Assessment of Mandibular Bone Invasion With Magnetic Resonance Imaging (MRI) Using Sweep Imaging Fourier Transformation (SWIFT)
Conditions: Oral Cancer
Sponsor: University of Minnesota

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Assessment of mandibular bone invasion with Magnetic Resonance Imaging 
(MRI) using SWeep Imaging with Fourier Transformation (SWIFT) 
 
Principal Investigator:  Samir Khariwala, MD MS 
Co Investigators: Bevan Yueh, MD MPH; Donald Nixdorf, DDS, MS,  Djaudat    
Idiyatullin, PhD 
 
 
 
 
 
 
 
 
 
 
 
 
Version Number:  2 
July 27, 2015 

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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event/Adverse Experience 
CMRR 
Center for Magnetic Resonance Research 
CRF 
Case Report Form 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IRB 
Institutional Review Board 
MRI 
Magnetic Resonance Imaging 
PI 
Principal Investigator 
SAE 
Serious Adverse Event/Serious Adverse Experience 

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PROTOCOL SUMMARY 
Title: 
Assessment of mandibular bone invasion with Magnetic Resonance 
Imaging (MRI) using SWeep Imaging with Fourier Transformation 
(SWIFT) 
Précis: 
MRI scanning in 3T and 4T MR magnet will be performed on up 
to 20 patients with possible maxillofacial and/or mandibular bone 
invasion by applying newly developed sequences and clinically 
established MR sequences. We will then compare the 
conventional imaging results of the patients with 3T and 4T MRI 
results and post operative pathology results.  
Objectives: 
The primary objective of this study is to improve the diagnostic 
accuracy and specificity of MRI in detecting the degree of bone 
involvement and invasion in oral cancer. The presence and 
degree of bone invasion determines the extent of surgery and 
has great effect on the morbidity of patients with oral cancer and 
bone/soft tissue tumors. 
 
Primary:  To demonstrate the efficacy of the MRI scanning in 3T 
and 4T MR magnet for patients with squamous cell carcinoma 
adjacent to, or involving, the mandible. Comparison will be made 
to histolopathological sections as the “gold standard.” 
Population: 
We plan to enroll 20 subjects with a diagnosis of advanced 
squamous cell carcinoma of the oral cavity or 
osteoradionecrosis. All of those subjects enrolled will have 
findings concerning for mandibular invasion on physical 
examination or computed tomography imaging. Prior to 
surgery, patients will be consented for SWIFT imaging. 
Imaging will be conducted during a seven-day period prior to 
surgery. 
Number of Sites: 
University of Minnesota- CMRR 
Study Duration: 
Four years 
Subject 
Participation 
Duration: 
1 ½ hours for the study visit with MRI 
Estimated Time to 
Complete  
3 Years 
 

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Schematic of Study Design: 
 
Screening 
 
 
 
Enrollment 
 
 
 
 
Visit 1  
Time Point 
 
 
 
 
 
 
 
 
 
 
 
Total 10:  Obtain informed consent, complete CMRR subject safety questionnaire, 
review medical history and confirm eligibility with surgeon. 
 Assessment 
                                               Obtain MRI images  
Completion of Study 
Participation 
Total 10:  Screen potential participants by inclusion and exclusion criteria; discuss 
eligibility with PI  

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1 INTRODUCTION:  BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
1.1 
Background Information and Study Rational 
The primary objective of this study is to improve the diagnostic accuracy and 
specificity of MRI in detecting the degree of bone involvement. The presence 
and degree of bone invasion determines the extent of surgery and has great 
effect on the morbidity of patients with oral cancer and bone/soft tissue tumors. 
The most important factor in the management is to accurately identify the 
presence of neoplastic invasion.  
Unfortunately, detecting bone invasion and extension of bone involvement prior 
to surgery is often difficult with the currently available imaging techniques. MRI 
with high contrast resolution and the ability to perform multiplanar imaging plays 
an integral role in the delineation of tumoral involvement of the bone. Although 
MRI is an excellent tool in the assessment of bone invasion in carcinoma, its 
overestimation of cortical invasion and tumor extent to the bone marrow have 
been a diagnostic challenge, leading to false positive results. Like many of the 
musculoskeletal system tissues, cortical bone produces no signal with 
conventional MRI techniques, limiting the characterization of image contrast 
and differentiation of adjacent soft tissues. 
A novel MRI technique called Sweep Imaging with Fourier Transformation 
(SWIFT) appears to be a suitable tool to overcome this challenge.  The main 
advantage of SWIFT is to obtain signal from the cortical bone. We believe that 
the SWIFT technique will overcome the false positive results.   
1.2 
Potential Risks and Benefits 
 This study has the following risks: 

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1.2.1 
Potential Risks 
Screening Questionnaire  
The questionnaire asks questions that are private in nature.  Also, some people can 
be embarrassed by the questions.  There is a risk that the information from the 
questionnaire could inadvertently be disclosed.  
Magnetic Resonance Imaging (MRI) 
MRI is routinely used in healthcare to look at tissues in the body. MRI scanners, the 
machines that take these images, have a strong magnetic field and have been 
cleared by the Food and Drug Administration (FDA) for routine use for patients.  
While there are no known health risks associated with these strong magnetic fields, 
some people report dizziness, mild nausea, headache, a metallic taste in the mouth, 
or sensations of flashing lights. These effects have been associated with movement 
of the head in a strong magnetic field. These symptoms, if present, disappear 
shortly after leaving the magnet. There are some risks linked with the MRI scanning 
procedure itself, which include: 
1.  Projectile Objects. Objects with magnetic properties, such as metallic objects, 
can be pulled into the magnet. These objects can be dangerous if they are brought 
into the magnet room. By keeping magnetic objects away from the magnet and by 
controlling access to the magnetic field area, we have minimized the chance of this 
occurring.  
2.  Claustrophobia. Some people may experience claustrophobia (fear of confined 
spaces), while inside the scanner.  Once inside it is possible to stop the scanning 
and be removed at any time.  Patients will be given a squeezable device, a bulb, 
which serves as an “emergency” button.  The squeeze bulb will let MRI staff know 
immediately if the patient is experiencing claustrophobia, and they will terminate the 
scan. The MRI operators will be able to talk during the entire scanning process by 
two-way earphones and microphone communication system. Patients can also 
press a button inside the scanner to get their attention. 
3. Energy waves. Another risk is presented by the energy waves used in the 
scanner. The power of the energy waves is well below the strength needed to heat 
the tissue in your body and cause harm, but any metal in contact with patient skin 
could heat up. This is why patients will be asked to remove all jewelry.  
It is also possible that the scanner will cause peripheral nerve stimulation  
(stimulation of the nerves or muscles). If patients feel any tingling or unusual 

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sensations during the scan, or muscle contractions, they can use the squeeze bulb 
to alert the researcher immediately. 
4.  Loud Sounds. The MRI scanner makes loud banging noises during operation. 
Patients will be given earplugs to reduce the noise level. The noise generated by 
the operation of the scanner during a study is loud enough to cause hearing 
damage if patients do not wear hearing protection, which we will provide. If, even 
with the hearing protection we give patients, patients may find the noise from the 
scanner to be uncomfortable or painful, and can ask the scanner operator to stop 
the experiment immediately. 
5. In addition, there is a risk of unknown effects related to participation in T4 tesla 
level MRI research. Long-term effects of exposure to high magnetic fields are 
unknown. Short term most people experience no ill effects from the strong magnetic 
field, but some people report dizziness, mild nausea, headache, a metallic taste in 
their mouth, or sensations of flashing lights. 
6.  The risks of exposure to high magnetic fields are unknown for fetuses.  
Therefore, if the participant is a female who is capable of becoming pregnant, and 
has any reason to believe that they might be pregnant, they should not participate in 
this study. The effects of taking MRIs on an unborn baby have not yet been proven 
to be safe or unsafe. If they think they may be pregnant, they must inform the 
investigator. The investigators strongly recommend that participants do not 
participate in this study if the participant thinks that they may be pregnant. 
Participants are ultimately responsible for their own decision to participate or not to 
participate in this study. 
 Potential Benefits 
There are no direct benefits to participation. However, if anything abnormal is found 
and is considered to be a significant finding it will be reported to the patient’s 
surgeon prior to surgery. 

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2 OBJECTIVES 
2.1 
Study Objectives 
To demonstrate the efficacy of the MRI scanning in 3T and 4T MR magnet for patients 
with mandibular bone invasion. Comparison will be made to histolopathological sections 
as the “gold standard.” 
 
2.2 
Study Outcome Measures 
To determine how well the MR images will predict the presence of mandibular invasion, 
we will compare our results with clinical, operative, radiological and pathological findings 
(gold standard). Thus, patients will be asked to give permission to the investigators to 
access the relevant medical records. 

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3 STUDY DESIGN 
This is a cross-sectional study to be conducted at the University of Minnesota. For this 
study we will enroll patients with possible maxillofacial and/or mandibular bone invasion. 
Patients 18 and older with oral cancer or osteoradionecrosis will be recruited for the 
study prior to their surgery. Subjects will be identified by their physician while seeking 
care for oral cancer or osteoradionecrosis in the Otolaryngology/Head and Neck 
Surgery 
clinic. 
Eligible 
patients 
will 
be 
recruited 
and 
consented 
in 
the 
Otolaryngology/Head and Neck Surgery clinic during their scheduled appointment. This 
appointment will occur before the patient undergoes surgery for their oral cancer or 
osteoradionecrosis. Patients that are deemed eligible, after reviewing their medical 
records, will complete the CMRR subject safety screening questionnaire.  
All eligible and consented participants will have MRI scans obtained at the CMRR using 
the 3T and 4T magnet. Patients will also be asked to sign a HIPPA waiver allowing 
researchers to access their medical records including their clinical, operative, 
radiological and pathological findings. 

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4 STUDY ENROLLMENT AND WITHDRAWAL 
Patients 18 and older with oral cancer or osteoradionecrosis will be recruited for the 
study prior to their surgery. Subjects will be identified by their physician while seeking 
care for oral cancer or osteoradionecrosis in the Otolaryngology/Head and Neck 
Surgery 
clinic. 
Eligible 
patients 
will 
be 
recruited 
and 
consented 
in 
the 
Otolaryngology/Head and Neck Surgery clinic during their scheduled appointment. 
Consent will take place in the privacy of an exam room and consent will be obtained by 
a member of the research team that is familiar with the study. This appointment will 
occur before the patient undergoes surgery for their oral cancer. 
Patients will have the study explained to them, will be given a full explanation of the 
risks of the study and the measures that will be taken to minimize them. Only individuals 
involved with this study will be obtaining consent from patients. The research staff will 
explain that the study is optional and participation will not influence the participant’s 
treatment or relationship with the doctor of the University. 
At any time during the course of the study participants can withdraw their consent and 
terminate their participation.  
4.1 
Subject Inclusion Criteria 
1. Patients with a diagnosis of oral cancer with clinical or imaging findings 
suggestive of maxillofacial or mandibular bone invasion. OR 
2. Patients with a diagnosis of osteoradionecrosis 
3. Patients who will be undergoing surgery as treatment for their oral cancer. 
4. Age is over 18 years olf 

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Subject Exclusion Criteria 
1. Pregnancy 
2. Ferromagnetic implant 
3. History of shotgun wounds and shrapnel 
4. Obesity (>250 pounds) 
5. Cardiac pacemaker 
6. MR incompatible medical device 
7. Severe claustrophobia 
8. Surgeries with potential ferromagnetic implants 
9. Metallic ink tattoo in close proximity to area of interest. 
4.2 
Subject Withdrawal 
Subjects may withdraw voluntarily from the study or the investigator may terminate a 
subject's participation at any point during the course of the study 
4.2.1 
Reasons for Withdrawal 
Subjects are free to withdraw from participation in the study at any time upon request.  
An investigator may terminate a study subject’s participation in the study if: 
• Any medical condition, event or situation occurs such that continued participation 
in the study would not be in the best interest of the subject. 
• The subject meets an exclusion criterion (either newly developed or not 
previously recognized) that precludes further study participation.   
 
4.3 
Premature Termination or Suspension of Study 
This study may be suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party.  If the study is 
prematurely terminated or suspended, the principal investigator will promptly inform the 
IRB and will provide the reason(s) for suspension or termination. 
Circumstances that may warrant termination include, but are not limited to: 

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• Determination of unexpected, significant, or unacceptable risk to subjects. 
• Insufficient adherence to protocol requirements. 
• Data that are not sufficiently complete and/or evaluable.  
 

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5 STUDY SCHEDULE 
5.1 
Screening/ Prior to Enrollment 
• Review of medical records of any potentially eligible participants scheduled for a 
clinic visit. (Potentially eligible participants are also identified during tumor board.) 
• Discuss the identified potential participant with PI to ensure eligibility prior to 
approaching participant about study.  
• Introduce the study to the participant prior to their surgery. This usually needs to 
be done at least a week before surgery to ensure that the MRI can be scheduled.  
• Review medical history to determine eligibility based on inclusion/exclusion 
criteria.  
5.2 
Enrollment 
• Obtain and document consent from participant on study consent form and HIPAA 
authorization form. 
• Verify inclusion/exclusion criteria with surgeon.   
• Complete the CMRR Subject Safety Screening Questionnaire. The requirements 
of the CMRR Subject Safety Screening Questionnaire must be met prior to the 
participant’s MRI visit.  
• Review medical history with physician if indicated by CMRR Subject Safety 
Questionnaire (example: surgical implants, etc).   
• Schedule study visits with CMRR for individuals who are eligible and available for 
the duration of the study.   
• Provide potential participants with instructions needed to prepare for first study 
visit including directions to the CMRR at the University of Minnesota.  
• Contact participant the day before their study visit to confirm their participation.  
 
5.3 MRI Visit (Visit 1)  
• Review CMRR Subject Safety Screening Questionnaire to ensure that nothing 
has changed between enrollment and visit 1. If something has changed, check 
with CMRR staff to make sure participant is still eligible.  
• Review MRI procedure with participant and answer any final questions.  
• Target gift card is given to participant.  

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• CMRR staff will obtain MRI scans. The total time required for scanning will be 
about 1 hour 
 
 
. 

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6 STUDY PROCEDURES/EVALUATIONS 
6.1 
Study Procedures/Evaluations 
The subject will be taken to the room where the magnet is located. As MRI scanning is 
noisy, subjects will be given ear plugs and will be shown how to place them. Subjects 
will be asked to lie on his/her back on the scanner table. He/she will be moved into the 
magnet while lying on his/her back. Brief scans will be obtained (less than 1 minute) to 
localize the area of interest. We will then obtain longer MRI scans (around 5-15 minutes 
each). The total time required for scanning will be about 1 hour.    
6.2 
Questionnaire Administration 
Prior to obtaining the MRI images all participants will complete, with the research staff, 
the CMRR subject safety screening questionnaire.  

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7 ASSESSMENT OF SAFETY 
7.1 
Specification of Safety Parameters 
Safety monitoring for this study will focus on unanticipated problems involving risks to 
participants, including unanticipated problems that meet the definition of a serious 
adverse event.   
7.1.1 
Serious Adverse Events  
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
• Results in death 
• Is life-threatening (places the subject at immediate risk of death from the event 
as it occurred) 
• Results in inpatient hospitalization or prolongation of existing hospitalization 
• Results in a persistent or significant disability or incapacity 
• Results in a congenital anomaly or birth defect 
An important medical event that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, the event may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
7.2 
Reporting Procedures 
To satisfy the requirement for prompt reporting, unanticipated problems will be reported 
using the following timeline:  
• Unanticipated problems that are serious adverse events will be reported to the 
IRB within 1 week of the investigator becoming aware of the event.  
• Any other unanticipated problem will be reported to the IRB within 2 weeks of the 
investigator becoming aware of the problem.  

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8 STUDY OVERSIGHT 
The investigator will be responsible for study oversight, including monitoring safety, 
ensuring that the study is conducted according to the protocol and ensuring data 
integrity.  The PI will review the data for safety concerns and data trends at regular 
intervals, and will promptly report to the IRB any Unanticipated Problem (UP), protocol 
deviation, or any other significant event that arises during the conduct of the study.   

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9 ETHICS/PROTECTION OF HUMAN SUBJECTS 
9.1 
Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with the 
principles set forth in The Belmont Report: Ethical Principles and Guidelines for the 
Protection of Human Subjects of Research, as drafted by the US National Commission 
for the Protection of Human Subjects of Biomedical and Behavioral Research (April 18, 
1979) and codified in 45 CFR Part 46 and/or the ICH E6.   
9.2 
Institutional Review Board 
The protocol, informed consent form(s), recruitment materials and all participant 
materials will be submitted to the IRB for review and approval.  Approval of both the 
protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the 
changes are implemented in the study.   
9.3 
Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to 
participate in the study and continues throughout study participation.  Extensive 
discussion of risks and possible benefits of study participation will be provided to 
participants and their families, if applicable.  A consent form describing in detail the 
study procedures and risks will be given to the participant.  Consent forms will be IRB-
approved, and the participant is required to read and review the document or have the 
document read to him or her.  The investigator or designee will explain the research 
study to the participant and answer any questions that may arise.  The participant will 
sign the informed consent document prior to any study-related assessments or 
procedures.  Participants will be given the opportunity to discuss the study with their 
surrogates or think about it prior to agreeing to participate.  They may withdraw consent 
at any time throughout the course of the study.  A copy of the signed informed consent 
document will be given to participants for their records.  The rights and welfare of the 
participants will be protected by emphasizing to them that the quality of their clinical 
care will not be adversely affected if they decline to participate in this study. 
The consent process will be documented in the clinical or research record.   
Participant Confidentiality 
Participant confidentiality is strictly held in trust by the investigators, study staff, and the 
sponsor(s) and their agents.  The study protocol, documentation, data, and all other 
information generated will be held in strict confidence.  The study monitor or other 
authorized representatives of the sponsor may inspect all study documents and records 
required to be maintained by the investigator, including but not limited to, medical 
records (office, clinic, or hospital) for the study participants.  The clinical study site will 
permit access to such records.   

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10 DATA HANDLING AND RECORD KEEPING 
The investigators are responsible for ensuring the accuracy, completeness, legibility, 
and timeliness of the data reported.  All source documents should be completed in a 
neat, legible manner to ensure accurate interpretation of data.  The investigators will 
maintain adequate case histories of study participants, including accurate case report 
forms (CRFs), and source documentation.   
10.1 
Data Management Responsibilities 
Data collection and accurate documentation are the responsibility of the study staff 
under the supervision of the investigator.  All source documents must be reviewed by 
the study team and data entry staff, who will ensure that they are accurate and 
complete.  Unanticipated problems must be reviewed by the investigator or designee.   
10.2 
Study Records Retention 
Study records will be maintained for at least five years from the study close out.   
10.3 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical study protocol, Good Clinical 
Practice, or Manual of Procedures requirements.  The noncompliance may be on the 
part of the subject, the investigator, or study staff.  As a result of deviations, corrective 
actions are to be developed by the study staff and implemented promptly. 
 
 

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APPENDIX A: Schedule of Events 
 
Procedures 
Enrollment  
(Day –X to –Y) 
Study Visit 1  
(Day 0) 
Signed Consent Form 
X 
 
Assessment of Eligibility Criteria 
X 
 
Review of Medical History 
X 
 
Completion of CMRR safety  
X 
 
Review of CMRR Safety Form  
 
X 
MRI performed 
 
X