Characterization of Signal Properties in Atherosclerotic
Plaque Components by Intravascular MRI
Walter J. Rogers, Jeffrey W. Prichard, Yong-Lin Hu, Peter R. Olson, Daniel H. Benckart,
Christopher M. Kramer, Diane A. Vido, Nathaniel Reichek
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Abstract—Magnetic resonance imaging (MRI) is capable of distinguishing between atherosclerotic plaque components
solely on the basis of biochemical differences. However, to date, the majority of plaque characterization has been
performed by using high-field strength units or special coils, which are not clinically applicable. Thus, the purpose of
the present study was to evaluate MRI properties in histologically verified plaque components in excised human carotid
endarterectomy specimens with the use of a 5F catheter– based imaging coil, standard acquisition software, and a clinical
scanner operating at 0.5 T. Human carotid endarterectomy specimens from 17 patients were imaged at 37°C by use of
an opposed solenoid intravascular radiofrequency coil integrated into a 5F double-lumen catheter interfaced to a 0.5-T
General Electric interventional scanner. Cross-sectional intravascular MRI (156⫻250 ␮m in-plane resolution) that used
different imaging parameters permitted the calculation of absolute T1and T2, the magnetization transfer contrast ratio,
the magnitude of regional signal loss associated with an inversion recovery sequence (inversion ratio), and regional
signal loss in gradient echo (gradient echo–to–spin echo ratio) in plaque components. Histological staining included
hematoxylin and eosin, Masson’s trichrome, Kossa, oil red O, and Gomori’s iron stain. X-ray micrographs were also
used to identify regions of calcium. Seven plaque components were evaluated: fibrous cap, smooth muscle cells,
organizing thrombus, fresh thrombus, lipid, edema, and calcium. The magnetization transfer contrast ratio was
significantly less in the fibrous cap (0.62⫾13) than in all other components (P⬍0.05) The inversion ratio was greater
in lipid (0.91⫾0.09) than all other components (P⬍0.05). Calcium was best distinguished by using the gradient
echo–to–spin echo ratio, which was lower in calcium (0.36⫾0.2) than in all plaque components, except for the
organizing thrombus (P⬍0.04). Absolute T1 (range 300⫾140 ms for lipid to 630⫾321 ms for calcium) and T2 (range
40⫾12 ms for fresh thrombus to 59⫾21 ms for smooth muscle cells) were not significantly different between groups.
In vitro intravascular MRI with catheter-based coils and standard software permits sufficient spatial resolution to
visualize major plaque components. Pulse sequences that take advantage of differences in biochemical structure of
individual plaque components show quantitative differences in signal properties between fibrous cap, lipid, and calcium.
Therefore, catheter-based imaging coils may have the potential to identify and characterize those intraplaque
components associated with plaque stability by use of existing whole-body scanners. (Arterioscler Thromb Vasc Biol.
2000;20:1824-1830.)
Key Words: atherosclerosis 䡲 catheters 䡲 MRI
A
alterations in the composition of arterial walls that cause
hardening, thickening, and loss of elasticity of the vessel
walls. Beginning with the deposition of lipid within the
intima within macrophages and myointimal cells, the process
of atherosclerosis proceeds as the lipid-laden cells rupture
and release their contents. Numerous cells and cellular
processes affect collagen regulation, including smooth muscle cells,4 macrophage-produced matrix metalloproteinase-1,5
matrix metalloproteinase-2,6 and calcification.7 Free lipid
collects and forms lipid pools with cholesterol crystal formation. The free lipids induce a fibrotic response. Fibroblasts
and collagen appear within the lesion, and a denser collage-
therosclerotic plaque is an actively evolving structure
with numerous components. Plaque composition and
morphology may determine whether plaque rupture is likely.
Spontaneous rupture of nonocclusive atherosclerotic plaque
with subsequent thrombosis is the most frequent cause of
acute coronary events, including myocardial infarction and
unstable angina.1,2 The main components of mature atherosclerotic plaques are conveyed in the name: the soft lipid-rich
atheromatous gruel and the hard, sclerotic, collagen-rich
tissue.3 The process of atherosclerosis is a pathological
cascade of lipid accumulation, collagenous fibrosis, ulceration, hemorrhage, thrombosis, and calcification, leading to
Received November 10, 1999; revision accepted March 20, 2000.
From the Departments of Medicine (W.J.R., Y-L.H., C.M.K., D.A.V., N.R.), Pathology (J.W.P., P.R.O.), and Surgery (D.H.B), Allegheny General
Hospital, Pittsburgh, Pa.
Correspondence to Walter J. Rogers, Jr, MS, Division of Cardiology, Allegheny General Hospital, 320 East North Ave, Pittsburgh, PA 15212. E-mail
[email protected]
© 2000 American Heart Association, Inc.
Arterioscler Thromb Vasc Biol. is available at http://www.atvbaha.org
1824
Rogers et al
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nous cap forms over the lipid pool separating the thrombogenic lipid from the coagulation factors within the blood. The
destabilizing atheromatous lipid pool lacks supporting collagen, is rich in extracellular lipids (predominantly cholesterol
and its esters), and is avascular and hypocellular (except at
the periphery, where macrophages are often found).8 The
mechanical instability of the lipid pool and the inflammatory
response may lead to weakening and fracturing of the fibrous
cap, resulting in hemorrhage and thrombosis of the artery.9,10
MRI at high field strength is able to detect plaque components, including lipid,11 collagen,12,13 and calcium,14,15 on the
basis of biochemical properties. At present, imaging of in
vivo atherosclerotic plaque is limited to the use of surface
coils for superficial vessels, such as the carotid arteries.11 To
discriminate plaque components within “deep” vessels, including the coronary arteries, the use of intravascular imaging
coils has been proposed.16 –20 Although there have been a
number of studies showing the potential for MRI to visualize
plaque components,11,21–25 these studies have either used
high–field-strength instruments inappropriate for clinical imaging or coil assemblies not appropriate for intravascular use.
The purpose of the present study was to evaluate the signal
properties of plaque components by use of a 5F catheter–
mounted intravascular imaging coil to attain high spatial
resolution, by use of standard imaging software, and by use of
a clinical (0.5-T) imaging system.
Methods
Seventeen human carotid endarterectomy specimens were included
in the present study. Specimens were frozen immediately after
excision at 4°C. It has been previously shown that the relaxation
properties of atherosclerotic plaque do not change when specimens
are stored at 4°C for up to 6 days.25
Intravascular MRI
Imaging was performed on a General Electric 0.5-T interventional
scanner. Details regarding this instrument have been previously
described in detail.26 Briefly, the design permits the operator access
to the center of the scanner for the purpose of surgery or other
interventions. This system requires the use of surface coils for
radiofrequency transmission and reception. In the present study,
endarterectomy specimens were positioned with the long axis parallel to the static magnetic field and patient couch. At physiological
temperatures, atheromatous lipids often exist near phase transition.27
Magnetic resonance signal properties will be affected by the temperature of the ex vivo specimen. Thus, specimens were warmed to
37°C in a saline solution and were maintained at this temperature
(⫾0.2°C) throughout imaging by use of a recirculating heater
(Polyscience). After the catheter coil was positioned within the
lumen of the vessel segment, the vessel specimen was wrapped in
saline-saturated gauze and placed in an airtight plastic case for
imaging. The cassette maintained the spatial relationship between the
specimen and coil. Bags of saline (500 mL, 150 mEq/L) were placed
above and below the sample to minimize temperature changes and
act as a “load” for the transmit coil. The transmit coil contained two
24-cm square elements positioned above and below the saline bags
and specimen. The temperature of the specimen was verified
between scans by use of a digital thermometer (model 08403,
Cole-Parmer) with an accuracy of ⫾0.2°C.
The receiver coil was an opposed solenoid design described by
Hurst et al.17 In contrast to standard coil designs, which make images
of the volume enclosed by the radiofrequency coil, the opposed
solenoid is an “inside-out” design, which permits imaging of the
walls of the carotid specimen with the coil positioned within the
lumen. The coil included two 10-turn solenoid elements wound in
opposite directions and separated by a 2-mm gap (Figure I, which
can be accessed online at http://atvb.ahajournals.org). The coil was
MRI Characterization of Atherosclerotic Plaque
1825
integrated into the distal end of a 5F dual-lumen catheter without
changing the catheter diameter. The miniaturized tuning circuit was
located immediately proximal to the coil inside one of the catheter
lumens. This lumen also contained a coaxial cable, which terminated
in a miniature connector fit into a Luer port at the proximal catheter
end. A second Luer port permitted access to the second lumen for
delivery of fluids or guidewire introduction. The coil was tuned to
resonate at the Larmor frequency (21.3 MHz) of the system, and
coils including attached coaxial cable had an average Q value of
28.9⫾2.1.
Imaging Protocol
After a stable temperature was achieved, axial and sagittal scout
images were used to identify the location of the coil and vessel
section. A scout image in the coronal plane showed the relationship
between the opposed solenoid coil and the overlying carotid artery
specimen. Regions of signal void occurring at each coil element
provided a means of registering the location of the cross-sectional
image plane to the specimen. This scout was also used to ensure that
the image plane was perpendicular to the vessel segment. A 3D
imaging sequence was used to acquire multiple short-axis images of
the specimen. Examination of these data verified that the atherosclerotic plaque was centered within the imaging volume of the catheter
coil. Subsequent 2D images were acquired at the center of the coil.
MRI parameters were selected to permit calculation of absolute T1
and T2 of the plaque components. All 2D acquisitions had a 3-mm
slice thickness, 4-cm field of view, a bandwidth of 7.81 kHz per
pixel, and 160 phase and 256 frequency lines resulting in in-plane
resolution of 250 ␮m in the phase direction and 156 ␮m in the
frequency direction. Two signal averages were obtained, and images
were interpolated to 256⫻256. Regional T1 was based on 6 image
acquisitions with use of a constant time to echo (TE, 17 ms) and
repetition times (TRs) of 300, 400, 500, 800, 1000, and 2000 ms.
Regional T2 was based on 5 image acquisitions with use of a fixed
1000-ms TR and TEs of 20, 40, 60, 80, and 100 ms. Magnetization
transfer contrast (MTC) was selected to identify connective tissue.22
Three-dimensional magnetization transfer sequences included a saturation pulse 1200 Hz off resonance applied for 14 ms during each
TR period. Three-dimensional parameters included a TR of 220 ms,
TE of 4.2 ms, bandwidth of 15.6 kHz per pixel, and a 1.5-mm
effective slice thickness. Inversion recovery (TE 17 ms, TR 1000 ms,
and time to inversion 350 ms), with use of a time to inversion
calculated to saturate the signal from water, was used to distinguish
water from lipid. Gradient echo sequences (TE 17 ms, TR 500 ms,
and flip angle 60°) were used to highlight regions of calcium
deposition, as has been previously described.14 A ratio of region-ofinterest (ROI) signal intensity between gradient echo and a similar
spin echo (SE) sequence (TR 500 ms, TE 17 ms), defined as the
GRE-SE ratio, was used to express the sensitivity of each plaque
component to GRE imaging. Total imaging time for each specimen
was ⬇3 hours.
Histology
Endarterectomy specimens of atherosclerotic plaque were refrozen at
4°C after MRI. Whole specimens were digitally photographed and
x-rayed. Each specimen was then cut at the location of MRI that had
been identified by an indelible marker at the time of intravascular
MRI (IV-MRI). The coil center was identified on the specimen
cassette and permitted accurate transfer of the imaging location to the
specimen before processing. Three-millimeter-thick cross sections
on either side of the imaging site were frozen to ⫺20°C in
Tissue-Tek OCT water-soluble embedding medium, and 6-␮m tissue
sections were cut from each block, stored overnight in 10% formalin
vapor, and stained with oil red O stain for lipids.28 The tissue blocks
were thawed, fixed in 10% formalin solution for 4 hours, and
partially decalcified in a formic acid (leaving calcium salts but
reducing large solid calcium deposits), formaldehyde, methanol, and
water solution for 8 hours. The tissue blocks were subjected to
standard tissue processing28 and embedded in paraffin. Sections
(4 ␮m) were cut and stained with hematoxylin and eosin (H&E),
Masson’s trichrome, Gomori iron, and Kossa calcium stains.28
Endarterectomy removes the atherosclerotic luminal lesion with a
plane of dissection usually within the innermost vascular media. The
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Arterioscler Thromb Vasc Biol.
July 2000
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Figure 1. A color-coded digital parametric image was created
by mapping the various histological components of the atherosclerotic endarterectomy cross section at the site of MRI for
correlation to the corresponding magnetic resonance images.
Regions of fibrous cap, edematous collagen, smooth muscle,
lipid, hemorrhage, organizing thrombus, and calcium were colorcoded and used to guide localization of ROIs on magnetic resonance images. Blue dense fibrous tissue is similar in composition to the dense fibrous cap but is external to the lipid
component. Fresh hemorrhage is not present in this example.
resected specimens, therefore, consisted primarily of the diseased
intima and very few smooth muscle cells of the media present at
the periphery.
The components of the arterial wall and the atherosclerotic plaque
were distinguished by histomorphology and histochemistry. In the
present study, we choose 7 categories of histological findings of
atherosclerotic vessels to correlate with the magnetic resonance
images: (1) loose, edematous, fibrous tissue, (2) dense fibrous cap,
(3) smooth muscle cells, (4) lipid, (5) fresh hemorrhage, (6)
organizing thrombus, and finally (7) calcification (Figure II, which
can be accessed online at http://atvb.ahajournals.org). The 7 categories of histological findings were identified by the following methods. The densely collagenous fibrous cap was identified by intense
green staining of fibrous tissue by Masson’s trichrome stain surrounding the vascular lumen and isolating the atheromatous lipid
(Figure IIA). The collagenous portion of the plaque that stained less
intensely green on Masson’s trichrome was examined for lipid
content, which was visualized histologically by the presence of foam
cells (Figure IID) and cholesterol clefts (Figure IIE) on H&E and
Masson’s trichrome and as red intracellular droplets and extracellular
lipid pools on oil red O stain (Figure IIF and IIG). Areas of decreased
density of fibrous tissue not containing lipid were interpreted as
edematous (Figure IIB). Smooth muscle cells of the vascular media
were stained red with the trichrome stain (Figure IIC). Fresh
hemorrhage consisted of collections of intact erythrocytes mixed
with fibrin in the plaque lesion. Organizing thrombosis was identified by the presence of red fibrin on trichrome (Figure II, panel I),
fibrovascular ingrowth (Figure II, panel K), and blue hemosiderin
deposits with Gomori iron stain (Figure II, panel J) from the
breakdown of erythrocytes. Calcium deposits were identified as
acellular purple crystals by H&E (Figure IIL) and confirmed as
brown crystals by Kossa stain (Figure IIM). A color-coded digital
parametric image (Figure 1) was created that mapped the various
histological components of the atherosclerotic endarterectomy cross
section at the site of MRI for correlation with the corresponding MRI
images. Regions of fibrous cap, edematous collagen, smooth muscle,
lipid, hemorrhage, organizing thrombus, and calcium were colorcoded and used to guide the localization of ROIs on magnetic
resonance images.
Image Processing
Magnetic resonance images were transferred to a SUN Ultra Sparc
workstation for processing. Registration between IV-MRI and digitized histological images was accomplished in 2 steps. IV-MR
images were centered between coil-induced signal voids. This same
location was transferred as an indelible mark on each specimen by
carefully opening the specimen cassette and transferring the location
of the coil center to the specimen. Rotational registration used the
longitudinal incision made in the vessel at the time of the procedure.
This cut was visible on IV-MRI and histology. On the basis of the
results of histology, circular ROIs were positioned within locations
containing predominantly 1 of the 7 plaque component categories.
Custom software was used to compute T1 and T2 values for specific
plaque components. Intensity curves were generated across the
sampled TRs for T1 calculations and TEs for T2 calculations. The
relaxation time of a selected region was estimated by least squares
fitting of its intensity curve with a nonlinear function by using the
method of gradient expansion (IDL software, Research Systems).
The inversion ratio (INV ratio) was defined as the ratio of signal
intensities in an ROI for an SE sequence with and without a 180°
Figure 2. Cross-sectional images of carotid plaque showing regional changes in signal intensity for IV-MRI by use of proton density
(A), T1 (B), inversion recovery (IR, C), T2 (D), and GRE (E). Histological staining used to confirm the presence and distribution of plaque
components included H&E (F), trichrome (G), oil red O (H), Prussian blue (I), and von Kossa (J). IR associated signal loss is seen in a
region of edema (box, C) confirmed on trichrome (box, G). Calcium confirmed by Kossa stain (box, J) resulted in focal signal loss on
GRE image (box, E).
Rogers et al
MRI Characterization of Atherosclerotic Plaque
1827
IV-MRI Signal Properties of Atherosclerotic Plaque Components
Cap
SMC
ORG
Edema
Fresh
Lipid
Calcium
ANOVA
T1, ms
419⫾111
588⫾161
465⫾167
532⫾148
467⫾147
300⫾141
625⫾323
NS
T2, ms
42⫾10
59⫾21
45⫾13
50⫾11
40⫾12
45⫾12
52⫾21
INV ratio
0.62⫾0.16
0.35⫾0.04
0.40⫾0.10
0.25⫾0.07
0.41⫾0.07
0.91⫾0.06*
0.28⫾0.05
ⱕ0.001
MTC ratio
0.62⫾0.13†
0.87⫾0.12
0.81⫾0.06
0.87⫾0.21
0.78⫾0.06
0.93⫾0.14
0.85⫾0.24
ⱕ0.0005
GRE ratio
0.78⫾0.42
0.75⫾0.12
0.66⫾0.22
0.88⫾0.05
101.0⫾0.17
0.69⫾0.10
0.36⫾0.21‡
ⱕ0.003
NS
Values are mean⫾SD. Cap indicates fibrous cap; SMC, smooth muscle cells; ORG, organizing thrombus; and fresh, fresh thrombus.
*P⬍0.05 vs all other components measured by INV.
†P⬍0.05 vs all components, except for ORG (P⫽0.06) by MTC.
‡P⬍0.04 vs all other components measured by GRE-SE.
inversion pulse. A similar ratio, the GRE-SE ratio, was constructed
comparing the signal from GRE and SE sequences.
Statistical Analysis
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Data are expressed as mean⫾SD. Differences among the 7 plaque
component categories for T1, T2, INV ratio, MTC ratio, and
GRE-SE ratio were analyzed by 1-way ANOVA (when data were
normally distributed) or nonparametric Kruskal-Wallis ANOVA on
ranks. Individual differences were analyzed by the Student t test for
independent samples or Mann-Whitney rank sum test when data
were not normally distributed.
(Figure 3B). H&E staining at low power (Figure 3C) and high
power (Figure 3E) verifies the presence of lipid and cholesterol crystals. Overall differences were also found between
components for the MTC ratio (Table 1; ANOVA, P⬍0.005).
The fibrous cap showed the greatest signal change after
off-resonance magnetization transfer pulses (0.62⫾0.13).
This was significantly different from smooth muscle cells
(0.87⫾12, P⬍0.05), organizing thrombus (0.81⫾0.06,
P⬍0.001), edema (0.87⫾0.21, P⬍0.001), fresh thrombus
(0.78⫾0.06, P⬍0.03), or calcium (0.85⫾0.24, P⬍0.05). The
dense fibrous cap overlying a region of organizing thrombus
Results
The average length of vessel segment visualized by use of the
constructed coils was 4.2⫾0.2 mm. Seven plaque components were evaluated in the specimens: a fibrous cap in 94%
(16 of 17), smooth muscle cells in 100% (16 of 16),
organizing thrombus in 59% (10 of 17), fresh thrombus in
47% (8 of 17), edema in 35% (6 of 17), lipid in 59% (10 of
17), and calcium in 59% (10 of 17). Figure 2 displays the
regional signal changes in cross-sectional IV-MRI by using
different imaging sequences. Proton density (Figure 2A) and
T1 images (Figure 2B) provide overall plaque morphology
with reduced regional contrast compared with H&E (Figure
2F) and trichrome (Figure 2G). Inversion recovery (Figure
2C) shows a loss of signal in regions of edema and loose
connective tissue (10 to 2 o’clock). T2-weighted imaging
(Figure 2D) shows signal loss in regions of connective tissue
and lipid, as verified by oil red O (Figure 2H) and trichrome
(Figure 2G). GRE shows multiple focal regions of signal loss
(Figure 2E) associated with calcium as seen by Kossa
staining (Figure 2J).
Plaque characterization parameters, derived from IV-MRI
signal intensity, are presented in the Table. There was
significant heterogeneity between INV ratio values for the
studied components (ANOVA, P⬍0.0005). Lipid regions
displayed little signal reduction after an inversion pulse
adjusted to saturate the water signal (0.91⫾0.06). This
resulted in a higher INV ratio in lipid compared with fibrous
cap (0.62⫾0.16, P⬍0.05), smooth muscle cells (0.35⫾0.004,
P⬍0.001), organizing thrombus (0.40⫾0.10, P⬍0.001),
edema (0.25⫾0.07, P⬍0.001), fresh thrombus (0.41⫾0.07,
P⬍0.001), or calcium 0.28⫾0.05, P⬍0.001). A specimen
containing a lipid pool is displayed in Figure 3. IV-MRI
proton density weighting shows a region (4 to 8 o’clock) of
slightly increased signal (Figure 3A), which is unaffected by
water signal suppression in an inversion recovery image
Figure 3. Carotid sample with lipid pool shows region of only
modestly elevated signal intensity in lower half of T1 image (A).
Water signal suppression in the inversion recovery sequence (B)
highlights persistent signal in region containing primarily lipid
and greater contrast between thrombotic lipid (upper half of
image) and the external fibrous intima. Enlargement (E) of corresponding region in H&E section (see box, C) confirms presence
of lipids and cholesterol crystals. Fibrous cap above lipid pool
(B) is confirmed on low-power (D) and high-power (F) trichrome
sections. Boxes indicates regions of enlargement.
1828
Arterioscler Thromb Vasc Biol.
July 2000
Figure 4. Carotid specimen containing
dense fibrous cap (FC) well visualized on
IV-MRI proton density (A), inversion
recovery (B), and GRE (C). Region of
loose connective tissue and edema (box)
on trichrome (E) is seen as region with
reduced signal on inversion recovery
image (box, B). Neither trichrome (E) nor
H&E (D) showed evidence of lipids
beneath cap.
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is well visualized by IV-MRI sequences (Figure 4). The
GRE-SE ratio (Table 1) indicated that calcium was particularly sensitive to GRE imaging, displaying a GRE-SE ratio of
0.36⫾0.21. This reduction was greater than in smooth muscle
cells (0.75⫾0.11, P⬍0.006), edema (0.88⫾0.05, P⬍0.001),
fresh thrombus (1.01⫾0.17, P⬍0.004), and lipid 0.69⫾0.10,
P⬍0.04). Organizing thrombus (0.66⫾0.22) showed a borderline difference (P⫽0.08). The effect of different MRI
sequences on intraplaque calcium is shown in Figure 2E and
confirmed by histology in Figure 2J. Absolute T1 values
ranged from 300⫾147 ms for lipid to 625⫾323 ms for
calcium. There was a wide range in observed T1 values in
calcium (230 to 970 ms). Although regional differences in
plaque component relaxation times provided contrast within
acquired images, there was no significant difference in
absolute T1 values between plaque components. Absolute T2
values ranged from 40⫾12 ms for fresh thrombus to 59⫾21
ms for smooth muscle cells. T2 values were not statistically
different between plaque components.
Discussion
In the present study, intravascular imaging coils, pulse
sequences, and MRI equipment with potential for clinical
application were used to characterize the signal properties of
histologically validated plaque components in excised human
carotid endarterectomy specimens. A number of imaging
approaches were applied to determine which approaches best
discriminated between plaque components. We found that
magnetization transfer contrast, inversion recovery, and gradient imaging approaches were time efficient and were also
able to distinguish the major atherosclerotic plaque components associated with plaque stability.
The stability of atherosclerotic lesions is dependent on the
presence and geometry of specific plaque components rather
than simply on plaque volume. The presence of a lipid pool
creates focal regions of increased stress due to the interface
between the soft lipid pool and stiff surrounding sclerotic
material.29 MRI is sensitive to both of these materials. It is
likely that differences in the amount of lipid in the evaluated
image or sample volume alter the measured T2 value. The
majority of lipids in the present study were found to be mixed
within organizing thrombus or connective tissue and were
best distinguished from the fibrous cap by the use of a
water-saturating inversion pulse rather than by differences in
T2. The lipid inversion ratio was 0.91⫾0.01 versus
0.62⫾0.16 for the fibrous cap (P⬍0.05).
The presence of large proteins, such as collagen, fibronectin, and elastin, may be detected by use of imaging sequences
that include an off-resonance saturation pulse. These pulses
preferentially affect the water molecules bound to macromolecules versus those in the free water pool. Images acquired in
the presence of such pulses have reduced signal intensity in
proportion to the amount of collagen or other macromolecules. Kim et al12 have previously shown that the ratio of
signal intensity between acquisitions with off-resonance saturation to those without saturation (Ms/Mo) varies dramatically between tissue type. For example, they showed that
lipid had an Ms/Mo ratio of 1.0, whereas articular cartilage,
whose macromolecular structure is primarily type I and type
II collagen, had an MTC ratio of 0.25. In the present study,
we calculated an MTC ratio of 0.62⫾13 for the fibrous cap
versus 0.93 for regions of lipid. The actual percentage or the
type of collagen or other macromolecules in these regions is
unknown, and the type of imaging scheme used would not be
expected to produce the same magnitude of signal change as
that used by Kim et al.12
Regions of intraplaque calcium were frequently observed
in the present specimens. Although the role and regulation of
calcium in plaque stability has not yet been fully determined,
its presence as detected by electron beam CT has recently
been evaluated as a indicator of underlying atherosclerosis.31
GRE imaging is more sensitive in the detection of calcium
than is SE imaging. This is caused by low proton density and
by dephasing of the local water molecules by calcium.
Henkelman and Kucharczyk14 have shown a linear relationship between calcium in the form of calcium hydroxyapatite
and T1 relaxation time. T1 ranged from ⬇500 ms at a
concentration of 50 mg calcium per milliliter of agarose gel to
⬎1500 ms at a 350 mg/mL concentration. We measured T1s
in the region of calcium between 230 and 970 ms. This range
Rogers et al
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may reflect differences in regional calcium concentration. In
the present study, intraplaque calcium was detected by greater
regional signal loss in GRE versus SE and reported as a
GRE-SE ratio. The quantitative association between the
magnitude of signal loss and amount of calcium was not
performed, and it should be noted that other components in
plaque, such as iron, would show a similar signal loss on GRE
images. Previous investigators have qualitatively detected the
presence of calcium by local signal loss.11,22
A number of IV-MRI coils have been proposed.16 –20 All
seek to capitalize on the increased signal to noise and
associated potential increase in spatial resolution, gained
through the proximity of the receiver coil to the vessel
segment being imaged. The thickness of the fibrous cap is an
important determinant of plaque stability, and the ability to
resolve its thickness may define IV-MRI spatial resolution
requirements. The differences between imaging coils presently under development are as follows: radial signal homogeneity, visualized vessel length, and the ability to produce
signal when not aligned along the axis of the static magnetic
field. The opposed-solenoid design17 used in the present study
provides excellent radial signal homogeneity. This is important in identification of plaque components based on regional
changes in signal intensity. However, this design images only
short segments of the vessel (4.2⫾0.2 mm in the present
study). Additionally, performance in this design is reduced as
the coil moves off axis from the main magnetic field.
Predicted loss of sensitivity at 45° off axis is 30%. Hurst et
al17 also evaluated simple loop, 4-wire birdcage, 4-wire
multipole, and 4-wire center return designs. Increasing the
number of conductors in these designs improves radial signal
homogeneity but causes the signal to fall off more rapidly as
one moves away from the coil. Atalar et al19 proposed a
catheter design that permits the imaging of longer vessel
segments and better performance when the coil is not parallel
to the main magnetic field, at the expense of reduced radial
signal homogeneity. In all currently proposed intravascular
coil designs, there must be a close match between the coil and
vessel diameter because of the fall off of the rapid radial
signal.
Determination of absolute T1 and T2 from acquired images
was time consuming and did not discriminate between plaque
components in the present study. However, pulse sequences
that take advantage of specific differences in biochemical
structure of individual plaque components, including magnetization transfer contrast, inversion recovery, and GRE, can
be acquired rapidly and are successfully discriminated on the
basis of changes in image signal intensity and may provide a
more efficient method of MRI plaque characterization.
For IV-MRI to achieve clinical application, development
must occur in a number of areas beyond imaging catheters
themselves. Many of the routine devices used in catheter
interventions, such as guiding catheters, introducers, and
guidewires, must be modified to be magnetic resonance
compatible and visible. Positioning MRI catheters within
either peripheral or coronary arteries requires tracking32,33
and visualization techniques.34 To efficiently survey longer
vessel segments, 2 approaches are currently under development. Atalar et al19 makes use of a catheter coil that images
an extended vessel segment. This design trades axial signal
inhomogeneity for a longer length of visualized vessel. Rivas
MRI Characterization of Atherosclerotic Plaque
1829
et al35 have proposed the use of the opposed-solenoid coil
with a rapid “real-time” imaging technique to overcome the
limited length of vessel seen with the use of this coil design.
It is likely that both methods will find clinical application.
Results of the present study indicate that IV-MRI with
clinically compatible catheter-based receiver coils, hardware,
and standard pulse sequences is capable of discriminating
major atherosclerotic plaque components, including lipids,
fibrous cap, and calcium, on the basis of inherent biochemical
differences. Pulse sequences that take advantage of differences in biochemical structure within plaque components,
including inversion recovery; MTC, and GRE imaging combined with intravascular imaging coils, may permit in vivo
evaluation of plaque components and characterization of its
stability.
Acknowledgment
This study was supported by a Sponsored Research Grant from
Cordis/Johnson & Johnson.
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Characterization of Signal Properties in Atherosclerotic Plaque Components by
Intravascular MRI
Walter J. Rogers, Jeffrey W. Prichard, Yong-Lin Hu, Peter R. Olson, Daniel H. Benckart,
Christopher M. Kramer, Diane A. Vido and Nathaniel Reichek
Arterioscler Thromb Vasc Biol. 2000;20:1824-1830
doi: 10.1161/01.ATV.20.7.1824
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