Predicting the electric field distribution in the brain for the treatment of glioblastoma

Abstract

The use of alternating electric fields has been recently proposed for the treatment of recurrent glioblastoma. In order to predict the electric field distribution in the brain during the application of such tumor treating fields (TTF), we constructed a realistic head model from MRI data and placed transducer arrays on the scalp to mimic an FDA-approved medical device. Values for the tissue dielectric properties were taken from the literature; values for the device parameters were obtained from the manufacturer. The finite element method was used to calculate the electric field distribution in the brain. We also included a “virtual lesion” in the model to simulate the presence of an idealized tumor. The calculated electric field in the brain varied mostly between 0.5 and 2.0 V/cm and exceeded 1.0 V/cm in 60% of the total brain volume. Regions of local field enhancement occurred near interfaces between tissues with different conductivities wherever the electric field was perpendicular to those interfaces. These increases were strongest near the ventricles but were also present outside the tumor’s necrotic core and in some parts of the gray matter-white matter interface. The electric field values predicted in this model brain are in reasonably good agreement with those that have been shown to reduce cancer cell proliferation in vitro. The electric field distribution is highly non-uniform and depends on tissue geometry and dielectric properties. This could explain some of the variability in treatment outcomes. The proposed modeling framework could be used to better understand the physical basis of TTF efficacy through retrospective analysis and to improve TTF treatment planning.

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.…”

“…Therefore, optimal TTFields delivery depends on multidirectional application of the electric fields to target cells undergoing mitosis in different spatial orientations. TTFields are delivered through two pairs of transducer arrays that sequentially deliver orthogonal or perpendicular fields within the tumor, thereby maximizing TTFields delivery to all cells comprising the tumor (5,21,37). In GBM, patient MRI data are used to individualize the transducer array placement, maximizing field intensity at the target tissue (38).…”

Skull Modeling Effects in Conductivity Estimates Using Parametric Electrical Impedance Tomography

“…However, in some applications such as classical imaging EIT [31] or modeling Tumor Treating fields [96], knowing the background conductivities at higher frequencies (typically in the kHz range) may be important. With a typical EIT equipment in the kHz range, the same pipeline followed in this work can be replicated to get this valuable information.…”

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

“…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.…”