Copper oxide nanoparticles (CuO NPs) have anticancer and antimicrobial activities. Moreover, they have a contrast enhancing effect in both MRI and ultrasound. Nonetheless, encapsulation is needed to control their toxic side effects and a mechanism for release on demand is required. A methodology is introduced herein for encapsulating and releasing CuO NPs from micelles by ultrasound induced hyperthermia and monitoring the process by MRI. For this aim, CuO NPs loaded poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles were prepared. Then, the profile of copper release with application of ultrasound was examined as a function of time and temperature using a colorimetric method. Finally, T1 weighted MRI images of suspensions and ex vivo poultry liver samples containing the CuO NPs loaded micelles were acquired before and after ultrasound application. The results confirmed that: (i) encapsulated NPs are detectible by MRI T1 mapping, depicting substantial T1 shortening from 1872 ± 62 ms to 683 ± 20 ms. (ii) Ultrasonic hyperthermia stimulated the NPs release with an about threefold increase compared to non-treated samples. (iii) Releasing effect was clearly visible by T1-weighted imaging (mean signal increase ratio of 2.29). These findings can potentially lead to the development of a new noninvasive methodology for CuO NPs based theranostic process.