Daniel S. Berman, MD

Approach addresses pitfalls that have held back widespread use of SPECT/CT for myocardial ischemia 

A major impetus for the growth of nuclear cardiology is the need for information beyond detection of coronary artery stenoses alone. Researchers have demonstrated in patients undergoing SPECT myocardial perfusion imaging that the amount of ischemia by SPECT MPI is the strongest determinant of the subsequent use of angioplasty or bypass surgery and an effective discriminator of patients likely to show a survival benefit with revascularization.1 In patients with suspected coronary artery disease and minimal symptoms that are not affecting daily living, objective documentation of myocardial ischemia, most commonly with SPECT MPI, often becomes the gatekeeper to the cath lab.2-4

The wide availability of 64-slice CT scanners will undoubtedly bring a marked growth in noninvasive coronary CT angiography, which provides excellent anatomic images. Use of coronary CTA will increase particularly in patients with an intermediate pretest likelihood of CAD. The limitations of anatomic imaging alone, however, are likely to become even more apparent with CT than they were with invasive coronary angiography. Coronary CTA results alone are often insufficient to guide patient management. A need for functional information will arise in many patients demonstrating anatomic coronary abnormalities on CT scans. Whether such information will be most practically provided at the same time as the anatomic findings or at a separate time is not yet clear.

All of the major scintillation camera manufacturers have commercially available SPECT/CT systems. GE Healthcare, the first to roll out a low-end CT system that provided proof of concept, has since announced a 64-slice system capable of coronary CTA as well. Siemens Medical Solutions has focused on a six-slice system that provides CT coronary calcium measurements along with attenuation correction. Philips Medical Systems is delivering 16-slice SPECT/CT systems capable of coronary CTA and has announced the development of a 64-slice SPECT/CT unit. Of course, the greater the number of slices of the CT part of the system, the greater the associated costs are likely to be.

Various advantages of combined SPECT/CT systems have a range of importance in cardiac imaging.

- Attenuation correction. All SPECT/CT systems offer the capability of performing CT-based attenuation correction. It is widely held that if the technical issues relating to AC can be solved, AC will become the standard way in which SPECT studies are acquired. This is not to say, however, that SPECT/CT per se solves these issues. Pitfalls related to the use of CT for attenuation maps must be recognized. Registration artifacts might occur, for example, when the CT is performed during a breath-hold and the SPECT MPI is performed during free breathing. Nonetheless, these technical issues will likely be solved in the future. While AC would be an advance, it alone is not likely to justify the large additional costs associated with the purchase of the six-slice or greater systems.

- CT coronary calcium scanning combined with SPECT MPI. With a four-slice CT system and rotation times of 500 msec or less, the coronary calcium score (CCS) with multislice CT is essentially equivalent to that assessed with electron-beam CT, the previous gold standard for CCS measurement.5 It has also been shown that assessment of the CCS provides useful information for guiding intensity of medical management beyond that provided by SPECT MPI.6 In a series of patients undergoing both SPECT and CCS studies, 56% of patients with normal SPECT had a CCS greater than 100, a score widely accepted as indicating the need for statin drugs in treatment of subclinical atherosclerosis. The degree of coronary atherosclerosis as assessed by the CCS can aid in determining the significance of borderline SPECT MPI abnormalities.2,3

It is likely that the accuracy of SPECT MPI for detecting angiographically significant CAD will increase when it is routinely performed with AC and combined with CCS. The confidence of the interpreter in making recommendations regarding patient management on the basis of the SPECT study should also increase. A multicenter randomized trial evaluating the added impact on medical management of combined CCS and SPECT measurements has been undertaken by Philips at sites equipped with the company's 16-slice SPECT/CT systems.

- CT coronary angiography combined with SPECT. Patients with borderline or equivocal findings on SPECT MPI are likely to become excellent candidates for coronary CTA. Similarly, patients with borderline findings by coronary CTA will probably be managed more effectively by further assessment by SPECT MPI than by direct invasive coronary angiography. As with PET/CT, the highest end SPECT/CT systems will allow these two assessments to be made in the same setting. How to effectively triage patients to undergo a single combined coronary CTA and SPECT study is not yet clear, however.

Another area in which the hybrid approach may become useful is in ascribing a region of myocardial ischemia to a particular coronary stenosis. Accurate methods for superimposing and displaying combined coronary CTA and SPECT MPI information would be key in this regard. The Image of the Year in the field of nuclear medicine, selected by Dr. Henry N. Wagner at the Society of Nuclear Medicine meeting in 2006, was actually a series of SPECT/CT images showing a right coronary artery stenosis and the associated area of inferior wall ischemia by SPECT.7

Dynamic PET studies have proven to be of value in measuring absolute myocardial perfusion at rest and during pharmacologic stress. Typically, SPECT MPI studies have required acquisitions over approximately 10 minutes, rendering Anger camera-based SPECT systems virtually incapable of the acquisition rates needed for dynamic SPECT perfusion measurements. Recent improvements in image processing have reduced SPECT acquisition times by a factor of two, but these times still remain far too long for absolute myocardial perfusion measurements. Novel camera systems that have been recently introduced, the D-SPECT (Spectrum Dynamics, Haifa, Israel) and CardiArc, may allow clinical dynamic SPECT MPI to be performed with standard SPECT perfusion tracers.

By employing a series of detector columns that rotate, the D-SPECT camera can detect the direction of travel of the incoming photon without having to rely purely on collimation for this information, enabling the use of wider bore collimation with five times the acceptance angle compared with standard high-resolution collimators. The use of cadmium-zinc-telluride (CZT) crystals allows the required minification, while at the same time improving energy resolution by a factor of 2. The net result is that sensitivity is increased by an order of magnitude, while at the same time spatial resolution can be doubled. Images containing the numbers of counts associated with clinical Anger camera SPECT can be obtained in two minutes with the same dose.

The possibility of rest technetium-99m/stress thallium-201 simultaneous dual-isotope imaging could become a reality with this system, allowing the efficiency of a single-acquisition study while at the same time improving stenosis detection. Its high sensitivity would also provide potential for sampling of the blood pool and the myocardium in as little as five to 10 seconds, so that absolute blood flow measurements and measurements of regional coronary flow reserve might become possible. If this capability becomes a clinical reality, perhaps the most worrisome limitation of SPECT-that it can miss patients with extensive CAD and balanced reduction of flow-could potentially be eliminated.

The CardiArc camera also has a novel design, and it has been reported to dramatically reduce the time of SPECT acquisition. In the future, these faster SPECT cameras might be combined with CT scanners.

Other approaches to improving the speed of SPECT are being investigated. All of the major camera manufacturers have announced that they have new software that may substantially affect the time required for myocardial perfusion SPECT. Early data suggest that these new approaches can reduce the scanning time by 50%, having a substantial effect on patient comfort and camera throughput.

Both the SPECT/CT and the dynamic SPECT cameras may prove to be useful vehicles through which molecular imaging could become a practical reality.8 Molecular cardiology applications may be the ones that most clearly support the need for hybrid systems.

Examples of the applications for which these systems might be employed include imaging of rupture-prone, vulnerable plaque with agents such as annexin V9 or matrix metalloproteinases or integrins, labeled with Tc-99m, iodine-123, or indium-111.4 For these applications, the need for precise anatomic localization of the tracers that are concentrated in the vulnerable plaques is clear. Additional applications could be in combining BMIPP imaging of myocardial fatty acid metabolism or MIBG imaging of myocardial sympathetic nervous system activity with coronary CTA.

Dr. Berman is director of cardiovascular imaging at Cedars-Sinai Medical Center in Los Angeles.

1. Hachamovitch R, Hayes SW, Friedman JD, et al. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation 2003;107:2900-2907.

2. Berman DS, Hachamovitch R, Shaw LJ, et al. Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance: assessment of patients with suspected coronary artery disease. J Nuc Med 2006;47:74-82.

3. Berman DS, Hachamovitch R, Shaw LJ, et al. Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance. Part II: noninvasive risk stratification and a conceptual framework for the selection of noninvasive imaging tests in patients with known or suspected coronary artery disease. J Nucl Med 2006;47:1107-1118.

4. Berman DS. Fourth annual Mario S. Verani, MD Memorial Lecture: noninvasive imaging in coronary artery disease: changing roles, changing players. J Nucl Card 2006;13(4):457-473.

5. Daniell AL, Wong ND, Friedman JD, et al. Concordance of coronary artery calcium estimates between MDCT and electron beam tomography. AJR 2005;185:1542-1545.

6. Anand DV, Lim E, Raval U, et al. Prevalence of silent myocardial ischemia in asymptomatic individuals with subclinical atherosclerosis detected by electron beam tomography. J Nucl Cardiol 2004;11:450-457.

7. 2006 Image of the Year: Focus on Cardiac SPECT/CT. J Nuc Med 2006;47(7):14N (Newline).

8. Braunwald E. Epilogue: what do clinicians expect from imagers? J Am Coll Cardiol 2006;47:C101-103.

9. Kietselaer BL, Reutelingsperger CP, Heidendal GA, et al. Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis. NEJM 2004;350:1472-1473.

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Approach addresses pitfalls that have held back widespread use of SPECT/CT for myocardial ischemia

Daniel S. Berman, MD

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