Ultraschall Med 2013; 34 - WS_SL24_10
DOI: 10.1055/s-0033-1354962

Imaging Microvasculature with Contrast Enhanced Ultraharmonic Ultrasound

D Maresca 1, I Skachkov 1, G Renaud 1, K Jansen 1, 2, G van Soest 1, N de Jong 1, 2, 3, AFW van der Steen 1, 2, 3
  • 1Thorax Centre Department of Biomedical Engineering, Erasmus University Medical Centre, Rotterdam, the Netherlands
  • 2Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands
  • 3Imaging Science and Technology Department, Delft University of Technology, Delft, the Netherlands

Purpose: Atherosclerotic plaque neovascularization was shown to be one of the strongest predictors of future cardiovascular events [1]. Yet, the clinical tools for coronary wall microvasculature detection in vivo are lacking. Here we report a contrast-enhanced ultrasound pulse sequence capable of detecting microvasculature invisible in conventional intracoronary imaging.

Material and Methods: Our approach consisted in imaging contrast microbubbles using first order ultraharmonics that arise at 1.5 times the transmit frequency. These signals are specific to the ultrasound contrast agent, preventing non-linear propagation artefacts, and can be captured with a transducer frequency bandwidth of 40%. The ultrasound pulse sequence consisted in pairs of phase inverted chirp excitations (26 MHz center frequency). The ultraharmonic content was extracted by summing A-lines acquired in response to the pairs of inverted excitations. Subsequently, the residual data was digitally filtered in the ultraharmonic band (centered at 39 MHz). We implemented the pulse sequence on an intravascular ultrasound probe (transducer bandwidth < 60%), and acquired images of the respiratory microvasculature of a 6 days old chicken embryo. Microvessels exhibited cross sections of the order of human atherosclerotic plaque neovascularization (diameters < 200 µm).

Results: In conventional intravascular ultrasound (IVUS) images, we could not disentangle microvessels from the connective tissue. On the contrary, ultraharmonic IVUS images successfully captured the ultrasound contrast agent spreading in the microvasculature. We confirmed experimentally the presence of an ultraharmonic frequency peak generated by the ultrasound contrast agent. Quantitatively, the contrast to tissue ratio between a microvessel and adjacent connective tissue was up to doubled (12.5 dB in ultraharmonic IVUS as opposed to 6 dB in conventional IVUS). For reference, a photograph of the microvasculature insonified with IVUS was acquired. It matched the ultraharmonic IVUS image with a strong agreement.

Conclusion: Contrast-enhanced ultraharmonic ultrasound revealed microvasculature invisible in conventional IVUS, clearing way towards a translation of the method to coronary plaque noevascularization detection in humans.

References:

[1] W. E. Hellings, W. Peeters, F. L. Moll, S. R. D. Piers, J. van Setten, P. J. Van der Spek, J. de Vries, K. A. Seldenrijk, P. C. De Bruin, A. Vink, E. Velema, D. P. V. de Kleijn, G. Pasterkamp, Composition of Carotid Atherosclerotic Plaque Is Associated With Cardiovascular Outcome A Prognostic Study. Circulation 121, 1941-U1111 (2010).