Effect of needle insertion speed on tissue injury, stress, and backflow distribution for convection-enhanced delivery in the rat brain.

Effect of needle insertion speed on tissue injury, stress, and backflow distribution for convection-enhanced delivery in the rat brain.
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DOI:
10.1371/journal.pone.0094919
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Sarntinoranont M
Sarntinoranont M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Casanova F;Carney PR;Sarntinoranont M

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在将药物直接输注(例如,对流增强递送(CED))到诸如脑的软组织中期间,沿针轨道沿着回流(回流)可能是一个问题。在这项研究中,针插入速度对局部组织损伤和回流的影响进行了评估,在体内大鼠脑。以三种插入速度(0.2、2和10 mm/s)引入针,然后进行伊文思蓝白蛋白(EBA)示踪剂的CED。组织切片中留下的孔用于重建穿透损伤。这些测量值也被输入到超弹性模型中,以估计输注前针头-组织界面处的径向应力(预应力)。发现快速插入速度会产生更多的组织出血和破裂; 10 mm/s时的平均孔面积是0.2 mm/s时的1.87倍。针回缩后10 min和25 min两个固定时间点的孔测量值也不同,表明预应力受时间依赖性组织肿胀的影响。计算的预应力为压缩应力(0至485 Pa),并沿针的长度沿着变化,白色物质(116 Pa)区域内的平均值小于灰质(301 Pa)区域。经计算,0.2 mm/s(351.7 Pa)时的平均预应力是10 mm/s时的1.46倍。对于CED回流实验(0.5、1和2 µL/min),在10 mm/s和0.2 mm/s插入速度之间,测得的EBA回流增加多达2.46倍。因此,发现插入速率依赖性损伤和预应力的变化直接影响回流的程度,较慢的插入导致较少的损伤和改善的靶向。
Flow back along a needle track (backflow) can be a problem during direct infusion, e.g. convection-enhanced delivery (CED), of drugs into soft tissues such as brain. In this study, the effect of needle insertion speed on local tissue injury and backflow was evaluated in vivo in the rat brain. Needles were introduced at three insertion speeds (0.2, 2, and 10 mm/s) followed by CED of Evans blue albumin (EBA) tracer. Holes left in tissue slices were used to reconstruct penetration damage. These measurements were also input into a hyperelastic model to estimate radial stress at the needle-tissue interface (pre-stress) before infusion. Fast insertion speeds were found to produce more tissue bleeding and disruption; average hole area at 10 mm/s was 1.87-fold the area at 0.2 mm/s. Hole measurements also differed at two fixation time points after needle retraction, 10 and 25 min, indicating that pre-stresses are influenced by time-dependent tissue swelling. Calculated pre-stresses were compressive (0 to 485 Pa) and varied along the length of the needle with smaller average values within white matter (116 Pa) than gray matter (301 Pa) regions. Average pre-stress at 0.2 mm/s (351.7 Pa) was calculated to be 1.46-fold the value at 10 mm/s. For CED backflow experiments (0.5, 1, and 2 µL/min), measured EBA backflow increased as much as 2.46-fold between 10 and 0.2 mm/s insertion speeds. Thus, insertion rate-dependent damage and changes in pre-stress were found to directly contribute to the extent of backflow, with slower insertion resulting in less damage and improved targeting.
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