Applied Radiology

The evaluation of patients who have had a myocardial infarction (MI) often starts with functional imaging, which usually consists of the acquisition of cine images and their analysis for wall motion abnormalities. Figure 1 demonstrates the use of myocardial tagging, a technique that aids in the evaluation of regional wall motion throughout the myocardium. In this case, it reveals severely disordered contraction of the myocardium. Wall motion analysis is unable to answer a crucial question, however: whether the areas of abnormal contraction are still viable or represent infarction. An assessment of myocardial viability using contrast techniques is, therefore, the next step.

In assessing myocardial viability, we acquire first-pass myocardial perfusion images following a single dose of gadolinium contrast media delivered at a 5 mL/sec, a fairly high injection rate (Table 1). We use power injectors for all viability and perfusion studies. Because these patients often are quite sick, they typically have a large-bore catheter already in place, which enables us to inject using a large-bore Angiocath.

We image the entire heart every 2 heart beats for about 1 minute after contrast injection to assess microvascular integrity. Next, we inject a second dose of gadolinium contrast, wait for 10 to 20 minutes, and obtain myocardial viability images using gradient-echo techniques with myocardial suppression.

Consider the application of MR viability imaging in a patient with an extensive MI. Even though many such patients have the infarct-related artery opened in the cardiac catheterization laboratory and undergo implantation of a coronary stent, some still have small-vessel disease or capillary occlusion. MR is the only noninvasive method that can assess disease at the capillary level reliably, and this is accomplished during first-pass perfusion imaging.

If on the first-pass images the capillaries remain occluded--evident as a dark area that is not perfused--we inject the second dose of contrast and wait for approximately 10 minutes. During this time, as contrast washes out from the rest of the myocardium, there is a redistribution of contrast between areas of nonviable and normal myocardium, such that the contrast agent is retained in the area of infarction. Figure 2 demonstrates this concept in a patient with large transmural infarction of the inferior and basal walls.

Even though infarcted myocardium can be mapped on delayed viability imaging, it is the core of the infarct, which appears on first-pass images and corresponds to microvascular obstruction, that predicts patient prognosis. Wu et al ¹ found that patients with evidence of microvascular obstruction following MI were more likely to experience a cardiovascular event during follow-up when compared to those without microvascular obstruction (45% versus 9%). The size and presence of microvascular obstruction predicted an increase in left ventricular mass and volume, and a decrease in ejection fraction, at 6 months.

MR can be used to evaluate both acute and chronic MI. The purpose of the study is often quite different in these two settings, however. In acute MI, the primary issue is the size of the infarction, an assessment that can sometimes be difficult to make clinically. For example, cardiac enzyme levels may be challenging to interpret in a patient who has received a thrombolytic agent. In another example, a woman may delay coming to the hospital for chest pain because her symptoms are atypical, thus skewing interpretation of the troponin levels.

In chronic MI, patients typically are being evaluated before revascularization procedures, and the question is one of viability, rather than infarct size. If the target myocardium is dysfunctional, but still viable, bypass grafting could markedly improve cardiac function.

In both acute and chronic MI, cine images demonstrate an absence of motion in the area of infarction. In the acute infarct, there may also be areas of dysfunctional myocardium that is stunned but will eventually recover.

Wall thickness can be analyzed by anatomic imaging. In acute MI, the myocardium typically does not show thinning, whereas after 3 to 6 months, the chronic infarct is characterized by thinning and remodeling of the myocardium with scar formation.

Both acute and chronic infarction demonstrate marked enhancement with gadolinium contrast, although the pathophysiologic mechanisms
are quite different. It is hypothesized that in acute MI, there is an increase in the distribution volume of the contrast agent in areas of nonviable myocardium, where myocytes have died. In the case of chronic infarction, in which the myocardium is replaced by fibrosis and scar, it is hypothesized that there is a difference in contrast distribution between the nonviable myocardium and the scar, when compared with the adjacent myocardium.

Viability imaging can also be useful in the assessment of patients with idiopathic hypertrophic subaortic stenosis, following alcohol ablation of the enlarged ventricular septum. ² In such patients, the anterior motion of the mitral valve leaflet is obstructed by the enlarged septum during systole, which obstructs aortic outflow. The standard treatment at our institution is coronary alcohol injection to ablate a portion of the myocardium. These procedures are done empirically and guided by evidence of decreased wall motion. Gauging how much of the myocardium has been treated can be quite difficult angiographically, however.

Using MR, functional images are obtained before the procedure to assess outflow obstruction. Following injection of alcohol into the coronary artery, first-pass perfusion images demonstrate areas without blood flow (Figure 3). On delayed imaging, approximately 10 minutes after injection, the areas of nonviable myocardium are clearly mapped out. Patients can also be followed over time to assess overall cardiac function as well.

Myocardial Perfusion

Myocardial perfusion imaging is typically used to evaluate patients with ischemic heart disease, rather than MI. An infusion of the vasodilator Adenoscan (Fujisawa Healthcare, Inc., Deerfield, IL), 140 µg/kg/min, augments coronary blood flow. After approximately 2 minutes, 0.1 mmol/kg gadolinium contrast media is delivered as a single, rapid-infusion bolus (5 mL/sec), as in the myocardial viability protocol described previously. Gradient echo, echo-planar notched interleaved pulse sequences are used to image the entire myocardium for about 1 minute after a contrast injection.

Because the protocol involves the use of the vasodilator adenosine to augment coronary blood flow, there are several contraindications to MR perfusion imaging, including wheezing, hypertension, the use of caffeine or aminophylline, or greater than first-degree atrioventricular heart block. Depending on the patient population, approximately 5% of patients are likely to experience discomfort during the exam. Approximately 0.5% experience a potentially serious adverse reaction to adenosine, such as arrhythmias or heart block. During stress testing, a staff member with Advanced Cardiac Life Support certification must be present.

Figure 4 shows a patient with reduced perfusion in the septal and anterior portion of the myocardium, and another patient with left ven-tricular hypertrophy and small subendocardial areas of decreased enhancement.

A major area of investigation involves the quantification of perfusion defects, as a better alternative to visual estimation of the extent of stenosis. ^3-6 Nonetheless, even with visual estimation, the overall correlation between perfusion abnormalities that are physiologically significant and angiographic stenosis has been quite good (Table 2)

Atherosclerosis

The imaging of atherosclerosis represents a major new and developing application of contrast administration. Often, MR angiography of patients with suspected heart disease shows an essentially normal coronary lumen. However, there can be tremendous amounts of disease in the vascular walls. Assessment of the atheromatous components of plaque represents an important and active area of investigation today. Key questions in determining whether a plaque is vulnerable to rupture include whether it has a large lipid core or is covered by a thin fibrous cap. Both are thought to increase the risk of plaque rupture, with the ultimate result being obstruction of the coronary artery and MI.

Figure 5 demonstrates the use of contrast in imaging atherosclerosis of the carotid artery, where most of the initial studies have been done. ^7,8 The area of fibrous cap is well enhanced, enabling assessment of cap thickness. The lumen is quite small, and adjacent to the fibrous cap is the lipid core. Within the lipid core is an area of calcification. All of the plaque components are well delineated on the MR image, which correlates closely with the histology specimen.

The imaging of atherosclerosis can be applied to other vascular beds as well. ⁹ Probably the most interesting and important are the coronary arteries. Patients with atherosclerosis may have only mild degrees of coronary arterial narrowing on angiographic sequences, but still have significant amounts of disease inside the vessel wall (Figure 6). The true extent of disease and risk for subsequent plaque rupture is probably best assessed using contrast-enhanced MR.

Conclusion

The use of contrast for myocardial viability imaging is a major new application of MR. Myocardial perfusion, stress imaging, and the evaluation of myocardial ischemia are active subjects of investigation as well. Contrast-enhanced imaging for atherosclerotic disease, particularly in combination with MR coronary angiography, holds great promise for evaluating the risk of cardiac events. *

Discussion

TG: Thank you very much, Dr. Bluemke. Let me ask a question specifically about the perfusion. You mentioned that you give the bolus at a high rate of injection. Do you use a power injector for that, or do you do that by hand?

DAVID BLUEMKE, MD: We are using power injectors for all of our studies. For first-pass perfusion studies, we typically inject at about 5 mL/sec. These patients are quite often very sick patients and they typically have large-bore catheters already in place. So it is quite feasible to inject using a large-bore angiocatheter with a high injection rate.

MP: I'd like to ask you about the tendency in nuclear medicine to obtain rest and stress images. Where do you think that fits in? Concerning injection, when you have to give dynamic gadolinium injection and pharmacologic injection simultaneously, then you would need multiple IVs. Or can they be piggybacked?

DB: As far as the the use of stress and rest images, the initial studies that were done with perfusion MRI definitely considered that model of application. The reason for doing stress and rest images is to distinguish viable from nonviable myocardium, ischemic myocardium versus infarction. That model was used initially. Now it is a development of these viability MR sequences, where the normal myo-cardium is suppressed with inversion recovery pulse sequences.

The standard model now is to do stress images during adenosine infusion, and then wait for 10 to 20 minutes, then look at the areas that are nonviable on the delayed images. There's been a movement then to not require multiple injections for those images, during first-pass conditions.

TG: The reason for that is because you don't need the resting image, because the viability image tells you where the infarct is, if it is there.

DB: That's right. The nonviable myocardium will light up very nicely, and can be delineated at about 10 to 20 minutes after contrast injection.

MP: So are you then suggesting that the need to image under stress may be completely eliminated by these new MR perfusion and viability sequences?

DB: No, we think that stress conditions are going to be necessary to distinguish narrowing prior to infarction. If a patient presents with chest pain and typical anginal type symptoms, the question is, is that coronary heart disease or is it some other cause of chest pain. In those conditions, in which an infarction has not occurred, it is very likely that only under stress conditions will those areas of coronary narrowing be revealed on the perfusion images, the first-pass images.

DR: During the stress imaging, who is monitoring the patients? Do you do it with the cardiologist?

DB: Yes, during the stress cases, someone who is ACLS certified has to be there. We typically have a very competent nursing assistant addressing the medication issues. They can be quite complicated procedures, although they are of relatively short duration. After 4 to 6 minutes, the stress imaging is completely done and the adenosine has a very short half life of about 1 to 2 minutes. So when we are done with that stress component, we can rapidly assess the patient to determine if there is any evidence of heart block, or any chest pain associated with the stress condition.

RUSSELL LOW, MD: What's the incidence of complications or symptoms?

DB: Well, the incidence of symptoms can be relatively high, depending on the patient population you are studying. Some discomfort can occur in probably <5% of the patients. As far as overall severe life-threatening conditions, the incidence for adenosine is on the order of about 0.5%, at least in the literature. If you talk to labs that do a lot of these studies, I think they believe that that number is a little bit high. But if you document a large number of cases in which arrhythmias and heart block are delineated accurately, it may very well be that those numbers are quite accurate. So you have to be prepared to treat patients and get them out of the room rapidly if complications should occur.

DR: In the first-pass images that you showed, I noticed some misregistration, which I presumed was motion artifact from breathing. Do you find that interferes with the creation of color maps of the mean transit time and other parameters?

DB: Yes, we try to do the first-pass images during an extended breath-hold and ask the patient to hold his or her breath for as long possible. For some patients, it is about one image. Other patients do quite well, and hold their breath for 30 or 40 seconds. The key time is the first 20 to 30 seconds. We have a pretty good success rate in having patients coordinated with the technologist in terms of the injection and the scanning, to be able to hold their breath during that period of time.

Right now most of these images are evaluated qualitatively. With quantitative evaluation, it's a huge issue. But there are motion correction software packages that will re-register the images, so we can place cursors over the areas of interest to map those signal changes quantitatively.

LK: How soon after a patient arrives in the emergency room, do you feel safe to do a stress perfusion study? At some point, you have to decide whether the patient's had an infarction or not.

DB: Well, there are a couple of issues there. Let's say the patient comes into the emergency room with chest pain. First of all, there are not a lot of MR centers that are set up to handle that patient in the acute setting. There have been studies in which MR scanners have been sited next to the emergency rooms. They have been used not so much for stress studies, but for nonstress studies for viability, since the areas of dead myocardium will light up very rapidly after the event occurs.

In animal studies with 90-minute occlusions of a LAD, immediately after imaging, those areas will show on the delayed enhancement images. The more common scenario is with someone with chest pain who was triaged and is in the CCU when we image them, if they need to be imaged at all. Usually it's patients who have more complicated courses, or who have atypical conditions that are imaged. Women may present differently; the troponin levels may have been missed because of delayed presentation in the emergency room. So usually it's a combination of factors.

Not all patients need viability imaging necessarily. We think that some routine myocardium infarction cases are treated very nicely, and they get very little imaging whatsoever in the hospital. It's probably in the sicker patients, more atypical presentations, that this will be a useful technique.

MP: Do you think MR has the potential in these emergency room patients to determine whether there has been a myocardium infarction? Would a normal MR allow safe discharge of the patient; thereby eliminating the more common pattern of watching the patient overnight and checking enzymes and so forth?

DB: Yes, and it is a very significant issue for hospital administrators, because of the substantial costs of keeping people in the hospital for 24 hours. So, there is a major reason to triage these patients quickly. Whether that will have an impact, I think will still unfold.

There have been studies at Washington Hospital, for example, in which they have triaged patients using MR to determine if they will be admitted, or if they will be observed for just a short period of time. Overall, they've shown reasonable success for mapping areas of myocardium infarction. One of the issues in the nonstress state is whether you can assess nonviable myocardium versus ischemic changes. You probably cannot. So in the acute setting, mapping the myocardium infarction to determine if an infarct has occurred may be quite useful. But these patients will still need some triaging and ischemic testing or stress testing, if they go home.

LK: Howard talked about perfusion imaging the brain, and measuring MTT blood volume and blood flow. Is there any use for those measurements in the myocardium?

DB: As I mentioned, most studies have looked at qualitative changes. There is a lot of investigation in the use of quantitative evaluation. Personally, I think it would be quite valuable. But the techniques are not widely applied at this point and the software is not widely available. There are many people who have subtle perfusion changes, which may be in the realm of normal, that we'd like to quantify. We think we can triage between the abnormal patient with ischemia or infarction, versus the normal individual.