Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy

Hynynen, Kullervo; Jones, Ryan M.

doi:10.1088/0031-9155/61/17/r206

Cited by 104 publications

(58 citation statements)

References 360 publications

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“…Sparse arrays have been proposed in the field of ultrasonics for both active (Turnbull & Foster, 1991; Davidsen & Smith, 1993; Lockwood & Foster, 1996) and passive (Coviello, et al, 2012) (O'Reilly, et al, 2014; Jones, et al, 2015) imaging, as well as for FUS therapy (Hynynen & Jones, 2016). In the current device, the transducer elements were randomly placed on a hemispherical shell in a configuration that was optimized through numerical simulations (Jones, et al, 2013), since grating lobes (on both transmit and receive) resulting from periodic, sparse arrangements can be suppressed by using an irregular layout (Goss, et al, 1996; Hutchinson, et al, 1996; Hand, et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping

et al. 2016

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Focused ultrasound (FUS) phased arrays show promise for non-invasive brain therapy. However, the majority of them are limited to a single transmit/receive frequency and therefore lack the versatility to expose and monitor the treatment volume. Multi-frequency arrays could offer variable transmit focal sizes under a fixed aperture, and detect different spectral content on receive for imaging purposes. Here, a three-frequency (306, 612 and 1224 kHz) sparse hemispherical ultrasound phased array (31.8 cm aperture; 128 transducer modules) was constructed and evaluated for microbubble-mediated transcranial therapy and simultaneous cavitation mapping. The array is able to perform effective electronic beam steering over a volume spanning [−40, 40] and [−30, 50] mm in the lateral and axial directions, respectively. The focal size at the geometric center is approximately 0.9 (2.1) mm, 1.7 (3.9) mm, and 3.1 (6.5) mm in lateral (axial) pressure full width at half maximum (FWHM) at 1224, 612, and 306 kHz, respectively. The array was also found capable of dual-frequency excitation and simultaneous multi–foci sonication, which enables the future exploration of more complex exposure strategies. Passive acoustic mapping of dilute microbubble clouds demonstrated that the point spread function of the receive array has a lateral (axial) intensity FWHM between 0.8-3.5 mm (1.7-11.7 mm) over a volume spanning [−25, 25] mm in both the lateral and axial directions, depending on the transmit/receive frequency combination and the imaging location. The device enabled both half and second harmonic imaging through the intact skull, which may be useful for improving the contrast-to-tissue ratio or imaging resolution, respectively. Preliminary in-vivo experiments demonstrated the system's ability to induce blood-brain barrier opening and simultaneously spatially map microbubble cavitation activity in a rat model. This work presents a tool to investigate optimal strategies for non-thermal FUS brain therapy and concurrent microbubble cavitation monitoring through the availability of multiple frequencies.

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Section: Discussionmentioning

confidence: 99%

A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping

et al. 2016

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“…Most T‐FUS procedures use a large array of electronically steered acoustic transducer elements to control the deposition of acoustic energy into the brain . These elements sit on a rigid, hemispherical frame whose surface, due to geometrical constraints, stands several centimeters off of the patient’s scalp.…”

Section: Introductionmentioning

confidence: 99%

Novel acoustic coupling bath using magnetite nanoparticles for MR‐guided transcranial focused ultrasound surgery

et al. 2019

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Purpose Acoustic coupling baths, nominally composed of degassed water, play important roles during transcranial focused ultrasound surgery. However, this large water bolus also degrades the quality of intraoperative magnetic resonance (MR) guidance imaging. In this study, we test the feasibility of using dilute, aqueous magnetite nanoparticle suspensions to suppress these image degradations while preserving acoustic compatibility. We examine the effects of these suspensions on metrics of image quality and acoustic compatibility for two types of transcranial focused ultrasound insonation regimes: low‐duty cycle histotripsy procedures and high‐duty cycle thermal ablation procedures. Methods Magnetic resonance guidance imaging was used to monitor thermal ablations of in vitro gel targets using a coupling bath composed of various concentrations of aqueous, suspended, magnetite nanoparticles in a clinical transcranial transducer under stationary and flowing conditions. Thermal deposition was monitored using MR thermometry simultaneous to insonation. Then, using normal degassed water as a coupling bath, various concentrations of aqueous, suspended, magnetite nanoparticles were placed at the center of this same transducer and insonated using high‐duty cycle pulsing parameters. Passive cavitation detectors recorded cavitation emissions, which were then used to estimate the relative number of cavitation events per insonation (cavitation duty cycle) and the cavitation dose estimates of each nanoparticle concentration. Finally, the nanoparticle mixtures were exposed to low‐duty cycle, histotripsy pulses. Passive cavitation detectors monitored cavitation emissions, which were used to estimate cavitation threshold pressures. Results The nanoparticles reduced the MR signal of the coupling bath by 90% in T2‐ and T2*‐weighted images and also removed almost all imaging artifacts caused by coupling bath motion. The coupling baths caused <5% changes in peak temperature change achieved during sonication, as observed via MR thermometry. At low duty cycle insonations, the nanoparticles decreased the cavitation threshold pressure by about 15 ± 7% in a manner uncorrelated with nanoparticle concentration. At high duty cycle insonations, the 0.5 cavitation duty cycle acoustic power threshold varied linearly with nanoparticle concentration. Conclusions Dilute aqueous magnetite nanoparticle suspensions effectively reduced MR imaging artifacts caused by the acoustic coupling bath. They also attenuated acoustic power deposition by <5%. For low duty cycle insonation regimes, the nanoparticles decreased the cavitation threshold by 15 ± 7%. However, for high‐duty cycle regimes, the nanoparticles decreased the threshold for cavitation in proportion to nanoparticle concentration.

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“…The previously discussed experience of scanned HT demonstrated the usefulness of a new skull-specific-transduced geometry, helmet-like, with an f value (radius/diameter) of about 0.5. Substantial research [92–97], including the advent of MR thermography [98–100] and phased-array transducers [101–103], led to the first pilot clinical trial of GBM ablation [15, 104]. While the temperature distribution in the brain was clearly detectable with MRI, it was impossible to reach ablation because of the limited power provided by the device.…”

Section: Methodsmentioning

confidence: 99%

Fast and high temperature hyperthermia coupled with radiotherapy as a possible new treatment for glioblastoma

et al. 2016

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BackgroundA new transcranial focused ultrasound device has been developed that can induce hyperthermia in a large tissue volume. The purpose of this work is to investigate theoretically how glioblastoma multiforme (GBM) can be effectively treated by combining the fast hyperthermia generated by this focused ultrasound device with external beam radiotherapy.Methods/DesignTo investigate the effect of tumor growth, we have developed a mathematical description of GBM proliferation and diffusion in the context of reaction–diffusion theory. In addition, we have formulated equations describing the impact of radiotherapy and heat on GBM in the reaction–diffusion equation, including tumor regrowth by stem cells. This formulation has been used to predict the effectiveness of the combination treatment for a realistic focused ultrasound heating scenario.Our results show that patient survival could be significantly improved by this combined treatment modality.DiscussionHigh priority should be given to experiments to validate the therapeutic benefit predicted by our model.Electronic supplementary materialThe online version of this article (doi:10.1186/s40349-016-0078-3) contains supplementary material, which is available to authorized users.

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Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy

Cited by 104 publications

References 360 publications

A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping

A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping

Novel acoustic coupling bath using magnetite nanoparticles for MR‐guided transcranial focused ultrasound surgery

Fast and high temperature hyperthermia coupled with radiotherapy as a possible new treatment for glioblastoma

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