Adjustment of operation of an ultrasound imaging system may be based at least in part on one or more characteristics represented in ultrasound return signals from two or more sample volumes. Adjustment may include adjusting a principal sample volume location or selecting a new principal sample volume. For example, a location of a principal sample volume may be adjusted or new principal sample volume selected so as to remain focused on an identified region of interest or to maintain the principal sample volume relative to some structure or reference. The principal sample volume may be maintained in the center or along a centerline of an artery or other structure, as the transducer array is moved along the artery or structure.
