State of the Heart: PET/CT Imaging
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Myocardial viability
F18-FDG PET is the current gold standard for the assessment of myocardial viability. The increased need for functional testing for detecting coronary stenosis and the growing use of CT angiography for this purpose has resulted in a transition to PET/CT, where both tests can be performed in a single imaging session, says Tommi Kokki, MSc, PhD student, Turku PET Centre, University of Turku in Finland.“Data indicate that FDG PET is the most sensitive test for detecting viable myocardium, more sensitive than MRI, thallium or technetium-99m based SPECT imaging and dobutamine echo,” says Robert S. Beanlands, MD, chief of cardiac imaging at University of Ottawa Heart Institute in Ontario, Canada. A recent randomized clinical trial in Canada, PARR-2 (PET and Recovery Following Revascularization-2), substantiated that when a subset of Ottawa patients subjected to on-site FDG-PET imaging was taken into account, there was a significant outcome benefit. “When you have access to the tracer, have experience in evaluating FDG-PET imaging and can integrate and communicate with the physicians who will be managing the patients, then you gain outcome benefits,” says Beanlands.
Myocardial perfusion
Another rapidly growing application of PET/CT is the imaging of myocardial perfusion using PET which will be further boosted by improved availability of the perfusion tracers in the near future. Looking at myocardial perfusion imaging allows you to make diagnostic assessments by describing the amount of ischemia that is present and which, in turn, is used for deciding who needs to go to medical therapy and who needs to have a surgical procedure for revascularization, shares says Marcelo F. DiCarli, MD, chief of nuclear medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston.PET/CT is a quantitative method to diagnose hemodynamically meaningful coronary artery disease (CAD) in patients with angina pectoris, says Kokki. “In our facility, patients first undergo a coronary computed tomography angiogram [CCTA] and if there is a suspicious coronary lesion, studies are continued with radiowater H2O perfusion imaging in the same session. With a stress study, it is possible to show the reserve capability of coronaries and inadequate rise in perfusion indicates hemodynamically meaningful stenosis.”
“PET is more sensitive than SPECT imaging and has better resolution with overall higher accuracy in the studies that have compared the two,” says Beanlands. “Rb PET is superior to SPECT in not only improved accuracy but also because the procedure is shorter for the patients. In the near future, this application will be growing even further as measurements of coronary flow reserves from the dynamic acquisition become more common,” says Daniel Berman, MD, director of cardiac imaging and nuclear cardiology at Cedars-Sinai Medical Center in Los Angeles.
Expanding horizons
Focal myocardial inflammation can be detected using F18-FDG PET in cardiac inflammatory diseases such as sarcoidosis, says Kokki. “For assessing overall vascular state of atherosclerosis, it is possible to do a whole-body F18-FDG study to see overall inflammatory state of vascular system. This, together with atherosclerosis risk factors, can give prognostic value and could be used to evaluate the need for medical treatment.”Other studies such as molecular imaging of platelet aggregation and adrenergic receptors are rare and cannot be performed in all imaging centers because of short physical half-life of radionuclides. Currently, such studies can only be performed in centers with an on-site cyclotron, notes Fatma Suna Kirac, MD, professor, department of nuclear medicine, Pamukkale University, School of Medicine, Denizli, Turkey.
“All other applications like endothelial dysfunction, microvascular disease, and identification of soft plaques remain experimental at this time with very limited clinical data to support its widespread clinical application,” says Vasken Dilsizian, MD, professor of medicine and radiology, department of diagnostic radiology and nuclear medicine, University of Maryland Medical Center in Baltimore.
“PET is a unique tool for molecular imaging research for both evaluating the vasculature as well as the myocardium because of two main characteristics—one is its very high sensitivity for picking up small amounts of signal coming out of abnormal structures and the second one is its quantitative ability,” says DiCarli. “We are looking at the role of quantitative PET in risk predication and diagnosis and have some protocols for looking into myocardial viability.” However, all research applications will not lead to a clinical application, but rather to a description of new biology or in the development of new drugs, DiCarli cautions.
Comparing modalities
Echocardiography is cheaper and more widely available to assess left ventricular function and valve diseases, without ionizing radiation, says Kokki. Invasive intracoronary ultrasound shows atherosclerotic plaques and detects vulnerable plaques, Kirac adds. However, both methods do not quantify perfusion and cannot reach the molecular targets, Kokki and Kirac agree. Rest and stress tissue Doppler imaging (TDI) are new imaging modalities for diagnosing CAD, but are not easily available and performed, adds Kirac.Coronary angiography gives true information about the structure of coronary arteries and lesions and cardiac function can be evaluated in the same session. But it does not assess myocardial perfusion and metabolism. “On the other hand, digital conventional angiography is an invasive procedure and depends on the operator. Computed tomography angiography and magnetic resonance angiography are noninvasive techniques, but microvascular lesions in the myocardium can not be detected, ” says Kirac.
Certainly the age of the patient, whether the patient has underlying irregular heart rhythm, calcified coronary artery or metal objects near the heart, renal insufficiency, lung disease, or contrast allergy will exclude a significant percentage of patients from being candidates for CT, and in these cases, myocardial perfusion imaging with PET would be preferable, Dilsizian says.
SPECT is currently the most used imaging technique for CAD. Its strengths lie in its established methodology and huge body of supporting evidence. However, the limitation is that perfusion cannot be quantified which leads to somewhat underestimation of the disease, says Kokki.
“There are several technical advantages of PET over SPECT related to spatial resolution, temporal resolution, sensitivity, quantitative ability and the data regarding attenuation correction and so on,” notes DiCarli.
PET/CT hybrid imaging & management
PET/CT hybrid imaging has opened up new possibilities in heart disease diagnosis, but there is an ongoing debate whether or not it is beneficial to combine PET/CT in one sitting or try to do one over the other.“With PET/CT, we routinely attain a coronary calcium scan at the time we are doing CT attenuation correction images,” Berman notes. “This knowledge of the amount of atherosclerosis can often be helpful in guiding management after the PET scan. The coronary calcium score also is effective when the PET scan has a borderline abnormality in determining how aggressively it can be evaluated.”
Dilsizian started using hybrid PET/CT imaging six years ago and has now changed to only sequential imaging rather than hybrid imaging. He questions the need for PET and CT done simultaneously given the additional high cost and additional radiation exposure from both tests. “Cardiac hybrid PET/CT imaging is not the same as the application of hybrid PET/CT imaging in oncology because often in cardiology you do not need to know both anatomy and perfusion simultaneously,” he says. “As a matter of fact, one could argue that if you have normal coronary anatomy on CT, you don’t need the myocardial perfusion data on PET, and conversely, if you have a normal myocardial perfusion PET study, you don’t need to know the anatomy. For as long as there is no evidence of significant myocardial ischemia, the presence of a coronary artery lesion on an anatomic basis shows no survival advantage from revascularization over medical therapy.”
Where is PET/CT useful?
PET/CT imaging may be the imaging technology of choice in the evaluation of myocardial viable tissue and perfusion reserve under stress in patients with severely depressed cardiac function, says Kirac. “Besides myocardial perfusion and metabolism, vascular pathologies can simultaneously be defined and PET/CT is the most valuable test before deciding coronary artery bypass grafting.”PET/CT also is likely to become the preferred tool in detecting CAD in patients with angina pectoris, Kokki predicts. “In these patients, CT angiography in combination with PET perfusion is a very powerful technique, ruling out or confirming hemodynamically relevant CAD. We have replaced SPECT imaging with hybrid PET/CT imaging in patients with suspected coronary artery disease [intermediate pretest likelihood of CAD]. However, in patients with known disease or patients after myocardial infarction or revascularization, Kokki uses SPECT. This is “due to limited experience of PET in these indications,” he says.
Patients with recurrent transient ischemic attack (TIA) episodes and many risk factors of atherosclerosis also may benefit from a PET/CT study of the carotid artery. Kokki adds, “PET can detect the carotid inflammation even if there has not been significant stenosis found in carotid ultrasound.”
PET/CT also differentiates itself in diabetic patients or patients with significant calcification on CT angiography since it may provide additional insight into the underlying coronary artery physiology, Dilsizian notes. “Among patients with diabetes mellitus who may have diffuse coronary artery disease and subclinical lesions, the information acquired from hybrid PET/CT could be used to monitor the progression or regression of coronary artery disease with aggressive risk factor modification and medical therapy,” he says.
Getting over the hurdles
With all of the benefits PET/CT offers, it is not without its challenges. “The obvious limitation of PET/CT is the limited availability [worldwide],” says Kokki. “PET/CT is more expensive than SPECT. Although it is the most valuable method for evaluating CAD, PET/CT will continue to be performed in selected cases in the future if its price does not go down,” opines Kirac.“PET comes with its own source of artifacts not seen in SPECT, including misregistration artifact when the CT scan and the PET data are misaligned resulting in artifactual defects during the attenuation correction process,” Berman adds. “Another disadvantage is that data subsets are much larger and perhaps it takes more time to transmit data from one place to another.”
The other major limitation is the availability of tracers which could swing utilization from SPECT imaging toward PET. Lantheus Medical Imaging’s myocardial perfusion tracer, BMS747158, an F18-labeled derivative that binds to the mitochondrial complex 1 (MC-1) inhibitor, has shown promise in preliminary clinical trials. “The tracer is superior to Rb because it uses an F18 agent which has a shorter travel distance in the body before annihilation resulting in increased resolution of the images—2 mm in resolution,” Berman says. “The other advantage of the tracer is that it is extracted in proportion to flow across the range of flow more avidly than the other available agents with either SPECT or PET. The superior uptake characteristic with high flow rate is an important quality that will allow this tracer to be more accurate with coronary flow rate than the existing methods.”
Dual-gated PET/CT eliminates most of the cardiac motion and it is possible to see spatially small vulnerable coronary plaque in PET and combine the information with the coronary anatomy derived from CT, says Kokki. “Currently, our group is developing the dual-gated PET/CT protocol to detect vulnerable coronary plaques of CAD patients. Recently we have published our dual-gating method and the promising results from phantom and mini pig studies. Now we have an ongoing study to perform dual-gated myocardial PET/CT study in patients with unstable angina.”
In the future, with better motion detection and correction methods together with more specific tracers, it could be possible to detect spatially smaller targets metabolically, Kokki says. This means that metabolic events like inflammation of the coronary vessel wall will become detectable noninvasively. Most acute events occur in patients who do not have hemodynamically significant CAD and this could lead to intensive medical therapy to prevent acute events such as myocardial infarction, he adds.
Further, the addition of quantified flow would enhance diagnosis and could become routine in most labs doing PET perfusion in future, Beanlands says. There will be numerous potential applications in metabolic and molecular imaging and the exceptional sensitivity of the technique will allow imaging of cellular molecular processes such as inflammation, gene expression and receptors, predicts Kokki.
Beanlands expects to see more translational research in the future. “There are now emerging small animal imaging cameras—microSPECT, microPET, microCT and so on—and each of these will enable us to take concepts from animal models and translate directly into humans in a rapid and efficient manner.”
PET/CT is an excellent noninvasive, fast imaging method and gives simultaneous information of coronary anatomy and myocardial perfusion and metabolic conditions of myocardium with myriad potential applications. However, the challenge remains in overcoming the rate limiting steps—developing new imaging agents, cost and more widespread scanner availability.