Intended for healthcare professionals

Clinical Review Science, medicine, and the future

Microbubble contrast agents: a new era in ultrasound

BMJ 2001; 322 doi: (Published 19 May 2001) Cite this as: BMJ 2001;322:1222
  1. Martin J K Blomley, senior lecturer in radiology (,
  2. Jennifer C Cooke, research fellow (cardiology)b,
  3. Evan C Unger, professor of radiologyc,
  4. Mark J Monaghan, director of echocardiographyb,
  5. David O Cosgrove, professor of clinical ultrasounda
  1. a Hammersmith Hospital, Imperial College School of Medicine, London W12 0HS
  2. b Kings College Hospital, London
  3. c University of Arizona, Tucson, Arizona, USA
  1. Correspondence to: M J K Blomley

    Contrast agents are widely used in imaging, but until recently they had little place in ultrasonography. This has changed with the introduction of microbubbles—small (typically 3 μm in diameter) gas filled bubbles that are usually injected intravenously. Injecting a gas into the circulation may seem potentially hazardous, but extensive clinical experience has shown that the tiny volume of air or gas given (under 200 μl) is not dangerous, and the safety of microbubbles compares well to that of conventional agents in radiography and magnetic resonance imaging.1 Although microbubbles were originally designed simply to improve conventional ultrasound scanning, recent discoveries have opened up powerful emerging applications. This article describes some of these applications in radiology and cardiology and discusses the potential of microbubbles for therapy.


    We prepared this review from contributions from researchers with special knowledge of the use of microbubbles in radiology, cardiology, and treatment. We combined our personal experience in research over several years with a review of recent literature on the subject.

    How microbubbles work

    Microbubbles work by resonating in an ultrasound beam, rapidly contracting and expanding in response to the pressure changes of the sound wave. By a fortunate coincidence, they vibrate particularly strongly at the high frequencies used for diagnostic ultrasound imaging. This makes them several thousand times more reflective than normal body tissues. In this way they enhance both grey scale images and flow mediated Doppler signals. As well as being useful in itself, the resonance that microbubbles produce has several special properties that can be exploited to improve diagnoses. Just as with a musical instrument, multiple harmonic signals—or overtones—are produced. Ultrasound scanners can be tuned to “listen” to these harmonics, producing strong preferential imaging of the microbubbles in an image. The selective excitation produced can also destroy microbubbles relatively easily, an effect that can be useful …

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