Analysis of a simulation algorithm for direct brain drug delivery
Open accessAbstract
Convection enhanced delivery (CED) achieves targeted delivery of drugs with a pressure-driven infusion through a cannula placed stereotactically in the brain. This technique bypasses the blood brain barrier and gives precise distributions of drugs, minimizing off-target effects of compounds such as viral vectors for gene therapy or toxic chemotherapy agents. The exact distribution is affected by the cannula positioning, flow rate and underlying tissue structure. This study presents an analysis of a simulation algorithm for predicting the distribution using baseline MRI images acquired prior to inserting the cannula. The MRI images included diffusion tensor imaging (DTI) to estimate the tissue properties. The algorithm was adapted for the devices and protocols identified for upcoming trials and validated with direct MRI visualization of gadoinium in 20 infusions in non-human primates. We found strong agreement between the size and location of the simulated and gadolinium volumes, demonstrating the clinical utility of this surgical planning algorithm.
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Convection-enhanced delivery increases the vector volume that can be delivered to the target site and enhances cell transduction in the targeted CNS substructure.
“This has the advantage of increased vector volume that can be delivered to the target site, which enhances cell transduction in the targeted CNS substructure”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [79]
The Introduction describes CED as a means of distributing viral vectors to brain targets, and Methods §2.1 reports vector co-infusions of 30–300 μL. The paper does not show that CED increases the volume of vector that can be delivered relative to another method or that a larger volume enhances cell transduction in the targeted CNS structure. (LLM, conf=0.84)
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- Fiandaca MS Varenika V 2009 Real-time MR imaging of adeno-associated viral vector delivery to the primate brain Neuroimage 47 Suppl 2 T27 35 19095069 PMC2730220
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AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease
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- Authors
- Rosenbluth, K. H., Eschermann, J. F., Mittermeyer, G., Thomson, R., Mittermeyer, S., & Bankiewicz, K. S.
- Affiliations
- University of California, San Francisco (US)
- Brainlab (Germany) (DE)
- Corresponding author
- Rosenbluth, Kathryn Hammond
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 59
- Issue
- 3
- Pages
- 2423-2429
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3254804
- OpenAlex
- W2034095106
- Cited by
- 36
- References
- 25
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 1
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P01CA118816)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- convection-enhanced delivery, simulation algorithms, diffusion tensor imaging, tissue anisotropy, surgical planning, gadolinium-enhanced MRI, non-human primates, blood-brain barrier bypass, gene therapy vectors, chemotherapy
- MeSH terms
- Algorithms, Animals, Blood-Brain Barrier, Brain, Catheterization, Computer Simulation, Contrast Media, Gadolinium, Image Processing, Computer-Assisted, Injections, Macaca fascicularis, Macaca mulatta, Magnetic Resonance Imaging, Pressure, Stereotaxic Techniques, Reproducibility of Results, Drug Delivery Systems, Gene Transfer Techniques, Convection, Diffusion Tensor Imaging
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