Toronto, ON - Cardiac imaging is a booming and expensive business, as any visit to the exhibition hall at the American College of Cardiology or American Heart Association annual meetings will reveal. It is also an industry that gives rise to journalistic clichés, as reporters, sales teams, and doctors alike bandy about hackneyed phrases such as "ready for prime time," or the "holy grail of cardiac imaging."

Eccentric atherosclerotic plaque seen in the aorta of a 69-year-old patient at risk for heart disease (Source: Drs Zahi A Fayad and Valentin Fuster, Mount Sinai, NY) [Click on the image for a larger view]

Still, cliché derives from repetition, and during the 1990s, the one-stop cardiac imaging shop, with high-tech images of clearly delineated coronary arteries, coupled with the ability to assess myocardial structure, function, perfusion, and coronary flow, had captured the imagination of many within the cardiology world. With its emergence on the clinical scene, many hoped magnetic resonance imaging (MRI) would evolve into the one modality for complete cardiovascular-disease assessment. When it wasn't able to deliver on all imaging fronts, including the assessment of coronary artery disease, there was a bit of a backlash, say those familiar with the technology.

While there is an undeniable craze for computed tomography (CT) and the noninvasive assessment of coronary disease, those familiar with cardiac MRI say the technology is constantly improving and still has unlimited potential to eliminate all other imaging modalities for the investigation and follow-up of patients with cardiovascular disease. While MR has "bread-and-butter" uses in functional imaging, many are excited about the technology's future applications.

Dr Valentin Fuster

"When you talk about future uses for MRI you are talking about future applications in vascular disease," said Dr Valentin Fuster (Mount Sinai School of Medicine, New York, NY). "It will be able to address all the aspects we are interested in with cardiovascular disease. . . . This is where I see noninvasive MR in broad use. It is advancing in all areas. I am projecting another 10 years, and not five, because this technology needs high sensitivity and good specificity. This is more than good pictures."

Fuster, one of the world's most highly regarded researchers in coronary disease, atherosclerosis, and thrombosis, told heartwire that his group continues to move cautiously with future applications of cardiac MRI and vascular imaging because they simply do not want to make a lot of unnecessary noise. However, he stressed the technology is moving very solidly and anticipates being able to noninvasively use MRI in high-risk patients where the amount of disease is unknown. MRI can then be used to quantify the disease to allow clinicians to be more aggressive in their treatments, he said.

Right now, say experts, in terms of a morphological assessment of the heart, as well as the assessment of right and left ventricular systolic and diastolic function and mass, cardiac MRI is the gold standard. It is also well established for the diagnosis and follow-up of cardiomyopathies, as it can characterize tissue and provide morphological definition [1].

In addition, MRI is also beginning to play a more important role in diagnosing and serially following patients with congenital heart disease, usually as a complement to echocardiography, as well as in the assessment of pericardial disease [2]. In valvular disease, echocardiography remains the imaging modality of choice, but clinicians are using MRI for following valvular heart disease patients to help determine the timing for surgery. Several studies have also shown that MRI can be used successfully in the screening, diagnosis, and follow-up of aortic diseases, especially in the diagnosis of aortic dissection.

The problem with this large list of things it can do is that there are a lot of green buttons to push. Somebody has to decide how to use the machine and for what purpose.

In terms of assessing myocardial viability and infarct detection, here again MR is quickly gaining ground, with contrast-enhanced MRI rapidly evolving as a means to predict potential for functional recovery, as well as overall risk and prognosis. MR is also emerging as a reliable tool in the assessment of myocardial perfusion and ischemia. Although it is considered cutting edge and far from routine use in clinical practice, some centers, such as Duke University Medical Center, perform approximately 2000 clinical stress tests with MR each year.

Dr Raymond Kim (Source: Duke University Medical Center)

Speaking with heartwire, Dr Raymond Kim, director of the Duke Cardiovascular Magnetic Resonance Center, said MR is a different kind of modality in that it is like many different techniques all rolled into one. Unlike CT, where most procedures are performed in the same way, there is "no green button to push to obtain an image."

"I could make the MR machine act like an echo machine and get information about wall motion, about how good the muscle is contracting," said Kim. "I could look at the valves and I could look for shunts for congenital heart disease. I could also make it behave like a CT machine and look at the vascular structures. I could make it behave more like nuclear imaging and look for myocardial viability, cell death, or perfusion. But the problem with this large list of things it can do is that there are a lot of green buttons to push. Somebody has to decide how to use the machine and for what purpose."

This, said Kim, creates a bottleneck in terms of the number of clinicians trained to use MR in all these different areas. There is also the additional problem of more up-front costs, as each use of MR requires its own unique learning base. "But that's also the power of the technology, that it can do all these different things, with some arguing it even does them the best in its class for each," he said.

(Source: Oklahoma Heart Institute)

Dr Edward Martin (Oklahoma Heart Institute, Tulsa, OK) has been using cardiac MR for seven years. His practice consists of 18 cardiologists, including interventional cardiologists, electrophysiologists, and clinicians with expertise in nuclear medicine, echocardiography, and peripheral medicine. With approximately 160 to 180 cardiovascular cases per month, Edwards told heartwire that the way he utilizes MR is to "stretch its legs." Of these cases, about 60% are vascular, that is, MR angiography studies, while the remaining 40% are cardiac cases.

"We run the gamut of MRI here," said Edwards. "We really do a good mix of cases. I took the concept of the one-stop imaging shop to heart. I think what holds it back somehow, especially in light of the CT craze that is going on now, is that it takes a little bit longer to learn the technology now than CT. But having learned how to use it, a clinical cardiologist sees just how powerful it is."

Dr J Paul Finn (Source: David Geffen School of Medicine, UCLA)

Dr J Paul Finn, a professor of radiology and medicine and director of MR research at University of California, Los Angeles, told heartwire that his group uses MR for functional imaging and anatomic imaging, as well as for viability and angiographic imaging, particularly in patients with complex congenital heart disease. Patients with supraventricular tachycardia considered for ablation therapy or cardiac surgery candidates—anywhere there is a need to have a close look at functional cardiac anatomy—are also routinely sent for MR imaging, he said.

"Cardiac MR has a number of strengths and it can do a lot of things well," said Finn. "At UCLA we look at congenital heart disease a great deal and we also have a very active arrhythmia service. For both of those applications we use cardiac MRI a lot. Other places tend to focus mainly on ischemic heart disease and, here again, MRI is very good, but it tends to end up competing with well-established, more mainstream modalities like nuclear medicine and stress echocardiography."

Longitudinal double-oblique black blood image (candy-cane view) of the aorta of a severely atherosclerotic 71-year-old patient (arrow points to atherosclerotic plaque (Source: Drs Zahi A Fayad and Valentin Fuster, Mount Sinai, NY) [Click on the image for a larger view]

It is the noninvasive cardiac scan and its "ability to stop a heart attack before it happens" that has really gotten the attention of cardiologists, as well as the mainstream media. Time magazine recently published a feature-length story on the new imaging modalities, including cardiac MRI and computed tomography (CT). Fuster and other cardiologists from Mount Sinai Hospital in New York City have appeared on Good Morning America, highlighting future uses of cardiac MR by putting the hosts through a detailed full-body MRI arterial scan.

Whole-body MR angiography to noninvasively detect vessel narrowing is one of the most exciting applications of MRI and is at the forefront of cardiovascular medicine at this time. MR angiography has been shown to have high specificity and sensitivity with x-ray angiography for the detection of luminal narrowing >50%. For about $2000, anyone can undergo a scan that allows doctors to light up their entire arterial tree. For now, however, whole-body MR angiography excludes the intracranial and coronary arteries because there is insufficient resolution to assess these vessels accurately.

Dr Zahi Fayad (Source: Mount Sinai School of Medicine)

Researchers have also been able to use MRI to quantify the degree of disease in the large arteries, such as the aorta and carotid arteries, where the location of the artery presents less of a technical challenge due to less motion.

"This is very exciting because we can look directly at the arteries, and this is not the degree of narrowing but the degree of disease," said Fuster. "It is a scan of the arterial wall, not of the lumen. From there we are able to use medications that alter the disease. With this, we are able to see whether we can stabilize or regress disease when scans are performed over time. We have done this with atorvastatin, for example, and are also working with other drugs as well."

Dr Zahi Fayad (Mount Sinai School of Medicine, New York, NY) is another expert excited about the prospect of using MR imaging to assess atherosclerosis in what he calls "a meaningful manner."

"MR is a tool that can give us the best noninvasive ways to determine whether a patient has plaque or doesn't have plaque," Fayad told heartwire. "It is also a means to assess the volume, or burden, of the disease. You can look at the carotid, the aorta, and the peripheral arteries, other than just the coronaries, to get a whole assessment, total body, of the patient's plaque burden."

The elusive holy grail, of course, remains the noninvasive angiographic assessment of the coronary arteries. MRI is already quite good at detecting anomalous origins of the coronary arteries, and some early studies have shown that MRI can detect proximal coronary artery disease, but most experts concede that CT is far superior to MR in this capacity. While imaging the coronaries has all but been surrendered to CT, not everyone has given up on MRI for this purpose just yet.

Dr Milind Desai (Source: Cleveland Clinic)

"In terms of bread-and-butter coronary artery disease detection, compared with what a cardiac catheterization can image, MRI is not there yet," Dr Milind Desai (Cleveland Clinic, OH) told heartwire. "The question then is, will it ever get there? I'd be willing to say it has the potential. As of today, computed tomography seems to have overtaken that aspect of MRI. If you're talking about noninvasive angiography, not many people talk about cardiac MRI. But I have been involved in the work, and I can personally say that it can be done. It needs to be validated in a larger population with bigger studies, but I would not say that it is impossible to do."

Imaging the coronaries, said Desai, is essentially target practice. "The target we're aiming at is only 1 to 3 mm in diameter and is moving up and down, contracting with the heart," he said. "It is embedded in a fatty envelope and you have to image it, noninvasively, over a period of 10 minutes to be able to produce an adequate image. It's not easy."

While the small size of the arteries and constantly mobility are problems, Desai said researchers have been able to adequately gate to the cardiac cycle, identifying a phase when it is completely at a standstill. Imaging at that time, while having developed sequences that eliminate the signal of the surrounding fat, as well as compensating for respiratory motion, have allowed MR researchers to image the entire epicardial tree in about five to 10 minutes, said Desai.

With the move into the vasculature, the promise of one day being able to noninvasively quantify disease and disease progression in the coronaries is alluring. However, some experts argue that the concept of using MR to image the coronary arteries is really missing the point. In fact, they see MRI as a practical but highly specialized tool that is used to its best advantage when able to home in on specific disease, such as those patients with congenital heart defects.

"Coronary artery disease, even just numerically, is a very important disorder," said Kim. "Probably two thirds of all the problems that a cardiologist might see have something to do with coronary artery disease. Clearly it is important, and it tends to capture the general imagination of the public and the general practitioner." Kim stressed that with MR, the patient population differs from those undergoing CT in that most patients undergoing MRI already have diagnosed heart disease.

Whole-body MR scan (Source: Drs Zahi A Fayad and Valentin Fuster, Mount Sinai, NY) [Click on the image for a larger view]

"MR can tease out nuances, like in heart failure, where all the patients are already sick, and you're trying to determine what type of heart failure they have, why, and how they should be treated," said Kim. "CT is used more for the general internist who wants to know what your coronary arteries look like or if you have disease or you don't. They might have some coronary artery disease, so instead of doing an angiogram invasively, we can quickly figure out if they have some blockages. It's a very different patient clientele."

MR as a noninvasive imaging test to look at the coronaries is not likely to be ready for clinical use in the next five or 10 years. According to Kim, although the concept of imaging the arteries, especially the coronaries, is exciting, there already exists a test that provides the same information, albeit in a more intrusive manner, he said.

"The angiogram is invasive, it's not so pleasant for the patient, and there might be some risks associated with it," said Kim. "But if you talk to interventional cardiologists, they'd say, 'I do 20 angiograms a day and it takes me 15 minutes to do one.' There are thousands of these things being done every single year in US hospitals. So a noninvasive imaging modality offers convenience and takes away a little bit of a safety risk, but you're not getting additional information. Maybe in the future you will, but as of right now, you're not."

While CT imaging is extremely good for imaging coronary artery disease, experts say the technology is limited, especially if the goal of the scan is functional imaging or viability imaging or in cases where clinicians need to assess congenital heart disease. Moreover, under all circumstances with CT, there is the undesirable radiation burden and the injection of potentially nephrotoxic contrast agents.

You don't get the easy detail right now that you get with CT angiography.

"People are embracing CT for coronary artery imaging and I think that's appropriate," said Finn. "Of course, even as the technology evolves, there are going to be things that CT won't be able to do that MR will. I think for assessment of coronary artery stenosis and atherosclerotic coronary artery disease, CT will be the primary choice over MR. If there are reasons why CT won't work or can't be done, and one still doesn't want to do cath as the first test, and if you're interested primarily in coronary anomalies, then MR is very good. But you don't get the easy detail right now that you get with CT angiography."

In the future, the integration of noninvasive coronary CT with MR imaging might be the best way to provide a full assessment of subclinical disease, the study of atherothrombotic disease progression, and response to therapy [4]. By June, Mount Sinai Hospital will have CT and MR equipment, allowing clinicians access to the different imaging technologies at the same time. In this way, clinicians can see the disease directly, not only in the narrowing of vessels, but also in the vessel walls that are already developing the disease.

"There is a lot of interest, with a lot of clinicians investing both in MR and CT scanners," said Desai. "There are a lot of training programs buzzing around. These technologies are here to stay, but on the flip side of that, I don't think any other technology is going to die away any time soon. This is a multimodality world now."

Black blood longitudinal section of a carotid artery of a patient with atherosclerosis showing lipid core and calcium deposition surrounded by a thin fibrous cap (vulnerable plaque) [Click on the image for a larger view]

As MRI technology evolves, researchers have also used the modality to expand their understanding of cellular and molecular events within the atherosclerotic plaque. Molecular MRI, for example, has been used in the research setting for plaque characterization through the introduction of contrast agents targeted to specific cells, molecules, or processes [3].

With molecular MRI, attaching an antibody or peptide to gadolinium creates targeted imaging agents that make the molecules visible in the cells. In this way, researchers have been able to image and identify specific components of the plaque, such as adhesion molecules, macrophages, lipid core, and fibrous plaque, as well as image angiogenesis, apoptosis, or cell trafficking.

"We are identifying thrombus and inflammation at this time," said Fuster. "We are also identifying extracellular lipid material inside the cell. This is the next step. This is the type of work that will help us use MRI in the coronary arteries. In fact, the future of the coronary arteries might be characterization of the tissue that is there on a molecular level."

With recent advances in understanding the biology of atherosclerosis and with the advances in imaging, experts anticipate that molecular imaging studies will prove useful in a variety of ways. For example, molecular MRI can help identify patients at high risk of cardiovascular events not identified by routine clinical evaluation and could characterize vulnerable lesions in high-risk areas of the coronary vasculature [4]. In addition, MRI imaging may allow researchers to develop novel antiatherosclerotic therapies that target biology rather than lipids and eventually might clear the way for individualized therapy based on the molecular profile of vulnerable plaques.

"The field is moving forward," Desai told heartwire. "The initial steps will be to identify these plaques and the subcomponents of the plaque and then be able to hook up these same molecules with therapeutic agents that can be directed at a nanoparticle level to shrink or destroy the plaque."

That a turf war is also simmering in the background should come as no surprise to those who know their medical history. Tomographic techniques have predominantly been the domain of radiologists, but with the blending of anatomy, physiology, and functional imaging in these scans, cardiologists are starting to make a great deal of headway into MRI. There are institutions where cardiologists read the image and there are institutions where all of the clinical cases are done by radiology. Others, like UCLA, compromise.

I don't frankly care who reads it, but you can't attend some fly-by-night course or do a minifellowship for 15 days and expect to be reading these studies.

"In our institution, MR is primarily run by radiology but we run this very much with a cardiology focus," said Finn. "The technology really works well only if you have radiologists and cardiologists working together. That might sound a little new age, but in practice it works out very well."

Radiologists, by and large, are pretty familiar with the imaging technology, as well as with the principles of cardiac MR imaging, he added. A radiologist also has to see things that are there, see things that might be unsuspected, and in general, be less telescopic when looking at the images, said Finn.

"There is also a lot to MRI," added Finn. "Certain aspects are relatively straightforward but not too many. It's very different from many of the other modalities in terms of fundamental principles, which is one of the reasons why it is so powerful. It can also be confusing, and when it is not used properly, you can generate some pretty poor studies that result in misdiagnosis."

Desai told heartwire that the best-trained person for the job should be reading the MRI.

"I don't frankly care who reads it, but you can't attend some fly-by-night course or do a minifellowship for 15 days and expect to be reading these studies," he said. "I don't care if you're a radiologist or cardiologist. There are plenty of programs now dedicated to teaching cardiac MRI where you can be really good at it."