Advances in Diagnostic and Therapeutic Ultrasound

Advances in Diagnostic and Therapeutic Ultrasound

Meairs Stephen
European Neurological Review - Volume 3 - Issue I
Published: November 2008
download article

| More
dots

Ultrasound now provides the first medical imaging technique to allow realtime visualisation of stroke. Going beyond new diagnostic applications, this non-invasive modality also offers novel therapeutic opportunities. Emergent treatment of acute ischaemic stroke includes the possibility of using ultrasound to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis.1,2 Moreover, intravenous microbubbles combined with transcranial ultrasound can open acute intracranial thrombotic occlusions.3

The first clinical studies using microbubbles and ultrasound for treatment of ischaemic stroke have shown encouraging results.4 Further new developments in neurovascular ultrasound involve molecular approaches to diagnostics and therapy. Recent studies document the possibility of using ultrasound to open the blood–brain barrier (BBB) for selective drug therapy, and for targeting gene therapy to the brain.

Realtime Ultrasound Imaging of Stroke
Since perfusion imaging can detect ischaemic lesions earlier than computed tomography (CT) and may distinguish the stroke subtype and severity of cerebral ischaemia, there is growing interest in perfusion imaging for predicting recovery, differentiating stroke pathogenesis and monitoring therapy. Diagnostic tools that are proportional indicators of cerebral blood flow in stroke include (99m)Tchexamethylpropylene amine oxime single-photon emission CT (Tc- HMPAO-SPECT), positron emission tomography (PET), Xenon-CT and perfusion-weighted magnetic resonance imaging (MRI). However, these methods can be time-consuming, may require the use of radioactive tracers, are expensive and/or may be intolerable for critically ill or restless patients. Clearly, non-invasive and easily available perfusion studies are needed. Low-mechanical-index ultrasound imaging with contrast agents is a promising new application for bedside assessment of brain perfusion. For the first time, this technique allows realtime visualisation of brain infarctions and cerebral haemorrhages.

Realtime ultrasound perfusion imaging (rt-UPI) combines pulse inversion harmonics and power modulation for extraordinary sensitivity for the detection of ultrasound contrast agents in the human brain. This method allows realtime monitoring of microbubbles flowing through the cerebral microvasculature via insonation through the transtemporal bone window. Parameters that can now be assessed in stroke patients include realtime time-to-peak (rt-TTP) after bolus injection of SonoVue™, microbubble destruction curves of contrast agent on standardised axial planes, realtime microbubble refill kinetics, dynamic microvascular microbubble maps and realtime visualisation of middle cerebral artery infarction.

In combination with contrast agents, ultrasound can highlight cerebral infarctions, as well as demarcated areas of failing or significantly diminished contrast enhancement. Such findings correlate well with perfusionweighted imaging in MRI. Dynamic microvascular microbubble maps show good demarcation of MCA infarctions and provide impressive displays of low-velocity tissue microbubble refill following destruction of bubbles with high-mechanical-index imaging. In brain regions showing delayed contrast bolus arrival on perfusion-weighted MRI, ultrasound shows decreased or absent microbubble refill kinetics.

123next ›last »
References:
  1. Alexandrov AV, Molina CA, Grotta JC, et al., Ultrasoundenhanced systemic thrombolysis for acute ischemic stroke, N Engl J Med, 2004;351(21):2170–78.
  2. Daffertshofer M, Gass A, Ringleb P, et al., Transcranial Low- Frequency Ultrasound-Mediated Thrombolysis in Brain Ischemia: Increased Risk of Hemorrhage With Combined Ultrasound and Tissue Plasminogen Activator: Results of a Phase II Clinical Trial, Stroke, 2005;36(7):1441–6.
  3. Culp WC, Porter TR, Lowery J, et al., Intracranial Clot Lysis With Intravenous Microbubbles and Transcranial Ultrasound in Swine, Stroke, 2004;35(10):2407–11.
  4. Molina CA, Ribo M, Rubiera M, et al., Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator, Stroke, 2006;37(2): 425–9.
  5. Leong-Poi H, Christiansen J, Klibanov AL, et al., Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins, Circulation, 2003;107(3): 455–60.
  6. Weller GE, Villanueva FS, Klibanov AL, Wagner WR, Modulating targeted adhesion of an ultrasound contrast agent to dysfunctional endothelium, Ann Biomed Eng, 2002;30(8):1012–19.
  7. Lawrie A, Brisken AF, Francis SE, et al., Microbubbleenhanced ultrasound for vascular gene delivery, Gene Ther, 2000;7(23):2023–7.
  8. Skyba DM, Price RJ, Linka AZ, et al., Direct in vivo visualization of intravascular destruction of microbubbles by ultrasound and its local effects on tissue, Circulation, 1998;98(4):290–93.
  9. Shohet RV, Chen S, Zhou YT, et al., Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium, Circulation, 2000;101(22):2554–6.
  10. Unger EC, Hersh E, Vannan M, et al., Local drug and gene delivery through microbubbles, Prog Cardiovasc Dis, 2001;44(1):45–54.
  11. Stroick M, Alonso A, Fatar M, et al., Effects of simultaneous application of ultrasound and microbubbles on intracerebral hemorrhage in an animal model, Ultrasound Med Biol, 2006;32(9):1377–82.
  12. Mesiwala AH, Farrell L, Wenzel HJ, et al., High-intensity focused ultrasound selectively disrupts the blood–brain barrier in vivo, Ultrasound Med Biol, 2002;28(3):389–400.
  13. Alonso A, Della Martina A, Stroick M, et al., Molecular imaging of human thrombus with novel abciximab immunobubbles and ultrasound, Stroke, 2007;38(5): 1508–14.
  14. Christiansen JP, Leong-Poi H, Klibanov AL, et al., Noninvasive imaging of myocardial reperfusion injury using leukocytetargeted contrast echocardiography, Circulation, 2002;105(15):1764–7.
  15. Lindner JR, Detection of inflamed plaques with contrast ultrasound, Am J Cardiol, 2002;90(10C):32L–35L.
  16. Shimamura M, Sato N, Taniyama Y, et al., Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound, Gene Ther, 2004;11(20):1532–9.
  17. Manome Y, Nakayama N, Nakayama K, Furuhata H, Insonation facilitates plasmid DNA transfection into the central nervous system and microbubbles enhance the effect, Ultrasound Med Biol, 2005;31(5):693–702.
  18. Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA, Noninvasive MR imaging-guided focal opening of the blood–brain barrier in rabbits, Radiology, 2001;220(3): 640–46.
  19. Meairs S, Alonso A, Ultrasound, microbubbles and the blood–brain barrier, Prog Biophys Mol Biol, 2007;93(1–3): 354–62.

Copyright® 2004 - 2010 Business Briefings, Ltd. All rights reserved.
Touch Neurology is for informational purposes and should not be considered medical advice, diagnosis or treatement recommendations.