A PVDF receiver for ultrasound monitoring of transcranial focused ultrasound therapy.

Department of Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON M4N3M5, Canada.
IEEE transactions on bio-medical engineering (Impact Factor: 2.15). 09/2010; 57(9):2286-94. DOI:10.1109/TBME.2010.2050483
Source: PubMed

ABSTRACT Focused ultrasound (FUS) shows great promise for use in the area of transcranial therapy. Currently dependent on MRI for monitoring, transcranial FUS would benefit from a real-time technique to monitor acoustic emissions during therapy. A polyvinylidene fluoride receiver with an active area of 17.8 mm (2) and a film thickness of 110 mum was constructed. A compact preamplifier was designed to fit within the receiver to improve the receiver SNR and allow the long transmission line needed to remove the receiver electronics outside of the MRI room. The receiver was compared with a 0.5 mm commercial needle hydrophone and focused and unfocused piezoceramics. The receiver was found to have a higher sensitivity than the needle hydrophone, a more wideband response than the piezoceramic, and sufficient threshold for detection of microbubble emissions. Sonication of microbubbles directly and through a fragment of human skull demonstrated the ability of the receiver to detect harmonic bubble emissions, and showed potential for use in a larger scale array. Monitoring of disruption of the blood-brain barrier in rats showed functionality in vivo and the ability to detect subharmonic, harmonic, and wideband emissions during therapy. The receiver shows potential for monitoring acoustic emissions during treatments and providing additional parameters to assist treatment planning. Future work will focus on developing a multi-element array for transcranial treatment monitoring.

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    ABSTRACT: 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. 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. 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 high-field-strength MR imaging or histologic examination 8 days after treatment. This study demonstrates that acoustic emissions can be used to actively control focused ultrasound exposures for the safe induction of BBB disruption.
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    ABSTRACT: Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB(1-5). The BBB is a significant obstacle to pharmaceutical treatments of brain disorders as it limits the passage of molecules from the vasculature into the brain tissue to molecules less than approximately 500 Da in size(6). FUS induced BBB disruption (BBBD) is temporary and reversible(4) and has an advantage over chemical means of inducing BBBD by being highly localized. FUS induced BBBD provides a means for investigating the effects of a wide range of therapeutic agents on the brain, which would not otherwise be deliverable to the tissue in sufficient concentration. While a wide range of ultrasound parameters have proven successful at disrupting the BBB(2,5,7), there are several critical steps in the experimental procedure to ensure successful disruption with accurate targeting. This protocol outlines how to achieve MRI-guided FUS induced BBBD in a rat model, with a focus on the critical animal preparation and microbubble handling steps of the experiment.
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    ABSTRACT: 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.
    Biomaterials 01/2012; 33(1):247-55. · 7.60 Impact Factor


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