OBJECTIVE Stereotactic deep brain stimulation surgery is most commonly performed while patients are awake. This allows for intraoperative clinical assessment and electrophysiological target verification, thereby promoting favorable outcomes with few side effects. Intraoperative CT and MRI have challenged this concept of clinical treatment validation. Image-guided surgery is capable of delivering electrodes precisely to a planned, stereotactic target; however, these methods can be limited by low anatomical resolution even with sophisticated MRI modalities. The authors are developing a novel method using convection-enhanced delivery to safely manipulate the extracellular space surrounding common anatomical targets for surgery. By altering the extracellular content of deep subcortical structures and their associated white matter tracts, the MRI visualization of the basal ganglia can be improved to better define the anatomy. This technique could greatly improve the accuracy and success of stereotactic surgery, potentially eliminating the reliance on awake surgery. METHODS Observations were made in the clinical setting where vasogenic and cytotoxic edema improved the MRI visualization of the basal ganglia. These findings were replicated in the experimental setting using an FDA-approved intracerebral catheter that was stereotactically inserted into the thalamus or basal ganglia of 7 swine. Five swine were infused with normal saline, and 2 were infused with autologous CSF. Flow rates varied between 1 μl/min to 6 μl/min to achieve convective distributions. Concurrent MRI was performed at 15-minute intervals to monitor the volume of infusion and observe the imaging changes of the deep subcortical structures. The animals were then clinically observed, and necropsy was performed within 48 hours, 1 week, or 1 month for histological analysis. RESULTS In all animals, the white matter tracts became hyperintense on T2-weighted imaging as compared with basal ganglia nuclei, enabling better definition of the deep brain anatomy. The volume of distribution and infusion (Vd/Vi ratio) ranged from 2.5 to 4.5. There were no observed clinical effects from the infusions. Histological analysis demonstrated mild neuronal effects from saline infusions but no effects from CSF infusions. CONCLUSIONS This work provides the initial foundation for a novel approach to improve the visualization of deep brain anatomy during MRI-guided, stereotactic procedures. Convective infusions of CSF alter the extracellular fluid content of the brain for improved MRI without evidence of clinical or toxic effects.
Keywords: CED = convection-enhanced delivery; DBS = deep brain stimulation; MER = microelectrode recording; MRI; MW = molecular weight; STN = subthalamic nuclei; UPDRS = Unified Parkinson's Disease Rating Scale; Vd = volume of distribution; Vi = volume of infusion; basal ganglia; convection-enhanced delivery; functional neurosurgery; image-guided; stereotactic neurosurgery.