IP Library Granted Patent US 10,188,851
Granted Patent B2
US 10,188,851 · App. 15/336,660 · Granted Jan 29, 2019

TTField treatment with optimization of electrode positions on the head based on MRI-based conductivity measurements

Inventors: Cornelia Wenger (Ericeira, PT); Pedro Michael Cavaleiro Miranda (Lisbon, PT); Zeev Bomzon (Kiyat Tivon, IL); Noa Urman (Pardes Hanna Carcur, IL); Eilon Kirson (Ramat Hasharon, IL); Yoram Wasserman (Haifa, IL); Yoram Palti (Haifa, IL)
Assignee: NOVOCURE LIMITED
A61N1/0456A61B5/0042A61B5/053A61B5/055A61N1/0476A61N1/08A61N1/32A61N1/36002A61N1/36025A61N1/40G06F19/00G16H50/50
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Quick Facts
Patent No.
US 10,188,851
App. No.
15/336,660
Granted
Jan 29, 2019
Kind
B2
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 (28)

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.

2. 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.

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

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

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

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

7. 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, σ v =s·d v , where σ v and d v are the v th eigenvalues of the conductivity and the diffusion respectively.

8. 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.

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

10. 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.

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

12. 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.

13. 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.

14. 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.

15. 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.

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

17. 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.

18. 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.

19. 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.

Assignments (13)
PATENT SECURITY AGREEMENT Recorded May 4, 2024
From: NOVOCURE GMBH (SWITZERLAND)
To: BIOPHARMA CREDIT PLC
Reel/Frame 067315/0399 →
RELEASE OF SECURITY INTEREST Recorded Apr 24, 2024
From: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
To: NOVOCURE GMBH
Reel/Frame 067211/0839 →
SECURITY INTEREST Recorded Nov 6, 2020
From: NOVOCURE GMBH
To: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 054344/0510 →
SUPPLEMENTAL RELEASE OF SECURITY INTEREST FOR PATENT SECURITY AGREEMENT FILED AT REEL/FRAME 45284 0851 Recorded Aug 25, 2020
From: BIOPHARMA CREDIT PLC
To: NOVOCURE LIMITED
Reel/Frame 053597/0253 →
RELEASE OF SECURITY INTEREST FOR PATENT SECURITY AGREEMENT FILED AT REEL/FRAME 45278 0825 Recorded Aug 25, 2020
From: BIOPHARMA CREDIT PLC
To: NOVOCURE LIMITED
Reel/Frame 053597/0335 →
RELEASE OF SECURITY INTEREST FOR PATENT SECURITY AGREEMENT FILED AT REEL/FRAME 50395/0398 Recorded Aug 19, 2020
From: BPCR LIMITED PARTNERSHIP
To: NOVOCURE GMBH
Reel/Frame 053538/0623 →
OMNIBUS CONFIRMATION OF ASSIGNMENT AGREEMENT Recorded May 21, 2020
From: BIOPHARMA CREDIT PLC
To: BPCR LIMITED PARTNERSHIP
Reel/Frame 052741/0173 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 20, 2019
From: NOVOCURE LIMITED
To: NOVOCURE GMBH
Reel/Frame 050110/0098 →
SECURITY INTEREST Recorded May 6, 2019
From: NOVOCURE GMBH
To: BIOPHARMA CREDIT PLC
Reel/Frame 050395/0398 →
SECURITY INTEREST Recorded Feb 7, 2018
From: NOVOCURE LIMITED
To: BIOPHARMA CREDIT PLC
Reel/Frame 045278/0825 →
SECURITY INTEREST Recorded Feb 7, 2018
From: NOVOCURE LIMITED
To: BIOPHARMA CREDIT PLC
Reel/Frame 045284/0851 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 10, 2017
From: WASSERMAN, YORAM
To: NOVOCURE LIMITED
Reel/Frame 040935/0222 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 28, 2016
From: WENGER, CORNELIA; MIRANDA, PEDRO MICHAEL CAVALEIRO; BOMZON, ZEEV; URMAN, NOA; KIRSON, EILON; WASSERMAN, YORAM; PALTI, YORAM
To: NOVOCURE LIMITED
Reel/Frame 040788/0783 →
Continuity (3)
Provisional Application 62294372 · Feb 12, 2016
Provisional Application 62247314 · Oct 28, 2015
Related Publication 20170120041A1 · May 4, 2017
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