- MRI Safety Update - RF Induced Heating presented to Society for Medical Innovation and Technology 11-14 May 2006 Pebble Beach, Monterey, CA, USA Jeffrey L. Helfer

Objective of this Presentation Share with you a medical situation that is simultaneously very positive and potentially very dangerous Briefly describe several options for helping to manage the risks 2 •

Acknowledgements Robert Gray (Biophan Scientist) Andreas Melzer, M.D. (CTO - Biophan Germany) Xingwu Wang, Ph.D. (Alfred University) Susan Stalls (Biophan Program Manager) Mark Bocko, Ph.D. (University of Rochester) W. Timothy Bibens (Biophan Director of Operations) Stuart G. MacDonald (Biophan VP of R&D) Luxtron Corporation University Medical Imaging (Rochester, New York) 3 •

Background Information MRI is rapidly becoming a premiere non-invasive imaging modality due to the following capabilities: 1. Superb soft tissue contrast (greater detection sensitivity) 2. Functional analysis capabilities 3. No ionizing radiation to patients or healthcare providers 4. Very low toxicity of MRI contrast agents Significantly less allergenic than iodinated contrast agents Significantly less damage to kidneys (only for very high dosage) 5. Superior flow and temperature sensitivity 6. Multiplanar images and 3-D data sets without patient repositioning 4 •

Evidence of Growth in MRI ISMRM 14th Scientific Meeting 6-12 May 2006 Musculoskeletal Imaging Diffusion – Perfusion MRI Multi-modal Functional MRI MRI Contrast Agents Advanced Brain MRI Interventional MRI Hematobiliary MRI Molecular Imaging Functional Breast Imaging Functional Lung MRI Cellular Imaging MRI of Cancer Cartilage Imaging Psychiatric MRS-I MR Spectroscopy of the Brain Imaging of the Mother & Fetus Cardiovascular Imagingc Spinal Cord Imaging Degenerative Disease MRI Flow and Motion Quantitation Pediatric Brain MRI Quantitative Neuro MRI MRI Angiography Whole Body MRI Myocardial Functional Imaging Plus + 88 additional topics 5 •

Simultaneous Growth in Use of Implanted Medical Devices Cardiac Rhythm Management Gastric Simulation Bone Fusion Stimulation Orthopedic Implants Cochlear hearing implants Bladder Control Implantable (Automatic) Cardioversion-Defibrillation Neuromodulation Pain Management Drug Infusion Pumps Cardiac Resynchronization Therapy Cardiovascular Stenting Plus Many Others 6 •

The Problem Implanted medical devices can create risks to their patients when exposed to MRI Excessive heating of the device (multiple causes) capable of producing uncontrolled tissue heating and thermogenic damage. Induced voltages in the device that can interfere with organ function and device diagnostic and therapeutic capabilities. 3. MR image disruption and distortion that prevents visualization of tissues “close” to the device. 7 •

A Dual Edged Sword! The risk of using of MRI The risk of not using MRI There are 2-3 million MRIs scanned per year in the U.S. and it is likely that hundreds of people receive scans despite the presence of a metallic implant. The risk of not using MRI Approximately 300,000 people per year are denied MRI and the associated health care and diagnostic benefits because of an implant. Moreover, other diagnostic tools, e.g., invasive angiogram procedures, have undesirable risks such as toxic contrast media and exposure to ionizing radiation. 8 •

Representative MR Images Brain Tumor 3-D MR Angiography 9 •

Managing MRI-induced Patient Risk is a Very Difficult Task! To Make Matters Worse Managing MRI-induced Patient Risk is a Very Difficult Task! While it is relatively easy to demonstrate a heating or induced voltage problem, it is far more difficult to prove a solution to these problems, due to their complex and unpredictable nature, which includes factors such as: • RF field strength • Patient position in the coil • Type of imaging sequence • Patient characteristics • Duration of imaging procedure • Body structure being imaged • Lead design • Specific type of medical device • Lead orientation within patient • The degree of perfusion near the device • Temp. measurement procedure • Respiratory phase Many of these parameters are currently either not recognized or inadequately addressed by existing testing methods 10 •

We believe that patients deserve devices that are inherently safe! To Make Matters Worse - continued Proper understanding of the MRI safety situation is further exacerbated by the underreporting of adverse events, due to: • Physician reluctance to report adverse events • Litigation that shrouds the dissemination of circumstances surrounding adverse events MR systems using higher and faster gradient fields, and stronger RF fields will become increasingly common (e.g. move to 3T), maintaining the potential for insufficient safety awareness and risk to patients. Guidelines alone do not guarantee patient safety. We believe that patients deserve devices that are inherently safe! 11 •

3-D Wire-in-Phantom Heating Heat Flux vectors showing conductive transport effect of the wire. Ambient = 25°C Ambient = 25°C 45°C Max 75°C Max 30°C Skin 30°C Skin Isothermal plot in phantom (Passive fixation lead) Close-up of isotherms (Active fixation lead) Substantial MRI-induced heating! 12 •

(i.e. 64MHz) electrical impedance of the lead Our Approach Tissue heating can be substantially reduced by increasing the high frequency (i.e. 64MHz) electrical impedance of the lead 13 •

Simple Model of Bipolar Lead Circuit Diagram IPG Circuit of pacing lead in MRI scanner is not simple… 14 •

Theory: Shifting Self Resonance Of Lead 64 MHz MR scanner’s frequency is fixed. So, we need to shift lead’s self-resonance frequency by changing coil (i.e. lead) inductance and capacitance properties. Maximum impedance at “self” resonance. 15 •

Theory: Air Core Coils Simplified Impedance Equation Rd ≡ Distributed Resistance Cd ≡ Distributed Capacitance Resonance Condition Cs ≡ Parasitic Shunt Capacitance Rs ≡ Series Resistance Maximum coil impedance occurs at “self” resonance. Source: R.Ludwig, P. Bretchko, RF Circuit Design Theory and Applications, Prentice Hall, 1999 16 •

Discrete Component Solution Attachment of components (side view). First Prototypes Attachment of wires (side view Smaller components are currently being evaluated (0.012” x 0.012” x 0.024”) as well as alternate (smaller) packaging designs 17 •

Experimental Setup 18 •

Results – Modified Wireform Leads designed with different inductance and capacitance. Changing the wire form design changes the capacitance-inductance characteristics of the lead and its impedance Two leads had less than 0.5°C temp. increase. Control 19 •

Coil Impedance Values at 64 MHz Lead Impedance at 64 MHz 287 186 – 219j 440 280 – 340j Modified Wire Form 484 200 – 441j 472 204 – 426j OEM #2 3-6 136 120 – 64j 75 57 – 48j Control #2 (OEM #2) 610 215 – 571j 606 223 – 563j OEM #2 1-6 533 124 – 518j 534 129 – 518j OEM #1 1-1 517 203 – 476j 527 207 – 485j OEM #1 3-3 528 208 – 485j 542 240 – 486j OEM #1 3-2 557 162 – 533j 568 179 – 539j OEM #1 1-2 783 220 – 751j 784 213 – 755j OEM #1 4-1 256 178 – 184j 232 210 – 99j OEM #1 4-2 117 96 – 67j 109 57 – 93j Control #1 (SJM 1688T) Zmag () Impedance () Sample In-Situ In Air   Coil Impedance Values at 64 MHz 20 •

Results - Discrete Component Solution Control #1 (Vendor A) Leads designed with different inductance and capacitance. Control #2 (Vendor B) Adding a discrete component, high frequency resonator to the lead changes the capacitance - inductance characteristics of the lead and its impedance 6 modified leads had < 1° C temp. increase. 21 •

MRI-induced Voltages Induced Voltage ≈ dB1 dt AVL x Where; AVL = Area of the “virtual loop” formed by the device, lead, and interconnecting tissue dB1/dt = Rate of change of applied magnetic field Biophan has measured1 induced voltages of ~ 250 – 1000 mV in “anatomically reasonable” cardiac pacing lead configurations Multiple solutions to this problem are available Note 1: Test conditions consisted of RF switched off, scan sequence: Fast Spin Echo, TR = 300, TE = 4, Echo Train Length = 2, Freq = 256, Phase = 256, NEX = 2, Phase FOV = 1, FOV = 18, Spacing = 1.0. 22 •

Conclusions Minimally disruptive lead design options are available to reduce worst-case lead heating to acceptable levels Biophan has also developed easy to implement solutions for reducing or eliminating MRI-induced voltages in leads When implanted, these designs provide the potential to: Provide a greater margin of patient safety Allow a greater number of patients access to MRI We believe that these design options can also be applied to other similar design conductive implants such as ICD and DBS leads as well as guidewires and catheters. 23 •

Typical Approach to Risk Management Training Warnings and precautions in product labeling Restrict product use (i.e. contraindications) Protective measures (e.g. patient monitoring) Product designs that reduce hazard likelihood Product designs that eliminate the hazard Increasing Safety It is possible to produce devices that are inherently safe! 24 •

Biophan Technology Overview The End 25 •