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Editorial
MRI of the Microarchitecture of Myocardial Infarction
Are We Seeing New Kinds of Structures?
Leon Axel, PhD, MD
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fibers are wound around the wall in a helical way that changes
smoothly with depth, changing from being oriented obliquely
with respect to the long axis of the ventricle in the subepicardium, to running circumferentially in a “hoop-like” manner in the mid wall, to being oblique in the opposite direction
in the subendocardium.2 There are also additional secondary,
but well-defined, “sheet-like” organizations of the fibers.3
The muscle fibers are held in their organizational structures
by a hierarchical network of collagen fibers.4 The muscle
fibers are the force-generating elements of the heart wall and
can only generate active tension along their length; these
forces get distributed through the heart wall by the collagenous fibers that hold them together. Thus, the spatial distribution of the fibers is an important determinant of the way
that the heart generates tension in the wall and thus the way
that it pumps blood. In addition, the heart fibers propagate
their electric depolarization and thus the initiation of mechanical contraction, from one to another. This propagation of
electric activation proceeds more rapidly along the direction
of the fibers than across them, which also produces an
important link between their spatial arrangement and the
development of mechanical contraction.5
MRI is playing an increasingly important role in the
management of MI and its complications. MRI is becoming
accepted as the gold standard way to assess global cardiac
function due to its ability to provide reliable measurements of
such aspects of function as the end-diastolic volume, the
stroke volume, and the ejection fraction. In addition, through
the use of contrast agents that are seen to be retained
relatively longer in regions of fibrosis, MRI can provide
images of late gadolinium enhancement that correlate extremely well with the areas of fibrosis in animal models of
MI6 and that have prognostic significance in human MI.7
Although not yet of practical utility, MRI can also provide
unique information on the spatial arrangement of the cardiac
muscle fibers through diffusion-weighted imaging. In diffusion MRI, strong pulses of magnetic field gradients are
applied in such a way that they reduce the signal from
diffusing water molecules, even though they may move
distances that are only on the order of tens of microns but
leave the signal from stationary molecules unchanged. Because the diffusion along the direction of the fibers is more
rapid than it is across them, the use of a suitable range of
directions and strengths of these diffusion-sensitizing gradients allows us to calculate the underlying distribution of the
fiber orientations within the region being imaged. These
methods have had only limited application to in vivo imaging,
due to technical difficulties such as their sensitivity to patient
motion and their relatively long acquisition times, although
they have been used to demonstrate the interruption of the
yocardial infarction (MI) is a leading cause of death
and disability. In addition to the immediate incidence
of death in acute infarction caused by pump failure or
arrhythmias related to the immediate loss of functioning
cardiac tissue and the possibility of later progression to
intractable pump failure in the subacute or chronic phases of
infarction, a significant number of patients with prior MI have
sudden death,1 presumably largely caused by arrhythmias
related to the infarction. There are various theories about the
mechanisms of infarction-related arrhythmias, many centering around the idea that the altered transmission through the
region of the infarction can alter the propagation of waves of
electric activation in such a way that they can set up
self-perpetuating foci of electric activity. However, there is
still much uncertainty about the area.
Article see p 206
In MI, there is ischemia of a portion of the heart wall that
is sufficiently severe and prolonged that cells in the heart wall
start to die. Whereas the myocytes, with their relatively high
metabolic demands, are likely to be irreversibly damaged by
such a significant period of ischemia and thus lost from the
wall, the fibroblasts in the heart wall are more resistant to
the effects of ischemia and thus are more likely to survive. In
the healing phases of MI, these fibroblasts can become
activated and effectively “patch” the wall with a meshwork of
collagen. The resistance of the heart wall to the effects of
ischemia is species-dependent, in part reflecting the different
capacities of different species for supplying collateral blood
to myocardium at risk. A correlate of this is seen in the degree
of definition of the infarcted myocardium from the adjacent
spared myocardium. Species such as dogs or rats, which have
excellent collateral blood supply, develop irregular and
patchy margins between infarcted and preserved myocardium, whereas animals such as sheep, which have poor collateral blood supply, develop much more sharply delineated
boundaries between infarcted and preserved myocardium;
human beings fall somewhere in between these extremes.
The architecture of the normal heart wall is highly ordered,
with a very regular arrangement of the muscle fibers. The
The opinions expressed in this article are not necessarily those of the
editors or of the American Heart Association.
From the Department of Radiology, NYU Langone Medical Center,
New York, NY.
Correspondence to Leon Axel, PhD, MD, Department of Radiology,
NYU Langone Medical Center, 660 First Ave, Room 411, New York,
NY 10016. E-mail [email protected]
(Circ Cardiovasc Imaging. 2009;2:169-170.)
© 2009 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at
http://circimaging.ahajournals.org
DOI: 10.1161/CIRCIMAGING.109.873372
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Circ Cardiovasc Imaging
May 2009
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normal orderly arrangement of the muscle fibers in the setting
of prior MI.8 However, they have been able to be used for
detailed mapping of the fiber arrangements in ex vivo heart
specimens (eg, reference 9).9 These fiber data can be obtained
in full 3D and provide information that would be difficult to
obtain with traditional serial-section histological methods.
In the article by Sosnovick et al10 in this issue of Circulation:
Cardiovascular Imaging, a variant MRI diffusion method,
diffusion spectrum MRI tractography, was used for myocardial fiber mapping. This approach seeks to recover information on both the distribution fiber directions within each voxel
imaged and the connections of the fibers between them. In
particular, diffusion spectrum MRI tractography was used to
study the effects of infarction on the myofiber architecture in
a rat model of MI; infarction was created by permanent
coronary artery ligation for 3 weeks. After MRI study of the
heart specimens, representative sections were also examined
with conventional histological methods. After the tractographic analysis is performed, the resulting processed images
are elegant and striking, with clear demonstration of both the
3D arrangement of the normal helical fibers and the interruption of this arrangement by the infarction. The irregular
boundary between the infarcted and preserved heart wall,
expected in this infarct model, is also clearly seen. In
addition, the authors claim to have discovered a novel feature
of the infarction through their tractographic analysis, “nodes
of orthogonal myofiber intersection or contact” (NOMIC). In
these regions, fibers with nearly orthogonal orientations,
which would normally be well separated from each other, are
found close together in portions of the region of the infarction. They also identified similar-appearing regions in the
corresponding conventional histological sections.
The fiber mapping results presented here are a technical
tour de force, with the detailed depiction of the diffusion
effects of the cellular architecture potentially providing an
effective understanding of structures well below the nominal
resolution of the imaging method itself. The question arises as
to the nature and significance of the new structures reported
here. Rather than new fibers growing into the infarct, it seems
likely that these are residual surviving muscle fibers that were
“trapped” in the contracting fibrosis of the healing infarct.
However, their electric and mechanical significance is still
uncertain. Electrically, even though they are close together, it
is not clear whether these fibers will be able to form true
electric connections, with the capacity to effectively reroute
waves of electric activation in ways that could lead to
self-sustaining foci of electric activation that could produce
potentially fatal arrhythmias. Mechanically, they will potentially have locally much more rapidly varying directions of
contraction force than would be present in the normal heart,
with its gradual changes in fiber orientation. However, the
significance of this is also uncertain, as the amount of force
that can be generated by such relatively isolated fibers
embedded in dense fibrosis is probably relatively small. The
relevance of the rat model of MI used to the kinds of MI
occurring in human beings is also uncertain. Furthermore, it
is not at all clear that these methods will be able to be
extended to clinical human studies. Nevertheless, the new
availability of such effectively high-resolution methods for
investigating the boundaries of infarctions, and for correlating
them with their functional consequences (at least in animal
models, for now), should lead to greater insight into the
mechanisms of both the electric and mechanical consequences
of MI, and, we hope, to improved means to treat them.
Disclosures
None.
References
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KEY WORD: Editorials
MRI of the Microarchitecture of Myocardial Infarction: Are We Seeing New Kinds of
Structures?
Leon Axel
Downloaded from http://circimaging.ahajournals.org/ by guest on May 7, 2017
Circ Cardiovasc Imaging. 2009;2:169-170
doi: 10.1161/CIRCIMAGING.109.873372
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