MRI Compatibility: Device Patient Access to State-of-the-Art Diagnostics Brian Urke Vice President & Brady General Manager Medtronic CRDM My name is Brian Urke. I am the General Manger of our Pacemaker business at Medtronic and primarily work with Electrophysiologists and cardiologists. So why am I here speaking to neuromodulation clinicians about MRI compatible devices? Before I answer this question, let me start with a simple question for the audience: please raise your hand if you have had an MRI? And this audience looks to be rather fit and youthful! Now imagine an audience of pacemaker patients over 65 years of age. Access to MRI diagnostics is critical to maintain and improve patient health and my goal is to bring greater awareness to the challenges and opportunities related to the adoption of MRI Conditional devices.

4 Million Pacemaker Patients Worldwide- 50-75% will likely need an MRI* 70% of SCS patients will likely need an MRI over the average lifespan of an SCS device** Globally there are nearly 4 million people who live with a pacemaker. An estimated 50-75% of these patients will need access to MRI while living with their device. In speaking with my Neuro colleagues, 70% of spinal cord stim patients will likely need an MRI over the lifespan of their device. Until recently, “warning” signs like this one were common on the doors of MRI diagnostic labs. This sign boldly states: No Pacemakers, No Metallic Implants, No Neurostimulators. Still today, major barriers exist that make it difficult and risky for most device patients to receive an MRI. *Kalin R,Stanton MS. Current clinical issues for MRI scanning of pacemaker and defibrillator patients, PACE. April 2005;28(4):326-328 **MarketScan® Commercial Claims and Encounters Database, 2008. Data Compiled from Truven Health Analytics, Inc.

Clear Diagnostic Advantages of MRI As I said, I work with Electrophysiologists. Due to the nature of their sub-specialty, they rarely refer patients for an MRI. As neuromodulation clinicians, your reliance and understanding of the advantages of magnetic resonance imaging is broad and deep. You know first hand what MRI diagnostics can offer versus CT scans and other alternative diagnostic tools. This brings me to the reason why I am here. I want all device patients in the future to get the best diagnostic care available. Who understands the value of MRIs better than you do. You along with oncologists, radiologists, and others who rely heavily on this technology, are best able to advocate for the expanded utilization of new devices which enable access to MRI for those device patients who will need them in the future.

MRI Utilization Growing as Standard of Care 2000 2001 2002 Europe USA 2008 2009 2010 2003 2004 2005 2006 2007 Japan Rest of World # of MRI procedures (M) 10 20 30 40 50 60 70 80 90 100 110 +12% Arguably MRI is the best option for soft tissue differentiation. Over the past decade there’s been explosive growth in MRI utilization around the world. The percent of the population getting MRI scans annually is 6% in Europe, 9% in the US and 13% in Japan and still growing. % of Population Getting MRI Scans Annually: Japan: 13%, US: 9%, Europe: 6% Japanese Surgical Procedure Volumes 2007, USSPV07, Millennium Research Group OECD Health Data 2012, http://www.oecd.org/statistics/ The World Bank Data Catalog, http://data.worldbank.org/

Medtronic MRI Innovation Leadership Initiated Research MR Conditional Labeling for Pumps MR Conditional Labeling for Reveal ILR Revo MRI MR Conditional Pacemaker (US) 1997 1999 2001 2003 2005 2007 2009 2011 2013 MR Conditional Labeling for DBS EnRhythm MRI MR Conditional Pacemaker (EU) MR Conditional Labeling for InterStim With the growth in MRI use, Medtronic saw that MRI Access was a growing unmet need for patients. In 1997, we initiated extensive research and development leading to MR Conditional labeling for Deep Brain Stimulation devices in 2003, Pumps in 2004, and Spinal Cord Stim in 2005. In 2008, our first MRI pacemaker was approved in Europe. In 2011, Medtronic’s REVO MRI pacemaker became the first and is still the only FDA approved pacemaker for MRI use. In the near future, we hope to add to the list of neurological and cardiac devices approved for use in the MR environment. MR Conditional Labeling for SCS

MRI Environment: Powerful Fields Creating implantable devices that could be approved for safe use in the MRI environment was not a simple challenge. MRI machines are powerful to say the least… this picture shows a hospital bed that was accidently placed too close to an MRI machine.

MRI: A Complex Environment for Medical Devices Static Field Coil 30,000 x Earth’s magnetic field Gradient Coils Creates loud scanner noise Radio Frequency (RF) Coil 1000’s of watts peak power Our extensive research began with understanding how the multiple fields within and MRI machine work and could impact an implanted device and patient.

Ensuring Device System Safety We needed to both ensure patient safety and prevent damage to the device leading to undue surgical replacement. The most serious concern we identified was with device electrodes and leads. In an MRI, Lead wires can collect RF energy and dissipate it at uninsulated portions of the system which is primarily at the electrodes. Heating increases as dissipation area decreases. The electrodes don’t actually get hot and transfer the heat to the tissue as in traditional cooking, this is more like microwave cooking where the water molecules in the tissue are excited and generate the heat directly.

Rigorous Pre-Clinical MRI Research After arriving at solutions to mitigate lead heating, we created human body and leads path models to analyze device system safety in over 400,000 different lead / body combinations. We leveraged what we learned from pacemaker systems and applied it to Neuromodulation where similar models are being developed for neurostimulator configurations. Created Human body and Leads path models to analyze over 400,000 different lead / body combinations* 1*Medtronic Revo MRI FDA Panel Pack: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/ MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm204585.htm.

Awareness of the Need for MRI & MR Conditional Devices MRI provides critical insight that other diagnostics alternatives cannot match Broad demand and need for Device Patient access to MRI across healthcare specialties MR Conditional Devices offer FDA approved MRI access We now have neurological and cardiac device solutions available that allow for safe MRI access, yet awareness of the need for these MR Conditional Devices is still a big challenge. We need greater understanding across medical specialties that MRI provides critical insight that other diagnostic alternatives cannot match. That MRI demand is broad and growing, and MR Conditional Devices offer FDA approved MRI access for device patients who critically need access to this state-or-the art diagnostic tool.

Are MRI Conditional Devices only for a small subset of patients? In the cardiology world, MRI awareness is mixed. This may be different with your specialties. Cardiologists only provide 5% of the referrals for MRI so it is understandable that for many MRI conditional cardiac devices are seen as niche products and “not for everyone”… the reality is, most people will need an MRI at some point in their lives. 4RSNA research, radiologists. December 2008

Pacemaker Patient Demographics 13% Ages 25-64 86% Age 65+ Elderly patients are primary users of MRI: Those over age 65 are twice as likely to need an MRI compared to younger recipients.3 Cardiac pacemaker patients are the exact demographic that is most likely to need an MRI. Statistics show that those over the age 65 are twice as likely to need an MRI compared to younger recipients. 86% of pacemaker recipients are over 65. Neuro devices like pumps, spinal chord and deep brain stimulators, and gastro-uro devices, also tend to be heavily weighted to older populations. 3 Medtronic Revo MRI FDA Panel Pack: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/ MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm204585.htm.

Prevalence of Common Comorbidities Aging Patient Populations If we look at stroke, prostate cancer, osteoarthritis, and colorectal cancer you can see by this chart that the prevalence rate for these issues dramatically increases at age 65. All of these conditions rely heavily on MRI for proper diagnosis. 1 National Cancer Institute April 2009. US estimated complete prevalence (including counts) by age on 1/1/2006. Based on Nov. 2008 SEER data submission; DCCPS, Surveillance Research Program, Statistical Research and Applications Branch. 2 Lawrence RC, et al. Arthritis Rheum. 1998;41:778-799. 3 AHA. Heart Disease and Stroke Statistics – 2010 Update: Learn and Live. Prevalence of stroke by age and sex (NHANES: 2003-2006).

10% of patients with a Revo MRI device received an MR scan by 18 months post-implant1 Consistent with the statistical data I’ve shown, we used our CareLink remote monitoring system to view data on 11,062 of the early implants of our Revo MRI pacemaker in the US. 10.2% of the patients with a Revo MRI device had received an MR scan by 18 months post-implant. *Based on de-identified US CareLink® data from 11,062 devices implanted with two 5086MRI leads 1 Data on File, Nov 5, 2012

Ensuring Device Patients Have Access to the Overall Care They Need 15% 0 comorbidities 30% 1 comorbidity 28% 2 comorbidities 27% 3 or more comorbidities 85% 1 or more comorbidities* Opthalmology Neurosurgery Otolaryngology Neurology Cardiothoracic Surgery Oncology Surgical Oncology Radiation Oncology Neurological and cardiac device patients don’t just suffer from one health condition. 85% of pacemaker patients have one or more co-morbidities. Choosing a neurological or cardiac device for a patient should whenever possible also ensure that these device patients will have access to the overall diagnostic care they need in the future, no matter their health concern or co-morbidity. The more you as neuromodulation clinicians share your knowledge of the value of MRI diagnostics and the need for MRI access with other physician specialties, the more awareness and eventual access we will provide to patients tomorrow. Nephrology Interventional Radiology Gynecologic Oncology Gastrointestinal Surgery Urology Orthopedic Surgery Rheumatology Vascular Surgery *Kalin R, Stanton MS. PACE. 2005;28:326-328.

“Understanding the Potential Effects of MRI on Patients with Spinal Cord Stimulation Systems” Poster #244 Presented by Dr. Yair Safriel Neuroradiologist at Pharmascan, and University of South Florida, Clearwater, FL To learn more about patient safety and device interactions during MRI scans of spinal chord stimulation patients, please visit Dr. Safriel’s poster during the conference. Thank you for your time and attention.