Opening the Blood-Brain Barrier with MR Imaging-guided Focused Ultrasound: Preclinical Testing on a Trans-Human Skull Porcine Model.
Opening the Blood-Brain Barrier with MR Imaging-guided Focused Ultrasound: Preclinical Testing on a Trans-Human Skull Porcine Model.
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DOI：
10.1148/radiol.2016152154
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发表时间：
2017-01
期刊：
影响因子：
19.7
通讯作者：
Hynynen K
中科院分区：
文献类型：
--
作者：
Huang Y;Alkins R;Schwartz ML;Hynynen K
开发和测试一项方案，为通过磁共振引导聚焦超声（MRgFUS）打开血脑屏障（BBBO）进行脑肿瘤化疗药物递送的临床试验做准备。该程序已获机构动物护理委员会批准。设计了跨人头颅猪模型进行临床前试验。对11头体重约15公斤的猪进行了宽开颅手术。在这只动物的大脑上放置了一部分人类头骨。改良的临床MRgFUS脑系统（ExAblate 4000, 230 kHz）与3T MR扫描仪（Signa MR750, GE Healthcare）一起使用。超声波束在超声过程中以3毫米的间隔在3×3网格上被操纵。测试了3 ~ 20 W的声功率级。每次超声均以4 ul/kg的剂量注射Definity微泡。分别采用磁共振成像、组织学和空化受体检测血脑屏障开放水平、出血水平和空化信号水平。根据测量结果的逻辑回归，开发了一种空化安全算法，并进行了测试，以尽量减少出血的风险。声波功率约为5w的gd增强MR成像显示体积约为1cm3的BBBO。组织学大体检查证实Evans蓝（与大分子白蛋白结合）外渗，H&E染色仅检出分散的红细胞外渗。在空化信号高于阈值的情况下，立即终止超声而不会引起出血。通过跨人猪颅骨模型，本研究展示了230 kHz ExAblate系统的BBBO，为临床试验做准备。
To develop and test a protocol in preparation for a clinical trial on blood-brain-barrier opening (BBBO) by magnetic resonance-guided focused ultrasound (MRgFUS) for chemo-drug delivery to brian tumors. The procedures were approved by the Institutional Animal Care Committee. A trans-human skull porcine model was designed for the preclinical testing. Wide craniotomies were applied on 11 porcine subjects (~15 kg). A partial human skull was positioned over the animal’s brain. A modified clinical MRgFUS brain system (ExAblate 4000, 230 kHz) was used with a 3T MR scanner (Signa MR750, GE Healthcare). The ultrasound beam was steered during sonications over a 3×3 grid at 3 mm spacing. Acoustic power levels from 3 to 20 W were tested. Bolus injections of Definity microbubble at 4 ul/kg were tested for each sonication. Levels of BBB opening, hemorrhage and cavitation signal were measured by MR imaging, histology and cavitation receivers, respectively. A cavitation safety algorithm was developed based on logistic regression of the measurements and tested to minimize risks of hemorrhage. BBBO of approximately 1 cm3 in volume were visualized by Gd-enhanced MR imaging post sonication at ~5 W acoustic powers. Gross examination of histology confirmed Evans blue (bound to macromolecule albumin) extravasation, and H&E staining detected only scattered extravasation of red blood cells. In cases where cavitation signals were above thresholds, sonications were terminated immediately without causing hemorrhage. With a trans-human skull porcine model, this study demonstrated BBBO with the 230 kHz ExAblate system in preparation for a clinical trial.
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影响因子：
19.7
作者：
Hynynen, K;McDannold, N;Jolesz, FA
通讯作者：
Jolesz, FA
影响因子：
11.2
作者：
McDannold N;Arvanitis CD;Vykhodtseva N;Livingstone MS
通讯作者：
Livingstone MS
DOI：
10.1109/tbme.2009.2034533
发表时间：
2010-01
期刊：
IEEE transactions on bio-medical engineering
影响因子：
--
作者：
Choi JJ;Feshitan JA;Baseri B;Wang S;Tung YS;Borden MA;Konofagou EE
通讯作者：
Konofagou EE
影响因子：
2.9
作者：
McDannold, Nathan;Vykhodtseva, Natalia;Hynynen, Kullervo
通讯作者：
Hynynen, Kullervo
影响因子：
158.5
作者：
Elias, W. Jeffrey;Huss, Diane;Wintermark, Max
通讯作者：
Wintermark, Max