期刊
NEUROIMAGE
卷 54, 期 -, 页码 S196-S203出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2009.08.069
关键词
MRI; Parkinson's disease; Convection-enhanced delivery; Cannula placement; Non-human primate
资金
- NIH-NCI [1 P01 CA118816-01A2]
- NATIONAL CANCER INSTITUTE [P01CA118816] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [U54NS045309, R01NS056107] Funding Source: NIH RePORTER
Optimal results in the direct brain delivery of brain therapeutics such as growth factors or viral vector into primate brain depend on reproducible distribution throughout the target region. In the present study, we retrospectively analyzed MRI of 25 convection-enhanced delivery (CED) infusions with MRI contrast into the putamen of non-human primates (NHP). Infused volume (V-i) was compared to total volume of distribution (V-d) versus V-d within the target putamen. Excellent distribution of contrast agent within the putamen was obtained in eight cases that were used to define an optimal target volume or green zone. Partial or poor distribution with leakage into adjacent anatomical structures was noted in 17 cases, defining blue and red zones, respectively. Quantitative containment (99 +/- 1%) of infused gadoteridol within the putamen was obtained when the cannula was placed in the green zone, 87 +/- 3% in the blue zone and 49 +/- 0.05% in the red zone. These results were used to determine a set of 3D stereotactic coordinates that define an optimal site for putaminal infusions in NHP and human putamen. We conclude that cannula placement and definition of optimal (green zone) stereotactic coordinates have important implications in ensuring effective delivery of therapeutics into the putamen utilizing routine stereotactic MRI localization procedures and should be considered when local therapies such as gene transfer or protein administration are being translated into clinical therapy. (C) 2009 Elsevier Inc. All rights reserved.
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