Dynamic Chest X-ray With Simultaneous Spirometry
Conditions: Cystic Fibrosis
Sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust

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Clinical Investigation Plan: 
DynaSSaur: Dynamic Chest X-ray with Simultaneous Spirometry 
Principal investigator: David Green  
Sponsor: Liverpool Heart and Chest Hospital 
 
IRAS reference number: 322890 
IRSCTN reference number: pending 
Sponsor number: NA 
Protocol version number: 4.1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of contents 
 
Contents 
Table of contents……………………………………………………………………………………………………………………………….2 
Table of figures and tables…………………………………………………………………………………………………………………4 
Signature page…………………………………………………………………………………………………………………………………..5 
Study Protocol contributors………………………………………………………………………………………………………….…..6 
Summary of protocol versions…………………………………………………………………………………………………………..8 
Overview and rationale……………………………………………………………………………………………………………………11 
 
Dynamic chest x-ray…………………………………………………………………………………………………………….11 
 
Spirometry………………………………………………………………………………………………..………………………..11 
 
Cystic Fibrosis…………………………………………………………………………………………………………………..…11 
 
Dynamic chest x-ray as an assessment of pulmonary function ……………………………………………12 
Aims and hypothesis………………………………………………………………………………………………………………………13 
Funding………………………………………………………………………………………………………………………………………….13 
Methods and Analysis………………………………………………………………………………………………………………………13 
 
Study setting……………………………………………………………………………………………………………………….13 
 
Part A: real-time paired DCR and Spirometry in a Health control Group……………………………13 
 
Part B: real-time paired DCR and spirometry in a CF subgroup………………………………………….13 
 
Part C: Retrospective review of longitudinal DCR data with regards to clinical markers of CF 
Status ……………………………………………………………………………………………………………………………………………14 
Schedule of Events…………………………………………………………………………………………………………………………15 
 
Dynamic chest X-ray procedure with paired Spirometry……………………………………………………16 
 
 
Spirometry……………………………………………………………………………………………………………16 
 
 
Dynamic Chest X-ray………………………………..…………………………………………………………….17 
Unexpected finding on imaging or spirometry……………………………………………………………………………….18 
Sample and Recruitment………………………………………………………..……………………………………………………….19 
Consent……………………………………………………………………………………………………………………………………………19 
Participation enrolment Criteria…………………………………………………………………………………………………….20 
Part A: Real-time paired DCR and Spirometry in Healthy control Group………………………………21 
Part B: Real-time paired DCR and spirometry in a CF subgroup………………………………………….22 

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Statistical analysis…………………………………………………………………………………………………………………………..23 
Proposed timetable of events………………………………………………………………………………………………………….23 
Safety…………………………………………………………………………………………………………………………………………….24 
 
Ionising Radiation……………………………………………………………………………………………………………..24 
 
X-ray machine Safety…………………………………………………………………………………………………………25 
 
Lung function testing safety………………………………………………………………………………………………25 
 
Reporting of adverse events……………………………………………………………………………………………..25 
Patient and public involvement………………………………………………………………………………………………………25 
Data Management…………………………………………………………………………………………………………………………26 
Protocol and Registration………………………………………………………………………………………………………………26 
Competing interests…………………………………………………………………………………………………………………………26 
Sponsorship……………………………………………………………………………………………………………………………………26 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Figures and Tables 
 
Tables 
Table 1 – Schedule of Events 
Table 2 – Schedule of Events for people with CF 
Table 3 – American Thoracic Society repeatability and Acceptability Criteria 
Table 4 – Gannt Chart of Projected Timetable December 2022- August 2023 
Table 5- Effective Doses for Common Radiological Examinations 
 
 
 
Figures 
Figure 1 – Room setup 
Figure 2 – CF cohort selection flow chart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Signature page 
 
The undersigned confirm that the following protocol has been agreed and accepted and that the 
Principal Investigator agrees to conduct the study in compliance with the approved protocol and will 
adhere to the Health Research Authority (HRA) and Ionising Radiation (Medical Exposure) 
Regulations 2017 (IR(ME)R) regulations, the Ionising Radiation Regulations 1999 (IRR99), any 
subsequent amendments of the study regulations, GCP guidelines, and other regulatory 
requirements as amended.  I agree to ensure that the confidential information contained in this 
document will not be used for any other purpose other than the evaluation or conduct of the clinical 
investigation.  I also confirm that I will make the findings of the study publicly available through 
publication or other dissemination tools without any unnecessary delay, that an honest, accurate 
and transparent account of the study will be given, and that any discrepancies from the study as 
planned in this protocol will be explained. 
 
Principal investigator 
Signature 
 
Date  
 
30/06/2023 
 
On behalf of the sponsor 
 
Signature 
………………………………………………………………………… 
Date  
 
………………………………………………………………………… 
 
 
 
 
 
 
 
 
 
 
 

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Study protocol contributors 
 
Primary investigator 
 
Dr David Green 
Clinical Research Fellow 
Department of Respiratory Medicine 
Liverpool Heart and Chest Hospital 
Thomas Drive, Liverpool L14 3PE 
Email: David.green2@lhch.nhs.uk 
 
 
Phone: 0151 254 3412 
 
Co- Primary Investigator 
Professor Martin Walshaw  
Consultant Respiratory Physician 
Department of Respiratory Medicine 
Liverpool Heart and Chest Hospital 
Thomas Drive. Liverpool L14 3PE 
Email: Martin.Walshaw@lhch.nhs.uk 
 
 
 
Phone: 0151 228 1616  
 
Co- Primary investigator 
Dr Dilip Nazareth 
Consultant Respiratory Physician 
Department of Respiratory Medicine 
Liverpool Heart and Chest Hospital 
Thomas Drive, Liverpool L14 3PE 
Email: Dilip.Nazareth@lhch.nhs.uk 
 
 
 
Phone: 0151 228 1616 
 
Co-investigator  
Mr Robert Peat respiratory physiologist 
Senior Clinical Respiratory Physiologist 
Liverpool Heart and Chest Hospital 
Thomas Drive, Liverpool L14 3PE 

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Email: Robert.peat@lhch.nhs.uk 
 
 
Phone: 0151 254 3032 
 
Co-investigator and Clinical Radiation Expert 
 
Dr Sukumaran binukrishnan  
Consultant Cardiothoracic Radiologist 
Liverpool Heart and Chest Hospital 
Thomas Drive, Liverpool L14 3PE 
Email: Sukumaran.binukrishnan@lhch.nhs.uk 
 
 
Phone: 0151 600 1303 
 
Co- Investigator  
Rachel Diamond 
Lead radiographer 
Liverpool Heart and Chest Hospital  
Thomas Drive, Liverpool L143PE 
Email: Rachel.Diamond@lhch.nhs.uk 
Phone: 0151 600 1236 
 
Co-investigator  
Mr Stephen Lomax 
Senior radiographer 
Liverpool Heart and Chest Hospital 
Thomas Drive, Liverpool L14 3PE 
Email: Stephen.Lomax@lhch.nhs.uk 
 
 
 
Phone: 0151 600 1236 
 
 
 
 
 
 
 
 

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Summary of Protocol versions 
V1                        30/01/2023- Original protocol version  
V2 
 
30/03/2023- Updated to reflect feedback from R&I committee meeting 
 
V3 
 
30/06/2023- Updated to reflect patient group information  
V4 
 
11/09/2023- Updated to reflect research and ethics committee conditions 
 
V4.1 
 
20/09/2023- Updated to reflect research and ethics committee conditions with 
tracked changes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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List of Abbreviations 
 
ARTP 
Association for Respiratory Technology and Physiology 
CF 
Cystic fibrosis 
COPD Chronic obstructive pulmonary disease 
CT 
Computed Tomography 
CXR 
Chest x-ray 
DAP 
Dose area product 
DCR 
Dynamic chest x-ray 
EED 
Estimated effective dose 
EPR 
Electronic Patient Records 
ERS 
European Respiratory Society 
ESD 
Entrance surface dose (sometimes expressed as Entrance Skin Dose) 
FEV1 
Forced expiratory volume in 1 second 
FDA 
Food and Drug Administration 
FPD 
Flat-panel detector 
FRC 
Functional residual capacity 
FSD 
Focus-to-skin distance 
FVCEx Forced vital capacity 
GCP 
Good Clinical Practice 
Gy 
Gray 
HRA 
Health Research Authority 
IR(ME)R 
Ionising Radiation (Medical Exposure) Regulations 
IRAS 
Integrated Research Application System 
IRS 
Integrated Radiological Services, Ltd. 
LHCH 
Liverpool Heart and Chest Hospital 
mA 
Milliamperes 
MHRA Medicine and Healthcare products Regulatory Agency 

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mSv 
Millisievert 
NHS 
National Health Service 
NSR 
Non-significant risk 
PA 
Posterior-anterior 
PEF 
Peak expiratory flow 
RCCP 
Registration Council for Clinical Physiologists 
RV 
Residual volume 
SID 
Source Image Distance 
SR 
Significant risk 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Overview and Rationale 
Dynamic Chest x-ray: 
Dynamic Chest x-ray (DCR) is a new imaging technique that allows us to visualise the thorax and 
diaphragm in motion throughout the respiratory cycle by recording a series of x-ray images over a 
10-20 second interval.  
Radiation doses are lower than compared to those used in fluoroscopic or computer tomography 
(CT) imaging and therefore more comparable to simple chest x-ray (CXR). 
Patient factors associated with respiratory disease may mean dynamic chest x-ray is better tolerated 
than conventional pulmonary function techniques such as spirometry and is also quick to perform. 
The temporal component of the imaging opens up possibilities for clinical utilisation beyond imaging 
techniques that we already have available; for example, the direct visualisation of the chest and lung 
field in motion may provide clinically relevant information. 
Computer analysis and image processing software available can facilitate the acquisition of 
quantitate data from the dynamic x-ray images. This information includes evaluation of 
Diaphragmatic motion; it is possible to measure diaphragmatic motion in terms of speed and 
distance throughout the respiratory cycle. Furthermore, analysis of DCR images by computer 
software one can automatically detect lung field area (projected lung area). The size of this 
projected lung area can be tracked over time through the entire series of images. 
 
Spirometry: 
The assessment of pulmonary function is essential for diagnosis and ongoing monitoring of most 
respiratory conditions. Spirometry – full inhalation and exhalation provides us with a forced 
expiratory volume of air in 1 second (FEV1) and a forced vital capacity (FVC) value as well as 
information in the form of flow volume loop and volume time graphs. Spirometry has a fundamental 
role in diagnosis and monitoring respiratory conditions such as asthma, chronic obstructive 
pulmonary disease (COPD), Cystic Fibrosis (CF) and pulmonary fibrosis.  spirometry is the gold 
standard yet not all people can perform spirometry. DCR has the potential to measure dynamic 
movements of the respiratory fields, providing quantitate assessment of some aspects of lung 
function. 
 
Cystic Fibrosis 
CF is an autosomal recessive multisystem disorder that arises in a defect in in the cystic fibrosis 
transmembrane conductance regulator protein (CFTR). Dysregulation of ion transport by the 
defective CFTR protein leads to build up of thick secretion and pro inflammatory response. These 
thick secretions provide a favourable environment for chronic microbial colonisation by pathogens 

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such as Pseudmonoas aeruginosa which manifest as drive chronic infection, inflammation, acute 
infective exacerbations and progressive decline in lung function over time. 
Cf is managed through a multi-disciplinary team (MDT) approach that requires careful monitoring of 
patients and the clinically relevant markers of their condition. The most prognostically important 
measurement of lung function is FEV1.  
Cystic fibrosis Transmembrane (CFTR) modulators are a relatively new development in management 
of people with cystic fibrosis (pwCF) and represent a paradigm shift; this therapy directly affects the 
malfunctioning protein responsible for CF as opposed to conventional management options which 
seek to treat the consequences of the condition. This in combination with the current model of CF 
care is resulting in improved life expectancy and quality of life for many pwCF. 
An important part of preserving pwCF’s health is a once yearly review process called annual review; 
this a nationally recognised process although there may be some regional variation in practice. 
Annual review is a detailed assessment of every aspect of the patient’s condition including a face-to-
face review.  At Liverpool Heart and Chest Hospital (LHCH) routine clinical care currently includes a 
dynamic chest x-ray and spirometry as part of this process 
 
Previous Work with DCR in relation to pulmonary Function  
Prior work has established that some DCR metrics correlate with some measures of lung function. 
For example, projected lung area has been demonstrated to correlate with total lung capacity. 
Furthermore, diaphragm motion has been shown to correlate with vital capacity and FEV1 in non – 
CF healthy volunteers.  
Further work conducted in our large adult CF centre at LHCH has demonstrated significant 
improvement in changes in diaphragm movement and change in projected lung area in those 
treated for exacerbations of cystic fibrosis. In a smaller study here at LHCH in a CF cohort DCR 
metrics have also been shown to correlate with measures of lung volume. This work also 
demonstrated that the DCR procedure was well tolerated by the CF population and the procedure 
acquisition time proportional to a standard posteroanterior (PA) x-ray.   
 
DCR as an assessment of pulmonary function  
DCR provides an assessment of structures involved in respiration over time period and therefore 
could provide us with alternative insights into respiratory function. It may be possible that relating 
DCR to conventional lung function testing allows it to be used as a surrogate tool to measure some 
of these parameters used to assessment pulmonary function. Alternatively, it may provide different 
parameters of lung function which don’t directly correlate with conventional testing, but in of 
themselves are clinically relevant. 
In order to further evaluate the utility of DCR as a tool for assessment of baseline respiratory 
physiology, it is important to be able to compare it with real time conventional pulmonary function 
tests such as spirometry.  Previous studies have compared sequential lung function testing to 
dynamic x-ray images; even if attempting a maximal effort there will be significant variability in 2 
separate manoeuvres (i.e when sequentially performing a dynamic x-ray and then contiguously  a 
spirometry). Currently there have been no studies which compare a dynamic chest x-ray with a 
simultaneous lung function study such as spirometry.  

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This study will therefore address this issue using performing simultaneous spirometry and DCR. 
Therefore one key aim of the study would be to establish how DCR compares with spirometry in a 
healthy population of individuals. 
We would seek to also perform the DCR with simultaneous spirometry in a cohort of CF patients. 
DCR and spirometry are already performed as part of the annual review process. As highlighted DCR 
is generally well tolerated by pwCF. Spirometry can be physically or psychologically more challenging 
for pwCF. By performing simultaneous spirometry and DCR it would allow for a comparison with the 
healthy control group. This would provide the second aim of the Study to understand how we can 
relate DCR to pwCF’s Spirometry.  
Finally, as mentioned above DCR has become part of our annual review process in LHCH since 2019.  
The annual review process seeks to capture the clinically relevant information needed to assess the 
overall health of pwCF.  By further analysing these DCR films with the other metrics of annual review 
process we may better understand how DCR relates to lung health over time. For example, are there 
any features of DCR which will predict future outcomes for pwCf. This study will therefore explore 
the relationship between longitudinal changes in DCR and key clinical measures of CF.  
 
Aims: 
1. Measure lung function via spirometry with simultaneous DCR in healthy controls 
2. Measure lung function via spirometry with simultaneous DCR in pwCF 
3. Investigate the relationship between spirometry and DCR in healthy controls, CF, and 
compare these two cohorts. 
4. Investigate the relationship between DCR imaging and key clinical markers of  CF recorded in 
the annual review process.  
 
Null hypothesis: there is no relationship between parameters recorded by DCR and that of 
conventional spirometry in healthy individuals 
Null hypothesis: there is no relationship between variables recorded by dynamic chest x-ray and 
that calculated by spirometry in people with CF.  
Alternative hypothesis: We can correlate the findings on DCR with that of recorded spirometry 
findings.  
Alternative hypothesis: there is a correlation between dynamic chest x-ray and that calculated by 
Spirometry in people with CF  
 
 
Funding 
This Study has received no specific resources from any funding agency either public or commercial. 
Konica Minolta have provided a grant in kind with the dynamic x-ray machine, workstation and 
imaging software and technical support.  Konica Minolta does not have any input in the clinical 
acquisition of data from relevant patient group.  

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Method and analysis 
Study Setting 
Single centre study based at Liverpool Heart and Chest Hospital. From a practical perspective the 
best place for the study given: 
1. 
Dynamic x-ray machine is novel and located on site here 
2. 
Tertiary centre for adult cystic fibrosis. 
 
Part A : Real-time paired DCR and Spirometry in Healthy control Group 
Aim: Explore relationship between the Dynamic CXR imaging and simultaneous spirometry in a 
healthy population with no known underlying lung condition.  
Study design: The study involves the recruitment of healthy volunteers from general population. We 
would aim to recruit n=100 participants. The key investigations are Dynamic chest x-ray and paired 
spirometry as outlined below. Individuals will be recruited through a poster campaign successful in 
previous studies 
 
Part B: Real-time paired DCR and spirometry in a CF subgroup. 
Aim: Explore relationship between the Dynamic CXR imaging and simultaneous spirometry in a CF 
population    
Study Design: This aspect of the study involves recruitment pwCF to perform DCR with paired 
spirometry, aiming to recruit n= 100 people. The above format would be repeated with paired 
spirometry and DCR in CF subgroup of LHCH patients. CF patients at LHCH attend a once yearly 
review process called annual review. The current format already includes a dynamic chest x-ray and 
spirometry as part of this Process (although not simultaneous).  Through CF data base co-ordinator, 
a letter will be provided to all pwCF if interested.  
This would allow for a Direct comparison of spirometry with DCR data. Furthermore, it therefore also 
allows for a comparison of Comparison with the control group. The structure of how these 
investigations are performed is outlined below. 
 
 
Part C: 
Retrospective Review of longitudinal DCR data with regards to clinical markers of CF status 
Aim: To see how changes in key quantitative markers from DCR imaging relate to key CF clinical 
parameters 
Study design:  pwCF consenting for part B of the study will also be consented for using their current 
imaging as part of a longitudinal review of DCR imaging.  Analyses will include an evaluation of the 
relationship between baseline DCR quantitative measurements and key clinical CF parameters  that 
are recorded as part of their ongoing monitoring and care. 

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Schedule of Events 
Below is highlighted a timetable for the schedule of events. 
 
Table 1 – Schedule of Events for Healthy Volunteers 
Contact Purpose 
Event 
Duration 
1 
Indirect Contact 
Individual contacts study 
team following poster 
campaign 
N/A 
1 
Initial Direct contact 
Provided with patient 
information sheet and 
consent information 
20 minutes 
2 
Consent 
Informed Consent taken  
20 minutes 
3 
Attendance for 
imaging 
Dynamic chest radiograph 
acquired with spirometry 
Completion of questionnaire 
30 minutes 
 
Table 2 – Schedule of Events for people with CF 
Contact Purpose 
Event 
Duration 
1 
Indirect Contact 
Contacted via letter, patient 
information sheet enclosed 
N/A 
1 
Initial Direct contact 
Ensure provided with patient 
information sheet and 
consent information 
20 minutes 
2 
Consent 
Informed Consent taken  
20 minutes 
3 
Attendance for 
imaging 
Dynamic chest radiograph 
acquired with spirometry 
Completion of questionnaire 
30 minutes 
 
Once recruited the individual will attend for radiology department for the acquisition of the imaging 
and spirometry.  
 

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Dynamic chest X-ray procedure with paired spirometry 
This study involves performing 2 simultaneous investigations – Dynamic x-ray and Spirometry, 
outlined below. For both parts of the Study A and B the process will be the same. 
Spirometry: 
Spirometry will be performed using validated and accredited spirometers  that are used in clinical 
practice. The Study would utilise Geratherm® Spirostik™ spirometers (which can be Bluetooth or 
not) and documented using Geratherm® Blue Cherry™ software. 
Subjects will perform spirometry in upright seated position which chest resting forward on the flat 
panel of the chest x-ray machine. The Spirometry instructions are given by a pulmonary physiologist 
who call out instructions. Spirometry requires a a deep inspiration followed by a maximal expiration 
into a hand held tube device. All pulmonary physiologists conducting the research at LHCH are 
accredited with the  association for respiratory technology and physiology practioners(ARTP) and 
with the registration council for clinical physiologists (RCCP). The first 2 attempts will be spirometry 
only (as opposed to DCR). This is inline American Thoracic Society/European Respiratory Society 
repeatability and acceptability criteria (see below) and will allow a comparison with third spirometry 
attempt. The two non-DCR manoeuvres will facilitate volunteer comfort with the technique and 
allow for further coaching if required before the DCR image is captured. The third ‘live’ attempt will 
be recorded in conjunction with a DCR. The investigator tells the radiographer when to start 
recording the x-ray and breathing instructions are called out as per conventional Spirometry 
instructions. 
All Spirometry will be reviewed by LHCH pulmonary physiologists and be entered on a clinical master 
datasheet. The following are the key Data points which will be recorded for the spirometry attempt 
with DCR (absolute and percentage predicted values): 
• 
FEV1  
• 
FVC 
• 
FEV-1/FVC ratio  
Table 3: ATS/ERS Repeatability and Acceptability Criteria 
Spirometry  
Spirometry Within-Manoeuvre Criteria  
Spirometry 
Between-Manoeuvre 
Criteria 
3x Acceptable flow volume loops performed free from significant 
artefact including; 
Cough during first second of exhalation, Glottis closure that influences 
the measurement  
Early termination or cut-off, Not maximal effort, Leak, Obstructed 
mouthpiece 
Duration ≥ 6s or until a plateau in the volume-time curve or if the 
subject cannot or should not continue to exhale 
 
 
The two largest values of FEV1 must be 
within 
0.150L 
of 
each 
other 
The two largest values of FVC must be 
within 0.150L of each other 

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Dynamic Chest X-ray 
Dynamic chest x-rays are performed in the x-ray room in Liverpool heart and chest Hospital. This is 
simultaneous with spirometry so will occur in the same place.   
A physical anatomical marker (left/right) is manually added to the detector.  Density is set to -2 on 
the control panel, and the dynamic study function selected.  The tube filter is set at 1.0mm Al, 
0.1mmCu (copper and aluminium).  The SID (distance to detector) is set to 200cm.  A 180cm focal 
distance grid (40L per cm, ratio 12:1, and 17 by 17 inch / 42.18cm x 42.18cm) is used.  Exposure 
factors are set at tube voltage 100kVP, tube current 80mA, exposure duration 4.0ms.  Collimation 
(the adjustment of the x-ray field size to the minimum needed to capture the required images for a 
specific patient) is performed as per a standard chest x-ray, usually around 40cm by 30cm.  The 
patient is positioned in a posterior-anterior position. 
The frame rate for those participants undergoing routine clinical imaging will be set at 15 frames per 
second (fps), the standard frame rate used clinically. 
Breathing instructions are called out as per Spirometry instructions. The image capture is stopped 
once the breathing the spirometry action is complete (this can be completed in around 10s or 150 
frames), or if the 220 frame limit is reached, whichever comes first. If the spirometry is suboptimal 
the procedure cannot be repeated.  
Once the image capture/spirometry is complete, exposure factors are recorded by the operator, 
including the total number of frames and total duration in seconds.  
The images captured are transferred to the local PACS server as well as an NHS server. Images are 
then downloaded from the NHS server onto a secure workstation for analysis in the research 
department. Images are anonymised to comply with data protection policies. Images are then 
processed using Konica Minolta DI-X1 software and re-uploaded to the server. 
The images acquired by the DCR are processed using the Di-X1 machine using the computer 
algorithms. Further updates to the machine may allow further analysis. Key quantitative measures 
derived from the D1-X1 analysis of the DCR currently include: 
1. Diaphragmatic excursion – maximal inspiratory and expiratory in mm 
2. Peak diaphragm velocity  
3. Peak diaphragm velocity at inspiration / expiration 
4. Peak distance from apex to diaphragm 
5. Lung field area during range of maximal inspiration / expiration – as calculated by Konica 
Minolta software. Reviewed individually to ensure algorthim accurately detecting lung field 
area.  
 
The Figure below demonstrates the room set up. The study volunteer attends room 2 where our 
DCR machine in LHCH is placed. The individual sits on a stool facing the FPD. The Radiographer , 
researcher and any pulmonary physiologist are by the control station. The volunteer holds the 
spirometer to their mouth. When instructions for Spirometry are given the Radiographer presses the 
button to record the DCR. The complete spirometry attempt is completed, and the x-ray ceased 
when the full motion completed. The DCR machine will stop after 220 frames the exposure will not 
continue if the full spirometry is not completed.  
 

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Figure 1- Room Setup  
 
 
 
 
Unexpected findings on imaging or spirometry 
Any unexpected or concerning findings that are observed either on dynamic chest radiograph or 
spirometry will be acted upon as soon as possible by a member of the investigating team. In the case 
of people with CF these findings will be communicated to the responsible physician caring for the 
individual, as well as to the individual themselves, as appropriate. For the healthy control group action 
will be governed by the nature of the abnormality and will facilitate communication with primary care 
physician; again, all actions and information will be communicated to the individual as appropriate.   
 
 
SID=2m 
Upright Radiographic stand 
Pulsed X-ray generator  
Generator 
Console PC 
Spirometer 

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Sample and Recruitment 
This study is exploratory work and is ultimately hypothesis generating and as such no formal 
statistical power calculation has been carried out. Target recruitment numbers are therefore based 
on pragmatic assessment of the ability to recruit and measure successfully. 
Recruitment Part A: The study involves the recruitment of healthy volunteers from general 
population. We would aim to recruit n=100 participants. Recruitment will be made through internal 
advertisement at LHCH hospital trust, University of Liverpool and Liverpool John Moore University 
Recruitment Part B: People for part B of the study will be recruited through annual review process 
at CF clinic. As part of this process all people will undergo DCR and spirometry. They will be exposed 
to no further radiation, but it will mean that they have to perform an extra spirometry procedures. 
Individuals participating in part B will consent to using their investigation in part of the longitudinal 
review. 
The Liverpool Heart and chest hospital has approximately 350 people with CF, however only 302 are 
present in the area (as opposed to being based in other areas which means they don’t come to 
clinic). Transplanted individuals will be excluded (totalling 7) as well as pregnant individuals 
(currently 15). There is approximately 20% exacerbation rate and approximately 30% do not attend 
any given appointment. This would give us a projected population of just over 150 individuals to 
recruit from (please see Figure 2 below). 
It is important to note that this is a conservative estimate pwCF who have a current exacerbation or 
who DNA appointment may return for their annual review study at a later date (however this may 
not be within the study recruitment period)  
 
Consent 
Informed consent will be obtained prior to the participant undergoing enrolment in the study. A 
patient information sheet will be provided prior to taking informed consent.  
The opportunity to ask questions will be given. Capacity will be assessed in order to determine that 
informed consent can be given.  
Participation will be voluntary, and consent can be withdrawn at any time. 
 
 
 
 
 
 

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Figure 2 - CF cohort selection flow chart 
 
 
 
 
 
 
 
Total  LHCH CF cohort 
(n = 350) 
CF Cohort attending for 
AR (n= 302) 
Not attending clinic 
locally (n=48) 
Excluded: 
Pregnancy/transplant 
recipient  (n= 22)  
CF cohort with baseline 
eligibility for study  (n= 
280) 
Projected Cohort 
number eligible for 
recruitment (n=157) 
Projected DNA rate at 
30% (n=84) 
 
CF cohort with Baseline 
eligibility + physical 
attendance at clinic for 
AR (n= 196) 
Projected exacerbation 
rate on attendance at 
20%  (n=39) 

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Participation enrolment criteria: 
 
Part A: Real-time paired DCR and Spirometry in Healthy control Group 
Inclusion criteria: 
• 
Age: ≥ 17 years old and ≤  50 years old 
and 
• 
No underlying respiratory illness (chronic or acute) 
and 
• 
Able to provide informed consent 
 
Exclusion criteria 
General exclusion criteria: 
Any of: 
• 
Potentially pregnant or lactating 
• 
Inability to provide informed consent 
• 
Unable or unwilling to sit to perform DCR/Spirometry in the radiology department 
• 
Unable or unwilling to follow Spirometry breathing instructions (e.g., holding breath or 
taking a deep breath) 
• 
Unable to perform reproducible spirometry and/or full pulmonary function studies within 
ATS-ERS criteria 
• 
Significant radiation exposure within the last year (for example, numerous CT scans of chest) 
• 
Involved, either currently or recently, in other studies involved non-routine exposure to 
sources of ionising radiation 
• 
Any serious or active medical or psychiatric illness, which in the opinion of the investigators, 
would interfere with subject treatment, assessment, or compliance with the protocol 
• 
Inability to complete spirometry performance in 20 seconds. 
• 
Current Chest infection  
 
Spirometry exclusion criteria 
Any of: 
• 
Unstable cardiovascular status, recent MI or PE (within 6 weeks) 
• 
Haemoptysis of unknown aetiology (within 6 weeks) 
• 
Pneumothorax (present, or occurring within 6 weeks) 
• 
Within 24 hours of bronchoscopy 
• 
Thoracic, abdominal or cerebral aneurysm 
• 
Recent eye surgery or increased intraocular pressure 
• 
Recent thoracic or abdominal surgery 
• 
Acute nausea, vomiting or diarrhoea 
• 
Pregnancy 
• 
Undergoing treatment for TB 

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• 
Part B: Real-time paired DCR and spirometry in a CF subgroup 
Inclusion criteria: 
• 
Age: ≥ 17 years old ≤ 50 
and 
• 
Attending the adult CF Unit at LHCH 
and 
• 
Confirmed CF diagnosis (positive sweat test in childhood and by genotyping) 
and 
• 
Able to provide informed consent 
 
Exclusion criteria 
General exclusion criteria, same as Group A (see above) plus: 
• 
Recipient of Lung transplant 
• 
Current exacerbation  
 
Spirometry exclusion criteria (same as for Group A, see above) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Statistical analysis 
Statistical analysis will be carried using the R software package, produced and supported by the R 
Foundation for Statistical Computing, under the GNU GPL v2 public license. 
All data will be collated electronically and stored on a secure server in line with data protection. 
Two-sided P-values of <0.05 will be considered as statistically significant.  Confidence intervals will 
be presented where appropriate and feasible. 
Comparison of the data will be primarily between dynamic chest x-ray results and spirometry data.  
Depending on the distribution of the dataset, paired t-tests or the relevant non-parametric 
equivalent will be used to analyse within groups.  Categorical data will be presented as frequency 
and percentage.  Continuous data will be presented as number of observations, mean, standard 
deviation, median and interquartile range as appropriate. 
 
Proposed timetable of events 
• 
December 2022 – Start of Protocol write up.  
• 
January 2023 – research proposal submission to local research committee 
• 
March 2023- Sure group review and revisions to protocol and study literature 
• 
July 2023 -Iras application  
• 
September 2023 to September 2024 - Data collection is projected to take around 365 days, 
aiming for completion end of July 2023. This allows for the recruitment of 2 ‘healthy volunteers’ 
and 2 people with CF a week.  
• 
September to October 2024- Data analysis  
• 
October/November/December 2024- write up of research results +/- publication 
 
Figure 3 – Gannt Chart of Projected Timetable December 2022 – December 2024 
Task 
D J F M A M J J A S O N D J F M A M J J A S O N   D 
Protocol Write 
up 
  
      
  
  
      
    
  
  
      
  
  
      
    
  
    
R&I committee 
meeting LHCH 
  
      
  
  
      
    
  
  
      
  
  
      
    
  
    
Sure Group 
review  
  
      
  
  
      
    
  
  
      
  
  
      
    
  
    
Iras Application 
  
      
  
  
      
    
  
  
      
  
  
      
    
  
    
Study period 
  
      
  
  
      
    
  
  
      
  
  
      
    
  
    
Data analysis 
  
      
  
  
      
    
  
  
      
  
  
      
    
  
    
Results write up 
  
      
  
  
      
    
  
  
      
  
  
      
    
  
    
 
 
 
 

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Safety 
 
Ionising Radiation 
This study requires exposure to ionising radiation. 
We are exposed to radiation in our daily lives and our annual average radiation exposure in the UK is 
2.7mSv 
An example of typical radiation doses from clinical investigations are included below. 
 
Table 4 - Effective Doses for Common Radiological Examinations 
Projection 
 
 
 
Estimated effective dose (mSv) 
Chest PA 
 
 
 
0.014 
Chest lateral 
 
 
 
0.038 
Coronary angiogram 
 
 
3.9 
CT chest 
 
 
 
6.6 
High resolution CT chest (HRCT)  
1.2 
 
The estimated effective dose in mSv as a consequence of a dynamic chest x-ray are determined by 
the settings of the machine. The settings used for the dynamic -xray machine in the LHCH 
environment are: 
tube filter is set at 1.0mm Al, 0.1mmCu (copper and aluminium).   
The SID (distance to detector) is set to 200cm.  A 180cm focal distance grid (40L per cm, ratio 12:1, 
and 17 by 17 inch / 42.18cm x 42.18cm) is used.   
Exposure factors are set at tube voltage 100kVP, tube current 80mA, exposure duration 4.0ms.  
Collimation (the adjustment of the x-ray field size to the minimum needed to capture the required 
images for a specific patient) is performed as per a standard chest x-ray, usually around 40cm by 
30cm.   
The patient is positioned in a posterior-anterior position. 
The frame rate for those participants undergoing routine clinical imaging will be set at 15 frames per 
second (fps), the standard frame rate used clinically.  
From a previous study ‘SPUDDS’ which utilised the dynamic chest X-ray in the same configuration 
the medical Physics Expert has calculated the procedural dose for the dynamic cxr at 15 fps for up to 
20s to be 0.24 mSv.  
Ionising radiation can cause cancer which manifests itself after many years or decades. Having a DCR 
at the above settings is approximately equivalent to 4 weeks background radiation. The risk of 
developing cancer as a consequence of taking part in this study is 0.0012%  for one DCR. The natural 
life time risk of developing cancer is 50%. For people with CF  there is no extra exposure to radiation 

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as this is part of routine clinical care. However, for the ‘healthy volunteers’ this is additional 
radiation exposure. This risk will be reflected in our patient information leaflet and consent process.  
 
X-ray machine Safety 
The Konica Minolta X-Ray imaging device to be used in the proposed study at Liverpool Heart and 
Chest Hospital is not an implanted device, nor a device that will support or sustain human life. 
Furthermore, imaging data from the device will not be used for diagnosing, curing, or otherwise 
altering patient management in any way. Usage of the device as proposed in this clinical protocol 
will not present a serious risk to the health, safety, or welfare of the subject. 
In order to assure safety, a risk assessment of the Konica Minolta X-Ray system was performed by 
Integrated Radiological Services (IRS), Ltd. to identify potential hazards that could cause an injury to 
the patient, user, or service personnel and to provide a plan that eliminates or reduces the 
possibility of a hazard.  This was conducted in April 2018 at LHCH, by IRS, Ltd., and updated in June 
2021 by IRS, Ltd. Following software and firmware updates to the DCR system. The risk assessment 
includes the following classes of hazards: radiation safety, electrical safety, mechanical hazards, and 
electromagnetic compatibility.  Testing has been performed to ensure compliance with applicable 
safety standards such as IEC 60601-1, IEC 60601-1-2, IEC 60601-1-3, IEC 60601-2-28, and IEC 60601-
2-45. 
In all areas of assessment, the Konica Minolta X-ray system was found to comply with applicable 
safety standards and, when used in accordance with the protocol and operating instructions, it is 
considered a non-significant risk, and possesses no known health hazards to patients, users or 
service personnel, outside of the inherent risks of ionizing radiation.  Information on the ionizing 
radiation dose can be found in the previous section.  The full report is available and can be provided 
by the investigating team. 
 
Lung function testing safety 
Spirometry will be carried out in line with ETS/ARS guidelines.  Standard exclusion criteria will be 
applied (see exclusion criteria).  All pulmonary physiologists conducting the research at LHCH are 
qualified ARTP practitioners and are RCCP registered. 
 
Reporting of adverse events 
Although there are no obviously identifiable adverse events foreseeable from the use of the dynamic 
chest x-ray machine, any adverse events will be recorded by any of the trial investigatory team and 
reported to the principal investigator, as well as by the Trust’s Datix adverse clinical event recording 
system if these occur during a patient hospital attendance/inpatient stay.  The principal investigator 
will notify the Research Ethics Committee of any significant adverse events. 
 
Patient and public involvement 
The study literature (Participant Information Sheet, consent documentation, questionnaire) will be 
discussed with the LHCH local patient involvement group (SURE group). 

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Data Management  
Any patient-identifiable information will be removed from any published or presented data.  For 
recording of patient information, patients will be assigned a unique patient identifying number, 
which will be used instead of their name in data analysis. 
Data gathered will include dynamic CXR images sequences, Spirometry and some clinical data. These 
will be transcribed to a Microsoft Excel© database, stored securely within hospital facilities and in 
accordance with the Data Protection Act 2018. 
All images will be stored and backed up via the local PACS system, and the unprocessed sequence 
data on a secure LHCH server.  The PACS data and unprocessed sequence data will be accessed from 
two secure, devoted workstations within the hospital, although data will not be stored locally on the 
workstations.  Any extrapolated or patient-specific data will be stored in accordance with the Data 
Protection Act 2018.  No patient identifiable information will be stored outside of hospital servers. 
Konica Minolta has provided the workstations and software necessary for image interpretation, 
although no patient identifiable information or images will be stored on third-party devices.  Data 
interpretation will be carried out on local machines, then re-uploaded to the secure server, with 
local data being deleted concurrently.  Support for the software package will be provided by Konica 
Minolta, and any adjustments or updates to the software will be provided by Konica Minolta. 
 
 
Protocol and Registration 
This study has received the following approvals: 
LHCH Research and Innovation Committee meeting 23/01/2023 
Sure group approval 16/06/2023 
 
 
Competing interests 
None of the contributors to this protocol declare any competing interests. 
 
Sponsorship 
This study will be sponsored by LHCH.  Konica Minolta, Inc. have provided the dynamic x-ray 
machine, workstation and analytics software for use under a Loan Agreement. 
 
 
 
 
 

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