A focused-ultrasound or other procedure for treating a target within a tissue region can be planned iteratively by creating a treatment plan specifying a treatment location pattern and stimuli applied thereto, simulating the treatment, computationally predicting an effect of the simulated treatment, comparing the predicted effect against one or more treatment constraints (such as efficacy and/or safety thresholds), and, if a constraint is violated, repeating the simulation for an adjusted treatment plan.
