Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice - PubMed (original) (raw)

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

D L Miller et al. Proc Natl Acad Sci U S A. 2000.

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 small middle dotkg(-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 small middle dotkg(-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].

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Figures

Figure 1

(Upper) The experimental setup. (Lower) The ultrasound image obtained during exposure with the attenuation phantom.

Figure 2

Examples of the effects found in the abdominal muscle and fat. (Lower) PHs and Evans blue extravasation with 5 ml⋅kg-1 contrast agent and 10 × 10s exposure at 2.8 MPa. (Upper) No effect with the same exposure but without injected contrast-agent gas bodies. (Scale bars: 1 mm.)

Figure 3

Mean PH counts with standard error bars in muscle and intestine for 5 ml⋅kg-1 contrast agent at the indicated pressure amplitudes. The curve plotted with the muscle results was fitted to the data means by linear regression against the square of the amplitude (_r_2 = 0.995).

Figure 4

The results for Evans blue extravasation for 5 ml⋅kg-1 contrast agent at the indicated pressure amplitudes, obtained from the same samples used for the points in Fig. 3.

Figure 5

Mean PH counts with standard error bars in muscle and intestine for 10 × 10s exposure at 2.8 MPa with the indicated contrast agent doses. The line indicates linear dependence of the muscle counts on dose (except the maximum dose) (_r_2 = 0.988).

Figure 6

The results for Evans blue extravasation for the indicated contrast agent doses, obtained from the same samples used for the points in Fig. 5.

Figure 7

A comparison of muscle PH counts after different exposure timing sequences at 2.8 MPa with 5 ml⋅kg-1 contrast agent.

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Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice - PubMed (original) (raw)