Transient tumor perfusion loss: evaluating the spatial and temporal dynamics of blood flow changes induced by...

Ultrasound‑mediated microbubble cavitation can induce transient tumor perfusion loss (TTPL), yet the pressure‑dependent magnitude and short‑timescale recovery of this effect remains poorly defined. This study investigated how acoustic pressure governs both the extent and duration of TTPL following a single cavitation exposure. Subcutaneous hepatocellular carcinoma tumors (HEPG2 human cell line) in athymic nude mice (n = 15) received a 1‑second cavitation treatment at peak‑negative pressures of 1.4, 2.8, or 4.1 MPa. Due to the small f-number of the transducer employed, the estimated average peak negative pressures of these conditions within the tumor were 0.6, 1.1, and 1.7 MPa respectively. Tumor perfusion was evaluated using contrast‑enhanced ultrasound (CEUS) immediately (within 1 min), 5, 15, 30, and 60 min after treatment. Perfused area loss was quantified with a maximum intensity projection time‑area curve (MIP‑TAC) metric. Cavitation activity was assessed using passive cavitation detection (PCD), and histology evaluated acute tissue effects. Low acoustic pressure produced only partial perfusion loss with full recovery within 5 min. Moderate acoustic pressure induced substantial TTPL followed by near complete recovery by 15 min. High‑pressure treatment caused complete perfusion loss in all tumors, with initial recovery at 15 min but also with a subsequent decline over the hour. Elevated broadband energy recorded with PCD confirmed inertial cavitation in the moderate and high conditions. Histology revealed damage‑associated staining in 1/5 moderate‑pressure tumors and 3/5 high‑pressure tumors, consistent with pressure‑dependent mechanical injury, possibly contributing to the gradual decline in tumor perfusion observed after initial rebound in the high-pressure condition.