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Journal of the American College of Cardiology
© 2006 by the American College of Cardiology Foundation
Published by Elsevier Inc.
EDITORIAL COMMENT
Positively Magnetic North*
Timothy F. Christian, MD, FACC
Burlington, Vermont
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 twodimensional 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.
See page 1641
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
*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.
From the University of Vermont, Burlington, Vermont. Dr. Christian is the
recipient of an American Heart Association Grant-in-aid award on MRI-based
high-field perfusion imaging.
Vol. 47, No. 8, 2006
ISSN 0735-1097/06/$32.00
doi:10.1016/j.jacc.2006.01.036
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.
The MR viability imaging has now been validated extensively with histopathology staining in animal models (2,3),
predicted improvement in wall motion with revasculariza-
JACC Vol. 47, No. 8, 2006
April 18, 2006:1646–8
Christian
Editorial Comment
1647
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.
tion and medical therapy (10,11), correlated with other
surrogate measures of infarct size (12), detected micronecrosis 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 insideout. By measuring the subendocardial infarct volume, we are
simultaneously measuring what did not infarct subepicardially. Together, these two volumes might provide a retro-
spective 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 im-
1648
Christian
Editorial Comment
proved 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.
Reprint requests and correspondence: Dr. Timothy F. Christian,
Baird 191, MCHV, University of Vermont, 111 Colchester Avenue,
Burlington, Vermont 05401. E-mail: [email protected].
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