Ultra Low Iodine Loaded Spectral CT Angiography (CTA) of the Aorta and Lower Limb: A Randomized Controlled Trial
Phase: NA
Conditions: Peripheral Arterial Disease, Renal Insufficiency
Sponsor: University Hospital, Akershus

Uploaded to Clinicaltrials.gov June 21 2022 
Research Protocol: Ultra low iodine loaded spectral CT angiography 
(CTA) of the aorta and lower limb: A randomized controlled trial.  
  
1. Background 
1.1 Aortic and peripheral arterial disease 
Aortic and peripheral arterial disease are important causes of morbidity and mortality. The 
prevalence of aortic and peripheral arterial disease (PAD) increases progressively with age, 
beginning after age 40. Total disease prevalence of PAD is in the range of 3% to 10%, 
increasing to 15% to 20% in persons over 70 years 2,3. CT angiography (CTA) of the aorta 
and the lower limb is one of the most important tools for diagnostic, evaluation of the severity 
of the disease, decision making, treatment planning and follow-up; but usually requires the 
use of iodine contrast medium. 
1.2 Renal impairment 
Due to the high prevalence of renal impairment (eGFR < 90 ml/min/1.73m) in the elderly 
hospitalized population (more than 90% among inpatients aged over 60 years) contrast-
medium-induced nephropathy is a major concern in this population. 1 This is found to be 
correlated with the ratio between dose in gram iodine and eGFR 4-8. Current practice at our 
hospital is to calculate the maximum amount of iodine contrast medium considered as safe 
using OmniVis calculator. There is however uncertainty whether this calculator is sufficiently 
validated for the patient population with stage 3-5 of chronic kidney disease.  
1.3 Contrast medium and diagnostic quality 
An iodine load of less than 20 g is considered insufficient for a standard diagnostic CT 
imaging of the abdominal aorta and arteries in the lower limb. The risk of contrast-medium-
induced nephropathy has limited options for diagnostic imaging in patients with severely 
reduced kidney function. Some of these patients have been offered CO2 angiography which 
is inferior in diagnostic quality. Others have not received imaging, thereby limiting the 
therapeutic options. 
1.4 Spectral CT 
The recently introduced spectral CT technique utilizes x-rays covering a spectrum of energy-
levels as opposed to conventional CT in which x-rays are set to one specific energy level. 
Spectral Detector CT (SDCT) utilises a single X-ray tube but has two layers of detectors to 
simultaneously collect low and high energy data in all patients. 
This technology offers many possibilities, such as “boosting” the x-ray contrast effect of 
iodine. This improves the vascular enhancement of the contrast medium using low-energy, 
virtual monoenergetic imaging (VNI).  
Akershus University Hospital has recently acquired the first spectral CT scanner in Norway, 
the Philips iQon. 
1.5 This study 
We plan to perform a randomized controlled trial for CT examinations of the abdominal aorta 
and lower extremities. In this RCT, a new ultra-low iodine contrast medium examination 
procedure tailored for spectral CT on the Philips iQon is compared to the standard 
examinations. 
 
2 Objectives: 
The objectives of this study are: 
Evaluation of ultra-low iodine load CTA protocols of the aorta and lower extremities. 

To investigate whether dual-layer in combination with virtual monoenergetic imaging (VNI) 
allows for reduction of contrast medium (CM) in CTA of the aorta and lower limbs with 
sustained objective and subjective examination quality parameters. 
 
 
3 Materials and Methods: 
3.1 Design 
Randomized Controlled Trial. 
Patients consenting to participation will be randomized to either examination by standard 
protocol or examination with ultra-low contrast medium protocol on the iQon scanner. 
Randomization will be conducted by opening consecutive numbered envelopes which 
assigns the patient either to "study" or "control". 
3.2 Population, Sample size and Recruitment (Inclusion & exclusion) 
In-patients and outpatients at AHUS. 
Sample size: alfa (level of significance): 0.05, beta (power) 80%. Assuming a mean 
difference of 0.5 points (on the subjective 5-point scale) with a standard deviation between 1 
and 1.5 results in a sample size of 100 in each group. 
 
With SD = 0.8 sample size is 50 in each group. 
With SD = 1 sample size is 63 in each group. 
Med SD 1.5 sample size is 141 in each group. 
 
Estimated inclusion time: 2 years. 
  
3.2.1 Inclusion Criteria 
 
- Inpatients and outpatients with kidney function (eGFR) allowing for safe 
administration of standard contrast dose (as calculated with the OmniVis calculator). 
 
- Patients with clinical suspicion of disease of the aorta and/or arteries in the lower 
limb.  
 
- Referral to CTA diagnosis, treatment planning or follow-up.  
3.2.2 Exclusion Criteria 
 
- Iodine contrast medium allergy 
 
- Age < 18 years 
 
- Lack of informed consent 
 
- Critical ischemia of the lower extremities 
3.3 Location 
Akershus University Hospital, Department of diagnostic imaging. 
3.4 CT Scanner and protocol 
Scanner: 
All patients: Philips Iqon Detector-based spectral CT (SDCT; Philips Healthcare, Clevland, 
OH, USA) 
Imaging protocols: 
Randomized either to standard CTA or a dilution DL (dual layer) CTA examination. 
In the dilution examinations the amount of injected iodinated contrast medium will be reduced 
by means of a dilution technique. The dilution technique is efficient and safe since it allows 
the use of the standard injection protocol (flow rate, volume, iodine concentration, saline 
chaser) from conventional CT. We set a limit for the contrast injection speed to less than 7,0 
ml/s. In order not to exceed this contrast flow rate limit, the maximum volume is limited to 130 
ml. Minimum contrast volume is limited to 60 ml. The contrast injection is followed by a flush 
of 50ml saline at the same flow rate. Injection rate will be determined using formula: 
 
Contrast medium volume (ml)/ Injection time  
Injection Speed (ml/s) = ----------------------------------------------------------------------------- 

21s (CTA of lower limb) 
 
The examination (study and controls) may be supplemented with a feet to hip scan after the 
main scan if there is suspicion of suboptimal examination quality. 
 
All dual layer dilution examinations are checked by radiologist before the patient leaves the 
lab. 
 
 
IQon Spectral CT 
CTA of lower limb 
K+ 
 
Patient related 
parameters 
 
 
Contrast concentration, 
mg I/ml  
350 
 
Volume iodine contrast 
medium, ml 
Control group: 
1.Bolus:1,4ml/kg 
max 130ml. 
2.Bolus: 50ml NaCl 
 
Study group:  
1.Bolus:70%NaCl 
and 30%iodine 
2.Bolus: 50ml NaCl 
 
Injection time:21s 
 
 
Technical related 
parameters 
 
 
Flow rate, ml/s 
Adjust to achieve 
desired injection  
 
Trigging threshold, HU 
120 
 
Post threshold delay, s 
15 
 
NaCl 
50ml 
 
 
 
 
 
 
 
 
 
Scan parameters 
CTA lower 
extremities 
 
kV 
120 
 
Scan 
Helical 
 
Scan type 
CTA Carotid 
 
Slice Thickness 
0,9mm 
 

Increment 
0,45mm 
 
Collimation 
Auto 
 
Average mAs 
228 
 
Min/max mAs 
70/200 
 
DRI 
27 
 
Dose right 
3D 
 
Pitch 
1,171 
 
Rotation time 
0,5 
 
Resolution 
Standard 
 
iDose 
4? 
 
IMR 
Routine level 1 
 
MonoE40 
Spectral 3 
 
MonoE45? 
Spectral 3 
 
CTDIw 
20,6mGy 
 
 
 
 
3.5 Patient data and Measurements: 
3.5.1 Patient data / Variables: 
Demographics: Age, gender, weight, height, BMI.  
Medical parameters: Creatinine, eGFR. 
Comorbidities: Diabetes, cardiovascular disease
Contrast medium: Iodine contrast medium concentration/volume, iodine injection flow rate.  
3.5.2 Objective examination quality analysis: 
From each imaging examination from the iQon a total of three datasets of vni at 40, 50 keV 
levels, and conventional, will be reconstructed with spectral 3 level. Conventional images 
from the control group are compared to vni at 40 and 50 keV in the study group.  
For study and control examinations arterial attenuation, image noise, Signal to Noise Ratio 
(SNR) and Contrast to Noise Ratio (CNR) is recorded. 
Arterial attenuation is measured by an experienced radiology technician (where appropriate) 
in the:  
• 
Abdominal aorta (at the midpoint between the renal arteries and the aortic bifurcation) 
• 
Iliaca communis (at the midpoint between the aortic bifurcation and iliac bifurcation) 
• 
Femoralis superficialis (ca 10 cm inferior to the branching of the deep femoral artery) 
• 
Poplitea (p3 – inferior part of a. Poplitea).  
The measurements are performed by placing a region of interest (ROI) within the artery at 
predefined levels. 
Image noise is measured by placing a ROI in air and measuring the standard deviation of the 
attenuation. 
Signal to Noise Ratio (SNR) is measured by dividing the mean arterial attenuation (at defined 
levels) by mean image noise. 
Contrast to Noise Ratio (CNR) is measured by dividing the difference between arterial and 
muscular attenuation by the image noise: (arterial attenuation - muscular attenuation) / 
Image noise 
 
Vascular pathology is classified according to the TASC II grading system by an interventional 
radiologist. 

 
Pas id: nummer – (0=standard, 1=studie, a = keV40, b=keV50) 
 
3.5.3 Subjective /semiquantiative assessment of examination quality: 
Subjective examination quality will be rated on a 4-point scale separately by 2 interventional 
radiologists who are blinded to each other’s rating. Discrepancies will be resolved by a third 
rater. 
The subjective rating is performed at the same anatomical levels as the objective 
measurements. Additionally subjective examination quality is rated in the calf as the best of 
the three arteries: a. tibialis post., a. tibialis ant. eller a. fibularis. 
 
The rating is performed separately on the left and right side and on conventional, MonoE 40 
keV and MonoE 50 keV. 
 
Images that cannot be assessed due to metal artifacts such as hip replacements are labelled 
“missing” - 9. 
 
Rating 
Definition 
1 
Excellent: The demarcation of the vessel lumen is 
excellent, more than sufficient for confident 
diagnosis or exclusion of stenosis or occlusion. 
2 
Good: The demarcation of the vessel lumen is 
sufficient for confident diagnosis or exclusion of 
stenosis or occlusion. 
3 
Adequate: The demarcation of the vessel lumen is 
adequate for diagnosis or exclusion of stenosis or 
occlusion but with limited confidence. 
4 
Non-diagnostic: There is insufficient demarcation of 
the vessel lumen for diagnosis or exclusion of 
stenosis or occlusion. 
8 
Thrombosis or occlusion at this anatomic level. 
Enhancement cannot be assessed 
9 
Missing 
 
 
3.6 End points:  
3.6.1 Primary endpoint: 
Mean attenuation in the aorta, common and external iliac artery, femoral artery. 
3.6.2 Secondary endpoints: 
Rate of diagnostic quality angiography (defined as arterial enhancement > 200 HU) 
Subjective examination quality 
3.7 Statistical Analysis 
Descriptive statistics of subjective and objective examination quality data. 
Comparison of subjective and objective examination quality between study and control 
group.  
Inter-observer agreement analysis of the measurements and ratings provided by the 
observers. 
4 Ethics and Approvals 
4.1 Ethics 
Both study- and control examinations performed in this study are clinically appropriate. Study 
examinations are performed with a reduced amount of iodine. There might be a very small 
increase in the risk of inconclusive examinations which will necessitate a repeat examination. 

However, the amount of iodine administered (even with a repeat examination) will be less 
than with the standard protocol. 
It is expected that the study examinations have equal (or even better) diagnostic quality 
compared to standard examination. Hence the risk to the patient is negligible. 
4.2 Data Protection Officer (Personvernombud) 
The study will comply with requirements of the Data Protection Officer, and Approval will be 
obtained prior to inclusion. Patient data will be de-identified. 
4.3 Regional committees for Medical and Health Research Ethics (REK) 
The study will comply with requirements of the Regional committees for Medical and Health 
Research Ethics, and approval will be obtained prior to inclusion. 
4.4 Consent 
All study participants will give informed, written consent to participate and to the use of their 
de-identified data.  
 
5 Funding 
The study is funded by Akershus University Hospital, Department of diagnostic imaging. 
 
6 Research Group 
• 
Cathrine Helgestad Kristiansen; MSc, Senior Radiographer CT, Department of 
Diagnostic Imaging and Intervention, Akershus University Hospital  
• 
Thien Trung Tran; Radiologist, Department of Diagnostic Imaging and Intervention, 
Akershus University Hospital 
• 
Owen Thomas; statistician, (Helse sør øst) Competence Center for Health Services 
Research, Akershus University Hospital. 
• 
Peter M. Lauritzen, Radiologist, PhD, Division of Radiology and Nuclear Medicine, Oslo 
University Hospital & Department of Diagnostic Imaging and Intervention, Akershus 
University Hospital 
• 
Sumit Roy, Radiolog, Radiologist, PhD, Department of Diagnostic Imaging and 
Intervention, Akershus University Hospital & Stavanger University Hospital. 
• 
Audun Sanderud MSc, PhD. Medical physicist og Associate Professor at Oslo 
Metropolitan University. 
• 
John Terje Geitung, Professor, Radiologist, Leader of Research, Department of 
Diagnostic Imaging and Intervention, Akershus University Hospital.a<xrt 
• 
Dan Levi; Radiologist, Department of Diagnostic Imaging and Intervention, Akershus 
University Hospital 
 
 
 
 
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