Improving Clinical

Outcomes and Workflow

*Image courtesy of The University of Pittsburgh Medical Center (UPMC), generated with P3T ® PA

Chest CTA for Pulmonary

Embolism Studies

John F. Kalafut, Ph.D

Director of Informatics Research and Strategy
MEDRAD Corporate Development and Innovations
 ulmonary Embolism (PE) is a blockage of the pulmonary artery or one of its branches due to a blood
P clot or other thrombus. PE Symptoms, which can include chest pain, shortness of breath, fainting and
sweating, are frequently non-specific and can mimic many other cardiopulmonary events.1 In many cases,
PE is a complication of a condition called deep vein thrombosis (DVT). In DVT, blood clots form in the deep
veins of the body. These clots, which occur most often in the legs, can break free and travel through the
bloodstream to the lungs and block an artery.2

PE Study Complexity and Its Impact

The greater the number of risk factors for DVT, the greater the chance of
developing PE. Factors that increase the risk for PE include:1
• Inherited conditions that cause increased risk for blood clotting
• Restricted or slow blood flow in a deep vein, due to injury, surgery,
or having to stay in bed for a long time
• Cancer and its treatment Unique imaging complexities
• Medical conditions such as varicose veins can inhibit diagnosis with a high
• Sitting for a long period of time, such as on long trips in a car or on degree of certainty. Jones and
an airplane Wittram show as many as one in
• During pregnancy and in the six week period after delivery every three CT Angiography
studies performed in the
• Being over age 60 (although PE and DVT can occur at any age)
Emergency Room on patients
• Being overweight or obese with suspected PE is interpreted
• Taking birth control or hormone replacement pills as “suboptimal.”6
• Having a medical condition that requires a central venous catheter
• Smoking
In the U.S., DVT and PE are associated with approximately 300,000 to
600,000 hospitalizations each year.3 The third most common cause of
cardiovascular death in the U.S.,4 PE results in as many as 50,000 deaths
a year.3 In most fatal PE incidents, death occurs within the first few
hours of the event.
Timely and accurate diagnosis is critical to patient safety. Chest CTA (CT
Angiography) has become a standard study for the radiological evaluation
of Emergency Department patients with suspected PE.5 If a definitive
diagnosis from the CTA study cannot be made, there are several
possible outcomes. A repeat CT study might be performed, another
diagnostic study might be ordered (such as a ventilation/perfusion exam),
or a therapeutic treatment is performed. When the patient does not have
a PE, these additional studies/procedures add unnecessary cost to the
healthcare system and potentially expose the patient to additional risk.
Unique imaging complexities can inhibit diagnosis with a high degree of
certainty. Jones and Wittram show as many as one in every three CT
Angiography studies performed in the Emergency Room on patients
with suspected PE is interpreted as “suboptimal.”6 There are multiple
causes of suboptimal studies; however, in the Jones and Wittram study,
readers singled-out respiratory motion artifact (74%) and poor contrast
enhancement (40%) as the two primary factors.7

2

To achieve the higher flow rates
mandated by faster scans and to
achieve adequately high contrast
enhancement, large bore
peripheral catheters (at least 20
Ga) and connector tubing of the
appropriate size and length are
required. In addition, it is helpful
to warm the contrast media to
lower the viscosity.
Technology Advances and Scan
Administration
In the past five years, CT acquisition times have been greatly
shortened due to advances in scanner technology. Using
contemporary CT scanners, radiologists can now achieve in one
second or less complete acquisition of the entire thorax. This scan
duration range has dropped from an estimated 20 to 30 second
thoracic CTA scan time common in the era of single and four-slice
scanners. Reduced breath-hold requirements associated with
reduced scan durations may help to diminish the incidence of
respiratory and other motion artifacts. Reduced scan duration,
however, has added complexity in calculating and executing
appropriate timing and iodine administration rates in CT Angiography.
Because the magnitude of contrast enhancement for CT Angiography
is directly related to injection flow rate, high flow rates are
mandatory to ensure a successful CT Pulmonary Angiography (CTPA)
study. With the short scan acquisitions common with modern CT
scanners, one may also use a shorter duration bolus. The shorter
bolus must be injected at a high flow rate to ensure high levels of
enhancement throughout the scan duration during the first-pass of
contrast through the pulmonary arteries. To achieve the higher flow
rates mandated by faster scans and to achieve adequately high
contrast enhancement, large bore peripheral catheters (at least
20 Ga) and connector tubing of the appropriate size and length are
required. In addition, it is helpful to warm the contrast media to
lower the viscosity.
Technologists can synchronize the triggering of contrast material to
image acquisition by one of two methods. One method is
administering a transit bolus, which uses a small volume of contrast
to measure peak enhancement arrival time at a specific area of
interest. The other is bolus tracking which triggers the scan when a
desired level of enhancement is measured in specified patient
anatomy. The advantages of each technique differ. Both methods
substantially improve synchronization when compared to the
traditional and rudimentary practice of fixed-delay techniques.
Administering a transit bolus also provides an estimate of the
patient’s true hemodynamics.
3

Figure 1: Simulated enhancement curves representing three patients of different weights
receiving the same injection protocol.12
Figure 1 illustrates simulated
enhancement curves for three
patients of different weights
when administered a fixed
injection protocol. The results
demonstrate the linear inverse
relationship existing between
weight and contrast
enhancement while also
showing the absence of relation
between contrast media
circulation time and patient
weight.
4
Optimal Opacification
In addition to individual variations in and the
challenges of scan timing, physiological and
contrast delivery factors can play an
increasingly significant role in achieving
consistent and adequate contrast enhance-
ment quality of thoracic CTA. A general
consensus in the radiology literature suggests
250 HU is the minimum acceptable vascular
enhancement for CT Angiography studies.
Wittram describes approaches necessary to
improve the quality of CT Pulmonary
Angiography. For example, he provides a
detailed and cogent rationale for
enhancement targets at CTPA, based on
the attenuation characteristics of
thromboembolism. He summarizes
published work reporting the mean
attenuation values of acute and chronic
thrombus as 33 HU and 87 HU respectively.
By accounting for statistical fluctuation in
embolic attenuation, a three-standard
deviation upper limit of embolus attenuation
is 78 HU and 180 HU (acute and chronic).8
Meaney et al. suggests that the mean
attenuation of vascular enhancement should
exceed the embolic attenuation by at least
one standard deviation.9 Therefore, assuming
this logic, the minimum vascular
enhancement sufficient for clinical use
(assuming a one-standard deviation of HU)
would be 211. However, CTPA attenuations
higher than this minimum value are likely
desirable for the detection of emboli in small
distal pulmonary arteries.10
The interdependency of patient and contrast
protocol design factors is a key consideration
in generating consistent and homogeneous
vascular contrast enhancement. To this end,
radiologists and technologists can adjust the
contrast protocol design to account for the
factors that relate directly to the degree and
timing of contrast enhancement. These
factors include:
• Body weight • Gender
• Cardiac output • Contrast concentration
• Height (higher concentration
• Age is better at CTA)
• Venous access • CT data acquisition
• Renal function duration
• Concomitant
comorbidities
Clinical research and experience has led to
greater understanding of the different
effects of fixed contrast dosing on image
enhancement. Increasingly, the practice of
weight-based dosing has been adopted for
patients of significantly different body
weight.11

The images below demonstrate
consistent image enhancement
across patients of widely
divergent BMIs and cardiac
output when using P3T® PA
(Pulmonary Angiography)
personalized patient protocol
software.3 In the study, 62
emergency department patients
referred for chest CTA to exclude
PE were randomized to
Personalized versus Standard
Protocol (control) groups. All had
18 gauge IV access; received the
contrast agent Ioversol (350
mg/ml iodine; Mallinckrodt, St
Louis, MO); and were scanned
on one 64 slice CT scanner (VCT,
GE® Healthcare; Milwaukee, WI).
Recorded patient parameters
were height, weight, age, sex
and heart rate. Estimated cardiac
output was computed using
standard look-up tables.
Images generated with P3T PA demonstrate consistent image enhancement while maintaining scan parameters: 0.625 mm collimation;
0.24 pitch; 9.6 mm/sec table speed; 350 msec rotation time; and 120 kV; 280 - 550 mAs.
More recent evidence supports extending protocol customization to
include factors beyond simply weight. Personalizing contrast
protocols to account for patient factors and study requirements/constraints
at the point of patient care can assist in accomplishing optimized scan
timing in relation to bolus arrival. Contrast protocols must factor in
patient and physiology characteristics, CT scan duration and scan
delay, and contrast media type.10
Individualized Contrast Protocols
Despite growing clinical evidence of its benefits, the practice of
consistently personalizing contrast protocols is not widely adopted
because of the time and attention constraints associated with
accounting for additional patient and study variables.11 Clinical
workflow complexities have led to the introduction of contrast
protocol personalization software.
Protocol personalization software can automate and simplify the
consistent calculation and efficient delivery of personalized contrast
protocols while adjusting for interdependent patient and study factors.
Contrast protocol personalization software also eliminates the need to
estimate injection protocols using ad hoc methods for complicated
studies, and removes the potential error associated with these
estimates.
Research Outcomes: Personalized Contrast
Dosing
A University of Pittsburgh Medical Center (UPMC) study presented at
the 2008 annual meeting of the Society of Thoracic Radiology
measured image quality outcomes of consistently administering
personalized contrast protocols at CT angiography to rule out
Pulmonary Embolism.
In the study, technologists computed personalized contrast protocols
through automated, clinically validated injector-based algorithms
(MEDRAD® P3T ® PA, Personalized Patient Protocol technology
software). The study resulted in a significantly greater percentage of
P3T PA CTPA exams ranked “diagnostic without limitation” when
compared to the Standard protocol.3
5
 Standard Protocol P3T PA
Pulmonary Angiography Enhancement Curve Pulmonary Angiography Enhancement Curve

Figure 2: Comparison of simulated

contrast enhancement in the
pulmonary artery using the Bae-
Brink-Heiken pharmacokinetic
model 11 and a simulated patient with
the following demographics: 275 lb,
45 year-old male. The scan duration
Figure 2: Simulated contrast enhancement of a patient administered the Standard Protocol versus was set to five seconds and the
P3T ® PA Protocol. Notice the enhancement was greater than 300 HU throughout the entire scan
duration for the simulated response using the P3T PA Contrast Injection Protocol. contrast concentration was 370 mgI/ml.
The enhancement curve on the left
was generated with a standard
contrast protocol (80 ml at 4 ml/s)
while the curve on the right was
generated (including the scan delay)
Figures 3 and 4 show study results. Two using a P3T® PA protocol of 6.2 ml/s
readers, blinded to injection method jointly and 82 ml. Notice the enhancement
measured density (HU) of main (MPA, RPA, was greater than 300 HU throughout
LPA) and segmental pulmonary arteries the entire scan duration for the
(bilateral upper & lower lobes). Three other simulated response using the P3T PA
blinded readers qualitatively scored scans protocol.
compared to an "adequate" example for image
quality to assess for PE, noting limitations:
poor contrast, motion, quantum mottle, and
SVC streak artifact.

Figure 4: Qualitative assessment of CTs obtained with

personalized protocol versus standard protocol.3

Figure 3: Comparison shows P3T PA enhancement when compared to standard protocol is

higher.3 The Wilcoxon rank sum test was used to test for significant differences in mean
contrast enhancement.

6
P3T ® PA Versus Standard
P3T PA Standard
Protocol Weight: 300 pound Weight: 295 pound
Contrast: 116 cc Contrast: 80 cc
P3T interactive touch screens simplify Main PA HU: 274 Main PA HU: 171
workflow associated with personalized
protocol administration. Technologists
use interactive touch screens to select
the appropriate module depending on
the body part being imaged (Figure 5).
Based on P3T PA pre-configured
parameters, along with the patient
weight and scan duration, contrast
volumes and flow rates are
automatically calculated to individualize
the protocol for the patient (Figure 6).
P3T PA is indicated for CT Angiography Clinically validated P3T PA algorithms adapt contrast flow in a non-linear fashion refined
using the Bae-Brink-Heiken pharmacokinetic model.11 Images are courtesy of The University
of the pulmonary vasculature, and the of Pittsburgh.
thoracic and abdominal aorta.*

As depicted in the clinical images above, the UPMC

study also showed that personalized dosing results in
higher contrast enhancement of the pulmonary arteries
when compared to standard exams, albeit at a slightly
higher contrast dose than standard protocol (94+/-12
vs. 80, excluding test bolus volume).3 P3T PA was
configured to compute a first-phase contrast bolus of
16 seconds for all subjects. This value is configurable.

Figure 5: P3T interactive Module Selection touch screen Figure 6: P3T PA interactive touch screen

*510(k) FDA clearance number: K082905.

7
Conclusions
Timely and accurate diagnosis is critical to the safety of patients with suspected PE. Despite this need, suboptimal PE
studies due to methodological protocol factors can inhibit diagnosis with a high degree of certainty. In fact, as many as
30 percent of CT angiography studies performed in the Emergency room on patients with suspected PE have been
reported to be “suboptimal.”5

Personalized CT contrast dosing has proven to decrease the number of suboptimal studies in at least one clinical
study.3 Using clinically validated injector-based algorithms, MEDRAD’s® personalized contrast protocol software
reduces variation in administering customized contrast delivery across patient populations while adjusting protocols
to account for unique and interdependent patient and study factors.

Software automation also enables radiologists and technologists to perform personalized studies with consistency
while working with a wide variety of scanners with which they may have different levels of familiarity. Therefore,
when integrated unobtrusively into clinical workflow, personalization software aids in resourcefully ensuring optimal
image opacification across patient and technologist populations, and can serve as a tool to improve patient care.

Summary of References:
1. http://www.nhlbi.nih.gov//health/dci/Diseases/pe/pe_what.html (accessed on February 05, 2010)
2. http://emedicine.medscape.com/article/361131-overview (accessed on February 05, 2010)
3. Presented at Society of Thoracic Radiology (2008) Poster Session; Christopher R. Deible, MD, PhD. Study supported by MEDRAD.
4. The Actual Role of CT and Ventilation-Perfusion Scanning in Workup for Suspected Pulmonary Embolism: Evidence from Hospitals; Mythreyi Behargaven, Jonathan H. Sunshine,
Sheleika L. Hervey, AJR 2009
5. Abstract: Patient Outcomes and Resource Utilization for Emergency Department Patients with Suspected Pulmonary Embolism and Initial Chest Computed Tomography Angiography
Studies Deemed Suboptimal for Interpretation; Weinstein, JM, Burton, JH, ED Albany Medical Center.
6. Stein, P.D., et al., Multidetector computed tomography for acute pulmonary embolism. N Engl J Med, 2006. 354(22): p. 2317-27.
7. The Indeterminate CT Pulmonary Angiogram: Imaging Characteristics and Patient Clinical Outcomes; Stephen E. Jones, MD PhD, Conrad Wittram, MB, ChB, Radiology 2005, 237:329-337
8. Wittram, C., How I Do It: CT Pulmonary Angiography. American Journal Roentgenology, 2007. 188: p. 6.
9. Meaney, T.F., et al., Detection of low-contrast lesions in computed body tomography: an experimental study of simulated lesions. Radiology, 1980. 134(1): p. 49-54.
10. Bae, K.T., Optimization of Contrast Enhancement in Thoracic MDCT. Radiol Clin N Am, 2010. 48: p. 20.
11. Factors affecting enhancement of liver parenchyma: Optimal Vascular and Parenchymal Contrast Enhancement:The Current State of the Art. Dominik Fleischmann, MD.
12. Bae, K.T., J.P. Heiken, and J.A. Brink, Aortic and hepatic contrast medium enhancement at CT. Part I. Prediction with a computer model. Radiology, 1998. 207(3): p. 647-55.

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