Clinical trial NCT03231397
Conditions: Abdominal Aortic Aneurysm (AAA)
Keywords: Abdominal Aortic Aneurysm (AAA)
Sponsor: Washington University School of Medicine
Start date: 2017-08-01; Completion date: 2020-04-30
Enrollment: 2 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
Eligible subjects in this study will have either a known abdominal aortic aneurysm (AAA) or because they do not have an AAA (control group).

The purpose of this research study is to further study, through FEA, changes that occur in the mechanical properties of the aortic wall. The investigator will compare two radiotracers, 18F-FDG and 11C-PBR28 to determine if one provides more useful and reliable information about inflammation. 18F-FDG and 11C-PBR28 are radioactive drugs that will be used for imaging during the PET-CT scan. The investigator will also compare the results describing the mechanical properties of the AAA wall to the degree of inflammation in that wall as determined by PET-CT imaging to define new and better predictors of AAA growth and/or rupture.

Detailed description:
Eligible subjects in this study will have either a known abdominal aortic aneurysm (AAA) or because they do not have an AAA (control group).

The aorta serves as the main artery to supply blood flow to the body. It is approximately the size of a garden hose. Due to the effects of high blood pressure (hypertension), atherosclerosis (hardening of the arteries), and tobacco use, the aorta may widen and enlarge to form an aneurysm. An abdominal aortic aneurysm (AAA) is a dilation (enlargement) or ballooning out of a section of blood vessel caused by disease or weakness in the wall of the aorta below the level of the kidney arteries. As an AAA dilates and increases in size, rupture of the AAA may occur. AAA rupture carries a significant risk of death.

Currently, aortic size is the primary factor used to assess aortic rupture risk. There are other imaging procedures (imaging modalities) that are being used and developed to assess AAA rupture risk. Finite element analysis (FEA) is a way to study the mechanical properties of the aortic wall, including areas of stress and strength that are used to calculate rupture risk. Positron Emission Tomography (PET) utilizes glucose (a form of sugar) labeled with a radioactivity to look at the metabolic activity and inflammation in the aortic wall.

The purpose of this research study is to further study, through FEA, changes that occur in the mechanical properties of the aortic wall. The investigator will compare two radiotracers, 18F-FDG and 11C-PBR28 to determine if one provides more useful and reliable information about inflammation. 18F-FDG and 11C-PBR28 are radioactive drugs that will be used for imaging during the PET-CT scan. The investigator will also compare the results describing the mechanical properties of the AAA wall to the degree of inflammation in that wall as determined by PET-CT imaging to define new and better predictors of AAA growth and/or rupture.

The radioactive tracers that are used in this study are 18F-fludeoxyglucose (FDG) and 11C-PBR28 (PBR) which stands for Peripheral Benzodiazepine Receptor. 11C-PBR28 is considered investigational, which means that it has not been approved by the U.S. Food and Drug Administration. FDG is an approved drug by the FDA, however in this study it is considered investigational.

Goal: Twenty-four subjects will be recruited for this study. Six control subjects (three males and three females), will be considered. Control subjects will have known atherosclerosis, without aneurysmal disease. Six subjects (three males and three females) with small AAAs (diameter 3.0-4.5cm), six subjects (three males, AAA \>5.5cm and three females, AAA \>5.0cm) with AAAs that are indicated for treatment, and six subjects (three males and three females) with rapidly expanding AAAs (\>0.5cm over 6 months and/or \>1.0cm over 12 months) will be considered.

Subjects will have blood drawn to perform a genetic test that will look at genes and proteins to determine subject eligibility. Once the blood work is assessed for eligibility, subjects will undergo the PET-CT scan. The imaging will take approximately 3 hours to complete.

Arms: arm 1: Six control subjects (three males and three females) with known atherosclerosis by standard clinical criteria without aneurysmal disease.

To assess AAA rupture risk by PET-CTA scans, participants will undergo PET-CT scan using 11C-PBR28 and 18F-fludeoxyglucose (FDG) tracer. Participants will have a blood draw for genetic testing, pregnancy testing if female and creatinine testing. arm 2: Six subjects (three males and three females) with small AAAs (diameter 3.0-4.5cm).

To assess AAA rupture risk by PET-CTA scans, participants will undergo PET-CT scan using 11C-PBR28 and 18F-fludeoxyglucose (FDG) tracer. Participants will have a blood draw for genetic testing, pregnancy testing if female and creatinine testing. arm 3: Six subjects (three males and three females) with rapidly expanding AAAs (\>0.5cm over 6 months and/or \>1.0cm over 12 months).

To assess AAA rupture risk by PET-CTA scans, participants will undergo PET-CT scan using 11C-PBR28 and 18F-fludeoxyglucose (FDG) tracer. Participants will have a blood draw for genetic testing, pregnancy testing if female and creatinine testing. arm 4: Six subjects (three males, AAA \>5.5cm and three females, AAA \>5.0cm) with AAAs that are indicated for treatment.

To assess AAA rupture risk by PET-CTA scans, participants will undergo PET-CT scan using 11C-PBR28 and 18F-fludeoxyglucose (FDG) tracer. Participants will have a blood draw for genetic testing, pregnancy testing if female and creatinine testing.
Interventions: intervention 1: Assess AAA rupture risk by PET-CTA scans intervention 2: 18F-fludeoxyglucose (FDG) intervention 3: 11C-PBR28
Intervention descriptions: intervention 1: Assess AAA rupture risk by PET-CTA scans intervention 2: Assess AAA rupture risk by PET-CTA scans using 18F-fludeoxyglucose (FDG)and 11C-PBR28 PET-CT and contrast-enhanced CTA imaging intervention 3: Assess AAA rupture risk by PET-CTA scans using 18F-fludeoxyglucose (FDG)and 11C-PBR28 PET-CT and contrast-enhanced CTA imaging

Protocol documents:
Prot_SAP_000.pdf: 
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Noninvasive Assessment of Abdominal Aortic Aneurysm 
Wall Structural Integrity and Inflammation as Predictors 
of Expansion and/or Rupture 
 
NCT 03231397 
 
Unique Protocol ID:  201702141 
 
Principal Investigator: Sean J English, MD. 
 
 
Protocol Version: 02 
 
 
Version date:  10/04/2018 
 
 
 
 


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Protocol Title: Noninvasive Assessment of Abdominal Aortic Aneurysm Wall Structural  
Integrity and Inflammation as Predictors of Expansion and/or Rupture 
 
 
Principal Investigator: Sean J English, MD. 
Protocol Version: 02 
Version date:  10/04/2018 
 
 
I. 
BACKGROUND AND SIGNIFICANCE 
Abdominal aortic aneurysm (AAA) is a significant medical problem, with a high mortality rate, 
accounting for approximately 150,000 hospital admissions per year. AAA is the 10th leading cause 
of death in Caucasian men, ages 65 - 74 years, and has accounted for nearly 16,000 deaths overall.1 
Necropsy studies from the United States and Europe suggest an overall prevalence for AAA of 2-
4% for men and 1-2% for women.2,3 Population based screening studies demonstrate a prevalence 
of approximately 9% in men and 2% in women.4 It has been demonstrated that the prevalence of 
AAA increases with increasing age, with an increased prevalence in males compared to females. 
Noninvasive screening in the elderly population has led to an overall increased incidence of 
asymptomatic AAA.2,3,4,5 Currently, 35,000 to 40,000 aneurysms are treated surgically in the 
United States.6 Once AAA formation has commenced, aneurysms will continue to grow at a 
variable rate, until they ultimately rupture. AAA rupture is associated with very high morbidity 
and mortality.  Perioperative mortality rates of approximately 45% have been reported for open 
AAA repair in the United States since the late 1980s.7 Approximately 60% of patients with 
ruptured AAA die before reaching the hospital,8 and emergency open surgical repair carries a 
mortality rate of 35-70%.9 The incidence of AAA rupture continues to increase despite aggressive 
attempts to screen at-risk populations.10,11,12 Improvements in early aneurysm detection and 
surveillance are necessary to decrease the incidence of AAA rupture and associated mortality.13 
 
It is believed that AAA rupture occurs when the aortic wall stress exceeds the tensile strength of the 
degenerated AAA wall. Finite element analysis (FEA) may be utilized to implement biomechanical 
principles in an effort to assess AAA expansion and/or rupture risk.14,15,16,17  Efforts have been made 
to include intraluminal thrombus (ILT) and the anisotropic AAA tissue behavior into the computer 
models of AAAs. AAA rupture occurs when the stress acting on the AAA wall exceeds its strength; 
therefore, the prediction of AAA rupture must include wall stress and strength distributions. 
Considering this, rupture potential index (RPI) is defined as the ratio of the acting wall stress to 
the wall strength, and the maximum RPI for AAA represents its rupture risk. Comparing peak 
stresses and strains using anisotropic and isotropic constitutive relations, we have demonstrated 
significant increases in peak stress when using the anisotropic relationship.18 Considering ruptured 
AAA patients (N=8) and non-ruptured AAA patients (N=4), we have demonstrated a significant 
decrease in AAA wall strength of those AAAs that went on to rupture. The differences in RPI 
values did not reach statistical significance, when comparing ruptured and non-ruptured AAAs; 
however, our initial data suggests that peak RPI may serve as a better predictor of AAA rupture 
than maximum diameter or peak wall stress alone.19  
 
It is hypothesized that the final event leading to aortic rupture involves the degradation of collagen 
within the media, extending out through the adventitia. This occurs through a catalytic process 
induced by inflammatory cells in the aortic wall. Macrophages and neutrophils are a major source 


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of key enzymes at play, particularly serine proteases and matrix metalloproteinases, and are 
believed to play a critical role in this tissue degradation.20 Inflammation of the vascular wall related 
to phagocytic macrophage activity can be demonstrated by increased uptake of 2-deoxy-2-
[18F]fluoro-D-glucose (18F-FDG) PET in the arterial wall.21 Accordingly, 18F-FDG PET has been 
used to assess AAA wall inflammation,22 and increased 18F-FDG uptake has been identified in 
symptomatic AAAs (pain on palpation of AAA) and with rapid aortic enlargement.23 Considering 
symptomatic AAA patients (N=3), Reeps et al. demonstrated significantly increased 18F-FDG 
AAA uptake that correlated with greater macrophage populations on AAA wall histology, as well 
as higher MMP9 expression and decreased collagen fiber content, when tissue was taken at the 
time of repair.24 In a follow-up manuscript, Reeps et al. demonstrated the ability to discriminate 
between symptomatic (N=5) and asymptomatic (N=18) AAA patients on the basis of 18F-FDG 
uptake. They then correlated this increased 18F-FDG uptake with aortic wall macrophage 
infiltration and MMP9 expression.25 We have reviewed 18F-FDG PET scans for AAA patients at 
a single institution compared with those of atherosclerotic, non-aneurysmal aortas and 
demonstrated significantly greater global 18F-FDG uptake by AAAs.26 Utilizing the porcine 
pancreatic elastase (PPE) exposure model in rats stimulated to rupture with β-aminopropionitrile 
(BAPN) exposure, we have demonstrated the ability of 18F-FDG microPET to identify 
metabolically active sites in a pre-rupture state that ultimately rupture.27  
 
Translocator protein (TSPO), formerly referred to as peripheral benzodiazepine receptor, is an 18-
kDa outer mitochondrial protein highly expressed in phagocytic inflammatory cells, such as 
macrophages in the periphery and macrophage-like microglial cells in the central nervous system. 
It has been demonstrated that other inflammatory cells including neutrophils, B cells, natural killer, 
as well as CD4- and CD8-positive cells express TSPO to varying degrees.28 The TSPO radioligand 
11C-PBR28 ([methyl-11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine) has been 
used for neuroimaging with primates  and humans, as well as imaging lung injury in humans.29,30 
Other TSPO radioligands, including 11C-PK1195, have been utilized to evaluate macrophage 
presence and behavior in rodent and human carotid plaques.31,32 
 
We have previously demonstrated the utility of 18F-FDG and 11C-PBR28 to study inflammation 
associated with the PPE model of AAA development in rats, thereby verifying similar 18F-FDG 
imaging characteristics in this model compared to humans.33 In conjunction with increased TSPO 
gene expression and protein expression in AAA, this data supports the potential role of 18F-FDG 
and TSPO radioligands for the assessment of aortic wall inflammation during the development of 
aortic aneurysms in patients. Based on macrophage uptake and autoradiographic findings, as well 
as the natural history of AAA rupture, we are seeking to explore the uptake and distribution of 
TSPO radiotracers compared to 18F-FDG and the potential of 11C-PBR28 for the prediction of 
AAA expansion and/or rupture.  This is the first study to assess the use of 11C-PBR28 to confirm 
the work we have performed in rat models of AAA expansion and rupture. The goal of this project 
at this point is not to change current subject management, but we plan to establish the groundwork 
that will serve as a basis for a larger scale study in the future. 
 
 
 
II. 
SPECIFIC AIMS 
The aim of this project is to assess the ability of three different imaging techniques to determine 


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abdominal aortic aneurysm (AAA) rupture risk individually and in concert. Currently, the primary 
factor considered for risk of human AAA rupture is aortic diameter; however, it is well documented 
that small AAAs (<5cm) rupture, while many large AAAs (>8cm) are incidentally discovered. 
Thus, there is no absolute diameter threshold at which AAAs rupture. Approximately 60% of 
patients with ruptured AAA die before reaching the hospital, and emergency open surgical repair 
carries a mortality rate of 35-70%. This suggests that a new diagnostic modality must to be 
developed to reliably predict AAA rupture risk.  
 
We will image subjects with atherosclerotic, non-aneurismal aortas as a control group. We will 
also image smaller, surveillance size (3.0-4.5cm) AAAs, AAAs that will undergo treatment 
(female >5.0cm, male >5.5cm), as well as rapidly expanding AAAs (>0.5cm over 6 months and/or 
>1.0cm over 12 months). The assessment of AAA wall structural integrity by FEA, generated 
utilizing CTA, will be studied in the context of increased metabolic activity and inflammation 
determined by 18F-FDG and 11C-PBR28 PET. We hypothesize that areas of increased 18F-FDG 
and 11C-PBR28 uptake will correlate; however, areas of more discrete, focal 11C-PBR28 uptake 
will correlate with areas of greatest RPI and decreased strength in the AAA wall, and this will be 
most pronounced in rapidly expanding AAAs. However, we also hypothesize that a fraction of 
smaller AAAs will exhibit a similar pattern, demonstrating areas of increased metabolic activity 
and inflammation that are at increased risk of expansion and/or rupture, independent of size or 
diameter.  
 
Aim 1. Perform coregistered, FEA, as well as 18F-FDG and 11C-PBR28 PET of the infrarenal aorta 
using PET-CTA.  
 
Approach. Consider a rapidly expanding AAA group that will demonstrate changes in the 
structural integrity and inflammatory cascade within the AAA wall validating a current approach 
to AAA treatment. Consider a surveillance group of AAA subjects that will demonstrate the ability 
of FEA as well as 18F-FDG and 11C-PBR28, to identify those subjects that are at increased risk of 
AAA expansion and/or rupture, independent of size. 
 
Aim 2. Compare patterns of decreased aortic strength with patterns of increased stress and 
inflammation across three subject groups to determine the appropriateness of expanding these 
analyses to a larger group of clinically relevant subjects. 
 
Approach. Utilizing evolving software to evaluate the same aortic volume across data sets, we 
will compare areas under greatest stress and lowest strength determined by FEA. Multiplanar and 
volumetric analyses of co-registered, FEA as well as 18F-FDG and 11C-PBR28 PET images will 
also be performed. With direct co-registration of the data sets for each subject, qualitative 
comparisons will be made regarding areas of 18F-FDG and 11C-PBR28 uptake, as well as stress, 
strength, and RPI. 
 
 
III. 
SUBJECT SELECTION 
Twenty-four subjects will be recruited for this study. Six control subjects (three males and three 
females), will be considered. Control subjects will have known atherosclerosis by standard clinical 
criteria, without aneurysmal disease. Six subjects (three males and three females) with small AAAs 


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(diameter 3.0-4.5cm), six subjects (three males, AAA >5.5cm and three females, AAA >5.0cm) 
with AAAs that are indicated for treatment, and six subjects (three males and three females) with 
rapidly expanding AAAs (>0.5cm over 6 months and/or >1.0cm over 12 months) will be 
considered. During a clinical visit, the treating physician will introduce the study to each subject, 
and the study coordinator will provide a comprehensive description and materials to the subject. 
 
Subjects 45 years of age or older will be considered and subjects from any at-risk populations (e.g.: 
cognitively impaired persons, prisoners) will not be included. A subject will not be eligible for 
inclusion if any exclusion criteria for PET-CTA apply. Any woman of childbearing age, who is 
planning to become pregnant, is breastfeeding, and/or suspects she may be pregnant, will not be 
enrolled in the study. 
A subject will not be eligible for inclusion in this study if any of the following criteria apply: 
- 
less than 45 years of age; 
- 
pregnant or breastfeeding; 
- 
any greater than normal potential for cardiac arrest; 
- 
Renal disease – defined as eGFR < 60mg/ml/1.73m2 
- 
claustrophobic reactions and/or is unable to lie comfortably on a bed inside the scanner for 
60 minutes as assessed by physical examination and medical history (e.g. back pain, 
arthritis); 
 
A TSPO polymorphism has been previously demonstrated, and quantitative interpretations of 
signal can be confounded by interindividual variability in binding affinity.34 To avoid this 
confounder, we will perform Ala147Thr TSPO polymorphism genotyping as part of the screening 
process.  Those subjects identified as mixed affinity or high affinity from the genetic testing results 
will continue with PET-CTA imaging.  Those subjects who are identified as low affinity will be 
considered screen failures and will not have PET-CTA scanning performed. 
 
Eligibility will be determined by a screening interview and review of the medical record. All 
subjects recruited for the study will be able to withdraw from the study at any time. 
 
 
IV. 
SUBJECT ENROLLMENT 
Subjects scheduled for a vascular surgery clinic visit who fulfill the eligibility criteria will be 
identified through the patient appointment log.  
 
The clinicians will introduce the study to the subject during a clinic visit and will obtain permission 
from the potential subject to be approached by study staff.  Subjects will then be approached in 
person (ideally, and whenever possible) by a study coordinator to undergo consent and schedule 
the study.  At this time, subjects will be informed that the PET-CTA scanning session will be 
performed on the BJH main campus.  
 
The subjects will be informed about the PET-CTA scans, including that these scans will have no 
benefit or impact on their management as well as the risks associated with receiving Iopamidol, a 
regularly used CTA contrast agent, as well as 18F-FDG and 11C-PBR28, the two radiotracers being 
studied.  
 


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Informed consent will be obtained from the subjects by a member of the study team prior to 
obtaining the TSPO polymorphism genotyping blood sample and before the imaging session.  The 
study team member obtaining consent will explain the purpose of the study and its potential 
benefits to society at large. The protocols for the scans will be explained in detail. Subjects will be 
informed about potential risks and benefits of PET-CTA and that the scans will have no benefit or 
impact on their management. Subjects will be informed that they may withdraw from the study at 
any time, for any reason. They will be informed that their refusal to participate in the study or 
choosing to terminate participation at any point will have no influence on their future care and 
treatment.  Study subject information will be protected under HIPAA guidelines.   
 
All subjects will receive a one-time $200 remuneration following completion of the study required 
PET-CTA scans.  All subjects will also be offered parking validation for BJH main campus 
parking. 
 
 
V. 
STUDY PROCEDURES 
Subjects who have not had an eGFR blood test performed within the previous 90 days will have 
approximately 10 ml or 2 teaspoons of blood drawn for creatinine testing prior to the scan being 
performed. 
 
Subject Screening - Subjects will be recommended by their treating physician for the study during 
a clinic visit. The study team member obtaining consent will reinforce with the subjects that 
participation is voluntary and any decision not to participate will not in any way affect their care, 
now or in the future. If the subject chooses to participate, the study team member will obtain 
written informed consent. Any woman of childbearing age, who is seeking to become pregnant, is 
breastfeeding, or who suspects she may be pregnant, will not be enrolled in the study. 
As part of subject screening a genetic test (Ala147Thr TSPO polymorphism genotyping) will be 
performed. During enrollment subjects will be informed about the genetic testing for study 
eligibility. If subjects decide to be part of the study and sign the consent, blood will be drawn by 
the study coordinator.  Only those subjects identified as mixed affinity or high affinity from the 
genetic testing results will continue with PET-CTA imaging.  Those subjects who are identified as 
low affinity will be notified by the study team and will not have PET-CTA scanning performed.  
Participation in the study will end for the low affinity subjects following the genetic testing. 
 
Any female subject of child bearing potential will have a serum or urine pregnancy test the day of 
the PET scans. 
 
Any subject under 45 years-old will not be enrolled in this study. No third parties will assist with 
recruitment of eligible subjects for this protocol.  
 
 
Imaging Details: 
Positron Emission Tomography (PET)- Computed Tomography Angiography (CTA) – 
Eligible participants will undergo 18F-FDG and 11C-PBR28 PET-CT and contrast-enhanced CTA 
imaging performed on the Siemens Biograph 40 PET-CT scanner.  All participants will be studied 
after at least 12-16 hrs of fasting.  Subjects will be positioned for maximum comfort on the imaging 


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table, supine and arms resting above the head or across the chest out of the field of view.  PET 
imaging will begin with 11C-PBR28.  A dosage range of 10-20 mCi is planned.  A low-dose CT 
attenuation scan of the abdomen and pelvis will be acquired for subsequent correction of photon 
attenuation.  Each subject will receive a single intravenous bolus injection of the maximum 
planned dosage of 20 mCi diluted with normal saline up to a total of 20 mL.  The imaging 
acquisition over the aneurysm site will begin immediately with a ~20-minute dynamic imaging 
scan.  At the end of this imaging scan a 20 min static scan will be performed in the adjacent 
abdominal or pelvic site (to serve as a reference location). Subject will remain in the scanner for 
the FDG injection and CT angiography.  Subjects will receive an intravenous bolus injection of 10 
mCi of 18F-FDG followed by a 90-minute period prior to reimaging. Next, subjects will receive a 
standard dose of the Iopamidol contrast agent (50cc) followed by CTA imaging of the abdomen 
and pelvis using standard acquisition parameters to identify the arterial region of interest (ROI) to 
determine the blood input function.  At the end of the CTA imaging scan, subjects will be removed 
from the scanner to rest in an uptake room to allow for the decay of 11C-PBR28.  Subjects will be 
asked to use the restroom to empty their bladder after being removed from the scanner after the 
CTA imaging and again prior to being repositioned on the imaging table for the FDG scan.  A 
second low-dose CT attenuation will be performed with subsequent ~20-minute dynamic imaging 
acquisition for FDG.  The entire imaging session, including both PET and CT acquisitions, will 
last up to approximately three hours. The CTA images will be used to identify the arterial region 
of interest (ROI) for use in determining the blood input function.  
 
Aortic wall 11C-PBR28 and 18F-FDG uptake will be considered in terms of standard uptake values 
(SUV) considering the infrarenal abdominal aorta from the crossing of the left renal vein to the 
iliac bifurcation.  Voxel-wise SUV values over the AAA will be qualitatively assessed across 
subjects and groups.  Maximum (SUVmax) and mean (SUVmean) values normalized to the blood 
pool and non-aneurysmal thoracic aorta will also be considered.  SUVmax and SUV mean values 
associated with areas of focal uptake will also be considered and compared across subjects and 
groups using a Students t-test, with P = 0.05 indicating significance. 
 
Image Evaluation: 
Images will be evaluated by an experienced vascular surgeon, who will only evaluate the infrarenal 
abdominal aorta. Other organs and anatomic structures in the field of view will be evaluated by a 
radiologist on the study team for incidental findings. 
 
While there is some subjectivity in the manner by which a region of interest (ROI) is determined 
for image analysis, this study may not be blinded between control and experimental subjects, as 
control subjects will have non-aneurysmal aortas. However, the analyzing vascular surgeon will 
be blinded to whether a subject has a small versus a rapidly expanding AAA. 
 
FEA Interpretation: 
FEA will be performed by Dr. David Vorp’s group at the University of Pittsburgh.  PET-CTA 
scans performed for the study will be copied onto CD, labeled with a study ID only and mailed by 
a member of the Washington University Study team.  No PHI will be provided to University of 
Pittsburgh. The PET-CTA scans and FEA performed by Dr. Vorp’s laboratory at the University 
of Pittsburgh will be saved for possible future analysis or data presentation. 
 


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VI. 
BIOSTATISTICAL ANALYSIS 
 
This is an exploratory (hypothesis generating) study.  Subject Maximum transverse diameters, 
mean and peak wall stresses, mean and minimum wall strengths, and mean and peak RPI values 
will be compared between groups using a Students t-test, with P < 0.05 indicating significance. 
Aortic wall 11C-PBR28 and 18F-FDG uptake will be considered in terms of standard uptake values 
(SUV) considering the infrarenal abdominal aorta from the crossing of the left renal vein to the 
iliac bifurcation. Voxel-wise SUV values over the AAA will be qualitatively assessed across 
subjects and groups. Maximum (SUVmax) and mean (SUVmean) values normalized to the blood 
pool and non-aneurysmal thoracic aorta will also be considered.  SUVmax and SUVmean values 
associated with areas of focal uptake will also be considered and compared across subjects and 
groups using a Students t-test, with P < 0.05 indicating significance. Multiplanar and volumetric 
analyses of coregistered FEA, with 11C-PBR28 and 18F-FDG PET images will also be performed. 
With direct coregistration of the data sets for each subject, qualitative comparisons will be made 
regarding areas of 11C-PBR28 and 18F-FDG uptake, stress, strength, and RPI. Quantitatively, 
correlations of each data set per subject will be determined. 
 
There will be experimental and control group analysis by comparing subject demographics and 
aortic image measures. ANOVA with post hoc analyses will be performed to compare the groups. 
 
Power Calculation:  
From clinical experience, we expect total 24 subjects, approximately six subjects (3 men and 3 
women) with small AAA size that will continue to undergo surveillance (3.0-4.5cm), six subjects 
(3 men and 3 women) with AAAs that will undergo treatment, and six subjects (3 men and 3 
women) with rapidly expanding  AAAs (>0.5cm over 6 months and/or >1.0cm over 12 months). 
Control group will be consist of 6 subjects (3 men and 3 women) with known atherosclerosis, by 
nature of carotid stenosis and no aortic aneurismal dilation.  Since  this is an exploratory study, 
there is no definite power calculation  for qualitative measures but quantitative analysis  for 
continues variables, to reach a power of 0.80 with confidence level of 95% at alpha level of 0.05, 
there are approximately 10 subjects are needed per group. This is a small exploratory study, and 
we will limit the subject enrollment to six subjects per group due to the financial reasons. 
 
Statistical analysis will be performed using the SAS statistical package (SAS Institute Inc., Cary, 
NC).  
 
Specific Data Variables 
• Demographic/Social 
• Age, sex, race, smoking status 
• Clinical 
• Height, weight, BMI 
• History of DM, HTN, CAD, COPD, CKD, CHF 
• Medication history (including current medications) 
• Hemodynamic laboratory results 
• Procedural 
PET image measures, FEA image measures 


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VII. 
RISKS AND DISCOMFORTS 
  
Risks of PET-CT: 
Subjects participating in this study who undergo PET-CTA, will be exposed to radiation from 
PET-CTA scans of the abdomen and pelvis. Please note that this radiation is not necessary for the 
subject’s medical care and is for research purposes only. 
 
This study will expose subjects to radiation from PET-CTA scans of the abdomen and pelvis and 
from the radiotracers 11C- PBR28 and 18F-FDG. For 11C-PBR28 a dosage range of 10-20 mCi is 
planned.  The Effective Dose for cumulative and maximal radiation dosimetry is 2.42 rem and 
2.73 rem, respectively.  This includes a single intravenous injection of the maximum planned 
administered dosage of 20 mCi of 11C-PBR28 and 10 mCi of 18F-fludeoxglucose plus two low-
dose CTAC scans with topogram and contrast-enhanced CTA imaging of the abdomen and pelvis.  
Maximal Radiation Dosimetry includes one additional low-dose CTAC scan with topogram for 
subjects who undergo a make-up study in the event of technical difficulties due to cyclotron 
radiopharmaceutical failure or with the PET-CT scanner.   
 
If a subject is pregnant or breastfeeding they may not participate in this research study. 
 
Since the effects of radiation can be cumulative, it is important to know of past research related 
radiation exposure. If the subject has participated in other research studies in the past 12 months 
that have involved radiation exposure, they will be asked to inform the investigators or study staff.  
If it is determined that the subject’s prior radiation exposure exceeds our current guidelines, it is 
possible that they will not be allowed to participate in this study. 
 
 
Risks of the Radiotracers 11C-PBR28 and 18F-FDG: 
There are no known side effects to these radioactive dyes.  FDG is approved by the FDA and is 
used daily across the United States. 11C-PBR28 is an investigational radioactive drug. An 
investigational drug is one that has not been approved by the U.S. Food and Drug Administration 
(FDA). This means that PBR28 can only be used in research studies. 
 
There are no known pharmacological risks or side effects of receiving 11C-PBR28 at the dose 
subjects will receive. However, as with any drug, an allergic reaction can occur. Allergic reactions 
can be mild or serious, and can even result in death in some cases.  Common symptoms of an 
allergic reaction are rash, itching, skin problems, swelling of the face and throat, or trouble 
breathing.  Subjects will be instructed to notify study staff right away if they think they are having 
an allergic reaction.   
 
18F-FDG is a type of radiation emitting product that may increase an individual’s risk of cancer. 
We use the smallest dose necessary for imaging and ensure safety during injection.   
 
Risks of the IV: 
Placing an IV catheter into the arm may cause some pain, discomfort, bruising, bleeding, swelling, 
and redness in that area. There is a slight risk of infection which can be treated, temporary loss of 
pulse at the wrist, and fainting.  There may be bruising, pain or discomfort for 2-3 days after the 


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IV catheter is removed.  Rarely, an infection may occur at this site, and if infection does occur, it 
will be treated appropriately. A urine or serum blood (about 2 teaspoons) of blood may be taken 
during this study for pregnancy test, if required.   
 
Risks of Iopamidol Dye: 
Rare side effects from the contrast dye Iopamidol include: 
- 
Nausea (up to 2 in 100 of people).  
- 
Hives (itchy red bumps on the skin, < 1 in 100 people) 
- 
Severe allergic reaction, which can be life threatening (very rarely happens, < 1 in 100,000 
people).  If you have any signs of allergic reaction, we will treat you immediately. 
 
Allergic reactions can be mild or serious, and can even result in death in some cases. Common 
symptoms of an allergic reaction are rash, itching, skin problems, swelling of the face and throat, 
or trouble breathing.  Subjects who think that they are having an allergic reaction, should notify 
the study physician immediately.  If they are having trouble breathing, they should tell the study 
physician immediately.  If experiencing any swelling of the face and/or throat, and/or experiencing 
any trouble breathing after leaving the imaging center, they should call 911 immediately and seek 
medical assistance.  
 
Risks of Unexpected Findings: 
We are performing PET-CTA scans in this study to answer research questions, not as part of the 
medical care.  The information created by this study will not become part of the subject’s hospital 
record.  The PET-CTA scans are not the same as a scan that another physician would order.  It 
may or may not demonstrate anatomy/pathology that would be found on standard PET or CTA 
scans.  
 
The imaging studies performed for this study are for research purposes only. We will only evaluate 
the infrarenal abdominal aorta. Other organs and anatomic structures in the field of view will be 
evaluated for incidental findings by a radiologist on the study team.   
 
 
VIII. POTENTIAL BENEFITS 
 
There is no expected direct benefit for subjects taking part in this study.   Results of this study may 
contribute to prevention of AAA rupture in the future. 
 
IX. 
MONITORING AND QUALITY ASSURANCE 
Any unanticipated problems and adverse events involving risk to human subjects will be reviewed 
by the Principal Investigator and will be reported to the Human Research Committee and the BJH 
RDRC, within the required time frame and to all participating investigators by the PI, according 
to the Human Research Protection Office guidelines. 
 
The imaging techniques utilized for this study are all FDA approved.  Each scanner has a built-in 
monitoring system that automatically shuts down the scanner, if parameters exceed safe levels.  In 
addition, imaging technicians constantly monitor the subjects’ physiologic status and quality of 
the raw data.  
 


English – Predictors of AAA Expansion 
 
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Subject data will be stored on a secure, limited-access, password protected, WU network shared 
drive. Access will be granted to members of the study team. If any new investigator is added to 
the protocol and approved by the IRB, the PI will provide network access to that specific 
investigator. 
 
Data entry will be done by the research coordinator /research nurse weekly and will be monitored 
by the PI.   
 
 
PROJECT TIMELINE 
Objective 
Months 1-8 
Months 9-10 
Months 11-12 
Perform coregistered FEA with /18F-
FDG &  11C-PBR28  PET  
 
 
 
Compare patterns of decreased aortic 
strength with patterns of increased stress, 
RPI, and inflammation 
 
 
 
 
Finalization of data analysis and abstract 
submission 
 
 
 
 
 
X. 
REFERENCES 
1. Guirguis-Blake J and Wolff TA. Screening for abdominal aortic aneurism. Am Fam 
Physician. 2005;71:2154-5. 
2. Bengtsson H, et al. Increasing prevalence of abdominal aortic aneurysms. A necropsy study. 
The European journal of surgery = Acta chirurgica. 1992;158:19-23. 
3. McFarlane MJ. The epidemiologic necropsy for abdominal aortic aneurysm. Jama. 
1991;265:2085-8. 
4. Singh K, et al. Prevalence of and risk factors for abdominal aortic aneurysms in a population-
based study : The Tromso Study. American journal of epidemiology. 2001;154:236-44. 
5. Lilienfeld DE, et al.. Epidemiology of aortic aneurysms: I. Mortality trends in the United 
States, 1951 to 1981. Arteriosclerosis (Dallas, Tex). 1987;7:637-43. 
6. Kozak LJ, et al. National hospital discharge survey: 2004 annual summary with detailed 
diagnosis and procedure data. Vital Health Stat 13. 2006:1-209. 
7. Eliason JL, et al. The effect of secondary operations on mortality following abdominal aortic 
aneurysm repair in the United States: 1988-2001. Vasc Endovascular Surg. 2005;39:465-72. 
8. Filardo G, et al.. Surgery for small asymptomatic abdominal aortic aneurysms. The Cochrane 
database of systematic reviews. 2012;3:Cd001835. 
9. Veith FJ, et al. Treatment of ruptured abdominal aneurysms with stent grafts: a new gold 
standard? Seminars in vascular surgery. 2003;16:171-5. 
10. Acosta S, et al. Increasing incidence of ruptured abdominal aortic aneurysm: a population-
based study. Journal of vascular surgery. 2006;44:237-43. 


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11. Cowan JA, Jr., et al. Epidemiology of aortic aneurysm repair in the United States from 1993 
to 2003. Annals of the New York Academy of Sciences. 2006;1085:1-10. 
12. Fleming C, et al. Screening for abdominal aortic aneurysm: a best-evidence systematic 
review for the U.S. Preventive Services Task Force. Annals of internal medicine. 
2005;142:203-11. 
13. Schermerhorn M, et al. Ultrasound screening for abdominal aortic aneurysm in medicare 
beneficiaries. Annals of vascular surgery. 2008;22:16-24. 
14. Fillinger MF, et al. Prediction of rupture risk in abdominal aortic aneurysm during 
observation: wall stress versus diameter. Journal of vascular surgery. 2003;37:724-32. 
15. Elger DF, et al. The influence of shape on the stresses in model abdominal aortic aneurysms. 
Journal of biomechanical engineering. 1996;118:326-32. 
16. Inzoli F, et al. Biomechanical factors in abdominal aortic aneurysm rupture. European 
journal of vascular surgery. 1993;7:667-74. 
17. Mower WR, et al. Effect of intraluminal thrombus on abdominal aortic aneurysm wall stress. 
Journal of vascular surgery. 1997;26:602-8. 
18. Vande Geest JP, et al.. The effects of anisotropy on the stress analyses of patient-specific 
abdominal aortic aneurysms. Annals of biomedical engineering. 2008;36:921-32. 
19. Vande Geest JP, et al. A biomechanics-based rupture potential index for abdominal aortic 
aneurysm risk assessment: demonstrative application. Annals of the New York Academy of 
Sciences. 2006;1085:11-21. 
20. Carmeliet P, et al. Urokinase-generated plasmin activates matrix metalloproteinases during 
aneurysm formation. Nat Genet. 1997;17:439-44. 
21. Rudd JH, et al. (18)Fluorodeoxyglucose positron emission tomography imaging of 
atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis 
therapy trials. J Am Coll Cardiol. 2007;50:892-6. 
22. Kotze CW, et al.. Increased metabolic activity in abdominal aortic aneurysm detected by 
18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography 
(PET/CT). European journal of vascular and endovascular surgery : the official journal of 
the European Society for Vascular Surgery. 2009;38:93-9. 
23. Sakalihasan N, et al. Positron emission tomography (PET) evaluation of abdominal aortic 
aneurysm (AAA). European journal of vascular and endovascular surgery : the official 
journal of the European Society for Vascular Surgery. 2002;23:431-6. 
24. Reeps C, et al. Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in 
positron emission/computed tomography is associated with inflammation, aortic wall 
instability, and acute symptoms. J Vasc Surg. 2008;48:417-23; discussion 424. 
25. Reeps C, et al. Quantitative assessment of glucose metabolism in the vessel wall of 
abdominal aortic aneurysms: correlation with histology and role of partial volume correction. 
Int J Cardiovasc Imaging. 2013;29:505-12. 
26. English SJ, et al. 18F-FDG PET is a Useful Test to Evaluate Inflammation Associated with 
Human Abdominal Aortic Aneurysm Development. Journal of vascular surgery. 58:1153-
1154. 
27. English SJ, et al. Increased 18F-FDG Uptake Is Predictive of Rupture in a Novel Rat 
Abdominal Aortic Aneurysm Rupture Model. Annals of surgery. 2014. 
28. Canat X, et al. Distribution profile and properties of peripheral-type benzodiazepine 
receptors on human hemopoietic cells. Life Sci. 1993, 52:107–118. 
29. Brown AK, et al. Radiation dosimetry and biodistribution in monkey and man of 11C-


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PBR28: a PET radioligand to image inflammation. J Nucl Med. 2007, 48:2072–2079.    
30. Kreisl WC, etl. Stroke incidentally identified using improved positron emission 
  tomography for microglial activation. Arch Neurol. 2009, 66:1288–1289. 
31. Laitinen I, et al. Uptake of inflammatory cell marker [11C]PK11195 into mouse 
atherosclerotic plaques. Eur J Nucl Med Mol Imaging. 2009, 36:73–80. 
32. Gaemperli O, et al. Imaging intraplaque inflammation in carotid atherosclerosis with 11C-
PK11195 positron emission tomography/computed tomography. Eur Heart J. 2012, 
33:1902–1910. 
33. English SJ, et al. Utility of 18F-FDG & 11C-PBR28 for the assessment of rat aortic aneurysm 
inflammation. EJNMMI Res. 2014: 4(1): 20. 
34. Owen DR, et al. An 18-kDa translocator protein (TSPO) polymorphism explains 
differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 
2012 Jan;32(1):1-5. 

ICF_001.pdf: 
Noninvasive Assessment of Abdominal Aortic Aneurysm Wall Structural 
Integrity and Inflammation as Predictors of Expansion and/or Rupture
NCT 03231397
Unique Protocol ID:  201702141
Principal Investigator: Sean J English, MD.
Protocol Version: 02
Version date:  10/09/2018


FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
English – Predictors of AAA Expansion 
Page 1 of 12 
Version 03 – 10/09/2018 
INFORMED CONSENT DOCUMENT 
Project Title: 
Noninvasive Assessment of Abdominal Aortic Aneurysm (AAA) Wall Structural 
Integrity and Inflammation as Predictors of Expansion and/or Rupture 
Principal Investigator: 
Sean English, M.D. 
Research Team Contact: 
Julie Wilson, RN      
314-747-7828
Ashley Burgess, RN, BSN        
314-362-6257
This consent form describes the research study and helps you decide if you want to participate.  It 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights and responsibilities as a research participant. By signing this 
form, you are agreeing to participate in this study. 
•
You should read and understand the information in this document including the procedures,
risks, and potential benefits.
•
If you have questions about anything in this form, you should ask the research team for more
information before you agree to participate.
•
You may also wish to talk to your family or friends about your participation in this study.
•
Do not agree to participate in this study unless the research team has answered your
questions and you decide that you want to be part of this study.
WHAT IS THE PURPOSE OF THIS STUDY? 
This is a research study.  We invite you to participate in this research study because you either have a 
known abdominal aortic aneurysm (AAA) or because you do not have an AAA (control group).   
The aorta serves as the main artery to supply blood flow to the body. It is approximately the size of a 
garden hose. Due to the effects of high blood pressure (hypertension), atherosclerosis (hardening of the 
arteries), and tobacco use, the aorta may widen and enlarge to form an aneurysm. An abdominal aortic 
aneurysm (AAA) is a dilation (enlargement) or ballooning out of a section of blood vessel caused by 
disease or weakness in the wall of the aorta below the level of the kidney arteries.  As an AAA dilates 
and increases in size, rupture of the AAA may occur. AAA rupture carries a significant risk of death. 
Currently, aortic size is the primary factor used to assess aortic rupture risk. There are other imaging 
procedures (imaging modalities) that are being used and developed to assess AAA rupture risk. Finite 
element analysis (FEA) is a way to study the mechanical properties of the aortic wall, including areas of 
stress and strength that are used to calculate rupture risk. Positron Emission Tomography (PET) utilizes 
glucose (a form of sugar) labeled with a radioactivity to look at the metabolic activity and inflammation 
in the aortic wall.  
The purpose of this research study is to further study, through FEA, changes that occur in the 
mechanical properties of the aortic wall. We would like to compare two radiotracers, 18F-FDG and 11C-
PBR28 to determine if one provides more useful and reliable information about inflammation. 18F-FDG 
and 11C-PBR28 are radioactive drugs that will be used for imaging during your PET-CT scan. We 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
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Page 2 of 12 
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would also like to compare the results describing the mechanical properties of the AAA wall to the 
degree of inflammation in that wall as determined by PET-CT imaging to define new and better 
predictors of AAA growth and/or rupture.   
 
The radioactive tracers that are used in this study are 18F-fludeoxyglucose (FDG) and 11C-PBR28 (PBR 
which stands for Peripheral Benzodiazepine Receptor.  11C-PBR28 is considered investigational, which 
means that it has not been approved by the U.S. Food and Drug Administration. FDG is an approved 
drug by the FDA, however in this study it is considered investigational  
 
WHAT WILL HAPPEN DURING THIS STUDY? 
Screening Procedures: 
If you agree to participate in this study, you will be asked to have a blood draw, approximately 1-2 
teaspoons of blood, taken from a vein in your arm, so that we can perform a genetic test.  This genetic 
test will look at genes and proteins that may be expressed more frequently in AAA.  Depending on the 
results of the genetic test your study doctor will determine whether you will be eligible to proceed to the 
PET-CT imaging portion of the study.  The study team will communicate to you a plan following the 
genetic test (proceed to scanning or ending participation). You will not be made aware of the results of 
the genotyping. 
 
If you go on to the scanning portion of the study, we will ask you some standard questions to make sure 
that it is safe for you to undergo a PET-CT scan. If you have not had a renal function blood test 
performed within the past 90 days, we will draw approximately 2 teaspoons of blood for a creatinine 
test. We will also ask for your permission to use a contrast dye for the CT portion of the PET-CT scan.  
The contrast agent helps us see the blood circulating (moving around) in your body and blood vessels.  
If you agree, we will ask you some additional questions to see if you are eligible to receive the contrast 
dye.    
 
Imaging will be performed using a combined PET-CT scanner to take pictures of your body.  A PET/CT 
(Positron Emission Tomography (PET) combined with Computed Tomography (CT) imaging camera.  
PET scanners allow us to image the function of different cells and organs in the body after you are 
injected with a radioactive tracer.  The CT scan (computed tomography) is an x-ray scanner that images 
the anatomy (size or structure) of the body giving us detailed images such as pictures of the aorta, other 
blood vessels, and surrounding tissues.  The PET-CT scanner is a large tube in the shape of a donut with 
a padded imaging table in the middle of the machine that records images of your body after the injection 
of the iodinated contrast and radioactive tracers.  A radioactive tracer is often a naturally occurring 
substance that contains a small amount of radioactivity so pictures can be taken of your abdomen and 
pelvis.   
 
You will be given an injection of a small amount of a radioactive drug/tracer (a chemical similar to 
sugar which is called FDG) into a vein in your arm.  The amount of radiation is very small, no more than 
what you would have during a normal x-ray.  It only stays in your body for a few hours.  The FDG will 
travel to particular parts of your body where glucose is used for energy, such as the aorta. 
 
 
 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
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PET scanning can make pictures of structures inside the body because the tracer “lights up” on the 
pictures. This shows us details of the aorta, other blood vessels, and surrounding tissues. The radioactive 
material breaks down and leaves your body gradually through the urine. It takes about 1 day for the 
radioactive material to exit your body completely. 
 
Since the effects of radiation can be cumulative, it is important to know about your past research related 
radiation exposure. If you have participated in other research studies in the past 12 months that have 
involved radiation exposure, please inform the investigators or study staff.  If it is determined that your 
prior radiation exposure exceeds our current guidelines, it is possible that you will not be allowed to 
participate in this study. 
 
Please place your initials in the blank next to ‘I have’ or ‘have not’ for each of the questions 
below: 
 
 
I have _______________have not ______________participated in research studies involving radiation 
exposure within the last 12 months. 
 
PET-CT with Contrast CT Angiography imaging: 
If you are to proceed to the imaging portion of the study, we will ask that you undergo PET-CT imaging 
that will last approximately 3 hours.  On the day of your imaging scan, you will be asked to come to the 
Center for Clinical Imaging Research Facility (CCIR) located within the Barnes-Jewish Hospital 
complex.  Wear comfortable clothing and bring an updated medication list. 
 
Your imaging visit will have the following procedures: 
• If you are a woman who can become pregnant, we will perform a urine or blood pregnancy test 
(blood test, approximately 2 teaspoons of blood) prior to performing the PET-CT scan.  Pregnant 
and breastfeeding women may not take part in this study.   
• We will require that you fast for approximately 12-16 hours prior to your PET-CT scan.  This 
means you will not eat solid food during that 12-16-hour period.  You may drink water and 
should drink at least two or three glasses of water during this time.   
• We will also ask that you refrain from heavy exercise for 24 hours prior to the study.  
• You may need to change into a hospital gown if you have anything on your body that contains 
metal, such as jewelry, piercings, or zippers.  
• You will have two (2) intravenous (IV) catheters placed in the veins of your arms, usually one IV 
in each arm for the purpose of radioactive tracer injections and the other for contrast agent 
injection or to draw blood samples.  An IV catheter is a thin, flexible tube that is placed in a vein 
with a needle. 
• We will also check your blood sugar using a drop of blood from your IV line or by a finger stick 
to make sure that it is low enough for us to get an accurate picture of inside your body.   
• Vital signs (blood pressure and heart rate) will be obtained prior to imaging.  Additional vital 
signs may be taken during the imaging scans. 
 
 
You will be positioned on the PET-CT imaging table lying flat with your arms resting above your head 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
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or across your chest out of the field of view.  You will be made to feel as comfortable as possible.  We 
will ask you to lie still during the imaging scan of your abdomen and pelvis.  The imaging table will 
slowly move you into the scanner.  You will be given the radiotracer 11C-PBR28 through your IV 
followed by up to 40-minutes of PET imaging.  Next, you will be given FDG tracer and then you will 
remain in the scanner and be given an iodine contrast material (dye) through your IV followed by 
approximately 10 minutes of CT imaging.  Upon completion of the CT imaging scan, you will be 
removed from the scanner and escorted to the bathroom and encouraged to empty your bladder.  Next, 
you will be placed in a quiet room to rest in a reclining chair before your next imaging scan.  You will 
not be able to eat during this time, but you may drink water.  Prior to the next imaging scan, you will 
again be escorted to the bathroom and encouraged to empty your bladder before placing you back in the 
in the PET/CT scanner.  You will again be positioned on the imaging table lying flat with your arms as 
they were for the first scan.  The imaging table will slowly move you into the scanner and you will have 
20 minutes of PET imaging performed.   
 
After the scan is completed: 
When you have completed the study, we will remove the IV catheters and place bandages the places on 
your arms. You may feel tired after the imaging scans because you have been fasting for several hours.  
We will offer you a snack while you rest before leaving the imaging facility.  You should drink plenty of 
water to help flush the radioactive material out of your body. This is a natural process for the body to rid 
itself of the radioactivity through your kidneys.   
 
Will you save my samples or research data to use in future research studies?  
As part of this study, we are obtaining blood samples and PET-CT scans from you. We would like to use 
the PET-CT scans and data obtained from those scans for studies going on right now as well as studies 
that are conducted in the future.  These studies may provide additional information that will be helpful in 
understanding vascular disease, or other diseases or conditions, including research to develop 
investigational tests, treatments, drugs or devices that are not yet approved by the U.S. Food and Drug 
Administration.  It is unlikely that what we learn from these studies will have a direct benefit to you.  
There are no plans to provide financial compensation to you should this occur.  By allowing us to use 
your PET-CT scan results you give up any property rights you may have in these scans. 
 
We will share your PET-CT scans with other researchers.  They may be doing research in areas similar 
to this research or in other unrelated areas.  These researchers may be at Washington University, at other 
research centers and institutions, or industry sponsors of research.  We may also share your research data 
with large data repositories (a repository is a database of information) for broad sharing with the 
research community.  If your individual research data is placed in one of these repositories only 
qualified researchers, who have received prior approval from individuals that monitor the use of the 
data, will be able to look at your information.   
 
If you change your mind and do not want us to store and use your PET-CT scans for future research you 
should contact the research team member identified at the top of this document.  The PET-CT scans will 
no longer be used for research purposes.  However, if some research with your PET-CT scans has 
already been completed, the information from that research may still be used. Also, if the PET-CT scans 
have been shared with other researchers it might not be possible to withdraw the PET-CT scans to the 
extent it has been shared. 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
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HOW MANY PEOPLE WILL PARTICIPATE? 
Approximately 30 people will take part in this study conducted by investigators at Washington 
University.  All will have a blood sample drawn for genetic testing and those that qualify will have PET-
CT imaging.  Approximately twenty-four (24) people will be enrolled into the imaging portion of the 
study.  Twelve (18) subjects will have a known AAA and six (6) will be free of any known AAA 
(control group).    
 
HOW LONG WILL I BE IN THIS STUDY? 
If you agree to take part in this study, your involvement will last until your imaging has been completed.  
If your study doctor notifies you that your genetic testing did not qualify you to continue with the 
imaging portion of the study, then your participation will end at that time. 
 
WHAT ARE THE RISKS OF THIS STUDY? 
You may experience one or more of the risks indicated below from being in this study.  In addition to 
these, there may be other unknown risks or risks that we did not anticipate, associated with being in this 
study.   
 
Some risks described in this consent document, if severe, may cause death.  
 
Risks associated with the IV: 
Placing an IV catheter into your arm may cause some pain, discomfort, bruising, bleeding, swelling, and 
redness in that area. There is a slight risk of infection which can be treated, temporary loss of pulse at 
the wrist, and fainting. You may have a bruise, feel pain, or be uncomfortable for 2-3 days after the IV 
catheter is removed.  Rarely, an infection may occur at this site, and if the infection does occur, it will be 
treated appropriately.   
 
Risks associated with the blood draw may include: 
Likely: 
Mild 
Pain at the needle stick site 
 
Less Likely / Less Common 
Mild 
The blood draw may cause bleeding or bruising. 
 
Rare: 
Serious 
Some people become dizzy or feel faint. 
There is also a rare risk of infection. 
 
Risks associated with PET/CT imaging: 
Likely:  Lying still in the scanner may produce some stiffness.  Study staff will be nearby to stop the 
study in case you become too uncomfortable.   
 
 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
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Less likely:  You may experience aching in your joints and muscles from lying very still.  This research 
may produce some anxiety and discomfort.  
 
Rare:  A small fraction of participants experience claustrophobia (anxiety due to being restrained or in a 
confined area) while some experience dizziness or feel faint.  If you experience any of these symptoms 
and do not wish to continue for any reason, the study will be stopped immediately.   
 
Medical Devices:  There is a rare risk of malfunction of worn or implanted electronic medical devices 
with MRI and CT scanning.  If you wear or have an electronic medical device implanted, such as an 
insulin pump, you will be asked to tell the study investigator and research staff. 
 
Risks of Unexpected Findings: 
We are doing the PET-CT scan in the study to answer research questions, not as part of your medical 
care. The information created by this study will not usually become part of your hospital record. This 
PET-CT scan is not the same as the one that your own doctor would order. It may or may not show 
problems that would be found on standard PET or CT scans.  
 
The imaging performed for this study is for research purposes only. We will only evaluate the infrarenal 
abdominal aorta. Other organs and anatomic structures in the field of view will be evaluated by a 
radiologist on the study team for incidental findings. You will be made aware of the results of incidental 
findings. The results of this study may be incorporated in the decision making regarding your aortic 
pathology; however, your ultimate management will be dictated by current standards of care.  
 
Risks associated with 11C-PBR28 and 18F-FDG radiotracers: 
Likely:  Radioactive tracers used for PET imaging, 11C-PBR28 and 18F-FDG are not expected to produce 
any health risks other than those associated with radiation exposure. 
 
Rare:  There are no known pharmacological risks or side effects of receiving 11C-PBR28 at the dose you 
will receive. However, as with any drug, an allergic reaction can occur. Allergic reactions can be mild or 
serious, and can even result in death in some cases. Common symptoms of an allergic reaction are rash, 
itching, skin problems, swelling of the face and throat or trouble breathing. If you think you are having 
an allergic reaction, let us know right away. 
 
18F-fludeoxyglucose (FDG) is a type of radiation emitting product, therefore, may increase the risk of 
cancer. We use the smallest dose necessary for imaging and ensure safety during injection.   
 
Risks associated with Radiation Exposure: 
Please note that this radiation exposure is not necessary for your medical care and is for research 
purpose only.   
 
Likely:  This study will expose you to radiation from the PET-CT imaging scans of your abdomen and 
pelvis and from the radiotracers 11C-PBR28 and 18F-FDG.  The amount of radiation from this, when 
averaged over your entire body, is approximately 48% of the amount a person who works with radiation 
is allowed to have in one year.  In the event of a failed radiotracer, you may be rescheduled for a make-
up imaging visit to complete the study.  The maximum amount of radiation from this, when averaged 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
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over your entire body, is approximately 55% of the amount a person who works with radiation is 
allowed to have in one year.  The risk from the radiation exposure in this study is too small to be 
measured.  It is not a big risk when compared with other risks you take every day.  If you want to know 
more about radiation exposure, please see the “Radiation Fact Sheet” at http://hrpo.wustl.edu or ask the 
study staff for a copy. 
 
Risks associated with the Iodinated Contrast Dye Iopamidol (Routine CT Scan dye): 
Rare: Side effects from the contrast dye Iopamidol include: 
- 
Nausea (up to 2 in 100 of people).  
- 
Hives (itchy red bumps on the skin, < 1 in 100 of people) 
- 
Severe allergic reaction, which can be life-threatening (very rarely happens, < 1 in 100,000 
people).  If you have any signs of allergic reaction, we will treat you immediately. 
 
Allergic reactions can be mild or serious, and can even result in death in some cases. Common 
symptoms of an allergic reaction are rash, itching, skin problems, swelling of the face and throat, or 
trouble breathing.  If you think that you are having an allergic reaction, notify the study physician or 
team member immediately.  If you are having trouble breathing, tell us immediately.  If you experience 
any swelling of the face and/or throat, and/or you experience any trouble breathing after you have left 
the imaging center, call 911 immediately and seek medical assistance.  
 
Radiation Exposure in Women Capable of Becoming Pregnant 
You may not participate in this study if you are pregnant or breastfeeding.  If you are capable of 
becoming pregnant, we will perform a pregnancy test before exposing you to research-related radiation.  
You must tell us if you think there is any chance that you may have become pregnant.  
 
Genetics 
There is a federal law called the Genetic Information Nondiscrimination Act (GINA). In general, this 
law makes it illegal for health insurance companies, group health plans and employers with greater than 
15 employees to discriminate against you based on your genetic information. However, it does not 
protect you against discrimination by companies that sell life insurance, disability insurance or long-
term-care insurance.  
 
Breach of Confidentiality 
One risk of participating in this study is that confidential information about you may be accidentally 
disclosed.  We will use our best efforts to keep the information about you secure.  Please see the section 
in this consent form titled “How will you keep my information confidential?” for more information. 
 
WHAT ARE THE BENEFITS OF THIS STUDY? 
You will not benefit from being in this study. 
 
However, we hope that, in the future, other people might benefit from this study because of what we 
may learn from this study.   
 
 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
English – Predictors of AAA Expansion 
 
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WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
You will not have any costs for being in this research study. 
 
You and/or your medical/hospital insurance provider will remain responsible for your regular medical 
care expenses. 
 
WILL I BE PAID FOR PARTICIPATING? 
You will be paid for being in this research study. You will need to provide your social security number 
(SSN) in order for us to pay you. You may choose to participate without being paid if you do not wish to 
provide your social security number (SSN) for this purpose.  You may also need to provide your address 
if a check will be mailed to you.  It should take approximately 2 – 4 weeks to receive payment for your 
participation in the study.  If your social security number is obtained for payment purposes only, it will 
not be retained for research purposes.    
 
We will pay you $200 for your participation if you complete the study PET-CT scan.  If you have to 
stop the PET-CT scan early for any medical reason or mechanical error, you will still receive the full 
payment. We will ask you if you are willing to complete the study, if you agree, we will schedule a visit 
to complete the study at your convenience. 
 
We will provide parking validation if you drive to your study sessions. 
 
WHO IS FUNDING THIS STUDY? 
The University and the research team are not receiving payment from other agencies, organizations, or 
companies to conduct this research study.  
 
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
Washington University investigators and staff will try to reduce, control, and treat any complications 
from this research. If you feel you are injured because of the study, please contact the investigator at 
(314) 362-3511 and/or the Human Research Protection Office at 1-(800)-438-0445.  
 
Decisions about whether payment for medical treatment for injuries relating to your participation in 
research will be made by Washington University. If you need to seek medical care for a research-related 
injury, please notify the investigator as soon as possible.  
 
HOW WILL YOU KEEP MY INFORMATION CONFIDENTIAL? 
We will keep your participation in this research study confidential to the extent permitted by law.  
However, it is possible that other people such as those indicated below may become aware of your 
participation in this study and may inspect and copy records pertaining to this research.  Some of these 
records could contain information that personally identifies you.  
• Government representatives, (including the Office for Human Research Protections) to complete 
federal or state responsibilities 
• The U.S. Food and Drug Administration 
• The University of Pittsburgh 
• Your primary care physician if a medical condition that needs urgent attention is discovered 
• Hospital or University representatives, to complete Hospital or University responsibilities 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
English – Predictors of AAA Expansion 
 
Page 9 of 12 
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• The last four digits of your social security number may be used in hospital or University systems 
to track billing information for research procedures 
• Washington University’s Institutional Review Board (a committee that oversees the conduct of 
research involving human participants) and the Human Research Protection Office. The 
Institutional Review Board has reviewed and approved this study.  
 
To help protect your confidentiality, paper/hard copy records will be stored in a locked suite/locked 
office by the study team in the Vascular Surgery Office with access limited to only those on the study 
team.  Electronic records for the study will be stored on a secure, password-protected, WU shared 
network drive with access limited to the study team.  FEA will be performed at the University of 
Pittsburgh.  PET-CT scans performed for the study will be copied onto CD, labeled with a study ID only 
and mailed by a member of the Washington University Study team.  No PHI will be provided to 
University of Pittsburgh and they will not be able to link the FEA or PET-CT back to you. Your blood 
samples will be labeled with your initials, study number, and date and time of collection.  The genetic 
samples will be drawn by the study team and then transported directly to the vascular surgery laboratory 
for analysis.  These samples will be labeled with your Study ID number, initials, and date/time of 
collection.  Urine pregnancy test (if required) will be performed by the study staff in the CCIR.   The 
pregnancy and genetic samples will be drawn by the study team and then transported directly to a 
laboratory for analysis.   
 
 
If we write a report or article about this study or share the study data set with others, we will do so in 
such a way that you cannot be directly identified. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time. 
 
Are there additional protections for my health information? 
Protected Health Information (PHI) is health information that identifies you. PHI is protected by federal 
law under HIPAA (the Health Insurance Portability and Accountability Act). To take part in this 
research, you must give the research team permission to use and disclose (share) your PHI for the study 
as explained in this consent form.  The research team will follow state and federal laws and may share 
your health information with the agencies and people listed under the previous section titled, “How will 
you keep my information confidential?” 
 
Once your health information is shared with someone outside of the research team, it may no longer be 
protected by HIPAA.   
 
The research team will only use and share your information as talked about in this form or as permitted 
or required by law.  When possible, the research team will make sure information cannot be linked to 
you (de-identified).  Once information is de-identified, it may be used and shared for other purposes not 
discussed in this consent form. If you have questions or concerns about your privacy and the use of your 
PHI, please contact the University’s Privacy Officer at 866-747-4975.  
 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
English – Predictors of AAA Expansion 
 
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Although you will not be allowed to see the study information, you may be given access to your health 
care records by contacting your health care provider.  
 
If you decide not to sign this form, it will not affect 
• your treatment or the care given by your health provider. 
• your insurance payment or enrollment in any health plans.   
• any benefits to which you are entitled. 
However, it will not be possible for you to take part in the study. 
 
If you sign this form: 
• You authorize the use of your PHI for this research 
• This authorization does not expire. 
• You may later change your mind and not let the research team use or share your information 
(you may revoke your authorization).  
• To revoke your authorization, complete the withdrawal letter, found in the Participant section 
of the Human Research Protection Office website at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ or you may request that the 
investigator sends you a copy of the letter.    
 
 
 
o If you revoke your authorization: 
 The research team may only use and share information already collected for 
the study. 
 Your information may still be used and shared as necessary to maintain the 
integrity of the research, for example, to account for a participant’s 
withdrawal from the research study or for safety reasons. 
 You will not be allowed to continue to participate in the study. 
 
IS BEING IN THIS STUDY VOLUNTARY? 
Taking part in this research study is completely voluntary.  You may choose not to take part at all.  If 
you decide to be in this study, you may stop participating at any time. Any data that was collected as 
part of your participation in the study will remain as part of the study records and cannot be removed.   
 
If you decide not to be in this study, or if you stop participating at any time, you won’t be penalized or 
lose any benefits for which you otherwise qualify.   
 
What if I decide to withdraw from the study? 
You may withdraw by telling the study team you are no longer interested in participating in the study or 
you may send a withdrawal letter. A sample withdrawal letter can be found at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ under Withdrawing from a Research 
Study. 
 
Will I receive new information about the study while participating? 
If we obtain any new information during this study that might affect your willingness to continue 
participating in the study, we’ll promptly provide you with that information. 
 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
English – Predictors of AAA Expansion 
 
Page 11 of 12 
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Can someone else end my participation in this study? 
Under certain circumstances, the investigator might decide to end your participation in this research 
study earlier than planned.  This might happen for no reason or because in our judgment it would not be 
safe for you to continue, because you are or became pregnant, or because funding for the research study 
has ended. 
 
WHAT IF I HAVE QUESTIONS? 
We encourage you to ask questions.  If you have any questions about the research study itself, please 
contact:  Dr. Sean English at (314) 362-3511.  If you experience a research-related injury, please 
contact: Dr. Sean English at (314) 362-3511.   
 
If you have questions, concerns, or complaints about your rights as a research participant, please contact 
the Human Research Protection Office at 660 South Euclid Avenue, Campus Box 8089, St. Louis, MO  
63110, 1-(800)-438-0445, or email hrpo@wustl.edu.   General information about being a research 
participant can be found on the Human Research Protection Office website, http://hrpo.wustl.edu.  To 
offer input about your experiences as a research participant or to speak to someone other than the 
research staff, call the Human Research Protection Office at the number above. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
FOR IRB USE ONLY 
IRB ID #: 201702141 
APPROVAL DATE: 03/11/20 
RELEASED DATE: 03/12/20 
EXPIRATION DATE: 03/10/21 
 
English – Predictors of AAA Expansion 
 
Page 12 of 12 
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This consent form is not a contract. It is a written explanation of what will happen during the study if 
you decide to participate. You are not waiving any legal rights by agreeing to participate in this study. 
As a participant you have rights and responsibilities as described in this document and including: 
• To be given enough time before signing below to weigh the risks and potential benefits and 
decide if you want to participate without any pressure from the research team or others. 
• To understand all of the information included in the document, have your questions answered, 
and receive an explanation of anything you do not understand. 
• To follow the procedures described in this document and the instructions of the research team to 
the best of your ability unless you choose to stop your participation in the research study. 
• To give the research team accurate and complete information. 
• To tell the research team promptly about any problems you have related to your participation, or 
if you are unable to continue and wish to stop participating in the research study. 
 
Your signature indicates that this research study has been explained to you, that your questions have 
been answered, and that you agree to take part in this study.  You will receive a signed and dated copy 
of this form. 
 
 
Do not sign this form if today’s date is after EXPIRATION DATE: 03/10/21. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Participant) 
 
 
 
 
(Date) 
 
 
____________________________________________ 
(Participant's name – printed) 
 
 
 
Statement of Person Who Obtained Consent 
The information in this document has been discussed with the participant or, where appropriate, with the 
participant’s legally authorized representative.  The participant has indicated that they understand the 
risks, benefits, and procedures involved with participation in this research study. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Person who Obtained Consent) 
 
(Date) 
 
 
___________________________________________ 
(Name of Person who Obtained Consent - printed)