School of Engineering, Queen's Building, Cardiff University, The Parade, Cardiff CF24 3AA, UK; Functional Neurosurgery Research Group, University of Bristol, School of Clinical Sciences, Learning & Research Building, Southmead Hospital, UK; Neurological Applications Department, Renishaw PLC, New Mills, Wotton-Under-Edge, Gloucestershire, GL12, UK.
Functional Neurosurgery Research Group, University of Bristol, School of Clinical Sciences, Learning & Research Building, Southmead Hospital, UK; Neurological Applications Department, Renishaw PLC, New Mills, Wotton-Under-Edge, Gloucestershire, GL12, UK.
J Neurosci Methods. 2018 Oct 1;308:337-345. doi: 10.1016/j.jneumeth.2018.08.029. Epub 2018 Sep 1.
The design and use of convection-enhanced delivery catheters remains an active field as clinical trials have highlighted suboptimal distribution as a contributory factor to the failure of those studies. Recent studies indicate limitations and challenges in achieving target coverage using conventional point source delivery.
The recessed step catheter(RSC), developed by this group, does not function as a point source delivery device, but instead uses 'controlled reflux' of the infusate to a flow inhibiting recess feature. Here we investigate a range of clinically useful step lengths in agarose gel and investigate proof-of-principle in vivo(n = 5). Infusion morphology was characterised in terms of length, width and distribution volume over a range of flow rates.
For a fixed infusion volume, increases in catheter step length strongly correlated with increases in the length and volume of distribution (r>0.90, p < 0.001) whilst there were small reductions in the width of distribution (r<-0.62, p < 0.001). Step lengths below 6 mm produced spherical distributions while steps above 12 mm produced elongated distributions. Increasing peak flow rates resulted in significant reductions in distribution volume at each step length, and an increased risk of reflux beyond the step. Modifications to the infusion morphology using changes in step length were confirmed in vivo.
The combination of the recessed step and the ability to adjust the step length with this catheter design make it highly suitable for tailoring the distribution volume of the infusate to meet specific morphological target volumes in the brain.
由于临床试验强调了分布不均是导致这些研究失败的一个因素，因此对流增强给药导管的设计和使用仍然是一个活跃的领域。最近的研究表明，使用传统的点源给药方式，在实现目标覆盖方面存在局限性和挑战。
该小组开发的凹进台阶导管（RSC）不作为点源给药装置，而是利用“灌注液的受控回流”到流动抑制凹进特征。在这里，我们在琼脂糖凝胶中研究了一系列临床有用的台阶长度，并在体内进行了原理验证（n=5）。在一系列流速下，根据长度、宽度和分布体积来描述灌注形态。
对于固定的灌注体积，导管台阶长度的增加与分布长度和体积的增加强烈相关（r>0.90，p<0.001），而分布宽度略有减小（r<-0.62，p<0.001）。台阶长度小于 6mm 会产生球形分布，而台阶长度大于 12mm 会产生拉长的分布。增加峰值流速会导致在每个台阶长度下分布体积显著减少，并且超过台阶的回流风险增加。通过改变台阶长度对灌注形态的修改在体内得到了证实。
凹进台阶与能够调整台阶长度的组合，使这种导管设计非常适合根据特定的脑形态目标体积来调整灌注液的分布体积。
