Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice

TLDR

Ultrasound interaction with gas‑filled contrast agents generates diagnostic contrast but can also cause bioeffects. The study used anesthetized hairless mice scanned with a 2.5‑MHz transducer after Optison and Evans blue injection, counting petechial hemorrhages 15 min post‑exposure and measuring dye extravasation. The results showed that muscle petechial hemorrhages increased with the square of peak negative pressure above 0.64 MPa and with contrast dose (significant even at 0.05 ml kg⁻¹), while intestinal hemorrhages and Evans blue leakage rose above 1.0 MPa; delayed exposure reduced effects to sham levels, and similar hemorrhage levels were observed across various exposure durations, confirming earlier findings.

Abstract

Interaction of diagnostic ultrasound with gas bodies produces a useful contrast effect in medical images, but the same interaction also represents a mechanism for bioeffects. Anesthetized hairless mice were scanned by using a 2.5-MHz transducer (610-ns pulses with 3.6-kHz repetition frequency and 61-Hz frame rate) after injection of Optison and Evans blue dye. Petechial hemorrhages (PHs) in intestine and abdominal muscle were counted 15 min after exposure to characterize capillary rupture, and Evans blue extravasation was evaluated in samples of muscle tissue. For 5 ml⋅kg -1 contrast agent and exposure to 10 alternating 10-s on and off periods, PH counts in muscle were approximately proportional to the square of peak negative pressure amplitude and were statistically significant above 0.64 MPa. PH counts in intestine and Evans blue extravasation into muscle tissue were significant above 1.0 MPa. The PH effect in muscle was proportional to contrast dose and was statistically significant for the lowest dose of 0.05 ml⋅kg -1 . The effects decreased nearly to sham levels if the exposure was delayed 5 min. The PH effect in abdominal muscle was significant and statistically indistinguishable for uninterrupted 100-s exposure, 10-s exposure, 100 scans repeated at 1 Hz, and even for a single scan. The results confirms a previous report of PH induction by diagnostic ultrasound with contrast agent in mammalian skeletal muscle [Skyba, D. M., Price, R. J., Linka, A. Z., Skalak, T. C. & Kaul, S. (1998) Circulation 98, 290–293].