrasound to generate thermal necrosis, has been proven successful in several clinical applications. This paper discusses a method for monitoring thermal treatment at different sonication durations (10 s, 20 s and 30 s) using the amplitude-modulated (AM) harmonic motion imaging for focused ultrasound (HMIFU) technique in bovine liver samples in vitro. The feasibility of HMI for characterizing mechanical tissue properties has previously been demonstrated. Here, a confocal transducer, combining a 4.68 MHz therapy (FUS) and a 7.5 MHz diagnostic (pulse-echo) transducer, was used. The therapy transducer was driven by a low-frequency AM continuous signal at 25 Hz, producing a stable harmonic radiation force oscillating at the modulation frequency. A pulser/receiver was used to drive the pulse-echo transducer at a pulse repetition frequency (PRF) of 5.4 kHz. Radio-frequency (RF) signals were acquired using a standard pulse-echo technique. The temperature near the ablation region was simultaneously monitored. Both RF signals and temperature measurements were obtained before, during and after sonication. The resulting axial tissue displacement was estimated using one-dimensional cross correlation. When temperature at the focal zone was above 48 degrees C during heating, the coagulation necrosis occurred and tissue damage was irreversible. The HMI displacement profiles in relation to the temperature and sonication durations were analyzed. At the beginning of heating, the temperature at the focus increased sharply, while the tissue stiffness decreased resulting in higher HMI displacements. This was confirmed by an increase of 0.8 microm degrees C(-1)(r=0.93, p<.005). After sustained heating, the tissue became irreversibly stiffer, followed by an associated decrease in the HMI displacement (-0.79 microm degrees C(-1), r=-0.92, p<0.001). Repeated

Bandwidth Limitations in Characterization of High Intensity Focused Ultrasound Fields in the Presence of Shocks

NASA Astrophysics Data System (ADS)

Khokhlova, V. A.; Bessonova, O. V.; Soneson, J. E.; Canney, M. S.; Bailey, M. R.; Crum, L. A.

2010-03-01

Nonlinear propagation effects result in the formation of weak shocks in high intensity focused ultrasound (HIFU) fields. When shocks are present, the wave spectrum consists of hundreds of harmonics. In practice, shock waves are modeled using a finite number of harmonics and measured with hydrophones that have limited bandwidths. The goal of this work was to determine how many harmonics are necessary to model or measure peak pressures, intensity, and heat deposition rates of the HIFU fields. Numerical solutions of the Khokhlov-Zabolotskaya-Kuznetzov-type (KZK) nonlinear parabolic equation were obtained using two independent algorithms, compared, and analyzed for nonlinear propagation in water, in gel phantom, and in tissue. Measurements were performed in the focus of the HIFU field in the same media using fiber optic probe hydrophones of various bandwidths. Experimental data were compared to the simulation results.

GPU-accelerated two dimensional synthetic aperture focusing for photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Liu, Siyu; Feng, Xiaohua; Gao, Fei; Jin, Haoran; Zhang, Ruochong; Luo, Yunqi; Zheng, Yuanjin

2018-02-01

Acoustic resolution photoacoustic microscopy (AR-PAM) generally suffers from limited depth of focus, which had been extended by synthetic aperture focusing techniques (SAFTs). However, for three dimensional AR-PAM, current one dimensional (1D) SAFT and its improved version like cross-shaped SAFT do not provide isotropic resolution in the lateral direction. The full potential of the SAFT remains to be tapped. To this end, two dimensional (2D) SAFT with fast computing architecture is proposed in this work. Explained by geometric modeling and Fourier acoustics theories, 2D-SAFT provide the narrowest post-focusing capability, thus to achieve best lateral resolution. Compared with previous 1D-SAFT techniques, the proposed 2D-SAFT improved the lateral resolution by at least 1.7 times and the signal-to-noise ratio (SNR) by about 10 dB in both simulation and experiments. Moreover, the improved 2D-SAFT algorithm is accelerated by a graphical processing unit that reduces the long period of reconstruction to only a few seconds. The proposed 2D-SAFT is demonstrated to outperform previous reported 1D SAFT in the aspects of improving the depth of focus, imaging resolution, and SNR with fast computational efficiency. This work facilitates future studies on in vivo deeper and high-resolution photoacoustic microscopy beyond several centimeters.

In vitro cell system for studying molecular mechanisms of action associated with low intensity focused ultrasound

NASA Astrophysics Data System (ADS)

Babakhanian, Meghedi; Fan, Richard E.; Mulgaonkar, Amit P.; Singh, Rahul; Culjat, Martin O.; Danesh, Shahab M.; Toro, Ligia; Grundfest, Warren; Melega, William P.

2012-03-01

Low intensity focused ultrasound (LIFU) is now being considered as a noninvasive brain therapy for clinical applications. We maintain that LIFU can efficiently deliver energy from outside the skull to target specific brain regions, effecting localized neuromodulation. However, the underlying molecular mechanisms that drive this LIFU-induced neuromodulation are not well-defined due, in part, to our lack of understanding of how particular sets of LIFU delivery parameters affect the outcome. To efficiently conduct multiple sweeps of different parameters and determine their effects, we have developed an in-vitro system to study the effects of LIFU on different types of cells grown in culture. Presently, we are evaluating how LIFU affects the ionic flux that may underlie neuronal excitation and inhibition observed in-vivo. The results of our in-vitro studies will provide a rationale for selection of optimal LIFU parameter to be used in subsequent in-vivo applications. Thus, a prototype ultrasound cell assay system has been developed to conduct these studies, and is described in this work.

High power phased array prototype for clinical high intensity focused ultrasound : applications to transcostal and transcranial therapy.

PubMed

Pernot, M; Aubry, J -F; Tanter, M; Marquet, F; Montaldo, G; Boch, A -L; Kujas, M; Seilhean, D; Fink, M

2007-01-01

Bursts of focused ultrasound energy three orders of magnitude more intense than diagnostic ultrasound became during the last decade a noninvasive option for treating cancer from breast to prostate or uterine fibroid. However, many challenges remain to be addressed. First, the corrections of distortions induced on the ultrasonic therapy beam during its propagation through defocusing obstacles like skull bone or ribs remain today a technological performance that still need to be validated clinically. Secondly, the problem of motion artifacts particularly important for the treatment of abdominal parts becomes today an important research topic. Finally, the problem of the treatment monitoring is a wide subject of interest in the growing HIFU community. For all these issues, the potential of new ultrasonic therapy devices able to work both in Transmit and Receive modes will be emphasized. A review of the work under achievement at L.O.A. using this new generation of HIFU prototypes on the monitoring, motion correction and aberrations corrections will be presented.

Drug delivery across the blood-brain barrier using focused ultrasound

PubMed Central

Burgess, Alison; Hynynen, Kullervo H.

2015-01-01

Introduction The presence of the blood-brain barrier (BBB) is a significant impediment to the delivery of therapeutic agents to the brain for treatment of brain diseases. Focused ultrasound (FUS) has been developed as a non-invasive method for transiently increasing the permeability of the BBB to promote drug delivery to targeted regions of the brain. Areas Covered The present review briefly compares the methods used to promote drug delivery to the brain and describes the benefits and limitations of FUS technology. We summarize the experimental data which shows that FUS, combined with intravascular microbubbles, increases therapeutic agent delivery into the brain leading to significant reductions in pathology in preclinical models of disease. The potential for translation of this technology to the clinic is also discussed. Expert Opinion The introduction of MRI guidance and intravascular administration of microbubbles to FUS treatments permits the consistent, transient, and targeted opening of the BBB. The development of feedback systems and real-time monitoring techniques improve the safety of BBB opening. Successful clinical translation of FUS has the potential to revolutionize the treatment of brain disease resulting in effective, less-invasive treatments without the need for expensive drug development. PMID:24650132

Drug delivery across the blood-brain barrier using focused ultrasound.

PubMed

Burgess, Alison; Hynynen, Kullervo

2014-05-01

The presence of the blood-brain barrier (BBB) is a significant impediment to the delivery of therapeutic agents to the brain for treatment of brain diseases. Focused ultrasound (FUS) has been developed as a noninvasive method for transiently increasing the permeability of the BBB to promote drug delivery to targeted regions of the brain. The present review briefly compares the methods used to promote drug delivery to the brain and describes the benefits and limitations of FUS technology. We summarize the experimental data which shows that FUS, combined with intravascular microbubbles, increases therapeutic agent delivery into the brain leading to significant reductions in pathology in preclinical models of disease. The potential for translation of this technology to the clinic is also discussed. The introduction of magnetic resonance imaging guidance and intravascular administration of microbubbles to FUS treatments permits the consistent, transient and targeted opening of the BBB. The development of feedback systems and real-time monitoring techniques improve the safety of BBB opening. Successful clinical translation of FUS has the potential to revolutionize the treatment of brain disease resulting in effective, less-invasive treatments without the need for expensive drug development.

Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responses in vivo

NASA Astrophysics Data System (ADS)

Fisher, Jonathan A. N.; Gumenchuk, Iryna

2018-06-01

Objective. The use of transcranial, low intensity focused ultrasound (FUS) is an emerging neuromodulation technology that shows promise for both therapeutic and research applications. Among many, one of the most exciting applications is the use of FUS to rehabilitate or augment human sensory capabilities. While there is compelling empirical evidence demonstrating this capability, basic questions regarding the spatiotemporal extent of the modulatory effects remain. Our objective was to assess the basic, yet often overlooked hypothesis that FUS in fact alters sensory-evoked neural activity within the region of the cerebral cortex at the beam’s focus. Approach. To address this knowledge gap, we developed an approach to optically interrogate patterns of neural activity in the cortex directly at the acoustic focus, in vivo. Implementing simultaneous wide-field optical imaging and FUS stimulation in mice, our experiments probed somatosensory-evoked electrical activity through the use of voltage sensitive dyes (VSDs) and, in transgenic mice expressing GCaMP6f, monitored associated Ca2+ responses. Main results. Our results demonstrate that low-intensity FUS alters both the kinetics and spatial patterns of neural activity in primary somatosensory cortex at the acoustic focus. When preceded by 1 s of pulsed ultrasound at intensities below 1 W cm‑2 (I sppa), the onset of sensory-evoked cortical responses occurred 3.0  ±  0.7 ms earlier and altered the surface spatial morphology of Ca2+ responses. Significance. These findings support the heretofore unconfirmed assumption that FUS-induced sensory modulation reflects, at least in part, altered reactivity in primary sensory cortex at the site of sonication. The findings are significant given the interest in using FUS to target and alter spatial aspects of sensory receptive fields on the cerebral cortex.

Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responses in vivo.

PubMed

Fisher, Jonathan A N; Gumenchuk, Iryna

2018-06-01

The use of transcranial, low intensity focused ultrasound (FUS) is an emerging neuromodulation technology that shows promise for both therapeutic and research applications. Among many, one of the most exciting applications is the use of FUS to rehabilitate or augment human sensory capabilities. While there is compelling empirical evidence demonstrating this capability, basic questions regarding the spatiotemporal extent of the modulatory effects remain. Our objective was to assess the basic, yet often overlooked hypothesis that FUS in fact alters sensory-evoked neural activity within the region of the cerebral cortex at the beam's focus. To address this knowledge gap, we developed an approach to optically interrogate patterns of neural activity in the cortex directly at the acoustic focus, in vivo. Implementing simultaneous wide-field optical imaging and FUS stimulation in mice, our experiments probed somatosensory-evoked electrical activity through the use of voltage sensitive dyes (VSDs) and, in transgenic mice expressing GCaMP6f, monitored associated Ca 2+ responses. Our results demonstrate that low-intensity FUS alters both the kinetics and spatial patterns of neural activity in primary somatosensory cortex at the acoustic focus. When preceded by 1 s of pulsed ultrasound at intensities below 1 W cm -2 (I sppa ), the onset of sensory-evoked cortical responses occurred 3.0  ±  0.7 ms earlier and altered the surface spatial morphology of Ca 2+ responses. These findings support the heretofore unconfirmed assumption that FUS-induced sensory modulation reflects, at least in part, altered reactivity in primary sensory cortex at the site of sonication. The findings are significant given the interest in using FUS to target and alter spatial aspects of sensory receptive fields on the cerebral cortex.

Magnetic resonance-guided focused ultrasound treatment of facet joint pain: summary of preclinical phase

PubMed Central

2014-01-01

Study design A phantom experiment, two thermocouple experiments, three in vivo pig experiments, and a simulated treatment on a healthy human volunteer were conducted to test the feasibility, safety, and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for treating facet joint pain. Objective The goal of the current study was to develop a novel method for accurate and safe noninvasive facet joint ablation using MRgFUS. Summary of background data Facet joints are a common source of chronic back pain. Direct facet joint interventions include medial branch nerve ablation and intra-articular injections, which are widely used, but limited in the short and long term. MRgFUS is a breakthrough technology that enables accurate delivery of high-intensity focused ultrasound energy to create a localized temperature rise for tissue ablation, using MR guidance for treatment planning and real-time feedback. Methods We validated the feasibility, safety, and efficacy of MRgFUS for facet joint ablation using the ExAblate 2000® System (InSightec Ltd., Tirat Carmel, Israel) and confirmed the system's ability to ablate the edge of the facet joint and all terminal nerves innervating the joint. A phantom experiment, two thermocouple experiments, three in vivo pig experiments, and a simulated treatment on a healthy human volunteer were conducted. Results The experiments showed that targeting the facet joint with energies of 150–450 J provides controlled and accurate heating at the facet joint edge without penetration to the vertebral body, spinal canal, or root foramina. Treating with reduced diameter of the acoustic beam is recommended since a narrower beam improves access to the targeted areas. Conclusions MRgFUS can safely and effectively target and ablate the facet joint. These results are highly significant, given that this is the first study to demonstrate the potential of MRgFUS to treat facet joint pain. PMID:24921048

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