当前位置： SCI文献检索 > PHYSICS IN MEDICINE AND BIOLOGY期刊下所有文献 > Real-time monitoring of focused ultrasound blood-brain barrier opening via subharmonic acoustic emission detection: implementation of confocal dual-frequency piezoelectric transducers.

Real-time monitoring of focused ultrasound blood-brain barrier opening via subharmonic acoustic emission detection: implementation of confocal dual-frequency piezoelectric transducers.

Abstract：

:Burst-tone focused ultrasound exposure in the presence of microbubbles has been demonstrated to be effective at inducing temporal and local opening of the blood-brain barrier (BBB), which promises significant clinical potential to deliver therapeutic molecules into the central nervous system (CNS). Traditional contrast-enhanced imaging confirmation after focused ultrasound (FUS) exposure serves as a post-operative indicator of the effectiveness of FUS-BBB opening, however, an indicator that can concurrently report the BBB status and BBB-opening effectiveness is required to provide effective feedback to implement this treatment clinically. In this study, we demonstrate the use of subharmonic acoustic emission detection with implementation on a confocal dual-frequency piezoelectric ceramic structure to perform real-time monitoring of FUS-BBB opening. A confocal dual-frequency (0.55 MHz/1.1 MHz) focused ultrasound transducer was designed. The 1.1 MHz spherically-curved ceramic was employed to deliver FUS exposure to induce BBB-opening, whereas the outer-ring 0.55 MHz ceramic was employed to detect the subharmonic acoustic emissions originating from the target position. In stage-1 experiments, we employed spectral analysis and performed an energy spectrum density (ESD) calculation. An optimized 0.55 MHz ESD level change was shown to effectively discriminate the occurrence of BBB-opening. Wideband acoustic emissions received from 0.55 MHz ceramics were also analyzed to evaluate its correlations with erythrocyte extravasations. In stage-2 real-time monitoring experiments, we applied the predetermined ESD change as a detection threshold in PC-controlled algorithm to predict the FUS exposure intra-operatively. In stage-1 experiment, we showed that subharmonic ESD presents distinguishable dynamics between intact BBB and opened BBB, and therefore a threshold ESD change level (5.5 dB) can be identified for BBB-opening prediction. Using this ESD change threshold detection as a surrogate to on/off control the FUS exposure in stage-2 experiments, we demonstrated both excellent sensitivity (92%) and specificity (92.3%) in discriminating BBB-opening occurrence can be obtained in animal treatments, while concurrently achieving a high positive predicted value (95.8%). Wideband ESD was also highly correlated with the occurrence and level of erythrocyte extravasations (r (2) = 0.81). The proposed system configuration and corresponding analysis based on subharmonic acoustic emissions has the potential to be implemented as a real-time feedback control structure for reliable indication of intact FUS-BBB opening for CNS brain drug delivery.

journal_name

Phys Med Biol

journal_title

Physics in medicine and biology

authors

Tsai CH,Zhang JW,Liao YY,Liu HL

doi

10.1088/0031-9155/61/7/2926

subject

Has Abstract

pub_date

2016-04-07 00:00:00

pages

2926-46

issue

eissn

0031-9155

issn

1361-6560

journal_volume

pub_type

杂志文章

在线工具

Real-time monitoring of focused ultrasound blood-brain barrier opening via subharmonic acoustic emission detection: implementation of confocal dual-frequency piezoelectric transducers.