THE USE OF GENERALIZED CELL-SURVIVAL DATA IN A PHYSIOLOGICALLY-BASED OBJECTIVE FUNCTION FOR HYPERTHERMIA TREATMENT PLANNING - A SENSITIVITYSTUDY WITH A SIMPLE TISSUE MODEL IMPLANTED WITH AN ARRAY OF FERROMAGNETIC THERMOSEEDS

Purpose: A physiologically based objective function for identifying a combination of ferromagnetic seed temperatures and locations that maxi mizes the fraction of tumor cells killed in pretreatment planning of l ocal hyperthermia. Methods and Materials: An objective-function is dev eloped and coupled to finite element software that solves the bioheat transfer equation. The sensitivity of the objective function is studie d in the optimization of a ferromagnetic hyperthermia treatment. The o bjective function has several salient features including (a) a physiol ogical basis that considers increasing the fraction of cells killed wi th increasing temperatures above a minimum therapeutic temperature (T- min,T-thera), (b) a term to penalize for heating of normal tissues abo ve T-min,T-thera, and (c) a scalar weighting factor (gamma) that has t reatment implications. Reasonable estimates for gamma are provided and their influence on the objective function is demonstrated. The cell-k ill algorithm formulated in the objective function is based empiricall y upon the behavior of published hyperthermic cell-survival data. The objective function is shown to be independent of normal tissue size an d shape when subjected to a known outer-surface, thermal boundary cond ition. Therefore, fractions of cells killed in tumors of different sha pes and sizes tan be compared to determine the relative performance of thermoseed arrays to heat different tumors. Results: In simulations w ith an idealized tissue model perfused by blood at various rates, maxi ma of the objective function are unique and identify seed spacings and Curie-point temperatures that maximize the fraction of tumor cells ki lled. In ferromagnetic hyperthermia treatment planning, seed spacing c an be based on maximizing the minimum tumor temperature and minimizing the maximum normal tissue temperature. It is shown that this treatmen t plan is less effective than a plan based on seed spacings that maxim ize the objective function. Conclusions: It is shown that under the as sumptions of the model and based on a desired therapeutic goal, the ob jective function identifies a combination of thermoseed temperatures a nd locations that maximizes the fraction of tumor cells killed.