Nuclear Medicine Imaging of Ventricular Function

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CHAPTER 56 Nuclear Medicine Imaging of Ventricular Function

Left ventricular (LV) function is an important, well-established indicator of patient prognosis. Radionuclide imaging techniques are established as the most highly reproducible methods to assess LV ejection fraction noninvasively. Comprehensive textbooks have summarized the results of studies over several decades showing the high reproducibility and accuracy of gated equilibrium blood pool scintigraphy and radionuclide angiography in determining LV and right ventricular (RV) ejection fraction measurements.¹^–⁴ Cardiac mortality is strongly associated with impaired ventricular function as assessed by decreased LV ejection fraction. Additionally, identifying dysfunctional segments in viable myocardium is crucial in clinical management. Numerous studies have shown an almost threefold higher incidence of cardiac mortality in medically treated patients with viable compared with nonviable myocardium.⁵ The identification of focal dysfunctional segments is highly relevant to clinical management.

The introduction of Tc-99m radiotracers has made gated myocardial perfusion imaging (MPI) readily available, easily feasible, and now a standard technique requiring little additional effort or cost.⁶ Because MPI is the most commonly performed procedure in nuclear cardiology, evaluation of LV function in nuclear cardiology is most often performed in conjunction with MPI. Similarly, assessment of ventricular function by gated MPI can be performed with positron emission tomography (PET).⁷

Gated equilibrium blood pool imaging is a well-established technique commonly used to assess ventricular function quantitatively in oncology patients receiving cardiotoxic chemotherapy. High reproducibility, technical simplicity, and availability, make this study the procedure of choice in evaluating LV function sequentially. Although first-pass radionuclide angiocardiography is a well-established and elegant technique to determine ejection fraction, equilibrium blood pool imaging provides the ability to view ventricular function from multiple planar projections, or in a fully three-dimensional manner using single photon emission computed tomography (SPECT).

For quantitative, functional analysis of the right ventricle by RV ejection fraction, first-pass angiocardiography currently remains the method of choice because planar equilibrium blood pool imaging cannot separate underlying or adjacent blood pool structures sufficiently for an accurate determination of RV ejection fraction. Newer techniques, such as tomographic ECG gated blood pool (GBP) imaging, are becoming more widespread as quantitative software programs are being developed and validated. These newer techniques have the potential to evaluate simultaneously and quantitatively RV and LV size and function, with high spatial and temporal resolution. Elegant first-pass techniques have been developed to evaluate intraventricular shunts quantitatively; the need for these is relatively uncommon, and they are described elsewhere.¹

This chapter describes the most commonly performed radionuclide techniques to assess ventricular function. First, gated SPECT MPI is discussed. These principles are generally applicable to gated PET assessment of ventricular function. As PET MPI becomes more prevalent in the future, this technique is expected to become increasingly important. Next, equilibrium GBP imaging is reviewed briefly. Finally, RV functional evaluation with first-pass radionuclide angiocardiography is discussed.

LEFT VENTRICULAR FUNCTIONAL ASSESSMENT FROM GATED MYOCARDIAL PERFUSION IMAGING

ECG gating to assess ventricular function is now a standard, integral part of MPI. The quantitative evaluation of LV ejection fraction has exhibited high reproducibility and accuracy. Compared with CT, LV ejection fraction assessed by SPECT is not significantly different, although absolute values for end-diastolic volume and end-systolic volume are different with SPECT.⁸ As expected, LV functional impairment quantified by SPECT is associated with a poor prognosis, including cardiac death. LV ejection fraction less than 45% and LV end-systolic volume greater than 70 mL were associated with approximately 8% to 9%/yr cardiac death rate compared with approximately 1%/yr for LV ejection fraction 45% or greater and end-systolic volume 70 mL or less.⁹ Although perfusion defect reversibility is most predictive of future myocardial infarction, LV ejection fraction is the strongest predictor of mortality.¹⁰

Several studies have shown the clinical utility with improved specificity by identifying normal wall motion and wall thickening in areas of decreased activity because of tissue attenuation. This improvement in specificity may be particularly important in women because of breast attenuation artifacts. The gating information also assists in improving the degree of certainty when interpreting studies as definitely normal or definitely abnormal.⁶^,¹¹ In a prospective study of 115 women, gated Tc 99m sestamibi significantly improved specificity (92%) compared with the same study without gating (84%; P = .0004) or with thallium 201 without gating (59%).¹²

In addition, gating improves sensitivity for detection of coronary artery disease (CAD) in the subset of patients with multivessel disease (“balanced disease”) who have transient, stress-induced wall motion abnormalities that are not detected by MPI alone.¹³ Additional wall motion information significantly increased the sensitivity for detection of multivessel CAD without adversely affecting specificity.¹⁴ In this study, the sensitivity for multivessel disease was significantly increased from 46% to 60%, and sensitivity for three-vessel disease significantly increased from 10% to 25%.¹⁴ Principles of gated MPI with SPECT are similar to gating with PET radiotracers such as ammonia N 13 or rubidium 82, providing regional and global wall motion information.¹⁵^,¹⁶ The more recent development of combined PET/CT and SPECT/CT instrumentation may also permit additional, independent, high spatial resolution CT assessment of regional myocardial function.¹⁷

Electrocardiogram Gated Acquisition

Analogous to traditional methods of acquiring planar gated studies, the ECG is used to bin counts from the various phases of the cardiac cycle temporally during data acquisition. Because of count limitations, most studies currently use eight time frames per cardiac cycle. In patients with irregular rhythms, such as atrial fibrillation, ventricular function may be better assessed with methods that do not rely on data from multiple, averaged heartbeats (e.g., echocardiography). If gated MPI is used, the averaged data may be subject to inaccuracies because of misplacement of counts within the cardiac cycle, and careful inspection of the ECG and gating data is necessary to ensure that appropriate beats with similar RR intervals are included for analysis.¹⁸^,¹⁹

Data Processing, Reconstruction, and Analysis

In most cases, appropriate binning of the data into the various phases of the cardiac cycle results in accurate representation of LV function. Tomographic images are typically reconstructed with filtered back-projection, and sophisticated edge detection programs are used to define ventricular boundaries. From these volumes, time-activity curves are generated, indices of ventricular function are derived, and a cine display is generated for visual assessment of regional and global LV function.

Well-developed programs to evaluate LV wall motion have been commercially available for several years.²⁰^–²² Generally, these use boundary detection algorithms, count densities, or a combination of variables to define the endocardial and epicardial borders for LV volume calculations. Another important parameter is LV wall thickening. Detected activity within the myocardium depends on radioactive concentration and volume (or thickness) of the myocardium. When small objects (LV myocardial wall thickness) are below twice the full-width half-maximum of the system resolution, detected activity within the ventricular wall appears lower than the true activity because of partial volume effects.²³ Because myocardial wall thickness is susceptible to the partial volume effect, a higher wall thickness at end-systole corresponds to higher detected activity by SPECT. The degree of regional wall thickening is related to the change in detected regional myocardial wall activity. Detected activity at end-diastole typically is lower than that at end-systole because of differences in ventricular wall thickness. Some algorithms assume there is an exact linear relationship between myocardial wall thickening and percent systolic count increases.

Cardiac volume and myocardial thickening can be appreciated visually for cine display formats of individual tomographic slices and computer-generated derived surface renderings. In addition, quantitative, physiologic indices are derived from tomographic volumes and from counts within the myocardium. Fourier analysis is applied to the time-activity curve of each data element in the volume (voxel) to generate parametric images of contraction. Fourier analysis forms the basis of phase and amplitude analysis by which the pattern of myocardial contraction and regional wall motion is assessed quantitatively. More recently, high correlation of LV ejection fraction measurements was reported between techniques in hybrid instrumentation combining high-resolution 64-slice CT with SPECT; mean values were not significantly different.⁸

As described earlier, the primary potential benefits of concurrent wall motion assessment include (1) improved specificity in cases of fixed regions of decreased activity (improving detection of attenuation artifacts), and (2) improved sensitivity in detection of multivessel CAD or three-vessel disease (i.e., detection of abnormal wall motion in patients with “balanced disease”). With respect to increased specificity, this may be particularly beneficial in women with severe anterior breast attenuation, and in men with severe inferior diaphragmatic attenuation. The presence of completely normal wall motion and wall thickening is strong evidence that large transmural infarction has not occurred. Although small subendocardial infarction may not be detected with gated perfusion imaging, normal wall motion and normal LV function are good prognostic indicators, which can greatly aid in the assessment of prognosis.

With respect to sensitivity, exercise-induced LV dysfunction has shown improvement in sensitivity for detection of multivessel CAD over perfusion information alone; it also provides further information regarding the clinical significance of known disease. This information may be clinically important in patients with multivessel CAD, who are among the patients most likely to benefit from further therapy.