Intraoperative intracerebral MRI-guided navigation for accurate targeting in nonhuman primates

Abstract

During in vivo intracerebral infusions, the ability to perform accurate targeting towards a 3D-specific point allows control of the anatomical variable and identification of the effects of variations in other factors. Intraoperative MRI navigation systems are currently being used in the clinic, yet their use in nonhuman primates and MRI monitoring of intracerebral infusions has not been reported. In this study rhesus monkeys were placed in a MRI-compatible stereotaxic frame. T1 MRIs in the three planes were obtained in a 3.0T GE scanner to identify the target and plan the trajectory to ventral postcommisural putamen. A craniotomy was performed under sterile surgical conditions at the trajectory entry point. A modified MRI-compatible trajectory guide base (Medtronic Inc.) was secured above the cranial opening and the alignment stem applied. Scans were taken to define the position of the alignment stem. When the projection of the catheter in the three planes matched the desired trajectory to the target, the base was locked in position. A catheter replaced the alignment stem and was slowly introduced to the final target structure. Additional scans were performed to confirm trajectory and during the infusion of a solution of gadoteridol (ProHance, Bracco Diagnostics; 2 mM/L) and bromophenol blue (0.16 mg/ml) in saline. Monitoring of the pressure in the infusion lines was performed using pressure monitoring and infusion pump controller system (Engineering Resources Group Inc.) in combination with a MRI-compatible infusion pump (Harvard). MRI during infusion confirmed successful targeting and matched postmortem visualization of bromophenol blue. Assessment of the accuracy of the targeting revealed an overall 3D mean ± SD distance error of 1.2 ± 0.6 mm and angular distance error of 0.9 ± 0.5 mm. Our results in nonhuman primates confirm the accuracy of intraoperative MRI intracerebral navigation combined with an adaptable, pivot point-based targeting system and validates its use for preclinical intracerebral procedures.

Figure 1

Pictures depicting the intracerebral infusion system. (A) MRI-compatible trajectory guide. (B) Micromanipulator with alignment pin inserted in the alignment stem of the base. (C) Base with remote introducer and guiding insert in place. (D) Full system set up for intracerebral infusions.

Figure 2

Intraoperative baseline T1 MRI imaging of the brain of a rhesus monkey for planning catheter trajectory, co-corresponding to (A) sagittal, (B) axial, and (C) coronal plane based on selected target point (black dot in the postcommissural ventral putamen nucleus). Scale bar: 10.3 mm (A), 10.2 mm (B), 10.0 mm (C).

Figure 3

T1 MRI imaging of the brain of a rhesus monkey showing alignment stem (arrow) filled with degassed water inserted in the stem before catheter introduction in the (A) coronal and (B) sagittal planes. The target point is not visible in these scans due to the angled trajectory. Scale bar: 10.0 mm (A), 11.2 mm (B).

Figure 4

T1 MRI imaging of the brain of a rhesus monkey during insertion of infusion catheter to confirm trajectory and plan final depth of introduction (A, B, C) and final catheter placement (D, E, F). Arrow points to inserted catheter. Images of (A) sagittal, (B) axial, and (C) coronal plane are based on selected target point. Scale bar: 8.2 mm (A, D), 7.3 mm (B), 10.0 mm (C, F), 6.8 mm (E).

Figure 5

T1 MRI imaging of the brain of a rhesus monkey after completing the infusion in the (A) axial, (B) coronal, and (C) sagittal planes. (D) Gross anatomy image of a coronal view of a rhesus monkey brain showing the distribution of bromophenol blue in the target structure. Arrow indicates catheter end. Scale bar: 20.7 mm (A), 14.3 mm (B), 18.5 mm (C), 10.0 mm (D).

Figure 6

Overlapped T1 MRIs of the planned trajectory and actual catheter placement, for each of the reported cases. A red cross identifies the planned catheter tip location in the overlaid targeting MRIs. (A) Rh91070, right hemisphere; (B) Rh03044, left hemisphere; (C) Rh03044, right hemisphere; (D) Rh03064, left hemisphere; (E) Rh03064, right hemisphere. Scale bar: 10.0 mm.

Figure 7

Graph representing mediolateral (ML) and anteroposterior (AP) positioning differences (Euclidean angular distance) for each infusion. The center represents the target position.