WO2020018283A1 - Method for measuring radio frequency induced heating and voltage with a novel phantom design - Google Patents

Abstract

The present invention provides a method for measuring radio frequency (RF) induced heating and voltage on or near an active implantable medical device (AIMD). The AIMD lead is immersed into a phantom comprising a first, a second, and a third homogeneous mediums. The body of the lead, but not the two ends thereof, is placed into the second homogeneous medium, which has a conductivity σb and a relative permittivity εrb different from those of first homogeneous medium and the third homogeneous medium. The conductivity σb is within the range of from 6 to 80 and the permittivity εrb is within the range of from 0 to 2 S/m. The second homogeneous medium successfully simulates a combination of two or more different tissues, such as a combination of fat tissue and muscle tissue.

Description

METHOD FOR MEASURING RADIO FREQUENCY INDUCED HEATING AND VOLTAGE WITH A NOVEL PHANTOM DESIGN

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application expressly claims the benefit of priority under the Paris Convention based on U.S. Provisional Application No. 62/699,726 filed on July 17, 2018, the entire disclosure of which is incorporated herein by reference.

FIELD OF THE INVENTION

[0002] The present invention generally relates to a method for measuring radio frequency (RF) induced heating and voltage with a novel phantom medium. More particularly, the method measures RF induced heating and voltage on or near an active implantable medical device (AIMD) and its surroundings during magnetic resonance imaging (MRI), so as to determine if the presence of the AIMD may cause injury to a patient with the AIMD during an MR procedure. Although the invention will be illustrated, explained and exemplified by an AIMD comprising an electronic system such as an implantable pulse generator (IPG) and implantable lead(s), it should be appreciated that the present invention can also be applied to other fields, for example, AIMDs comprising an non-IPG electronic system, external fixation devices, percutaneous needles, catheters or tethered devices such as ablation probes, and the like.

BACKGROUND OF THE INVENTION

[0003] A harmful interaction of an object with a piece of MR equipment into which the object is brought into, especially with the static magnetic field, the gradient fields and the RF fields of the MR equipment, can pose hazards to patients or other persons. Interactions of medical devices and other items with the MR environment may result in serious injuries and death of patients and other individuals. Additionally, hazards may stem from equipment malfunction. Potential direct causes of hazards include direct causes such as (1) mechanical causes, including magnetically induced displacement force, torque, and vibration, (2) electromagnetic causes, including induction (heating, stimulation) and discharge (spark gap), and (3) acoustic causes. Potential indirect causes of hazards include malfunction of items, for example of vital components such as valves, monitors and pumps. Other possible safety issues to consider for the hazard assessment include, but are not limited to, thermal injury, induced currents/voltages, interaction with the switched gradient field (dB/dt) for all items that may go inside the magnet bore, electromagnetic compatibility, neurostimulation, acoustic noise, interaction among devices, and the malfunction of the item and the malfunction of the MR equipment and accessories.

[0004] For example, during magnetic resonance imaging (MRI) procedures, for patients with active implantable medical devices (AIMDs), the AIMDs can interact with radio-frequency (RF) fields produced by the MRI RF coil. Such interactions result in the induced voltage/current on device circuits which can cause device malfunction or damage and the induced heating in human tissues which can cause tissue injury. Thus, the assessment of the MRI RF safety for AIMD is important for patients.

[0005] In order to evaluate the MRI RF safety for AIM Ds, four-tier approaches for determining the in vivo RF power deposition around an AIMD exposed to incident RF fields are proposed. In the tier 1 approach, measurements of the RF -induced heating and voltage are performed in tissue simulating media under predetermined incident electric field levels. The tier 2 approach is similar, but the incident field levels in the tier 2 approach are determined by electromagnetic human body simulations. The tier 3 approach requires the electromagnetic human body simulations to extract the tangential incident electric fields along the AIMD implanted path. It also requires a validated model of the AIMD. With the combination of the incident electric fields and the AIMD model, the RF -induced heating and voltage can be predicted. The tier 4 approach requires electromagnetic simulations of a human body together with an AIMD. The tier 1 and tier 2 approaches have certain limitations and can only be applied to electrically short AIMDs, and the tier 4 approach is difficult to achieve due to the high cost of accurately simulating a human model together with an implantable lead with submillimeter coil features. The tier 3 approach is widely used to assess the RF-induced voltage and heating for AIMDs.

[0006] As mentioned before, the tier 3 approach requires a validated model to depict the behaviors of AIMDs in the RF fields. A transfer function model for AIMDs and a transfer function model based on reciprocity have been proposed. We denote the tier 3 approach using the transfer function model as the transfer function approach or the transfer function method. The transfer function method effectively decouples the evaluation of the AIMD MRI RF safety into two separate procedures: the evaluation of AIMDs and the evaluation of the incident fields in human bodies. However, when establishing the transfer function model for AIMDs, the measurements of AIMDs should be performed in the human body environment. Since it is not feasible to measure the transfer function in a human body, a tissue simulating medium is used.

[0007] Thus, in both numerical simulation and measurement approaches, and in tier 1 to tier 3 approaches, a tissue simulating medium is required. Several standard tissue simulating media, including the high permittivity medium (HPM) with e_t = 78 and s = 0.47 or 0.65 or 1.2 S/m and the low permittivity medium (LPM) with e_r = 11.5 or 15.1 and s = 0.045 S/m, were proposed. However, the inhomogeneous human tissues along different AIMD implanted paths can vary significantly, and the several predetermined standard media may not well simulate all the situations. Instead of using several standard media, different AIMDs with different implanted paths should have different tissue simulating media. Therefore, there exists a need to investigate a valid method to determine the optimal tissue simulating medium for certain AIMDs. Advantageously, the present invention can meet such a need.

SUMMARY OF THE IN VENTION

[0008] One aspect of the present invention provides a method for measuring radio frequency (RF) induced heating and voltage on or near an active implantable medical device (AIMD) and its surroundings during magnetic resonance imaging (MRI), so as to determine if the presence of the AIMD may cause injury to a patient with the AIMD during an MR procedure. The method includes at least the following steps: (i) providing an AIMD comprising an electronic system and a lead, wherein the lead consists of a proximal end, a distal end, and a lead body between the proximal end and the distal end; wherein the proximal end is electronically connected to the electronic system; and wherein the lead body is designed to pass through an inhomogeneous tissue path within the patient’s body; (ii) providing a phantom that simulates the electrical and thermal properties of a human body, wherein the phantom comprises a first homogeneous medium, a second homogeneous medium, and a third homogeneous medium, wherein the second homogeneous medium has a conductivity ab and a relative permittivity erb different from those of first homogeneous medium and the third homogeneous medium, and wherein the conductivity ob is within the range of from 6 to 80 and the permittivity erb is within the range of from 0 to 2 S/m; (iii) immersing the proximal end, the lead body and the distal end of the lead entirely into the first homogeneous medium, the second homogeneous medium, and the third homogeneous medium, respectively; and (iv) placing the phantom with the AIMD in a magnetic resonance (MR) test system and measuring RF induced heating and voltage on or near the AIMD.

[0009] The above features and advantages and other features and advantages of the present invention are readily apparent from the following detailed description of the best modes for carrying out the invention when taken in connection with the accompanying drawings.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0010] The present invention is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings and in which like reference numerals refer to similar elements. All the figures are schematic and generally only show parts which are necessary in order to elucidate the invention. For simplicity and clarity of illustration, elements shown in the figures and discussed below have not necessarily been drawn to scale. Well-known structures and devices are shown in simplified form, omitted, or merely suggested, in order to avoid unnecessarily obscuring the present invention.

[0011] Serving to illustrate various exemplary embodiments of the present invention, Figure 1 A is a block diagram of a method for measuring RF-induced heating and voltage on or near an implant such as an AIMD. Figure 1B schematically illustrates an AIMD, its placement in a phantom, and a MR test system for the AIMD and the phantom. Figure 1C illustrates a forward problem of a transfer function method. Figure 1D illustrates a reciprocal problem of the transfer function method. Figure 2A shows a lead in human tissues. Figure 2B shows a lead in an inhomogeneous tissue simulating medium. Figure 2C shows the transmission line model for a lead in human tissues. Figure 2D shows the transmission line model for a lead in the inhomogeneous tissue simulating medium. Figure 3 shows a clinically accurate implantable lead path of a neurostimulator, and its lead path in a human model. Figure 4A demonstrates tissues that are straightened and built using cuboid voxel. Figure 4B illustrates the structure of an implantable lead. Figure 5A shows a lead in straightened human tissues. Figure 5B shows a lead in an inhomogeneous tissue simulating medium. Figure 6 shows the dimensions of straightened human tissues and an insulated solid lead. Figure 7 A shows MR] RF -induced heating T(l) in the tissue simulating medium and in human tissues for an adult male lead path. Figure 7B shows MRI RF-induced heating T(l ) in the tissue simulating medium and in human tissues for a fat male lead path. Figure 8A shows MRI RF-induced voltage T(l) in the tissue simulating medium and in human tissues for an adult male lead path. Figure SB shows MRI RF-induced voltage T(i) in the tissue simulating medium and in human tissues for a fat male lead path. Figure 9A shows MRI RF-induced heating T(l) in mediums with u_b = 0.1 S/m, a_rb = 10, 40, and 80. Figure 9B shows MRI RF-induced heating T(l) mediums with e_rb = 10, u_b = 0.1 S/m, 0.6 S/m, and 1.2 S/m. Figure 10A shows MRI RF-induced heating T(l) mediums with a different lead conductor radius. Figure 10B shows MRI RF-induced heating T(l) mediums with a different lead insulator radius. Figure 10C shows MRI RF-induced heating T(l) mediums with a different lead insulator dielectric constant. Figure 10D shows MRI RF-induced heating T(l) mediums with another different lead insulator dielectric constant. Figure 11 shows a lead with a helical conductor in human tissues. Figure 12 MRI RF-induced heating T(l) in a tissue simulating medium and in human tissues (an adult male path) for leads with a helical conductor. Figure 13 shows a lead of increased size in human tissues. Figure 14 shows MRI RF-induced heating T(l ) in the tissue simulating medium of 1 cm cross-section vs. 1.8 cm cross-section. Figure 15 illustrates a lead placed in a homogeneous tissue simulating medium with ¾ and m,. Figure 16 shows MRI RF -induced heating T(l) in a homogeneous tissue simulating medium and in human tissues (adult male path). Figure 17 shows MRI RF -induced heating T(l) in a tissue simulating medium with _¾ = 78 and in human tissues (adult male path). Figure 18 is an illustration of the clinically relevant pathways of active implantable medical devices. In Figure 19, Panel (a) shows a typical clinical pathway together with its surrounding tissues; Panel (b) shows a muscle tissue modeled as cylinder; and Panel (c) shows a lead embedded in a homogeneous (i.e. equivalent medium). Figure 20 shows a 3D plot of the error-function for a simplified lead model searching for the dielectric parameters of the equivalent medium parameters. Panel (a) of Figure 21 is an illustration of numerical modeling for electrode with multiple inner conductors. Panel (b) of Figure 21 is an illustration of numerical modeling for helical electrodes. Figure 22 illustrates an inhomogeneous phantom for modeling and measurement in which Panel (a) shows phantom for electromagnetic modeling, Panel (b) shows phantom for physical testing, Panel (c) shows a part of a simplified device for measurement validation, and Panel (d) shows the entire simplified device for measurement validation. Panel (a) of Figure 23 illustrates three different pathways developed inside an inhomogeneous phantom for equivalent medium determination and measurement validation. Panel (b) of Figure 23 is a top view of the measurement setup for pathway 3 validation. Panel (c) and Panel (d) of Figure 23 illustrate the MITS system at 1.5-T. Panel (e) of Figure 23 illustrates the position of a temperature probe bonded to a lead tip electrode. Panels (a), (b) and (c) of Figure 24 show comparisons of extracted transfer functions from an inhomogeneous medium and equivalent medium for two, three, and four inner inductors, respectively. Panels (d), (e) and (f) of Figure 24 show comparisons of extracted transfer functions for helical coils with different insulator materials with dielectric constant of 3, 10, 30, respectively. Panels (g), (h) and (i) of Figure 24 show comparisons of extracted transfer functions for helical coils with various helical radius (0.08 mm, 0.1 mm, and 0.12 mm, respectively). Panels (j), (k) and (1) of Figure 24 show comparisons of extracted transfer functions for helical coils with different pitches (1 mm, 2 mm, and 2.5 mm, respectively). Panel (a) of Figure 25 shows a histogram of the determined conductivity value for 41 different lead pathways. Panel (b) of Figure 25 shows a histogram of the determined permittivity value for 41 different lead pathways. Figure 26 shows a comparison of extracted transfer functions of a simplified lead using numerical and experimental method in both heterogeneous and equivalent medium (<¾= 0.675 S/m, E_b=78). Figure 27 shows Magnitude in Panel (a) and phase in Panel (b) of the electric fields distribution along three pathways extracted from the numerical modeling. Panel (c) of Figure 27 shows a comparisons of the temperature rises obtained using direct measurement, predicted using the transfer function from inhomogeneous medium extraction, and predicted using the transfer function from the equivalent medium. Figure 28 shows a comparison of extracted transfer functions using an inhomogeneous human tissue, and an equivalent medium (ob=0.2 S/m, eb=25) and the tissue averaged medium (ob=0.3 S/m, b=38).

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0012] In the following description, for the purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present invention. It is apparent, however, to one skilled in the art that the present invention may be practiced without these specific details or with an equivalent arrangement.

[0013] Where a numerical range is disclosed herein, unless otherwise specified, such range is continuous, inclusive of both the minimum and maximum values of the range as well as every value between such minimum and maximum values. Still further, where a range refers to integers, only the integers from the minimum value to and including the maximum value of such range are included. In addition, where multiple ranges are provided to describe a feature or characteristic, such ranges can be combined.

[0014] It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the invention. For example, when an element is referred to as being“on”,“connected to”, or“coupled to” another element, it can be directly on, connected or coupled to the other element or intervening elements may be present. In contrast, when an element is referred to as being“directly on”, “directly connected to”, or“directly coupled to” another element, there are no intervening elements present.

[0015] In the present invention, a magnetic resonance system (MR system) is defined as an ensemble of MR equipment, accessories, including means for display, control, energy supplies, and the MR environment. Magnetic resonance equipment (MR equipment) is defined as medical electrical equipment which is intended for in-vivo magnetic resonance examination of a patient. The MR equipment comprises all parts in hardware and software from the supply mains to the display monitor. The MR equipment is a Programmable Electrical Medical System (PEMS). A magnetic resonance (MR) environment is defined as a volume within the 0.50 mT (5 gauss (G)) line of an MR system, which includes the entire three dimensional volume of space surrounding the MR scanner. For cases where the 0.50 mT line is contained within the Faraday shielded volume, the entire room shall be considered the MR environment. Radio frequency (RF) magnetic field is defined as the magnetic field in MRI that is used to flip the magnetic moments. The frequency of the RF field is gBO where g is the gyromagnetic constant, 42.56 MHz/T for protons, and BO is the static magnetic field in Tesla. Tesla (T) is the SI unit of magnetic induction equal to 10⁴ gauss (G), Specific absorption rate (SAR) is defined as radio frequency power absorbed per unit of mass (W/kg). SAR may be the mass normalized rate at which RF energy is deposited in biological tissue. Local SAR is defined as specific absorption rate (SAR) averaged over any 10 g of tissue of the patient body and over a specified time.

[0016] In the present invention, conductivity s is defined as the inverse of resistivity, and it has SI units of“Siemens per meter” (S/m). Absolute permittivity (AKA permittivity or distributed capacitance) is denoted by the Greek letter e (epsilon), and is the measure of capacitance that is encountered when forming an electric field in a particular medium. Permittivity describes the amount of charge needed to generate one unit of electric flux in a particular medium. Accordingly, a charge will yield more electric flux in a medium with low permittivity than in a medium with high permittivity. Permittivity is the measure of a material’s ability to store an electric field in the polarization of the medium. The SI unit for permittivity is farad per meter (F/m or F nT¹). The lowest possible permittivity is that of a vacuum. Vacuum permittivity, sometimes called the electric constant, is represented by eq and has a value of approximately 8.85x lCT¹² F/m. The permittivity of a dielectric medium is often represented by the ratio of its absolute permittivity to the electric constant. This dimensionless quantity is called the medium’s relative permittivity, which is also commonly referred to as the dielectric constant.

[0017] With reference to Figure 1A and Figure 1B, various embodiments of the present invention provide a method for measuring radio frequency (RF) induced heating and voltage on or near an implant such as an active implantable medical device (AIMD) 11 and its surroundings during a process of acquiring data by magnetic resonance from the patient, e.g. magnetic resonance imaging (MRI), or any other applicable MR examinations. Magnetic resonance (MR) is defined as resonant absorption of electromagnetic energy by an ensemble of atomic nuclei situated in a magnetic field. MRI is defined as an imaging technique that uses static and time varying magnetic fields to provide images of tissue by the magnetic resonance of nuclei.

[0018] The method of the invention may be used to determine if the presence of the AIMD 11 may cause injury to a patient with the AIMD 11 during a MR procedure. Potentially, some AIMD 11 could inflict hazard to the patient or other individual in the MR environment, for example, RF field-induced heating and RF field-induced rectified (lead) voltage. Radiofrequency (RF) induced heating may occur with any electrically conductive item inside the MRI bore. RF induced heating depends on: (a) the electrical conductivity and permittivity of the device (impedance of electronic device parts), (b) the geometric dimension of the device and configuration, (c) conductivity and permittivity of the surrounding tissue, (d) the energy of the RF pulses (SAR), induced E field, and Bl field, (e) the geometric arrangement of the object relative to the RF transmit coil, (f) the patient body orientation relative to the RF transmit coil, (g) the specific MR coil electromagnetic field characteristics, and (h) the center frequency of the specific MR system. [0019] In exemplary embodiments, the method of the invention includes at least the following steps (i)-(iv), as shown in Figure 1A and Figure 1B. Step (i) is providing a suitable implant comprising an elongated conductor. The implant may be an object, structure, or device intended to reside within the body for diagnostic, prosthetic, or other therapeutic purposes. The implant may be a passive implant or active implant, i.e. it may serve its function with or without the supply of electrical power. For example, AIMD 11 may comprise (or consist of) an electronic system 12 and a lead 13. The lead 13 may consist of a proximal end 13r, a distal end l3d, and a lead body l3b between the proximal end 13r and the distal end l3d. The proximal end 13r is electronically connected to the electronic system 12. The lead body l3b is designed to pass through an inhomogeneous tissue path (not shown) within the patient’s body in a MRI procedure. Lead 13 may be straight or curved, and in some embodiments, the lead 13 may comprises a helical conductor with submillimeter coiling structures.

[0020] Step (ii) is providing a phantom 20 that simulates the electrical and thermal properties of a human body. The phantom 20 is featured with the inventor’s unique medium profile. Specifically, the phantom 20 comprises (or consists of) a first homogeneous medium 21, a second homogeneous medium 22, and a third homogeneous medium 23. The second homogeneous medium 22 has a conductivity ob and a permittivity arb different from those of first homogeneous medium 21 and the third homogeneous medium 23. The first homogeneous medium 21 and the third homogeneous medium 23 may have same or different conductivity and/or permittivity. While the second homogeneous medium 22 may simulate a combination of two or more different tissues, such as a combination of fat tissue and muscle tissue, the first homogeneous medium 21 simulates a fat tissue or a muscle tissue, and the third homogeneous medium 23 simulates a muscle tissue or a fat tissue. For example, the first homogeneous medium 21 is a high permittivity medium (HPM) e g. with eΐ = 78 and s = 0.47 or 0.65 or 1.2 S/m; or a low permittivity medium (LPM) e.g. with ar = 11.5 or 15.1 and s = 0.045 S/m. Similarly, the third homogeneous medium 23 may be a high permittivity medium (HPM) e.g. with ar = 78 and s = 0.47 or 0.65 or 1.2 S/m; or a low permittivity medium (LPM) e.g. with ar = 11.5 or 15.1 and s = 0.045 S/m

[0021] With respect to the second homogeneous medium 22, the conductivity ob may be within the range of from 6 to 80 and the permittivity srb may be within the range of from 0 to 2 S/m. The conductivity ob may be within the range of from X to Y, X<Y, and X and Y are independently of each other selected from 6, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 and 80. The relative permittivity srb is within the range of from U to Y, U<V, and U and V are independently of each other selected from 0.01 S/m, 0 1 S/m, 0.2 S/m, 0 3 S/m, 0.4 S/m, 0.5 S/m, 0.6 S/m, 0.7 S/m, 0.8 S/m, 0.9 S/m, 1.0 S/m, 1.1 S/m, 1.2 S/m, 1.3 S/m, 1.4 S/m, 1.5 S/m, 1.6 S/m, 1.7 S/m, 1.8 S/m, 1.9 S/m, and 2.0 S/m. In a specific but exemplary embodiment, the conductivity ob and the permittivity rb of the second homogeneous medium are 30 and 0.2 S/m, respectively.

[0022] Conductivity and relative permittivity of the phantom material, particularly the conductivity ab and relative permittivity srb, may be measured in a test frequency of 64-180 MHz such as 64 MHz and 128 MHz. The phantom material may have thermal properties similar to those of the body which has diffusivity of about l.3xl0⁷ m²/s and heat capacity 4150 J/kg°C at 2l°C (close to the heat capacity of water). There is a linear rise of 2.35 J/(kg K) per degree kelvin in the specific heat from 20 to 40°C. The phantom viscosity is great enough so that the phantom material does not allow bulk transport or convection currents

[0023] In embodiments of the invention, the phantom medium 21/22/23 comprises a gelled saline consisting of a saline solution and a gelling agent. For example, the gelled saline may include sodium chloride and a suitable gelling polymer such as polyacrylic acid (PAA), hydroxy ethylcellulose (HEC), or any mixture thereof. The conductivity and relative permittivity of the first homogeneous medium 21, the second homogeneous medium 22, or the third homogeneous medium 23 may be individually controlled by adjusting or fine-tuning the amount of NaCl and the gelling polymer in the medium material, as desired.

[0024] Ingredients of PAA gelled saline may include deionized or distilled water with a conductivity less than 1 mS/m; NaCl of reagent grade and >99 % pure; and Poly acrylic acid such as Aldrich product number 436364,‘Polyacrylic acid partial sodium salt’, CAS no. 76774-25-9. It is preferred to follow the mixing protocol and use the given ingredients in order to achieve reliable and repeatable results, as described in ASTM F2l82-lla. Preparation of the PAA gelled saline may include (1) Add NaCl to water and stir to dissolve completely. Verify that the conductivity and permittivity parameters meet the requirements according to the present invention. (2) Add PAA, stir to suspend completely. (3) After one hour, blend the suspension into a slurry. A kitchen grade immersion blender with a blade can be used for blending. The blender is turned on intermittently for at least 20 min in order to remove all lumps of any discernable size. (4) The slurry is ready to use after 24 h. Stir occasionally. The appearance of the slurry should be semi-transparent, free of bubbles, and free of lumps of any discernable size. (5) Verify that the conductivity and permittivity parameters meet the requirements according to the present invention.

[0025] Ingredients of HEC gelled saline include deionized or distilled water with conductivity less than 1 mS/m, NaCl of reagent grade and >99 % pure, and Hydroxy Ethyl Cellulose (e.g. from Sigma Aldrich, product number 09368 (Fluka), CAS no. 9004-62-0). The preparation of HEC gelled saline may include the following steps. 1. Add NaCl to water, stir to dissolve completely. Verify that the conductivity and permittivity parameters meet the requirements according to the present invention. 2. Stir in the HEC powder slowly. If powder is added too quickly, lumps will form. 3. Stir as required to keep the suspension homogeneous while it thickens. Take care to prevent the formation of a more viscous layer at the bottom of the container. Stir continuously for at least 3 h until a uniform gelled saline is formed. It is preferred that an electric stirrer be used. 4. The slurry is ready to use after 24 h. The appearance of the slurry is transparent and free of bubbles. 5. Verify that the conductivity and permittivity parameters meet the requirements according to the present invention.

[0026] Bothe the PAA gelled saline and the HEC gelled saline may have a shelf life of two months. However, a new batch of gelled saline is needed when there is a change in any property, such as volume, conductivity, color, or viscosity. The phantom material is preferably sealed in an airtight container whenever possible to prevent evaporation and/or contamination. Evaporation will alter the gelled saline properties.

[0027] A PAA gelled saline that meets the properties required according to the present invention can be made by adjusting or fine-tuning the amount of NaCl and polyacrylic acid (PAA) in water. For example, the amount of Nad may be in the range of 0.5-4.0 g/L such as 1.32 g/L; and the amount of polyacrylic acid (PAA) may be in the range of 5-20 g/L such as 10 g/L in water. A HEC gelled saline that meets the properties required according to the present invention can be made by adjusting or fine-tuning the amount of NaCl and hydroxyethylcellulose (HEC) in water. For example, the amount of NaCl may be in the range of 0.5-4.0 g/L such as 1.55 g/L; and the amount of EEC may be in the range of 10-50 g/L, such as 31 g/L in water.

[0028] In preferred embodiments, the three mediums 21, 22, and 23 may be placed in three containers or chambers 2:1 c, 22c and 23c. The phantom containers 2lc, 22c and 23c and all its parts are made of materials that are electrical insulators and non-magnetic and non-metallic. A side wall W12 between (and preferably shared by) containers 2lc and 22c may be used to separate medium 21 and medium 22 from each other, and another side wall W23 between (and preferably shared by) containers 22c and 23 c may be used to separate medium 22 and medium 23 from each other.

[0029] In step (iii), the proximal end 13r, the lead body l3b and the distal end l3d of the lead 13 are immersed entirely into the first homogeneous medium 21, the second homogeneous medium 22, and the third homogeneous medium 33, respectively. The electronic system 12 may be an implantable pulse generator (IPG), and may also be immersed into the first homogeneous medium with the proximal end 13r of the lead 13. Temperature sensors/probes may be placed at locations where the induced implant heating is expected to be the greatest. If necessary, pilot experiments may be carried out to determine the proper placement of the temperature probes. Preferably, the temperature sensor will have a resolution of no worse than 0.1 °C, a temperature probe spatial resolution not to exceed 1 mm along the specific axis of measurement in any direction, and a temporal resolution of at least 4 s. The temperature probe should be transparent to the applied RF field and must not disturb the local E-field (electric Fields) significantly. The lead 13 may pass through a hole in wall W12 so as to extend the lead 13 from container 2lc to container 22c, and then pass through a hole in wall W23 so as to further extend the lead 13 from container 22c to container 23c. Then, the two holes are preferably sealed with a sealant to prevent a cross flow (or cross“contamination”) between the mediums 21 and 22, and/or between the mediums 22 and 23.

[0030] In step (iv), the phantom 20 immersed with the AIMD 11 is placed in a magnetic resonance (MR) test system 30. MR test system 30 may be any suitable magnetic resonance diagnostic device or a simulation thereof. A magnetic resonance diagnostic device is defined as a device intended for general diagnostic use to present images which represent the spatial distribution or magnetic resonance spectra, or both, which reflect frequency and distribution of nuclei exhibiting nuclear magnetic resonance. Other physical parameters derived from the images or spectra, or both, may also be produced.

[0031] Subsequently, RF induced heating and voltage on or near the AIMD 11 may be measured using any known protocols. As an indicator of RF induced heating, the amount of RF-induced temperature rise for a given specific absorption rate (SAR) will depend on the RF frequency, which is dependent on the static magnetic field strength of the MR system, e.g. 1.5 Tesla (T) or 3 Tesla cylindrical bore MR systems. The RF-induced temperature rise for an implant in MR systems of other static magnetic field strengths or magnet designs can be evaluated by suitable modification of a standard method, e.g. ASTM F2182-1 la.

[0032] In preferred embodiments, the method of the present invention is carried out by following a standard method mutatis mutandis , e.g. ASTM F2182- 11 a, which is incorporated herein by reference, except that the phantom and specimen placement in the standard method are modified to the 3 -medium profile of the invention and AIMD 11 placement as described above.

[0033] For example, an RF field producing a sufficient whole body averaged SAR of about 2W/kg averaged over the volume of the phantom 20 is applied for e.g. approximately 15 min, or other time sufficient to characterize the temperature rise and the local SAR. The measurement may be divided into two sub-steps (A) and (B). In sub-step (A), the temperature rise on or near AIMD 11 at several locations is measured using fiber-optic thermometry probes (or equivalent technology) during e.g. approximately 15 min of RF application. Temperature rise is also measured at a reference location during sub-step (A). In sub-step (B), AIMD 11 is removed and the same RF application is repeated while the temperature measurements are obtained at the same probe locations as in sub-step (A). All measurements are preferably done with AIMD holders (not shown) in place. The local SAR is calculated from the temperature measurements for each probe location, including the reference location. The local SAR value at the temperature reference probe is used to verify that the same RF exposure conditions are applied during sub-steps (A) and (B). These measurements estimate the local SAR and the local additional temperature rise with AIMD 11. The results may be used as an input to a computational model for estimating temperature rise due to the presence of AIMD 11 in a patient. The combination of the test results and the computational model results may then be used to help assess the safety of a patient with AIMD 11 during an MR scan.

[0034] Based on the safety assessment, one can mark AIMD 11 that might be brought into the MR environment and recommend information that should be included in the marking. For example,“MR Safe” means that an object (e g. a cotton blanket or a silicone catheter) poses no known hazards resulting from exposure to any MR environment. MR Safe items are composed of materials that are electrically nonconductive, nonmetallic, and nonmagnetic.“MR Unsafe” described an item (e.g. a pair of ferromagnetic scissors) which poses unacceptable risks to the patient, medical staff or other persons within the MR environment.“MR Conditional” describes an item with demonstrated safety in the MR environment within defined conditions. At a minimum, it can address the conditions of the static magnetic field, the switched gradient magnetic field and the radiofrequency fields. Additional conditions, including specific configurations of the item, may be required. In other words,“MR Conditional” may characterize an item that has been demonstrated to pose no known hazards in a specified MR environment with specified conditions of use. Field conditions that define the specified MR environment include field strength, spatial gradient, dB/dt (time rate of change of the magnetic field), radio frequency (RF) fields, and specific absorption rate (SAR).“MR-compatible” describes a device that, when used in the MR environment, is MR-safe and has been demonstrated to neither significantly affect the quality of the diagnostic information nor have its operations affected by the MR device. The MR conditions in which the device was tested are generally specified in conjunction with the term MR-compatible since a device which is compatible under one set of conditions may not be found to be so under more extreme MR conditions.

[0035] As shown in Figure 1B, a typical AIMD 11 usually includes the electronic system 12 such as an implantable pulse generator (IPG) and implantable lead(s) 13. The proximal end 13r of the lead is connected to the IPG 12, and the distal end l3d of the lead (i.e. lead tip) is attached to human tissues.

The First Group of Embodiments

[0036] Without being bound by any particular theory, an exemplary method on how to determine specific conductivity ob and the relative permittivity srb of the second homogeneous medium 22 will be described in the following, based on (1) a transmission line model for the lead 13, (2) a full-wave simulation of human tissues along a path of the lead 13, and (3) a reciprocity -based transfer function model as a criterion for optimizing the medium 22 parameters. As background information, the following references are incorporated herein in their entirety: [1] R. Kalin and M. S. Stanton,“Current clinical issues for MRI scanning of pacemaker and defibrillator patients,” Pacing Clin. Electrophysiol ., vol. 28, no. 4, pp. 326-328, 2005. [2] S. Achenbach, W. Moshage, B. Diem, T. Bieberlea, V Schibgilla and K. Bachmann,“Effects of magnetic resonance imaging on cardiac pacemakers and electrodes,” Arner Heart J , vol. 134, no. 3, pp. 467-473, 1997. [3] ISO/TS l 0974:20T2(E) Assessment of the safety of magnetic resonance imaging for patients with an active implantable medical device. [4] S.-M. Park, R. Kamondetdacha, and J. A. Nyenhuis,“Calculation of MRI-induced heating of an implanted medical lead wire with an electric field transfer function,” J. Magn. Reson. Imag, vol. 26, no. 5, pp. 1278-1285, Nov. 2007. [5] S. Feng, R. Qiang, W. Kainz and J. Chen,“A technique to evaluate MRI-induced electric fields at the ends of practical implanted lead,” IEEE Trans. Microw. Theory Tech, vol. 63, no. 1, pp. 305-313, Jan. 2015. [6] J. Liu, J. Zheng, Q. Wang, W. Kainz, and J. Chen,“A transmission line model for the evaluation of MRI RF-induced fields on active implantable medical devices,” IEEE Transactions on Microwave Theory and Techniques , 66(9), 4271-4281, 2018. [7] H. G. Mond and D. Grenz,“Implantable transvenous pacing leads: The Shape of Things to Come,” Pacing Clin. Electrophysiol, vol. 27, no. 1, pp. 887-893, May 2004.

[0037] In the following embodiments, a method based on full-wave simulations of human tissues along implantable lead paths is used to determine the optimal tissue simulating medium. Numerical investigations and validations are given for a neurostimulator with several clinically accurate implanted paths in both adult male and fat male human models. One embodiment illustrates the procedure of finding the tissue simulating medium and explains the rationale using the transmission line model for implantable leads. Another embodiment provides an example of finding the tissue simulating medium for a neurostimulator, and numerical validations for the method.

[0038] When a patient with an AIMD 11 takes an MRI scan, the AIMD 11 can interact with the fields generated by the MRI RF coil, which raises safety concerns. As shown in Figure 1(a), an implantable lead 13 is under incident fields

a total induced electric field P^toial is generated on the end of the lead. ^Etotd on the proximal end 13p can result in RF-induced voltages on the IPG, and ^toM on the distal end l3d can cause RF-induced heating in human tissues near the lead tip electrodes. Figure 1C illustrates the forward problem of the transfer function method; and Figure 1D illustrates the reciprocal problem of the transfer function method.

[0039] The transfer function method can be used to calculate ^totel as:

[0040] In equation (1), * is a unit vector along the lead direction, and ^ is a unit vector with the direction of the infinitesimal dipole

shown in Figure 1D. 1(1) is the transfer function, which transfers the incident electric field

along the lead to the total electric field

at the lead end. T(l) of the AIMD 11 can be extracted in the reciprocal problem as shown in shown in

Figure 1D. A unit infinitesimal electric dipole ^ is placed at one end of the lead 13, and the current 1(1) is induced on the lead. The magnitude and phase of T(l) are equal to those of 1(1).

[0041] Figure 2A shows a lead in human tissues, and Figure 2B shows a lead in the inhomogeneous tissue simulating medium. Figure 2C shows the transmission line model for a lead in human tissues. Figure 2D shows the transmission line model for a lead in the inhomogeneous tissue simulating medium. For a lead implanted in a human body, the media surrounding the lead are inhomogeneous human tissues as shown in Figure 2A. Instead of specifying the distal end l3d (the lead end with tip electrodes) and the proximal end 13r (the lead end with the IPG), we label the two ends as excitation end and load end. For the MRI RF-induced voltage assessment, the excitation end is the proximal end and the load end is the distal end; for the MRI RF-induced heating assessment, the excitation end is the distal end and the load end is the proximal end.

[0042] The implantable lead in human tissues can be modeled as a coaxial transmission line with the lead conductor as the inner conductor, and human tissues as the outer conductor. As shown in Figure 2C, the excitation end is modeled as impedance Z_s, the load end is modeled as impedance Z_L, and the lead body is modeled as a transmission line. Since there are different human tissues along the lead path, the lead body transmission line is modeled as a cascaded transmission line with different characteristic impedances and propagation wavenumbers. When the excitation 7_S is chosen to be a 1 A unit source, the value of the current 1(1) on the lead is the value of the transfer function T(I).

[0043] Figure 2B shows the proposed tissue simulating medium and Figure 2D shows the transmission line model for a lead in such medium. The tissue with e and er_s can have influence on Z_s, and the tissue with e_rL and a_L ean have influence on Z _L. Thus, the clinical medium conductivity and permittivity may be assigned to achieve accurate termination impedances. In the equivalent medium shown in Figure 2B, medium 1 is chosen to have e_rs and s_% to give accurate Z_s and medium 3 is chosen to have e_rL and U_L to give accurate Z_L. The standard medium can be used in these two regions. The tissues surrounding IPG are usually fat tissues, which can be simulated using the LPM; and tissues surrounding the lead tip are usually muscle tissues, which can be simulated using the HPM.

[0044] Medium 2 in Figure 2B is the tissue simulating medium for the lead body. Since a lead path can go through different kinds of human tissues such as fat, blood, and muscle, it is not accurate to simply use a standard medium to simulate the tissues.

[0045] Next, procedures to find optimal e_rb and er_b are described. The ideal procedures to find the optimized a_rb and u_b include: Step 1 : Full-wave simulate the lead in the human body and extract /(/). Step 2: Full-wave simulate the same lead in the medium as shown in Figure 2B and extract T(f). In the simulations, the clinical medium conductivities and permittivities are assigned to medium 1 and medium 3. Step 3: Repeat step 2 with different e_rb and <r_b to match the T(l) from step 2 to step 1, and the optimized e_rb and u_b are the solution.

[0046] Since it is not easy to accurately simulate the implantable lead together with the entire human body, a simplified setup is used. First, for the human tissues, instead of simulating the entire human model, only tissues close to the lead paths are modeled. Figure 3 shows a clinically accurate implantable lead path of a neurostimulator, and its lead path in a human model. A rectangular face centered on the lead path is placed at the beginning of the lead path, and the face is moved along the lead while keeping the center on the path. The tissue information on the face is recorded while moving the face. After gathering all the tissue information, the tissues are straightened and built using cuboid voxel as shown in Figure 4A. Thus, the simulation of the human model is simplified to the simulation of inhomogeneous tissues along the lead path. Second, for the implantable lead as shown in Figure 4B, an insulated solid lead is used in simulations. While some practical implantable leads have such solid lead conductor design, many implantable lead conductors have helical designs with submillimeter coiling structures, which is not easy to be accurately simulated. A properly-chosen solid lead can replace the helical lead when searching for the tissue simulating medium. Specifically, in simulations, a solid lead that is more sensitive to the medium parameters than the practical implantable lead should be used. For example, a solid lead with very thin insulator can be chosen as a thin insulator would result in more fields distributed in tissues. Validations may be performed for the tissue simulating medium with different leads. Also, the cross-section in Figure 4A should be chosen large enough so that fields are distributed within the region. Validations should be performed by comparing T(l) in tissues with the chosen cross-section and T(l) in tissues with an increased cross-section.

[0047] If a more sensitive solid lead is chosen and the tissue cross-section is large enough (the lead 7(7) do not change as the tissue cross-section increases), the optimized medium for the solid lead would work for the implantable lead.

[0048] In simulations, the solid lead in Figure 4B is placed inside the human tissues in Figure 4A with a straight shape. Since the lead in tissues can be modeled as a coaxial transmission line with quasi -TEM mode fields inside the lead insulator, whether the lead having a straight shape or a curved shape have little impact on 1(1) or T(I), as long as the tissues along the lead remain the same.

[0049] With the simplified setup, the procedure of finding the optimized e_rb and cr_b is adjusted to the following: Step 1: Full-wave simulate the lead in straightened human tissues and extract T(l). Figure 5A shows a lead in straightened human tissues. The straightened human tissues are submerged in a medium with e_r and <r as shown in Figure 5 A. Figure 5B shows a lead in an inhomogeneous tissue simulating medium. Step 2: Full-wave simulate the same lead in the inhomogeneous medium as shown in Figure 5B and extract T(J). Step 3: Repeat step 1 and step 2 with different e_rb and er_b to match the T(I) from step 2 to step 1. The optimized £¾, and cr_b are the solution.

[0050] The difference between step 2 in Figure 5B and step 1 in Figure 5A is that tissues surrounding the lead body are removed. For the optimized e_rb and er_b, the existence of the human tissues along the lead body does not influence T(J). Therefore, such medium can be used as the tissue simulating medium.

[0051] In an embodiment, the tissue simulating medium of a neurostimulator was investigated using the commercial full-wave simulation tool ANSYS HFSS at 64MHz, which is the 1.5 T MRI RF coil working frequency. Six lead paths in the adult male human model and six lead paths in the fat male human model were investigated. All the lead paths were clinically accurate. The tissue simulating medium for both MRI RF-induced voltage and heating was investigated.

[0052] Figure 6 shows the dimensions of straightened human tissues and the insulated solid lead. As shown in Figure 6, in the straightened human tissues simulation, the length of the tissues was 50 cm, and the cross-section of the tissues was 1 cm by 1 cm. The cuboid voxels had dimensions of 2 mm by 2 mm by 10 mm. Therefore, the tissues had a resolution of 2 mm on the lead radial direction and a resolution of 10 mm on longitudinal direction. The radius of the lead conductor was 0.4 mm and the radius of the lead insulator was 0.5 mm. The insulator dielectric constant was 3. The thickness of the insulator was chosen to be small to increase the sensitivity of the lead to the environment.

[0053] A coaxial cable was connected to one end of the lead as an excitation. The inner conductor of the coaxial cable was connected to the lead conductor, and the outer conductor of the coaxial cable was submerged in the tissues. The load end of the lead was a 5 mm bare conductor. For the MRI RF-induced voltage case, the excitation was placed at one end of the lead where the tissues near this end were tissues surrounding the IPG; for the MRI RF-induced heating case, the excitation was placed at the other end of the lead where the tissues near this end were tissues surrounding the lead tip. Since the IPG was implanted in fat tissues and the lead tip surrounding tissues were dominantly muscle, e_rs, a_s and a_rL, <r_L were chosen to be parameters of fat and muscle.

[0054] The extracted optimized ¾ and er_b are shown in Table I. It is noticed that the optimized g_rb and or_b for MRI RF-induced voltage and heating can be different even for the same lead path. This is because the voltage and heating case had different excitation ends, therefore the tissues at the same distance / to the excitation can be different, which would result in different T(J).

Table I

Tissue Simulating Medium Parameters for MRI RF -Induced Heating and Voltage of Different

Lead Paths in Adult Male and Fat Male Model

[0055] Figure 7A shows MRI RF-induced heating T(l) in the tissue simulating medium and in human tissues for adult male lead path 1. Figure 7B shows MRI RF-induced heating 7(7) in the tissue simulating medium and in human tissues for fat male lead path 6. Figure 8A shows MRI RF-induced voltage T(F) in the tissue simulating medium and in human tissues for adult male lead path 2. Figure 8B shows MRI RF-induced voltage T(J) in the tissue simulating medium and in human tissues for fat male lead path 4. Figure 9A shows MRI RF-induced heating T(J) in the medium with = 0.1 S/m, e* = 10, 40, and 80. Figure 9B shows MRI RF-induced heating T(f) in the medium with £_rb = 10, er_b = 0.1 S/m, 0.6 S/m, and 1.2 S/m.

[0056] MRI RF-induced heating T(l) for adult male path 1 and fat male path 6 are compared with T(l) in the medium in Figures 7A and 7B, and MRI RF-induced voltage T(I) for adult male path 2 and fat male path 4 are compared with T(t) in the medium in Figures 8A and 8B. Also, it is shown in Figures 9A and 9B that, in media with different ¾ and cr_b, T(l) of the lead can be significantly different. Since the lead had an insulator with 0.1 mm thickness, which is relatively thin compared with the 0.4 mm lead conductor radius, this lead is sensitive to the surrounding medium parameter change.

[0057] After the extraction of optimized s_lb and a_h for different lead paths in different human models, an average could be taken to determine the optimized tissue simulating medium parameters s_rb and a_b for heating and voltage case respectively.

[0058] In the previous embodiments, a lead with conductor radius of 0.4 mm, insulator radius of 0.5 mm, and insulator dielectric constant of 3 was used. Next, the equivalency of the medium to the tissues was validated using different leads. 7(7) of these leads were extracted and compared inside the straightened tissues and the medium. The heating case of adult male model lead path 1 was used in all validations. From Table I, the extracted medium parameters are ¾ = 30 and o_b = 0.2 S/m. Referring back to Figures 1A and 1B, the conductivity ob and the permittivity srb of the second homogeneous medium may be 30 and 0.2 S/m, respectively. For comparison, the conductor radius was changed to 0.1 mm as shown in Figure 10A; the insulator radius was changed to 0.8 mm as shown in Figure 10B; and the insulator dielectric constant was changed to 1 and 9 respectively as shown in Figure 10C and Figure 10D. Figures 10A, 10B, 10C and 10D show MRI RF -induced heating 7(7) in the tissue simulating medium and in human tissues (adult male path 1) for leads with different parameters: (a) Lead with conductor radius of 0.1 mm. (b) Lead with insulator radius of 0.8 mm. (c) Lead with insulator dielectric constant of 1. (d) Lead with insulator dielectric constant of 9. The agreement shows that the medium can work for different leads.

[0059] The previous embodiments all used an insulated solid lead, but practical implantable leads may have helical conductor designs. Figure 11 shows a lead with a helical conductor in human tissues. The pitch of the helix was 1 mm. The wire radius was 0.1 mm, and the helix radius was 0.3 mm. Next, the solid conductor was replaced by a helical one as shown in Figure 11. Figure 12 shows MRI RF-induced heating T(l) in the tissue simulating medium and in human tissues (adult male path 1) for leads with a helical conductor, demonstrating a good agreement between the helical lead 7(7) in the medium and that in human tissues. [0060] Next, the amount of the tissues in Figure 6 was increased. Figure 13 shows a lead in human tissues with increased size. As shown in Figure 13, the cross-section dimensions of the tissues were increased from 1 cm by 1 cm to 1.8 cm by 1.8 cm. The dimension of the cuboid voxels was still 2 mm by 2 mm by 10 mm, therefore the tissue voxel number was increased by 3.24 times. Figure 14 shows MRI RF-induced heating T{1) in the tissue simulating medium, 1 cm cross-section human tissues, and 1.8 cm cross-section human tissues, demonstrating that the extracted medium works for the increased size tissue. Also, T(l) of the 1 cm cross-section tissues and T(l) of the 1.8 cm cross-section tissues are almost identical, which means that the 1 cm by 1 cm tissue size was sufficient to characterize the human body environment for this case.

[0061] An inhomogeneous tissue simulating medium for MRI RF safety assessment was proposed as shown in Figure 2B. The medium includes three different portions with different parameters, which are embodiments of the first homogeneous medium 21, the second homogeneous medium 22, and the third homogeneous medium 23. as shown in Figure 1B. Such medium scheme can give a more accurate prediction of the MRI RF-induced voltage and heating than the standard homogeneous medium.

[0062] To reduce the work in measurements, some simplifications can be made. First, when the differences of parameters of medium 1, medium 2, and medium 3 in Figure 2B are relatively small, an optimized homogeneous medium can be used. In step 2 of the simplified setup, instead of placing the lead inside an inhomogeneous medium as shown in Figure 5B, the lead is placed in a homogeneous tissue simulating medium with

as shown in Figure 15. Step 1 and step 3 may remain the same. For example, the optimized homogeneous tissue simulating medium parameters for the heating case of the adult male path 1 are £*

= 0.1 S/m. The comparison between T(l) in tissues and T(F) in the homogeneous medium was made. Figure 16 shows MRI RF-induced heating T(l ) in a homogeneous tissue simulating medium and in human tissues (adult male path 1). The agreement is not as good as Figure 7A where the inhomogeneous medium is used, but as compared with the standard medium with fixed parameters, these medium parameters are still optimized under certain restrictions. [0063] Second, the extracted e_rb and u_b in Table I can vary significantly for different AIMDs with different implanted paths. It is not easy to make such medium in lab measurements, especially for MRI RF-induced heating measurements, where the medium should also be capable of capturing the temperature rise on the AIMD. A simplification can be made. When searching for the optimized medium parameters, c_rb can be fixed to 78, and only a_h is optimized. In RF-induced voltage measurements, such medium can be made with saline with different concentrations, and in RF-induced heating measurements, such medium can be made with polyacrylic acid (PAA) gel with different concentrations.

[0064] For example, the optimized <r_b ⁼ 0.2 S/m was extracted for the heating case of adult male model lead path 1. Figure 17 shows the comparison of T(T) in human tissues with that in the medium. Figure 17 shows MRI RF-induced heating T(J in the tissue simulating medium with e_r = 78 and in human tissues (adult male path 1). Since c_rb is restricted to 78, the agreement is not as good as Figure 7 A, but in cases where the optimized a_rb and r/_h medium is not feasible, such medium can still give a good prediction.

[0065] In various embodiments of the invention, an inhomogeneous tissue simulating medium for assessing the MRI RF safety for patients with AIMDs is provided based on the transfer function method and the transmission line model. A full-wave simulation based method is provided to find the parameters of the tissue simulating medium. The medium is optimized for each AIMD with its specific implanted paths in human bodies.

[0066] In various embodiments of the invention, a full-wave simulation based method is used to determine the optimal tissue simulating medium for magnetic resonance imaging (MRI) radio-frequency (RF) safety assessment for patients with active implantable medical devices (AIMDs). Compared to the standard medium, the tissue simulating medium of the invention is optimized for each AIMD lead path in human bodies. The reciprocity based transfer function model is used as a criterion for optimizing the medium parameters. Numerical investigations and validations are performed for a neurostimulator to demonstrate the method. The Second Group of Embodiments

[0067] Without being bound by any particular theory, and similarly to the first group of embodiments, the second group of embodiments provides further development of an equivalent medium (i.e. second homogeneous medium 22 as shown in Figure 1B) for active implantable device RF safety assessment. The equivalent medium theorem can be used to perform accurate evaluation of implantable device safety under MRI exposure. Numerical methods were used to determine the equivalent medium parameters along clinically relevant trajectories inside a human body model. Additionally, numerical and experimental investigations were performed using both a computational human body model and an inhomogeneous phantom to demonstrate the effectiveness of the method.

[0068] The results from the second group of embodiments demonstrate that the equivalent medium parameters, which are determined from a simplified lead configuration, are independent of the lead types and lead design parameters and only depend on the lead trajectories. Experimental investigations using an inhomogeneous phantom showed excellent agreement between the computational predicted values and the direct measured temperature rises indicating the effectiveness and accuracy of this method. For the models based on multiple patients trajectories studied, it demonstrates that the equivalent medium theorem is valid for leads of different types and designs, as long as the lead trajectories are determined.

[0069] To illustrate the method for equivalent medium development, clinically relevant pathways based on the sleep apnea device were developed as shown in Figure 18. These pathways were developed for the Duke model from the virtual family. Total 41 pathways were developed based on consultation with medical professionals. The IPG was located near the rib cage region at the height around fifth Lumbar vertebrae. The tip electrodes were located near the tongue muscles and the lead length was fixed to 45 cm. A typical pathway together with its surrounding tissues is shown in Panel (a) of Figure 19. To mimic a realistic clinical scenario, the tip of the electrode was implanted inside muscle tissue while the IPG was implanted between a fat and a muscle layer. The lead was embedded in fat, muscle, and skin tissue as indicated in Panel (a) of Figure 19.

[0070] The proposed equivalent medium is a homogeneous medium which has the transfer function closely matched to the transfer function for the inhomogeneous medium. The homogeneous medium is assessed via electromagnetic modeling at 64 MHz (1.5T) by: step (1) embedding a simplified lead model into the inhomogeneous medium, step (2) performing the numerical modeling to obtain the electrode transfer function for the inhomogeneous medium, step (3) embedding the same electrode model in a homogeneous medium with initial relative permittivity and conductivity values close to tip medium, and (4) performing the numerical modeling of the transfer function and optimizing the parameters of the homogeneous medium until the transfer function of the equivalent homogeneous medium matches the one from step 2. The numerical simulation in this paper was performed using the commercial full-wave simulation tool ANSYS HFSS 2018.

Equivalent Medium Parameters Determination Using Simplified Electrode Model

[0071] The simplified lead model had an inner conductor with a radius of 0.4 mm and was embedded in an insulation layer with a radius of 0.5 mm and a dielectric constant of 3. The entire simulation volume was 56 x 56 x 100 cm³. The length of the lead model was 45 cm with 3 cm of the center conductor, i.e., the electrode, in contact with muscle tissue. The muscle tissue was modeled as cylinder as shown in Panel (b) of Figure 19. On the IPG side, the center electrode was inserted into the IPG and connected to the metallic case with impedance of 2+3] Ohm to mimic the internal IPG impedance. The IPG itself was surrounded by fat tissue. The length of the lead body embedded in the inhomogeneous tissue was 45 cm. The transfer function for the lead embedded in the inhomogeneous medium was calculated by applying a current source of 1 A to the electrode tip, as shown in Panel (b) of Figure 19, and extracting the induced current along the entire lead body.

[0072] The same procedure was then applied to assess the transfer function of the lead embedded in a homogeneous, i.e., the equivalent medium, as shown in Panel (c) of Figure 19. The relative permittivity and conductivity of the equivalent medium was derived by comparing the transfer function of the inhomogeneous medium with the transfer function of the homogeneous medium. The dielectric parameters for the equivalent medium are those which produce the closest match of the transfer function between the inhomogeneous and homogeneous, i.e., the equivalent, medium.

[0073] The dielectric parameter search is divided into two stages: first a coarse search is performed, followed by a fine search. The coarse searching boundaries of relative permittivity and conductivity are determined by the maximum and minimum values of the tissues surrounding the AIMD lead. For the coarse search, the following parameters were used: the boundaries for the relative permittivity are 13 (fat) to 92 (skin), and for the conductivity, they are 0.06 (fat) to 1.21 S/m (artery) with a step size of 10 for the relative permittivity and 0.1 S/m for the conductivity, respectively. In an intermediate step between coarse and fine search, the inventor reduced the step size to 5 for the relative permittivity and 0.01 S/m for the conductivity. The search boundaries for the fine search are based on the results of the coarse search and the coarse step size, e.g., if the best fit for the coarse search are 20 and 0.2 S/m, the boundaries for the fine search are 10 to 30 for the relative permittivity and 0.1 S/m to 0,3 S/m and 10-30. Figure 20 shows a 3D plot of the error-function for a simplified lead model searching for the dielectric parameters of the equivalent medium parameters. Figure 20 demonstrates the 3D plot of the cost-function for one grid searching of equivalent medium parameters. Panel (a) of Figure 20 shows the result of coarse searching, and panel (b) of Figure 20 shows the result of fine searching. The searching boundaries for coarse searching are 0.06-1.21 S/m and 13-92. The steps are 0.1 S/m and 10. The best fitting parameters of the coarse searching are 0.2 S/m and 20 for conductivity and relative permittivity, respectively. The fine searching is performed from 0.1 to 0.3 S/m and 10 to 30 with searching steps of 0.01 S/m and 5. The best fitting parameters are 0.24 S/m (conductivity) and 25 (relative permittivity).

Validation of the Equivalent Medium Parameter Invariance for Different Lead Designs [0074] The equivalent medium parameters were assessed for a single lead and a single lead trajectory inside the human body model. Because the IPG and the lead can be modeled as a transmission line and the surrounding tissue can be considered as the return current pathway, it is believed that the determined equivalent medium parameters would be invariant for different lead designs. To verify, the inventor examined the following two scenarios.

[0075] Validation of the equivalent medium in multi -conductor systems: In the first scenario, the inventor determined the equivalent medium parameters for leads with two, three, and four straight inner conductors. Panel (a) of Figure 21 is an illustration of numerical modeling for electrode with multiple inner conductors. All conductors had a radius of 0.1 mm with an insulator thickness of 0.5 mm and a dielectric constant of 3. The transfer functions extracted from both environments were compared against each other to verify that the equivalent medium was independent of the number of inner conductors, which was the case for 2, 3, and 4 inner conductors. For two inner conductors’ simulations, it converged when AS = 0.0063 after 3 adaptive passes. The total simulation time was 72 minutes, including 31 minutes for adaptive meshing, running on the machine which has Inter Xeon E5-2697, 2.7GFIz CPU, and 128 GB installed memory. The total number of elements was 1379861.

[0076] Validation of the equivalent medium for helical electrodes systems: In addition to the validation for multiple straight inner conductor electrodes, helical electrodes as shown in Panel (b) of Figure 21 were also used. Panel (b) of Figure 21 is an illustration of numerical modeling for helical electrodes. The inventor has validated three sets helical electrodes: (1) helical electrode with a radius of 0.1 mm, pitch distance of 1 mm, embedded inside an insulator with dielectric constants of 3, 10, and 20; (2) helical electrode with a radius of 0.1 mm, dielectric constant of 3, with three different pitches of 1 mm, 2 mm, and 5 mm; and (3) helical electrode with a dielectric constant of 3, pitch distance of 1 mm, and three different radii of 0.1 mm, 0.12 mm, and 0.15 mm. These three sets of helical electrodes were embedded into both the inhomogeneous medium and the determined equivalent medium to demonstrate that the determined parameters for the equivalent medium were also valid for various helical electrode configurations.

[0077] Statistical Analysis of the determined equivalent parameters for different pathways: As shown in the Figure 18, the leads can be implanted along multiple pathways inside the human body during the surgeries. Along different pathways, the surrounding tissue can be different and therefore, the determined equivalent medium parameters may have a certain range. To understand such variations and investigate the robustness of equivalent medium method, the equivalent medium parameters along all 41 pathways were determined and analyzed using the grid searching illustrated above. The inventor determined both relative permittivity and conductivity of the equivalent medium. The statistical analysis was performed on two parameters variation.

Measurement Validation

[0078] To further validate the approach of the equivalent medium for practical application, an inhomogeneous phantom as shown in Panel (a) of Figure 22) was developed. The entire ASTM phantom was divided into three compartments. Each compartment has a width of 42 cm. Two acrylic sheets were used to divide the phantom into compartments with lengths of 24 cm, 15 cm, and 24 cm. Three 2 mm holes were drilled at the height of 4.5 cm from the bottom of the sheets with distance of 2 cm, 7 cm, and 12 cm from the sidewall of the ASTM phantom. The compartments were filled with gel whose dielectric constant was 78 and the conductivities were 0.65 S/m, 0.47 S/m, and 1.2 S/m. These values are chosen since they represent the conductivity values of muscle, the standard ASTM medium, and blood, respectively. Due to the difficulty of developing media with the exact relative permittivity values of muscle and blood (i.e., 72.2 and 86.4), the inventor used saline with a relative permittivity of 78. The holes in the separation sheets were filled with plastic plugs if no lead was routed through them.

[0079] The lead used in this testing was a solid wire as shown in Panel (c) of Figure 22. An IPG shaped copper sheet was connected to the center conductor of the solid wire with 2.2 Ohms resistor. The center conductor wire, the resistor, and the section near the resistor were insulated using glue, as shown in the Panel (c) of Figure 22. An SMA connector was connected to the copper sheet so that the input impedance between the copper sheet, i.e., the IPG ground, and the solid center conductor could be measured directly. The total length of the lead was 45 cm.

[0080] Based on the configuration shown in Panel (a) of Figure 22, the inhomogeneous phantom as shown in Panel (b) of Figure 22 was used to determine the equivalent medium parameters for the experimental and the numerical investigations.

[0081] To validate the accuracy of the equivalent medium approach, two sets of investigations need to be performed. The first set compared the transfer functions for the following scenarios: 1) the transfer function obtained from simulations using the inhomogeneous medium, 2) the transfer function obtained from simulations using the equivalent medium, 3) the experimentally measured transfer function using the inhomogeneous medium, and 4) the experimentally measured transfer function using the determined equivalent medium.

[0082] To measure the transfer function in the inhomogeneous phantom, the reciprocity method was used. The tip electrode was excited at the exposed center conductor connected to the output port of a network analyzer, while the input of the network analyzer was connected directly to a current probe. For the measurement of the transfer function under the equivalent medium, the phantom would be filled with homogeneous gel using the conductivity value determined in the simulation performed in 2) above.

[0083] The second set of the study was to place the inhomogeneous phantom inside the RF coil and measure temperature rises of the electrode tip. Three different pathways were developed as shown in Panel (a) of Figure 23. Since the three pathways had different lengths inside the three different compartments, the length inside the center compartment will change accordingly. In the experiments, the IPG mimicking copper sheet was inserted into a box filled with tap water to emulate an IPG embedded into low-conductive fat tissue. An illustration of the measurement setup is shown in Panel (b) of Figure 23. To measure the RF induced heating of the electrode tip exposed to an MRI RF coil the measurement setup was placed inside the Medical Implant Test System MITS 1.5 (Ziirich MedTech ZMT, Switzerland), illustrated in Panels (c) and (d) of Figure 23. Numerical simulation was used to calculate the required input power level for phantoms Filled the inhomogeneous medium when whole body averaged SAR at 2W/Kg using the ZMT coil. The corresponding input powers level is at 59.6 W. This input power was then delivered to the ZMT coil from the MITS system.

[0084] Based for the numerical and experimental procedures described above, the results will be used to demonstrate the effectiveness of the equivalent medium method.

[0085] Equivalent medium parameter determination with single conductor leads: Using one of the pathways shown in Figure 19 Panel (a), the determined electrical parameters for the equivalent medium has a dielectric constant of 25 and conductivity of 0.2 S/m. These parameters were determined by minimizing the difference between the equivalent medium transfer function derived from the equivalent medium and that from the inhomogeneous medium using the following equation (2):

[0086] For this particular solid leads, it requires seven minutes simulation time to calculate transfer function using HFSS software package on CPU with 3.3 GHz clock speed. To sweep through the entire search spacing (both dielectric and conductivity), it requires twelve hours. To determine the equivalent medium parameters for multiple conductors and the helical electrode, it took around 10 hours for each transfer function evaluation due to increased numbers of meshing elements in HFSS.

[0087] Validity of the equivalent medium for other electrodes: The RF induced heating for an implantable system can be assessed using the transmission line theorem, where the tissue itself acts as the return ground. Therefore, for different lead structures, the return ground is unchanged. Consequently, the determined equivalent medium would be independent of the electrode design. To demonstrate this, different electrode designs were simulated for the inhomogeneous and the equivalent medium, and the extracted transfer functions were compared. Regarding straight leads with different number of inner conductors, the comparisons of the extracted transfer functions for leads with two, three, and four straight inner conductors are shown in Panels (a)-(c) of Figure 24. Both the magnitude and phase of the transfer functions for the inhomogeneous and the equivalent medium are shown therein. As clearly shown in Panels (a)-(c) of Figure 24, although the transfer functions for leads with two, three, and four inner conductors are different from each together, the transfer functions extracted using the inhomogeneous medium and the equivalent medium agree with each other well. This shows that the equivalent medium is independent of the number of inner conductors. Regarding helical leads with different parameters, the effectiveness of the equivalent medium for helical lead designs was also investigated. The design configurations are outlined in Panel (b) of Figure 21. The comparisons of extracted the transfer functions for the equivalent and the inhomogeneous medium are given in Panels (d)-(l) of Figure 24. For different helical electrode design parameters, the magnitude and the phase of the transfer functions can change significantly. However, the transfer functions developed in the equivalent medium agree very well with ones extracted from the inhomogeneous medium, which demonstrates the equivalent medium is independent of specific electrode designs. The parameters of equivalent medium in all cases are a_b=0.20 S/m, e_b=25.

[0088] Statistical Analysis of the Determined Equivalent Parameters: Previously, the determined equivalent medium was based on a single selected pathway. In clinical application, different pathways can be used for implantation. To understand the impact of pathway variations on the accuracy of the determined equivalent medium parameters, the inventor assessed the equivalent parameters for 41 pathways shown in Panels (a) and (b) of Figure 25. The determined conductivity values have a mean value of 0.18 S/m with a standard deviation of 0.024 S/m, which is equivalent to a percentage variation at 13.2%. The determined relative permittivity values have a mean value of 33.6 with a standard deviation of 5.12, which is equivalent to a percentage variation of 15.2%.

[0089] Based on the inhomogeneous phantom described above, the equivalent medium parameters were determined. Because it may be difficult to develop phantoms with arbitrary dielectric constant, in the experimental study, all dielectric constant was at 78 while the conductivity varied. The equivalent medium conductivity for the three pathways (as shown in Panel (a) of Figure 23) were determined. Due to different lead lengths inside the 0.47 S/m medium, the determined conductivity changed slightly. For the first experimental pathway, the equivalent conductivity is 0.675 S/m; while for the other two pathways, the equivalent conductivity is 0.65 S/m. Both modeling and the measurements were used to develop the transfer function for the three pathways. The transfer functions along the first pathway for the inhomogeneous medium and the equivalent medium were extracted numerically and experimentally. The results are shown in Figure 26. The transfer functions from the inhomogeneous medium match very well with those from the equivalent medium, which further proves that the equivalent medium theorem is validated experimentally.

[0090] The direct measurement of the temperature rises was also compared with those from the predictions. In the prediction, the temperature rise near the device tip was evaluated using the following equation (3):

where E_inc is the incident electric field along the trajectories of the implantable leads and the T(l) is the normalized transfer function, in V°C/F. The incident electric field along all three pathways were extracted at an exposure level of 2W/kg whole body SAR, and shown in Panels (a) and (b) of Figure 27. Referring to Panel (a) of Figure 27, there is a discontinuity of the electric field due to the 2 mm acrylic sheet thickness. This incident fields along the lead pathways were then integrated with the equivalent medium and inhomogeneous transfer functions developed earlier to obtain the temperature rises along the three different pathways.

[0091] The exposure time for the heating assessment was 5 minutes for each pathway. The results of the measured temperature rise and the simulated temperature rises for all three pathways are shown in supporting information Table Sl. All temperature rises are normalized to an exposure level of 2W/kg whole body SAR. Table Sl : The measured temperature rises after 5 minutes scanning by 1.5T RF coil

[0092] The uncertainty budget for the validation measurements was l5.8%±l.0°C, The uncertainty of l.0°C is due to readout error of temperature probe. The detailed information about uncertainty evaluation is shown in supporting information Table S2. As shown in Panel (c) of Figure 27, all data points are within a±l.0°C uncertainty boundary, with a standard deviation s of 15.8%.

Table S2: Uncertainty of the validation tests

[0093] These results indicate that the equivalent medium is valid for multi-conductor lead and helical electrode designs. Therefore, as long as the lead pathways are determined, the developed equivalent medium can be used for different lead and electrode designs. Furthermore, the comparison of the extracted transfer functions in two different media is shown in Figure 28. It shows that the magnitude and phase of the transfer functions using the inhomogeneous human tissue and its equivalent medium, whose parameters are 25 and 0.2 S/m, agree closely. For comparison purpose, the tissue averaged dielectric constant and conductivity values along the lead pathway were also obtained following ASTM standard. The averaged value for dielectric constant was 38 while the averaged conductivity was 0.3 S/m, which are calculated by volume average of all tissue boxes surrounding the AIMD. Both values are inconsistent with the optimized parameters for the equivalent medium which are 25 and 0.2 S/m, respectively. The transfer function using averaged tissue dielectric constant and conductivity values was also extracted and shown in Figure 28. Using the equivalent medium extracted transfer function showed a better agreement with the real clinical scenario.

[0094] The results from the above statistical analysis show that one can use the mean value of the determined conductivity and relative permittivity values as the parameters for the equivalent medium and include extra values of 13.24% and 15.23% in the overall uncertainty analysis. In this particular investigation, the sleep apnea pathways from an adult male model was used to demonstrate that one can use the equivalent medium together with the associated uncertainty to efficiently and accurately address the RF safety for active implantable devices. This theorem can be applied to any other clinical pathways, such as for cardiac pacing or deep brain stimulation devices. In some cases, due to potential routine variations, the determined equivalent medium values can be clustered into more than one group along different pathways. One can use one equivalent medium with large uncertainty or more than one sub- set of equivalent media with smaller uncertainties to achieve accurate and efficient RF heating evaluation.

[0095] The above measurement further validated that the equivalent medium theorem works very well, and it can be used to accurately predict the RF induced heating for implanted medical devices. Although the work was performed for 1.5T MRI system, this method can be easily extended to 3T MRI system safety evaluation by simply replacing the human tissue parameters with those at 128 MHz.

[0096] The equivalent medium theorem is thus established for the RF heating safety evaluation of active implantable devices under MRI exposure. The method is based on rigorous electromagnetic simulation to determine the medium parameters based on clinical lead trajectories. The equivalent medium parameters are independent of the leads and electrode types and are only related to the surrounding tissues of the device pathway inside a patient. Both numerical and direct measurements were used to demonstrate the effectiveness of the equivalent medium for implantable device heating evaluations.

[0097] In the foregoing specification, embodiments of the present invention have been described with reference to numerous specific details that may vary from implementation to implementation. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense. The sole and exclusive indicator of the scope of the invention, and what is intended by the applicant to be the scope of the invention, is the literal and equivalent scope of the set of claims that issue from this application, in the specific form in which such claims issue, including any subsequent correction.

Claims

CLAIMS:

1. A method for measuring radio frequency (RF) induced heating and voltage on or near an active implantable medical device (AIMD) and its surroundings during magnetic resonance imaging (MRI), so as to determine if the presence of the AIMD may cause injury to a patient with the AIMD during a MR procedure, comprising:

providing an AIMD comprising an electronic system and a lead, wherein the lead consists of a proximal end, a distal end, and a lead body between the proximal end and the distal end;

wherein the proximal end is electronically connected to the electronic system; and wherein the lead body is designed to pass through an inhomogeneous tissue path within the patient’s body; providing a phantom that simulates the electrical and thermal properties of a

human body, wherein the phantom comprises a first homogeneous medium, a second

homogeneous medium, and a third homogeneous medium, wherein the second homogeneous medium has a conductivity ob and a relative permittivity erb different from those of first homogeneous medium and the third homogeneous medium, and wherein the conductivity ob is within the range of from 6 to 80 and the permittivity crb is within the range of from 0 to 2 S/m; immersing the proximal end, the lead body and the distal end of the lead entirely into the first homogeneous medium, the second homogeneous medium, and the third homogeneous medium, respectively; and

placing the phantom with the AIMD in a magnetic resonance (MR) test system and measuring RF induced heating and voltage on or near the AIMD.

2. The method according to Claim I, wherein the conductivity ob is within the range of from X to Y, X<Y, and X and Y are independently of each other selected from 6, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 and 80.

3. The method according to Claim 1, wherein the relative permittivity erb is within the range of from U to V, U<V, and U and V are independently of each other selected from 0.01 S/m, 0.1 S/m, 0.2 S/m, 0.3 S/m, 0.4 S/m, 0.5 S/m, 0.6 S/m, 0.7 S/m, 0.8 S/m, 0.9 S/m, 1.0 S/m, 1.1 S/m, 1.2 S/m, 1.3 S/m, 1.4 S/m, 1.5 S/m, 1.6 S/m, 1.7 S/m, 1.8 S/m, 1.9 S/m, and 2.0 S/m.

4. The method according to Claim 1, wherein the conductivity ob of the second homogeneous medium is in the range of 25-35, and wherein the permittivity erb of the second homogeneous medium is in the range of 0.17-0.2 S/m.

5. The method according to Claim 1, wherein the conductivity ob and relative permittivity erb are measured in a test frequency of 64-180 MHz such as 64 MHz and 128 MHz.

6. The method according to Claim 1, wherein the electronic system comprises an implantable pulse generator (IPG), and it is also immersed into the first homogeneous medium with the proximal end of the lead.

7. The method according to Claim 1, wherein the lead comprises a helical conductor with submillimeter coiling structures.

8. The method according to Claim 1, wherein the second homogeneous medium simulates a combination of two or more different tissues.

9. The method according to Claim 8, wherein the second homogeneous medium simulates a combination of fat tissue and muscle tissue.

10. The method according to Claim 1, wherein the first homogeneous medium simulates fat tissue or muscle tissue, and the third homogeneous medium simulates muscle tissue or fat tissue.

11. The method according to Claim 1 , wherein the first homogeneous medium is a high permittivity medium (HPM) with e_t = 78 and s = 0.47 or 0.65 or 1.2 S/m; or a low permittivity medium (LPM) with e_T = 11.5 or 15.1 and s = 0.045 S/m.

12. The method according to Claim 1, wherein the third homogeneous medium is a high permittivity medium (HPM) with e_t = 78 and s = 0 47 or 0.65 or 1.2 S/m; or a low permittivity medium (LPM) with e = 11.5 or 15.1 and s = 0.045 S/m.

13. The method according to Claim 1, wherein the first homogeneous medium, the second homogeneous medium, and the third homogeneous medium each comprises a gelled saline.

14. The method according to Claim 13, wherein the gelled saline comprises a saline (sodium chloride) solution and a gelling agent.

15. The method according to Claim 14, wherein the gelling agent is a gelling polymer selected from polyacrylic acid (PAA), hydroxy ethylcellulose (HEC), or any mixture thereof.

16. The method according to Claim 15, wherein the conductivity and relative permittivity of the first homogeneous medium, the second homogeneous medium, or the third homogeneous medium are individually controlled by adjusting or fine-tuning the amount of NaCl and the gelling polymer in the medium material.

17. The method according to Claim 1, wherein the conductivity ob and the relative permittivity srb of the second homogeneous medium are determined based on (1) a transmission line model for the lead, (2) a full-wave simulation of human tissues along a path of the lead, and (3) a reciprocity-based transfer function model as a criterion for optimizing the medium parameters.

18. The method according to Claim 17, wherein e* is fixed to 78, and only s_¾ is optimized.

19. The method according to Claim 1, further comprising a step of marking the AIMD with a MR safety assessment and including recommended information in the marking.

20. The method according to Claim 1 , further comprising one or more steps in standard method ASTM F2182-1 l a, mutatis mutandis.