Journal
JOURNAL OF NEUROSURGERY
Volume 133, Issue 2, Pages 530-537Publisher
AMER ASSOC NEUROLOGICAL SURGEONS
DOI: 10.3171/2019.4.JNS19826
Keywords
convection-enhanced delivery; gene therapy; Parkinson's disease; putamen; infusion; surgical technique
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Funding
- NIH [P01 CA118816]
- Kinetics Foundation
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OBJECTIVE To develop and assess a convective delivery technique that enhances the effectiveness of drug delivery to nonspherical brain nuclei, the authors developed an occipital infuse-as-you-go approach to the putamen and compared it to the currently used transfrontal approach. METHODS Eleven nonhuman primates received a bilateral putamen injection of adeno-associated virus with 2 mM gadolinium-DTPA by real-time MR-guided convective perfusion via either a transfrontal (n = 5) or occipital infuse-as-you-go (n = 6) approach. RESULTS MRI provided contemporaneous assessment and monitoring of putaminal infusions for transfrontal (2 to 3 infusion deposits) and occipital infuse-as-you-go (stepwise infusions) putaminal approaches. The infuse-as-you-go technique was more efficient than the transfrontal approach (mean 35 +/- 1.1 vs 88 +/- 8.3 minutes [SEM; p < 0.001]). More effective perfusion of the postcommissural and total putamen was achieved with the infuse-as-you-go versus transfronatal approaches (100-mu l infusion volumes; mean posterior commissural coverage 76.2% +/- 5.0% vs 32.8% +/- 2.9% [p < 0.001]; and mean total coverage 53.5% +/- 3.0% vs 38.9% +/- 2.3% [p < 0.01]). CONCLUSIONS The infuse-as-you-go approach, paralleling the longitudinal axis of the target structure, provides a more effective and efficient method for convective infusate coverage of elongated, irregularly shaped subcortical brain nuclei.
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