Contrast enhanced diagnostic ultrasound induces capillary injury in rat intestine

Contrast enhanced diagnostic ultrasound (CEDUS) can lead to microvascular injury through nucleation of cavitation. Capillary hemorrhage previously has been noted in heart, kidney, pancreas, and liver, which are common subjects of CEDUS examination. This research examined CEDUS injury of intestine. The abdomens of anesthetized rats were scanned by a 1.6 MHz diagnostic ultrasound probe during infusion of microbubble suspensions simulating the clinical ultrasound contrast agent Definity. Dual image frames were triggered intermittently, and the peak rarefactional pressure amplitude was varied to assess the exposure-response. Petechiae counts in small intestine mucosa and muscle layers increased with increasing trigger interval from 2 s to 10 s, indicative of a slow refill after microbubble destruction (cavitation nucleation). Counts increased with increasing output above a threshold of 1.4 MPa. Petechiae were also seen in Peyer’s patches, and occult blood was detected in many affected segments of intestine. For comparison, thresholds were 0.73 MPa, 0.95 MPa, 1.1 MPa, and 1.7 MPa in kidney, heart, pancreas, and liver. Threshold variation may be related to differences in capillary size (largest in liver) and blood refill time (1 s in kidney). Clinically, such bioeffects can be mitigated by avoiding contrast agent destruction.