We would like to thank Toni Haun, Keith Vogel and Shawn Fisher for their technical help and support. This work was supported by the University of Washington Mary Gates Endowment (R.I.), National Institute of Health NIH 5R01NS116464 (T.B., A.Y.), NIH R01 NS119395 (D.J.G., A.Y), the Washington National Primate Research Center (WaNPRC, NIH P51 OD010425, U42 OD011123), the Center for Neurotechnology (EEC-1028725, Z.A., D.J.G.) and Weill Neurohub (Z. I.).

Automated 3D Brain and Skull Modeling from MRI for NHP Neurosurgical Planning

<ol>
	<li>Mitchell, A. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continued+need+for+nonhuman+primate+neuroscience+research.">Continued need for nonhuman primate neuroscience research.</a> Current Biology. 28 (20), R1186-R1187 (2018).</li><li>Stanis, N., Khateeb, K., Zhou, J., Wang, R. K., Yazdan-Shahmorad, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Protocol+to+study+ischemic+stroke+by+photothrombotic+lesioning+in+the+cortex+of+nonhuman+primates.">Protocol to study ischemic stroke by photothrombotic lesioning in the cortex of nonhuman primates.</a> STAR Protocols. 4 (3), 102496 (2023).</li><li>Tremblay, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+open+resource+for+nonhuman+primate+optogenetics.">An open resource for nonhuman primate optogenetics.</a> Neuron. 108 (6), 1075-1090 (2020).</li><li>Zhou, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroprotective+effects+of+electrical+stimulation+following+ischemic+stroke+in+nonhuman+primates.">Neuroprotective effects of electrical stimulation following ischemic stroke in nonhuman primates.</a> 2022 44th Annual International Conference of the IEEE Engineering in Medicine &amp; Biology Society (EMBC). 2022, 3085-3088 (2022).</li><li>Yao, Z., Yazdan-Shahmorad, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+quantitative+model+for+estimating+the+scale+of+photochemically+induced+ischemic+stroke.">A quantitative model for estimating the scale of photochemically induced ischemic stroke.</a> 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). 2018, 2744-2747 (2018).</li><li>Yazdan-Shahmorad, A., Silversmith, D. B., Kharazia, V., Sabes, P. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Targeted+cortical+reorganization+using+optogenetics+in+nonhuman+primates.">Targeted cortical reorganization using optogenetics in nonhuman primates.</a> eLife. 7, e31034 (2018).</li><li>Macknik, S. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advanced+circuit+and+cellular+imaging+methods+in+nonhuman+primates.">Advanced circuit and cellular imaging methods in nonhuman primates.</a> The Journal of Neuroscience. 39 (42), 8267-8274 (2019).</li><li>Griggs, D. J., Belloir, T., Yazdan-Shahmorad, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Large-scale+neural+interfaces+for+optogenetic+actuators+and+sensors+in+non-human+primates.">Large-scale neural interfaces for optogenetic actuators and sensors in non-human primates.</a> SPIE BiOS. , (2021).</li><li>Yazdan-Shahmorad, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Large-scale+interface+for+optogenetic+stimulation+and+recording+in+nonhuman+primates.">A Large-scale interface for optogenetic stimulation and recording in nonhuman primates.</a> Neuron. 89 (5), 927-939 (2016).</li><li>Ruiz, O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optogenetics+through+windows+on+the+brain+in+the+nonhuman+primate.">Optogenetics through windows on the brain in the nonhuman primate.</a> Journal of Neurophysiology. 110 (6), 1455-1467 (2013).</li><li>Griggs, D. 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J., Khateeb, K., Zhou, J., Liu, T., Wang, R., Yazdan-Shahmorad, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multi-modal+artificial+dura+for+simultaneous+large-scale+optical+access+and+large-scale+electrophysiology+in+nonhuman+primate+cortex.">Multi-modal artificial dura for simultaneous large-scale optical access and large-scale electrophysiology in nonhuman primate cortex.</a> Journal of Neural Engineering. 18 (5), 055006 (2021).</li><li>Belloir, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Large-scale+multimodal+surface+neural+interfaces+for+primates.">Large-scale multimodal surface neural interfaces for primates.</a> iScience. 26 (1), 105866 (2023).</li><li>Khateeb, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+practical+method+for+creating+targeted+focal+ischemic+stroke+in+the+cortex+of+nonhuman+primates.">A practical method for creating targeted focal ischemic stroke in the cortex of nonhuman primates.</a> 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). , 3515-3518 (2019).</li><li>Griggs, D., Belloir, T., Zhou, J., Yazdan-Shahmorad, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convection+Enhanced+Delivery+of+Viral+Vectors.">Convection Enhanced Delivery of Viral Vectors.</a> Vectorology for Optogenetics and Chemogenetics. , (2023).</li><li>Khateeb, K., Griggs, D. 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R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=3D+printing+and+modelling+of+customized+implants+and+surgical+guides+for+nonhuman+primates.">3D printing and modelling of customized implants and surgical guides for nonhuman primates.</a> Journal of Neuroscience Methods. 286, 38-55 (2017).</li><li>Prescott, M. J., Poirier, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+MRI+in+applying+the+3Rs+to+nonhuman+primate+neuroscience.">The role of MRI in applying the 3Rs to nonhuman primate neuroscience.</a> NeuroImage. 225, 117521 (2021).</li><li>Basso, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Using+non-invasive+neuroimaging+to+enhance+the+care,+well-being+and+experimental+outcomes+of+laboratory+nonhuman+primates+(monkeys).">Using non-invasive neuroimaging to enhance the care, well-being and experimental outcomes of laboratory nonhuman primates (monkeys).</a> NeuroImage. 228, 117667 (2021).</li><li>Ahmed, Z., Agha, N., Trunk, A., Berger, M., Gail, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Universal+guide+for+skull+extraction+and+custom-fitting+of+implants+to+continuous+and+discontinuous+skulls.">Universal guide for skull extraction and custom-fitting of implants to continuous and discontinuous skulls.</a> eNeuro. 9 (3), (2022).</li><li>Blonde, J. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Customizable+cap+implants+for+neurophysiological+experimentation.">Customizable cap implants for neurophysiological experimentation.</a> Journal of Neuroscience Methods. 304, 103-117 (2018).</li><li>Ojemann, W. K. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+MRI-based+toolbox+for+neurosurgical+planning+in+nonhuman+primates.">A MRI-based toolbox for neurosurgical planning in nonhuman primates.</a> Journal of Visualized Experiments. (161), e61098 (2020).</li><li>Make STL of 3D array (Optimal for 3D printing). MathWorks Available from: <a target="_blank" href="https://www.mathworks.com/matlabcentral/fileexchange/68794-make-stl-of-3d-array-optimal-for-3d-printing">https://www.mathworks.com/matlabcentral/fileexchange/68794-make-stl-of-3d-array-optimal-for-3d-printing</a> (2018)</li><li>. stlwrite - Write binary or ascii STL file Available from: <a target="_blank" href="https://www.mathworks.com/matlabcentral/fileexchange/36770-stlwrite-write-binary-or-ascii-stl-file">https://www.mathworks.com/matlabcentral/fileexchange/36770-stlwrite-write-binary-or-ascii-stl-file</a> (2023)</li><li>Michikawa, T., Suzuki, H., Moriguchi, M., Ogihara, N., Kondo, O., Kobayashi, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automatic+extraction+of+endocranial+surfaces+from+CT+images+of+crania.">Automatic extraction of endocranial surfaces from CT images of crania.</a> PLoS One. 12 (4), 0168516 (2017).</li><li>Overton, J. A., Cooke, D. F., Goldring, A. B., Lucero, S. A., Weatherford, C., Recanzone, G. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+methods+for+acrylic-free+implants+in+nonhuman+primates+for+neuroscience+research.">Improved methods for acrylic-free implants in nonhuman primates for neuroscience research.</a> Journal of Neurophysiology. 118 (6), 3252-3270 (2017).</li><li>Ortiz-Rios, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+methods+for+MRI-compatible+implants+in+nonhuman+primates.">Improved methods for MRI-compatible implants in nonhuman primates.</a> Journal of Neuroscience Methods. 308, 377-389 (2018).</li></ol>

Nothing to disclose.

This paper outlines a straightforward and precise method of neurosurgical planning that is not only beneficial for the development of components used for NHP cranial window implantation but also transferrable to other areas of NHP neuroscience research13,15,25. In comparison to other current methods of NHP implant planning and design25,29,30<...

Nonhuman primates (NHPs) are invaluable models for translational medical research because they are evolutionarily and behaviorally similar to humans. NHPs have gained particular importance in neural engineering preclinical studies because their brains are highly relevant models of neural function and dysfunction1,2,3,4,5,6,7,8. Some powerful brain stimulation and recording techniques, such as optogenetics, calcium imaging, and others, are best served with direct access to the brain through cranial windows9,10,11,12,13,14,15,16,17,18,19,20,21,22,23. In NHPs, cranial windows are often achieved with a chamber and an artificial dura to protect the brain and support long-term experimentation8,10,12,17,18,24,25,26,27. Likewise, headposts often accompany chambers to stabilize and align the head during experiments14,15,25,26,28,29,30. The effectiveness of these components is heavily dependent on how well they fit into the skull. A closer fit to the skull promotes bone integration and cranial health by decreasing the likelihood of infection, osteonecrosis, and implant instability31. Conventional design methods, such as manually bending the headpost during surgery25,29 and estimating the skull curvature by fitting circles to coronal and sagittal slices of magnetic resonance (MR) scans9,12 can introduce complications due to imprecision. Even the most precise of these create 1-2 mm gaps between the implant and the skull, providing space for granulation tissue to accumulate29. These gaps additionally introduce difficulty placing screws in surgery9, compromising the stability of the implant. Customized implants have more recently been developed to improve osseointegration and implant longevity9,29,30,32. Additional costs have accompanied advancements in custom implant design because of the reliance on computational models. The most accurate methods require sophisticated equipment such as computerized tomography (CT) machines in addition to MR Imaging (MRI) machines30,32,33 and&#160;even computer numerical control (CNC) milling machines for developing implant prototypes25,29,32,34. Gaining access to both MRI and CT, particularly for use with NHPs, may not be feasible for labs in need of custom-fitted implants like cranial chambers and headposts.
As a result, there is a need in the community for inexpensive, accurate, and non-invasive techniques of neurosurgical and experimental planning that facilitate the design and validation of implants prior to use. This paper describes a method of generating virtual 3D brain and skull representations from MR data for craniotomy location planning and the design of custom cranial chambers and headposts that fit the skull. This streamlined procedure provides a standardized design that can benefit experimental outcomes and the welfare of the research animals. Only MRI is required for this modeling because both bone and soft tissue are depicted in MRI. Instead of using a CNC milling machine, models can be 3D printed inexpensively, even when multiple iterations are required. This also allows for the final design to be 3D printed in biocompatible metals such as titanium for implantation. Additionally, we describe the fabrication of an artificial dura, which is placed inside the cranial chamber upon implantation. These components can be validated pre-surgically by fitting all parts onto a life-size, 3D-printed model of the skull and brain.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3D Printing Software (Simplify 3D) (Paid)</td>
			<td>Simplify3D</td>
			<td>Version 4.1</td>
			<td>Used for 3D printing using MakerGear printer</td>
		</tr>
		<tr>
			<td>C-Clamp</td>
			<td>Bessey</td>
			<td>CM22</td>
			<td>Used for artificial dura fabrication, 2-1/2 Inch Capacity, 1-3/8 Inch Throat</td>
		</tr>
		<tr>
			<td>Formlabs Form 3+ 3D Printer</td>
			<td>Formlabs</td>
			<td>Form 3+</td>
			<td>Used for precise 3D printing</td>
		</tr>
		<tr>
			<td>MakerGear M2 3D Printer</td>
			<td>MakerGear</td>
			<td>M2 revG</td>
			<td>Used for 3D printing implant prototypes</td>
		</tr>
		<tr>
			<td>MATLAB (Paid)</td>
			<td>MathWorks</td>
			<td>R2021b</td>
			<td>Used for brain and skull isolation, virtual craniotomy visualization and skull STL reduction</td>
		</tr>
		<tr>
			<td>Phillips Acheiva MRI System</td>
			<td>Philips</td>
			<td>4522 991 19391</td>
			<td>Used for non-human primate imaging</td>
		</tr>
		<tr>
			<td>Photopolymer Resin</td>
			<td>Formlabs</td>
			<td>FLGPGR04</td>
			<td>1L, Grey, used for precise 3D prints with Formlabs printer&#160;</td>
		</tr>
		<tr>
			<td>PreForm Print Preparation Software</td>
			<td>Formlabs</td>
			<td>Version 2.17.0</td>
			<td>Used for 3D printing with Formlabs printer&#160;</td>
		</tr>
		<tr>
			<td>Printing Filament (PLA)</td>
			<td>MatterHackers</td>
			<td>88331</td>
			<td>PLA 1.75 mm White. Used for 3D printing with MakerGear printer</td>
		</tr>
		<tr>
			<td>Silicone CAT-1300</td>
			<td>Shin-Etsu</td>
			<td></td>
			<td>Used for artificial dura fabrication</td>
		</tr>
		<tr>
			<td>Silicone KE1300-T</td>
			<td>Shin-Etsu</td>
			<td></td>
			<td>Used for artificial dura fabrication</td>
		</tr>
		<tr>
			<td>SolidWorks (Paid)</td>
			<td>Dassault Systems</td>
			<td>2020</td>
			<td>Used for chamber and headpost design</td>
		</tr>
		<tr>
			<td>Syn.Flex-S Multicoil</td>
			<td>Philips</td>
			<td>45221318123</td>
			<td>Used for non-human primate imaging</td>
		</tr>
	</tbody>
</table>

a neural implant design toolbox for nonhuman primates

This paper describes an in-house method of 3D brain and skull modeling from magnetic resonance imaging (MRI) tailored for nonhuman primate (NHP) neurosurgical planning. This automated, computational software-based technique provides an efficient way of extracting brain and skull features from MRI files as opposed to traditional manual extraction techniques using imaging software. Furthermore, the procedure provides a method for visualizing the brain and craniotomized skull together for intuitive, virtual surgical planning. This generates a drastic reduction in time and resources from those required by past work, which relied on iterative 3D printing. The skull modeling process creates a footprint that is exported into modeling software to design custom-fit cranial chambers and headposts for surgical implantation. Custom-fit surgical implants minimize gaps between the implant and the skull that could introduce complications, including infection or decreased stability. By implementing these pre-surgical steps, surgical and experimental complications are reduced. These techniques can be adapted for other surgical processes, facilitating more efficient and effective experimental planning for researchers and, potentially, neurosurgeons.

Author Spotlight: Streamlined Brain and Skull Modeling for Enhanced Neurosurgical Planning in NHP Research

A Neural Implant Design Toolbox for Nonhuman Primates

Our research offers an efficient and automated method for brain and skull modeling, which is beneficial for neurosurgical planning and designing custom implants. It facilitates a simultaneous extraction of brain and skull models using a single software platform, which eliminates a requirement for extra imaging processes like commuted tomography scans. Virtual brain and skull modeling for medical imaging such as MRI or CT scans has been increasingly adopted for NHP neurosurgical planning in recent years.These models, used alongside 3D design software and 3D printing, enable the creation of customized implants tailored to specific experiments and animals. Many non-human primate neuroscience experiments require the use of chronic cranial chambers and head posts. The use of generic implants introduces gaps between the implant and the skull, which can result in higher rates of infection, osteonecrosis, and implant instability, therefore compromising experiments and the wellbeing of the animal.Our custom implants reduce gaps and subsequent issues. Our protocol provides researchers with a more accurate and time-effective neurosurgical planning procedure. It increases surgical planning efficacy, and reduces complications associated with NHP neuroscience experiments, thus improving scientific results overall.

These components were previously validated using a combination of MRI visualizations and 3D-printed anatomical models. By comparing the automated craniotomy visualization to the 3D printed craniotomy and the MRI at the location of the craniotomy, it is evident that the virtual craniotomy representation accurately reflects the region of the brain that can be accessed with the specified craniotomy location (Figure 2A-F). Additi...

Watch this Scientific Journal Video about Streamlined Brain and Skull Modeling for Enhanced Neurosurgical Planning in NHP Research at JoVE.com

This paper outlines automated processes for nonhuman primate neurosurgical planning based on magnetic resonance imaging (MRI) scans. These techniques use procedural steps in programming and design platforms to support customized implant design for NHPs. The validity of each component can then be confirmed using three-dimensional (3D) printed life-size anatomical models.

This paper describes an in-house method of 3D brain and skull modeling from magnetic resonance imaging (MRI) tailored for nonhuman primate (NHP) ...

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Research

JoVE Journal

Bioengineering

Visualizing the Brain and Craniotomized Skull for Virtual Surgical Planning

823 Views.  University of Washington.  This paper outlines automated processes for nonhuman primate neurosurgical planning based on magnetic resonance imaging (MRI) scans. These techniques use procedural steps in programming and design platforms to support customized implant design for NHPs. The validity of each component can then be confirmed using three-dimensional (3D) printed life-size anatomical models.

Automated 3D Brain and Skull Modeling from MRI for NHP Neurosurgical Planning

Summary