More than 50 to 60 million Americans have hypertension. While only approximately 2% to 5% of these patients have renovascular hypertension, this still represents a significant number of patients with a potentially treatable disease. There is a definite need for a cost-effective, noninvasive screening examination. The advent of innovative magnetic resonance imaging (MRI) technology has led the way for single breath-hold 3D contrast-enhanced magnetic resonance angiography (MRA) to potentially replace conventional angiography in many clinical instances. This technique is safe, accurate, noninvasive, and has the advantage of avoiding nephrotoxic iodinated contrast in the many patients with renal insufficiency and suspected renovascular hypertension.
Dr. Devane is a third-year resident at the University of
Alabama at Birmingham. He completed an internship in internal
medicine at UAB and his first year of radiology at the University
of Florida. He graduated from the University of Florida College
of Medicine and will begin his fellowship training in vascular
and interventional radiology at UAB in 2002.
Hypertension is one of the most prevalent diseases in the United
States, affecting an estimated 50 to 60 million people.
Renovascular disease is the most common potentially curable cause
of hypertension. While only 2% to 5% of hypertension cases have a
renovascular cause, this still represents a significant number of
patients. The need for a safe, cost-effective, noninvasive
screening examination is clear. Three-dimensional contrast-enhanced
magnetic resonance angiography (CE-MRA) has evolved into an
important diagnostic tool that may fulfill this need.
Causes and treatment options
Renovascular hypertension is caused by an arterial stenosis that
incites the renin-angiotensin system to increase glomerular
filtration. The angiotensin II that helps improve glomerular
vasoconstriction also causes peripheral vasoconstriction and thus
systemic hypertension. History and signs suggesting renovascular
disease include hypertension refractory to multiple medications,
new onset hypertension before age 25 or after age 55, or an
The two most common causes of renovascular hypertension are
atherosclerosis and fibromuscular dysplasia.
Atherosclerosis is the leading cause of renal artery stenosis,
primarily affecting the ostium, the proximal renal artery, or both.
This disease typically affects older patients. Fibromuscular
dysplasia affects a younger population, usually women between the
ages of 30 and 40 years. Unlike atherosclerosis, fibromuscular
dysplasia usually affects the mid and distal renal arteries.
Both forms of renal artery stenosis can be treated with
percutaneous transluminal angioplasty (PTA), without or with
stenting, often with varying degrees of success. Fibromuscular
dysplasia is generally considered more amenable to angioplasty than
atherosclerotic disease. Tegtmeyer et al
reported a 39% cure rate and 59% rate of symptom improvement for
patients with fibromuscular dysplasia treated with PTA. Surgical
revascularization such as splenorenal or aortorenal bypass are
therapeutic options for disease not amenable to angioplasty.
Accurate determination of disease presence and extent prior to
anticipated therapy can expediently direct patients to the
preferred mode of treatment, and can help avoid unnecessary
additional tests and procedures with their associated risks.
Diagnosis of renal artery stenosis
Conventional catheter angiography has historically been the gold
standard diagnostic test for renal artery stenosis. Unfortunately,
this test is expensive, invasive, and requires nephrotoxic contrast
material. Angiography can also overestimate or underestimate
disease because lesions cannot be viewed from more than one or two
perspectives. Furthermore, conventional an-giography does not yield
information about the physiologic significance of visibly narrowed
arteries; not all apparent stenoses produce hypertension.
The most commonly performed noninvasive functional test has been
captopril renal scintigraphy. The sensitivity and specificity of
this procedure have been reported to be 80% and 100%, respectively.
Captopril scintigraphy is less effective in patients with bilateral
disease or significant renal insufficiency. Scintigraphy also does
not provide anatomic information that can be crucial in planning
Some institutions use ultrasound to detect renal artery
stenosis, with variable and often limited success. Ultrasound is
highly operator dependent and is a technically difficult exam, even
with expert operators. Also, standardized methods and criteria for
stenoses have not achieved widespread acceptance.
CT angiography (CTA) is a promising emerging modality,
particularly with the advent of multidetector technology. CTA is
noninvasive and provides three dimensional information.
Unfortunately, like conventional an-giography, CTA exposes the
patient to radiation and to the risks of iodinated contrast, such
as nephrotoxicity and possible allergic reactions.
The various problems associated with all of the above modalities
make MRA an intrinsically appealing alternative, if it can provide
accurate information in a cost-competitive manner.
Magnetic resonance angiography
Prior to the development of 3D CE-MRA, the most commonly used
methods of MRA were non-contrast time- of-flight and phase
contrast. Time-of-flight MRA utilizes short TR (repetition time),
short TE (echo time), partial flip angle gradient echo techniques
to saturate signal from stationary tissue. Blood flowing into the
plane or volume of imaging is unsaturated and consequently produces
a much brighter signal. Flow signal from multiple different slices
can then be combined to create an image resembling an angiogram.
Though each individual slice can be acquired quickly, complete
studies can be time consuming.
Phase-contrast MRA works by subtracting background tissue from
the signal from flowing blood.
An accurate estimation of the velocity within the renal artery is
required, which is often difficult to accomplish.
It is also a time-consuming sequence, usually taking even longer
than time-of-flight techniques covering comparable territory.
The limitations of non-contrast time-of-flight and
phase-contrast techniques include artifact from breathing or other
patient movements, limited contrast to noise resolution, signal
loss from turbulence, and in-plane flow saturation.
Because of the oblique orientation of the renal arteries relative
to the aorta, and because of motion from breathing, renal MRAs
using these techniques are often disappointing. Only the proximal
renal arteries can be reliably imaged, and successfully identifying
accessory renal arteries can also be difficult (figure 1).
3D contrast-enhanced magnetic resonance
The advent of systems with improved gradient strengths and
software makes dynamic, contrast-enhanced MRA possible. This is a
3D spoiled gradient echo sequence which covers the entire territory
of interest in a single breath hold immediately following
intravenous (IV) administration of a gadolinium chelate contrast
material. Compared to non-contrast techniques, this method is very
fast, gives improved contrast-to-noise resolution, and virtually
eliminates motion artifacts in cooperative patients. Signal loss
from in-plane flow is eliminated, and signal loss from turbulence
is substantially reduced. The renal arteries have proven ideal
targets for this new technique. Multiple studies have shown 3D
CE-MRA to be both sensitive and specific in detecting renal artery
Gadolinium-based contrast agents solve many problems that plague
non-contrast MRA. Gadolinium causes marked T1 shortening, providing
a bright signal. The short TE/TR 3D spoiled gradient echo sequence
is very sensitive to these T1 shortening effects. If the sequence
is timed so acquisition occurs when the contrast bolus is highly
concentrated in the arteries, the result is a set of images in
which the arteries are the only bright objects. The images can then
be combined and reformatted in any plane, giving a truly
Gadolinium agents' advantages over iodinated contrast include
lack of significant nephrotoxicity in standard doses and extremely
low incidence of allergic reactions.
The lack of nephrotoxicity is important with the high incidence of
concomitant renal insufficiency in patients with renal artery
stenosis. Like iodinated contrast, IV gadolinium chelates remain
exclusively in the arteries for only a short period of time. To be
most effective, the MR sequence must be completed during a brief
interval between arrival of contrast in the target arteries and the
appearance of contrast in the nearby veins. This time frame is
usually under 30 seconds, thus requiring careful coordination
between contrast administration and scanning.
The basic sequence for 3D contrast-enhanced renal MRA is a three
dimensional spoiled gradient echo sequence with minimum TR and TE,
and medium-to-high flip angle (45 to 60 degrees). The imaging
volume is oriented in a coronal or coronal-oblique plane, reaching
from just above the celiac axis to the groin, with slices under 3
mm thick. On most modern high field magnets, this sequence can be
completed in under 30 seconds. Either a body coil or phased array
torso coil can be utilized. The patient is placed in the supine
position with arms elevated above the head to avoid phase wrap
artifact. Images are acquired during a single breath hold to limit
breathing artifacts that can severely degrade the images.
Supplemental oxygen may be helpful to increase breath hold
IV contrast consists of 0.1 to 0.2 mmol/kg gadolinium (some
institutions prefer to give every patient two bottles or 40 mL,
which is equivalent to 0.2 mmol/kg in many patients). The contrast
can be given with either hand or machine injection, though many
institutions prefer power injectors to improve consistency. The
timing of the bolus is crucial; there is not much margin for error
as venous enhancement occurs just seconds after the arterial bolus
reaches the kidneys, contaminating the images.
It is also important to understand the order in which data are
acquired during the study, in order to be sure that the key
portions of the sequence occur during optimal arterial enhancement.
"k-space" refers to the Fourier data acquired during the imaging
sequence. The center of k-space encompasses the low frequency data
which provides most of the image contrast, while the periphery of
k-space is the high-frequency data mostly responsible for image
detail. In MRA, it is important to acquire the center of k-space
during peak arterial enhancement. Two commonly utilized methods of
forming k-space data are sequential and elliptical-centric. The
elliptical-centric method samples near the center of k-space first,
providing the best chance of capturing only the arterial signal, if
the bolus of contrast was properly timed (figure 2).
Machines limited to sequential filling of k-space can still perform
high quality studies, though correct timing can be more
There are several commonly used methods for aligning the
contrast bolus with the acquisition of the center of k-space:
* Making a "best guess" estimate, which in most patients is
approximately 15 to 20 seconds. This is the easiest but runs the
greatest risk of being either too early or too late, which cause
artifacts that can complicate interpretation (figure 3).
* Giving a 1 to 2 mL test bolus of gadolinium while doing
sequential images at a fixed level in order to time the flow of
contrast from the injection site to the aorta.
The best time for beginning the sequence is then calculated
depending on the method chosen for filling k-space. An additional
minor limitation of this method is slight venous and parenchymal
enhancement can contaminate the subsequent arterial images.
* Using an automated bolus tracking technique (such as SmartPrep
[GE Medical Systems, Waukesha, WI] or Bolus Trak [Philips Imaging
Systems, Shelton, CT]) to detect contrast bolus arrival in the
aorta and trigger the scan.
* Performing serial preliminary scans at the level of the renal
arteries during injection of contrast and manually triggering the
actual MRA sequence when arterial enhancement occurs; this method
is commonly referred to as "MR fluoroscopy" (figure 2).
* Repeatedly performing a complete but very rapid MRA sequence
during and after contrast injection, analogous to conventional
digital subtraction angiography (DSA). This eliminates the need for
Additional features that can improve a CE-MRA study include
partial Fourier (or partial NEX) data sampling,
rectangular field of view, and zero fill interpolation. All of
these features can improve spatial resolution, temporal resolution,
or both, depending on what one chooses.
Post processing and image review
--Post processing and interactive review of images is a critical
component of CE-MRA. This requires using either a free-standing
workstation or the operating console of the MR scanner to view the
data from multiple perspectives and ultimately record images that
will be accurate and convincing for both the interpreting
radiologist and the referring clinician. Because a correctly timed
renal MRA has little or no signal from background tissue, there is
generally no need for time-consuming manual excision of surrounding
structures from the images. Total post-processing time is generally
less than 5 to 10 minutes.
Multiplanar reformatting is the simplest method for viewing the
data. Many workstations do this automatically, allowing the
radiologist to view slices of the data in coronal, axial, sagittal,
or oblique planes. The thickness of the reformats can be chosen by
the operator, with thin slices often being most useful in image
review. Axial reformats, in particular, are useful in identifying
accessory renal arteries and unusual branching patterns.
The most common way to record the images for final display is
with a maximum intensity projection (MIP) technique. An MIP image
is a two-dimensional image that maps the brightest pixels in the
data set from a given perspective looking through the entire data
volume. Darker pixels in front of or behind the arteries are not
included in the MIP display. Background tissue, which is mostly
dark pixels, will also not interfere. The result is an image that
looks like a conventional angiogram. Unlike a conventional
angiogram, however, the data are three-dimensional; a MIP image can
be rotated to view the vessels from any perspective.
Subvolume MIP images can be constructed from a limited volume
within the original full volume of data. This subvolume MIP can be
obtained in any desired plane to exclude overlapping arteries and
venous contamination. This technique is particularly useful for
renal MRA, as signal from the mesenteric, splenic, hepatic, and
lumbar arteries can obscure the renal arteries on full-volume MIP
displays. Subvolume MIPs can also help deal with venous
contamination by locating the volume behind the renal veins.
Subvolume MIP images are often especially effective at conveying
the study's information in a way that referring clinicians can
readily perceive and accept. The radiologist or technologist
performing the post processing should always be sure to record and
film the images that accurately reflect what the radiologist
reports in his or her interpretation (figures 4 and 5).
MRA data can also be displayed in a surface-rendering format
that can be used to analyze the internal or external surface of the
vessel wall. These displays are limited by their inability to
provide accurate information about the degree of stenosis, and are
not usually used for routing image interpretation. Workstations
with more advanced volume rendering capabilities can also be used
for MRA interpretation, but since CE-MRA does not have much signal
from nonvascular structures, there is little benefit.
Advantage and disadvantages
Three-dimensional CE-MRA is noninvasive, nonnephrotoxic,
provides images in three dimensions, and doesn't expose patients to
ionizing radiation. The 3D capability is a clear diagnostic
advantage over catheter angiography. In fact, many investigators
believe that in some instances MRA is just as sensitive, if not
more sensitive, than catheter angiography because of the
Overlapping vessels can be eliminated to demonstrate accessory
vessels and eccentric stenoses that could not be detected by
The noninvasive and safe nature of MRA appeals to both patients
and referring clinicians. Patients also appreciate that this study
can easily be completed within a routine 30 to 45 minute time slot,
avoiding the need for a night in the hospital, an observation
period, or even time away from work. Consequently, MRA may promote
increased referrals, leading to increased or earlier detection of
disease and, it is hoped, improved treatment of renal artery
stenosis (figures 6 and 7).
Although 3D CE-MRA provides accurate anatomic information about
renal arteries, the technique described above fails to provide
physiologic information about the significance of any detected
disease. Like catheter angiography, and unlike captopril renal
scintigraphy, MRA is an ana-tomic study. Some investigators favor
using phase-contrast MRA as an adjunct to CE-MRA in order to gain
more physiologic information. The presence of signal loss due to
dephasing on a phase-contrast study suggests that the stenosis is
The value of performing additional phase-contrast MRA is
controversial. It still does not prove that the patient has
renovascular hypertension, and its adds a significant amount of
time to the examination.
Some institutions perform captopril scintigraphy in addition to
MRA. Other institutions obtain only CE-MRA without a phase-contrast
study and either treat the patient based on anatomic information
alone or in combination with data from captopril scintigraphy. An
argument can be made that if two tests will always be necessary,
then catheter angiography should be pursued in all patients with a
positive captopril scintigram, making MRA unnecessary. The weakness
of this argument lies with the intrinsic weaknesses of the
captopril study, discussed above. Nevertheless, the limited
physiologic information provided by current MRA techniques leaves
room for future improvements, such as the possibility of combined
Currently the spatial resolution of DSA and CTA are superior to
that of MRA (1 mm
). Many investigators feel that the spatial resolution of MRA is
insufficient to evaluate for fibromuscular dysplasia and stenoses
in small branches and accessory vessels. Young patients with a
higher likelihood of having fibromuscular dysplasia may thus be
better served by catheter angiography, given current MR
capabilities. However, continued improvements in MR technology may
settle the issue in MRA's favor in the near future.
CE-MRA also requires skill, experience, and patience on the part
of both radiologists and technologists. The dynamic nature of the
examination, the precise timing required, and the differing
capabilities of different equipment necessitate attention to detail
and good communication among the MR imaging team. Some practice is
necessary before excellent images can be consistently obtained. The
equipment is expensive, with study working best on
state-of-the-art, high field magnets. Additional technologist
training may be necessary to perform the study reliably. Some
radiologists prefer to monitor the study in person and perform the
post processing themselves.
At our institution, we perform the study in about 30 minutes
with reformats and image interpretation requiring about 10 more
minutes. If the radiologist supervises the whole exam, this time
commitment may be comparable to performing a catheter angiogram.
However, once technologists become accustomed to the technique,
radiologist involvement during the scan can shrink substantially.
Similarly, experience with post processing can reduce the time
required for that component and technologists can be trained to
perform most of the post processing and filming.
The future of angiography
Some radiologists speculate on whether MRA will completely
replace catheter angiography, not only for renal arterial imaging,
but for all vascular imaging, including coronary angiography.
Limitations of spatial and temporal resolution with MRA make this
an unrealistic goal in the near future, though MRA may soon replace
diagnostic angiography for many indications. Renal and carotid
artery studies, and perhaps lower extremity runoff examinations,
are currently better suited for MRA than other types of vascular
studies, such as coronary imaging.
Much debate has arisen as to how MRA will impact the field of
vascular-interventional radiology. Many an-giographers feel it will
threaten their livelihood. It is clear that MRA will alter the
nature of the angiographer's business, though not necessarily in an
adverse fashion. Vascular-interventional radiologists can keep
themselves involved with diagnostic angiography by becoming
experienced with MRA. MRA may also identify more patients who could
benefit from percutaneous intervention, in addition to
noninvasively determining who will not benefit. Thus, the
interventional radiologist may see an increase in numbers of
patients referred for therapy, while the number of negative
diagnostic angiograms should drop. Both the patient and the
radiologist will thus benefit.
Three-dimensional breath-hold contrast-enhanced MRA is a safe,
noninvasive, and sensitive test for renal artery stenosis. When
utilized in patients with a high clinical likelihood of
renovascular hypertension, CE-MRA can provide highly diagnostic
images, leading the way to treatment by angioplasty or surgical
revascularization. Current limitations in spatial resolution reduce
MRA's value in diagnosing fibromuscular dysplasia and peripheral
stenosis. However, in older patients more likely to have
atherosclerotic disease, CE-MRA is a highly effective tool.
Patients with renal insufficiency or allergy to iodinated contrast
are ideal candidates for CE-MRA. With continuing technologic
improvements and development of techniques providing more
physiologic information, MRA is likely to become the test of choice
for most patients with suspected renovascular hypertension.
The author would like to thank Dr. Brian Jones for mentoring
this project and Dr. J. Kevin Smith for editorial assistance,
Anthony Zagar for photography, and Pat Moore for technical