David Maresca

Imaging Microvasculature with Contrast-Enhanced Ultraharmonic Ultrasound

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.

Acoustic Sizing of an Ultrasound Contrast Agent

Because the properties of ultrasound contrast agent populations after administration to patients are largely unknown, methods able to study them noninvasively are required. In this study, we acoustically performed a size distribution measurement of the ultrasound contrast agent Definity(®). Single lipid-shelled microbubbles were insonified at 25 MHz, which is considerably higher than their resonance frequency, so that their acoustic responses depended on their geometrical cross sections only. We calculated the size of each microbubble from their measured backscattered pressures. The acoustic size measurements were compared with optical reference size measurements to test their accuracy. Our acoustic sizing method was applied to 88 individual Definity(®) bubbles to derive a size distribution of this agent. The size distribution obtained acoustically showed a mean diameter (2.5 μm) and a standard deviation (0.9 μm) in agreement within 8% with the optical reference measurement. At 25 MHz, this method can be applied to bubble sizes larger than 1.2 μm in diameter. It was observed that similar sized bubbles can give different responses (up to a factor 1.5), probably because of shell differences. These limitations should be taken into account when implementing the method in vivo. This acoustic sizing method has potential for estimating the size distribution of an ultrasound contrast agent noninvasively.

Acoustic size distribution analyzer for microbubbles

In this study, an acoustic size distribution measurement of the ultrasound contrast agent Definity™ was performed. Single lipid shelled microbubbles were insonified at 25 MHz, high above their resonance frequencies, so that their acoustic responses depend on their physical cross sections only. We calculated the size of each microbubble from the measured absolute backscattered pressures. The acoustic size measurements were compared to optical reference size measurements to test their accuracy. Our acoustic sizing method was applied to 88 individual Definity™ bubbles to derive a size distribution of this agent. The result showed agreement with the optical measurements of the same contrast agent population. The averaged sizes obtained acoustically differed by 26% with the optical measurement. This novel acoustic sizing method shows potential for estimating the size distribution of an ultrasound contrast agent noninvasively.

Contrast-enhanced intravascular ultrasound 3D reconstruction of a vasa vasorum mimicking model

It is increasingly recognized that the development of new microvessels (vasa vasorum) within and surrounding atherosclerotic plaques is essential to enable artery lesion growth and plays a central role in rendering it vulnerable to rupture. Currently, there is no established clinical technique capable of imaging the vasa vasorum (VV) in the coronary arteries of humans. It has been shown that contrast-enhanced intravascular ultrasound (CE-IVUS) is capable of imaging VV in vivo. This study aims at reconstructing in three dimensions (3D) a VV model using CE-IVUS with a clinical coronary imaging catheter. A polyvinyl alcohol based VV model was manufactured, exhibiting a VV mimicking branch pattern with a diameter ranging from 200 to 100 um. After perfusion of the VV model with the ultrasound contrast agent Definity®, a manual pullback consisting of 93 cross sectional IVUS images spaced every 200 µm was performed. Perfused areas were segmented in two registered CE-IVUS planes and compared to coregistered 10 um thick slices of the VV model. The VV mimicking microchannel diameters measured with CE-IVUS agreed within 30% with the slice diameters. As CE-IVUS imaging can be carried out in-vivo, this method could be used during clinical IVUS investigations as an additional diagnostic for plaque vulnerability.∗

Two contrast detection sequences for bandwidth-limited intravascular ultrasound transducers

Atherosclerosis is associated with the formation of microvessels in the arterial wall, referred to as vasa vasorum (VV). VV imaging may constitute a new intravascular ultrasound (IVUS) metric of coronary artery plaque vulnerability. The potential of nonlinear contrast IVUS to detect VV in vivo was demonstrated using a prototype transducer with dual-peak frequency response. In this study, we report the feasibility of pulse-inversion ultraharmonic IVUS contrast imaging and chirp reversal contrast IVUS imaging. Their performance is compared for VV detection. Both sequences operate with limited transducer bandwidths (<;60%), and are therefore implementable on clinical IVUS catheters.

Intravascular ultrasound chirp imaging

We demonstrate the feasibility of intravascular ultrasound chirp imaging. Chirp excitations were emitted with a 34 MHz single crystal intravascular transducer and compared to conventional Gaussian modulated pulses of equal peak negative pressure. The signal to noise ratio of the chirp images was increased up to 9 dB. The method shows potential for intravascular imaging of structures in and beyond coronary atherosclerotic plaques.

Intravascular ultrasound: Assessment of atherosclerosis

Intravascular ultrasound (IVUS) is a technology that uses an ultrasound element on the tip of a catheter. This catheter is advanced through the groin into the coronary arteries. In this way a tomographic image of the vascular wall and atherosclerotic plaques can be produced.