It is well known now that a phase-change contrast agent (PCCA) can be activated from a liquid (nanodroplet) state using pulsed ultrasound (US) energy to form a larger highly echogenic microbubble (MB). Since nanodroplet activation is highly dependent on the hydrostatic pressure exerted on it, any increases in this stabilizing force demands higher US energies to induce phase transition. Herein we explore this basic relationship as a potential direction for noninvasive pressure measurement and foundation of a new technology we are developing termed tumor interstitial pressure estimation using US (TIPE-US). TIPE-US was developed using a programmable US research scanner (Vantage 256, Verasonics Inc). A custom scan sequence was implemented and interleaved pulsed US transmissions for both PCCA activation and subsequent MB detection. An automated US pressure sweep is performed (peak negative pressures from 3 to 6 MPa, N = 200 discrete intervals), and US images are acquired at each increment. PCCAs were formulated in house using the popular condensation method. Pressurized samples were then studied using the TIPE-US system. The activation threshold required to convert PCCA from the liquid to gaseous state was recorded for various PCCA conditions. Overall, PCCA activation threshold was lowered with increasing sample temperature while PCCA concentration appeared to play no role.