Accuracy of Ultra-Low-Dose-CT (ULDCT) of the Chest Compared to Plain Film in an Unfiltered Emergency Department Patient Cohort
Phase: NA
Conditions: Chest Pain, Cough, Thoracic Diseases, Lung Diseases
Sponsor: Medical University of Vienna

 
 
 
 
 
 
Accuracy of Ultra-Low-Dose CT (ULDCT) of the 
Chest Compared to Plain Film in an Unfiltered 
Emergency Patient Cohort 
 
 
 
Study protocol and statistical analysis plan 
 
 
 
 
English Version 
 
 
 
 
 
 
Version 1.3 
24th of April 2019 
 
 

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Table of contents 
 
 
1 
AUTHORS ............................................................................................................. 3 
2 
PARTICIPANTS ....................................................................................................... 3 
3 
PROJECT TITLE ..................................................................................................... 4 
4 
BACKGROUND AND SUMMARY .................................................................................... 5 
5 
STUDY DESIGN ....................................................................................................... 7 
6 
HYPOTHESES AND OUTCOME MEASURES .................................................................... 10 
7 
INCLUSION CRITERIA ............................................................................................. 11 
8 
EXCLUSION CRITERIA ............................................................................................ 12 
9 
ETHICAL CONSIDERATIONS ..................................................................................... 12 
10 
RECRUITMENT ..................................................................................................... 13 
11 
STUDY DURATION ................................................................................................ 13 
12 
RADIATION DOSE .................................................................................................. 13 
13 
RADIOLOGICAL ANALYSIS ....................................................................................... 14 
14 
STATISTICAL ANALYSIS PLAN .................................................................................. 15 
15 
COMPENSATION ................................................................................................... 15 
16 
STUDY SUSPENSION .............................................................................................. 16 
17 
DATA MANAGEMENT AND DATA PROTECTION .............................................................. 16 
18 
FUNDING ............................................................................................................ 16 
 
 
 

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ULDCT project 
1 Authors 
- 
Univ.Prof. Univ.-Doz. Dr.med.univ. Helmut Ringl, MBA 
- 
Mag.rer.soc.oec. Dr.med.univ. Christian Wassipaul 
- 
Mag. Dr. Michael Weber 
- 
ao.Univ.-Prof. Dipl.-Ing. Dr. Peter Homolka 
- 
Ass.-Prof. Priv.-Doz. Dr.med.univ. Paul Apfaltrer, MBA 
- 
Assoc.Prof. Priv.-Doz. Dr.med.univ. Dietmar Tamandl 
- 
Dr.med.univ. Mathias Lazar 
- 
Assoc.Prof. Priv.-Doz. Dr.med.univ. Helmut Prosch 
- 
Assoc.Prof. Priv.-Doz. Dr.med.univ. Thomas Mang 
- 
Assoc.Prof. Priv.-Doz. Dr.med.univ. Rüdiger Schernthaner 
- 
Dr.med.univ. Ulrika Asenbaum 
- 
o.Univ.-Prof. Dr.med.univ. Christian Herold 
- 
ao.Univ.-Prof. Dr.med.univ. Hans Domanovits 
- 
Ass.-Prof. Dr.med.univ. Karin Janata-Schwatczek 
- 
Dr.med.univ. Sebastian Schnaubelt 
- 
Dr.med.univ. Filippo Cacioppo 
2 Participants 
 
Intended number of participants 
250 
Limiting age, minimum 
18 years 
Limiting age, maximum 
92 years 
Ability to provide informed consent 
Yes 
Male participants 
Yes 

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Female participants 
Yes 
Duration of participation in the trial for 
each participant 
Approximately two hours for each patient from 
inclusion in the study until the therapeutic 
consequences are established. 
Active phase 
Six months 
Follow-ups 
Within the trial no follow-up is intended. 
However, if clinically indicated follow-ups are 
performed, this data may be used in the analysis 
phase of the study for final diagnosis. 
Estimated duration of the trial 
One year 
(six months of acquisition, six months of 
evaluation) 
3 Project title 
 
Brief title 
Accuracy of Ultra-Low-Dose-CT of the Chest Compared to Plain Film in an Unfiltered 
Emergency Department Patient Cohort 
 
Acronym 
UP-Chest 
 
Official title 
Accuracy of Ultra-low-dose-CT (ULDCT) of the Chest Compared to Plain Film in an Unfiltered 
Emergency Department Patient Cohort 
 
 

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4 Background and summary 
 
For nearly a century, chest X-ray (plain film, projectional radiography) has been the established 
primary imaging modality for patients with acute chest pain, suspected pneumonia, and / or acute 
dyspnoea in the diagnostic pathway of emergency departments, although the sensitivity and 
specificity of this X-ray technique are moderate. (Long et al. 2017; Andronikou et al. 2017; 
Chalmers 2016; Martindale et al. 2016; Cardinale et al. 2014; Chawla et al. 2016) 
 
The widespread availability and use of chest X-ray is due to the low acquisition and operating 
costs for projectional radiography equipment, the short examination time, and the very low 
radiation exposure. In addition, projectional radiography of the chest often serves as a guide for 
further, more sensitive, diagnostical procedures. However, these advantages are partially offset 
by the disadvantages inherent to projectional methods: anatomical structures may superpose or 
mask pathological structures. As a result, some areas of the lung may be obscured, and 
assessment may therefore be limited. 
 
Whereas computed tomography was reserved for certain clinical questions over the last few 
decades, and, in most cases, served as a second imaging approach after plain film radiography, it 
has increasingly evolved as a primary imaging modality for several indications (e.g., suspicion of 
pulmonary embolism, highly suspected aortic dissection). This rise of computed tomography was 
due not only to its significant advantage of no superposition, but also partly driven by the marked 
reduction in radiation dose needed without sacrificing image quality. This was driven by the 
development of new detectors, modulation of tube current and voltage, as well as iterative 
reconstruction techniques. As a result, recent computed tomography scanners currently offer not 
only a more precise visualization of differences in tissue-attenuation and the significant 
advantage of the absence of artefacts due to superposition, but also allow for imaging with a 
considerably reduced radiation dosage compared to older scanners. (Zinsser et al. 2018; Anon 
2014; Brenner and Hall 2007; Berrington de González et al. 2009) (O’Hora and Foley 2018; 
Moser et al. 2017; Kubo et al. 2014; Kubo et al. 2017) Therefore, computed tomography may 
now be utilized as screening method in specific indications that carry an increased risk of certain 
pathologies (e.g., in long-time smokers) (Horeweg et al. 2014; Walter et al. 2016; Yousaf-Khan, 

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van der Aalst, de Jong, Heuvelmans, Scholten, Lammers, et al. 2017; Yousaf-Khan, van der 
Aalst, de Jong, Heuvelmans, Scholten, Walter, et al. 2017; National Lung Screening Trial 
Research Team et al. 2011; van der Aalst et al. 2016; Ruchalski and Brown 2016; Fintelmann et 
al. 2017). The introduction of the latest generation of computed tomography devices about three 
years ago allowed for an even further reduction in dose by filtering out low-energy photons using 
a tin filter, which offers the possibility of a reduction in radiation dose by another 50 % or more 
for established CT indications. For specific indications (e.g., lung nodules in follow-up), the 
radiation dose may even be reduced to a tenth or one-hundredth of a standard-dose CT (SDCT). 
(Braun et al. 2015; Suntharalingam et al. 2018; Haubenreisser et al. 2015) 
 
The current reference dose-length-product (DLP) in Germany for thoracic standard-dose CT 
(SDCT) is ~350 mGycm (effective dose ~6 mSv) and, for thoracic low-dose-CT (LDCT / HR-
CT), ~100 mGycm (effective dose ~1.7 mSv) (Schegerer 2016). However, the latest devices 
(third-generation dual-energy CT) provide the opportunity to considerably reduce the reference 
dose of thoracic low-dose CT. In the current literature, these scans are referred to as Ultra-Low-
Dose-CT (ULDCT) and are usually associated with a radiation dosage of 0.14 to 0.5 mSv. For 
this dose range, no standardized reference values have been published as yet. (Macri et al. 2016; 
Messerli, Ottilinger, et al. 2017; Messerli, Giannopoulos, et al. 2017; Messerli, Hechelhammer, et 
al. 2017; Vardhanabhuti et al. 2017; Martini et al. 2016; Rob et al. 2017; Moore et al. 2015; 
Braun et al. 2015) 
 
The limiting factors of ULDCT are quantum noise, loss of spatial resolution, and other image 
artefacts (Kim et al. 2015). Therefore, careful selection of appropriate CT protocols and dosage is 
mandatory in order to achieve sufficient image quality to answer the respective diagnostic 
question. 
 
Several papers have been published on the subject of ULDCT, which are dedicated to the 
comparison of ULDCT with LDCT and/or SDCT. These papers conclude that this technology 
may be used with sufficient sensitivity and specificity for indications such as dyspnea, 
emphysema, or lung nodules. (Macri et al. 2016; Messerli, Ottilinger, et al. 2017; Messerli, 
Giannopoulos, et al. 2017; Messerli, Hechelhammer, et al. 2017; Vardhanabhuti et al. 2017; 

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Martini et al. 2016; Rob et al. 2017; Moore et al. 2015) Due to the potential to reduce the 
radiation dose to less than 1/30 of a standard-dose CT while still providing acceptable image 
quality with the latest generation of devices, ULDCT of the chest is emerging as an interesting 
alternative to conventional chest X-ray. 
To the best of the authors' knowledge, there are currently no studies comparing and evaluating 
ultra-low-dose-CT as a primary imaging alternative to chest X-ray in emergency department 
patients. 
 
This study aims to compare ULDCT and plain film of the chest with regard to their accuracy in 
an unfiltered patient cohort of an emergency department. For this purpose, our ULDCT protocol 
will use the lowest possible dose at which image quality is diagnostically sufficient 
(approximately 0.2 mSv effective dose). This corresponds to less than 1/30 of the radiation dose 
of a standard-dose CT of the chest and to only about 2.5 times the dose of a chest X-ray in two 
views. This dose is equal to less than a month of natural background radiation in Austria and less 
than the radiation exposure on an intercontinental flight. (Bundesministerium für Arbeit, 
Soziales, Gesundheit und Konsumentenschutz 2018b; Bundesministerium für Arbeit, Soziales, 
Gesundheit und Konsumentenschutz 2018a; Ditto et al. 2013) 
 
In addition to the accuracy of ULDCT of the chest compared to plain film of the chest, this trial 
also aims to analyze the clinical relevance of both methods by assessing the respective impact on 
final diagnosis, as well as possible changes in therapy. 
5 Study Design 
 
Study Type 
 
 
Interventional 
Primary Purpose 
 
Diagnostic 
Number of Arms 
 
2 
Masking (prospective) 
None (open label) 
Allocation 
 
 
Randomized 
Enrolment 
 
 
250 

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Arms 
Assigned Interventions 
Reporting-order: Plain Film - ULDCT  
The plain film of half the participants (randomized) 
will be submitted for reporting by a radiologist as a 
first imaging method. After finishing this report, 
the same radiologist will assess the ULDCT of this 
participant. In this second report, the findings of 
both examinations will be summarized, and a 
second report will be filed. 
Emergency physicians will first receive the report 
for the plain film of the chest and will be asked for 
the diagnosis and its probability. Next, the report 
for ULDCT will be presented to them. Again, 
diagnosis and probabilities will be documented. 
Diagnostic Test: ULDCT  
Ultra-Low-Dose-CT (ULDCT) of the chest 
using tin filters with third-generation dual-
energy CT devices. The projected dose 
used will be approximately 0.2 mSv per 
ULDCT of the chest. 
Reporting-order: ULDCT - Plain Film  
For half the participants (randomized) radiologists 
will first receive the data from ULDCT of the chest 
and write a report. Subsequently, they will receive 
the data from the plain film of the chest and may 
expand their report (explicitly separated). 
Emergency physicians will first receive the report 
for the ULDCT of the chest and will be asked for 
probabilities of the nine most frequent diagnoses in 
chest-imaging plus "other". Next, they will be 
presented with the report for the plain film and will 
again be asked to give an estimation of the 
probabilities for the same diagnoses as before. 
Diagnostic Test: ULDCT  
Ultra-Low-Dose-CT (ULDCT) of the chest 
using tin filters with third-generation dual-
energy CT devices. The projected dose 
used will be approximately 0.2 mSv per 
ULDCT of the chest. 

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6 Hypotheses and outcome measures 
 
Null hypothesis: 
• 
There is no difference in accuracy between ULDCT of the thorax and plain film of the 
thorax regarding the primary diagnosis. 
Alternative hypothesis: 
• 
ULDCT of the thorax offers higher accuracy than plain film of the thorax regarding the 
primary diagnosis. 
 
Primary Outcome Measure: 
Accuracy of ultra-low-dose-CT of the chest and plain film of the chest 
Description: 
Initial radiologic diagnostic accuracy of both methods will be assessed by analyzing the number 
of reports that are changed after the images of the second modality become available to the 
radiologist in Arm 1 compared to Arm 2. 

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In a final approach, the diagnostic accuracy will be analyzed by retrospectively comparing all 
reports with the gold standard, which will be built from all available patient data at the end of the 
study, including all follow-up imaging studies and laboratory tests. 
 
Secondary Outcome Measures: 
• 
Sensitivity and specificity in ULDCT and plain film 
• 
Frequency of change in radiological diagnosis 
• 
Frequency of change in emergency physician’s diagnosis 
• 
Frequency of change in (planned) therapeutic course of action by emergency physician 
• 
Frequency of accidental diagnosis in ULDCT of the chest and plain film of the chest 
• 
Frequency of additional diagnostic imaging needed 
• 
Frequency of unclear reports in ULDCT and plain film 
• 
Diagnostic confidence in ULDCT and plain film by radiologist 
• 
Diagnostic confidence in ULDCT and plain film by emergency physician 
7 Inclusion criteria 
 
Sex 
All 
Gender-based 
No 
Age limits 
Minimum: 18 years 
Maximum: 92 years 
Accept healthy volunteers 
No 
Participants 
All patients who are assigned to a clinically indicated chest 
X-ray by the emergency department of Vienna General 
Hospital 
Consent 
Ability to provide informed consent 
 
Informed consent after detailed patient briefing 
 
 

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8 Exclusion criteria 
 
Clinical status 
A critical clinical condition that does not allow the 
examination with both modalities 
(ULDCT of the chest, chest X-ray) 
Assignment 
 
 
 
Assigned to chest X-ray as follow-up 
Pregnancy 
 
 
 
Women with positive ß-HCG-test 
9 Ethical considerations 
 
• 
The mean effective dose of a chest X-ray examination in two views (pa, lat) is 0.08 mSv 
(Wachabauer and Röthlin 2017). 
• 
The targeted mean effective radiation dose for one thoracic ultra-low-dose-CT (ULDCT) 
is approx. 0.2 mSv. This corresponds to approximately one month of natural background 
radiation in Austria. Compared to standard-dose CT examinations, ULDCT of the thorax 
causes about one-twentieth to one-fortieth of effective radiation dosage. Therefore, its 
dosage is much closer to a chest X-ray in two views than to a standard-dose CT, or even a 
low-dose CT examination. 
• 
Even the cumulative dose of both examinations comes with a negligible radiation dose. 
Thus, no negative effects are to be expected. 
• 
A delay in diagnosis can be ruled out since each examination is promptly evaluated – 
before the examination for the second imaging modality is performed. 
• 
Since no contrast medium is applied, adverse effects or events – in this context – can be 
ruled out. 
 
 

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10 Recruitment 
 
All patients who are assigned to receive a clinically indicated chest X-ray by the emergency 
department of Vienna General Hospital – regardless of indication – are offered participation in 
this trial. Thus, only clinically indicated cases may be included. 
Patients who meet the eligibility criteria and provide informed consent become participants in 
this trial and receive an ultra-low-dose-CT examination of the thorax in addition to a chest X-ray. 
11 Study duration 
 
Based on a preliminary analysis of frequency, the anticipated total study duration, including 
analysis of all parameters, is one year. 
12 Radiation dose 
 
• 
Chest X-ray: The reference dose for a chest X-ray in two views is approx. 0.08 mSv 
(effective dosage) (Wachabauer and Röthlin 2017). 
• 
Thorax-ULDCT: based on recent publications regarding imaging in emphysema and 
dyspnea, as well as on measurements with a thorax-CT test-phantom performed with the 
specific CT devices used for the study (Siemens Somatom Drive and Siemens Somatom 
Force), an effective dose of approx. 0.2 mSv (corresponding to DLP 12.5) appears to be 
optimal for ULDCT (lowest dose possible with sufficient image quality). This dose is 
below the effective dose of one month of natural background radiation, which is 
referenced as 0.23 mSv per month in Austria (2.8 mSv per year). (Bundesministerium für 
Arbeit, Soziales, Gesundheit und Konsumentenschutz 2018a; Bundesministerium für 
Arbeit, Soziales, Gesundheit und Konsumentenschutz 2018b; Ditto et al. 2013) 
 

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The thorax-CT test-phantom used is model RS-111 by "Radiology Support Devices", Long 
Beach, California, USA. 
13 Radiological analysis 
 
Rationale behind the study design: 
 
Prospective: 
For ethical, practical, and legal reasons, the emergency physician always needs an immediate 
consensus report on both methods written by a single specialist in radiology in order to make a 
final treatment decision. This would not be possible without a significant delay, if two 
radiologists had to create two separate reports. The frequency with which diagnoses and therapies 
by radiologists and emergency physicians differ between Arm 1 and Arm 2 will be measured. 
 
Retrospective: 
This will involve a multi-reader analysis by four radiologists in training and four specialists. All 
eight physicians will independently read and report all examinations by means of structured 
reporting. The reading time is not specified. Two groups with all 300 patients each will be 
created: In the 1st group, the chest X-ray examinations of Pts. 1-150 and the Ultra-Low-Dose-CT 
examinations of Pts. 150-300 will be available. In the 2nd group, this will be reversed. All 
patients will be fully anonymized and randomized. Two radiologists in training and two 
specialists will first read and report on group 1, the other four doctors will first read and report on 
group 2. Between the evaluations of group 1 and group 2 there will be at least one month to 
prevent a possible recognition of a case. 
The gold standard will be built from all available patient data at the end of the study, including 
the results of all imaging procedures, follow-up examinations, physical medical examinations, 
laboratory and histopathological tests and further diagnostic procedures (concerns all available 
data, regardless of whether the patient is admitted as an inpatient). 
The structured findings are then compared with the gold standard to determine the accuracy, 
sensitivity and specificity of both procedures. 

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Documentation: 
• 
Waiting time for the ULDCT will be logged. 
• 
Waiting time for the X-ray will be logged. 
14 Statistical analysis plan 
 
Power and sample size: 
A total of 250 participants is targeted. 
This is based on the following assumptions: 
• 
Accuracy of a chest X-ray is 80% 
• 
Accuracy of a ULDCT of the chest is 93% 
• 
Dropout rate is 20% (one in five potential participants) 
According to calculations using NQuery Advanced (version 8.3.0.0), 123 participants per arm 
(total of approx. 250 participants) will be required to reach a power of 85% in a one-sided test 
(alpha 2.5%). Due to the assumption of a dropout rate of 20% (approx. one in five potential 
participants), a sample size of 300 is required. 
 
Cross tabulation and chi2-tests will be used to compare percentages (e.g., accuracy, sensitivity, …). 
Diagnostic confidence will be compared by applying a Mann-Whitney U test. 
15 Compensation 
 
None. 
Participants will not receive any compensation. 

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16 Study suspension 
 
Since no negative effects on patients are expected, the trial will be suspended or stopped only if it 
becomes obvious that ultra-low-dose-CT examinations do not offer any benefit. 
17 Data management and data protection 
 
Only patients with clinical indications for chest X-rays will be included. During the active 
diagnostic phase, these patients will be diagnosed and treated in the usual clinical setting and 
documented using the RIS (Radiology Information System). Thus, in this part of the study, open 
data will be used. 
The evaluation of prospective and retrospective data will be subject to complete anonymization 
and randomization and will not be un-blinded at any time thereafter. Anonymization is performed 
by the vb.net - RND function, local software, and complete deletion of all personal, public, and 
private DICOM tags in the header. 
The data will remain at the Medical University of Vienna (MUW) and the Vienna General 
Hospital (AKH Vienna). Backup copies, which will remain in-house, will be made to protect the 
data. 
18 Funding 
 
Administration and analysis will be carried out by an employee funded for one year by Siemens 
Healthineers, Erlangen, Germany. No additional funds are available. 
 

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