With interventional magnetic resonance imaging (MRI), the anatomy and function of disease processes can be evaluated simultaneously. Both diagnosis and therapy can be performed without subjecting patients to the potential risks of ionizing radiation. Unlike other forms of interventional MRI, catheter-based applications can be performed using conventional magnets, allowing for widespread use. Pioneering research in atherosclerosis is one example of how catheter-based interventional MRI provides a new understanding of disease processes and therapeutic effects.
is currently a 4th-year Radiology Resident at Vanderbilt
University Medical Center, Nashville, TN. He received his MD from
the University of New Mexico in 1999. Prior to obtaining his MD,
he was involved in robotics research for 18 years, with the later
years focused on biomedical technology development. He owns four
U.S. patents. He will begin a 2-year Neuroradiology Fellowship at
the University of Utah, Salt Lake City in 2004.
Catheter-based interventional magnetic resonance imaging
(CBiMRI) is an emerging area of intense interest whereby
intravascular catheters are manipulated under magnetic resonance
(MR) imaging guidance for a variety of diagnostic and therapeutic
indications. Applications range from the treatment of patent
foramen ovale to gene therapies for cardiovascular disease.
CBiMRI not only allows visualization of the lumen of the blood
vessel, the vessel wall, and all aspects of the anatomy within the
field of view (FOV),
but also evaluates flow through the vessels
and function of the solid organs
supplied by the vessels. For example,
blood-oxygenation-leveldependent (BOLD) functional MRI takes
advantage of deoxyhemoglobin in areas of ischemia to establish
activation maps for investigating motor function recovery.
Although positron emission tomography is the gold standard, it is
limited by accessibility and it cannot be implemented for real-time
applications of catheter intervention. Computed tomography (CT) can
also be utilized for catheter interventions; however, radiation
exposure limits its use in the pediatric population. CT is also
limited in its ability to characterize soft tissue as compared with
MRI. In comparison, conventional catheter angiography shows the
vessel lumen well but provides little extravascular anatomical
detail--it has been described as lumenography.
Passive catheter tracking
CBiMRI is necessarily dependent on tracking the catheter tip, as
is conventional angiography. Passive localizing and tracking a
catheter is best accomplished by using MR projection imaging in a
fashion analogous to conventional X-ray angiography.
This is accomplished by using a thick imaging slice, thus
optimizing the probability that the catheter or vessel will fall
within the imaging FOV. One method of catheter tracking is
accomplished using a two-dimensional (2D) inversion recovery
(IR)prepared fast low-angle shot (FLASH) spoiled gradient-echo
sequence (Figure 1). Several methods for passively visualizing the
catheter itself include filling the catheter with contrast, filling
a balloon on the catheter tip with carbon dioxide to generate a
void, or placing contrast within the balloon.
Active catheter tracking
Active catheter tracking is implemented by incorporating a
radiofrequency coil or antenna into an interventional device, such
as a guidewire or catheter.
An example of a multicoil catheter is provided in Figure 2. The
term "active" implies that the catheter and/or guidewire are
generating a signal as a direct result of the increased signal
generated from the guidewire or radiofrequency (RF) coil. Catheter
position within the 2D projection slab can be "visually" monitored
based on the strong signal detected by
this coil (Figure 3).
Active tracking can also have a very different meaning; rather
than just allowing visualization of the catheter, one can generate
spatial coordinates for the catheter position in three-dimensional
(3D) space and register with the MR image set for visualization.
The small MRI receive coils incorporated into the catheter generate
transverse spin magnetization when the transmit coil (typically,
the body coil) emits a nonselective RF pulse. The resultant MRI
signal from the small tracking coils is detected. The MRI signal is
then processed to determine the X, Y, and Z coordinates of the
coils. This information can then be registered with the MR
Although active catheter tracking produces a strong MR signal and
high temporal resolution, there are several practical limitations.
Adding a coil to the tip of a catheter can alter its mechanical
which can impede catheter movements within tortuous blood vessels.
Only the portion of the catheter or guidewire possessing the RF
receiver coil will be imaged, and buckling of the nonvisualized
portions of the catheter may impede manipulation or may cause
injury. Active methods may also cause tissue heating due to the RF
coils placed within the body.
Theory and experiments have shown an electric-fielddependent
heating of the ends of long wires of as much as 6°C.
found increases in the guidewire tip temperature from 26°C to 74°C
after 30 seconds of scanning in a 1.5T magnet, presumably resulting
from resonant waves within the wire. Still others found a 17°C
increase in temperature with nitinol wires in a 1.5T magnet.
Temperature increases of this magnitude can injure tissue and cause
blood coagulation, which is why many researchers have investigated
alternatives to metallic wires. Quarter-wavelength chokes are
proposed to remedy the heating problem.
Clinical experience with CBiMRI has primarily taken place within
the European research community. Two such examples follow.
Congenital heart disease diagnosis and therapy
Congenital heart anomalies have a reported incidence varying
from 3 to 12 per 1000 live births, depending on the methods used
for detection and diagnosis. Ventricular septal defects are the
most common at 29%. A child who is born with cyanosis will be
diagnosed promptly with a congenital heart defect because of
clinical presentation. Heart disease may go undiagnosed for years
in asymptomatic patients. The most common defect with associated
cyanosis is tetrology of Fallot.
Current methods of diagnosis rely on conventional angiographic
techniques that can result in substantial radiation exposure.
Recent research has shown the need to reduce radiation exposure,
especially in children to minimize the probability of developing
radiation-related neoplasms later in life.
One pooled study reported a linear relationship between exposure
and relative risk of thyroid cancer in children younger than 15
years of age.
Research also showed that radiologic studies as low as 0.1 Gy
result in a statistically significant increase in relative risk for
subsequent thyroid cancer development.
used a combined X-ray fluoroscopy and MR imaging (XMR) to carry out
cardiac catheterization on children and adults with congenital
heart disease, with the goal of decreasing radiation exposure and
utilizing flow and cardiac motion information provided by MRI to
improve on diagnostics and therapy. Eight diagnostic cardiac
catheterizations, 1 device closure of atrial septal defect, 1
intracardiac coil occlusion, and 2 radiofrequency ablations for
tachycardia were performed. Catheters were placed in all chambers
of the heart and great vessels by MR guidance, with the tip of the
catheter visualized by means of passive contrast from a carbon
dioxide balloon. Using a movable tabletop, researchers moved the
patients between a 1.5T Philips Intera 1-T MRI scanner and a
Philips Pulsera cardiac X-ray unit (both products from Philips
Medical Systems, Bothell, WA) that were co-located. Because the MR
flexible coil arrays are sufficiently radiotranslucent, they could
be left in place during X-ray imaging without image quality
degradation. The Intera MRI system provided 10 to 20
frames-per-second imaging for passive catheter tracking with a
carbon-dioxidefilled balloon at the catheter tip by using
MR-compatible catheters without guidewires. Three-dimensional
imaging, flow quantification, and myocardial motion assessment
provided clinically useful information not otherwise available by
using conventional angiographic techniques. Figure 4 shows passive
catheter manipulation under MR guidance. Razavi
found that radiation exposure was significantly decreased while
clinically useful information regarding flow and cardiac motion was
provided that would otherwise not be available using conventional
Diagnosis and therapy of atherosclerosis
Heart disease and stroke, the principal sequelae of cardiovascular
disease, are the first and third leading causes of death in the
United States, accounting for >40% of all deaths. Approximately
950,000 Americans die of heart disease or stroke each year, which
amounts to 1 death every 33 seconds. Atherosclerosis is by far the
most common cause of arterial stenosis. Although new developments
continue to shed light on the pathogenesis, one of the most widely
accepted hypotheses, formulated by Ross,
explains atherosclerosis as a response to injury. Atherosclerosis
produces symptoms through blood flow reduction, thrombotic
occlusion, plaque ulceration with distal embolization, and, rarely,
by penetration into the media.
Atherosclerotic disease of the iliac arteries is typically
diffuse and bilateral with clinically significant disease in the
distal aorta extending into the common iliac arteries. The disease
is unusual in people younger than 40 years, and men are more
frequently affected than women.
Current methods of therapy include medical management for
patients with mild to moderate claudication or interventional
methods. Interventional methods include conventional balloon
angioplasty and stenting or surgical graft placement. The choice
between percutaneous methods or surgery depends on the nature and
location of the stenosis. Studies have shown that iliac stenosis
can be treated with percutaneous angioplasty with a 95% technical
success rate and 1- and 3-year patency rates of 80% and 70%,
respectively. With conventional stent placement, the patency rates
improve to 90% and 85%, respectively.
To assess the feasibility of MR-guided stent placement, Manke
studied the treatment of focal iliac stenoses in patients with
chronic limb ischemia by using passive catheter-tracking in a
conventional 1.5T magnet. Even though the mean degree-of-stenosis
after stent placement was significantly higher at contrast-enhanced
MR angiography than at digital subtraction angiography (DSA) (24.6%
versus 6.2%) and the mean procedure time was 74 minutes, Manke
successfully treated the iliac stenoses in 10 of 13 patients by
using MR imaging-guided intervention alone. The other 3 patients
were treated with additional fluoroscopic guidance, because
complications (ie, panic attack, subintimal recanalization, and
stent misplacement) occurred with MR guidance. Postprocedure stent
placement evaluation using MR angiography was expectedly limited
owing to stent-induced signal loss of the lumen (Figure 5).
Manke et al
used a 1.5T MR imaging unit (Magnetom Symphony; Siemens, Erlangen,
Germany) with a circular polarized, phased-array body coil. Coronal
contrast-enhanced 3D fast imaging with steady-state precession MR
angiography was used to verify the intraluminal position of the
catheter and localize the stenosis (Figure 6), as well as for
post-interventional evaluation. Stent placement and balloon
angioplasty were monitored with a 2D fast low-angle shot (FLASH)
sequence with flow compensation. The acquisition time for a single
section was 1.88 seconds per image, with a delay of approximately
0.5 second between acquisition and display.
One promising area for future CBiMRI research is in diagnosis
and treatment of atherosclerotic disease. A substantial amount of
work has already been undertaken to improve imaging of the disease
with using conventional and catheter-based imaging, although this
research will not be discussed here.
Neovascularity is thought to be involved in the pathogenesis of
New theories, based on pathologic studies, have shown an
association between the degree of neovascularity and the presence
of inflammatory cells.
With neovascularity, inflammatory cells are recruited to form the
lipid core of a plaque.
The presence and degree of neovascularity within unstable plaque
are potential markers for vulnerability.
Contrast-enhanced MRI of the carotid arteries provides
significant differentiation of neovascularity from other
nonvascular regions within unstable carotid plaques.
In addition, MRI identification of fibrous cap rupture (Figure 7)
is strongly associated with patients who have a recent history of
transient ischemic attack or stroke.
Using a modified American Heart Association classification for
carotid plaque, researchers have demonstrated that high-resolution
MRI can detect characteristics of vulnerable plaque with a high
degree of sensitivity and specificity,
such as: a thin or ruptured fibrous cap, a large lipid or necrotic
core, and intraplaque hemorrhage. Quantification of the degree of
based on dynamic contrast enhanced studies, provides a means for
prospectively studying the link between neovasculature and plaque
Conventional MR imaging has some limitations because most
arteries are internal to the body at a distance from the skin
surface, where surface coils provide limited benefit. To address
this issue, investigators such as Hillenbrand et al
(Figure 8), Qiu et al
(Figure 9), and others have studied high-resolution imaging of the
vessel walls with intravascular imaging coils incorporated into a
conventional catheter. Promising improvements can be seen in
vessel-wall definition with resolution on the order of several
Various options for therapy exist to treat carotid
atherosclerosis. Medical management, including cholesterol-lowering
therapies, has been explored.
In a prospective study of 18 patients, atherosclerotic plaques
showed regression in size after Simvastatin (Merck Pharmaceuticals,
Darmstadt, Germany) therapy by using high-resolution MR. Reduction
in plaques occurred after
12 months of therapy without significant change in the lumen
diameter. This supports the hypothesis that lipid-lowering
medications help to stabilize the plaque. This study also helps to
explain why prior conventional catheter angiographic studies showed
minimal change in lumen diameter in patients after
The physiologic changes were occurring within the vessel wall, not
visualized with conventional angiography.
Gene therapy is also being investigated to treat
Using catheter-based delivery, researchers are performing
efficient, high-dose transfer of genes into the endothelial cells
and smooth muscle cells of the target vessels during balloon
angioplasty while minimizing any undesirable systemic transfection.
Prior in vitro studies showed improved transfection by using a
specialized catheter with application of heat.
The intravascular heating coils also provide for high-resolution
intravascular imag-ing as has been shown by Qiu et al.
Researchers positioned a 0.032-inch MRI guidewire along with a 5F
balloon and a 0.6-mm fiber-optic temperature sensor, into the aorta
of each of 6 New Zealand white rabbits (Figure 10). Then, while
inflating the balloon with saline, researchers heated the targeted
aorta for 20 minutes by operating the catheter microwave generator
at 20 to 25 W, resulting in a temperature increase to 41°C at the
target aortic wall. High-resolution axial and sagittal images were
obtained in a 1.5T MRI system (GE Medical System, Milwaukee, WI).
During MR imaging, the MRI was connected to the MRI preamplifier
and operated in the receive-only mode for high-resolution imaging.
In early studies using gene therapy, Qiu et al
have demonstrated longer-term vessel patency in the gene-therapy
treated iliac arteries with atherosclerosis as compared with the
contralateral iliac artery treated with angioplasty alone.
Catheter-based interventional MRI is proving to be a powerful
tool in the diagnosis and therapy of vascular and cardiac diseases.
Treatment of congenital heart disease in the pediatric population,
in particular, is one application that provides a great benefit
while minimizing the hazards of ionizing radiation. Recent
developments in high-resolution imaging of atherosclerotic disease
are creating avenues for evaluation of disease progression and
therapeutic options. In addition, new developments in gene therapy
may provide an option that could augment conventional medical and
interventional methods by providing local genetic transfection to
reverse atherosclerosis. As has been shown, CBiMRI can be
implemented with conventional MRI systems (without the need for the
open-MRI magnets), allowing for widespread use. Increased research,
technology development, and clinical application can be expected in
the future. More research into safety issues will help to ease the
technology into clinical application.
The author wishes to thank Drs. Joseph M. Aulino, Peter Bream,
Thomas Dina, and Theodore Larson for their valued, thoughtful
review of the manuscript. Special thanks are extended to Charles
Dumoulin for providing a figure, and to Martha Tanner and John
Bobbitt for providing assistance with the figures.