title: Imaging microvasculature with contrast-enhanced ultraharmonic ultrasound.
abstract: Atherosclerotic plaque neovascularization was shown to be one of the strongest predictors of future cardiovascular events. Yet, the clinical tools for coronary wall microvasculature detection in vivo are lacking. Here we report an ultrasound pulse sequence capable of detecting microvasculature invisible in conventional intracoronary imaging. The method combines intravascular ultrasound with an ultrasound contrast agent, i.e., a suspension of microscopic vascular acoustic resonators that are small enough to penetrate the capillary bed after intravenous administration. The pulse sequence relies on brief chirp excitations to extract ultraharmonic echoes specific to the ultrasound contrast agent. We implemented the pulse sequence on an intravascular ultrasound probe and successfully imaged the microvasculature of a 6 days old chicken embryo respiratory organ. The feasibility of microvasculature imaging with intravascular ultrasound sets the stage for a translation of the method to studies of intra-plaque neovascularization detection in humans.
authors.affiliation: Biomedical Engineering Department, Thorax Centre, Erasmus University Medical Centre, Rotterdam, The Netherlands. Electronic address: david.maresca@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Maresca
authors.affiliation: Biomedical Engineering Department, Thorax Centre, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Ilya
authors.initials: I
authors.lastname: Skachkov
authors.affiliation: Biomedical Engineering Department, Thorax Centre, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Renaud
authors.affiliation: Biomedical Engineering Department, Thorax Centre, Erasmus University Medical Centre, Rotterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
authors.forename: Krista
authors.initials: K
authors.lastname: Jansen
authors.affiliation: Biomedical Engineering Department, Thorax Centre, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Gijs
authors.initials: G
authors.lastname: van Soest
authors.affiliation: Biomedical Engineering Department, Thorax Centre, Erasmus University Medical Centre, Rotterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands; Imaging Science and Technology Department, Delft University of Technology, Delft, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: de Jong
authors.affiliation: Biomedical Engineering Department, Thorax Centre, Erasmus University Medical Centre, Rotterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands; Imaging Science and Technology Department, Delft University of Technology, Delft, The Netherlands.
authors.forename: Antonius F W
authors.initials: AF
authors.lastname: van der Steen
mesh_terms: D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D003287:Contrast Media; D004867:Equipment Design; D005466:Fluorocarbons; D055806:Microvessels; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging; D018084:Ultrasonography, Interventional / Q000379:methods*; D014651:Vasa Vasorum / Q000000981:diagnostic imaging*
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; C042852:perflutren
keywords: Contrast-enhanced ultrasound; Intravascular ultrasound; Microvasculature; Pulse inversion; Ultraharmonic; Ultrasound contrast agent; Vasa vasorum