A novel imaging technique that identifies high-risk plaque associated with heart attacks made headlines this week — but this technology is just one of several such tests in the works.

Researchers at the University of Edinburgh in Scotland tested the use of PET/CT with radioactive tracer sodium fluoride (NaF) to identify high-risk plaque that had either already ruptured or was at risk for rupture.

"It's the first study that shows that with a simple hour and a half test, we could evaluate the blockages that are at the highest risk of rupturing and worsening," said Dr. Gregory Thomas, medical director for the MemorialCare Heart & Vascular Institute at Long Beach Memorial in California, who authored an editorial on the Edinburgh study.

But this isn't the only plaque imaging technique of its kind — near infrared spectroscopy and optical coherence tomography also aim to identify high-risk plaque and help doctors prevent heart attacks before they occur.

Vulnerable plaque

What complicates comparisons between these different tests is that scientists still haven’t reached full consensus on what constitutes high-risk plaque.

While scientists are able to identify certain common characteristics in unstable plaque — such as elevated levels of microcalcification, inflammation and cell injury and death — they are still unable to pinpoint what exactly causes this culprit plaque to rupture.

Furthermore, it’s very difficult to establish whether this plaque is definitively responsible for causing heart attacks, since scientists can only identify and study the plaque before and after the cardiac event, not during.

For example, prior autopsy studies had established that ruptured lipid core plaque, a type of high-risk plaque, was present in most heart attack patients and was strongly suspected to be the cause of heart attacks.

But in July, DOTmed News reported on a study in which researchers were able to spot lipid core plaque in living patients for the first time using a technique called near infrared spectroscopy. However, further studies need to be done before researchers are able to establish that lipid core plaque imaging can accurately predict heart attacks.

The advantage of this test lies in its speed and automation — the image is available within seconds after pullback from the artery. It’s also easy to read.

Another imaging technique called optical coherence tomography takes a different approach to vulnerable plaque imaging by enabling doctors to assess the thickness of the fibrous cap, a layer of connective tissue found in high-risk plaque which is prone to rupture and instability. Unlike near infrared spectroscopy, however, accurate reading of the images largely depends on the skill and experience of the observer.

A better tracer

The novel imaging technique developed by the University of Edinburgh takes yet another approach toward heart attack prediction by visualizing unstable plaque with high levels of microcalcification.

A key innovation of the study was using NaF (sodium fluoride) a tracer commonly used to image bone, instead of FDG (fluorodeoxyglucose) which had been the gold standard for plaque imaging up until now.

The study, which used both FDG and NaF to image 40 patients with acute myocardial infarction and 40 with stable angina, showed that NaF may, indeed, be better at showing these high-risk blockages.

Ruptured plaque of heart attack patients absorbed 34 percent more NaF than nonculprit plaques. Additionally, nearly all of the patients (93 percent) had increased NaF in the ruptured part of their heart. This distinction was not apparent between culprit and nonculprit plaques when FDG was used, however.

NaF works by being drawn to active microcalficiation in the plaque. When the molecule is absorbed by ruptured or rupture-prone plaque, it lights up the culprit site in heart scans.

But microcalcification isn’t just an indicator of risk — it also provides additional information to doctors because it indicates whether the plaque is still metabolically active or dormant.

“The main difference between this method and others that are available or under investigation now is that sodium fluoride PET/CT indicates metabolic activity — it describes the dynamics of the plaque rather than a snapshot of its chemical composition,” said Dr. Reka Haraszti from the University of Massachusetts Medical School in Worcester.

In other words, researchers hope that this information will go beyond just identifying plaque as high-risk by predicting with greater accuracy whether that plaque is at risk for rupturing in the near future.

"With other imaging techniques, we can tell the risk is higher, but we can’t guarantee if that plaque will rupture soon," said Haraszti.

The test also uses equipment readily available in most hospitals, whereas near infrared spectroscopy would require purchasing new technology.

New research ahead

Experts agree more research needs to be done to explore the methods and techniques that are in the works now before declaring one of them the gold standard.

“I think that it’s always good to look into more techniques, I think complementary information could be useful especially since different techniques will tell us different information and more information might make it easier to help predict heart attacks,” said Haraszti.

Thomas does caution that the Edinburgh study has limitations — it only studies a limited number of people, and of the patients they studied who had a heart attack, 36 of those 40 patients were men.

The common trigger behind women’s heart attacks, plaque erosion, may work differently than the plaque examined in this study so its results might not apply to them, experts say. "So we don't know how this will work in women," said Thomas.

"I’d be interested to see if this method would detect those plaques too. It would also be good validation for this theory. Let’s say it doesn’t detect plaque erosion, only plaque rupture — we could distinguish between these two and learn more about what causes heart attacks. I think it would be very useful research," said Haraszti.

Researchers also still don't know for certain whether this calcification occurs pre- or post-rupture. This is important to establish, since detecting the plaque only after rupture would significantly limit its usefulness.

And there's still no treatment available for patients who have high-risk plaque, meaning this imaging test may precede the cure needed to make it useful. But this may quickly change as the industry comes up with new treatments or therapies to treat this plaque.

On the other hand, the scan could still be used as a novel research tool to come up with new therapies to stabilize plaque.

"I think it's a landmark study," said Thomas.