Quantification of the skeletal muscle response can help better understand the fundamentals of the musculoskeletal system and can serve as a diagnostic measure or recovery assessment tool during rehabilitation for neurological injuries. Surface electromyography (EMG) is commonly used to measure muscle activity, but it is limited to detecting myoelectric signals without anatomy associated information. In this study, we proposed to use ultra-fast ultrasound imaging and introduced a new image analysis methodology to quantify a muscle's spatialtemporal mechanical response. The methodology is based on analyzing the spatial-temporal change of the impulsive kinetic energy during the period of muscle contraction. The analysis can derive an anatomy-registered muscle activation metric map that localizes regions of muscle activation. To demonstrate this, we intentionally evoked regional muscle responses in five participants without disabilities by electrically stimulating the median nerve and individual forearm muscle groups, respectively. Both ultrasound images and high-density EMG (HD-EMG) data were recorded and processed. We presented the ultrasound image-derived activation localization from five participants and compared the results with HD-EMG measurements. The comparison indicates a good resemblance for describing muscle recruitment pattern. The proposed methodology can potentially become an alternative or complementary approach to surface EMG for the study of skeletal muscle activation and for diagnosis and prognosis in clinical settings.