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.).

All procedures involving animals were approved by the Institute for Animal Care and Use Committee at the University of Washington. A total of four adult male rhesus macaques (Macaca mulatta) were used in this study. At the time of MRI acquisition, monkey H was 7 years old, monkey L was 6 years old, monkey C was 8.5 years old, and monkey B was 5.5 years old. Monkeys H and L were implanted with custom chronic chambers at 9 years of age.
1. Skull and brain isolation (<strong class=...

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

<ol>
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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) ...

a-neural-implant-design-toolbox-for-nonhuman-primates

Research

JoVE Journal

Bioengineering

723 ビュー.  University of Washington. 私たちの研究は、脳と頭蓋骨のモデリングのための効率的で自動化された方法を提供し、脳神経外科の計画とカスタムインプラントの設計に有益です。単一のソフトウェアプラットフォームを使用して脳モデルと頭蓋骨モデルの同時抽出を容易にし、通勤断層撮影スキャンなどの追加のイメージングプロセスの必要性を排除します。近年、MRIやCTスキャンなどの医用画像...

ビデオ: 著者スポットライト:NHP研究における脳神経外科計画の強化のための脳と頭蓋骨の合理化モデリング

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...

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a mri-based toolbox for neurosurgical planning in nonhuman primates

A MRI-Based Toolbox for Neurosurgical Planning in Nonhuman Primates

The method outlined below aims to provide a comprehensive protocol for the preparation of nonhuman primate (NHP) neurosurgery using a novel combination of three-dimensional (3D) printing methods and MRI data...

visualizing the brain and craniotomized skull for virtual surgical planning

Visualizing the Brain and Craniotomized Skull for Virtual Surgical Planning

radiation planning assistant - a streamlined, fully automated radiotherapy treatment planning system

Radiation Planning Assistant - A Streamlined, Fully Automated Radiotherapy Treatment Planning System

Radiation therapy is a highly complex cancer treatment that requires multiple specialists to create a treatment plan and provide quality assurance (QA) prior to delivery to a patient. This protocol describes the use of a fully automated system, the Radiation Planning Assistant (RPA), to create high-quality radiation treatment...

orienteering as a tool for cognitive research: an implementation guide

Author Spotlight: Utilizing Orienteering in Research to Improve Brain Health and Spatial Memory

The sport of orienteering is emerging as an effective way to train both the body and brain as it combines physical activity with spatial navigation. The current manuscript offers a guide on how to implement the sport of orienteering in...

Implementing Orienteering for Body and Brain Training 

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radiation planning assistant - a web-based tool to support high-quality radiotherapy in clinics with limited resources

Author Spotlight: Improving Radiation Therapy Access with Radiation Planning Assistant

This protocol describes a series of automated tools designed for high-quality radiotherapy autocontouring and autoplanning that are being packaged into a web-based service to maximize robustness and scalability while minimizing operational...

Enhancing Radiotherapy with Web-Based Radiation Planning Assistant

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acupuncture treatment in a mouse model of chronic hypoxia-induced cognitive dysfunction

Author Spotlight: Improving Anesthesia Protocols for Enhanced Mouse Acupuncture Research

Here, we describe a protocol for implementing mild anesthesia and acupuncture treatment on a chronic hypoxia mouse model and conducting behavioral tests to assess the cognitive alterations post-treatment.

Cognitive Improvement in Chronic Hypoxia Mice with Acupuncture

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pioneering patient-specific approaches for precision surgery using imaging and virtual reality

Author Spotlight: Segmentation and VR for Advanced Neurovascular Interventions

Advancements in endovascular treatment have replaced complex open surgical procedures with minimally invasive options, like valve replacement and aneurysm repair. This paper proposes using three-dimensional (3D) modeling and virtual reality to aid in C-arm positioning, angle measurements, and roadmap generation for neuro-interventional catheterization lab procedural planning, minimizing procedure time.

Virtual Reality-3D Modeling for Minimally Invasive Neuro-Interventional Planning

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early unguided human brain organoid neurovascular niche modeling into the permissive chick embryo chorioallantoic membrane

Author Spotlight: Optimizing the Neurovascular Development of Human Brain Organoid in Chick Embryo

Here, we present a protocol to engraft human brain organoids at multiple maturation stages into the chick chorioallantoic membrane (CAM). Brain organoids were grown following unguided standardized protocols.

Grafting Human Brain Organoids into the Chorioallantoic Membrane of the Chick Embryo

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three-dimensional reconstruction for the whole lung with early multiple pulmonary nodules

Author Spotlight: Advancing 3D Modeling for Enhanced Diagnosis and Treatment of Pulmonary Nodules in Early-Stage Lung Cancer 

This study introduces a three-dimensional (3D) reconstruction method for the entire lung in patients with early multiple pulmonary nodules. It offers a comprehensive visualization of nodule distribution and their interplay with lung tissue, simplifying the assessment of diagnosis and prognosis for these...

Enhancing Pulmonary Nodule Diagnosis Using Whole-Lung 3D Reconstruction

advanced abdominal aortic aneurysm modeling in mice by combination of topical elastase and oral &#223;-aminopropionitrile

Author Spotlight: Enhanced Murine AAA Model Using Elastase to Mimic Human Aneurysms

This protocol describes a methodical surgical approach to modeling advanced abdominal aortic aneurysms in mice by a combination of directly applying elastase to the infrarenal aorta and administering &#223;-aminopropionitrile through drinking water.

Abdominal Aortic Aneurysm Development in Mice Using the Elastase and BAPN Method

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generating and analyzing high-parameter histology images with histoflow cytometry

Author Spotlight: Enhanced Multiplex Immunofluorescent Microscopy Protocol for Neuroscience Research

Described here is a method that can be used to image five or more fluorescent parameters by immunofluorescent microscopy. An analysis pipeline for extracting single cells from these images and conducting single-cell analysis through flow cytometry-like gating strategies is outlined, which can identify cell subsets in tissue...

Immunofluorescent Microscopy and Analysis for High-Parameter Tissue Imaging

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enhancing density maps by removing the majority of particles in single particle cryogenic electron microscopy final stacks

Author Spotlight: Optimizing Cryo-EM Analysis with CryoSieve for Enhanced Particle Selection Efficiency

An advanced particle selection method for cryo-EM, namely CryoSieve, improves density map resolution by removing a majority of particles in final stacks, as demonstrated through its application on a real-world...

Enhancing Cryo-EM Map Quality with CryoSieve Particle Selection

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vr modeling using patient-specific segment anatomy for precision fluoroscopy planning

VR Modeling Using Patient-Specific Segment Anatomy for Precision Fluoroscopy Planning

isolating immune cells from mouse brain and skull

Author Spotlight: Investigating the Complex Immune Response Following Brain Ischemia

To investigate the immune response to brain disorders, one common approach is to analyze changes in immune cells. Here, two simple and effective protocols are provided for isolating immune cells from murine brain tissue and skull bone...

Isolating Immune Cells from Mouse Brain and Skull

two-photon calcium imaging of forebrain activity in behaving adult zebrafish

Author Spotlight: Advancements in Adult Zebrafish Brain Research 

Here, we present a protocol to perform two-photon calcium imaging in the dorsal forebrain of adult...

Behavior Tracking and Neural Activity Pattern in the Zebrafish Forebrain

combining imaging and electrophysiology to visualize and record spreading depolarizations in mice

Author Spotlight: Deciphering the Connection Between Spreading Depolarizations and Mild Traumatic Brain Injuries

This protocol demonstrates the combination of imaging and electrophysiology to reliably detect spreading depolarizations in adult mice following a mild traumatic brain...

Detecting Spreading Depolarization Using AC Amplifiers and Non-Invasive Imaging

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exposure of the pig cns for histological analysis: a manual for decapitation, skull opening, and brain removal

Exposure of the Pig CNS for Histological Analysis: A Manual for Decapitation, Skull Opening, and Brain Removal

The goal of this paper and instructional video is to describe how to expose and remove the postmortem pig brain and pituitary gland in an intact state, suitable for subsequent macroscopic and histological...

hand-rearing method for infant marmosets

Author Spotlight: Marmoset Research - Scope and Challenges 

Here, we describe a hand-rearing method for raising infant marmosets in an animal incubator. This method greatly increases the survival rate of marmoset infants, which provides the opportunity to study the development of marmoset infants with similar genetic backgrounds raised in different postnatal...

Enhancing Survival and Development of Marmosets Using a Hand-Rearing Approach

isolation of primary porcine retinal pigment epithelial cells for in vitro modeling

Author Spotlight: Modeling Retinal Pathologies with Enhanced RPE Cell-Based Disease Models

This protocol outlines the procedure for obtaining and culturing primary retinal pigment epithelial (RPE) cells from locally sourced porcine eyes. These cells serve as a high-quality alternative to stem cells and are suitable for in vitro retinal...