When the use of contrast media was first introduced into the clinical practice of magnetic resonance (MR) imaging, it was used exclusively for central nervous system (CNS) applications. Over time, its use was expanded to include spinal and head and neck imaging as well. With the recent advances in MR technology, particularly high-performance magnets and power injectors, more advanced applications have come into practice. These commonly used clinical applications--many of which are off-label indications--include perfusion imaging, contrast-augmented MR angiography (MRA), breast imaging, cardiac imaging, and a variety of body applications including liver, kidney, and pelvic imaging.
This presentation will provide a brief overview of several of these advanced clinical applications of MR contrast agents, with particular attention to the use of power injection.
Lawrence N. Tanenbaum, MD Assistant Professor,
Neuroscience, Seton Hall University, and Section Chief,
Neuroradiology, MRI & CT at the New Jersey Neuroscience
Institute, JFK Medical Center, Edison Imaging Associates,
Edison, New Jersey
When the use of contrast media was first introduced into the
clinical practice of magnetic resonance (MR) imaging, it was used
exclusively for central nervous system (CNS) applications. Over
time, its use was expanded to include spinal and head and neck
imaging as well. With the recent advances in MR technology,
particularly high-performance magnets and power injectors, more
advanced applications have come into practice. These commonly used
clinical applications--many of which are off-label
indications--include perfusion imaging, contrast-augmented MR
angiography (MRA), breast imaging, cardiac imaging, and a variety
of body applications including liver, kidney, and pelvic
This presentation will provide a brief overview of several of
these advanced clinical applications of MR contrast agents, with
particular attention to the use of power injection.
Power Injection Issues
The use of power injection of contrast media for MR imaging
brings additional concerns to the clinical setting. The most
important consideration is that of restricted patient access.
Typically during power injection, the patient is fairly deep in the
bore. Although the magnets in today's MR units are not as long as
they used to be, the patient is often some distance from the
clinician as the agent is being rapidly injected. This distance,
combined with the fact that extravasation may occur at a point
distant from the injection site, makes patient monitoring a
challenge. Use of a non-ionic contrast agent, which is generally
less toxic to the tissue, may help reduce the adverse effects of
extravasation. In general, a lower-viscosity agent will require
lower pressures to achieve rapid injection rates and, consequently,
may be better tolerated.
A second consideration with the use of power injection is the
need for very high patient tolerance since many of these images
will be first-pass studies, e.g., a study of the arterial phase in
the liver or a first-pass study of contrast through the vascular
tree. Any local adverse effect or intolerance by the patient will
most likely ruin a first-pass study.
To address these clinical concerns, clinicians need to consider
several agent-specific attributes when choosing a gadolinum-based
contrast agent for rapid injection. Agents that are non-ionic and
low osmolar will result in fewer negative inotropic changes. This
is particularly important for cardiac patients. Low-viscosity
agents require less pressure to inject and allow for the use of
smaller gauge needles and catheters. Gadolinium-based contrast
agents with a cyclic molecular structure also have greater
stability and, therefore, less potential for the release of free
gadolinium into the body. This can be a concern over time in
patients subjected to repeated injections, however, the role of
free gadolinium is beyond the scope of this presentation.
Perfusion Imaging Studies
In recent years, perfusion imaging has become an essential tool
in the radiologic armamentarium. It is used in the characterization
and surveillance of brain neoplasm, the diagnosis of stroke and
ischemia, and has indications in neuropsychology and psychiatry, as
well as cardiology.
Perfusion imaging requires a rapid bolus injection of contrast
agent. At our institution, we typically use a power injection rate
of 3 to 5 mL/sec for perfusion studies. Some institutions use
injection rates as high as 10 mL/sec.
Figure 1 illustrates a typical scenario in which perfusion
imaging can be beneficial in the diagnosis of a patient with a
treated brain neoplasm. In this case, MR images reveal high T2
signal, significant mass effect, and edema. A non-specific area of
blood-brain barrier breakdown is also visible. Spectroscopy, which
is often used in such circumstances, shows elevation of the choline
peak. These findings are all suspicious for residual tumor. The
critical question is, "Are these simply postoperative changes,
signs of radiation necrosis, or is there residual viable tumor
Perfusion imaging can help answer that question. A
pixel-by-pixel perfusion map of the negative susceptibility
enhancement curve reveals a ring of increased capillary density
corresponding to the area of blood-brain barrier breakdown. This is
a very compelling sign; in a generally hypovascular field, this
ring of increased capillary density is indicative of vital tissue.
In this case, not only was radiation necrosis present, but
perfusion imaging revealed clear evidence of associated viable
In addition, perfusion imaging is often superior to blood-brain
barrier breakdown imaging for assessment of lesion extent,
particularly in cases involving primary brain tumors. Such tumors
can have a degree of intact blood-brain barrier and, consequently,
the enhancement seen in traditional studies may underestimate the
extent of such lesions.
Figure 2 illustrates the case of a patient with a high-grade
glioma. A blood-brain barrier breakdown study performed with fat
suppression reveals a relatively unimpressive area of blood-brain
barrier breakdown. With perfusion imaging, however, the lesion is
far more striking and extensive. This particular tumor is much more
impressive in its density of vascularity than in its integrity.
Stroke and Ischemia
Perfusion imaging can be used to assess the volume of ischemic
brain in patients who present with brain attack or acute stroke.
Results of a first-pass imaging study can provide an assessment of
relative cerebral volume and mean time to enhance, providing an
estimation of how much of the brain tissue is ischemic.
With mild alterations in flow, abnormally prolonged transit time
is typically seen. As the flow alterations become more severe, it
may manifest on a cerebral blood volume study as an area of
compensatory increase. In the most severe cases, often correlating
with frank infarction, a decrease in cerebral blood volume is
Figure 3 shows the initial presentation of a patient who had
suffered an internal carotid artery occlusion and small stroke. The
mean-time-to-enhance map shows prolonged transit to the middle and
anterior cerebral artery territory with very low perfusion in the
actual area of infarcted brain. Several days later, after
ineffective intervention, there was significantly more extensive
volume of infarcted brain tissue, closely approximating the initial
volume judged to be at risk.
Perfusion imaging is also used in neuropsychology, particularly
for the diagnosis of diseases that are occult to structural imaging
interrogation. One such circumstance is the dementias; perfusion
imaging can be used to differentiate between the types of dementia.
Figure 4 shows an elderly patient who presented with altered mental
status. In such cases, it is necessary to differentiate Alzheimer's
disease from other possible causes such as normal pressure
hydroencephalus and multiple infarction-type dementia. In dementias
of the Alzheimer's type, both perfusion MR imaging and nuclear
medicine SPECT imaging will manifest temporal-parietal lobe
hypoperfusion. In this particular case, a distinct decrease in
perfusion in the temporal and parietal regions is present,
suggesting a diagnosis of Alzheimer's disease. Similar findings
would be seen on a metabolic test such as positron emission
Perfusion imaging is also used to augment findings in cases of
traumatic brain injury. Figure 5 illustrates the case of a
30-year-old woman with a traumatic brain injury in whom
neuropsychological testing suggests a frontal lobe cognitive
deficit. MR imaging reveals subtle structural abnormalities,
particularly, volume loss in the frontal lobes. Although these
changes are subtle, they were not present on a similar study
performed 2 years earlier. This is a definitive finding and
provides good structural correlation with the clinical findings in
this case. The results of functional imaging, either SPECT or
contrast-enhanced perfusion MR imaging, however, reveal an
absolutely striking alteration in perfusion to the frontal lobes
(figure 6). The functional imaging findings support the subtle
structural findings and confirm the clinical diagnosis.
Myocardial Perfusion Imaging
With the current technology, it is possible to image a
first-pass perfusion study of the whole heart. This exam is
typically performed under adenosine stress and followed with a
second exam approximately 5 minutes later after rest. This study is
performed using a standard dose of contrast agent, power injected
at a rate of 5 mL/sec. Any patient intolerance, either locally or
with nausea, will ruin the study. Figure 7 shows a uniform left
ventricular blush on the resting exam and an ovoid area of near
transmural perfusion deficit on the interior wall.
The extremely short half-life of the stress agent used in such
studies (approximately 7 seconds) permits the entire exam to be
completed in the clinical setting in approximately 30 minutes.
Another important concept in contrast-enhanced MR imaging is
that of delayed hyperenhancement.
In infarction, contrast agent passes through the injured
myocardial cell membrane. Hyperenhancement results from the
combined signal of enhanced intracellular and extracellular spaces
(figure 8). To obtain hyperenhanced images, a T1 prepared fast
gradient echo scan is performed 10 to 15 minutes after
administration of 0.1 to 0.2 mmol/kg of contrast agent. The extent
of transmural enhancement correlates negatively with the likelihood
of improved contractility in a segment of dysfunctional heart. This
technique has the potential to become the ultimate assessment of
MRA and Other Applications
Contrast-enhanced MRA studies overcome many of the limitations
of traditional flow-based MRA, particularly when studying
challenging areas, such as the thoracic outlet and great vessel
origins. Enhanced MRA at our site typically involves a 1.0 to 1.5
mL/sec power injection of from 0.05 to 0.2 mmol/kg gadoteridol.
Contrast-enhanced MRA is now routinely used for renal artery
assessment as well. In fact, MRA and CT angiography are close to
eliminating conventional angiography from the initial work-up of
patients with aorto-iliac and runoff disease. Prior to the use of
contrast enhancement, brain arteriovenous malformations (AVMs) were
very difficult to visualize. Now, in a 24-second scan, using
half-dose contrast, striking images of AVMs can be obtained with
the arterial nidus and venous structures in phase (figure 9).
Body applications have benefited from the recent technological
advances in MR imaging as well. Faster scan acquisition coupled
with tight power-injected contrast boluses routinely provides
arterial and venous phase hepatic imaging. Figure 10 shows a
patient with a hemangioma demonstrating early peripheral nodular
enhancement on the arterial and portal venous phases with
considerable contrast filling in on the delayed phase study.
Enhanced breast imaging is becoming increasingly important in
clinical practice. Used to characterize lesions, this may someday
have a routine role in the staging of breast cancer.
In summary, power injection of contrast agents for MR imaging is
being used in a wide array of clinical settings including oncology,
stroke and ischemia, neuropsychology, myocardial perfusion imaging,
Power injection requires high patient tolerance. In over 5 years
of clinical experience at Edison Imaging Associates with power
injection of contrast agents, mainly ProHance
(gadoteridol), we have had a very low reaction rate with virtually
no interrupted or suboptimal studies.