Future of MR imaging shows promise: Part Two

Wider clinical applications may be seen as new data emerge.

Cardiology Today held a wide-ranging discussion before a live audience in Atlanta during the recent ACC meeting. Moderated by Carl J. Pepine, MD, and Roger Blumenthal, MD, the round table highlighted the use of MR imaging, whether it is ready for more widespread use, and issues related to cost of incorporating its use into a medical practice. Part two is printed below; part one was in our June issue.

Moderators
Carl J. Pepine, MD Eminent Scholar, Professor and Chief, Division of Cardiovascular Medicine, University of Florida, Gainesville, and Chief Medical Editor of Cardiology Today.	Roger S. Blumenthal, MD Director, Ciccarone Preventive Cardiology Center, Johns Hopkins University, and member of Cardiology Today's Editorial Board, Preventive Cardiology Section.
James A. Hill, MD Professor of Medicine and Pharmacology, Co-director of CTMR for CV Medicine, University of Florida, Gainesville.	Greg Hundley, MD Associate Professor of Radiology and Medicine (Cardiology), Wake Forest University Health Sciences, Winston Salem.
Nathaniel Reichek, MD Director, Cardiac Imaging Research Program, St. Francis Hospital-The Heart Center, Roslyn, New York, and Professor of Medicine and Biomedical Engineering, Stony Brook University.	Samuel Wann, MD Clinical Professor of Medicine, University of Wisconsin and the Medical College of Wisconsin, and Director of Cardiology, Wisconsin Heart Hospital, Milwaukee
Norbert Wilke, MD Associate Professor in Radiology and Medicine, Chief of the CV MR/CT, University of Florida, Jacksonville.

ROGER S. BLUMENTHAL, MD: Let’s talk about a hypothetical patient with moderate ischemia on a $2,000 stress nuclear test. Many of us would probably say we need to push those risk factors (eg, lipids and systolic blood pressure) down more, maybe add some beta-blockade, and consider doing a less expensive treadmill stress echo test just to make sure that that moderate ischemia on stress nuclear is much less in six months down the road. The emphasis of this approach is more on aggressive risk factor reduction and beta-blockade as opposed to referring to MR to quantitate the amount of ischemia.

Dr. Hill, what do you think about that approach, and is that typically what you would recommend when you have someone who was referred to you for moderate ischemia and they want MR to quantify the ischemia?

JAMES A. HILL, MD: It’s pretty clear that if we have a much better sense of what a moderate ischemia in a nuclear study means than any quantitative measurement on MR at this point in time. It then becomes a clinical practice philosophy of what you believe is the best way to treat a patient.

Obviously, you need risk factor modification and some sort of beta-blocker or calcium channel blocker. We’re almost getting too much information here. We have to decide precisely how we’re going to integrate that in the care of an individual patient, and we are still struggling with that issue.

PETER A. MCCULLOUGH, MD, (from the audience): What about using MR in the overweight and obese? With the standard nuclear and echo techniques like stress echo and stress nuclear, we lose our sensitivity. We have one of the biggest prevention centers in the country, and the mean BMI of our patients is about 42. At a BMI of about 38, they no longer fit in the MR scanner. Are there any data about what type of strategies we can use?

NATHANIEL REICHEK, MD: Cardiac MR has now been supersized, and there’s one large bore scanner that’s been shown to provide equivalent image information to the standard ones.

MCCULLOUGH: That’s reassuring. Our center developed a PET protocol for the morbidly obese. Apparently the energy from a PET image is so much more intense that you can see it better through the fat.

NORBERT WILKE, MD: In general, large patients are challenging for any imaging modality, including PET. Any diagnosis by cardiac MR or CT is challenging at this point if the patient weighs more than 350 pounds.

CARL J. PEPINE, MD: What do you think about MR spectroscopy and creating images from P31 spectroscopy or other spectroscopic acquisitions?

REICHEK: The great limiting factor has been the low abundance of P³¹ working in a 1.5 Tesla scanner and you’re on the edge having enough signal to get reliable data. It becomes more feasible at 3 Tesla, but it is not, to this point, a situation where a sampling of the heterogeneity of the heart, say in ischemic heart disease, in a systematic way, which you ordinarily need to with other imaging modalities is very feasible. I don’t see P³¹ spectroscopy becoming a widespread clinical tool.

JAMES H. CHESEBRO, MD: One thing mentioned but not discussed is tissue characterization. This can go further in detecting the kind of plaque that is present, certainly in the aorta or the carotids. With calcification being gender and age dependent, I pick up a number of ugly plaques noncalcified and thus have started aggressive therapy.

We’re picking up amyloid now and using that as the first test and then going to on to prove it by biopsy. MR is very good at tissue characterization, a strength that’s not been utilized to date.

PEPINE: Has that been applied to coronary arteries?

REICHEK: It’s been applied in a very limited research sense, but again, being able to sample the coronary artery wall widely is not yet a practical undertaking with MR in human beings. As Dr. Chesebro pointed out, there are quite a number of new tissue characterizations that are coming to the fore. The technique for amyloid is really very effective and extremely useful.

In addition, MR has really remade the rules of the game for looking for myocardial iron overload. That’s an area where the tools were inadequate and now MR is clearly becoming a very good guideline both of who to treat and whether you’ve had effective treatment or not.

We’re still learning some new things about myocardial infarctions from it. One of the physicists in my group wandered into the fact that, unknown to 99.99% of cardiologists, the majority of chronic infarcts have a large amount of fat in the infarcts. Nobody seems to have been aware of that and nobody knows its physiologic or clinical significance.

BLUMENTHAL: Can you comment on use of MR to more precisely evaluate endothelial function?

GREG HUNDLEY, MD: The way others and we have used it is to assess flow-mediated arterial dilation. One advantage of MR is that you can asses that in medium-sized arteries. We use the femoral artery, and we don’t have the acoustic window limitations. We’re interested in exercise capacity, and we feel that lower extremity blood flow is probably more of a contributor to exercise capacity than the arm.

To do this, we put a cuff around the leg and measure the blood flow. You can also look at the shear stress, look at the area of the artery at rest, inflate a cuff for four minutes or so, release the cuff, and then sample the arterial area two minutes after that cuff release. It’s very robust, and there is less variability than with the ultrasound techniques.

If you choose to use MR for this particular outcome measure, just like with LV mass and other things, you can substantially reduce your sample size.

REICHEK: We’ve been using on a research basis the brachial artery FMD (flow-mediated vasodilatation) technique and that has been a tremendous improvement over ultrasound in terms of reproducibility. We’ve also, again on a research basis, been doing two things directly in the coronaries. One is borrowing a technique that Dr. Hundley first developed quite some years ago for looking at the coronary flow. We’ve used direct imaging in the proximal LAD of the vessel lumen size and of the phase-contrast velocities at rest and as a perturbation we have used both isolated hand grip and cold pressor tests and used sublingual nitroglycerin as a control.

That works, but is a challenging imaging issue because the LAD cross-section is relatively small. More recently, we’ve been using those same stressors with perfusion, and we’re getting very good results with myocardial perfusion to look at coronary function. Now, how much of it is really endothelial and how much of it is microvascular resistance is certainly not clear at this point in time. But we can show changes, for example, in the up-slope measure that’s often used for perfusion that are approaching the magnitude of the adenosine response.

TY J. GLUCKMAN, MD: I have another question about viability. I know it may be institution dependent, but do you get a sense of what percentage of clinicians at your institutions are using MR for viability as opposed to PET, rest-redistribution thallium or dobutamine echo?

REICHEK: At our place, it’s a minority.

GLUCKMAN: Do you know why?

Nathaniel Reichek, MD

REICHEK: I think it’s just a gradual process of adoption primarily, but also location. We don’t have a first-line cardiac scanner in the hospital. Ours is at an outpatient research center a couple of miles away. We’re going to be putting a new cardiac scanner in the hospital this year. With that, I think we’ll be seeing a lot more opportunities.

HUNDLEY: I’d agree with that. We talk about the elegance of the technology, but if you can’t get patients scheduled and you can’t get out a report in a timely fashion - it needs to be within 20 minutes of the procedure being performed - you don’t have many people using it.

We’ve overcome some of those limitations and now what I’m watching is a movement, particularly in the cardiology faculty, in just doing viability with MR. It has caught on because of its accuracy and ease of implementation.

I think the practitioners like the flexibility of being able to see delayed enhancement or low-dose dobutamine, and I have seen a marked drop-off in the radionuclide studies for viability and a commensurate rise in the MR.

HILL: We’re starting to see a shift as well, but it’s still very slow and depends on your local expertise. Dobutamine stress echo is the thing to do in the places that do it, nuclear studies is the thing to do in the places that do it. I mean you go to Midas, you get a muffler. That’s sort of the way it works at this point, and I think it’s going to remain that way.

BLUMENTHAL: Dr. Hill, I wanted to go back to your answer to Dr. Gluckman’s question before about real-time MR. My office at Hopkins Hospital is situated between the cardiac CT and cardiac MR. Some have said that electrophysiologists will be using both those technologies on a more routine basis. Do you agree?

HILL: I think that the utility will be probably more in the sort of the complex EP ablation type of thing for localization and reduction of radiation. The slick interventionalist still is going to rely mostly on the angiography and traditional cath methods, but I think EP is where it’s probably going to go.

HUNDLEY: I’m not in total agreement on this. In addition to EP, there may be other uses. I realize that it will be an expensive technology, but, for example, investigators at the University of California San Francisco are working with interventional MR techniques that may be applicable to pediatric patients. These newer interventional MR procedures may facilitate correcting pulmonic stenosis without exposing the children to ionizing radiation. In nonhuman experimental models, they can measure flow right after the intervention, and they believe it will move to children.

Also, I think if it becomes important that we start putting things into the myocardium – some of the work out of the NIH indicates that one can image in 3-D and precisely locate where new substances are placed. In short, I’m not certain of the future role of interventional MR in coronary artery intervention, but there may be other developments for which interventional MR may be the preferred imaging modality.

WILKE: I must agree. Preliminary results we have seen in interventional MR imaging utilizing real-time imaging are amazing. However, the interventional MR market won’t happen if not supported by industry. Manufacturers are not into developing dedicated interventional MR catheters and devices at this point. Even so, there have been honorable contributions from various manufacturers to help out with the supplies for some initial studies performed nationwide in major MR research centers.

Norbert Wilke, MD

There is a discrepancy between what would be possible for the benefit of the patient and what currently is invested for interventional MR. Just think about radiation and related problems MR could solve. However the industry is currently not ready to support interventional cardiac MR as needed. That’s the reason why these otherwise novel, innovative, interventional, cardiovascular MR techniques have not been clinically implemented over the last 10 years.

BLUMENTHAL: Dr. Hill, you have unique expertise in MR and CT. What are your thoughts about patients with conditions that may be headed for combining an MR/CT?

HILL: Dr. Wilke has alluded to the fact that they are complementary in the sense that one can amplify the findings of the other and that you can get the coronary imaging with the CT. That obviously will improve as time goes on. You can get functional assessment with MR without the radiation exposure.

WILKE: We and others have conducted over the last two years studies where we used coronary CT and MR complementary, particularly in patients with atypical chest pain admitted to the ED. It is a very effective diagnostic tool in order to stratify these patients. There is a reduction of radiation dosage using MR and overall cost savings are evident as diagnosis and rule-out of CAD can be derived much faster while cutting back on unnecessary admissions to hospital. An MR rest-stress perfusion imaging, for example, takes only about 30 minutes to perform if a well-functioning cardiac MR infrastructure is at hand.

REICHEK: One of the things that I’ve found since I’ve got MR and CT scanners nearly side by side is that it is not a rare event for us to put a patient referred for one test to the other modality for one reason or another. The patient set for a CT study may turn out to have more renal dysfunction than as billed, so we put them through the MR scanner. Or the patient is referred for an MR for anomalous coronaries, but there’s a problem with the imaging, so you put them through the CT scanner.

We do a lot of trading patients back and forth trying to optimize the trajectory that the patient takes through the imaging armamentarium.

BLUMENTHAL: Dr. Thadani [in the audience], as a clinical cardiologist, do you see a growing role for referrals for cardiac MR and what would you like to see before you send your patients for an MR as opposed to echo, stress echo, dobutamine echo or stress radionuclide studies?

UDHO THADANI, MD: One concern I have with currently available stress testing modalities is the expense associated with these procedures and the uncertain information one gets, especially in special patient populations such as women with chest pain. Until the role of MR can be better defined and we show that it provides superior information compared with currently available stress modalities, I do not see a growing role for MR as a central referral process.

I see a role of MR in patients referred for cardiac arrhythmias needing an ablation procedure. MR does provide important cardiac anatomical information including the detailed anatomy of the pulmonary veins.

I see a possible role of MR in ascertaining the etiology of chest pain in women with normal coronary arteries, as a research tool initially and maybe as a clinical tool sometime in the future.

BLUMENTHAL: Dr. Wilke, what are your thoughts about how to make MR more cost effective in the cardiovascular armamentarium, and what changes we may see in a few years?

WILKE: One of the incentives for the health care systems in the future to turn to new cardiac CT imaging will be to save money and to stratify patients more quickly and cost effectively. For instance, there’s one indication we are particularly interested in, and these are patients who get admitted to the emergency department with atypical chest pain, especially the intermediate risk group.

There are significant costs accumulating in the hospital systems where those people have to be admitted for two days to three days. Meanwhile they may undergo an echo test or a nuclear test and still not have a final diagnosis. Some early studies are soon to be started and published demonstrating how cardiac CT and MR will substantially shorten the period needed to diagnose and rule-out patients and better stratify patients who do not need to be admitted to the hospital on the basis of coronary disease.

Some cardiac CT studies may need to be followed up with an MR rest-stress perfusion test on an outpatient basis and the patient can be out of the hospital in two to three hours.

BLUMENTHAL: Dr. Hill, what is your approach to the atypical chest pain patient in terms of both CT and MR? Is it being used as a way to cut down on health care costs?

HILL: We’re starting to do that more than we have in the past. In the next five years or so, I think we’re going to see a lot more perfusion type imaging with CT and I think the radiation dose will be improved.

I think we are going to have much higher resolution imaging for perfusion than we have in the past, with the exception of MR.

CHESEBRO: One thing that has to be remembered is the CHEER study for assessment of chest pain in the emergency room and that low-risk patients can go home. Obviously, if there’s any question, you could stress them. The high-risk come in and they get cathed, but the intermediate-risk patients, if they have an assessable ECG by stress testing, you don’t need any sophisticated imaging.

WILKE: Other studies have shown that up to 60% of low-to-intermediate risk patients with mild-to-moderate (noncalcified plaque) coronary artery disease are missed by ECG and treadmill exercise alone. Those patients are sent home and about 30% are coming back within six months with an acute coronary syndrome. Many of those are going to be dead by the time they reach the hospital.

We’ll have to show data in the future where cardiac CTA and its capability to early identify overall noncalcified plaque burden noninvasively will have a major role of improving the situation of missing subclinical but high-risk coronary artery disease, particularly in patients aged 50 and younger.

HILL: I think that brings up a whole problem of where all these different methods fit, and that gets back to your clinical practice philosophy. You don’t necessarily need the most expensive complicated test to get decent information.

You still have to do lipid lowering, you still have to think about asking about aspirin, think about giving beta-blockers. Dr. McCullough was talking about his patient with a body mass index of 42. They are high-risk patients, any way you cut it. None of the techniques we have talked about obviate the need for close follow-up and for appropriate patient care.

BLUMENTHAL: Dr. Hundley, what changes do you expect in imaging over the next several years?

Greg Hundley, MD

HUNDLEY: I think we’ll see MR use grow in patients and when you need more than one piece of information to make a decision. Examples include the simultaneous acquisition of perfusion, wall motion, and infarct detection. Also, because of the quantitative nature of the technique, I think MR will be useful for patient conditions in which longitudinal follow-up is needed. Examples of these patients include those with valvular heart disease or those receiving chemotherapy in need of monitoring for cardiac dysfunction. Importantly, MR data are acquired noninvasively, without ionizing radiation or ionic contrast.

I am not certain of the future role of MR in coronary imaging, in spectroscopy, or in interventional procedures, but there is promise of exciting research in those areas. I think for assessment of the vascular system and assessment of the heart in patients with cardiovascular disease with multiple problems, it will have a large role. The simultaneous study of the peripheral vascular system and the heart will be possible with this study. Finally, I believe we will learn about new information from several large population-based studies that will produce results in the next few years.

REICHEK: At our institution, MR has become kind of a go-to technology when people can’t figure out a problem. MR is where the patient ends up and very, very often there is added value. Beyond that, we’re going to see over the next several years the beginnings of the kind of outcomes-oriented research in a few selected areas.

I think the MADIT-2 story is likely to be one of them, but there will be many others and one will begin to see wider clinical applications as the data emerges.

WILKE: MR rest-stress perfusion imaging, viability and functional assessment today is a very valuable, clinical, alternative test to comprehensively assess the heart. There’s no reason to compromise your diagnostic accuracy with nondiagnostic echo or nuclear tests if you have MR available. For certain indications — women’s heart disease, microvascular disease, ischemic and nonischemic cardiomyopathy, and heart failure — the addition of the multitude of diagnostic information by one modality, MR alone is superior and recommended for better diagnosing and managing these patients.

MR rest-stress perfusion imaging will also become the modality of choice in determining the significance of coronary artery disease based on prior CT coronary artery angiograms showing significant coronary calcifications or borderline noncalcified plaques and stenosis.

HILL: I echo everything that’s been said. However, I think from a practical, day-to-day standpoint the real advances and real uses over the next couple years is going to be much more in perfusion and viability.

Audience participants whose comments are included: James H. Chesebro, MD, is professor of medicine at the Mayo Medical School, Mayo Clinic, St. Luke’s Hospital; Ty J. Gluckman, MD, is a fourth-year fellow at Johns Hopkins and a member of Cardiology Today’s Fellows Advisory Board; Peter A. McCullough, MD, is chief, division of nutrition and preventive medicine, medical director, preventive cardiology and consultant cardiologist at William Beaumont Hospital, Royal Oak, MI; Udho Thadani, MD, is professor of medicine, cardiovascular section at The University of Oklahoma Health Sciences Center and is a member of Cardiology Today’s Cardiovascular Pharmacology Section.