Transcranial cavitation detection in primates during blood-brain barrier opening-a performance assessment study

Wu, Shih-Ying; Tung, Yu-Chi; Marquet, Fabrice; Downs, Matthew; Sanchez, Carlos Sierra; Chen, Cherry Chen; Ferrera, Vincent P.; Konofagou, Elisa E.

doi:10.1109/tuffc.2014.2992

Cited by 89 publications

(74 citation statements)

References 46 publications

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“…In FUS-induced BBB opening, 20,[32][33][34][35][36][37] sonothrombolysis, [38][39][40][41][42] and histotripsy 43,44 studies, correlations between the cavitation activity measured using a single-element passive cavitation detector (PCD) and treatment outcome have been reported. Moreover, microbubble emissions have been used to select treatment pressures 36 and modulate them in real-time between subsequent therapy pulses 35 during FUS-induced BBB opening.…”

Section: Introductionmentioning

confidence: 99%

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Jones

O’Reilly

Hynynen³

2015

Medical Physics

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Purpose: Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981-5005 (2013)]. Methods: A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11-0.33 MPa, 306 kHz driving frequency) Definity™ microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water-path control images. Results: For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors' previous experimental measurements using source-based skull corrections O'Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285-1294]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood-brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position obtained using source-based corrections. Conclusions: Taken together, these results demonstrate the feasibility of using the method to guide bubble-mediated ultrasound therapies in the brain. The technique may also have application in ultrasound-based cerebral angiography. C 2015 American Association of Physicists in Medicine.

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Section: Introductionmentioning

confidence: 99%

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Jones

O’Reilly

Hynynen³

2015

Medical Physics

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“…Stable cavitation dose with harmonics (SCD h ) was for volumetric oscillation; inertial cavitation dose (ICD) identified drastic bubble oscillation and bubble collapse; stable cavitation dose with ultraharmonics (SCD u ) was thought to identify asymmetric oscillation and shell waves [23]. Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Three types of cavitation dose (SCD h , stable cavitation dose using harmonics; SCD u , stable cavitation dose using ultraharmonics; ICD, inertial cavitation dose) were quantified as described previously [22, 23]. First, each pulse of the PCD signal was calculated into the frequency spectrum in MATLAB (Mathworks Inc., Natick, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Effects of the microbubble shell physicochemical properties on ultrasound-mediated drug delivery to the brain

Chen

Tung

et al. 2015

Journal of Controlled Release

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Lipid-shelled microbubbles have been used in ultrasound-mediated drug delivery. The physicochemical properties of the microbubble shell could affect the delivery efficiency since they determine the microbubble mechanical properties, circulation persistence, and dissolution behavior during cavitation. Therefore, the aim of this study was to investigate the shell effects on drug delivery efficiency in the brain via blood-brain barrier (BBB) opening in vivo using monodisperse microbubbles with different phospholipid shell components. The physicochemical properties of the monolayer were varied by using phospholipids with different hydrophobic chain lengths (C16, C18, and C24). The dependence on the molecular size and acoustic energy (both pressure and pulse length) were investigated. Our results showed that a relatively small increase in the microbubble shell rigidity resulted in a significant increase in the delivery of 40-kDa dextran, especially at higher pressures. Smaller (3 kDa) dextran did not show significant difference in the delivery amount, suggesting the observed shell effect was molecular size-dependent. In studying the impact of acoustic energy on the shell effects, it was found that they occurred most significantly at pressures causing microbubble destruction (450 kPa and 600 kPa); by increasing the pulse length to deliver the 40-kDa dextran, the difference between C16 and C18 disappeared while C24 still achieved the highest delivery efficiency. These indicated that the acoustic energy could be used to modulate the shell effects. The acoustic cavitation emission revealed the physical mechanisms associated with different shells. Overall, lipid-shelled microbubbles with long hydrophobic chain length could achieve high delivery efficiency for larger molecules especially with high acoustic energy. Our study, for the first time, offered evidence directly linking the microbubble monolayer shell with their efficacy for drug delivery in vivo.

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“…Five-seconds-long PCD signals were acquired before the microbubbles injections and used as a control baseline. The stable cavitation dose using harmonics (SCDh) was quantified based on the previous method (Wu et al; 2014). For the standard waveform, the harmonic signal (n*f; n = 2, 3, 4, 5, 6; f = 1.5 MHz; maximum amplitude within a bandwidth of 200 Hz around the harmonic frequency) was filtered after taking the root mean square (RMS) of the voltage spectral amplitude.…”

Section: Methodsmentioning

confidence: 99%

Chirp- and random-based coded ultrasonic excitation for localized blood-brain barrier opening

Kamimura

Wang

et al. 2015

Phys. Med. Biol.

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Chirp- and random-based coded excitation methods have been proposed to reduce standing wave formation and improve focusing of transcranial ultrasound. However, no clear evidence has been shown to support the benefits of these ultrasonic excitation sequences in vivo. This study evaluates the chirp and periodic selection of random frequency (PSRF) coded-excitation methods for opening the blood-brain barrier (BBB) in mice. Three groups of mice (n=15) were injected with polydisperse microbubbles and sonicated in the caudate putamen using the chirp/PSRF coded (bandwidth: 1.5-1.9 MHz, peak negative pressure: 0.52 MPa, duration: 30 s) or standard ultrasound (frequency: 1.5 MHz, pressure: 0.52 MPa, burst duration: 20 ms, duration: 5 min) sequences. T1-weighted contrast-enhanced MRI scans were performed to quantitatively analyze focused ultrasound induced BBB opening. The mean opening volumes evaluated from the MRI were 9.38±5.71 mm3, 8.91±3.91 mm3 and 35.47 ± 5.10 mm3 for the chirp, random and regular sonications, respectively. The mean cavitation levels were 55.40±28.43 V.s, 63.87±29.97 V.s and 356.52±257.15 V.s for the chirp, random and regular sonications, respectively. The chirp and PSRF coded pulsing sequences improved the BBB opening localization by inducing lower cavitation levels and smaller opening volumes compared to results of the regular sonication technique. Larger bandwidths were associated with more focused targeting but were limited by the frequency response of the transducer, the skull attenuation and the microbubbles optimal frequency range. The coded methods could therefore facilitate highly localized drug delivery as well as benefit other transcranial ultrasound techniques that use higher pressure levels and higher precision to induce the necessary bioeffects in a brain region while avoiding damage to the surrounding healthy tissue.

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Transcranial cavitation detection in primates during blood-brain barrier opening-a performance assessment study

Cited by 89 publications

References 46 publications

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Effects of the microbubble shell physicochemical properties on ultrasound-mediated drug delivery to the brain

Chirp- and random-based coded ultrasonic excitation for localized blood-brain barrier opening

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