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Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task.在执行认知任务的非人灵长类动物中,通过聚焦超声联合微泡重复打开血脑屏障的长期安全性。
PLoS One. 2015 May 6;10(5):e0125911. doi: 10.1371/journal.pone.0125911. eCollection 2015.
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Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior.在一个小鼠模型中发现的阿尔茨海默病:MR 影像引导的聚焦超声靶向海马区打开血脑屏障,改善病理异常和行为。
Radiology. 2014 Dec;273(3):736-45. doi: 10.1148/radiol.14140245. Epub 2014 Sep 15.
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Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques.利用超声和微泡暂时破坏血脑屏障:恒河猴的安全性和有效性评估。
Cancer Res. 2012 Jul 15;72(14):3652-63. doi: 10.1158/0008-5472.CAN-12-0128. Epub 2012 May 2.
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Low-frequency ultrasound irradiation increases blood-tumor barrier permeability by transcellular pathway in a rat glioma model.低频超声辐射通过细胞旁路增加大鼠脑胶质瘤模型血-肿瘤屏障通透性。
J Mol Neurosci. 2012 Sep;48(1):281-90. doi: 10.1007/s12031-012-9770-0. Epub 2012 Apr 20.
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Blood-brain barrier: real-time feedback-controlled focused ultrasound disruption by using an acoustic emissions-based controller.血脑屏障:基于声发射的控制器实现实时反馈控制的聚焦超声破坏。
Radiology. 2012 Apr;263(1):96-106. doi: 10.1148/radiol.11111417. Epub 2012 Feb 13.
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Ultrasound insertion loss of rat parietal bone appears to be proportional to animal mass at submegahertz frequencies.大鼠顶骨的超声插入损耗似乎与亚兆赫兹频率下的动物质量成正比。
Ultrasound Med Biol. 2011 Nov;37(11):1930-7. doi: 10.1016/j.ultrasmedbio.2011.08.001. Epub 2011 Sep 16.
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Increasing of blood-tumor barrier permeability through paracellular pathway by low-frequency ultrasound irradiation in vitro.体外低频超声辐射通过细胞旁途径增加血-肿瘤屏障通透性。
J Mol Neurosci. 2011 Mar;43(3):541-8. doi: 10.1007/s12031-010-9479-x. Epub 2010 Nov 23.
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Mechanism of low-frequency ultrasound in opening blood-tumor barrier by tight junction.低频超声通过紧密连接打开血脑肿瘤屏障的机制。
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9
Multi-modality safety assessment of blood-brain barrier opening using focused ultrasound and definity microbubbles: a short-term study.应用聚焦超声和 Definity 微泡打开血脑屏障的多模态安全性评估:一项短期研究。
Ultrasound Med Biol. 2010 Sep;36(9):1445-59. doi: 10.1016/j.ultrasmedbio.2010.06.005.
10
Effect of focused ultrasound applied with an ultrasound contrast agent on the tight junctional integrity of the brain microvascular endothelium.聚焦超声联合超声造影剂对脑微血管内皮紧密连接完整性的影响。
Ultrasound Med Biol. 2008 Jul;34(7):1093-104. doi: 10.1016/j.ultrasmedbio.2007.12.015. Epub 2008 Apr 18.

使用聚焦超声反复破坏血脑屏障的安全性验证

Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound.

作者信息

Kobus Thiele, Vykhodtseva Natalia, Pilatou Magdalini, Zhang Yongzhi, McDannold Nathan

机构信息

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Ultrasound Med Biol. 2016 Feb;42(2):481-92. doi: 10.1016/j.ultrasmedbio.2015.10.009. Epub 2015 Nov 23.

DOI:10.1016/j.ultrasmedbio.2015.10.009
PMID:26617243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4816071/
Abstract

The purpose of this study was to investigate the effects on the brain of multiple sessions of blood-brain barrier (BBB) disruption using focused ultrasound (FUS) in combination with micro-bubbles over a range of acoustic exposure levels. Six weekly sessions of FUS, using acoustical pressures between 0.66 and 0.80 MPa, were performed under magnetic resonance guidance. The success and degree of BBB disruption was estimated by signal enhancement of post-contrast T1-weighted imaging of the treated area. Histopathological analysis was performed after the last treatment. The consequences of repeated BBB disruption varied from no indications of vascular damage to signs of micro-hemorrhages, macrophage infiltration, micro-scar formations and cystic cavities. The signal enhancement on the contrast-enhanced T1-weighted imaging had limited value for predicting small-vessel damage. T2-weighted imaging corresponded well with the effects on histopathology and could be used to study treatment effects over time. This study demonstrates that repeated BBB disruption by FUS can be performed with no or limited damage to the brain tissue.

摘要

本研究的目的是调查在一系列声学暴露水平下,使用聚焦超声(FUS)结合微泡多次破坏血脑屏障(BBB)对大脑的影响。在磁共振引导下,每周进行6次FUS治疗,声压在0.66至0.80MPa之间。通过治疗区域的对比增强T1加权成像的信号增强来评估BBB破坏的成功与否及程度。在最后一次治疗后进行组织病理学分析。反复破坏BBB的后果各不相同,从无血管损伤迹象到出现微出血、巨噬细胞浸润、微瘢痕形成和囊腔等迹象。对比增强T1加权成像上的信号增强对预测小血管损伤的价值有限。T2加权成像与组织病理学效应吻合良好,可用于研究随时间变化的治疗效果。本研究表明,FUS反复破坏BBB可对脑组织造成无损伤或有限损伤。