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−1. 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−1, independent of modelling assumptions. In the future, computational models may be useful to optimize delivery of TTFields.
Highlights
Tumour Treating Fields (TTFields) are alternating electric fields of intermediate frequencies (100-300 kHz) with intensities between 1 and 3 V/cm that are delivered via capacitively coupled transducer arrays
The impact of anisotropic conductivity on the electric field distribution was analysed based on three versions of model s2: one with isotropic conductivity values and two with anisotropic grey matter (GM) and white matter (WM) values
This is in agreement with a study on the electric field distribution in transcranial magnetic stimulation (TMS), where the authors reported that taking anisotropy into account consistently increases the average field strength in the brain for all conductivity mappings (Opitz et al 2011)
Summary
Tumour Treating Fields (TTFields) are alternating electric fields of intermediate frequencies (100-300 kHz) with intensities between 1 and 3 V/cm that are delivered via capacitively coupled transducer arrays. This non-invasive and anti-mitotic treatment is intended to selectively target dividing cells. TTFields were approved in 2011 by the U.S Food and Drug Administration (FDA) for the treatment of recurrent glioblastoma multiforme (GBM). The application of TTFields leads to distinct biophysical effects observed during in vitro experiments. Kirson et al (Kirson et al 2004) reported that when cells were treated with TTFields, was the mitotic phase prolonged or completely arrested, but a variety of abnormal mitotic figures were observed. If the cell proceeded to telophase, membrane blebbing and rupture occurred in one fourth of the tested cells, leading to cell death
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