EDITORIAL COMMENT
Positively Magnetic North*
Timothy F. Christian, MD, FACC2,*
University of Vermont, Burlington, Vermont.
* Reprint requests and correspondence: Dr. Timothy F. Christian, Baird 191, MCHV, University of Vermont, 111 Colchester Avenue, Burlington, Vermont 05401. (Email: timothy.christian{at}uvm.edu).
But I am as constant as the northern star, of whose true-fixed and resting quality there is no fellow in the firmament.
—William Shakespeare, Julius Caesar, Act III, scene i
Although Oscar Wilde maintained that "consistency is the last refuge of the unimaginative," readers should not skip over the imaging reproducibility study by Thiele et al. (1) in this issue of the Journal. This short and eloquent study provides a view into the power behind new digital imaging technologies. Magnetic resonance viability imaging after a bolus of gadolinium-based contrast and computed tomography coronary angiography comprise the two most important recent advances in cardiac imaging. Magnetic resonance infarct imaging provides a close-up view of cardiac pathology after myocardial infarction with vivid reflections of necrosis staining in animal models (2,3). This has the potential to revolutionize the field of myocardial viability. Although magnetic resonance imaging (MRI) provides a resolution of approximately 1 to 2 mm in the two-dimensional plane for infarct sizing, there have been issues raised regarding its reliability (4,5). Precision is important because reproducibility is the keystone for the evaluation of ischemic heart disease.
Coronary artery disease tends to generate serial diagnostic testing. We order serial echocardiograms to assess changes in left ventricular (LV) function and nuclear single-photon emission computed tomography (SPECT) studies to follow the progression of ischemia over time. Central to this behavior is an assumption that a change in the measures from these tests represents a real change in individual patient physiology. The threshold for a real change is very much a function of how reproducible the test is over time in the absence of change. One cannot simply acquire an image once and read it blinded twice or even acquire it twice on the same day to get a handle on temporal variability. To know what is real, we need to know what noise is. Although this might seem self-evident, the cardiology literature is largely devoid of carefully performed temporal reproducibility studies, with exceptions (6,7). Consequently, for many tests, we do not have a handle on how consistent they are over time in the absence of physiological change.
In the present study by Thiele et al. (1), with simple subjective manual tracing of digital images in patients with a history of acute or chronic infarction, the reproducibility of an MRI viability image acquired on two separate days was quite close (95% confidence limits were ±2.4% infarct size as a percent of the LV) and virtually identical to values obtained previously with same-day dual acquisitions (8). This is a new level in precision for the temporal imaging of ischemic heart disease. Consequently, the dichotomization of tissues on the basis of viability by MRI seems to contain little noise within the measure. But it does not provide more than a dichotomization. There is no information regarding the metabolic state of the remaining viable tissue, although much can be inferred in conjunction with regional wall motion and perfusion (usually obtained in the same examination).
Why are the reproducibility results for MRI infarct sizing so impressive? Unlike SPECT perfusion imaging or echocardiographic wall motion, MRI deals with a positive image. Infarcts can be seen and at high spatial resolution. This is because of the accumulation of gadolinium within the extracellular space of the necrotic tissue. We are not dealing with the absence of something where the boundaries have to be estimated. Viability imaging is about separating tissues. Consequently, a threshold must be selected on the basis of some aspect of the image that reflects viability. Usually this is a function of the signal intensity that a tracer generates (either positively or negatively) on the basis of its distribution within the myocardium: the sharper the borders, the cleaner the cut.
Tc-99m sestamibi imaging has been used effectively in the past for infarct sizing. Because of the lower resolution of SPECT image acquisition and the associated photon scatter, even in a severely transmural defect like the one shown in Figure 1, the borders between viable and necrotic myocardium are sloped. Because such thresholds are usually taken as a percent of the maximal myocardial activity, they are subject to some variability by threshold choice and normalization zone. The depth at which a threshold is placed will alter the infarct size measure (9). Magnetic resonance viability imaging is a scatter-free high resolution technique and, therefore, is relatively independent of the threshold value. With such sharp interfaces, reproducibility is not impacted by physical parameters. Automated quantitation programs might further improve consistency; however, most inexperienced observers could consistently trace a magnetic resonance (MR)-derived infarct volume from Figure 1.
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Figure 1 Two short-axis midventricular images from separate patients who have suffered transmural myocardial infarction. The top row shows data from a patient with inferolateral infarction (arrows) demonstrated by single-photon emission computed tomography (SPECT) imaging with Tc-99m sestamibi, and the bottom row is a patient with anteroseptal infarction demonstrated by magnetic resonance imaging (MRI) delayed hyperenhanced imaging using an inversion recovery gradient sequence after gadolinium administration. The graphs on the right side represent a circumferential intensity profile from each image. For these types of displays, the short-axis circular image is divided into 360° with the tracer or signal intensity displayed linearly with the location angle (x-axis). The signal intensity (y-axis) along the thin circular region of interest is plotted as a function of angle location. Note the inverted wave-like shape of the SPECT curve as compared with the delta function–like appearance of the MR curve when the infarct is encountered. The shaded arrows represent 70% (light gray), 60% (dark gray), and 50% (black) threshold values of signal intensity for infarct size measurements (arrow width). There is more potential variability for SPECT determinations.
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The MR viability imaging has now been validated extensively with histopathology staining in animal models (2,3), predicted improvement in wall motion with revascularization and medical therapy (10,11), correlated with other surrogate measures of infarct size (12), detected micro-necrosis post-intervention (13), resolved subendocardial from transmural infarction (14), and been reproducible to a high level in both patients with chronic and recent infarction (1,8). Although the authors focused on the immediate benefit of reduced sample sizes required to a show an impact on infarct size for clinical trials, the more important benefit is in clinical care. By accurately quantifying infarct volume and transmurality, MRI provides a tool in-hand to gauge the benefit of reperfusion therapy in individual patients and to quantify potential jeopardized myocardium for the future. That is a lesson that should not be lost. The lateral edges of an infarct are crisp and established early in the course of an acute occlusion (15), with necrosis proceeding from inside-out. By measuring the subendocardial infarct volume, we are simultaneously measuring what did not infarct subepicardially. Together, these two volumes might provide a retrospective quantitation of the myocardial risk area. The potential value of this measure should not be underestimated (16).
There are two phases to the evaluation of clinical tests: the efficacy phase, where the feasibility and accuracy of the test is evaluated; and the effectiveness phase, where the technology is applied broadly to a clinical population. The efficacy phase of MR viability imaging is over. It is a powerful, nonradioactive, non-nephrotoxic tool that consistently provides measures of infarct volume with little declination from "true north."
The effectiveness phase is in progress. There are issues to tackle for MR viability imaging. The cost is high and variable and reflects billing codes developed in the earlier days of long MR exams. A complete cardiac exam for ischemic heart disease may be acquired within 45 min. A 15-min "viability only" exam, where contrast is injected before the patient enters the magnet, might provide improved effectiveness at lower cost. Arrhythmias and implanted cardiac devices remain issues for MRI.
It is hard to abandon methods that have worked well in the past. But the essence of advancement is willingness to accept change. We should not be afraid to jump into this technology. The MR viability imaging is a simple sequence, easy to perform, packed with information that will be shown to be prognostically powerful and begs for a chance to prove its clinical effectiveness.
Set the imaging compass to the constant northern star and you won’t get lost. There is no fellow in the firmament.
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Footnotes
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* Editorials published in the Journal of American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. 
2 Dr. Christian is the recipient of an American Heart Association Grant-in-aid award on MRI-based high-field perfusion imaging.
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References
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