Photoacoustic Radar Lights Up Dangerous Arterial Plaque

Atherosclerosis is a killer. Although it may result in a sudden end, the process often begins decades before with minor inflammation caused by the body trying to get rid of lipids like cholesterol that have congealed on the artery wall. The buildup of this plaque is atherosclerosis.

The plaque often reveals itself by peeling off the artery wall and traveling to some vital location where it blocks the blood flow, causing a stroke or heart attack. But, it turns out that not all arterial plaques are created equal—some appear to be far more likely to be dangerous. Unfortunately, there was, until recently, no way to accurately identify the most dangerous arterial plaques.

This is where the work of PhD student Sung Soo Sean Choi, principal investigator Andreas Mandelis, and his research team at the Center for Advanced Diffusion-Wave and Photoacoustic Technologies comes in. They have created a catheter-based system to image and identify the most dangerous arterial plaques.

For years, researchers have been working to understand the details of plaque buildup. The process involves a combination of low-density lipids, high-density lipids, white blood cells, and the ability of the artery wall to repair itself. The structure of the resulting plaque determines, to a large extent, whether a plaque will ultimately break and cause an obstruction.

For instance (and this is an oversimplification), a plaque may consist of a thin tough outer layer of cholesterol attached to the artery wall, while the inside is filled with dead tissue (white blood cells and arterial wall cells) that is not well attached to the artery wall. Mechanically, the capping layer is not well supported, meaning that it can easily break, leaving the cap and the inner contents free to wreak havoc.

To identify plaques that are most likely to rupture, the presence of a thin cap (< 65 μm thick) must be revealed. That requires both spatial resolution and the ability to distinguish the cholesterol cap from the inner contents.

To meet these requirements, the Toronto team turned to a version of photoacoustic imaging. This choice makes sense: lipids can be distinguished from necrotic tissue optically because they have different absorption spectra, whereas acoustic waves travel farther with less scattering, enabling easier detection of the response.

It requires some innovative engineering to fit a photoacoustic imaging system in a catheter. Normally, photoacoustic imaging requires a relatively high-powered pulsed laser and lots of acoustic energy transducers—basically microphones. Here the researchers do not use a pulsed laser, and the acoustic signal is collected by only a single transducer, placed right next to the optical output. Since a single detector cannot image, the team uses radar techniques to create an image.

To obtain high contrast between the cholesterol shell and the necrotic core of the plaque, the researchers use two laser wavelengths: one is tuned to the peak of a lipid's optical absorption, while the second is at a shorter wavelength for which lipid absorption is minimal. The difference between these two signals will automatically remove almost everything but the lipid.

Image of the atherosclerotic artery phantom. From doi.org/10.1117/1.JBO.24.6.066003

The key is that the subtraction cannot be performed in a traditional way—image with one laser then image with the next. Arteries tend to move about, leading to artifacts. And, the subtraction process adds noise, reducing the image clarity. Instead, the team uses a form of coherent detection to obtain differences in a single measurement. When the two modulated optical beams are absorbed, sound waves that have the same modulation are generated. The modulation can be extracted to obtain an amplitude and phase, which are determined by the material—that is, cholesterol has a different phase and amplitude than the dead tissue and the arterial walls. If the modulation is set to destructively interfere, then optically identical absorbers (like the necrotic tissue) will disappear and only the difference remains.

The team modulates the laser intensities in a sweep from low frequency to high frequency with the required phase difference. This automatically performs the subtraction at the transducer, meaning that only the signal from the cholesterol remains. Furthermore, the sweep provides a time signature which locates the distance from the transducer to the cholesterol.

The researchers tested their system on phantoms in pigs' arteries and showed that they could successfully image cholesterol plaques. That said, there is still some way to go before this tool sees the inside of a patient because further miniaturization is required before the circuit design will fit inside a catheter. It takes a lot of careful tuning of laser intensities and modulation phase differences to remove the dead tissue from the image. Nevertheless, this is an excellent beginning.

Read the original research article in the Journal of Biomedical Optics. S. S. S. Choi et al., "Frequency-domain differential photoacoustic radar: theory and validation for ultrasensitive atherosclerotic plaque imaging," J. Biomed. Opt. 24(6), 066003 (2019). https://doi.org/10.1117/1.JBO.24.6.066003

Chris Lee is a physicist and writer living and working in Eindoven, the Netherlands.