A computer-implemented method for registering a medical image with a coordinate space of an ultrasound treatment system, the steps of the method comprising: (a) providing a medical image of a subject that depicts an anatomical feature, wherein the anatomical feature is a skull of a subject; (b) acquiring ultrasound data from the subject using an array of ultrasound transducer elements that forms a part of an ultrasound treatment system, wherein the ultrasound transducer elements have known spatial locations; (c) computing a time-of-flight measurement for each transducer element from the ultrasound data; (d) determining locations associated with the anatomical feature from the provided medical image of the subject; (e) determining registration parameters from the computed time-of-flight measurements and the locations determined in step (d); and (f) registering the provided medical image with the coordinate space of the ultrasound system using the registration parameters determined in step (e); wherein step (e) includes minimizing a cost function that is based at least in part on distances, each of them being associated with a different transducer element, wherein each distance is the minimum distance between a spherical surface centered about a transducer element and the determined locations associated with the anatomical feature; wherein the cost function additionally includes for each transducer element a penalty function that penalizes further solutions to the cost function; wherein the penalty function has a zero value when the skull sits above a spherical surface centered about the transducer element, and has the value of the distance the skull has penetrated the spherical surface centered about the transducer element, times a weighting factor α equal to 0.25, 0.5, 0.75, or 1, if any points on the skull surface lie closer to the transducer element than the radius of the spherical surface centered about the transducer element; and wherein a spherical surface centered about a transducer has a radius defined by the computed time-of-flight measurement for the associated transducer element. (a) providing a medical image of a subject that depicts an anatomical feature, wherein the anatomical feature is a skull of a subject; (b) acquiring ultrasound data from the subject using an array of ultrasound transducer elements that forms a part of an ultrasound treatment system, wherein the ultrasound transducer elements have known spatial locations; (c) computing a time-of-flight measurement for each transducer element from the ultrasound data; (d) determining locations associated with the anatomical feature from the provided medical image of the subject; (e) determining registration parameters from the computed time-of-flight measurements and the locations determined in step (d); and (f) registering the provided medical image with the coordinate space of the ultrasound system using the registration parameters determined in step (e); wherein step (e) includes minimizing a cost function that is based at least in part on distances, each of them being associated with a different transducer element, wherein each distance is the minimum distance between a spherical surface centered about a transducer element and the determined locations associated with the anatomical feature; wherein the cost function additionally includes for each transducer element a penalty function that penalizes further solutions to the cost function; wherein the penalty function has a zero value when the skull sits above a spherical surface centered about the transducer element, and has the value of the distance the skull has penetrated the spherical surface centered about the transducer element, times a weighting factor α equal to 0.25, 0.5, 0.75, or 1, if any points on the skull surface lie closer to the transducer element than the radius of the spherical surface centered about the transducer element; and wherein a spherical surface centered about a transducer has a radius defined by the computed time-of-flight measurement for the associated transducer element.