1. A method for determining a treatment response of a treatment for a region of interest, comprising: registering at least a first image data and a second image data of a region of interest, the first image data corresponding to a first time point, the second image data corresponding to a second time point, the first time point and the second time point being different with respect to a session and/or treatment stage; determining a treatment response, by a computer having a processor and a memory, based on at least the registered image, treatment plan information associated with the treatment, or a combination thereof, the determining including: processing the registered image to determine a difference image; processing at least the difference image to determine one or more signal regions, each signal region corresponding one or more voxels that are grouped together based on location and signal value; and determining a treatment response associated with the signal value of the one or more signal regions, a positive signal region indicating a treatment-resistant region and a negative signal region indicating a respondent region; and outputting treatment response results.