Power-Doppler ultrasonic (PD-US) imaging is sensitive to echoes from blood cell motion in the microvasculature but generally nonspecific because of difficulties with filtering nonblood-echo sources. We are studying the potential for using PD-US imaging for routine assessments of peripheral blood perfusion without contrast media. The strategy developed is based on an experimentally verified computational model of tissue perfusion that simulates typical in vivo conditions. The model considers directed and diffuse blood perfusion states in a field of moving clutter and noise. A spatial registration method is applied to minimize tissue motion prior to clutter and noise filtering. The results show that in-plane clutter motion is effectively minimized. While out-of-plane motion remains a strong source of clutter-filter leakage, those registration errors are readily minimized by straightforward modification of scanning techniques and spatial averaging.