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聚焦超声致血脑屏障开放:应用动态对比增强磁共振成像分析与机械指数和空化指数的关系。

Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

机构信息

Department of Electrical Engineering, Chang-Gung University, Taoyuan, 333, Taiwan.

Department of Diagnostic Radiology and Intervention, Chang-Gung Memorial Hospital, Taoyuan, 333, Taiwan.

出版信息

Sci Rep. 2016 Sep 15;6:33264. doi: 10.1038/srep33264.


DOI:10.1038/srep33264
PMID:27630037
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5024096/
Abstract

Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening. This study investigates the feasibility of gauging FUS-induced BBB opened level via the two indexes, MI and CI, through dynamic contrast-enhanced (DCE)-MRI analysis as well as passive cavitation detection (PCD) analysis. Pharmacodynamic/pharmacokinetic parameters derived from DCE-MRI were characterized to identify the scale of FUS-induced BBB opening. Our results demonstrated that DCE-MRI can successfully access pharmacodynamic/pharmacokinetic BBB-opened behavior, and was highly correlated both with MI and CI, implying the feasibility in using these two indices to gauge the scale of FUS-induced BBB opening. The proposed finding may facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS drug delivery.

摘要

聚焦超声(FUS)联合微泡可以暂时打开血脑屏障(BBB),而微泡的空化活动在 BBB 开放过程中起着关键作用。之前的尝试使用对比增强磁共振成像(CE-MRI)将机械指数(MI)与 BBB 开放程度相关联,但 MI 仅部分评估了声活动,而 CE-MRI 并未充分探索药效学/药代动力学行为的相关性。最近,已经衍生出了空化指数(CI)来作为微泡-超声稳定空化的指标,并且也可能作为评估 FUS 诱导的 BBB 开放水平的有效指标。本研究通过动态对比增强(DCE)-MRI 分析和被动空化检测(PCD)分析,研究了通过 MI 和 CI 两个指标来评估 FUS 诱导的 BBB 开放水平的可行性。从 DCE-MRI 中得出的药效学/药代动力学参数用于表征 FUS 诱导的 BBB 开放程度。我们的结果表明,DCE-MRI 可以成功地获得药效学/药代动力学 BBB 开放行为,并且与 MI 和 CI 高度相关,这意味着使用这两个指标来评估 FUS 诱导的 BBB 开放程度是可行的。这一发现可能有助于设计使用聚焦超声作为一种安全可靠的非侵入性中枢神经系统药物输送方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/68d8f8c92de8/srep33264-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/1a3002bb1530/srep33264-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/929627599c39/srep33264-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/0603832de733/srep33264-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/96fa803ff59f/srep33264-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/da27c2896bb4/srep33264-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/e618290b8259/srep33264-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/c20c7787917e/srep33264-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/68d8f8c92de8/srep33264-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/1a3002bb1530/srep33264-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/929627599c39/srep33264-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/0603832de733/srep33264-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/96fa803ff59f/srep33264-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/da27c2896bb4/srep33264-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/e618290b8259/srep33264-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/c20c7787917e/srep33264-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8c1/5024096/68d8f8c92de8/srep33264-f8.jpg

相似文献

[1]
Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

Sci Rep. 2016-9-15

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
Real-time monitoring of focused ultrasound blood-brain barrier opening via subharmonic acoustic emission detection: implementation of confocal dual-frequency piezoelectric transducers.

Phys Med Biol. 2016-4-7

[8]
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[9]
Magnetic-resonance imaging for kinetic analysis of permeability changes during focused ultrasound-induced blood-brain barrier opening and brain drug delivery.

J Control Release. 2014-6-23

[10]
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Neurosurg Focus. 2018-2

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[2]
Aducanumab delivery via focused ultrasound-induced transient blood-brain barrier opening in vivo.

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[3]
Ultrasound-responsive nanoparticles for imaging and therapy of brain tumors.

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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Inertial cavitation initiated by polytetrafluoroethylene nanoparticles under pulsed ultrasound stimulation.

Ultrason Sonochem. 2016-2-6

[2]
Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening.

Phys Med Biol. 2015-12-7

[3]
Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening.

Sci Rep. 2015-10-22

[4]
Focused ultrasound-induced blood-brain barrier opening for non-viral, non-invasive, and targeted gene delivery.

J Control Release. 2015-6-11

[5]
Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task.

PLoS One. 2015-5-6

[6]
Drug-loaded bubbles with matched focused ultrasound excitation for concurrent blood-brain barrier opening and brain-tumor drug delivery.

Acta Biomater. 2015-3

[7]
Magnetic-resonance imaging for kinetic analysis of permeability changes during focused ultrasound-induced blood-brain barrier opening and brain drug delivery.

J Control Release. 2014-6-23

[8]
Submicron-bubble-enhanced focused ultrasound for blood-brain barrier disruption and improved CNS drug delivery.

PLoS One. 2014-5-2

[9]
The size of blood-brain barrier opening induced by focused ultrasound is dictated by the acoustic pressure.

J Cereb Blood Flow Metab. 2014-7

[10]
Mechanical bioeffects of acoustic droplet vaporization in vessel-mimicking phantoms.

Ultrason Sonochem. 2014-9

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