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.

Practical Considerations of Convection Enhanced Delivery for Novel Therapies Treating Spinal Cord Injury Related Neuropathic Pain

“…CED-based in vitro, ex vivo and in vivo animal models have led to active genetherapy trials for treating Parkinson disease (PD)and are supported by histological studies on disease pathology [9].Use of MRI navigation in some clinical trials, helps accurately targeting and providing real time monitoring of viral vector delivery (rCED). Several researcher labs including ours adopted different small and large animal models exploring use of CED in brain [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. The results from these studies are promising with a suggestion of superiority over intrathecal (IT) injection.…”

Strategies for the Delivery of Multiple Collinear Infusion Clouds in Convection-Enhanced Delivery in the Treatment of Parkinson's Disease

“…This is a stepped ramp protocol in which infusion rate increases from 1.0 to 5.0 µl/min in 1.0-µl steps every 5 min over 25 min for a final infusion volume of 75 µl. Clinical trials have employed this same protocol [12,13]. …”

The Relation between Catheter Occlusion and Backflow during Intraparenchymal Cerebral Infusions

“…The surgical and targeting procedure was performed under isoflurane anesthesia following our previously published protocol [20]. The catheters were targeted to the ventral postcommissural right and left putamen, approximately 1–2 mm posterior to the coronal plane presenting the anterior commissure, and centered laterally at least 5 mm deep within the nucleus.…”

“…Catheters were targeted using an MRI compatible external trajectory guide (Navigus, Medtronic Inc., Minneapolis, Minn., USA) and a novel, real time intraoperative guidance system [21, 22], following a modified published protocol [20]. The animals were fasted for 12 hours prior to the surgery.…”

“…The MR-visible trajectory guide was adjusted to the correct location using real-time MRI guidance. The trajectory guide was then removed and replaced with a remote introducer, which was then used to insert the infusion catheter to the prescribed depth, as previously described [20]. …”