The electric field distribution in the brain during TTFields therapy and its dependence on tissue dielectric properties and anatomy: a computational study

Abstract

Tumor Treating Fields (TTFields) are a non-invasive, anti-mitotic and approved treatment for recurrent glioblastoma multiforme (GBM) patients. In vitro studies have shown that inhibition of cell division in glioma is achieved when the applied alternating electric field has a frequency in the range of 200 kHz and an amplitude of 1 - 3 V/cm. Our aim is to calculate the electric field distribution in the brain during TTFields therapy and to investigate the dependence of these predictions on the heterogeneous, anisotropic dielectric properties used in the computational model. A realistic head model was developed by segmenting MR images and by incorporating anisotropic conductivity values for the brain tissues. The finite element method (FEM) was used to solve for the electric potential within a volume mesh that consisted of the head tissues, a virtual lesion with an active tumour shell surrounding a necrotic core, and the transducer arrays. The induced electric field distribution is highly non-uniform. Average field strength values are slightly higher in the tumour when incorporating anisotropy, by about 10% or less. A sensitivity analysis with respect to the conductivity and permittivity of head tissues shows a variation in field strength of less than 42% in brain parenchyma and in the tumour, for values within the ranges reported in the literature. Comparing results to a previously developed head model suggests significant inter-subject variability. This modelling study predicts that during treatment with TTFields the electric field in the tumour exceeds 1 V/cm, independent of modelling assumptions. In the future, computational models may be useful to optimize delivery of TTFields.

The effects of tumor treating fields and temozolomide in MGMT expressing and non-expressing patient-derived glioblastoma cells

“…There are two physical phenomena which underlie the effect of TTFields: dielectrophoresis which occurs mainly during cytokinesis, and dipole alignment. Electric field simulations have demonstrated that the frequencies expected to cause maximal dielectrophoretic forces during cytokinesis are within the range of 100-200 kHz, while the maximal effect on dipole alignment is expected to appear at higher frequencies (towards 1 MHz) [30]. It is therefore possible that the biphasic nature of the observed response is the outcome of dielectrophoresis induced at 200 KHz, and dipole alignment occurring at higher frequencies.…”

Tumor-Treating Fields: A Fourth Modality in Cancer Treatment

“…TTFields are nonuniformly distributed within the treated region based on multiple parameters, which include the geometry of the treated organ, the distance between transducer arrays applied to the patient's skin, and the tissue's dielectric properties (20)(21)(22). The fields do not attenuate in correlation to the distance from the array, and may therefore be used for the treatment of deeply located tumors (21,22).…”

“…The fields do not attenuate in correlation to the distance from the array, and may therefore be used for the treatment of deeply located tumors (21,22). As electric fields do not have a half-life time, TTFields are continuously delivered during the course of treatment.…”

Planning TTFields treatment using the NovoTAL system-clinical case series beyond the use of MRI contrast enhancement

“…Electric field distribution within the brain is nonuniform, and is a function of the direction of a field, individual dielectric properties of adjacent tissue structures, and the orientation of the interfaces between them [9, 10]. The algorithm will compute the optimal paired configuration of transducer arrays that should be applied directly to a patient’s shaved scalp that will locally deliver the highest intensity of TTFields at the site of a tumor.…”

“…In general, high energy gamma radiation has a frequency in the order of exahertz (10 20 ), with a wavelength of picometers (10 −19 ), less than the diameter of an atom [8]. As the frequency of TTFields is much lower at 200 kHz, and the wavelength much longer (~1 mile), TTFields cannot be precisely focused and delivered to discrete regions of the brain in the same focal manner as RT [9, 10]. Treatment can, however, be optimized to ensure that field intensity is maximal at the site of a tumor [11–13], a process which involves planning with the NovoTAL System software.…”