In recent years, multidetector computed tomography (CT) technology has advanced rapidly as commercial scanners have progressed from 4 to 16- to 64-detector rows, making coronary CT angiography (CTA) a clinical reality. In addition to providing better spatial resolution, multi-detector CT scanners are significantly faster, resulting in shorter breath-hold requirements, reduced motion artifacts, and decreased contrast volume requirements when compared with single-detector-row helical scanners or conventional nonhelical scanners.
Dr. Boonn
is currently a Chief Radiology Resident at the Hospital of the
University of Pennsylvania, Philadelphia, PA and expects to
complete his diagnostic radiology residency in 2007. He completed
medical school training at the Mount Sinai School of Medicine in
New York City in 2002 and a transitional medicine internship at
the Albert Einstein Medical Center in Philadelphia in 2003.
During research track residency, he participated in the Imaging
Informatics Fellowship program at the University of Maryland
Medical Center and Baltimore VA Medical Center, Baltimore, MD. He
plans to continue his training at the Hospital of the University
of Pennsylvania as a Cardiovascular Imaging Fellow. In addition
to his radiology training, Dr. Boonn is also Founder and
President of MedicalPocketPC.com Inc. as well as co-Founder of
iVirtuoso Inc.
Dr. Litt
is an Assistant Professor of Radiology and Section Chief of
Cardiovascular Imaging, Department of Radiology, the Hospital of
the University of Pennsylvania, Philadelphia, PA.
Dr. Charagundla
is an Assistant Professor of Radiology, Department of Radiology,
the Hospital of the University of Pennsylvania, Philadelphia,
PA.
Coronary artery computed tomographic angiography (CTA)
demands specialized contrast injection techniques to optimize
enhancement of the coronary vasculature while minimizing
artifact. An overview of the theories behind contrast injection
protocols in CTA, the metrics that are currently employed to
assess the quality of contrast injection, and the variables
affecting contrast enhancement will be presented as an
introduction to bolus geometry. The current application of these
theories will be discussed in modifications of injection
protocols, opinions on contrast media selection and timing
methods, specialized indications for cardiac CT, and future
developments.
In recent years, multidetector computed tomography (CT)
technology has advanced rapidly as commercial scanners have
progressed from 4 to 16- to 64-detector rows, making coronary CT
angiography (CTA) a clinical reality. In addition to providing
better spatial resolution, multi-detector CT scanners are
significantly faster, resulting in shorter breath-hold
requirements, reduced motion artifacts, and decreased contrast
volume requirements when compared with single-detector-row helical
scanners or conventional nonhelical scanners. The advent of
64-slice CT promises not only to enhance the utility of coronary
CTA in a broad range of patients, but also to eliminate the need
for conventional, invasive diagnostic coronary angiography in an
appropriately selected population of patients (Figure 1).
The effectiveness of multidetector CTA in assessing coronary
artery pathology is supported by a growing number of research
reports that detail various techniques in the clinical setting.
1-7
Among the consensus findings of these and other studies is that
optimized contrast injection protocols are critical in providing
uniform enhancement of the coronary arteries for diagnostic
accuracy.
8-11
This article provides an overview of the theories behind contrast
injection protocols in CTA, the metrics currently employed to
assess the quality of contrast injection, and the recognized
variables affecting contrast enhancement. Modifications of
injection protocols, opinions on contrast media selection and
timing methods, specialized indications for cardiac CT, and future
developments in customized injection protocols will be
discussed.
Theory
An optimum contrast injection protocol for coronary CTA must
provide uniform enhancement of structures being evaluated with
minimum contrast-bolus related streak artifacts as well as minimal
contrast load to reduce the risk of contrast-induced nephropathy.
Achieving each of these goals simultaneously calls for a delicate
balance of technique and has been the subject of substantial
theoretical and practical research.
Bolus geometry and time-density curves
Contrast-bolus geometry is usually graphed as a time-density
curve (TDC), in which the enhancement of a selected vessel is
measured over time. An ideal TDC would have an immediate increase
in enhancement at the start of CT acquisition, maintain a uniformly
flat plateau throughout the scan, and return to zero at the end of
the scan (Figure 2). The actual bolus geometry usually indicates a
steady rise in enhancement to a peak enhancement value, followed by
a steady decline (Figure 3). A CT scan acquisition typically occurs
over the upslope and downslope of the curve, resulting in
nonuniform enhancement. Several techniques for the optimization of
contrast injection parameters, including mathematical models that
predict bolus geometry, are aimed at "flattening" the plateau of
the curve to more closely match the ideal TDC.
Becker et al
12
have suggested that optimal enhancement of coronary arteries in CTA
is between 250 and 300 HU and have also suggested that levels
>350 HU should be avoided because of difficulties in
differentiating contrast from coronary calcifications. Although
this group's original work was performed on a 4-slice CT unit,
these suggestions remain relevant and are used in a number of
currently recommended techniques and mathematical approaches to CTA
contrast enhancement.
Mathematical models
Several complex mathematical models have been developed to
predict bolus geometry. A detailed description of these models is
beyond the scope of this article; however, familiarity with the
general approaches and utility of the most widely used models is
important to understand both current and novel approaches to CTA
contrast investigations. Cademartiri et al
13
have provided an excellent review of parameters affecting bolus
geometry in CTA, including experimental and human studies and a
detailed description of methods of bolus timing.
The model proposed by Fleischmann et al
14,15
considers the patient to be a "black box," so that empirical data
from inputs (test bolus parameters) and outputs (TDCs) can be used
to calculate a transfer function to optimize parameters for
contrast injection. As part of this customized approach to imaging,
the group has proposed the use of a biphasic injection
protocol.
Bae at al
16
have proposed a mathematical compartmental model based on patient
body habitus (including weight, height, and gender) and physiologic
factors (cardiac output and blood volume) to predict bolus
geometry. This model has correlated well with experimental porcine
data
16
and has been applied successfully to predict the geometry of a
multiphasic injection protocol in humans.
17
Mathematical models of bolus geometry must make accommodations
for variations in patient habitus and physiology. Increased body
weight correlates with a decrease in peak enhancement, likely as a
result of increased intravascular volume.
18
Cardiac output is inversely correlated with time to peak
enhancement and contrast-to-noise ratio (CNR), thus patients with
higher cardiac outputs will have shorter times to peak enhancement
and lower CNRs.
19
Measurements
Several metrics have been used to quantify image quality in
coronary CTA. The most common is CNR, calculated by subtracting the
CT attenuation of surrounding connective tissue from the CT
attenuation of the lumen of the coronary artery and dividing that
by image noise in the lumen of the aortic root at the level of the
left coronary artery. Image noise is defined as the standard
deviation of CT attenuation within a circular region of interest
(ROI).
9
The other common metric is the length of each coronary artery and
various branches where the enhanced lumen is clearly visible
without motion artifact. Several groups, most recently Ferencik et
al,
9
have discussed approaches to quantifying image quality in 64-slice
CTA of coronary arteries.
Current issues
Selection of contrast media
A wide variety of intravenous (IV) contrast media-with a range
of iodine concentrations and osmolarity-exist for use in coronary
CTA. Increasing concentrations of contrast media result in
increasing vascular enhancement--a simple relationship complicated
by a number of confounding factors that must be considered in the
selection of optimal contrast media for coronary CTA.
20,21
The highest level of enhancement is seen with 400 mgI/mL
(iomeprol);
22
however, iomeprol is not approved by the U.S. Food and Drug
Administration (FDA). Commonly used high-concentration contrasts in
the United States include iohexol (350 mgI/mL), iopromide (370
mgI/mL), and iopamidol (370 mgI/mL).
Multiphasic injections: Varying contrast concentration with
saline bolus-chase
A saline bolus-chase is the IV injection of normal saline
immediately after the injection of the contrast material, usually
through a double-barrel injector or with 2 injectors joined by a
T-connection.
24,25
The saline bolus-chase provides several benefits in coronary CTA.
Its use results in a tighter contrast column, increased enhancement
within the coronary arteries, reduced contrast volume requirement,
and decreased streak artifact from the superior vena cava and right
atrium (Figure 4). Poor timing of the saline chase may result in
near complete filling of the right side of the heart with saline,
making morphologic characterization of the right ventricle and
interventricular septum difficult (Figure 5), which may be
important when evaluating patients with congenital heart disease.
Several institutions have addressed this problem by implementing
triphasic injections: 100% contrast injection, followed first by a
50%/50% or 60%/40% mix of contrast and saline, and finally by a
100% saline bolus chase to increase opacification in the right side
of the heart without streak artifact (Figure 6).
Multiphasic injections: Varying injection rate
Contrast injection rates for coronary CTA typically ranges from
4 to 6 mL/sec. For consistency, most institutions have standardized
administration protocols to injection in the antecubital vein with
an 18- to 20-gauge peripheral IV catheter.
The TDC of a standard IV injection of contrast indicates a
slowly increasing enhancement profile that peaks just after
completion of the injection (Figure 3). As noted previously,
several techniques have been proposed to "flatten" this curve and
provide a more uniform enhancement profile throughout the scan.
"Biphasic" injection may imply different rates of contrast
injection (rather than different concentrations as described
above). For example, a contrast injection with an initial high rate
followed by a lower rate
14,15
has been reported to show a more uniform enhancement pattern than a
monophasic injection rate (Figure 7). Bae et al
16,17
has shown in both computer and porcine models that a variable-rate
multiphasic injection using an exponential decay profile provides
an even flatter TDC and a more uniform enhancement.
Test bolus versus bolus tracking
As scanners have become faster and scan durations have
decreased, the time window for optimal contrast enhancement within
the coronary arteries has narrowed significantly, so that fixed
delays for initiating the scan after contrast injection are not
recommended.
26
Two commonly used methods for timing the start of the scan are
based on a test bolus or automated bolus tracking.
For test-bolus timing, a small amount of contrast (10 to 20 mL)
is injected while acquiring a series of dynamic, low-dose
monitoring scans at the level of the vessel of interest. An ROI is
drawn within this vessel, and a time-enhancement curve is generated
with a time to peak enhancement. These data are used to calculate
the injection delay for the diagnostic scan. Several published
injection protocols for 64-slice coronary CTA using the test bolus
technique are included in Table 1.
The automated bolus-tracking technique involves real-time
monitoring of the vessel of interest with a series of low-dose
monitoring scans during the diagnostic injection.
27
When the enhancement within the ROI reaches a threshold level
(usually between 100 and 140 HU above baseline), the table is moved
into position for the beginning of the diagnostic scan. Table 2
includes several published injection protocols for 64-slice
coronary CTA using bolus tracking.
Controversy remains over the optimal timing method for coronary
CTA. Advocates of the test-bolus technique suggest several
advantages to this method. The small amount of contrast injected
initially for the test bolus helps to ensure that the IV catheter
is in place and is functioning properly. The test bolus injection
also may help prepare the patient for the various side effects of
contrast injection, including warmth and unusual taste sensations.
This initial acclimation to side effects may make the patient less
likely to move during the diagnostic injection.
28
One drawback to bolus tracking is that breath-holding instructions
must be delivered within the very short interval (4 to 5 seconds)
between achieving threshold enhancement and initiating the
diagnostic scan. The test-bolus method does not have this
restriction, so that more time can be devoted to coaching the
patient before the scan, which likely results in fewer motion and
breathing artifacts. The injection of a test bolus may also allow
for the calculation of estimated cardiac output-a parameter that
will be essential in efforts to customize and individualize
injection protocols.
29
The advantages of bolus tracking are its practicality and
efficiency: a single injection is needed, and the elimination of
the test bolus reduces the total contrast load by a small amount.
In one of the few studies that compared the 2 techniques,
Cademartiri et al
26
recently suggested that the bolus-tracking technique also yields
more homogeneous enhancement than does the test bolus technique.
Others, however, have indicated that use of appropriate timing and
delays in the test-bolus technique can yield similar results to
bolus tracking.
30
Congenital heart disease
Cardiac CT in congenital heart disease presents a number of
challenges for contrast administration.
31,32
Complicated anatomy, combined with possible shunts, postsurgical
changes, and, often, poor cardiac function, requires customized
injection protocols for each patient. Coronary artery evaluation is
typically performed to evaluate for anomalies rather than stenotic
disease.
31
Additionally, evaluation of the right ventricle is often the
central clinical question, for example, in patients who have
undergone operative repair of tetralogy of Fallot or transposition
of the great arteries (Figure 8). Since standard injection
protocols focus on left ventricular enhancement, it is important to
modify scanning technique to improve right ventricular
visualization in these patients. Several authors have recommended
the use of a pulmonary embolism protocol using automated bolus
tracking with tracker ROI placement that is based on indication and
presumed anatomic anomaly.
32
For example, the ROI when evaluating for coarctation of the aorta
may be placed in the ascending aorta; however, for a right-to-left
shunt, the ROI would be placed in the right atrium, and in a
left-to-right shunt the ROI would be in the left atrium. Knowledge
of the underlying clinical condition combined with anatomic and
physiologic data can help to tailor the contrast protocol
appropriately. Imaging during multiple phases of enhancement may be
used as well, with pre-contrast or delayed imaging to evaluate for
calcification or venous anomalies, respectively.
32
Future considerations: 256 slices and beyond
Shorter boluses, decreased volume
As CT scanners continue to advance in both spatial and temporal
resolution using ever-increasing numbers of detector rows,
increased gantry speed, and other novel technologic developments,
acquisition times will continue to decrease. New dual-source
64-slice CT, for example, may permit imaging of the coronary
arteries without motion artifacts in a substantially larger
percentage of patients than possible with previous scanners.
33,34
The advent of 256-slice scanners allow imaging of the heart in a
single gantry rotation, which offers the possibility of true
dynamic imaging of the heart. Contrast injection parameters and
protocols will need to be modified to accommodate each of these
advances. The contrast volume needed to achieve optimal results is
likely to decrease with more rapid acquisition techniques.
Functional assessment and perfusion analysis of the
heart
In addition to the assessment of the coronary arteries, cardiac
CT has been considered for the evaluation of cardiac function and
perfusion, a domain currently dominated by cardiac MR and nuclear
cardiology. For example, Nikolaou et al
35
have reported that chronic myocardial infarction can be detected in
most individuals using multidetector CTA but that the technique
cannot yet reliably detect ischemic perfusion defects under resting
conditions. Koyama et al
36
recently described a 2-phase technique that, when performed after
reperfusion therapy, could serve as a predictor of left ventricular
functional recovery.
Current contrast injection protocols have been designed to
facilitate the evaluation of coronary arteries, and modifications
may be necessary to provide more uniform enhancement of all 4
chambers for better functional and morphologic assessment.
Alternatively, a coronary CTA immediately followed by a delayed
equilibrium phase scan using a low-dose coronary calcium protocol
can result in the equal enhancement of both sides of the heart for
improved anatomic and morphologic characterization.
37
Customized injection protocols
As noted previously, bolus geometry and the resultant TDC are
related to cardiac output. The hemodynamic status of the patient
has been reported to have a significant effect on coronary artery
opacification, with vessel opacification decreasing as stroke
volume and cardiac output increase.
19
Studies have shown that cardiac output can be estimated by the
TDC from a test-bolus injection.
29
Tailoring the injection profile to the estimated cardiac output
based on the test-bolus injection may provide more consistent
enhancement of the coronary arteries.
Contrast injection volume can also be customized to the
patient's weight. Several studies have found an inverse
relationship between patient weight and peak enhancement.
18
Modifying the volume of contrast based on the patient's weight can
avoid excess contrast administration to thinner patients while
ensuring optimal enhancement in heavier patients.
Technology currently exists to take these multiple factors into
account and to customize an injection protocol for each patient.
However, the workflow to achieve this is cumbersome, and more
automated and efficient mechanisms need to be developed to
integrate individualized injection protocols into routine clinical
practice.
Conclusion
Rapid advances in multidetector CT technology have been
paralleled by corresponding advances in contrast injection
techniques. In addition to delivering contrast at a higher rate and
for a shorter duration to keep up with today's faster scanners,
techniques have been developed to improve the consistency of
enhancement while minimizing artifact and reducing the overall dose
of contrast material. The ability to further customize and
individualize contrast injection during coronary CTA will be
important in tailoring the protocol to the clinical question while
taking into account the patient's physiology and anatomy. Further
improvements in scan performance will require adaptation of
scanning technique to patient-related factors, such as cardiac
output and body weight, and may make use of more sophisticated
bolus geometries.
Exciting new applications of cardiac CT that will require
customized injection protocols include assessment of biventricular
function and myocardial perfusion. Continuing advances in CT
scanner design, coupled with the improved use of contrast media,
will no doubt improve the reliability and clinical applicability of
this promising imaging technique.