Magnetic Resonance Imaging for Restenosis
Robert Jan M. van Geuns, MD , P h D and Timo Baks, MD
C
ONTENTSI
NTRODUCTIONS
AFETY OFS
TENTSS
TENTR
ELATEDA
RTEFACTSMR F
LOWM
EASUREMENTSMR C
OMPATIBLE(T
RANSPARENT) S
TENTSS
UMMARYR
EFERENCES17
INTRODUCTION
Magnetic resonance imaging (MRI) of the coronary arteries is a difficult subject.
Owing to the motion of the heart during contraction and respiration artefact free imag- ing needs extremely fast techniques that MRI does not fully qualify yet. However, con- stant progress is made (1) and with electrocardiography triggering and respiratory motion correction techniques, submilliter resolution can be achieved with reasonable acquisition times (2). Only one study focussed on the use of magnetic resonance (MR) coronary angiography techniques for the detection of restenosis after coronary angioplasty (3). In this study, in which 118 patients after percutaneous transluminal coronary angioplasty were investigated, sensitivity for restenosis detection was 73%
(11/15) and specificity was 49%. Overall accuracy was 53% for MRI, which was sig- nificantly (p = 0.014) lower compared with electron beam computed tomography.
Unfortunately, MR coronary angiography of restenosis is currently hindered by the obligatory use of coronary artery stents to decrease the incidence of restenosis. Still MRI for the detection of restenosis is being performed using different alternative tech- niques and this subject will be reviewed in this chapter.
SAFETY OF STENTS
Coronary artery stents have demonstrated their efficacy as additional treatment in angioplasty, initially for treatment of abrupt vessel closure or dissection, but later also for reducing restenosis as demonstrated in the STRESS and BENESTENT studies (4,5).
From: Contemporary Cardiology: Essentials of Restenosis: For the Interventional Cardiologist Edited by: H. J. Duckers, E. G. Nabel, and P. W. Serruys © Humana Press Inc., Totowa, NJ
277
Since then stents have been used in more than 80% of percutaneous coronary interven- tion (PCI) procedures in 2000 and presently this approaches 100%. As most stents are produced of 316 low-carbon Stainless steel, safety in MRI scanners has always been an issue. First, the magnetic field deploys a force on the stent depending on the static magnetic field strength (usually 1 or 1.5 T, in the future 3 T) and the applied gradients during the examination (6), the materials used (degree of ferromagnetism), the mass of the implant used, and the location and orientation relative to the magnetic field. These induced forces may in theory lead to displacement of the stent. Nevertheless these forces are much smaller then those used during implantation or those that the stents experience during motion of the heart at the time of contraction (7). The second issue is heating because stents are closed loops of conductive low-ferromagnetism materials and rapid changing magnetic forces can induce electrical currents that can cause local heating. Thermal injuries during MR examination associated with electrical monitoring devices have been described (8). Radiofrequency (RF) pulses used are a second source of heating. Several studies have evaluated the heating effects in MR scanners, in one study on a nitinol-based guidewire, temperature rose by a maximum of 48°C in a phan- tom (9,10). Heating of MR tracking catheters has also been reported (11), although to a lesser degree. Studies on coronary artery stents on the other hand showed a maximum rise of 0.3 °C in one study (12) and no significant heating effects in another (7,13,14).
This is explained by the length of the conducting material used and by flow phantoms that allow some cooling by continuous refreshment of the blood within the stent.
MRI after stent implantation is considered to be safe once endothelialization has occurred (15), because endothelialization presumably opposes possible dislodgement (16,17). Actual patient information on the Internet by the American Heart Association advises to postpone MR imaging till 4 wk after the procedure. On the contrary, the American Heart Association Diagnostic and Interventional Catheterization Committee does not preclude MRI in the presence of coronary stents when it is clinically indicated (18). Additionally, Gerber et al. (19) have demonstrated in a retrospective clinical trial the safety of MRI within 8 wk (median of 18 d) after stent implantation in 111 patients;
no stent thrombosis or cardiac death occurred within 30 d. Recent studies in celltrans- plantation mostly treated with PCI including stent implantation, using repetitive MRI measurements (TOPCARE-AMI and BOOST, mean 4.7 and 3.5 d postPCI, respectively) showed no adverse events (20,21). Supported by these last studies no restrictions on MRI after coronary stent implantation are applied in the institution.
STENT RELATED ARTEFACTS
Currently, the majority of coronary stents are nonferromagnetic and considered MRI safe as explained earlier, but stents remain the source of image artefacts owing to local magnetic field inhomogeneities and provoked eddy currents in the conductive material of the stent, hampering image interpretation. The size of the artefacts is dependent on the materials and imaging sequences used. Here in principle Spin-echo techniques and its derivatives show significant smaller artefacts than gradient echo-sequences (7).
Comparing 14 different stents lumen was visible in all except one colbalt stent, and in
10 of the 14 stents artificial lumen narrowing was less than 33%, using a contrast
enhanced magnetic resonance angiography sequences that can be considered standard
for noncoronary angiography (22). Best results were obtained with Nitinol (a
nickel–titanium alloy) and Tantalum stents, although within the Nitinol stents a variable
appearance was observed depending on the stent geometry. Artefacts are reduced by
using short echo-times wherein the shorter echo-times in gradient-echo sequences can compensate for the increased sensitivity of GE imaging to field inhomogeneities. Besides the materials and techniques used it was shown that the angle β to B0 was the main fac- tor that influenced the artefact size, with a larger angle increasing the artefact in a non- linear relationship (23–25). As artefacts hamper lumen visualization on most MRA and all MR coronary angiography techniques after current stent treatment, alternative analy- sis techniques and stent material and design are being investigated.
MR FLOW MEASUREMENTS
A very attractive tool in MRI is the ability to noninvasive measure flow with dedi- cated MR flow sensitive techniques. This has been used to quantify valve regurgitation and stenosis (26) and is frequently used in congenital heart disease (27). The same technique has been used to quantify flow in the coronary arteries and detection of flow- limiting stenosis in native coronary arteries (28–30) and bypass grafts (31–33) using vasodilatators. In these settings a reasonable sensitivity and specificity for graft func- tion has been obtained. Hundley et al. (34) used these flow techniques to measure flow reserve in patients with recurrent angina after balloon angioplasty. For a flow reserve of less than 2, 100% and 82% sensitive and 89% and 100% specific, detecting a luminal diameter narrowing of less than or equal to 70% and 50%, respectively was achieved (Table 1). The same approach was used by Saito et al. (35) for the detection of instent restenosis, with the modification that flow was measured just distal from the stent to avoid the imaging artefact related to stainless steel stents. They demonstrated that flow could accurately be measured just distal to the stent (Fig. 1). Nagel et al. (36) studied 38 patients after successful PCI with stent deployment with this approach and coronary flow velocity reserve with MRI similar to Doppler results (r = 0.87), with a mean rela- tive difference of 7.5%. Using a threshold of 1.2 for coronary flow velocity reserve, a sensitivity of 83% with a specificity of 94% was achieved for more than or equal to 75% stenoses. In both these studies imaging was limited to the proximal vessels and left anterior descending coronary arteries were nearly exclusively included, addition- ally, patients with suspected microvasculare disease were excluded.
MR COMPATIBLE (TRANSPARENT) STENTS
Metallic stents signal attenuation within the stent is caused by RF (RF shielding) of the metallic stent material. Induced eddy currents in the stent may also lead to a lower nominal RF excitation angle inside the stent (37,38). Only with large-diameter nitinol stents in the iliac arteries have sufficiently small artefacts been reported to allow diag- nostic follow-up, either by standard MRA (39) or by increasing the excitation angle of the MRA sequence (23). As the material of stent is of great influence on stent artefact,
Table 1
Sensitivity and Specificity of MR Coronary Flow Measurements for the Detection of Restenosis After PCI
Restenosis Year Treatment Patients Sign Sensitivity Specificity
Hundley 2000 Ballon 17 ≤50% 82 100
Saito 2001 Stent 10 – – –
Nagel 2003 Stent 38 ≥75% 83 94
a quest for metal alloys with minimal artefacts was started to develop a truly MR trans- parent stent. One alloy consisting of copper (75%), silver (8%), platinum (2%), gold (14%), and palladium (1%) was proposed to minimize susceptibility artefacts (40).
The examined prototypes of fully MR-compatible MRI stents allowed artefact-free visualization of the stent lumen with phase-contrast and contrast-enhanced T1-weighted angiography, as well as phase-contrast flow measurements in the stented area (41).
As copper can induce an inflammatory reaction causing in-stent restenosis, the large amount in this alloy is worrying, but biocompatible coatings of the MR stent may solve this problem. Another alloy proposed by van Dijk et al. (42) consists mainly of palla- dium and silver and is iron- and nickel-free. The mechanical properties of ABI alloy resemble Stainless steel. Using 2D and 3D gradient echo sequences artefacts of this ABI alloy stent was significantly smaller than Nitinol or Tantalum stent. So far only a simple helix has been built out of this material.
The BIOTRONIK absorbable metal stent (BIOTRONIK, Bulach, Switzerland) is a
magnesium alloy stent that undergoes degradation over 2- to 3-mo period after deploy-
ment. This stent is reported compatible with MR angiography. As the stent is absorbable
their use does not require prolonged antiplatelet therapy and neointimal proliferation,
restenosis, and chronic inflammation may be reduced. Recently, results from a first-
in-man BEST BTK trial, in which absorbable metal stents were implanted below the
knee were reported (EuroPCR2004). Between December 2003 and January 2004, 63
patients with critical limb ischemia were enrolled just before limb amputation
Fig. 1. (A) Definition of slice location for MRI blood flow measurements in the LAD artery on dou- ble oblique scout magnetic resonance imaging (MRI) images. (B) Magnitude and phase-difference images acquired with fast velocity-encoded cine MRI acquisition. (C) MRI blood flow velocity curves in the LAD artery before and after intravenous injection of dipyridamole. Reproduced from ref. 35.(Rutherford 4 and 5). At 3 mo, 89% of the stented vessels remained patent and a ran- domized trial is planned by the company. One limitation is that the magnesium alloy is not visible on fluoroscopy, which is partly resolved by two markers on the balloon that guide the procedure. With this kind of stent, instent thrombus has been identified for the first time noninvasively (43) (Fig. 2).
Another interesting approach to visualize the stent lumen is to use the stent as a receiver coil itself (44). To achieve this stents need to be designed to act as active reso- nant structures at the Larmor frequency of the MR system. The stents thus acted as local RF signal amplifiers. The first generation used a coaxial cable to transport the signal to the scanner system. However, such a cable-based approach for high-resolution in-stent imaging is invasive and thus is limited to the time of the intervention. Follow- up studies would be difficult to achieve, because the approach requires electrical con- tact between the stent and the MR scanner, and hence repeated invasive access. In a more sophisticated way, Quick et al. (45) employed the principle of inductive coupling wherein the B(1) fields of the stents were coupled to that of an outside surface coil.
Thus, the signal from the stent antenna could be wireless and received by a surface coil connected to the MR system (Fig. 3). This concept has been tested in vitro and in vivo and a near 30 times improvement in signal intensity in the stent lumen has been demon- strated. Unfortunately, several limitations are to be noted. First, low flip angle sequences were necessary as transmit flip angles were also amplified and artefacts were intro- duced owing to inhomogeneity of the B1 field of the stent.
Fig. 2. In vivo magnetic resonance imaging of Gd-labeled fibrinogen clots. (A,D) Coronary MRA before (A) and after (D) thrombus delivery. On both scans, no apparent thrombus is visible (circle).
(B,E) Black-blood inversion recovery TFE scans before (B) and after (E) clot delivery (same view as A and D). After thrombus delivery (E), 3 bright areas are readily visible (arrows and circle), consis- tent with location of thrombus. No apparent thrombus was visible on prethrombus (B) images (arrow and circle). (C) X-ray angiogram confirming MR finding of thrombus in mid-LAD (circle). (F) Magnified view of C. LM indicates left main. Reproduced from ref. 43.
Additionally, the use of RF-intensive sequences potentially by this amplification can
lead to local concentration of RF energy (hot spots) in the vicinity of the stent, which
could result in heating of surrounding tissues. Decoupling, i.e., detuning of the resonant
structure during RF transmission, would decrease the potential risk of RF heating, and
can be achieved passively by incorporation of additional electronic elements (e.g.,
Fig. 3. (A) Photograph of a solenoidal stent prototype (length 35 mm, inner diameter 4 mm). The 14- turn solenoidal stent mesh was tuned with a chip capacitor (arrow) to the resonant frequency of the scanner. (B) Photograph of a balloon-expandable self-resonant stent prototype (length 28 mm, inner diameter before/after expansion 1.8/4 mm); stent in the folded state, (C) stent mounted on a 5F bal- loon catheter (balloon 40 × 4 mm2) after full inflation of balloon, (D) fully deployed stent, and (E) MR image acquired with the stent immersed in an NaCl phantom acquired with the following sequence: FLASH 2D sequence, TR/TE = 200/11 ms, flip = 2°, FOV = 60 × 60 mm2, matrix= 512 × 512, slice = 2 mm2, time= 1:44 min, in-plane resolution 117 × 117 m2. Reproduced from ref. 45.crossed diodes) in the design. Second, optimal stent design for balloon-expandable delivery is more difficult and the redesigned solenoidal design with a zigzag pattern of the stent wire resulted in local signal cancellations (Fig. 3). Third, the stents should be coated with a polymer to guarantee electric isolation from the surrounding tissue and blood, otherwise electricity and therefore signal may be lost. One author performed a study on heating of coronary artery stents with the intention to induce cell necrosis and thereby restenosis (46). Afterwards with maximum energy power output they were able to raise the temperature of the stent to 80
°C with necrosis on microscopy.
SUMMARY
In the past coronary artery stents where regarded as possible contraindications for MRI.
Additional safety studies have resolved this issue and MRI is now frequently performed even within the first days of implantation. Artefacts related to the stent hinder image inter- pretation but flow measurement just distal of a stent have proven to be able to detect sig- nificant instent restenosis. More recent development includes MR transparent stents and in the future, stent might serve as local imaging coils to increase signal to noise ratio.
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