Abstract: The disclosed subject matter provides systems and methods for targeting tissue structures and applying ultrasound thereto. A method according to the disclosed subject matter for targeting a tissue structure using corresponding tissue structure image data includes inputting the tissue structure image data into a targeting simulator, determining acoustic properties of the tissue structure from the corresponding tissue structure image data, and utilizing the determined acoustic properties to align a simulated transducer with the tissue structure such that the tissue structure is targeted. The method can further include acquiring the tissue structure image data, aligning the image data with an atlas of a body structure encompassing the tissue structure and/or selecting parameters of the simulated transducer such that a focal region of an ultrasound wave generated by the simulated transducer targets the tissue structure.