# US 10,188,851 B2 · TTField treatment with optimization of electrode positions on the head based on MRI-based conductivity measurements

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- Number: US 10,188,851 B2
- Document ID: US10188851B2
- Status: Granted
- Kind: B2
- Application number: 15/336,660
- Filed: 2016-10-27
- Published: 2017-05-04
- Granted: 2019-01-29
- Earliest claimed: 2015-10-28
- Assignees: Novocure GmbH
- Applicants: Novocure Limited
- Inventors: Cornelia Wenger; Pedro Michael Cavaleiro Miranda; Zeev Bomzon; Noa Urman; Eilon Kirson; Yoram Wasserman; Yoram Palti
- Web page: https://patentgrep.com/patent/US10188851B2

## CPC

- A61N 1/0456: {Specially adapted for transcutaneous electrical nerve stimulation [TENS]}
- A61B 5/0042: {for the brain}
- A61B 5/05: Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves (measuring movement of the entire body or parts thereof A61B5/11; detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof A61B5/24)
- A61B 5/053: Measuring electrical impedance or conductance of a portion of the body
- A61B 5/055: involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
- A61B 5/24: Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B 5/316: Modalities, i.e. specific diagnostic methods
- A61B 5/4064: {Evaluating the brain (for intracranial pressure A61B5/031; for cerebral blood gases A61B5/14553; using EEG A61B5/369)}
- A61N 1/0476: {Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)}
- A61N 1/32: alternating or intermittent currents {(applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02)}
- A61N 1/36002: {Cancer treatment, e.g. tumour}
- A61N 1/36025: {for treating a mental or cerebral condition}
- A61N 1/40: Applying electric fields by inductive or capacitive coupling (microwave apparatus A61N5/00); {Applying radio-frequency signals}
- G16H 50/50: for simulation or modelling of medical disorders
- G16Z 99/00: Subject matter not provided for in other main groups of this subclass
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16Z: INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS, NOT OTHERWISE PROVIDED FOR

## Abstract

When electrodes are used to impose an electric field in target tissue within an anatomic volume (e.g., to apply TTFields to treat a tumor), the position of the electrodes can be optimized by obtaining electrical conductivity measurements in an anatomic volume and generating a 3D map of the conductivity directly from the obtained electrical conductivity or resistivity measurements, without segmenting the anatomic volume into tissue types. A location of the target tissue is identified within the anatomic volume, and the positions for the electrodes are determined based on the 3D map of electrical conductivity and the position of the target tissue.

## Claims

### Claim 1

A method of optimizing positions of a plurality of electrodes placed on a subject's body, wherein the electrodes are used to impose an electric field in target tissue within an anatomic volume, the method comprising the steps of:
obtaining electrical conductivity or resistivity measurements in the anatomic volume;
generating a 3D map of electrical conductivity or resistivity of the anatomic volume directly from the obtained electrical conductivity or resistivity measurements, without segmenting the anatomic volume into tissue types;
identifying a location of the target tissue within the anatomic volume; and
determining positions for the electrodes based on the 3D map of electrical conductivity or resistivity generated in the generating step and the location of the target tissue identified in the identifying step.

### Claim 2 (depends on 1)

The method of claim 1, further comprising the steps of:
affixing the electrodes to the subject's body at the positions determined in the determining step; and
applying electrical signals between the electrodes subsequent to the affixing step, so as to impose the electric field in the target tissue.

### Claim 3 (depends on 1)

The method of claim 1, wherein the measurements obtained in the obtaining step represent the diffusion of molecules.

### Claim 4 (depends on 1)

The method of claim 1, wherein the obtaining step comprises acquiring MRI data using diffusion weighted imaging.

### Claim 5 (depends on 1)

The method of claim 1, wherein the obtaining step comprises acquiring MRI data using customized multi echo gradient sequences.

### Claim 6 (depends on 1)

The method of claim 1, wherein the obtaining step comprises acquiring MRI data using diffusion tensor imaging.

### Claim 7 (depends on 6)

The method of claim 6, wherein the step of acquiring MRI data using diffusion tensor imaging comprises a direct mapping method that assumes a linear relationship between eigenvalues of diffusion and conductivity tensors, σv=s·dv, where σv and dv are the vth eigenvalues of the conductivity and the diffusion respectively.

### Claim 8 (depends on 6)

The method of claim 6, wherein the step of acquiring MRI data using diffusion tensor imaging comprises a volume normalized method in which a geometric mean of conductivity tensors eigenvalues in each volume element in the anatomic volume are matched locally to specific isotropic conductivity values of a tissue type to which the volume element belongs.

### Claim 9 (depends on 1)

The method of claim 1, wherein the anatomic volume comprises white matter and grey matter of a brain.

### Claim 10 (depends on 1)

The method of claim 1, wherein the anatomic volume is a brain, and
wherein the determination of positions for the electrodes is based on a composite model in which the 3D map of electrical conductivity or resistivity of the brain is surrounded by a model of a first shell having a first constant conductivity.

### Claim 11 (depends on 10)

The method of claim 10, wherein the model of the first shell represents a scalp, a skull, and CSF, taken together.

### Claim 12 (depends on 10)

The method of claim 10, wherein the model of the first shell represents CSF,
wherein the composite model further includes a second shell that represents a skull, the second shell having a second constant conductivity, and
wherein the composite model further includes a third shell that represents a scalp, the third shell having a third constant conductivity.

### Claim 13 (depends on 10)

The method of claim 10, wherein the step of determining positions for the electrodes comprises adding a dipole to the composite model at a location that corresponds to the target tissue and selecting external positions at which a potential attributable to the dipole is maximum.

### Claim 14 (depends on 1)

The method of claim 1, wherein the step of determining positions for the electrodes comprises calculating positions for the electrodes that will provide a maximum intensity of the electric field in the target tissue.

### Claim 15 (depends on 1)

The method of claim 1, wherein, in the generating step, the 3D map has a resolution that is higher than 1 mm×1 mm×1 mm.

### Claim 16 (depends on 1)

The method of claim 1, wherein the step of generating a 3D map comprises generating a simple geometric object representing the anatomic volume.

### Claim 17 (depends on 1)

The method of claim 1, wherein the step of generating a 3D map comprises classifying a tissue type for each volume element based on a fractional anisotropy.

### Claim 18 (depends on 1)

The method of claim 1, wherein the step of generating a 3D map comprises classifying a tissue type for each volume element based on a mean conductivity.

### Claim 19 (depends on 1)

The method of claim 1, wherein the step of generating a 3D map comprises matching geometric means of conductivity tensors' eigenvalues to specific isotropic reference values.