An ovine model of cerebral catheter venography for implantation of an endovascular neural interface

Abstract

OBJECTIVE Neural interface technology may enable the development of novel therapies to treat neurological conditions, including motor prostheses for spinal cord injury. Intracranial neural interfaces currently require a craniotomy to achieve implantation and may result in chronic tissue inflammation. Novel approaches are required that achieve less invasive implantation methods while maintaining high spatial resolution. An endovascular stent electrode array avoids direct brain trauma and is able to record electrocorticography in local cortical tissue from within the venous vasculature. The motor area in sheep runs in a parasagittal plane immediately adjacent to the superior sagittal sinus (SSS). The authors aimed to develop a sheep model of cerebral venography that would enable validation of an endovascular neural interface. METHODS Cerebral catheter venography was performed in 39 consecutive sheep. Contrast-enhanced MRI of the brain was performed on 13 animals. Multiple telescoping coaxial catheter systems were assessed to determine the largest wide-bore delivery catheter that could be delivered into the anterior SSS. Measurements of SSS diameter and distance from the motor area were taken. The location of the motor area was determined in relation to lateral and superior projections of digital subtraction venography images and confirmed on MRI. RESULTS The venous pathway from the common jugular vein (7.4 mm) to the anterior SSS (1.2 mm) was technically challenging to selectively catheterize. The SSS coursed immediately adjacent to the motor cortex (< 1 mm) for a length of 40 mm, or the anterior half of the SSS. Attempted access with 5-Fr and 6-Fr delivery catheters was associated with longer procedure times and higher complication rates. A 4-Fr catheter (internal lumen diameter 1.1 mm) was successful in accessing the SSS in 100% of cases with no associated complications. Complications included procedure-related venous dissection in two major areas: the torcular herophili, and the anterior formation of the SSS. The bifurcation of the cruciate sulcal veins with the SSS was a reliable predictor of the commencement of the motor area. CONCLUSIONS The ovine model for cerebral catheter venography has generalizability to the human cerebral venous system in relation to motor cortex location. This novel model may facilitate the development of the novel field of endovascular neural interfaces that may include preclinical investigations for cortical recording applications such as paralysis and epilepsy, as well as other potential applications in neuromodulation.

Endovascular Neuromodulation: Safety Profile and Future Directions

“…The SSS in sheep was chosen as an initial target primarily because of its ease of access through catheter venography and its parallel orientation to the ovine motor area. Furthermore, it has a diameter of 1.2 to 2.4 mm (37), which is comparable to the diameter of the human CSV (2.3 to 4.9 mm) (14). The CSV is the ideal corresponding target in humans because it is adjacent and parallel to the coronally orientated primary motor cortex in the human brain.…”

“…These may have been secondary to a longer procedure time associated with the 6 F catheter. Somewhat reassuringly, all catheterisations performed with the 2 and 4 F catheters were uncomplicated, suggesting that a small diameter catheter is favored for navigation into the anterior SSS for successful Stentrode TM deployment (37).…”

“…For any novel biomedical device, rigorous animal testing is a necessary precursor to human trials. Whilst proof of concept for the Stentrode TM currently only exists in ovine models (14,15,23,37), these experiments provide important insights into the safety characteristics of the device.…”

“…The CSV is the ideal corresponding target in humans because it is adjacent and parallel to the coronally orientated primary motor cortex in the human brain. However, unlike the SSS, it lacks a dural wall which may have significant implications for stent safety and electrode incorporation into the vessel wall (37). Additionally, the clinical endpoints measured in the sheep model were limited to gross motor function.…”

The future potential of the Stentrode

“…Neuromodulation or stimulation of the brain has offered life-changing treatments for people with neurological conditions such as Parkinson's disease and epilepsy, usually by deep-brain stimulation. Using the venous approach, the Stentrode TM can reach prefrontal brain regions, motor and somatosensory regions, and parietal regions adjacent to the interhemispheric fissure [1,10]. Although more challenging, an intravascular device like the Stentrode TM may potentially reach the thalamus, fornix, nucleus accumbens, subgenual cingulate white matter, and ventral capsule [11].…”