Clinical trial NCT02478255
Conditions: Radiation Injury
Keywords: Radiation induced lung injury Xenon gas hyperpolarized
Sponsor: Bastiaan Driehuys
Start date: 2016-03-21; Completion date: 2022-01-13
Enrollment: 25 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether magnetic resonance imaging (MRI) using inhaled hyper polarized xenon-129 (129Xe) gas, and conventional contrast can help visualize impaired lung function and detect changes over time in patients receiving treatment as well as those who don't. 129Xe is a special type of xenon gas and when inhaled during MRI may be able to show areas of abnormal thickening of parts of the lungs. These images combined with images taken with injected contrast agents or other special types of MRI such as conventional proton (1H) MRI may provide a better way to look at lung structure and function. The ultimate goal is to predict the degree of radiation-induced lung injury that will develop in a given patient for a given treatment plan. The investigators anticipate that these images will provide more specific information about lung disease than standard lung function tests. The use of 129Xe MRI is investigational. Investigational means that these tests have not yet been approved by the US Food and Drug Administration and are only available in research studies like this one. In addition, standard MRI with contrast is not typically done as standard of care for monitoring changes due to thoracic radiation therapy, therefore, its use in this study is also considered investigational.

Healthy volunteers are being asked to participate in this study because to develop a database of functional images that are representative of healthy lungs.

Detailed description:

Arms: arm 1: Patients scheduled to undergo Radiation Therapy (RT) for lung cancer, or other malignancies such as breast cancer or lymphoma that involve significant irradiation of the thoracic cavity. arm 2: None
Interventions: intervention 1: Hyperpolarized 129-Xenon gas intervention 2: MRI
Intervention descriptions: intervention 1: Hyperpolarized xenon will be administered in multiple doses in volumes up to 25% of subject total lung capacity (TLC) followed by a breath hold of up to 15 seconds. Subsequent 129Xe doses will only be administered once the subject is ready to proceed. intervention 2: Conventional 1H MRI will be used to provide anatomical reference scans, as well as pulmonary perfusion.

Protocol documents:
Prot_SAP_000.pdf: 
Protocol Title: Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment 
 
 
NCT02478255 
 
 
Protocol Version Date: 26Jul2018 
 
 


CONFIDENTIAL 
The information contained in this document is regarded as confidential, and may not be disclosed to another party unless such disclosure 
is required to initiate the study, to conduct study-related activities, or to comply with national, state, or local laws and regulations.  
Written authorization from the coordinating site and sponsor is required for disclosure otherwise. 
PT-RR v05.22.12 
Longitudinal MR Imaging of Pulmonary Function 
in Patients Receiving Thoracic Radiation 
Treatment 
 
Sponsor: 
PI – Duke Cancer Institute 
 
 
Funding Source: 
NIH 
 
 
Protocol Source: 
PI - Duke Cancer Institute 
 
 
Duke IRB#: 
Pro00059856 
 
 
 
 
 
 
Principal Investigator 
Joseph Mammarappallil, MD PhD  
(919) 684-2051  
 joseph.mammarappallil@duke.edu  
Co-Principal Investigator(s) 
(Main Contact) 
Bastiaan Driehuys, PhD 
bastiaan.driehuys@dm.duke.edu 
 (919)684-7786 
 
Sub-Investigator(s) 
Christopher Kelsey, MD 
kelse003@mc.duke.edu 
 
 
 
Statistician 
Xiaofei Wang 
xiaofei.wang@duke.edu 
 
Lead Study Coordinator and 
Regulatory Coordinator 
Samantha Womack 
sam.womack@duke.edu 
Data Manager 
Bastiaan Driehuys, PhD 
 
 
 
Original version: 
Date 
 
Amended version 
Date 26Jul2018 
 


Version Date 26Jul2018 Pro59856 
Page 1 of 12 
 
1. Protocol Title: Longitudinal MR Imaging of Pulmonary Function in Patients Receiving 
Thoracic Radiation Treatment Pro00059856   
2. Purpose of the Study: The purpose of this study is to evaluate a comprehensive MRI-based 
protocol designed to image alterations in regional lung function that occur when patients receive 
thoracic radiation therapy. Radiation therapy (RT), when applied to tumors in or around the 
thorax, is known to cause regional lung injury (as defined by imaging changes reflecting reduced 
perfusion, reduced ventilation, and increased density) typically evolving 1-6 months post-RT. 
Approximately 5-20% of patients experience global lung dysfunction manifested as dyspnea 
after RT. This often occurs before imaging abnormalities are detected by conventional modalities 
(CT, SPECT). The exact linkage between the changes in imaging and the development of 
symptoms is unclear (for example, the time course of the two do not match exactly).  
Presently, there are no well-accepted methods to predict a given patient’s risk of developing 
dyspnea after RT, and none of the prior studies have addressed regional gas exchange (which 
might be considered the inherent function of the lung).  Thus, there exists a considerable need to 
develop new methods to accurately detect and monitor radiation-induced injury, especially in the 
early post-RT time period when most patients develop clinical symptoms. 
The protocol will leverage advances in MRI imaging that facilitate the assessment gas exchange, 
as well as pulmonary structure, ventilation, and perfusion within a single integrated MRI exam. 
Pulmonary ventilation and gas exchange are assessed 3-dimensionally by using inhaled 
hyperpolarized 129Xe MRI, which has been developed at Duke over the past 4 years under IRB 
protocol Pro00025110 and IND #109,490. In addition to this, pulse sequences have been 
implemented that complement this information with 3D isotropic 1H MR imaging of pulmonary 
structure and pulmonary perfusion. Perfusion is imaged following i.v. injection of an approved 
macrocyclic MRI contrast agent. Hence, the technology is now available at Duke, for a fully 3D 
MRI protocol capable of assessing all relevant aspects of pulmonary structure and function in a 
single exam. Since this approach does not use ionizing radiation, it can more safely be utilized to 
follow patients over time.  
Our aim is to now apply this set of imaging tests to objectively assert RT-associated changes in 
regional lung function.  Patients undergoing radiation therapy will be scanned at baseline prior to 
RT, and serially post-RT over a temporal window ranging out to 6 months post- RT. The exact 
timing of these post-RT assessments will be altered based on our initial results. The primary 
study objective is to evaluate dose- and time–dependence of RT-induced changes in MRI-
defined local function/structure. Our primary hypothesis is that pulmonary function measured by 
MRI will worsen after radiation therapy compared to baseline. The secondary study objective 
will test whether particular imaging features at baseline can predict the degree of radiation-
induced lung injury that will develop. We will compare the sensitivity with which MRI can 
detect changing pulmonary status to that of conventional pulmonary function testing. 


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3. Background and Significance: Radiation therapy when applied to tumors in or around the 
thorax is known to cause regional lung injury. Approximately 5-20% of patients experience 
dyspnea after RT and a larger fraction exhibits subclinical reductions in pulmonary function. 
Unfortunately, there are no well-accepted methods to predict a given patient’s risk of developing 
dyspnea after RT. Potential risk has been proposed to be predictable by patient-specific factors 
(age, smoking history, tumor location, gender) and treatment-specific factors (chemotherapy 
regimen and dose). However none of these have been consistently demonstrated across different 
studies. Moreover, controversy persists about which radiation dose parameters optimally predict 
the risk of radiation pneumonitis (lung volume or total dose). Furthermore, several medications 
have been evaluated for their ability to reduce radiation pneumonitis, but results have been 
mixed. A fundamental impediment to addressing all of these questions is that the pulmonary 
toxicity of irradiation does not significantly alter most standard pulmonary function tests. This is 
further compounded by the fact that radiation-induced injury is focal, whereas PFTs can only 
assess the lung as a whole.  
The shortcomings of global pulmonary function tests have led to increasing interest in using 3-
dimensional functional imaging to evaluate radiation-induced lung injury (RILI). Marks and 
others have conducted seminal studies of single-photon computed tomography (SPECT) to 
assess perfusion changes longitudinally in RT patients. However, SPECT imaging requires 
injection of radioactive 99mTc contrast agent, and suffers from relatively poor spatial and 
temporal resolution. Moreover, SPECT can currently only image pulmonary perfusion and not 
pulmonary structure, ventilation or gas-exchange. Instead, MRI now presents the opportunity to 
deploy a much more comprehensive and non-invasive approach to imaging pulmonary structure 
and function in a single exam. This capability should provide fundamental new insights 
regarding the origins of radiation-induced lung injury (RILI) and lay the groundwork to find 
ways to both predict it and treat it.  
Over the past 4 years of development, hyperpolarized 129Xe MRI has demonstrated the ability 
visualize pulmonary ventilation with high resolution. Moreover, by exploiting the moderate 
solubility of 129Xe in blood and pulmonary tissues, combined with its unique frequency shifts, it 
is now feasible to image the transfer of this gas from airspaces into the pulmonary capillary 
blood. Such 3-dimensional imaging of gas exchange has not been previously possible by any 
technique and provides a fundamentally new window on regional pulmonary gas exchange. The 
technique has been shown to be safe and well tolerated in human subjects. This was 
demonstrated by a phase I clinical trial for HP 129Xe MRI that was completed at Duke and 
published in the journal Radiology in 2012. This study enrolled 44 patients and healthy 
volunteers and demonstrated that inhalation of up to four 1 liter doses of HP 129Xe was well-
tolerated, generated no notable changes in measured physiologic parameters and resulted in no 
SAEs or withdrawals. The study involved developing a substantial technical infrastructure 
(polarizers, coils, phantoms, scanner upgrades) that is now available and used for clinical 
research at Duke. Since the completion of that study 100 additional patients and volunteers have 
been scanned, each of whom have inhaled with multiple doses of 129Xe without incident.  


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While ventilation and gas exchange as assessed by hyperpolarized 129Xe MRI provide a useful 
view on pulmonary function, there is additional value in adding structural and functional 
information provided by conventional 1H MRI. Lung structure can now be imaged using an 
ultrashort-echo time (UTE) sequence during a 4 min free-breathing scan. Such a scan will reveal 
local tissue density, edema, and other anatomical landmarks. Moreover, with the addition of a 
single injection of MR contrast agent, a 3D isotropic image of pulmonary perfusion can also be 
obtained. Thus, by combining HP 129Xe and 1H MRI, we can comprehensively assess both the 
structure and function of the irradiated lung longitudinally. 
4. Design and Procedures: This will be an unblinded, open-label study enrolling patients who 
are scheduled to undergo thoracic radiation therapy as part of their standard clinical care as well 
as healthy volunteers.  Approximately 35 subjects will be consented including screen fails. 
Subjects to be enrolled will include males and females over 18 years old, for a targeted 
enrollment of 20 subjects undergoing RT. An additional 10 healthy volunteers will be enrolled to 
optimize the MRI parameters and provide reference images for normal pulmonary function. 
After consent and screening, healthy volunteers will undergo just one study visit. Patients 
scheduled for RT will be seen up to 2 time points after consent and screening with an optional 
3rd time point− a baseline Visit 1 (before RT begins), Visit 2 (at ten-fourteen weeks post RT) 
and optional visit 3 (thiry-two to forty weeks post RT). For patients who participate in 2 visits, 
their participation will last until approximately 4 months after RT is completed, while patients 
completing the optional 3rd visit will participate until 12 months after RT. At each visit, subjects 
will undergo pulmonary function testing and MRI. The objective of the MRI session is to acquire 
3D images of pulmonary structure, ventilation, gas exchange and perfusion. Each session should 
take approximately 3 hours of the subject’s time.  
The study begins with detailed pulmonary function testing and the collection of relevant patient 
history and symptoms. Pulmonary function testing will include one or more of spirometry, lung 
volumes, DLCO and impulse oscillometry. The subject will be escorted to the MRI suite where 
they will be fitted with a 129Xe transmit-receive vest coil. They will then be positioned supine on 
the scanner bed. They will be coached about how to inhale hyperpolarized 129Xe from the dose 
delivery bags. Then the subject and bed will be moved into the scanner and they will undergo 
basic 1H localizer and anatomical scans. Once localization is complete, subjects will undergo 
several MRI scans after inhalation of HP 129Xe. Each dose will be limited to a volume less than 
25% of subject lung capacity (TLC) as is the case for our ongoing protocol Pro00025110. After 
each 129Xe dose, the table will be moved out of the magnet bore and the subject queried for any 
symptoms. The next 129Xe dose and scan will be administered when the subject and study 
personnel are ready. Subjects will undergo a calibration 129Xe MR spectroscopy scan, 129Xe 
ventilation MRI, and 129Xe gas exchange MRI. A given 129Xe MRI scan may be repeated, if 
necessary. There is no limit to the number of 129Xe scans allowed during the session although 
current 129Xe production capabilities are only sufficient to generate 5 129Xe doses per imaging 
session. After completing the 129Xe portion of the scan, the 129Xe coil will be removed and 


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patients fitted with a torso array 1H coil. They will then undergo a free-breathing ultra-short-echo 
time 1H MRI to delineate lung structure.. This completes the MRI exam, after which subjects 
will be free to go home or continue with their standard clinical care. All subjects will be 
evaluated at one center, Duke University, in Durham, NC, USA.   
5. Selection of Subjects: In addition to healthy volunteers, the population to be studied will 
consist of patients scheduled to undergo RT for either lung cancer or other malignancies such as 
breast cancer or lymphoma that involve significant irradiation of the thoracic cavity. Before each 
MRI session, the following criteria will be assessed in order to minimize risk to the subjects.  
Inclusion Criteria 
1. Patient scheduled to undergo thoracic RT at Duke University to a dose of at least 20 Gy  
2. Willing and able to give informed consent and adhere to visit/protocol schedules 
 
Exclusion Criteria:  
1. Subject is less than 18 years old 
2. MRI is contraindicated based on responses to MRI Screening questionnaire 
3. Subject is pregnant or lactating 
4. Respiratory illness of a bacterial or viral etiology within 30 days of MRI 
5. Subject has any form of known cardiac arrhythmia 
6. Subject does not fit into 129Xe vest coil used for MRI 
7. Subject cannot hold his/her breath for 15 seconds 
8. Subject deemed unlikely to be able to comply with instructions during imaging 
9. Medical or psychological conditions which, in the opinion of the investigator, might 
create undue risk to the subject or interfere with the subject’s ability to comply with the 
protocol requirements. 
 
Inclusion/Exclusion Criteria for Healthy Volunteers  
1.  Subject meets all criteria above but does not have a clinical diagnosis of respiratory   
disease. 
 
Subject Identification: Upon providing consent, the subject will be assigned a subject 
identification number (SIN), which will be used for all data collection and imaging studies. The 
SIN will consist of a study identifier and four digit extension (e.g. -0001 for the first subject). 
6. Subject Recruitment and Compensation: Healthy volunteers as well as patients who will be 
undergoing thoracic radiation therapy will be recruited via flyers and website postings. Patients 
scheduled to undergo thoracic radiation at Duke University may also be informed about study 
participation by their physician or physician’s staff. If they are interested in participating and 
appear to meet all inclusion criteria they will be referred to the study coordinator for formal 
consenting. It is expected that up to 10 healthy volunteers and 25 patients scheduled for RT will 


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be recruited in this first phase of the study. Recruitment will be open to all demographic groups. 
Subjects will be compensated after each study visit for their travel/parking and time. If a 
procedure has to be cancelled for technical reasons after a subject has arrived on site, the subject 
will be compensated as though he/she had completed the study. The subject will be encouraged, 
but not required to return at a later date to complete the procedure. If the subject returns, he/she 
will be compensated again.  
7. Consent Process: The study coordinator will consent prospective participants. If necessary, 
the participants will have no less than 24 hours to consider their participation. Consenting will 
take place in a private room. The prospective participant may have family or a friend present 
during the consent process if they wish.  At least an hour will be slotted for the consent process 
but we will not prevent the subject from asking questions beyond that time. If the subject wishes 
to consider the study overnight or longer, an additional appointment will be made for the subject 
to continue the consent process. From the time of initial contact until the participant completes 
the study they will have complete freedom to access the coordinator by phone, email, or in 
person. 
 8. Subject’s Capacity to Give Legally Effective Consent: Subjects without capacity to give 
consent will not be recruited in this study. 
9. Study Interventions: Hyperpolarized xenon will be administered in multiple doses in 
volumes up to 25% of subject TLC followed by a breath hold of up to 15 seconds. Subsequent 
129Xe doses will only be administered once the subject is ready to proceed. Hyperpolarized 129Xe 
MRI will be used to acquire one or all of the following data: 
1. 129Xe calibration dose to test coil tuning and loading in each subject to permit optimal 
setting of imaging parameters. 
2. 129Xe distribution after inhalation and breath-hold as an indicator of regional pulmonary 
ventilation.  
3. 129Xe signal dissolved in the pulmonary interstitial spaces and capillary blood as an 
indicator of pulmonary gas exchange. 
4. 129Xe spectroscopy to follow the dynamics of gaseous and dissolved-phase 129Xe.  
Conventional 1H MRI will be used to provide anatomical reference scans, as well as pulmonary 
perfusion. These will include some or all of the following: 
1. 3-Plane Localizer 
2. Breath-hold steady-state-free-precession image to highlight the vasculature. 
3. Breath-hold 3D radial MRI to delineate the thoracic cavity 
4. Free-breathing UTE 1H MRI to image tissue density and edema 
 
10. Risk/Benefit Assessment: As this is the first comprehensive study of its kind in patients 
undergoing RT, it is not known if the data generated will be of direct benefit to the patients.  It is 
certainly possible that images obtained from these studies will assist in the clinical management 
of the patients. For example, the pre-radiation scans may provide information regarding the 


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distribution of function within the lung that may aid in the design of radiation therapy portals. 
The post-radiation images may help in better understanding the causes of pulmonary symptoms 
that the patients may develop. For healthy volunteers, there will be no direct benefit. However, 
the knowledge gained from these studies is expected to benefit future patients who may undergo 
thoracic RT. 
 
Risks of Hyperpolarized 129Xe Inhalation of hyperpolarized 129Xe may carry some minor risks. 
Xenon is a general anesthetic when breathed continuously at concentrations greater than 70% for 
extended periods of time. In the proposed study, xenon will be delivered in a single breath, with 
alveolar concentrations below 25%. At these concentrations, subjects may experience transient 
effects including dizziness, slight tingling or numbness of the extremities, nausea, smelling of 
flowers, or a feeling of well-being and euphoria. These effects will wane within 1-2 minutes of 
exhaling the xenon and are documented in the consent forms.  
A second risk comes from administering HP 129Xe without oxygen. This is necessary to preserve 
good image quality, because O2 is paramagnetic and depolarizes the HP 129Xe. Administration of 
a single anoxic 1-liter breath has been well tolerated by subjects undergoing both 3He MRI and 
129Xe MRI because for a single breath, the residual oxygen in the subject’s lungs is sufficient to 
maintain blood O2 saturation during the breath-hold. For each subject, their blood-oxygenation 
will be monitored throughout the time they are in the MRI scanner. If deemed necessary, 
supplemental O2 will be provided by nasal cannula to maintain baseline O2 satuation.  
Incidental Findings - Anatomic 1H MR images will not be routinely reviewed by a radiologist. 
However, if the technologist or study personnel note suspicious findings in the anatomic (1H) 
images at the time of MRI, images from those subjects will be reviewed by a radiologist within 
10 business days for incidental findings (tumors, hernias, aneurisms, etc). Such incidental 
findings will be communicated to the subject’s physician. Copies of images will be made 
available to the subject’s physician upon their request. 
11. Costs to the Subject and Compensation: There are no additional costs to the subject for the 
MRI examination and the subjects will be compensated after each study visit for travel/parking 
and time for each study visit.  
12. Data Analysis & Statistical Considerations: The primary objective of this study is to 
evaluate if the pulmonary function measured by MRI will worsen after radiation therapy 
compared to baseline. 129Xe Ventilation images will be quantitatively assessed by semi-
automated segmentation to determine their ventilation defect percentage (VDP). Similar metrics 
can be applied to 129Xe gas exchange images, and 1H perfusion images. Each of these images 
will have a corresponding defect score for exchange defect percentage (EDP), and perfusion 
defect percentage (PDP). Although we expect radiation therapy to exert a greater effect on gas 
exchange (EDP) and perfusion (PDP), the bulk of our experience to date is with the more well-
established VDP metric. Thus, for the purpose of hypothesis testing and power justification, we 
chose VDP to be the primary endpoint for measuring the worsening pulmonary function after 


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radiation therapy relative to baseline. We have preliminary experience with this measurement in 
patients with idiopathic pulmonary fibrosis (IPF), which shares some functional similarities to 
radiation-induced pneumonitis. In 8 patients with IPF, we observe VDP=20.5+8.8 compared to 
10 age-matched healthy control subjects with a mean VDP of 8.1+2.9.  
We plan to enroll a total of 25 patients who undergo radiation therapy. Taking 20% attrition rate 
into account, the study will have a total of 20 treated patients who have VDP measures at both 
baseline and Visit 2 (at 10-14 weeks post RT). With valid VDP measures from 20 patients, the 
study has approximately 81% power to detect a 12% increase in VDP after RT at Visit 2 relative 
to baseline. This calculation assumes a one-sided significance level of 0.05 using a Wilcoxon 
Signed-Rank Test. These results are based on 2000 Monte Carlo samples and the assumption that 
the paired VDP measures follow a bivariate normal distribution with standard deviation 16 and 
correlation 0.2. 
In addition to VDP, pulmonary functional images pre- and post RT will also be evaluated using 
the EDP and PDP metrics described above, as well as the regional differences in 129Xe uptake in 
barrier tissues vs RBCs. Functional imaging maps will be co-registered with the patient’s dose 
plan. Functional metrics such as RBC:barrier ratio will be computed in isodose regions and 
correlation plots will be generated.  
The mean, standard deviation, median and range of VPD and other pulmonary function measures 
and the changes relative to baseline will be estimated for each visit at which MRI imaging is 
undertaken. The 95% confidence interval for means and averaged changes relative to baseline 
will be provided. The VDP increase 6 weeks after radiation therapy compared to baseline will be 
tested using Wilcoxon Singed-Rank test. To control overall type I error, formal hypothesis 
testing will not be conducted for the secondary endpoints for pulmonary functions. The trajectory 
changes of these endpoints over time and the dose-dependent damage effect will be evaluated 
using linear models for repeated measures. Point estimates and confidence intervals for relevant 
parameters will be provided for descriptive purpose. Appropriate transformation will be taken on 
these endpoints if normality assumption is clearly violated in the regression analysis. 
13. Data and Safety Monitoring: Subjects will be monitored before, during and after each 
treatment with xenon to assess for adverse events and changes in vital signs. The parameters 
monitored include the following: subject assessment of anesthetic/analgesic effects, heart rate, 
and SPO2. The subjective sense of analgesia is assessed by an inquiring about how the subject 
feels after administration of the xenon dose. The subject will be asked to describe how they feel 
as well as about specific symptoms including: dizziness, light-headedness, numbness, euphoria, 
sleepiness, and tingling in extremities. Heart rate will be measured before and after each xenon 
treatment. Changes in heart rate of greater than +/- 20% are considered significant. If the subject 
is to receive another dose, the next dose will not be administered until the heart rate is within 20 
% of its baseline value. If the subject has received their last dose, they will be observed until 
their heart rate is within +/- 20% of its base line value or until the end of the observation period, 


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whichever is longer. SPO2 is measured at baseline and after each xenon treatment. A decrease of 
SPO2 by greater than 5% is considered significant. If the subject is to receive another dose, the 
next dose will not be administered until the SPO2 is within 5 % of its baseline value. If the 
subject has received their last dose, they will be observed until the SPO2 is within 5% of its 
baseline value or until the end of the observation period, whichever is longer. The subject will be 
monitored for the duration of the xenon treatment and post procedural period by a qualified 
medical professional. If deemed necessary, supplemental O2 will be provided by nasal cannula to 
maintain baseline O2 satuation. 
Discontinuation - Participation in this study is voluntary and subjects are free to withdraw at any 
time and for any reason. Furthermore, the individual subject will be withdrawn from the trial 
should they develop any worsening of health or new medical illness that is deemed to be a result 
of this study. Parameters to be evaluated include but are not limited to: shortness of breath, heart 
rate or decreased blood oxygenation related to xenon administration. If a subject experiences a 
decrease in oxygenation that is greater than or equal to 5% that persists for more than 5 minutes, 
and cannot be resolved by administering supplemental oxygen, they will be withdrawn from the 
trial. Similarly, if patients experience a change in heart rate of more than 20% on more than one 
occasion after xenon administration they will be withdrawn. Other reasons for discontinuation 
include subject becomes uncomfortable in the magnet, subject becomes unresponsive or is 
unable to protect their airway, subject requests study discontinuation, or other concerns. 
If any subject experiences a serious adverse drug experience (as defined in 21 CFR Part 
312.32(a)), the trial will be discontinued immediately. 
This clinical research study will be monitored both internally by the PI and institutionally by the 
Duke Cancer Institute (DCI).  In terms of internal review the PI will continuously monitor and 
tabulate adverse events.  Appropriate reporting to the Duke University Medical Center IRB will 
be made.  If an unexpected frequency of Grade III or IV events occur, depending on their nature, 
action appropriate to the nature and frequency of these adverse events will be taken.  This may 
require a protocol amendment, dose de-escalation, or potentially closure of the study.  The PI of 
this study will also continuously monitor the conduct, data, and safety of this study to ensure 
that: 
• Interim analyses occur as scheduled; 
• Stopping rules for toxicity and/or response are met; 
• Risk/benefit ratio is not altered to the detriment of the subjects; 
• Appropriate internal monitoring of AEs and outcomes is done; 
• Over-accrual does not occur; 
• Under-accrual is addressed with appropriate amendments or actions; 
• Data are being appropriately collected in a reasonably timely manner. 
 


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DCI review and monitoring of this protocol occurs in accordance with the NCI-approved Data 
and Safety Monitoring Plan.  Briefly, protocol review begins with an initial review by the Cancer 
Protocol Committee (CPC), which assesses the ethics and safety of the protocol.  Documentation 
of these assessments will be maintained.  Formal, independent monitoring will be conducted by 
the DCI Monitoring Team after the first 3 subjects are enrolled, followed by annual monitoring 
of 1-3 subjects until the study is closed to enrollment and subjects are no longer receiving study 
interventions that are more than minimal risk.  DCI Monitoring Team reports and additional 
data/safety/toxicity reports submitted by the PI will be reviewed by the Safety Oversight 
Committee (SOC) on an annual basis.  Additional monitoring may be prompted by findings from 
monitoring visits, unexpected frequency of serious and/or unexpected toxicities, or other 
concerns.  Monitoring visits may also be initiated upon request by DUHS and DCI Leadership, 
CPC, SOC, a sponsor, an investigator, or the IRB.     
14. Privacy, Data Storage & Confidentiality: All consent and case report forms will be stored 
in a locked filing cabinet in the office of the study coordinator or principal investigator. Any 
other digital data (images, image analysis) will be associated only with the subject identification 
number and the date and time of the images. Image data will be retrieved and analyzed only by 
study personnel. The data is stored in a password protected, controlled access account with 
authentication and mandatory password change features. All CRF's will use the subject 
identification number as the only identifier. At the end of the study the key to the code will be 
destroyed. 


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Schedule of Events 
Protocol Activities 
Screening 
(V0)1 
Study  
Visit (V1)1 
Study 
Visit (V2)1 
 Optional 
Study 
Visit (V3)1  
Informed Consent1 
X 
 
 
 
Medical History 
X 
(X) 
 
 
MRI Screening Form 
X 
(X) 
(X) 
(X) 
Pulmonary Function Testing2  
X 
X 
X 
Pregnancy Test3  
(X) 
(X) 
(X) 
(X) 
MRI Session4 
 
X 
X 
X 
Subject monitoring and vital 
signs  
 
X 
X 
X 
Adverse events followup6 
 
X 
X 
X 
Hemoglobin 
(optional) 
Finger sensor machine  
X 
X 
X 
X 
 
1. For most subjects, screening and study visit 1 will occur on the same day. However, these 
visits can be conducted separately if needed as long as it is completed before the initial 
RT treatment. Visit 2 will occur ten to fourteen weeks post RT. Optional Visit 3 will 
occur thirty-two to forty weeks  post RT.                                              
2. Pulmonary function testing will include one or more of spirometry, lung volumes, DLCO 
and impulse oscillometry. For healthy volunteers taking part in the technical optimization 
part of the study, PFTs are not required, but may be collected if desired by the study 
team. If some or all PFT information is already available from the patient record and 
deemed sufficient by study personnel, PFTs may not be collected. Pulmonary function 
testing will be conducted at Duke Clinical Research Unit (DCRU). Key personnel will 
accompany the subject from the beginning through the completion of each study visit. 
3. Any female patients of child-bearing potential scheduled for radiation therapy should 
have a negative pregnancy test per standard of care. However, if such information is not 
available, or for female healthy volunteers of child bearing potential participating for 
technicial optimization, a serum pregnancy test will be performed at screening. The test 
must be negative and the participant must agree to use an acceptable method of birth 
control for the duration of the study.  Then a urine pregnancy test will be completed with 
a negative result before each MRI if the MRI is conducted on a different day than the 
screening visit or other study visits. The pregnancy test will be conducted and interpreted 


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by study personnel who have completed competency training from the Duke Office of 
Clinical Research (DOCR).  
4. The MRI session will be conducted on the CAMRD research MRI scanner. 
Hyperpolarized 129Xe is produced and delivered by the study team.  
5. During the 1-hr MRI session, a qualified medical professional (MD, DO, PA, LNP, RN, 
RT or MT) will be on hand to monitor subjets during MRI and note any symptoms 
related to xenon MRI.  
6. Based on the known pharmacokinetics of xenon, no additional effects are expected after 
subject is released from the imaging study. However, subjects will be provided contact 
information for the study coordinator so they can report any concerns over the 24 hours 
after undergoing MRI.  
 
 

ICF_001.pdf: 
Protocol Title: Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment 
 
 
NCT02478255 
 
 
Consent Reference Date: 26Apr2021 
 
 


                                                                                                                                                                                    
Con
Consent to Participate in a Research Study
Longitudinal MR Imaging of Pulmonary Function in Patients 
Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment
Page 1 of 9
Subject Initials:
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
You are being asked to take part in this research study because you are healthy and do not have lung 
disease, or you are scheduled to undergo Radiation Therapy (RT) for lung cancer, or other malignancies 
such as breast cancer or lymphoma that involve significant irradiation of the thoracic cavity. Research 
studies are voluntary and include only people who choose to take part. Please read this consent form 
carefully and take your time making your decision. As the study doctor or study staff discusses this 
consent form with you, please ask him/her to explain any words or information that you do not clearly 
understand.  We encourage you to talk with your family and friends before you decide to take part in this 
research study. The nature of the study, risks, inconveniences, discomforts, and other important 
information are listed below.
Please tell the study doctor or study staff if you are taking part in another research study.
WHO WILL BE MY DOCTOR ON THIS STUDY?
If you decide to participate in this study, your doctors will be Drs. Joseph Mammarappallil, MD PhD 
and Christopher Kelsey, MD. They will be in contact with your regular health care provider throughout 
the time that you are in the study and afterwards, if needed. Please note that Dr. Driehuys, PhD is a 
meber of the study team and holds several patents related to the technology used in this study. These 
patents are licensed to Polarean, Inc for commercial development. While Polarean, Inc. is not sponsoring 
the present study, Dr. Driehuys does have an ownership stake in this company. 
A grant from the National Institutes of Health (NIH) will sponsor this study.  Portions of Drs. 
Mammarappallil’s and Dr. Driehuys’ salaries and their research team’s salaries will be paid by this 
grant.
WHY IS THIS STUDY BEING DONE?
The purpose of this study is to determine whether magnetic resonance imaging (MRI) using inhaled 
hyperpolarized  129Xe gas, and conventional contrast can help visualize impaired lung function and 
detect changes over time in patients receiving treatment as well as those who don’t. 129Xe is a special 
type of xenon gas and when inhaled during MRI may be able to show areas of abnormal thickening of 
parts of the lungs. These images combined with images taken with other special types of MRI such as 
1H MRI may provide a better way to look at lung structure and function.  Our ultimate goal is to predict 
the degree of radiation-induced lung injury that will develop in a given patient for a given treatment 
plan. We anticipate that these images will provide more specific information about lung disease than 
standard lung function tests.  The use of 129Xe MRI  is investigational.  Investigational means that these 
tests have not yet been approved by the US Food and Drug Administration and are only available in 
research studies like this one.  
Healthy volunteers are being asked to participate in this study because we need to develop a database of 
functional images that are representative of healthy lungs.
DUHS IRB
IRB NUMBER: Pro00059856
IRB REFERENCE DATE: 04/26/2021
IRB EXPIRATION DATE: 05/14/2022


                                                                                                                                                                                    
Con
Consent to Participate in a Research Study
Longitudinal MR Imaging of Pulmonary Function in Patients 
Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment
Page 2 of 9
Subject Initials:
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY?
Approximately 35 participants consisting of 10 healthy volunteers and 25 patients scheduled to undergo 
thoracic radiation therapy will take part in this study at Duke University Medical Center.  
WHAT IS INVOLVED IN THE STUDY?
If you agree to be in this study, you will be asked to sign and date this consent form. The study involves 
the following visits:

Screening Visit – You will be asked to sign and date this consent form.  At the screening 
visit, you will be asked for your medical history, record of medications, and your vital 
signs (including Hemoglobin (optional) Finger sensor machine) will be measured . You 
will be asked to fill out a questionnaire to ensure that you are eligible to undergo an MRI 
scan. If you are female of child-bearing potential, you will be required to undergo a 
serum pregnancy test and it must be negative before you can continue to participate in 
this study. 

Visit 1  - Baseline imaging study. If you are a healthy volunteer, this visit will take place at the 
same time as the screening visit or shortly after and will be your only study visit.  If you are a 
subject that is about to begin thoracic radiation therapy, this visit may also occur at the same time 
as the screening visit or shortly after, but must be done before you begin radiation therapy. 

Visit 2- Ten to fourteen weeks after Radiation Therapy is completed.

Optional Visit 3 Thirty-two to forty weeks after Radiation Therapy is completed.

Please initial one of the options below to indicate you are willing to be contacted for visit 3 

____ Yes, I agree to be contacted for the optional visit 3, thirty-two to forty weeks after 
Radiation Therapy is completed.

____ No, I do not agree to be contacted for the optional visit 3, thirty-two to forty weeks after 
Radiation Therapy is completed.
Each of these visits will take about 4 hours.  Each visit will begin with a review of your relevant history, 
symptoms, medications and rescreening for eligibility to participate, including a serum sample for 
pregnancy testing for women of child-bearing potential and your vital signs (including optional 
hemoglobin by finger sensor) will be measured. Either after screening or on a separate day you will 
undergo pulmonary function testing to assess your global lung function using standard clinical tests. 
However, if pulmonary function test results are already available from your medical record, the 
pulmonary function tests will not be done.
DUHS IRB
IRB NUMBER: Pro00059856
IRB REFERENCE DATE: 04/26/2021
IRB EXPIRATION DATE: 05/14/2022


                                                                                                                                                                                    
Con
Consent to Participate in a Research Study
Longitudinal MR Imaging of Pulmonary Function in Patients 
Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment
Page 3 of 9
Subject Initials:
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
After pulmonary function testing you will participate in the MRI portion of the study. For the MRI 
examination, you will lie on your back on a table, wearing a vest that transmits and receives signals for 
the MRI and a small sensor will be applied to your finger to monitor your pulse rate and blood oxygen 
levels. The table will be slid into the bore of the MRI scanner (a tunnel about 6 feet long and 25 inches 
in diameter) and we will obtain one or more MRI scans of your lungs. After this, you will be instructed 
to inhale a small calibration dose of hyperpolarized 129Xe from a plastic bag through a mouthpiece.  
Following this, you will be asked to inhale additional doses of hyperpolarized 129Xe to acquire different 
kinds of lung scans. For each 129Xe dose you will be asked to hold your breath for approximately 15 
seconds while the scan is obtained. During each scan, your heart rate and your oxygen saturation will be 
monitored. After each 129Xe dose, the table will slide out of the MRI bore so that you can communicate 
with study personnel. When you are ready, the next xenon dose will be administered. Following 129Xe 
MRI, you will be fitted with a different MRI coil vest for high-resolution imaging of your anatomy. 
After the MRI examination, you will remain with study personnel until you feel recovered from any 
study effects and your heart rate and oxygen saturation are within an acceptable range. You will then be 
free to go home. The study coordinator will give you her contact information at the time of your initial 
visit. If you feel that you are having any symptoms or effects related to your participation in the study, 
please contact the study coordinator or the physicians listed in this consent.  
In addition, the team may obtain information from your DUHS medical record and use this data to 
analyze the MRI scans obtained as part of this study.  The study doctor may stop your participation in 
this study at any time without your consent. Potential reasons for ending your participation may include 
safety concerns or general reasons related to the conduct of the research study itself.
HOW LONG WILL I BE IN THIS STUDY?
Your participation in the study will require about 4 hours for each visit depending upon whether or not 
your screening, pulmonary function testing, and imaging sessions are performed on the same day. If you 
are a healthy volunteer it may require only a screening visit and an MRI study visit.  That decision will 
be made by you and the study personnel based upon your availability and that of the MRI scanner.  
Subjects who are undergoing thoracic radiation therapy will be in the study from the time this consent 
form is signed until the completion of the study visit 2; they will be given the option to participate in 
visit 3. For patients who participate in 2 visits, their participation will last until approximately 4 months 
after RT is completed, while patients completing the optional 3rd visit will participate until 12 months 
after RT.
You can choose to stop participating at any time without penalty or loss of any benefits to which you are 
entitled.  If you decide to stop participating please notify the study team by Joseph Mammarappallil, 
DUHS IRB
IRB NUMBER: Pro00059856
IRB REFERENCE DATE: 04/26/2021
IRB EXPIRATION DATE: 05/14/2022


                                                                                                                                                                                    
Con
Consent to Participate in a Research Study
Longitudinal MR Imaging of Pulmonary Function in Patients 
Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment
Page 4 of 9
Subject Initials:
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
MD PhD at (919) 684-2051 during regular business hours or at (270) 232-6617) after hours or on 
weekends.
Note: in the event of scan cancellation for any reason or inadequate image quality, you may be asked to 
return for a single repeat scan (and additiona reimbursement). We anticipate this will happen in less than 
5% of the cases. 
WHAT ARE THE RISKS OF THE STUDY?
There is a potential risk of loss of confidentiality.  Every effort will be made to protect your confidential 
information but this cannot be guaranteed.
Venipuncture – Taking blood from a vein in your arm by needle stick
Risks associated with drawing blood from your arm include momentary discomfort and/or bruising. 
Infection, excess bleeding, clotting, or fainting are also possible, although unlikely.
MRI Risks:
Magnetic resonance imaging (MRI) uses a magnet and radio waves to make diagnostic medical images 
of the body.  There have been no ill effects reported from exposure to the magnetism or radio waves 
used in this test.  However, it is possible that harmful effects could be recognized in the future.  A 
known risk is that the magnet could attract certain kinds of metal.  Therefore, we will carefully ask you 
about metal within your body (this includes certain dyes found in tattoos).  If there is any question about 
potentially hazardous metal within your body, you will be excluded from participation in this research 
study.  
The study involves entering a large room in which a magnet is present.  You will be placed on a narrow 
bed and then slid into a small tunnel approximately 6 feet in length and 25 inches in diameter.  You will 
be asked to lie still for about one hour on this bed.  During MRI scanning you will hear a loud machine-
like noises.  You may be asked to have a harmless monitoring device applied during the study.  During 
the study, you can have voice contact and physical contact with someone in attendance if you desire. 
The MRI scan can be stopped at any time if you request it.
Risks of Xenon Gas:
Inhalation of xenon gas may cause you to feel the following effects: 
•
Slight numbness in the legs
•
Nausea
•
A sensation similar to smelling flowers
•
A feeling of well-being or elation 
•
Mild tingling in the fingertips
DUHS IRB
IRB NUMBER: Pro00059856
IRB REFERENCE DATE: 04/26/2021
IRB EXPIRATION DATE: 05/14/2022


                                                                                                                                                                                    
Con
Consent to Participate in a Research Study
Longitudinal MR Imaging of Pulmonary Function in Patients 
Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment
Page 5 of 9
Subject Initials:
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
Female
Being a part of this study (MRI) while pregnant may expose the unborn child to significant risks, some 
of which may be currently unforeseeable.  Therefore, pregnant women will be excluded from the study.  
If you are a woman of childbearing potential, you will be required to undergo a serum pregnancy test 
and it mus be negative before you can continue to participate in the study.  A urine pregnancy test will 
also be completed on the day of your MRI if done on a different day from screening and/or other study 
visits. For the duration of the study you agree to use an approved method of birth control. Medically 
acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) 
approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) 
barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device 
(IUD). Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are 
not acceptable methods for routine use. If you do become pregnant during this study or if you have 
unprotected sex, you must inform your study physician immediately.  
There may be risks, discomforts, drug interactions or side effects that are not yet known.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
This research study is not an established diagnostic medical test and will be of no direct benefit to you. 
We hope that in the future the information learned from this study will benefit other people with lung 
disease. The pictures obtained during this study are for research purposes and are not designed to search 
for any existing lung, heart, abdominal, or other abnormalities. In the unlikely event that the technologist 
or investigator evaluating your scans notices something that appears abnormal, these scans will be 
reviewed by a radiologist, and the results of his/her evaluation will be provided to you and/or your 
primary care physician. The decision to proceed with any further evaluation or treatment based upon this 
information lies with you and your physician. If you choose to pursue further evaluation or treatment, 
you will be responsible for any additional costs incurred.
WILL MY INFORMATION BE KEPT CONFIDENTIAL?
Participation in research involves some loss of privacy. We will do our best to make sure that 
information about you is kept confidential, but we cannot guarantee total confidentiality. Your personal 
information may be viewed by individuals involved in this research and may be seen by people 
including those collaborating, funding, and regulating the study. We will share only the minimum 
necessary information in order to conduct the research. Your personal information may also be given out 
if required by law.
As part of the study, results of your study-related laboratory tests, x-rays, and procedures may be 
reported to National Institutes of Health (NIH) and its affiliates. These could include pulmonary 
function tests and MRI scans of the lungs. In addition, the team may obtain information from your 
DUHS medical record and use this to analyze the MRI scans obtained. The date and time included in 
DUHS IRB
IRB NUMBER: Pro00059856
IRB REFERENCE DATE: 04/26/2021
IRB EXPIRATION DATE: 05/14/2022


                                                                                                                                                                                    
Con
Consent to Participate in a Research Study
Longitudinal MR Imaging of Pulmonary Function in Patients 
Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment
Page 6 of 9
Subject Initials:
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
your MRI will be stored on the images indefinitely. In addition, your records may be reviewed in order 
to meet federal or state regulations. Reviewers may include representatives from the Food and Drug 
Administration], representatives and affiliates of NIH, the Duke University Health System Institutional 
Review Board, [the Duke Cancer Institute, Duke Ethics and Compliance Office and other authorized 
organizations], and others as appropriate. If any of these groups review your research record, they may 
also need to review your entire medical record.
The study results will be retained in your research record forever.  Any research information in your 
medical record will also be kept indefinitely.
This information may be further disclosed by the sponsor of this study.  If disclosed by the sponsor, the 
information is no longer covered by federal privacy regulations.
If this information is disclosed to outside reviewers for audit purposes, it may be further disclosed by 
them and may not be covered by federal privacy regulations.
While the information and data resulting from this study may be presented at scientific meetings or 
published in a scientific journal, your name or other personal information will not be revealed.
Some people or groups who receive your health information might not have to follow the same privacy 
rules. Once your information is shared outside of DUHS, we cannot guarantee that it will remain private. 
If you decide to share private information with anyone not involved in the study, the federal law 
designed to protect your health information privacy may no longer apply to the information you have 
shared.  Other laws may or may not protect sharing of private health information.
The Department of Health and Human Services (HHS) has issued a Certificate of Confidentiality to 
further protect your privacy.  With this Certificate, the investigators may not disclose research 
information that may identify you in any Federal, State, or local civil, criminal, administrative, 
legislative, or other proceedings, unless you have consented for this use. Research information protected 
by this Certificate cannot be disclosed to anyone else who is not connected with the research unless:  
1) there is a law that requires disclosure (such as to report child abuse or communicable 
diseases but not for legal proceedings); 
2) you have consented to the disclosure, including for your medical treatment; or 
3) the research information is used for other scientific research, as allowed by federal 
regulations protecting research subjects. 
Disclosure is required, however, for audit or program evaluation requested by the agency that is funding 
this project or for information that is required by the Food and Drug Administration (FDA).
 
You should understand that a Confidentiality Certificate does not prevent you or a member of your 
DUHS IRB
IRB NUMBER: Pro00059856
IRB REFERENCE DATE: 04/26/2021
IRB EXPIRATION DATE: 05/14/2022


                                                                                                                                                                                    
Con
Consent to Participate in a Research Study
Longitudinal MR Imaging of Pulmonary Function in Patients 
Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment
Page 7 of 9
Subject Initials:
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
family from voluntarily releasing information about yourself or your involvement in this research. If you 
want your research information released to an insurer, medical care provider, or any other person not 
connected with the research, you must provide consent to allow the researchers to release it. This means 
that you and your family must also actively protect your own privacy.
Finally, you should understand that the investigator is not prevented from taking steps, including 
reporting to authorities, to prevent serious harm to yourself or others.
WHAT ARE THE COSTS?
There will be no additional costs to you as a result of being in this study and there is no charge for the 
MRI scan. However, routine medical care for your condition (care you would have received whether or 
not you were in this study) will be charged to you or your insurance company. You may wish to contact 
your insurance company to discuss this further. In order to make sure that tests and studies done solely 
for research purposes are charged correctly, we will carefully monitor your Duke Hospital and Clinic 
charges as long as you are participating in this study. These tests and studies are not a part of routine 
care, and people who are not part of the study do not usually have them performed. Please ask your 
study personnel if you would like to know more about which tests and studies are being done solely for 
research purposes.
WHAT ABOUT COMPENSATION?
You will be reimbursed for your time and expenses related to your participation as follows: 
Screening V1 $50
Imaging V1 $50
V2 $100
V3 $100
Please note that payment received as compensation for participation in research is considered taxable 
income to the research subject. If payment to an individual exceeds $600 in any one calendar year, Duke 
University is required to report this information to the Internal Revenue Service (IRS). Research subject 
payments to a non-employee of Duke University exceeding $600 during any calendar year will result in 
a 1099 (Miscellaneous Income) form being issued to the individual and a copy sent to the IRS.
WHAT ABOUT RESEARCH RELATED INJURIES?
Immediate necessary medical care is available at Duke University Medical Center in the event that you 
are injured as a result of your participation in this research study.  However, there is no commitment by 
Duke University, Duke University Health System, Inc., or your Duke physicians to provide monetary 
compensation or free medical care to you in the event of a study-related injury.
DUHS IRB
IRB NUMBER: Pro00059856
IRB REFERENCE DATE: 04/26/2021
IRB EXPIRATION DATE: 05/14/2022


                                                                                                                                                                                    
Con
Consent to Participate in a Research Study
Longitudinal MR Imaging of Pulmonary Function in Patients 
Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment
Page 8 of 9
Subject Initials:
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
For questions about the study or research-related injury, contact Joseph Mammarappallil, MD PhD at 
(919) 684-2051 or Bastiaan Driehuys, PhD at (919) 684-7786 during regular business hours.  After 
hours and on weekends and holidays, contact Dr Joseph Mammarappallil, MD PhD at (270) 232-6617 
or Bastiaan Driehuys, PhD at (919) 923-1981.
WHAT ABOUT MY RIGHTS TO DECLINE PARTICIPATION OR WITHDRAW FROM THE 
STUDY?
You may choose not to be in the study, or, if you agree to be in the study, you may withdraw from the 
study at any time. If you withdraw from the study, no new data about you will be collected for study 
purposes unless the data concern an adverse event (a bad effect) related to the study. If such an adverse 
event occurs, we may need to review your entire medical record.  
Your decision not to participate or to withdraw from the study will not involve any penalty or loss of 
benefits to which you are entitled, and will not affect your access to health care at Duke.  
Nonparticipation or withdrawal from this study will not affect your job status if you are a Duke 
employee and will not affect your grades if you are a Duke student.  If you do decide to withdraw, we 
ask that you contact Dr. Driehuys in writing and let him know that you are withdrawing from the study.  
His mailing address is DUMC Box 3302, Durham, NC 27710.  
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or research-related injury, contact Dr Joseph Mammarappallil, MD PhD 
at (919) 684-2051 or Bastiaan Driehuys PhD at (919) 684-7786 during regular business hours. After 
hours and on weekends and holidays, contact Dr. Joseph Mammarappallil, MD PhD  at (270) 232-6617 
or Bastiaan Driehuys, PhD at (919) 923-1981.
For questions about your rights as a research participant, or to discuss problems, concerns or suggestions 
related to the research, or to obtain information or offer input about the research, contact the Duke 
University Health System Institutional Review Board (IRB) Office at (919) 668-5111.
We will tell you about new information that may affect your health, welfare, or willingness to stay in 
this study.
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.
DUHS IRB
IRB NUMBER: Pro00059856
IRB REFERENCE DATE: 04/26/2021
IRB EXPIRATION DATE: 05/14/2022


                                                                                                                                                                                    
Con
Consent to Participate in a Research Study
Longitudinal MR Imaging of Pulmonary Function in Patients 
Longitudinal MR Imaging of Pulmonary Function in 
Patients Receiving Thoracic Radiation Treatment
Page 9 of 9
Subject Initials:
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
STATEMENT OF CONSENT
"The purpose of this study, procedures to be followed, risks and benefits have been explained to me. I 
have been allowed to ask questions, and my questions have been answered to my satisfaction. I have 
been told whom to contact if I have questions, to discuss problems, concerns, or suggestions related to 
the research, or to obtain information or offer input about the research. I have read this consent form and 
agree to be in this study, with the understanding that I may withdraw at any time. 
I have been told that I will be given a signed and dated copy of this consent form."
__________________________________________
___________/___________
Signature of Subject
Date
Time
__________________________________________
___________/___________
Signature of Person Obtaining Consent
Date
Time
DUHS IRB
IRB NUMBER: Pro00059856
IRB REFERENCE DATE: 04/26/2021
IRB EXPIRATION DATE: 05/14/2022