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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1824.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

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 wrogers{at}wpahs.org

	Abstract

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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 (156x250 µm 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.

Key Words: atherosclerosis • catheters • MRI

	Introduction

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Atherosclerotic 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 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 collagenous 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 17 18 19 20} Although there have been a number of studies showing the potential for MRI to visualize plaque components,^{11 21 22 23 24 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

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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 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.

View larger version (49K): [in this window] [in a new window]   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 color-coded 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.

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 µm in the phase direction and 156 µm in the frequency direction. Two signal averages were obtained, and images were interpolated to 256x256. 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-of-interest (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-µm 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 µm) 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 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 color-coded 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° inversion pulse. A similar ratio, the GRE-SE ratio, was constructed comparing the signal from GRE and SE sequences.

Statistical Analysis
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.

	Results

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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).

View larger version (61K): [in this window] [in a new window]   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).

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 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 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.

View this table: [in this window] [in a new window]   Table 1. IV-MRI Signal Properties of Atherosclerotic Plaque Components

View larger version (100K): [in this window] [in a new window]   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.

View larger version (92K): [in this window] [in a new window]   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.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
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 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 17 18 19 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 tracking^{32 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 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.

	Acknowledgments

 
This study was supported by a Sponsored Research Grant from Cordis/Johnson & Johnson.

Received November 10, 1999; accepted March 20, 2000.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Fuster V, Badimon J, Chesebro JH, Fallon JT. Plaque rupture, thrombosis, and therapeutic implication. Haemostasis. 1996;26:269–284.
2. Falk E. Why do plaques rupture? Circulation. 1992;86(suppl III):III-30–III-42.
3. Fernandez-Ortiz A, Badimon JJ, Faulk E, Fuster V, Meyer B, Mailhac A, Weng D, Shah PK, Badimon L. Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol. 1994;23:1564–1569.
4. Rekhter MD, Gordon D. Does platelet-derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques? Circ Res. 1994;75:410–417.[Abstract/Free Full Text]
5. Lee RT, Schoen FJ, Loree H, Lark MW, Libby P. Circumferential stress and matrix metalloproteinase 1 in human coronary atherosclerosis: implications for plaque rupture. Arterioscler Thromb Vasc Biol. 1996;16:1070–1073.[Abstract/Free Full Text]
6. Li Z, Li L, Zielke HR, Cheng L, Xiao R, Crow MT, Stetler-Stevenson WG, Froehlich F, Lakatta EG. Increased expression of 72-kd type IV collagenase (MMP-2) in human aortic atherosclerotic lesions. Am J Pathol. 1996;148:121–128.[Abstract]
7. Shanahan CM, Cary NRB, Metcalfe JC, Weissberg PL. High expression of genes for calcification-regulating proteins in human atherosclerotic plaques. J Clin Invest. 1994;93:2393–2402.
8. Ravn HB, Falk E. Histopathology of plaque rupture. Cardiol Clin. 1999;17:263–270.[Medline] [Order article via Infotrieve]
9. Fuster V. Human lesion studies. Ann N Y Acad Sci. 1997;811:207–225.[Abstract/Free Full Text]
10. van der Wal AC, Becker AE, van der Loos CM, Tigges AJ, Das PK. Fibrous and lipid-rich atherosclerotic plaques are a part of interchangeable morphologies related to inflammation: a concept. Coron Artery Dis. 1994;5:463–469.[Medline] [Order article via Infotrieve]
11. Toussaint JF, LaMuraglia GM, Southern JF, Fuster V. Kantor HL. Magnetic resonance images lipid, fibrous, calcified, hemorrhagic, and thrombotic components of human atherosclerosis in vivo. Circulation. 1996;94:932–938.[Abstract/Free Full Text]
12. Kim DK, Ceckler TL, Hascall VC, Calabro A, Balaban RS. Analysis of water-macromolecule proton magnetization transfer in articular cartilage. Magn Reson Med. 1993;29:211–215.[Medline] [Order article via Infotrieve]
13. Seo GS, Aoki J, Moriya H, Karakida O, Sone S, Hidaka H, Katsuyama T. Hyaline cartilage: in vivo and in vitro assessment with magnetization transfer imaging. Radiology. 1996;201:525–530.[Abstract/Free Full Text]
14. Henkelman M, Kucharczyk W. Optimization of gradient-echo MR for calcium detection. Am J Neuroradiol. 1994;15:465–472.[Abstract]
15. Tenner MS, Spiller M, Koenig SH, Valsamis MP, Childress S, Brown RD, Kasoff SS. Calcification can shorten T2, but not T1, at magnetic resonance imaging fields: results of a relaxometry study of calcified human meningiomas. Invest Radiol. 1995;30:345–353.[Medline] [Order article via Infotrieve]
16. Kantor HL, Briggs RW, Balaban RS. In vivo ³¹P nuclear magnetic resonance measurements in canine hearts using a catheter coil. Circ Res. 1984;55:261–266.[Abstract/Free Full Text]
17. Hurst GC, Hua J, Duerk JL, Cohen AM. Intravascular (catheter) NMR receiver probe: preliminary design analysis and application to canine iliofemoral imaging. Magn Reson Med. 1992;24:343–357.[Medline] [Order article via Infotrieve]
18. Martin AJ, Henkelman RM. Intravascular MR imaging in a porcine animal model. Magn Reson Med. 1995;32:224–229.
19. Atalar E, Bottomley PA, Ocali O, Correia LC, Kelemen MD, Lima JA, Zerhouni EA. High resolution intravascular MRI and MRS by using a catheter receiver coil. Magn Reson Med. 1996;36:596–605.[Medline] [Order article via Infotrieve]
20. Ocali O, Atalar E. Intravascular magnetic resonance imaging using a loopless catheter antenna. Magn Reson Med. 1997;37:112–118.[Medline] [Order article via Infotrieve]
21. Pearlman JD, Southern JF, Ackerman JL. Nuclear magnetic resonance microscopy of atheroma in human coronary arteries. Angiology. 1991;42:726–733.
22. Skinner MP, Yuan C, Mitsumori L, Hayes CE, Raines EW, Nelson JA, Ross R. Serial magnetic resonance imaging of experimental atherosclerosis detects lesion fine structure, progression and complications in vivo. Nat Med. 1995;1:69–73.[Medline] [Order article via Infotrieve]
23. Pearlman JD, Zajicek J, Merickel MB, Carman CS, Ayers CR, Brookeman JR, Brown MF. High resolution 1H NMR spectral signature from human atheroma. Magn Reson Med. 1988;7:262–279.[Medline] [Order article via Infotrieve]
24. Maynor CH, Charles HC, Herfkens RJ, Suddarth SA, Johnson GA. Chemical shift imaging of atherosclerosis at 7.0 Tesla. Invest Radiol. 1989;24:52–60.[Medline] [Order article via Infotrieve]
25. Soila K, Nummi P, Ekfors T, Viamonte M, Kormano M. Proton relaxation times in arterial wall and atheromatous lesions in man. Invest Radiol. 1986;20:411–415.
26. Schenck JF, Jolesz FA, Roemer PB, Cline HE, Lorensen WE, Kikinis R, Silverman SG, Hardy CJ, Barber WD, Laskaris ET, et al. Superconducting open-configuration MR imaging system for image guided therapy. Radiology. 1995;195:805–814.[Abstract/Free Full Text]
27. Berr SS, Brookeman JR. On MR imaging of atheromatous lipids in human arteries. J Magn Reson Imaging. 1995;5:373–374.[Medline] [Order article via Infotrieve]
28. Prophet EB, Mills, B, Arrington JB, Sobin LH, eds. Armed Forces Institute of Pathology Laboratory Methods in Histotechnology. Washington, DC: American Registry of Pathology; 1992.
29. Loree HM, Tobias BJ, Gibson LJ, Kamm RD, Small DM, Lee RT. Mechanical properties of model atherosclerotic lesion lipid pools. Arterioscler Thromb. 1994;14:230–234.[Abstract/Free Full Text]
30. Deleted from proof.
31. Arad Y, Spadaro LA, Goodman K, Lledo-Perez A, Sherman S, Lerner G, Guerci AD. Predictive value of electron beam computed tomography of the coronary arteries. Circulation. 1996;93:1951–1953.[Abstract/Free Full Text]
32. Aoki S, Nanbu A, Araki T, Ma X, Araki T, Kumagai H, Dumoulin CL, Darrow RD, Shimazu N, Tsukamoto T, et al. Active MR tracking on a 0.2 Tesla MR imager. Radiat Med. 1999;17:251–257.[Medline] [Order article via Infotrieve]
33. Unal O, Korosec FR, Frayne R, Strother CM, Mistretta CA. A rapid 2D time-resolved variable-rate k-space sampling MR technique for passive catheter tracking during endovascular procedures. Magn Reson Med. 1998;40:356–362.[Medline] [Order article via Infotrieve]
34. Adam G, Glowinski A, Neuerburg J, Bucker A, van Vaals JJ, Gunther RW. Visualization of MR-compatible catheters by electrically induced local field inhomogeneities: evaluation in vivo. J Magn Reson Imaging. 1998;8:209–213.[Medline] [Order article via Infotrieve]
35. Rivas PA, McConnell MV, Nayak K, Scott G, Meyer C, Pauly JM, Nishimura DG, Macovski A, Hu BS. Real-time intravascular magnetic resonance receiver probe: In vivo observations in the rabbit aorta. Proc Int Soc Magn Res Med. 1999;9:82. Abstract.

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