Clinical Techniques of Positron Emission Tomography and PET/CT

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CHAPTER 24 Clinical Techniques of Positron Emission Tomography and PET/CT

Positron emission tomography (PET) is a powerful tool that provides high-quality assessment of myocardial diseases. Although PET has been used for more than 25 years as a powerful investigative tool to understand physiologic processes such as myocardial perfusion and metabolism, neuronal and receptor function, and, more recently, molecularly targeted imaging, it is increasingly being accepted in routine clinical practice as a noninvasive tool to evaluate patients with known or suspected coronary artery disease (CAD). The reasons for this increased acceptance are likely multifactorial and related to the exponential growth in the number of PET/CT systems, attributable primarily to the widely accepted role of the technology in clinical oncology, which has led to increased availability; approval by the U.S. Food and Drug Administration of PET radiopharmaceuticals for cardiac imaging; changes in reimbursement; and the increasing documentation of clinical efficacy of PET/CT. All of these factors have contributed to help advance the clinical role of PET/CT in clinical cardiovascular medicine. This chapter reviews the current clinical uses of cardiac PET/CT imaging with a focus on the diagnosis of CAD and assessment of myocardial viability.

RADIOPHARMACEUTICALS

Although several tracers have been used for evaluating myocardial perfusion with PET, the most widely used in clinical practice are rubidium 82 and ammonia N 13. In addition, 18FDG is the radiotracer of choice for the evaluation of myocardial viability.1

Ammonia N 13

Being a cyclotron product, ammonia N 13 use in routine clinical practice is limited to institutions that have a cyclotron on site. It has a physical half-life of 9.96 minutes and has a shorter positron range compared with rubidium 82, resulting in higher signal-to-noise ratio. After injection, ammonia N 13 rapidly disappears from the circulation, permitting the acquisition of images of excellent quality. Although the sequestration of ammonia N 13 in the lungs is usually minimal, it may be increased in patients with depressed left ventricular systolic function or chronic pulmonary disease and, occasionally, in smokers; this may adversely affect the quality of the images. In these cases, it may be necessary to increase the time between injection and image acquisition to optimize the contrast between myocardial and background activity. When inside the myocyte, ammonia N 13 is incorporated into the glutamine pool and becomes metabolically trapped. Only a small fraction diffuses back into the intravascular space.3

Myocardial retention of ammonia N 13 is heterogeneous, with retention in the lateral left ventricular wall being about 10% lower than that of other segments, even in normal subjects. This heterogeneous retention could result in an apparent perfusion defect in the inferolateral wall, limiting its evaluation. Ammonia N 13 allows the acquisition of ungated and gated images of excellent quality. These studies take full advantage of the superior resolution of PET relative to single photon emission computed tomography (SPECT) because the half-life of ammonia N 13 is sufficiently long, and its average positron range is very short. Gated ammonia N 13 imaging can provide accurate assessments of regional and global cardiac function.4 This imaging agent is not well suited for peak stress gated imaging, however, because of the 3- to 4-minute time interval between radiotracer injection and start of imaging, and the relatively long (20 minutes) acquisition time.

ASSESSMENT OF MYOCARDIAL PERFUSION

Imaging Protocols

Figure 24-1 illustrates common protocols used for imaging myocardial perfusion with PET/CT, where the low-dose CT scan is used for attenuation correction.1 This scan is also called a CT-based attenuation correction scan (CTAC).

image

image FIGURE 24-1 A-D, Protocols for clinical cardiac PET/CT imaging. CAC, coronary artery calcium; CTA, CT angiography; CTAC, CT-based attenuation scan.

(From Di Carli MF, Dorbala S, Meserve J, et al. Clinical myocardial perfusion PET/CT. J Nucl Med 2007; 48:783-793.)

Emission Scans

For rubidium 82, approximately the same dose (40 to 60 mCi) is injected for the rest and stress myocardial perfusion studies because of the short physical half-life of rubidium 82 (76 seconds). For ammonia N 13, the general trend is to use a lower dose for the rest images (10 mCi) and a higher dose for the stress images (30 mCi), analogous to 1-day SPECT imaging protocols. The low-dose/high-dose protocol is faster than same-dose protocols for rest and stress because it does not require waiting for decay of ammonia N 13 to background levels before a second dose can be administered. Large patients may require large doses for the rest and stress studies. Some laboratories perform stress imaging first because a normal scan may avoid the need for rest imaging. This approach limits the ability to assess rest myocardial blood flow and coronary vasodilator reserve, however, limiting the ability to identify patients with extensive CAD and “balanced” ischemia, as discussed subsequently.

Different protocols can be used to acquire emission scans (see Fig. 24-1), as follows:

2 Multiframe or dynamic imaging. Imaging begins with the bolus (short infusion) of rubidium 82 or ammonia 13 N and continues for 7 to 8 minutes or 20 minutes (see Fig. 24-1C). The advantage of this approach is that it allows quantification of myocardial blood flow (in mL/min/g) by fitting regional tissue and blood time-activity curves to a suitable kinetic model. Its main disadvantage is that one needs to perform a separate radionuclide injection to obtain ECG gated images from which to assess cardiac function, especially when using rubidium 82. Using ammonia 13 N, one can acquire a short multiframe or dynamic scan (4 minutes) that can be followed with a separate, approximately 15-minute ECG gated scan to assess myocardial perfusion and left ventricular ejection fraction (LVEF), without the need of an additional radionuclide injection owing to its longer physical half-life (approximately 10 minutes) (see Fig. 24-1D). To measure the left ventricular blood time-activity curves noninvasively, one must acquire many dynamic PET image frames while the tracer bolus passes through the right ventricle, the lungs, and the left ventricle. During this interval, it is common for a large amount of activity (approximately 20 to 30 mCi) to be located entirely within the PET scanner’s axial field of view. Because of possible count-rate limitations under such conditions, particularly in three-dimensional scan mode, great care must be taken to ensure the accuracy of the PET system’s corrections for random and scatter coincidences and dead time.

Stress testing is most commonly performed using adenosine, dipyridamole, or dobutamine. Protocols using exercise stress testing with PET/CT have been described.5 The use of exercise PET in clinical practice is very limited, however, especially with shorter half-life agents such as rubidium 82 (half-life 76 seconds).

Quality Assurance for Cardiac PET/CT

Hybrid imaging using PET/CT is prone to significant artifacts if not performed correctly. Quality control measures, including routine inspection of the transmission and emission data and the transmission-emission alignment, should always be enforced to obtain high-quality studies. These quality control measures include the following:

3 Transmission-emission misalignment. Misregistration of transmission and emission images can result from respiratory or patient motion, and can lead to inaccurate clinical results (Fig. 24-2). Because transmission and emission imaging are sequential, patient or respiratory (e.g., deep inspiration) motion during the emission images is most likely to lead to transmission-emission misalignment and potential attenuation-correction artifacts (see Fig. 24-2). The extent and direction of this misalignment determine whether artifacts are apparent in the attenuation-corrected images. Most commercial PET/CT systems now include software tools to correct for transmission-emission misalignments.

Diagnostic Accuracy

Table 24-1 summarizes the published studies documenting the diagnostic accuracy of myocardial perfusion PET imaging for detecting obstructive CAD.7 The average weighted sensitivity for detecting at least one coronary artery with greater than 50% stenosis is 90% (range 83% to 100%), and the average specificity is 89% (range 73% to 100%). The corresponding average positive and negative predictive values are 94% (range 80% to 100%) and 73% (range 36% to 100%), and the overall diagnostic accuracy is 90% (range 84% to 98%). Most of the available data have been obtained with dedicated PET cameras, rather than with PET/CT systems. In a more recent study using PET/CT (where the CT was used only for attenuation correction), Sampson and colleagues8 reported a sensitivity of 93%, a specificity of 83%, and a normalcy rate of 100%. In this study of patients without known prior CAD, the positive and negative predictive values of PET/CT were 80% and 94%, with an overall accuracy of 87%. All patients with a low likelihood for CAD showed normal scans, for a normalcy rate of 100%. The sensitivity for detecting CAD in patients with single vessel and multivessel (two or more vessels) disease was 92% and 95%. These results were applicable to men and women and to obese and nonobese individuals.

Comparative Studies of Positron Emission Tomography versus Single Photon Emission Computed Tomography

Two studies have performed a direct comparison of the diagnostic accuracy of rubidium 82 myocardial perfusion PET and thallium 201 imaging in the same patient populations. Go and colleagues9 compared PET and SPECT in 202 patients and showed higher sensitivity with PET than with SPECT (93% vs. 76%), without significant changes in specificity (78% vs. 80%). Stewart and coworkers10 compared PET and SPECT in 81 patients and observed a higher specificity with PET than with SPECT (83% vs. 53%), without significant differences in sensitivity (86% vs. 84%). The differences between these two studies are likely to be attributable to patient selection resulting in differences in prescan likelihood of CAD.

More recently, Bateman and associates11 compared rubidium 82 PET and Tc 99m sestamibi SPECT in two matched patient cohorts undergoing clinically indicated pharmacologic stress perfusion imaging using contemporary technology for SPECT and PET. Overall diagnostic accuracy was higher for PET than for SPECT (87% vs. 71% with a 50% angiographic threshold, and 89% vs. 79% with a 70% angiographic threshold). Differences in diagnostic accuracy reflected primarily the increased specificity (with a marginal advantage in sensitivity) of PET versus SPECT, and applied to men and women and to obese and nonobese individuals.

Evaluation of Multivessel Coronary Artery Disease

The diagnosis of multivessel or left main CAD with diffuse balanced ischemia using MPI remains a challenge. PET (similar to SPECT) often uncovers only the coronary territory supplied by the most severe stenosis. The use of ancillary high-risk markers often helps in ascertaining the presence of multivessel CAD. ECG gating provides a unique opportunity to assess left ventricular function at rest and during peak stress (as opposed to poststress with gated SPECT). More recent data suggest that in normal subjects, LVEF increases during peak vasodilator stress.12 In the presence of CAD, changes in LVEF (from baseline to peak stress) are inversely related to the magnitude of perfusion abnormalities during stress (reflecting myocardium at risk) (Fig. 24-3) and the extent of angiographic CAD (Fig. 24-4). In patients with three-vessel or left main CAD, LVEF during peak stress decreases even in the absence of apparent perfusion abnormalities (Fig. 24-5). In contrast, patients without significant CAD or with one-vessel disease show a normal increase in LVEF. Consequently, the negative predictive value of an increase in LVEF (from rest to peak stress) of 5% or greater to exclude the presence of three-vessel or left main CAD or both is 97%.12

image

image FIGURE 24-3 Bar graph showing the relationship between the magnitude of stress-induced perfusion abnormalities and the delta change in left ventricular ejection fraction (LVEF) (from baseline to peak stress).

(From Dorbala S, Vangala D, Sampson U, et al. Value of vasodilator left ventricular ejection fraction reserve in evaluating the magnitude of myocardium at risk and the extent of angiographic coronary artery disease: a 82Rb PET/CT study. J Nucl Med 2007; 48:349-358.)

image

image FIGURE 24-4 Bar graph showing the relationship between the delta change in left ventricular ejection fraction (LVEF) and the extent of angiographic coronary artery disease (CAD) (>70% stenosis).

(From Dorbala S, Vangala D, Sampson U, et al. Value of vasodilator left ventricular ejection fraction reserve in evaluating the magnitude of myocardium at risk and the extent of angiographic coronary artery disease: a 82Rb PET/CT study. J Nucl Med 2007; 48:349-358.)