From the University of Alabama at Birmingham.
Correspondence to Gerald M. Pohost, MD, BDB 101 Diabetes Research and Education Bldg, 1808 Seventh Ave S, Birmingham, AL 35294-0012. E-mail gpohost{at}uab.edu
Magnetic resonance is
the newest of the clinical imaging technologies to evaluate the
cardiovascular system. The ability to image the aorta
and the ileofemoral and carotid arteries is now a clinical reality.
Imaging of the large epicardial coronary arteries is rapidly
developing as a clinical tool. The next step will be to characterize
atherosclerotic plaque in vivo in larger vessels and then, potentially,
in human coronary arteries. In this issue of
Circulation, Fayad et al1 take a step
forward in the imaging of atherosclerotic plaque by MR. They report on
their experience with high-field MRI of "magnetic resonance
microscopy" in small mice, some of which were "wild-type"
controls and others genetically engineered to produce severe
atherosclerosis (apolipoprotein E knockout). Using
commonly available NMR hardware, the investigators were able to
visualize aortas with a total area of 0.3
mm2 in wild-type mice and 0.6
mm2 in the apolipoprotein E–knockout mice. To
image such small structures, they achieved a spatial resolution of
47 µm per pixel. MR measurements of wall area versus
histopathology correlated well (slope=1, r=0.86). In
addition, the grading of lesion shape and type from MR images also
correlated well with that by histopathology (r=0.91 and
r=0.90, respectively). Correlations of linear
regression analysis of MR and histopathology gradings of
atherosclerotic severity also were good (slope=0.64, r=0.90,
n=58).
Of course, the ideal model for human
atherosclerosis is Homo sapiens, and the
versatility of NMR methods allows such studies to be performed in
humans. Thus, the importance of the present work is not only that
it sets the stage for clinical studies but also that it demonstrates
the usefulness of MR microscopy in the "in vivo" setting.
Unfortunately, the term in vivo in this context cannot be extrapolated
to clinical work. The mice were effectively immobilized by
the small radiofrequency coil, and anesthesia was used; as
a result, there were fewer of the difficulties (body, respiratory, and
cardiac motion) that are present clinically. In addition, the
imaging procedure resulted in a 23% mortality rate. Although image
quality in humans would be improved under these circumstances, such a
method would not survive in clinical practice.
Previous experience with MR in small animals has demonstrated its
usefulness in true in vivo imaging. MRI has detected herpes simplex
virus–associated changes in the brains of mice2
and bromobenzene-induced liver toxicity in rats.3
Rehwald and colleagues4 described techniques that
can be used for high-speed, high-resolution cardiac MRI in rats and
rabbits. Summers et al5 described the use of
implanted imaging coils in rats to follow balloon-induced carotid
injury in vivo, with good correlation between images and
histopathology. Wehr and coworkers6 used MR to
serially image transplanted segments of carotid arteries in rats as a
model of transplant vasculopathy. Franco and
colleagues7 successfully measured in vivo
myocardial mass in a transgenic mouse model of hypertrophy,
using gated multislice, multiphase MRI. Larger animals, like
rabbits,8 9 10 pigs,11 and
primates,12 have also been studied. Imaging of
small arteries, such as the distal coronary arteries and branch
vessels, in humans has been progressing, but with a set of obstacles
somewhat different from those in the Fayad study. Both cardiac and
respiratory motion combined are the principal difficulties to be
overcome in MR coronary angiography. As technology has
improved, so has image acquisition speed and image quality. New and
innovative gating methods have also been used to reduce the effects of
cardiac and respiratory motion. There is little doubt that MR
coronary angiography will evolve into an effective clinical
tool.
Plaque research in humans has already been demonstrated to be well
suited to the strengths of MRI. Toussaint et
al13 14 used MR techniques to demonstrate plaque
in human carotid arteries and to characterize certain components of
plaque, including the fibrous cap and lipid core, by measuring T2
changes. Furthermore, this same group identified alterations in
diffusion properties of human plaque in vitro.15
Pan and colleagues16 demonstrated a good
correlation between MR imaged carotid artery lumen area and
pathological specimens from patients undergoing
endarterectomy. Development and application of new
intravascular (IV) coils also holds promise for future work on plaque
characterization by MRI.17 18 19 Although it lacks
the attractive noninvasive aspect of MRI, IV MRI may have the ability
to truly characterize plaque, not just by morphological criteria but
also by applying spectroscopy to the plaque and vessel wall. Currently,
attempts at using standard NMR spectroscopy to characterize in vivo
plaque have been hampered by the limitation of depth accessibility with
small surface coils and the distance from the surface of most large
arteries. In vitro characterization of human atherosclerotic plaque
components has been shown to be feasible with
MR,20 so there is promise that more than
justifies the ongoing studies.
Oshinski and colleagues21 also studied plaque
indirectly in humans by use of phase velocity mapping (PVM) techniques.
These techniques emphasize the inherent sensitivity of MRI to blood
velocity and turbulence. PVM was used to measure the wall shear stress
of different segments of aorta, with the finding of higher wall shear
stress in the suprarenal aorta and lower wall shear stress in the
infrarenal aorta. Because plaque is more commonly found in the
infrarenal aorta, wall shear-stress measurements by PVM appear to
provide insight into a mechanism associated with plaque formation.
Accordingly, the study by Fayad et al1
complements the existing literature on the application of MR to the
study of atherosclerotic plaque. It successfully extends the use of MR
to a model that allows the researcher more flexibility in a number of
areas. The use of mice allows more control, because the mouse genome is
well characterized, can be easily manipulated, and allows the
researcher to take advantage of using small laboratory animals. As the
authors mention, the study suggests the potential for the serial
evaluation of therapies for atherosclerosis in
genetically engineered laboratory animals. The study applied hardware
that is found in many laboratories, so that researchers at many centers
would be able to apply such methods to their own experiments.
The study did not incorporate one of the most important aspects of MR
technology that could be of great value for biochemical
characterization, namely spectroscopy. In future work, it would seem
appropriate to use MR spectroscopy to assess plaque lipid, for example.
This might require IV MRI methods. The combination of T2-weighted
imaging and 1 H spectroscopy could have even more
potential than either one alone. However, many hurdles need to be
overcome before spectroscopy can be applied appropriately to plaque
characterization. The interesting finding of Casscells et al that
active plaque may be detectable by differences in
temperature22 paves the way for in vivo
evaluation by MR diffusion-weighted echo-planar
imaging.23
In summary, MRI has a number of unique characteristics that make it
especially useful for the study of atherosclerosis. As
a high-resolution, nondestructive technique, it is ideal for serial
study. It is noninvasive, allowing study of
atherosclerosis without the need for potentially
confounding catheter manipulation (except for the possibility of IV
MRI) or ionizing radiation. It has the theoretical ability to
characterize plaque constituents with NMR spectroscopy and to a lesser
extent T2 imaging and to provide real insight into plaque formation,
rupture, and stabilization. MRI is an excellent tool for plaque
research, whether the bearer of the plaque be large or small.
Footnotes
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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© 1998 American Heart Association, Inc.
Editorials
From the Microscope to the Clinic
MR Assessment of Atherosclerotic Plaque
Key Words: Editorials • atherosclerosis • plaque • magnetic resonance
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