Systems and methods are disclosed that facilitate obtaining two dimensional (2D) ultrasound images, using two or more ultrasound imaging modes or modalities, to generate 2D multi-parametric ultrasound (mpUS) images and/or to generate a three-dimensional (3D) mpUS image. The different ultrasound imaging modes acquire images in a common frame of reference during a single procedure to facilitate their registration. The mpUS images (i.e., 2D or 3D) may be used for enhanced and/or automated detection of one or more suspicious regions. After identifying one or more suspicious regions, the mpUS images may be utilized with a real-time image to guide biopsy or therapy the region(s). All these processes may be performed in a single medical procedure.
