Non-human primate (NHP) research has become an essential step in the translation of medical technologies from animal models to clinical trials. This is especially so in neural research, as there is a large discrepancy between rodent and human brains in both anatomy and size. For some techniques such as optogenetics, which requires viral transduction of neurons, traditional diffusion-based viral injection approaches are effective in rodent brains but are impractical for large NHP ones. Convection-enhanced delivery (CED), a large-scale injection approach, currently lacks a practical quantitative bench-side injection modeling method to guide neurosurgical preparation. We aim to develop a gel model of the NHP brain and replicate surgical injections of it in order to reduce the risks of directly injecting into a NHP without sufficient preparation. We are testing the validity of our model by monitoring the spread of the injection through the gel and comparing the data with those from MRI scans of the injections in NHP. Since CED can behave differently depending on the location of injection in the brain, we are testing bench-side injections at different depths to validate the versatility of our model. We are seeing that the injections in the gel model mirror that of the injections in NHP brains as expected. Our next steps are to test the effectiveness of smaller injection cannula sizes with our bench-side model to assess if injection results remain consistent. This would indicate that tissue damage could be minimized in surgeries while still achieving desired injection parameters.

Non-human primate (NHP) research is a pivotal step in the progression of neuroscientific and neural engineering research from animal models to human trials. In most NHP neuroscience experiments, neurosurgery is required to implant devices such as head posts, recording arrays, and optical windows. Current practices for these surgeries use methods for surgical preparation that carry a degree of unavoidable uncertainty. This comes from an inability to visualize and test the physical compatibility of complex components and anatomy prior to neurosurgery. This project details methods for creating 3D printed models of a subject’s brain and skull, as well as an agarose gel model of the brain. These models can be obtained from magnetic resonance imaging (MRI) using brain extraction software for the brain model, and custom code for the skull. The preparation protocol takes advantage of state-of-the-art 3D printing technology to combine models of the brain and skull with neuroprosthesis. With the addition of a craniotomy using the custom code, the skull and brain models can visualize brain tissue inside the skull, enabling better preparation for surgeries. Using the methods outlined in the protocol, the accuracy of the 3D printed brain, skull, and craniotomy placement were successfully validated through a comparison to the original MRI scan. The gel brain was additionally used to visualize delivery of a mock viral vector through the craniotomy of a skull model. By preoperatively fitting a headpost to the physical model of the skull, we successfully shortened the implantation surgery time by 40% and greatly reduced the risk of operative complications. These methods are designed for surgeries involving neurological stimulation and recording as well as injection in NHPs, but the versatility of the system allows for future expansion of the protocol, extraction techniques, and models to a wider scope of surgeries.