The possibility of quantifying myocardial blood flow (MBF) with PET imaging has existed for decades, but its clinical use has been limited. MBF is assessed more often in relative terms, with visible differences in flow between regions of myocardium, used as an indicator of problems. Now, new developments in tracers could make cardiac PET the more precise approach for absolute quantification.
Current methods of visually assessing MBF with SPECT have several limitations and can lead to an underestimation of the magnitude of a patient's coronary artery disease (CAD). There is low spatial resolution and high levels of soft tissue attenuation hindering image quality, and SPECT also is unable to quantify MBF in absolute terms. Relative assessment of MBF has certain weaknesses, according to Vasken Dilsizian, MD, chief of the division of nuclear medicine at the University of Maryland Medical Center in Baltimore.
Relative assessment involves visually evaluating the homogeneity of radiotracer distribution across the three coronary vascular territories. If the pattern of uptake is different between a normal reference region and the other territories, it could be an indication of CAD. The problem, Dilsizian says, is blood flow in the reference region also could be abnormally decreased, causing the physician to underestimate the reduction of blood flow in the other regions.
"When reading these images, we are always comparing it to a normal reference region, where in some patients, there is no normal reference region. Everything is abnormal," says Dilsizian.
What's more, if all regions are similarly occluded, the physician could misinterpret the exam as normal.
PET, with its higher image quality and robust attenuation algorithm, can measure MBF in absolute terms, thus avoiding the problems of relative assessment. Kajander et al studied the benefit of absolute quantification using PET over relative assessment using conventional angiography. They found that absolute quantification had a positive predictive value, negative predictive value and accuracy of detecting obstructive CAD of 86 percent, 97 percent and 92 percent, respectively (Circ Cardiovasc Imaging 2011;6:678-684). This is compared with values of 61 percent, 83 percent and 73 percent, respectively, for relative assessment.
However, the application of absolute MBF quantification by PET has been limited clinically. Part of this is due to limitations of PET tracers, as well as the restricted availability of PET cameras for cardiac studies conducted in academic centers.
Searching for the perfect tracer
Absolute blood flow measurements have been conducted with Rb-82, N-13 ammonia and O-15 water tracers, though each has its own set of drawbacks:
- O-15 water: Typically, this tracer is used only in research as it is not FDA approved and not reimbursed by the Centers for Medicare & Medicaid Services (CMS), according to Dilsizian. It requires an onsite cyclotron, a cost most facilities would like to avoid, and with a two-minute half-life, unit dose orders are impractical. Also, the myocardium cannot be visualized with O-15 water.
- N-13 ammonia: This tracer is both FDA approved and reimbursed by CMS. Like O-15 water, though, N-13 ammonia is cyclotron produced with a half-life of 10 minutes, which restricts its use to clinics equipped with cyclotrons, according to Georges El Fakhri, PhD, of the department of radiology at Massachusetts General Hospital in Boston.
- Rb-82: Rubidium tracers have only a 72 second half-life, but are produced by a column generator, not a cyclotron. El Fakhri says while there are high costs for a generator— approximately $30,000 for a month's use—it is still a more accessible piece of equipment than a cyclotron.
While the current crop of tracers is held back by costly equipment, a new F-18-based flow agent could shake up the nuclear cardiology space, says El Fakhri. F-18 labeled flow agents, such as flurpiridaz, have a half-life of 110 minutes, which means a dose order could be manufactured and shipped rather than having to be produced onsite. While still undergoing clinical trials, preliminary results are spreading optimism about its potential future clinical use.
The results have demonstrated that the extraction fraction of F-18 perfusion "is much better than that of ammonia," and if F-18 flow agents get FDA clearance, El Fakhri predicts it "could have a major impact on cardiac PET imaging."
Studies, such as one by Sherif et al, have shown the usefulness