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August 14, 2006

State of the Art?
By Beth W. Orenstein
Radiology Today
Vol. 7 No. 16 P. 17

Not yet, but researchers hope one-stop fusion imaging one day will replace diagnostic coronary angiography in low- and moderate-risk cardiac patients.

Since F. Mason Sones, Jr, MD, a pediatric cardiologist working at The Cleveland Clinic in the 1950s, accidentally injected angiography dye into the mouth of a coronary artery instead of the aortic valve, physicians have been using coronary angiography to diagnose coronary artery disease (CAD).

In 2004, more than 3 million coronary angiographies were performed to find narrowing caused by plaque, which most often starts gradually but can build up over time to cause a heart attack, cardiac arrest, or sudden death.

In the United States, cardiovascular disease is a leading cause of death for both men and women. CAD is the most common cause of cardiovascular disease; as many as 3 to 4 million Americans may have ischemic episodes without knowing it.

Angiography is performed under local anesthesia in the angiography suite. Under fluoroscope guidance, a tiny catheter is advanced from the patient’s groin or arm into the opening of the arteries. A small amount of radiographic contrast material is injected into each artery and x-rays are taken to reveal any blockages and their extent. The procedure takes approximately 20 to 30 minutes. Because it is invasive, angiography carries a small risk to patients and is relatively expensive.

Physicians have been searching for less invasive and less costly diagnostic procedures and have come close with CT scans of the heart. “The 64-slice CT angiography [CTA] is an x-ray–based technique that can visualize coronary artery morphology and abnormalities with a quality that gets close to conventional coronary angiography,” says Oliver Gaemperli, MD, a nuclear cardiologist at University Hospital Zurich in Switzerland.

Physicians also use SPECT to detect oddities in the flow of blood through the heart’s vessels. “Myocardial perfusion imaging using SPECT is an established method for assessing the physiologic significance of coronary lesions in patients with chest pain,” says Zohar Keidar, MD, PhD, deputy director of the nuclear medicine department at Rambam HealthCare Campus in Haifa, Israel.

One Noninvasive Exam
Fusing the CT and SPECT images has the potential to provide both the anatomical and functional information to better diagnose heart disease. Gaemperli and Keidar are part of research teams in Switzerland and Israel that presented the first series of patients to undergo the SPECT/CT exam at the Society of Nuclear Medicine’s (SNM) annual meeting in San Diego in June. In some cases, the device may allow patients to be diagnosed without having to undergo costly and invasive coronary angiography.

“The SPECT/CT device can provide—in a single imaging session—an accurate evaluation of cardiac blood vessel narrowing and blood supply to the heart muscles,” says Keidar, who adds that the initial results suggest combining the two technologies provides a more accurate view of the patient’s blood flow to the heart than either imaging test could alone.

“Each modality shows a different aspect of coronary artery disease, anatomy of vessel narrowing [CT] vs. blood supply and its effect on the corresponding part of the myocardium, the heart muscle [SPECT],” Keidar says. “The combination of the two modalities in a single device will allow for accurate cardiac assessment in a single noninvasive session.”

Gaemperli has also been working on a combined SPECT/CT device with his colleague, Philipp A. Kaufmann, MD, FACC, director of nuclear cardiology at University Hospital Zurich. He says the information provided by SPECT or CT alone is sometimes insufficient to identify the vessel responsible for causing ischemia or a decrease in blood supply. That’s why the combined technique “is pretty exciting.”

The Israeli researchers used the Infinia LS SPECT/CT, a noncommercial research device specifically designed for their study. The device was introduced in early 2005.

They used the device to assess coronary lesions and determine which should be treated invasively and which could be treated more conservatively. “The fused SPECT/CT images were found to be particularly helpful for correlating the location of the anatomic arterial lesion with the corresponding perfusion defect,” Keidar says.

Evaluating Lesions
In all, 170 lesions were evaluated. With SPECT/CT, the researchers found that 24 (14%) of the coronary lesions detected by the imaging needed further treatment while 138 (81%) were not hemodynamically significant and did not need further invasive treatment procedures, Keidar says.

Each lesion found on CTA and SPECT/CT was compared with the corresponding territory on myocardial perfusion SPECT imaging and coronary angiography, which serve as the gold standard, Keidar says.

Keidar says it took approximately 35 minutes to perform the SPECT/CT. That time included rest and stress scintigraphy with CT-based attenuation correction and planning and acquisition of CT for calcium scoring and angiography.

Since the introduction of the combined device, there have been additional technological developments, Keidar says. The developments have been based in part on the initial clinical results.

The research device they used consisted of a 16-slice CT scanner and conventional dual-head SPECT gamma cameras from GE Healthcare Technologies. Both need to be upgraded to state-of-the-art imaging technology—64-slice CT or more and advanced dedicated faster cardiac cameras—before the technique can have clinical applications, Keidar says. Faster cameras would shorten the acquisition time, he notes. Keidar says theirs are the first results of cardiac SPECT/CT in a clinical setting of which he is aware.

Keidar says more clinical studies are needed. “What we need now are studies in larger patient populations in order to prove the clinical role of this emerging cardiac hybrid imaging modality and justify its widespread use,” he says.

Avoiding Diagnostic Procedures
If the technique were to become the gold standard, cardiologists and their patients would be the primary beneficiaries, Keidar says. “The cardiologists will be the ones to use the results of the combined imaging data for better treatment decisions, guiding interventional therapy, and avoiding invasive diagnostic procedures.”

The Swiss researchers studied 100 consecutive patients ranging in age from 33 to 89 with suspected or known CAD, performing electrocardiographic gated myocardial perfusion imaging and 64-slice CTA on each. They analyzed 399 coronary arteries and 1,386 coronary segments, including 12 bypass grafts.

The cardiac CT scans took only roughly 5 to 7 seconds. However, it required the placement of an IV line and multiple low-dose scans for orientation and planning, so it took approximately 20 minutes for each patient, Gaemperli says.

The SPECT half of their study was a bit more time-consuming. “We performed routinely a one-day protocol with one scan after pharmacological stress and one scan at rest,” Gaemperli says. The pharmacological stress procedure was performed first and took approximately 20 minutes; each scan took roughly 20 to 30 minutes. “For a whole exam, we calculate roughly two hours,” Gaemperli says.

The researchers used a commercially available radioactive tracer, 99mTc-tetrofosmin, at rest and during cardiac pharmacological stress.

Functional Information
They were able to show that CTA with a 64-slice CT scanner has an excellent ability (99% to 100%) to rule out coronary lesions that cause impaired blood flow to the heart. The positive predictive value was low, which means that the lesions identified by coronary CTA did not necessarily need to be functionally significant on myocardial perfusion SPECT, Gaemperli says. “Conversely, we found that a normal myocardial perfusion SPECT does not exclude the presence of subclinical coronary artery disease, which may become significant as age progresses and for which cardiovascular risk modification may be warranted.”

The results, Gaemperli says, underline the value of a combined assessment of coronary morphology (the visualization of coronary plaque) and function (blood supply to the heart muscle), which may easily and efficiently be accomplished with future hybrid SPECT or PET/CT scanners.

However, Gaemperli does not believe the new hybrid devices will ever fully replace conventional coronary angiography. He believes invasive coronary angiography will continue to have a role in the diagnosis and treatment of CAD because it allows the physician to immediately perform treatment procedures should the catheterization identify a severely blocked artery. Several procedures, including balloon angioplasty and stenting, may be used to open the artery and done while the patient still is sedated and in the angiography suite.

Gaemperli expects that conventional coronary angiography will remain the diagnostic method and treatment of choice in emergency situations where vessels are occluded suddenly and a quick revascularization (restoration of the blood flow to the heart muscle) is necessary and life-saving. Also, he expects coronary angiography to be the first choice for patients with a very high likelihood of obstructive CAD and who likely will need a revascularization procedure.

Still, he says, the significant mortality inherent in invasive coronary angiography and high cost of the invasive procedure should not be neglected. Of the more than 3 million invasive coronary angiographies performed in 2004, a large portion were purely diagnostic, he says. “No revascularization procedure was performed.”

Gaemperli says his team is focusing on finding noninvasive tools that can provide the same morphological information as coronary angiography while avoiding its risks and costs. Such a Holy Grail is more likely now, he says, thanks to the advances in CT technology, especially in the last six years. The new generation of CT scanners, he says, has enhanced spatial and temporal resolution “that in our view may be an excellent alternative to invasive coronary angiography in diagnosing patients with a low to intermediate pretest probability for CAD.”

Looking at Limitations
Several factors still limit the clinical use of CTA, he says. Heavy calcifications, commonly found in older adults and patients with a high-risk profile, and motion artifacts particularly in the presence of high and irregular heart rates may affect the quality of the images.

Some referring physicians are also concerned about the high radiation exposure with SPECT/CT—it is two to five times higher than conventional coronary angiography. Others don’t see that as an onerous concern.

“All these limitations are the focus of ongoing research,” Gaemperli says.

The next step is to improve the resolution of the CT scanner, Gaemperli says. Gaemperli and Kaufmann are currently evaluating the feasibility and reproducibility of SPECT/CT image fusion, an important prerequisite for any further research with hybrid imaging, he says. “We have to evaluate whether hybrid imaging really has an additive value in the cardiac nuclear field compared to separate image analysis from standalone scanners,” he says. “This information will be important for those involved with the development of hybrid scanners with high-end CT devices.”

A SPECT/CT image showing both the coronary arteries and blood flow to the heart was awarded the 2006 Image of the Year at the SNM meeting (and reported in Radiology Today’s July 3 issue). In announcing the selection, Henry N. Wagner Jr, MD, director of the division of radiation health sciences at Johns Hopkins University in Baltimore and SNM past president and historian, said it illustrates the “complementary nature” of the two imaging modalities. The image was part of Gaemperli and Kaufmann’s study, “Comparison of 64-Slice Spiral CT Angiography and Myocardial Perfusion Imaging in Noninvasive Evaluation of Functionally Relevant Coronary Stenoses.”

— Beth W. Orenstein is a freelance medical writer and regular contributor to Radiology Today. She writes from her home in Northampton, Pa.