Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index.

Ultrasound in Medicine & Biology
Nathan McDannoldKullervo Hynynen

Abstract

This work investigated the effect of ultrasonic frequency on the threshold for blood-brain barrier (BBB) disruption induced by ultrasound pulses combined with an ultrasound contrast agent. Experiments were performed in rabbits using pulsed sonications at 2.04 MHz with peak pressure amplitudes ranging from 0.3 to 2.3 MPa. BBB disruption was evaluated using contrast-enhanced magnetic resonance imaging. The threshold for BBB disruption was estimated using probit regression. Representative samples with similar amounts of contrast enhancement were examined in light microscopy. Results from these experiments were compared with data from previous studies that used ultrasound frequencies between 0.26 and 1.63 MHz. We found that the BBB disruption threshold (value where the probability for disruption was estimated to be 50%) expressed in terms of the peak negative pressure amplitude increased as a function of the frequency. It appeared to be constant, however, when the exposures were expressed as a function of the mechanical index (peak negative pressure amplitude estimated in situ divided by square root of frequency). Regression of data from all frequencies resulted in an estimated mechanical index threshold of 0.46 (95% confidence int...Continue Reading

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Citations

Apr 23, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Muna AryalNathan McDannold
Aug 26, 2009·Radiology·Krisztina FischerFerenc A Jolesz
Sep 3, 2013·Pharmaceutical Research·Linfeng WuTao L Lowe
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Jan 28, 2014·Advanced Drug Delivery Reviews·Muna AryalNathan McDannold
Aug 12, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Alison BurgessKullervo Hynynen
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Feb 6, 2013·ACS Chemical Neuroscience·Alison Burgess, Kullervo Hynynen
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