Estimation of TTFields Intensity and Anisotropy with Singular Value Decomposition: A New and Comprehensive Method for Dosimetry of TTFields

Abstract

Tumor-treating fields (TTFields) are a new cancer treatment that inhibits tumor growth with alternating electrical fields. Finite element (FE) methods are used to calculate the intensity of TTFields as a measure of therapeutic “dose.” However, the antitumor efficacy also depends on the direction and exposure time of the induced fields. We recently proposed a new FE approach for TTFields dosimetry that incorporates all these parameters in order to estimate both the unwanted directional field correlation (fractional anisotropy, FA) and the average field intensity. The method uses singular value decomposition to decompose the sequential TTFields over one duty cycle into principal components. Using this method, we showed that significant unwanted FA occurs in many brain regions, potentially affecting therapeutic efficacy. The distribution of FA in the brain varies between different transducer array layouts, and in fact the FA estimate indicates a different order of array performance than predicted from the more conventional estimate of field intensity. Furthermore, we found that resection of the tumor tends to nullify field distribution differences between array layouts while also significantly increasing FA. Contrary to the current practice, these results suggest that it may be more effective to place the TTFields arrays to maximize the field intensity in the tumor, rather than trying to maintain macroscopic orthogonality between the layout pairs. This principal component analysis framework has a number of potential applications, including technology development, outcome prognostication, improved treatment planning, and activation cycle optimization. This chapter describes the framework for the principal component calculations and recapitulates the current results. Furthermore, it provides a detailed outline of how patient-specific head models can be used to calculate the field distribution for individual patients.