Microbubble-size dependence of focused ultrasound-induced blood-brain barrier opening in mice in vivo.
Microbubble-size dependence of focused ultrasound-induced blood-brain barrier opening in mice in vivo.
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DOI：
10.1109/tbme.2009.2034533
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Konofagou EE
中科院分区：
文献类型：
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作者：
Choi JJ;Feshitan JA;Baseri B;Wang S;Tung YS;Borden MA;Konofagou EE
神经药物的治疗效果受到严重限制，因为大的化合物不能穿过血脑屏障（BBB）。在微泡存在下的聚焦超声（FUS）超声处理已被证明可以暂时打开BBB，允许全身给药的药物进入大脑。到目前为止，使用多分散的微泡（直径1-10 μm），因此，更适合诱导开口的气泡尺寸仍然未知。在这里，FUS诱导的血脑屏障开放依赖于微泡的大小进行了研究。在对小鼠（n = 28）全身给药之前，使用差速离心法分别对直径为1-2和4-5 μm的气泡进行大小分离。通过改变峰值稀疏压力幅度来确定BBB开放压力阈值。通过全身给药的荧光标记的3-kDa葡聚糖引起的荧光增强来确定BBB开放。对于1-2 μm气泡的情况，确定的阈值在0.30至0.46 MPa之间，对于4-5 μm气泡的情况，确定的阈值在0.15至0.30 MPa之间。在所研究的每个压力下，4-5 μm气泡的荧光均大于1-2 μm气泡的荧光。在0.61MPa压力下，1-2 μm气泡的荧光量和面积在丘脑大于海马。总之，确定FUS诱导的BBB开放取决于注射微泡体积和靶向脑区域的尺寸分布。
The therapeutic efficacy of neurological agents is severely limited, because large compounds do not cross the blood–brain barrier (BBB). Focused ultrasound (FUS) sonication in the presence of microbubbles has been shown to temporarily open the BBB, allowing systemically administered agents into the brain. Until now, polydispersed microbubbles (1–10 μm in diameter) were used, and, therefore, the bubble sizes better suited for inducing the opening remain unknown. Here, the FUS-induced BBB opening dependence on microbubble size is investigated. Bubbles at 1–2 and 4–5 μm in diameter were separately size-isolated using differential centrifugation before being systemically administered in mice (n = 28). The BBB opening pressure threshold was identified by varying the peak-rarefactional pressure amplitude. BBB opening was determined by fluorescence enhancement due to systemically administered, fluorescent-tagged, 3-kDa dextran. The identified threshold fell between 0.30 and 0.46 MPa in the case of 1–2 μm bubbles and between 0.15 and 0.30 MPa in the 4–5 μm case. At every pressure studied, the fluorescence was greater with the 4–5 μm than with the 1–2 μm bubbles. At 0.61 MPa, in the 1–2 μm bubble case, the fluorescence amount and area were greater in the thalamus than in the hippocampus. In conclusion, it was determined that the FUS-induced BBB opening was dependent on both the size distribution in the injected microbubble volume and the brain region targeted.