A Preliminary Study on the Accuracy of MRI-Guided Thalamic Infusion of AAV2-GFP and Biodistribution Analysis Using Cryo-Fluorescence Tomography in Nonhuman Primates
Abstract
1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Animals
2.3. Test Article
2.4. MRI-Guided Intracerebral Infusion
2.5. Clinical Observations
2.6. Tissue Processing
2.7. Histological Staining and Analysis (Chromogenic Detection)
2.8. Cryo-Fluorescence Tomography
2.9. MRI and 3D Volume Reconstruction
3. Results
3.1. Performance of ClearPoint Navigational Software
3.2. AAV2-GFP Vector Distribution
3.3. Biodistribution of GFP Transgene
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AAALAC | Association for assessment and accreditation of laboratory animal care |
AAV | Adeno-associated viral |
AAV2 | Adeno-associated viral serotype 2 |
CED | Convection-enhanced delivery |
CFT | Cryo-fluorescence tomography |
CMV | Cytomegalovirus |
CNS | Central nervous system |
CSF | Cerebrospinal fluid |
DAB | 3, 3′-Diaminobenzidine |
ECG | Electrocardiogram |
EMA | European medicines agency |
FDA | U.S. Food and drug administration |
GFP | Green fluorescent protein |
IACUC | Institutional animal care and use committee |
MRI | Magnetic resonance imaging |
ms | milliseconds |
NHP | Nonhuman primate |
OCT | Optimal cutting temperature |
ROI | Region-of-interest |
T1w | Time-1-weighted |
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Metric | Animal #1 | Animal #2 | |
---|---|---|---|
Right Side | Right Side | Left Side | |
Projected Radial Error | 0.7 mm | 0.3 mm | 0.5 mm |
Actual Radial Error | 0.6 mm | 0.2 mm | 0.3 mm |
Difference in Radial Error | 0.1 mm | 0.1 mm | 0.2 mm |
Final Depth Error | −0.1 mm | 0.6 mm | −0.2 mm |
Brain Region | Structures Transduced | GFP Expression |
---|---|---|
Cerebral gray/white matter | Axons, neurons | Strong, 1 or 3 * |
Internal capsule | Axons | Strong, 1 or 3 * |
Lateral ventricle | Ependymal cells | Moderate, 1 |
Hypothalamus | Axons, neurons | Light to strong, 2 |
Thalamus | Axons, neurons | Light to strong, 2 |
Caudate nucleus | Axons | Light to moderate, 1 |
Pons | Axons, neurons | Light to strong, 2 |
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Salegio, E.A.; Espinosa, R.; Smith, G.R.; Shoshan, D.; Silva, M.; White, E.; McDonald, J. A Preliminary Study on the Accuracy of MRI-Guided Thalamic Infusion of AAV2-GFP and Biodistribution Analysis Using Cryo-Fluorescence Tomography in Nonhuman Primates. Pharmaceutics 2025, 17, 1167. https://doi.org/10.3390/pharmaceutics17091167
Salegio EA, Espinosa R, Smith GR, Shoshan D, Silva M, White E, McDonald J. A Preliminary Study on the Accuracy of MRI-Guided Thalamic Infusion of AAV2-GFP and Biodistribution Analysis Using Cryo-Fluorescence Tomography in Nonhuman Primates. Pharmaceutics. 2025; 17(9):1167. https://doi.org/10.3390/pharmaceutics17091167
Chicago/Turabian StyleSalegio, Ernesto A., Reinier Espinosa, Geary R. Smith, David Shoshan, Matthew Silva, Eli White, and Jacob McDonald. 2025. "A Preliminary Study on the Accuracy of MRI-Guided Thalamic Infusion of AAV2-GFP and Biodistribution Analysis Using Cryo-Fluorescence Tomography in Nonhuman Primates" Pharmaceutics 17, no. 9: 1167. https://doi.org/10.3390/pharmaceutics17091167
APA StyleSalegio, E. A., Espinosa, R., Smith, G. R., Shoshan, D., Silva, M., White, E., & McDonald, J. (2025). A Preliminary Study on the Accuracy of MRI-Guided Thalamic Infusion of AAV2-GFP and Biodistribution Analysis Using Cryo-Fluorescence Tomography in Nonhuman Primates. Pharmaceutics, 17(9), 1167. https://doi.org/10.3390/pharmaceutics17091167