Development of a novel frameless skull-mounted ball-joint guide array for use in image-guided neurosurgery

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Successful convection-enhanced delivery of therapeutic agents to subcortical brain structures requires accurate cannula placement. Stereotactic guiding devices have been developed to accurately target brain nuclei. However, technologies remain limited by a lack of MRI compatibility, or by devices’ size, making them suboptimal for direct gene delivery to brain parenchyma. The goal of this study was to validate the accuracy of a novel frameless skull-mounted ball-joint guide array (BJGA) in targeting the nonhuman primate (NHP) brain.


Fifteen MRI-guided cannula insertions were performed on 9 NHPs, each targeting the putamen. Optimal trajectories were planned on a standard MRI console using 3D multiplanar baseline images. After cannula insertion, the intended trajectory was compared to the final trajectory to assess deviation (euclidean error) of the cannula tip.


The average cannula tip deviation was 1.18 ± 0.60 mm (mean ± SD) as measured by 2 independent reviewers. Topological analysis showed a superior, posterior, and rightward directional bias, and the intra- and interclass correlation coefficients were > 0.85, indicating valid and reliable intra- and interobserver evaluation.


The data demonstrate that the BJGA can be used to reliably target subcortical brain structures by using MRI guidance, with accuracy comparable to current frameless stereotactic systems. The size and versatility of the BJGA, combined with a streamlined workflow, allows for its potential applicability to a variety of intracranial neurosurgical procedures, and for greater flexibility in executing MRI-guided experiments within the NHP brain.

ABBREVIATIONS AC-PC = anterior commissure–posterior commissure; BJGA = ball-joint guide array; CED = convection-enhanced delivery; DICOM = Digital Imaging and Communications in Medicine; iMRI = intraoperative MRI; MPR = multiplanar reconstruction; NHP = nonhuman primate; PEEK = polyetheretherketone; T1W = T1-weighted.

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Article Information

Correspondence Krystof S. Bankiewicz: University of California, San Francisco, CA.

INCLUDE WHEN CITING Published online February 15, 2019; DOI: 10.3171/2018.10.JNS182169.

V.S. and A.M. contributed equally to this work.

Disclosures Drs. Bankiewicz and Kells report that they are inventors on a patent (WO2018044933A1) describing the BJGA. Dr. Kells was an employee of Voyager Therapeutics, a publicly traded company, and has direct stock ownership in that company. Drs. Kells and Fiandaca, as current employees of Brain Neurotherapy Bio, Inc., a private company, have direct stock ownership in that company.

© AANS, except where prohibited by US copyright law.



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    Schematics of the BJGA: measurements, implantation landmarks, and device assembly. A: Main parts and dimensions of the BJGA. The 3-hole ball array with adjustable side screw (black dot) is the core of the device, and guides the cannula to the targeted structure (1). The threaded skull-mounted base is secured onto the skull by 3 titanium fasteners (2). The knurled threaded locking collar interlocks with the base and secures the device in the desired position (3). B: Apical view of the ball array and the skull-mounted base with the most relevant measurements. C: Assembly of the BJGA with all parts. D: Another essential piece of the BJGA is the gadolinium-based fluid–filled guiding tubing that is placed inside the ball array during trajectory planning (1). As depicted in the cross-section diagram (2), this fiducial consists of a threaded cap (red arrowheads), a small chamber (blue arrowheads), and 3 PEEK tubes (green arrowheads) filled with a 2-mM solution of a gadolinium-based MR contrast agent. E: Representative T1W MR image of the BJGA and the fiducial tubes, demonstrating the gadolinium signal from the chamber and the tubing. The BJGA is not visible on MRI and has been contoured with dashed lines. Red arrowheads represent the threaded cap, blue arrowheads represent the gadolinium-filled chamber, and green arrowheads represent the PEEK tubes. F: Lateral view of the BJGA on an NHP skull model with the fiducials inserted in the ball. The maximum angulation of 16° is shown in red. G: Superior view of bilateral implantation of the BJGA on an NHP skull model with the fiducials inserted in the ball. The maximum angulation of 16° is shown in red. H: Posterior view of the BJGA with (right) and without (left) the locking collar. The maximum angulation of 16° is shown in red. I: Posterior view of an NHP skull with the skull-mounted base placed bilaterally. Relevant anatomical landmarks on the NHP skull model—the midline (black arrowheads) and the nuchal ridge (white arrowheads), are noted.

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    Workflow for the digital alignment of the fiducial’s gadolinium signal of the guiding device using the MPR toolbox. Before target selection and trajectory planning, the xyz planes must be oriented such that the entire fiducial length is visible in the MRI sequences. First, T1W MRI sequences were acquired, and a portion of the gadolinium-positive fiducial tubes was visualized (white arrowhead). Step 1: The x plane is oriented on top of the midline (axial); the z plane is oriented parallel to the AC-PC line (sagittal). Step 2: The crosshair (white circle) is placed on top of one of the fiducial signals (straight arrow), and the z plane is oriented to the fiducial signal (sagittal; curved arrow). Step 3: The x plane is rotated to align with the gadolinium signal in the axial plane (curved arrow). Small refinements can be done in the sagittal plane to correctly align the z plane to the fiducial signal. Step 4: The crosshair is located in the center of the fiducial tube in the coronal view. Numbers 1–3 label each of the 3 holes of the ball array.

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    Schematic workflow for appropriate BJGA manipulation to the selected target (i.e., putamen). Once the BJGA is mounted and secured on the skull, the array can be manually adjusted to target the selected structure. Initially, if the array is not targeting the structure (A, white arrowheads depict missing putamen) multiple adjustments in the medial-lateral and superior-inferior direction can be made until the trajectory targets the structure (B [left panel, white arrowhead], shows the trajectory medial to the putamen, and B [right panel, white arrowhead], shows the trajectory appropriately targeting the putamen). Once the trajectory is defined (C), the surgeon selects the appropriate access hole (D). The surgeon must then ensure that the trajectory is not proximal to sulci or ventricles, to avoid a potential large-vessel insult. If the trajectory is not satisfactory, the surgeon can manually adjust the BJGA to redefine the trajectory. Image (E) shows an example of suboptimal trajectory that crosses too close to a sulcus (white arrowhead). Image (F) shows how the previous trajectory is altered by superiorly adjusting the BJGA, and changing the entry hole from lateral to medial (insets, panels E and F). The new trajectory satisfies the safety check with regard to the sulcus (white arrowhead). The surgeon then measures the depth from the bottom of the gadolinium-filled chamber (white arrow) to the target point (i.e., putamen), subtracts 3 mm to account for the distance between the bottom of the chamber and the top of the BJGA (see Fig. 1D and 1E), and marks the distance on the cannula. A depth stop is placed at the target mark, the cannula is introduced through the selected entry hole to the target, and the cannula location is determined (G). If the cannula tip is in an optimal position, the infusion can begin (H).

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    Error magnitude analysis of the BJGA. A box-and-whisker plot of 180 error vector magnitudes shows a normal distribution (median = 1.10 mm, mean = 1.18 mm), with a minimum-maximum range of 0.06 mm and 2.58 mm, respectively, an interquartile range of 0.72–1.58 mm, and an SD of ± 0.60 mm.




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