1. Brain MRI in patients with VNS Optimizing safety and image quality Eliana Bonfante MD Rajan Patel MD Elliott Friedman MD Roy Riascos MD Control #: 1692 eEdE#: eEdE-20

2. NO DISCLOSURE

3. Epilepsy is a common neurologic disease Epilepsy is the fourth most common neurologic disorder in the United States and Europe. According to the WHO, the estimated worldwide prevalence of epilepsy is 50 million people. One in 26 people will develop epilepsy during their lifetime.

4. Epilepsy treatment--medical Goal of epilepsy therapy is for patients to be free of seizures and medication side effects. 60-70% of patients with newly diagnosed epilepsy will enter remission with antiepileptic drugs. Pharmacoresistant epilepsy is defined as failure of seizures to respond to at least two appropriately chosen medications for a sufficient period of time.

5. Pharmacoresistant epilepsy Patients with pharmacoresistant epilepsy are more likely to have an underlying structural lesion. Seizure freedom requires complete resection of the entire epileptogenic zone. Vagal nerve stimulator implantation is an alternative therapy in patients with pharmacoresistant epilepsy who are not candidates for epilepsy surgery or who continue to seize after surgery.

6. Vagus nerve stimulation (VNS) VNS was approved by the US FDA in 1997 as an adjunctive treatment for medically refractory epilepsy. Considered for use in: – Poor candidates for resection – Resection has failed – VNS was approved only for adults and adolescents with partial epilepsy – Its efficacy in children and in patients with generalized epilepsy remains unclear.

7. Vagus nerve stimulation (VNS) Meta-analysis of VNS efficacy in epilepsy – 74 clinical studies with 3321 patients suffering from intractable epilepsy. – 3 blinded, randomized controlled trials (Class I evidence) – 2 nonblinded, randomized controlled trials (Class II evidence) – 10 prospective studies (Class III evidence) – numerous retrospective studies. After VNS: – Seizure frequency was reduced by an average of 45% – Patients with generalized epilepsy and children benefited significantly from VNS – Posttraumatic epilepsy and tuberous sclerosis were positive predictors of a favorable outcome. Englot et al. Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. J Neurosurg 2011 Dec;115(6):1248-55

8. Vagus nerve stimulation (VNS) Review of 20 selected publications between 1980 and 2010 in pediatric and adult population. – 2 articles provided Class I evidence – 7 articles met criteria for Class II evidence – 11 articles provided Class III evidence The majority of evidence supports VNS usage in partial epilepsy with a seizure reduction of 50% or more in the majority of cases and freedom from seizure in 6%-27% of patients who responded to stimulation. Predictors of positive response included absence of bilateral interictal epileptiform activity and cortical malformations. Connor et al. Vagal nerve stimulation for the treatment of medically refractory epilepsy: a review of the current literature. Neurosurg Focus 2012 Mar;32(3):E12.

9. Epilepsy imaging Epilepsy imaging is preferred on a 3T system over 1.5T when medically feasible, due to improved resolution of subtle abnormalities and higher signal to noise ratio (SNR) MRI at 3T results in higher specific absorption rate (SAR), which is a measure of the rate at which energy is absorbed by the human body when exposed to a radio frequency (RF) electromagnetic field, resulting in increased the risk of heating.

10. VNS system components A.VNS Therapy lead: electrodes and anchor tethered to the left vagus nerve. B.VNS Therapy pulse generator (single receptacle or dual receptacle) implanted in a pocket in the chest wall.

11. VNS system components

12. VNS system operation The pulse generator is programmed using Cyberonics provided software on a laptop or handheld computer dedicated only to programming the VNS Therapy System. A programming wand connected to a compatible computer running the programming software is needed to communicate with the pulse generator. A magnet can be used for one-way communication to the pulse generator by activating a reed switch in the electronic circuitry. The magnet can be used to initiate stimulation, temporarily inhibit stimulation, perform Magnet Mode diagnostics, and reset the pulse generator. Both the Wand and the Magnet are MR unsafe devices that can not enter the MRI environment.

13. VNS modes of operation Normal mode Magnet Mode – Patients with epilepsy or their caregivers pass the magnet over the implanted pulse generator to activate on-demand delivery of a single train of vagus nerve stimulation and help abort or diminish a seizure. – Magnet Mode is not used for patients with depression.

14. MRI with the VNS VNS Therapy System is an MR Conditional device Potential risks: Heating effects around the VNS Therapy System, especially electrodes, from RF energy Non-significant levels of current induced through the VNS lead wire by the time-varying gradient level Inadvertent device reset, which erases historical information stored on the device (possibly including device serial number) Inadvertent Magnet Mode activation (i.e., brief magnet application and removal, which initiates a stimulation) from magnetic fields Image distortion and artifacts Magnetic field interactions Device malfunction or damage Hazards from Cyberonics magnets (not implanted) in the vicinity of the MRI scan room VNS Therapy® System Physician’s Manual Cyberonics, Oct 2014

15. Imaging patients with VNS INTACT VNS Do not use the transmit RF body coil for 3T or 1.5T imaging. Not all head RF coils are transmit and receive type. Open MRI scanners or systems other than 1.5T and 3T should not be used for scanning VNS patients. EXPLANTED VNS Surgical removal of the VNS Therapy System will be required if – MRI using a transmit RF body coil is needed. – An MRI of the exclusion zone is needed. – An MRI of the brain with multichannel coil is needed.

16. MRI with intact VNS The VNS Therapy System can be scanned safely immediately after placement under the following conditions: Static magnetic field of 1.5T or 3T only Spatial gradient field of 720 Gauss/cm or less Normal operating mode only Use only head or local transmit/receive coils. In non-clinical testing using a head transmit coil, the VNS Therapy System produced a maximum temperature rise of less than 2°C at a maximum head-averaged specific absorption rate (SAR) of 3.2 W/kg, which was determined by a validated calculation for 15 minutes of MRI scanning in a 1.5T or 3T scanner. Safety has not been demonstrated in patients with implanted devices in addition to VNS Therapy. VNS Therapy® System Physician’s Manual Cyberonics, Oct 2014

17. MRI with intact VNS Exclusion zoneClinical implications: MRI of the cervical spine, neck, thoracic spine and chest are contraindicated. Protocols for MRI of included areas are limited to the use of a Transmit/Receive coil.

18. Protocol optimization for MRI with intact VNS In order to maintain a safe SAR, Gorni et al propose to divide the series into two or three acquisitions (each with a reduced number of slices), depending on patient weight and desired spatial coverage. The multiple image acquisitions (e.g., the three parts of the T1-FLAIR) were retrospectively bound into a single series for presentation in PACS. PROPELLER T2 imaging can replace the axial FSE on patients who were prone to movement during the exam. Gorni et al. 3 Tesla MRI of Patients With a Vagus Nerve Stimulator: Initial Experience Using a T/R Head Coil Under Controlled Conditions. J. Magn. Reson. Imaging 2010;31:475–481.

19. MRI with intact VNS High resolution T1 and T2WI acquired at 3T with single channel head coil in a patient with intact VNS

20. Removal of the VNS system If removal is medically necessary, Cyberonics recommends removing as much of the VNS Therapy System as can be safely accomplished: Assess the degree of fibrotic in- growth in and around the helices. Remove the entire system, if possible. If fibrotic encapsulation hinders safe removal of the entire system, transect as much of the lead wire as possible. Removal of the pulse generator alone does not alter the hazards associated with certain MRI procedures.

21. MRI with PARTIALLY explanted VNS MRI can be performed safely under the following conditions: 1.5T or 3T with T/R Head Coil or T/R Extremity Coil If there is a suspected lead break (IPG is still connected) If any length (43 cm or less) remains (no IPG)

22. Partially explanted VNS Although the generator has been removed, the wires are still in place. Therefore only TR coils can be used.

23. MRI with explanted VNS MRI can be performed safely under the following conditions: 1.5T or 3T with transmission of RF with the Body Coil (any landmark) If there is ≤2 cm of lead (i.e., electrodes remain implanted)

24. CONCLUSION Brain MRI with an intact VNS can be safely performed at 1.5 and 3T using only T/R head single channel coil, with protocols that maintain a low SAR. Patients with partially explanted VNS with long remaining wires and patients with fractured wires are scanned with the same protocol of an intact VNS. Patients with explanted VNS with less than 2 cm remaining wires can be scanned with 1.5T or 3T with transmission of RF with the Body Coil.

25. References 1.Benbadis, S. R. et al. MRI of the brain is safe in patients implanted with the vagus nerve stimulator. Seizure 2001;10:512–515 2.de Jonge, J. C., Melis, G. I., Gebbink, T. A., de Kort, G. A. P. & Leijten, F. S. S. Safety of a dedicated brain MRI protocol in patients with a vagus nerve stimulator. Epilepsia 2014;55:e112– 115 3.Gorny, K. R., Bernstein, M. A. & Watson, R. E. 3 Tesla MRI of patients with a vagus nerve stimulator: initial experience using a T/R head coil under controlled conditions. J. Magn. Reson. Imaging JMRI 2010;31:475–481 4.Rezai, A. R. et al. Neurostimulation system used for deep brain stimulation (DBS): MR safety issues and implications of failing to follow safety recommendations. Invest. Radiol. 2004;39:300– 303 5.Englot, D. J., Chang, E. F. & Auguste, K. I. Vagus nerve stimulation for epilepsy: a metaanalysis of efficacy and predictors of response. J. Neurosurg. 2011;115:1248–1255