This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schlachetzki, F. Articles by Bogdahn, U. Search for Related Content PubMed PubMed Citation Articles by Schlachetzki, F. Articles by Bogdahn, U.

Observation on the Integrity of the Blood-Brain Barrier After Microbubble Destruction by Diagnostic Transcranial Color-Coded Sonography

Departments of Neurology (F.S., T.H., B.D., A.M., U.B.) and Psychiatry (H.J.K.) and Institute for Neuroradiology (G.S.), University of Regensburg, Bezirksklinikum Regensburg, Regensburg, Germany.

Address correspondence and reprint requests to Felix Schlachetzki, MD, University of Regensburg, Bezirksklinikum Regensburg, Universtitaetsstrasse 84, 93053 Regensburg, Germany.

Objective. To investigate alteration of the blood-brain barrier from ultrasonic contrast agent destruction by diagnostic transcranial color-coded sonography using gadolinium-enhanced magnetic resonance imaging. Methods. Healthy male volunteers received 10 mL (400 mg/dL) of Levovist (SH U 508A; Schering AG, Berlin, Germany; n = 6) or 3 mL of Optison (FS069; Mallinckrodt Inc, St Louis, MO; n = 4) followed by 0.3 mmol/kg magnetic resonance imaging contrast agent (Magnevist; Schering) intravenously. Then transcranial color-coded sonography was performed with a conventional color duplex sonographic system, which insonated the brain in a slightly angulated axial plane with temporal average intensity of less than 700 mW/cm² or acoustic pressure amplitude of less than 2.69 MPa, attenuated by the temporal bone. Before, immediately after, and 2 hours after insonation, T1-weighted axial magnetic resonance imaging was performed. All magnetic resonance images were individually assessed, and T1 signal intensities were measured in 2 regions of interest in both hemispheres at the 3 time points. Results. No focal contrast enhancement or damage to the brain and no significant difference between T1 signal intensities in the right and left brain regions could be detected during early or late phases when either ultrasonic contrast agent was used.Conclusions. This bioeffects study gives further evidence of the safety of ultrasonic destruction of Levovist and Optison microbubbles by diagnostic transcranial color-coded sonography. However, more subtle local effects may have been missed by gadolinium-enhanced magnetic resonance imaging. Studies on diagnostic contrast-enhanced transcranial color-coded sonography as well as microbubble-based drug delivery strategies should consider ultrasonic contrast agent microbubble characteristics and concentration as well as ultrasound transmission power levels.

Abbreviations: BBB, blood-brain barrier • Gd, gadolinium • HIFU, high-intensity focused ultrasound • MI, mechanical index • MRI, magnetic resonance imaging • ROI, region of interest • SAE, stimulated acoustic emission • SPECT, single photon emission computed tomography • TCCS, transcranial color-coded sonography • TCD, transcranial Doppler • T, time point of MRI • TD, triple-dose • UCA, ultrasonic contrast agent

Key Words: blood-brain barrier • drug delivery • stimulated acoustic emission • transcranial color-coded sonography • ultrasonic bubble destruction • ultrasound safety

This article has been cited by other articles:

				D. L. Miller, M. A. Averkiou, A. A. Brayman, E. C. Everbach, C. K. Holland, J. H. Wible Jr, and J. Wu Bioeffects Considerations for Diagnostic Ultrasound Contrast Agents J. Ultrasound Med., April 1, 2008; 27(4): 611 - 632. [Abstract] [Full Text] [PDF]

				K. D. Evans, B. Weiss, and M. Knopp High-Intensity Focused Ultrasound (HIFU) for Specific Therapeutic Treatments: A Literature Review Journal of Diagnostic Medical Sonography, November 1, 2007; 23(6): 319 - 327. [Abstract] [PDF]