Two is better than one. At least that may prove to be the case with hybrid approaches that combine PET’s ability to assess myocardial blood flow with other modalities for diagnosing coronary artery disease.

Fewer invasive procedures

CT-based coronary angiography (CTCA), which allows radiologists and cardiologists to visualize anatomical traits of coronary arteries, shines as a way to rule out obstructive CAD. But it falls short on its ability to confirm significant obstruction, which then requires invasive procedures such as fractional flow reserve (FFR) for functional assessment. PET, on the other hand, offers a highly sensitive and noninvasive modality for detecting perfusion defects to gauge the hemodynamic severity of the disease.

Ibrahim Danad, MD, of VU Medical Center in Amsterdam, and colleagues hope to combine the best of those two worlds with a hybrid approach using quantitative O-15 water PET and CTCA to noninvasively and accurately diagnose the presence and severity of CAD. “This [O-15 water] is the ideal tracer to use for quantifying myocardial perfusion because it is a diffusible tracer and it has excellent kinetic properties,” Danad says.

In a retrospective study, they enrolled 120 patients with suspected CAD who underwent quantitative O-15 water PET/CTCA and invasive coronary angiography (J Nucl Med 2013;54:55-63). Of these, 37 enrollees with intermediate coronary lesions received FFR measurements. Their goal was to determine the diagnostic accuracy of this approach and compare hyperemic myocardial blood flow and coronary flow reserve.

They showed that hyperemic myocardial blood flow was better than coronary flow reserve for detecting CAD, and that a single measurement appeared to be sufficient. The hybrid approach improved diagnostic accuracy significantly and reduced the number of false positives on CTCA from 47 to six, thanks to the addition of hyperemic myocardial blood flow. But it also incorrectly reclassified 12 of 49 true positives.

“You lose a little bit of the ability of the CT to rule out CAD by combining these two imaging modalities,” Danad acknowledges.

The findings paved the way for a prospective study that will allow them to do a head-to-head comparison of SPECT/CT and PET/CT. All patients in the trial will be referred to the catheterization laboratory to undergo invasive coronary angiography in conjunction with invasive intracoronary pressure measurements. Danad says the study will answer the question of whether modern SPECT/CT devices are similar to PET for diagnostic accuracy.

Ultimately, they want to develop a staged protocol that would spare some patients from undergoing invasive procedures. “First we start with a CT scan and if the CT is negative, then we can discharge the patient,” Danad says. “If the CT is positive, we can add functional imaging to it.”

Lower radiation dose

CTCA and O-15 water PET aren’t the only marriages under consideration for the detection of CAD. Pamela Woodward, MD, head of advanced cardiac imaging and director of the Center for Clinical Imaging Research at Washington University in St. Louis, and her team presented promising early results for N-13 ammonia PET/MR stress perfusion imaging during the 2014 Society of Nuclear Medicine and Molecular Imaging Annual Meeting. MR’s ability to provide high resolution quickly at a lower radiation dose made it an attractive candidate for their pilot study.

Comparing cardiac PET/MR to gated SPECT myocardial perfusion imaging in six patients, they reported that PET/MR had equivalent sensitivity (100 percent for both modalities), superior specificity and diagnostic accuracy compared to SPECT.

“With this very small number of patients, we are getting 77 percent to 78 percent vs. 60 percent for SPECT,” Woodward says. Astellas Pharma, which makes the agent regadenoson, funded the pilot.

The researchers received support from Washington University to assess myocardial blood flow in a comparison of PET/MR and PET/CT, using MR for the attenuation correction. “If PET/MR is demonstrated to be consistent with PET/CT, then you would have a modality that quantitatively and qualitatively could provide you with a lot of information,” she says, adding that MR also offers functional information obtained with echocardiography.

Not for everyone

Only a handful of facilities house the hybrid PET/MR devices, which she estimates cost between $7 million and $7.5 million. Pediatric oncology programs may be able to make a case for the expense based on the long-term benefit of reduced radiation exposure to young patients as well as case volumes. Cardiology programs would more likely be secondary users.

“It is a new modality and in the cardiac realm it has a specific niche,” Woodward says. “The groups who will probably purchase the scanner will be interested in oncologic imaging and cardiac imaging that would be done alongside of it.”

Given the expense of testing and limited access, PET/MR is unlikely to be a first-line approach for assessing coronary artery disease, ischemia or MI, Woodward suggests. Rather, it may be best for complex cases or patients who are obese or prone to attenuation artifacts on SPECT.

“You could get the functional information, the perfusion information from PET/MR with the PET being highly sensitive and the MR being very high resolution,” she says, to better assess the perfusion deficit. “Does it affect a small portion of the thickness of the myocardium or does it affect the full thickness?”    

Ultimately, true hybrid PET/CT imaging is uncommon in clinical practice, Danad notes. Additionally, the tracers O-15 water and N-13 ammonia that allow for quantification of myocardial blood flow pose potential challenges due to their short half-lives. Consequently, they require a nearby cyclotron.

That barrier will become easier to surmount in Europe with the use of approved tabletop cyclotrons, he points out. “You can put it in the same room where you have the scanner and you can take the water from the cyclotron and inject it in the patient.”

Eventually, PET/CTCA or PET/MR could give interventional cardiologists tools to guide treatment decisions for patients with CAD. The studies in the Netherlands and the U.S. take the promise of a noninvasive assessment that provides more information than traditional modalities one step closer to reality.