Brady Martin L, Raghavan Raghu, Alexander Andrew, Kubota Ken, Sillay Karl, Emborg Marina E
Therataxis LLC, Baltimore, MD 21218, USA.
Stereotact Funct Neurosurg. 2013;91(2):69-78. doi: 10.1159/000342492. Epub 2013 Jan 22.
New strategies aiming to treat Parkinson's disease, such as delivery of trophic factors via protein infusion or gene transfer, depend upon localized intracerebral infusion, mainly into the putamen nucleus. Convection-enhanced delivery (CED) has been proposed as a method to improve intracerebral distribution of therapies. Yet analysis of controversial results during the clinical translation of these strategies suggests that intracerebral misdistribution of infusate may have affected the outcomes by limiting the amount of treatment into the target region.
This study aimed to identify possible pathways of infusate loss and their relative impact in the success of targeted CED into the postcommissural ventral putamen nucleus.
Thirteen adult macaque monkeys received intraputaminal CED infusions of 100 µl of 2.0 mM gadoteridol and bromophenol blue (0.16 mg/ml) solution at a rate of 1.0 µl/min under intraoperative magnetic resonance imaging (MRI) guidance. Quantitative maps of infusate concentration were computed at 10-min intervals throughout the procedure in a 3-Tesla MRI scanner. The fraction of tracer lost from the putamen as well as the path of loss were evaluated and quantified for each infusion.
All injections (total 22) were successfully placed in the ventral postcommissural putamen nucleus. Four major paths of infusate loss from the putamen were observed: overflow across putamen boundaries, perivascular flow along large blood vessels, backflow along the inserted catheter and catheter tract leakage into the vacated catheter tract upon catheter removal. Overflow loss was observed within the first 30 µl of infusion in all cases. Measurable tracer loss following the path of an artery out of the putamen was observed in 15 cases, and in 8 of these cases, the loss was greater than 10% of infusate. Backflow that exited the putamen was observed in 4 cases and led to large loss of infusate (80% in 1 case) into the corona radiata. Loss into the vacated catheter tract amounted only to a few microliters.
Our analysis demonstrates that after controlling for targeting, catheter type, infusion rate and infusate, the main issues during surgical planning are the identification of appropriate infusate volume that matches the target area, as well as mapping the regional vasculature as it may become a pathway for infusate loss. Most importantly, these results underscore the significance of presurgical planning for catheter placement and infusion, and the value of imaging guidance to ensure targeting accuracy.
旨在治疗帕金森病的新策略，如通过蛋白质输注或基因转移递送神经营养因子，依赖于局部脑内输注，主要注入壳核。对流增强递送（CED）已被提议作为一种改善脑内治疗药物分布的方法。然而，对这些策略临床转化过程中存在争议的结果进行分析表明，注入物在脑内的分布不均可能通过限制进入靶区域的治疗量而影响治疗结果。
本研究旨在确定注入物损失的可能途径及其对靶向CED注入连合后腹侧壳核成功与否的相对影响。
13只成年猕猴在术中磁共振成像（MRI）引导下，以1.0 μl/min的速率向壳核内注入100 μl 2.0 mM钆特醇和溴酚蓝（0.16 mg/ml）溶液进行CED输注。在整个过程中，每隔10分钟在3特斯拉MRI扫描仪中计算注入物浓度的定量图。对每次输注评估并量化从壳核损失的示踪剂分数以及损失路径。
所有注射（共22次）均成功置于连合后腹侧壳核内。观察到注入物从壳核损失的四条主要途径：越过壳核边界溢出、沿大血管的血管周围流动、沿插入导管的回流以及导管移除时导管道泄漏到空的导管道中。在所有情况下，在输注最初30 μl内均观察到溢出损失。15例观察到注入物沿动脉路径从壳核流出的可测量示踪剂损失，其中8例损失大于注入物的10%。4例观察到从壳核流出的回流，导致大量注入物（1例中为80%）损失到放射冠中。损失到空的导管道中的量仅为几微升。
我们的分析表明，在控制靶点、导管类型、输注速率和注入物后，手术规划中的主要问题是确定与靶区域匹配的合适注入物体积，以及绘制区域血管系统图，因为它可能成为注入物损失的途径。最重要的是，这些结果强调了术前导管放置和输注规划的重要性，以及成像引导对确保靶向准确性的价值。
