INVITED COMMENTARY How Accurate Is Quantitative Gated SPECT?

SPECT information into the imaging agents, but at least 4 involved 201Tl ew clinicians would dispute the analysis increases specificity for ruling based protocols. The analysis of most importance of knowing both the perfu out coronary disease by improving rec of the studies focused on the Spearman sion status and the left ventricular ognition of attenuation artifacts (7). correlation coefficient, which averaged function of patients with various coro To our knowledge, a formal analysis 0.87 (8). Virtuallyall the studiescon nary artery disease syndromes. In the of the cost-effectiveness of incorporat cluded that estimates of LVEF obtained setting of stable and unstable coronary ing gated SPECT perfusion imaging through gated SPECT were accurate artery disease, knowledge of left yen routinely into imaging protocols has compared with the gold standards. tricular function (usually as ejection not been reported. However, the cost of However, not all the reports provided fraction) has important management performing, analyzing, and interpreting information on variability around the implications, because different out gated SPECT in conjunction with stan reported correlation line, such as the comes have been shown after mechani dard perfusion imaging should be rela SEE, which indicates the likelihood cal revascularization versus medical tively modest, in comparison with an that the ejection fraction measured by therapy (1,2). Moreover, the widely entirely separate analysis of left yen the new technique will be within a acknowledged clinical relevance of tnicular function by radionuclide yen certain range of the ejection fraction these parameters is supported by stud tniculography or echocardiography. If measured by the gold standard. In ies showing the statistically incremen we accept the importance of left yen some studies in which this variability tal prognostic value afforded by knowl tnicular functional information in deriv was reported, the gated SPECT ejec edge of left ventricular function even ing a management strategy for patients, tion fraction could be assumed to be when perfusion status is known, particu the cost-effectiveness of gated SPECT between 5% and 10% of the gold larly after myocardial infarction (3). is a reasonableassumption. standard, a fairly large range. In others, The powerful clinical management How accurate are gated SPECT mea however, the SEE was relatively small, implications of combined knowledge surements of ejection fraction and left indicating more reliable data. Few of of myocardial perfusion and left yen ventricular volume? To some degree, the analyses reported data on agree tricular function are a factor underlying the answer may be influenced by many ment between techniques using Bland the rapid growth and diffusion of gated variables, including the gold standard Altman plotting (8), which more pre SPECT technology in nuclear cardiol against which gated SPECT is mea cisely determines agreement between 2 ogy laboratories. This growth has also sured and the accuracy, repeatability, techniques measuring the same param been facilitated by the now widespread and reproducibility of that gold stan eter and examines nonrandom van availability of multidetector camera sys dard. How does one determine accu ability across the range of values tems allowing uniformly good count racy with the greatest statistical preci measured. statistics in SPECT studies and by sion? As reyiewed by Germano and The choice of gold standard in these software such as the easy-to-use quan Berman (8), by the middle of 1998 studies should strongly influence inter titative gated SPECT (QGS) program more than 20 studies had been pub pretation of the data. Comparing a (Cedars-Sinai Medical Center, Los An lished on the correlation between quan quantitative, predominantly operator geles, CA) (4—6)and the Emory Car titative measurements obtained through independent methodology such as QGS diac Toolbox (Emory University, At gated SPECT perfusion imaging (using (8,9) with a technique such as 2-dimen lanta, GA). The coupling of the imaging various algorithms) and through other sional echocardiography (10,11), which hardware and software to more power measures of left ventricular ejection has significant operator interaction as ful microprocessors has made the every fraction (LVEF). The studies used dif well as significant variability, creates day use of these software programs ferent gold standards, some quite quan problems in determining the value of routine in most laboratories. Besides titative and reproducible (such as the new technique. More recently, stud providing clinicians with clinically rel first-pass RNA or radionuclide ventnicu ies comparing gated SPECT with MRI evant information on both perfusion lography) and others less so (such as have begun to emerge (12,13). and function, the incorporation of gated 2-dimensional echocardiography and Several issues relevant to everyday thermodilution techniques). Some of clinical imaging have not been fully Received Dec. 2, 1999; revision accepted Dec. these reports were published in full in addressed by many of these studies 29, 1999. For correspondence or reprints contact: James peer review journals, and the remain correlating gated SPECT ejection frac E. Udelson, MD, Division of Cardiology, New En der were published as abstracts. Most tion with other techniques. These is gland Medical Center, Box 70, 750 Washington St., Boston, MA 02111. concerned the use of 99mTc@based sues include the influence of a stress

How ACCURATEIs QUANTITATIVEGATED SPECT? •Udelson and Fares 883 perfusion defect on the (usually post peatability when the algorithm was tion. Not all of the few previous studies stress) gated SPECT calculation of ejec applied to 2 sequentially acquired im comparing QGS in humans with MRI tion fraction, as well as the influence of ages. The correlation coefficient be measurements have used similarly rig varying degrees of extracardiac back tween the sequentially measured LVEFs orous methodology for evaluation of ground activity on the accuracy of the during a 30-mn interval was signifi the MRI studies (12,13). The use of this method. In most of the reported stud cantly better after a high-dose ses methodology as the gold standard ies, data from large numbers of patients tamibi rest study than after a low-dose would tend to magnify any inaccura with both normal and abnormal stress adenosine stress study. cies in the commercially available QGS perfusion are combined to examine the Background activity also had a strong system, particularly in a study with correlation, but few studies have fo influence. Repeatability of measure relatively few data points. Larger stud cused on patients with abnormal stress ments during a 30-ruin interval was ies that involve gold standards with perfusion. Johnson et al. (14) reported poor in studies in which the back their own inherent inaccuracies (even that the poststress ejection fraction may ground activity was considered exces first-pass RNA and radionuclide yen be significantly lower (by more than sive but very good in studies with tniculography) may tend to homog 5%) than the gated SPECT ejection minimal extracardiac background enize such differences, particularly fraction derived from a separate resting counts. Generally, left ventricular vol when examined over large numbers of perfusion study in a considerable minor umes and particularly LVEF were over patients using correlation analysis. ity of patients. These patients generally estimated by the QGS algorithm com Another factor in the apparent dimi had substantial stress perfusion abnor pared with MRI. This overestimation nution of QGS accuracy in this setting malities, raising the possibility that the was particularly profound among the is the size ofthe hearts. Other investiga diminished poststress ejection fraction animals with a perfusion defect im tors have reported that in small hearts, relative to the resting ejection fraction posed by occlusion of the left anterior the relatively limited spatial resolution may represent postischemic stunning. descending artery. The authors con of SPECT makes endocardial border As pointed out by Bonow (15), how cluded that although the QGS software definition at end-systole problematic, ever, the quantitative border detection provides a highly reproducible esti leading to overestimation ofLVEF (19). algorithms used in programs such as mate of LVEF, the background activity Different filtering algorithms may be QGS may not be as accurate in detect has a strong influence (which in part an approach to this problem (20). In ing endocardial borders near signifi would relate to the time of imaging addition, count-based recognition meth cant stress perfusion defects. This pos after injection), as do the injected dose ods rather than border detection meth sibility exists even though the algorithm and the presence of a perfusion defect. odsmayobviatethesediscordancesin is seeking count distribution profiles These provocative results raise ques small hearts (21). The size of the that are not necessarily visible to the lions. How can we reconcile the results ventricular cavity in the dog model of naked eye (16). Williams and Taillon with the many reports in humans on the Vallejo et al. (18) favors measurements (1 7) used image inversion to better accuracy of gated SPECF algorithms in detect the true borders in the territory detennining ejection fraction and vol by the technique with the higher spatial resolution. ofa perfusion defect, but this methodol umes? Do the results undermine the ogy is not widely available. general usefulness of applying QGS Do the results of this study under The accuracy, repeatability, and re results in everyday practice? mine the general usefulness of QGS producibility of the widely used QGS The apparent discordance has 5ev estimates of ejection fraction in routine program are critically examined in an eral potential explanations. The first is imaging studies? Perhaps among the important study by Vallejo et al. (18) in the choice of gold standard. In the most important findings of the study of this issue of The Journal of Nuclear study of Vallejo et al. (18), careful Vallejo et al. (18) is the critical impor Medicine. They examined the effect of quantitative measurements from cine tance of minimizing extracardiac back injected dose, timing of imaging, ex MRI were used. As the authors pointed ground activity. In studies of resting tent and magnitude of background ac out, this technique has distinct poten perfusion, vasodilator pharmacologic tivity, and presence or absence of a tial advantages over almost all other stress, and submaximal exercise stress, perfusion defect on the accuracy of techniques for accurate determination hepatic uptake may be excessive, as, in QGS measurements of LVEF and vol of LVEF and volumes. The technique some cases, may large-bowel activity umes relative to quantitative MRI mea is truly 3-dimensional,structuresare adjacent to the myocardium. In addi surements in a dog model. They found, completely separated, full interroga tion to affecting the accuracy of the as others have (8), that the QGS method tion of the entire left ventricular cham automated QGS program, these foci of is extremely reproducible when the ber is possible, attenuation is not an extracardiac activity can also affect the algorithm is applied twice to the same issue, and no geometric assumptions summed perfusion imaging data and image set, as would be expected for a are needed because the high spatial can confound all quantitative analysis fully automated algorithm. However, resolution of the study allows a reason programs. As Germano et al. (22) re count statistics strongly influenced re ably accurate endocardial border defini ported, excessive hepatic uptake rela

884 THE JOURNALOF NUCLEARMEDICINE •Vol. 41 •No. 5 •May 2000 tive to cardiac uptake may cause yisu The next step in determining how accuracy of software programs such as ally apparent artifactual perfusion widely applicable the implications of QGS have fueled the rapid growth of defects. Hence, the study of Vallejo et the data of Vallejo et al. (18) are to adjunct gated SPECT in many laborato al. further emphasizes the importance clinical practice would be to repeat the ries and have been significant develop of optimizing the image acquisition comparison using similarly robust cine ments in the field ofnuclear cardiology. parameters to minimize extracardiac MRI measurements in humans, who This ease of use and general accuracy activity. This process often will have generally larger hearts, with and as reported in many studies should not, prolong the waiting time between in without perfusion defects. We need to however, preclude critical evaluation jection and imaging and requires knowl examine whether count-based gated of limitations of this or any other edgeable technologists who can recog SPECT ejection fraction methodolo program. Users should routinely appre nize excessive extracardiac activity gies are significantly better than border ciate the potential limitations, as illus early, stop the acquisition, and restart it detection methodologies in determin trated in the study of Vallejo et al., and when the ratio of cardiac activity to ing LVEF in a perfusion defect setting. methods to overcome those limitations. background activity is better. Also needed is an examination of the Of course, this approach is similar to The effect of a perfusion defect on influence of extracardiac activity and a that taken with commercially available the accuracy of QGS measurements of comparison with gold-standard, state quantitative analysis programs for stan ejection fraction and volume has never, of-the-art cine MRI measurement in dad perfusion imaging, which are also to our knowledge, been examined as humans. Such studies would go a long affected by count statistics and extracar closely as in the study of Vallejo et al. way toward resolving some of the issues diac activity. As in visual interpreta (18). The data at hand still do not allow raised by the study of Vallejo et al. tion, optimal use of any quantitative us to determinewhetherthe discor Nonetheless, the importance of incor program requires an experienced opera dance between rest and poststress LVEF porating information on left ventricular tor and reader and meticulous attention that some studies reported truly repre function into management decisions to quality control. With that require sents prolonged postischemic dysfunc for patients with myocardial perfusion ment met, use of QGS to acquire tion (stunning) or is a problem with abnormalities is widely accepted, and clinically relevant information that cost border recognition by the automated clinicians have embraced the informa effectively optimizes patient care is algorithm. The study of Vallejo et al. tion provided by gated SPECT and the likely to become widespread. was not designed to examine this issue. commercially available software algo The study does, however, raise some rithms. Indeed, a position statement by James E. Udelson caveats about whether geometry-based the American Society ofNuclear Cardi Maan A. Fares measurements with assumptions about ology recommends that gated SPECT New England Medical Center Hospitals left ventricular shape are appropriate in be routinely incorporated in all perfu Tufts University School of Medicine Boston, Massachusetts studies of the accuracy of ejection sion imaging acquisitions (24). The fraction measurements in the presence study by Vallejo et al. (18) highlights of a perfusion defect. Determining the importance of quality control dur REFERENCES

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886 Tw@JOURNALOF NUCLEARMEDICINE •Vol. 41 •No. 5 •May 2000