Optimal region of the putamen for image-guided convection-enhanced delivery of therapeutics in human and non-human primates - PubMed (original) (raw)

Optimal region of the putamen for image-guided convection-enhanced delivery of therapeutics in human and non-human primates

Dali Yin et al. Neuroimage. 2011 Jan.

Abstract

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.

Keywords: MRI; Parkinson’s disease; cannula placement; convection-enhanced delivery; non-human primate.

Copyright © 2009 Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1

Correlation of spatial coordinates and length of backflow with distribution of MRI tracer in the putamen

Figure 2

Figure 2. Stepped cannula placement in the putamen

(A) Schematic shows both step and tip portion of the cannula placement in green, blue and red zone for each case are shown. (B) Distribution is plotted as Vd in putamen vs. total Vd for each zone is shown (p<0.01). (C) Representative MR images showing distribution of Gadoteridol in the putamen for green, blue and red zones. Cannula placement and initial infusion are shown in panels C, D and E for each zone. Panels F, G and H show distribution of Gadoteridol in the brain after infusion into respective RGB zones. Note slight leakage into white matter tracts in G (blue) but pronounced leakage in H (red). Infusion into green zone (F) resulted in tracer distribution in putamen only.

Figure 3

Figure 3

RGB zones for step outlined in the putamen of NHP (A) and predicted for human putamen (B) based on the RGB parameters obtained in the NHP and compared on the same scale

Figure 4

Figure 4. 3D reconstruction of green zone and representative volumes of “green zone” in NHP (A and C) and human putamen (B and D)

Area of green zone was defined from MR images as a volume at least 3 mm ventral to the CC, at least 6 mm away from the AC (3 mm from cannula tip to AC plus 3 mm of tip length) vertically, greater than 2.75 mm from EC laterally, and more than 3 mm from IC medially.

Figure 5

Figure 5

Representative MR images showing distribution of Gadoteridol in the putamen and leakage into white matter tract at small and large infusion volume of MRI tracer

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