Ultrafast contrast-enhanced ultrasound for PAD patients shows promise in early feasibility research

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Majorie van Helvert (University of Twente, Enschede, The Netherlands) and Michel Reijnen (Rijnstate Hospital, Arnhem, The Netherlands) are currently conducting research on ultrafast contrast-enhanced ultrasound blood flow quantification in peripheral arterial disease (PAD) patients after endovascular treatment. Early findings show that the new technique could offer an innovative imaging alternative.

Vascular News recently spoke with both van Helvert and Reijnen, and they went into more detail about their findings. Traditionally, conventional ultrasound systems are used in the diagnostic work-flow of PAD. These systems have limited temporal resolution which is typically capped out at 10–100 frames per second. However, with the novel technique that Reijnen and van Helvert used, they were able to increase that framerate to thousands or even tens of thousands of frames per second. This may be necessary to adequately quantify very high velocities and short-lived flow disturbances, for instance, in and around stenoses.

“Within that technique we use a new type of ultrasound transmissions, which is called plane wave ultrasound,” Reijnen explained. “When you look at regular ultrasound, and its image reconstruction, it’s done line-by-line. So, they make the image in separate lines, and all these lines are combined into one image. With plane wave, all transducer elements are simultaneously active in transmit and receive, thus you construct the image in one go. That enables you to get much more frames per second.”

Besides the increased framerate, the team also used contrast microbubbles. For this purpose an IV [intravenous drip] needs to be inserted to allow for contrast administration prior to the ultrasound acquisitions. “Once we use the ultrasound, these contrast microbubbles make sure that the echogenicity of the blood is enhanced,” van Helvert said. “Next to that, they can be used as tracer particles; that is really the basis for this technique in deeper structures, like the iliac arteries. When we’re looking at more superficial arteries, we don’t really need the contrast as we can perform our analysis based on the bloodspeckle signal itself.”

Reijnen explained that, when you look at anatomy, you are going to mostly use computed tomography (CT) angiography or magnetic resonance imaging (MRI). “Those are the two most important modalities,” Reijnen said. “When we look at functional imaging, there’s mostly duplex ultrasound. A duplex ultrasound is a regular ultrasound combined with doppler. It gives us flow velocities in one direction, generally in the middle of the vessel.”

He continued by saying that there are some drawbacks to duplex ultrasound, next to the aforementioned temporal resolution. “One of them is that it’s only in one directional. Also it requires a beam-to-flow angle correction which makes it highly operator dependent.”

While MRI technologies offer acceptable imaging, there are still some drawbacks to that as well. Namely, Reijnen explains, it’s time consuming, expensive, and the fact that multiple cardiac cycles are combined during image reconstruction may filter out important diagnostic information. “Another important drawback for example,” Reijnen said, “when there are stents, metal and MR is not a good combination. So, there may be disturbances because of the material of the stent.”

Once the images from the ultrafast contrastenhanced ultrasound have been compiled, the more technical aspect comes into play. In order to determine blood flow patterns, the recorded images from the contrast-enhanced ultrasound are divided into different sub-windows. An algorithm then registered how the microbubbles moved across the images.

“We calculate a cross correlation, and the peak in this cross correlation defines the most probable movement that these microbubbles made between two consecutive images that we captured,” van Helvert stated. “Combined with the time in between the frames, we can calculate a velocity vector per sub-window.”

After the images are captured, they must be filtered to see the microbubble contrast compared to the tissue clutter. The thousands of images that the team captures through ultrasound and thereafter analyse, allows them to build a velocity vector field over time. However, one unfortunate downside of this is that the images and the velocity vector field are still twodimensional compared to the three-dimensional flow characteristics.

“But, the upside of this technique compared, for instance, to MRI-based flow imaging, is that we measure a couple of cardiac cycles and its proven feasible inside stents.. So, it does provide added information in that sense,” van Helvert explained.

Reijnen went into more detail. “We can really track these bubbles during the cardiac cycle, and we can assess different patterns from that. So, we can see recirculations, we can see stasis of blood, we can see forward flow and backflow. We can also see that there is difference in blood flow at the anterior wall and the dorsal wall of the blood vessel where there a re bifurcations.”

“What we’re aiming for is, at least my view on things, that in an early disease stage you can do such measurements reliably and minimally invasive to assess if patients have favorable or unfavorable blood flow with respect to disease progression,” van Helvert said.

As for the next steps, Reijnen noted: “At this stage we’re looking at the technique itself, so we’re looking at which parameters can we reliably derive. How can we standardise them and how can we quantify them? And when we’ve done that, then we can do clinical studies in which we start to look at the predictive value of each of them.”

“There’s a lot of steps ahead of us,” van Helvert told us. “We’re in the very first stage.”


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