Microbubble Contrast Agents Open The Blood-brain Barrier And Transgenic Experiments

Objective Over the past few years microbubble has become the focus of a wide and rapidly expanding field of research, with their bioeffects being demonstrated in ultrasonic field. To explore the local effects on rat brain tissue with different frequency and intensity ultrasound exposure in the presence of microbubble.Methods Eighty-four Wistar rats were randomly divided into 4 groups:low-frequency ultrasound sonication with microbubble or saline infused, microbubble with TCD sonication or without ultrasound exposure. The group of low-frequency ultrasound sonication with microbubble presence was subdivided into 4 groups according to acoustic power. We infused 0.2ml QUANFUXIAN (microbubble,a perflurocarbon contrast agent made by NanFang Hospital) into femoral vein followed by 1ml nomal saline before three minute ultrasound sonication with different frequency and intensity. The Indian ink irrigation method to demonstrate brain microvasculature, intravenous injections of Evans blue and fluorescence microscopy to detect increased vascular permeability (blood-brain barrier damage), and routine histologic examination of the brain to detect damage. Results 1. Low frequency ultrasound with 43 kHz may be admitted with a tolerable attenuation through the intact skull bone in rats and showed efficacy in disrupting microbubbles. It was demonstrated that ultrasonic destruction gas-filled microbubble caused microvessel rupture, with local extravasation of red blood cells and BBB opening, with lower intensity of 1.2W/cm2. The extent of BBB opening and brain damage was closely related to the ultrasound power levels. 2. This bioeffect study provides further evidence of the safety of ultrasonic destruction of microbubbles by diagnostic transcranial Doppler. Conclusions Microbubbles destroyed by ultrasound with a frequency of 43 kHz and intensity of 1.2W/cm2 could induce BBB opening in rats, with minimal damage to brain tissue.