Design and Validation of a Multi-Point Injection Technology for MR-Guided Convection Enhanced Delivery in the Brain.
Design and Validation of a Multi-Point Injection Technology for MR-Guided Convection Enhanced Delivery in the Brain.
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DOI：
10.3389/fmedt.2021.725844
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发表时间：
2021
影响因子：
--
通讯作者：
Vitale F
中科院分区：
文献类型：
--
作者：
Prezelski K;Keiser M;Stein JM;Lucas TH;Davidson B;Gonzalez-Alegre P;Vitale F
对流增强输送（CED）允许直接颅内给药的神经治疗。CED的成功依赖于特异性靶向和广泛的体积分布（VD）。然而，为了防止脱靶输送和组织损伤，CED通常使用小套管和低流速进行，这严重限制了可实现的最大VD。此外，在基因治疗等应用中，需要将大量液体注射到广泛的皮质下区域，低流速意味着较长的注射时间和多种手术轨迹。导管设计是实现宽VD的主要限制因素，同时最大限度地减少输液时间和回流。在这里，我们提出并验证了一种新的多点插管，专门设计用于优化mri引导的颅内CED基因治疗的分布和递送时间。首先，我们评估了我们的导管与MRI和基因治疗的常见病毒载体的兼容性。然后，我们在琼脂糖脑幻影中进行了CED测试，并将结果与单针递送进行了基准测试。3T MRI在脑幻影中显示最小的敏感性诱发伪影，与设备尺寸相当。腺相关病毒的台式CED未显示病毒丢失或失活。琼脂糖脑幻影中，3、6和9 μL/min剂量下的CED与单针给药相比，体积分布增加了50倍，时间减少了60%。本研究证实了多点输注方法在临床相容的时间尺度上改善输注分布的有效性，并支持了我们的新型套管设计的可行性，以提高核磁共振引导的CED到中枢神经系统的安全性和有效性。
Convection enhanced delivery (CED) allows direct intracranial administration of neuro-therapeutics. Success of CED relies on specific targeting and broad volume distributions (VD). However, to prevent off-target delivery and tissue damage, CED is typically conducted with small cannulas and at low flow rates, which critically limit the maximum achievable VD. Furthermore, in applications such as gene therapy requiring injections of large fluid volumes into broad subcortical regions, low flow rates translate into long infusion times and multiple surgical trajectories. The cannula design is a major limiting factor in achieving broad VD, while minimizing infusion time and backflow. Here we present and validate a novel multi-point cannula specifically designed to optimize distribution and delivery time in MR-guided intracranial CED of gene-based therapeutics. First, we evaluated the compatibility of our cannula with MRI and common viral vectors for gene therapy. Then, we conducted CED tests in agarose brain phantoms and benchmarked the results against single-needle delivery. 3T MRI in brain phantoms revealed minimal susceptibility-induced artifacts, comparable to the device dimensions. Benchtop CED of adeno-associated virus demonstrated no viral loss or inactivation. CED in agarose brain phantoms at 3, 6, and 9 μL/min showed >3x increase in volume distribution and 60% time reduction compared to single-needle delivery. This study confirms the validity of a multi-point delivery approach for improving infusate distribution at clinically-compatible timescales and supports the feasibility of our novel cannula design for advancing safety and efficacy of MR-guided CED to the central nervous system.
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DOI：
10.1115/1.4006404
发表时间：
2012-04-01
影响因子：
1.7
作者：
Casanova, Fernando;Carney, Paul R.;Sarntinoranont, Malisa
通讯作者：
Sarntinoranont, Malisa
DOI：
10.15586/codon.glioblastoma.2017.ch18
发表时间：
2017-01-01
期刊：
GLIOBLASTOMA
影响因子：
--
作者：
Elenes, Egleide Y.;Rylander, Christopher G.
通讯作者：
Rylander, Christopher G.
影响因子：
12.4
作者：
Foust, Kevin D.;Salazar, Desiree L.;Kaspar, Brian K.
通讯作者：
Kaspar, Brian K.
影响因子：
2
作者：
Linninger, Andreas A.;Somayaji, Mahadevabharath R.;Zhang, Libin
通讯作者：
Zhang, Libin
用于针对小儿疾病的脊髓，大脑和周围组织的大物种中的全身基因递送。
DOI：
10.1038/mt.2011.157
发表时间：
2011-11
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
通讯作者：
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