The electric field distribution in the brain during TTFields therapy and its dependence on tissue dielectric properties and anatomy: a computational study.
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.
Institute of Biophysics and Biomedical Engineering, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.
Cornelia
C
Wenger
Ricardo
R
Salvador
Peter J
PJ
Basser
Pedro C
PC
Miranda
D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000033:anatomy & histology*; D001932:Brain Neoplasms / Q000628:therapy*; D058256:Brain Waves; D004553:Electric Conductivity; D004599:Electric Stimulation Therapy / Q000295:instrumentation / Q000379:methods*; D005260:Female; D020342:Finite Element Analysis; D005909:Glioblastoma / Q000628:therapy*; D006257:Head / Q000033:anatomy & histology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008953:Models, Anatomic; D008959:Models, Neurological; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D055815:Young Adult