Pilot Feasibility Study of Dynamic Contrast-enhanced Fluorescence Imaging to Guide Total Shoulder Arthroplasty Approach
Phase: NA
Conditions: Shoulder Pain, Shoulder Arthritis, Shoulder Arthroplasty
Sponsor: Dartmouth-Hitchcock Medical Center

PROTOCOL TITLE: Pilot feasibility study of dynamic contrast-enhanced fluorescence 
imaging to guide total shoulder arthroplasty approach
V. 29Dec2021
Page 1 of 21
PROTOCOL TITLE:
Pilot feasibility study of dynamic contrast-enhanced fluorescence imaging to guide total 
shoulder arthroplasty approach 
D-HH IRB OVERSIGHT:
One of the following must be true in order to submit to the D-HH IRB. Please check all 
that apply:
☒ The Principal Investigator is employed by D-H
☒ The study will utilize any D-H data or specimens
☒ The study will enroll D-H patients or recruit from D-H sites
☒ The study will utilize any D-H resources, e.g. study procedures will occur at 
     D-H locations and/or use of D-H equipment or shared resources
PRINCIPAL INVESTIGATOR:
John-Erik Bell, MD
Department of Orthopaedics
(603)650-5133
John-Erik.Bell@hitchcock.org
SCIENTIFIC CO-INVESTIGATOR:
Jonathan T. Elliott PhD
Department of Surgery
603 650-1910
Jonathan.T.Elliott@Hitchcock.org
SUB- INVESTIGATOR:
Corey Resnick, MD
Department of Orthopaedics
(603)650-5133
Corey.T.Resnick@hitchcock.org 
VERSION NUMBER/DATE:
Version 1: 12/29/2021

PROTOCOL TITLE: Pilot feasibility study of dynamic contrast-enhanced fluorescence 
imaging to guide total shoulder arthroplasty approach
V. 29Dec2021
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REVISION HISTORY
Revision 
#
Version Date
Summary of Changes
Consent 
Change?
Table of Contents
1.0
Study Summary ........................................................................................................4
2.0
Objectives* ...............................................................................................................5
3.0
Background*.............................................................................................................5
4.0
Study Endpoints*......................................................................................................5
5.0
Study Intervention/Investigational Agent.................................................................5
6.0
Procedures Involved* ...............................................................................................7
7.0
Data and Specimen Banking*...................................................................................8
8.0
Sharing of Results with Subjects* ............................................................................9
9.0
Study Timelines*......................................................................................................9
10.0
Inclusion and Exclusion Criteria* ............................................................................9
11.0
Vulnerable Populations*...........................................................................................9
12.0
Local Number of Subjects ......................................................................................10
13.0
Recruitment Methods..............................................................................................10
14.0
Withdrawal of Subjects*.........................................................................................10
15.0
Risks to Subjects*...................................................................................................11
16.0
Potential Benefits to Subjects* ...............................................................................11
17.0
Data Management* and Confidentiality.................................................................11
18.0
Provisions to Monitor the Data to Ensure the Safety of Subjects*.........................12
19.0
Provisions to Protect the Privacy Interests of Subjects ..........................................13
20.0
Compensation for Research-Related Injury............................................................14
21.0
Economic Burden to Subjects.................................................................................14
22.0
Consent Process......................................................................................................14
23.0
Process to Document Consent in Writing...............................................................17
24.0
Setting.....................................................................................................................17
25.0
Resources Available ...............................................................................................18
26.0
Multi-Site Research* ..............................................................................................18

PROTOCOL TITLE: Pilot feasibility study of dynamic contrast-enhanced fluorescence 
imaging to guide total shoulder arthroplasty approach
V. 29Dec2021
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1.0
Study Summary
Study Title
Pilot feasibility study of dynamic contrast-enhanced 
fluorescence imaging to guide total shoulder arthroplasty 
approach
Study Design
Cross sectional study
Primary Objective
To evaluate the feasibility of open wide-field imaging of 
indocyanine green ingress and egress during total shoulder 
arthroplasty.
Secondary 
Objective(s)
To characterize the relationship between tissue perfusion 
measured with DCE-FI and different approaches and 
techniques used in total shoulder arthroplasty.
Research 
Intervention(s)/ 
Investigational 
Agent(s) 
Assignment of research participants to subscapularis peel or 
tenotomy techniques utilized during total shoulder 
arthroplasty surgical approach. Indocyanine Green (ICG) 
indicated for soft-tissue perfusion assessment
IND/IDE # 
N/A
Study Population
Patients who are undergoing open surgery for shoulder 
arthroplasty
Sample Size
10 patients
Study Duration for 
individual 
participants
4-6 weeks
Study Specific 
Abbreviations/ 
Definitions 
AIF: arterial input function
CDC: Centers for Disease Control and Prevention 
CRF: Case Report Forms
DCE-FA: Dynamic Contrast Enhanced Fluorescence  
Arthroscopy
DCE-FI: Dynamic Contrast Enhanced Fluorescence Imaging
DoD: US Department of Defense
D-HH: Dartmouth-Hitchcock Health
DHMC: Dartmouth Hitchcock Medical Center 
FI: fluorescence imaging
GCP: Good Clinical Practice
GFR: glomerular filtration rate
HRPP: Human Research Protection  Program
ICG: Indocyanine Green
NSF: nephrogenic sclerosing fibrosis 
  PDD: Pulse Dye Densitometer
ROI: Region of interest
SSI: Surgical Site Infection

PROTOCOL TITLE: Pilot feasibility study of dynamic contrast-enhanced fluorescence 
imaging to guide total shoulder arthroplasty approach
V. 29Dec2021
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2.0
Objectives
The purpose of this pilot study is to evaluate the feasibility of open, wide-field imaging of 
indocyanine green ingress and egress during total shoulder arthroplasty.
The long-term goal of this work is to use DCE-FA for the assessment of subscapularis 
tendon perfusion and to determine potential relationships between perfusion and patient 
reported outcomes and subscapularis failure.
Primary Research Question:
To what degree does the relative perfusion of the subscapularis tendon—measured using 
DCE-FI—change after tenotomy vs peel technique and subsequent intra-operative repair? 
Hypothesis: Perfusion of the subscapularis tendon will be reduced from baseline after 
tenotomy and peel techniques during shoulder arthroplasty.
Secondary Question:
Does DCE-FI with indocyanine green, used in a real time, intra-operative setting, 
highlight technique-dependent variations in subscapularis tendon perfusion during 
shoulder arthroplasty?
Aim: To determine if intra-operative ICG administration during shoulder arthroplasty can 
be coupled with an intra-operative surgical fluorescence detection device to determine 
alterations in subscapularis tendon perfusion before and after repair using peel and 
tenotomy takedown techniques for a deltopectoral approach.
3.0
Background*
Shoulder arthroplasty is a commonly utilized and routinely successful surgery 
performed for management of glenohumeral joint arthritis. Upwards of 90% of 
primary anatomic total shoulder arthroplasty surgeries are considered successful 
(Lapner et al., 2020). Albeit rare, complications do occur. Complications include 
glenoid or humeral component loosening, periprosthetic fracture, infection and 
rotator cuff failure. Of the four muscles that comprise the rotator cuff, the 
subscapularis is of particular concern in total shoulder arthroplasty surgery due to 
the approach used to access the glenohumeral joint. The deltopectoral approach is 
the standard approach used for shoulder arthroplasty and necessitates performing 
a subscapularis takedown in order to obtain adequate visualization of the 
glenohumeral joint. Three techniques to perform a subscapularis takedown are 
common, with an absence of consensus in the literature as to which technique is 
superior (Buckley et al., 2014). The techniques include a subscapularis peel, a 
subscapularis tenotomy and a lesser tuberosity osteotomy. 

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Each subscapularis takedown technique requires repair at the conclusion of the 
procedure when performing shoulder arthroplasty. Repair is crucial for proper 
force coupling of the shoulder to keep the humeral head implant centered on the 
glenoid component (Shields et al., 2017). Takedown is still performed in a reverse 
total shoulder arthroplasty but repair is not required to maintain stability. Each 
takedown technique is reliant on either tendon to tendon, tendon to bone, or bone 
to bone interface for healing. Failure of the subscapularis tendon repair can result 
in pain, instability, decreased functional outcomes and ultimately the need for 
revision surgery (Choate et al., 2018). Subscapularis tendon failure can 
sometimes be asymptomatic, however it can also be symptomatic and present 
with the aforementioned signs. Subscapularis failure rates may approach 50% in 
long term studies although symptomatic cases likely occur in less than 1% of total 
shoulder arthroplasties (Entezari et al., 2020). Due to the devastating impact on 
patients with symptomatic subscapularis failure, there is interest in investigating 
which subscapularis takedown technique produces the best outcomes. Prior 
randomized controlled trials as well as systematic reviews have previously been 
conducted looking at these different takedown techniques, but demonstrated no 
statistically significant difference in primary endpoints of subscapularis strength 
at various time endpoint and no statistically significant difference in patient 
reported outcomes (Lapner et al., 2020). These prior studies did not evaluate 
subscapularis perfusion post repair, adequate perfusion is necessary for healing to 
occur with any subscapularis takedown technique.
The takedown method of the subscapularis has previously been shown to have no 
statistically significant differences with regards to strength, or patient reported 
outcomes, however if there was a difference noted in tendon perfusion post repair 
this may provide rationale to choose one technique over another as improved 
perfusion may correlate to lower risk of repair failure. As this study aims to 
monitor subscapularis perfusion pre and post repair, the two techniques that the 
involve the tendon itself for healing will be utilized, peel and tenotomy.
The indocyanine green based DCE-FI will NOT be used to guide treatment or 
patient care. The data acquired using the SPY Elite or SPY PHI or EleVision will 
be anonymized and exported to a secure PC for additional analysis and 
processing. The analysis techniques will be more sophisticated than the current 
commercial system, and involve a correction for the patient-specific arterial input 
function (AIF) (Elliott et al., 2020)—the cardiac and circulatory variations that 
can modify the time and manner in which the ICG dye arrives in the imaging 
field-of-view.
Indocyanine green (ICG) is a well-studied water soluble, light absorbing tracer 
that has been used in other capacities to help quantify tissue perfusion during 

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imaging to guide total shoulder arthroplasty approach
V. 29Dec2021
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surgery. ICG is able to be injected into a patient intravenously and subsequently 
circulate systemically while bound to albumin, quickly undergoing hepatic 
metabolism in just several minutes (Faybik and Hetz, 2006). The concentration of 
ICG in specific tissue is able to be quantified as a surrogate for tissue perfusion. 
ICG due to its IV administration and quick metabolism is able to help quantify 
perfusion in real time, such as intra-operatively (Lutken et al., 2021). Systemic 
reviews as well as case studies, most commonly in plastic surgery, have been 
performed showing its utility to determine adequate or inadequate perfusion in 
downstream tissue in situations where microanastomoses are performed, such as 
with flaps (Krishnan et al., 2005) and in hand surgery (Li et al., 2018). Other 
studies have also been conducted showing the ability to use ICG as a surrogate for 
tissue perfusion in the achilles paratenon in humans and in rabbits who had 
undergone rotator cuff repair to determine tissue perfusion after different types of 
repair. The use of ICG imaging in orthopaedic surgery is relatively nascent, and 
our institution (Gitajn et al., 2020) as well as other collaborators (Sepehri et al., 
2021) have demonstrated its promise in these applications.
4.0
Study Endpoints*
Primary end point:
To assess the technology and its ability to see blood supply in the subscapularis 
tendon before takedown and after employed repair. The benchmark for this is the 
rise and fall of fluorescence signal approximately 10-40 seconds after injection. 
Given our experience in DCE-FI for bone fractures, it will be more or less self-
evident whether the DCE-FA signal is sufficient for further analysis.
5.0
Study Intervention/Investigational Agent
5.1
Description:
This study is neither a drug nor a device trial. Patients will be administered FDA 
approved ICG through intravenous injection and imaged by a FDA approved 
surgical fluorescence imaging device (Spy Elite or SPY PHI or Medtronic 
EleVision) which is 0.5 meter away from the subject. Both ICG fluorescence 
and the imaging system have been used for routine clinical practice for many 
years. ICG fluorescence imaging utilizes intravenously injected ICG, which is a 
fluorescent dye that is FDA-approved for clinical use, illuminated with near-
infrared light. The ICG dye is indirectly activated and the dynamic fluorescence 
due to tendon perfusion can be captured by a video rate imaging system. The 
subscapularis takedown technique will alternate between tenotomy and peel for 
every other patient taken to the operating room. There is no reason 
intraoperatively to choose one technique over the other and therefore this puts 

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imaging to guide total shoulder arthroplasty approach
V. 29Dec2021
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the patient at no added risk. If the surgeon feels that neither of these techniques 
are appropriate for the treatment of the patient then the patient will not be 
approached for enrollment. 
5.2
Drug/Device Handling
Indocyanine green (ICG) used in this study will be ordered from the investigational 
pharmacy and supplied through the usual pharmacy dispensing mechanisms.
ICG is FDA approved for routine clinical practice in is currently available through the 
investigational pharmacy at DHMC. The results of this study are not intended to 
produce a new indication for the drug and will not be reported to the FDA. Nor will the 
results of this study significantly change the way that the drug is marketed in the United 
States. The medication will be utilized for an indication, and in a clinical setting, where 
it is currently utilized as part of usual care at this institution. ICG is lawfully marketed 
in the United States. The research will be conducted in compliance with the marketing 
limitations described in the FDA Code of Federal Regulations (21 CFR §312.7).ICG is 
FDA approved for routine clinical practice. No return or destruction of study drug is 
needed for this study.
The pulse dye densitometer (PDD) device used in this study is developed and tested by 
the Orthopaedics Translational Engineering Lab at DH. It is a modified pulse oximeter 
which is considered under the abbreviated IDE mechanism (see Section 6.2 for more 
information).
5.3
Dose Rationale
We plan a sample size of 10 patients in this open label prospective observational study of 
ICG fluorescence imaging for assessment of subscapularis tendon blood flow. 
After the subscapularis tendon is visualized during the surgical approach, 0.1 mg/kg ICG 
will be injected intravenously. Video rate ICG fluorescence images will be acquired 20 
seconds before and 4 minutes after ICG injection. This process will be repeated towards 
the end of the procedure after the subscapularis is repaired, but prior to skin closure.   
This dose has been used to effectively assess bone perfusion in a previous study at our 
institution which was an IRB-approved pilot study.  A total does of 0.2 mg/kg is within 
the range of previous studies. Indeed, this is 10 times less than the maximum 
recommended dose by FDA of 2 mg/kg. 
6.0
Procedures Involved*
The research design for this study is a single cohort longitudinal study employing a 
consecutive sampling methodology. Eligible patients regardless of ethnicity or health 

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imaging to guide total shoulder arthroplasty approach
V. 29Dec2021
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status, will be identified and recruited subject to inclusion and exclusion criteria listed in 
section 10.  Patients who meet eligibility criteria will be asked to participate in the trial.  
If they agree written informed consent will be obtained from the patient or their legal 
authorized representative. To obtain informed consent, study personnel (surgeon or 
research coordinator) will adhere to the following procedures: (1) present study 
information in a manner that is understandable to the patient; (2) discuss the study with 
the patient and answer any questions; (3) allow the patient an opportunity to discuss 
participation with their family; (4) confirm that the patient understands the risks and 
benefits of participating in the study and that their participation is voluntary; (5) complete 
the consent process and obtain signatures from the patient and research team.  The 
process of obtaining and documenting informed consent forms will be completed in 
accordance with local Good Clinical Practice (GCP) recommendations.
If the research team member obtaining consent is at all unsure about the patient's ability 
to consent, s/he will consult with the study PI.
Patients will be randomized to undergo either a subscapularis peel or subscapularis 
tenotomy. 
Recognizing that consent is an ongoing process, the study team will encourage the 
participants to ask additional questions that may arise during the course of their 
participation in the study.
On the surgery day, the patient will be prepared and transported to surgery as per routine 
at Dartmouth-Hitchcock. In the OR, patient positioning, preparation of the surgical field, 
and draping will follow standard practice for arthroplasty of the involved shoulder joint. 
A Pulse dye densometer (PDD; in-house developed), similar to a pulse oximetry probe, 
which is used clinically both in the operating room, in inpatients as well as outpatients to 
assess oxygen saturation.  This is completely non-invasive.  In the context of this study 
the pulse dye densometer collects data on the ICG injection parameters so that the kinetic 
curves can be normalized to injection-related differences. The PDD will be placed on the 
patient’s finger to acquire an arterial blood input function during ICG injection.  
After the subscapularis tendon is visualized during the surgical approach, 0.1 mg/kg ICG 
will be injected intravenously.  Video rate ICG fluorescence images will be acquired 20 
seconds before and 4 minutes after ICG injection. This process will be repeated towards 
the end of the procedure after the subscapularis is repaired, but prior to skin closure.   
ICG will be administered by an anesthetist in the operating room. Patients are under the 
care and observation of the anesthesia and surgical teams during this time.  Postoperatively, 
patients are transferred to the Post-Anesthesia Care Unit (PACU) where they are monitored 

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imaging to guide total shoulder arthroplasty approach
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continuously by nursing staff supervised by anesthesiologists.  During this entire time vital 
signs (including temperature, pulse, respiratory rate and blood pressure) are collected as 
standard of care.  All clinical data will be reviewed for adverse events for a period of 30 
minutes post-injection.
Day of surgery Procedures
Pre-
Infusion
0-30 
minutes 
post-
infusion
Pulse
X
X
Blood Pressure
X
X
Temperature
X
X
Respiratory Rate
X
X
Adverse Events
X
Study patients will be seen per usual protocol for wound assessment and general health 
assessment after their shoulder arthroplasty at approximately 4 weeks post operatively.
6.2 Pulse Dye Densitometry Device
A Pulse dye densometer (Pulsion Medical Systems), similar to a pulse oximetry probe, 
which is used clinically both in the operating room, in inpatients as well as outpatients to 
assess oxygen saturation. This is completely non-invasive. In the context of this study the 
pulse dye densometer collects data on the ICG injection parameters so that the kinetic 
curves can be normalized to injection-related differences. We have a manuscript that was 
submitted for publication recently demonstrating the importance of collecting this data.
Data obtained as part of this study will not be submitted to or held for inspection by the 
FDA. The device is a custom device and is not being used to determine safety or 
effectiveness for commercial distribution.
Exemption Status: The device used is being evaluated on an observational basis. 
However, it is not exempt due to the fact it introduces energy into the subject. We request 
an abbreviated IDE under 21 CFR 812, given it is a non-significant risk device.
Description: The device comprises of a single Texas Instruments AFE4490SPO2EVM 
connected to (1) a Microsoft surface (Windows OS) and a (2) Nihon-KodhenTL-301P 
finger probe. The TI AFE4490SPO2EVM is an evaluation board with analog front-end 
that allows control and digitization of detected signal from a pulse oximeter. These 
devices come with a standard 660nm/900nm pulse oximeter finger probe, however, the 
Nihon-Kodhen probe (805nm/900nm) is used instead. A custom interface is built to 

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imaging to guide total shoulder arthroplasty approach
V. 29Dec2021
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connect the NK probe (circular din connector) with the standard RS-232 connector on the 
TI board. The light produced by the NK probe is comparable to that of a pulse-oximeter 
and has a similar safety profile. The emission is well below the ANSI limits for skin 
exposure.
The IDE is not banned by the FDA, is labeled in accordance with FDA regulations and 
will not be marketed or promoted. The nature of the risk of the device is minimal. It does 
not present a potential for serious risk to the health, safety or welfare of the study subject. 
The device is not of substantial importance in diagnosing, curing, mitigating or treating 
disease. 
7.0
Data and Specimen Banking*
Not applicable
8.0
Sharing of Results with Subjects*
Results will not be shared with subjects or others associated with the subject’s medical 
care.
9.0
Study Timelines*
All patients will participate in the following events shown in the table below. Follow up 
visits will be conducted during standard postoperative clinical visits or over the phone.
Assessment
Visit 1:
Enrollment
Visit 2:
Surgery
Visit 3:
1 month
Eligibility Screening
●
Informed Consent
●
Collection of Demographic & Shoulder Pathology Data
●
Collection of Surgical Data (e.g. DCE-FI and AIF)
●
Collection of Peri-Operative Data (e.g., tHb and SaO2) 
●
Collection of Serious Adverse Events
●
●
●
We anticipate enrolling patients for 4-6 weeks for monitoring of serious adverse events. 
We anticipate completing preliminary analyses within about 6 months given the 
relatively small patient sample size and relatively high volume of total shoulder 
arthroplasty surgeries performed at Dartmouth-Hitchcock.
10.0
Inclusion and Exclusion Criteria*

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imaging to guide total shoulder arthroplasty approach
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The clinical schedule of the orthopaedic surgeon who is the principal investigator will be 
reviewed by members of the research team for eligible study participants. Identified 
patients who meet inclusion criteria for the study will be provided information about the 
study by the orthopaedic surgeon, or a qualified member of their care team, at the time of 
their pre-operative clinic visit. Patients who wish to participate in the study will then 
undergo an informed consent process for the study.
Inclusion criteria:
a.
Participant must be 18 years of age or older 
b. Meet clinical and radiographic parameters necessary to undergo shoulder 
arthroplasty
c.
Subscapularis tendon intact clinically on exam or via advanced imaging
d. Subject has the ability to have their shoulder arthroplasty completed using either the 
tenotomy or peel technique.
Exclusion criteria:
a.
Inability of patient to provide informed consent
b. Iodine allergy
c.
Subscapularis tendon tear or concern for tear
d. Incarceration
e.
Pregnant women
f.
Patients less than 18 years of age 
g. Prior deltopectoral approach to the ipsilateral shoulder 
11.0
Vulnerable Populations*
No Vulnerable patients will be enrolled in this study.
12.0
Local Number of Subjects
All 10 patients will be enrolled at this facility by the primary surgeon. This is a modest 
number of subjects to allow us to properly evaluate the feasibility of evaluating 
subscapularis tendon perfusion by two different takedown techniques in shoulder 
arthroplasty. 
13.0
Recruitment Methods 
Participation in this research requires informed consent according to Institutional Review 
Board (IRB) guidelines and a signed IRB-approved Consent Form as the means of 
documenting this understanding. 
Patients, 18 years of age or older who present to DHMC with shoulder arthritis who meet 
the inclusion criteria will be considered for enrollment. This study requests a partial waiver 

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imaging to guide total shoulder arthroplasty approach
V. 29Dec2021
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of HIPAA for recruitment purposes. The partial waiver would allow for the surgeon to share with 
the research coordinator the patient name, sex, MRN number, age, underlying conditions as well 
as type and location of injury. There is an adequate plan to protect identifiers from improper use 
and disclosure as information will only be used by study team members to determine whether a 
patient may be eligible. Information will only be communicated and stored using D-HH approved 
secure platforms. Information is only being used to determine if a patient is eligible for the study, 
for recruitment purposes. Once approached, if a patient is not interested, information will be 
destroyed. Protected health information will not be re-used or disclosed for another purpose. It 
will only be used for recruitment. This research could not practically be done without a partial 
waiver of HIPAA. This information is needed for recruitment. Patients will sign a full HIPAA 
Authorization when consenting to the study.
Upon identification, study personnel will screen the patient for eligibility and if eligible, 
the study will be introduced to the patient by a member of their care team. If the patient 
agrees, a member of the study team will approach them for informed consent. Screening 
will occur from the daily orthopaedic patient clinic schedule for the principle 
investigator. Study participants will be enrolled in the clinic setting prior to their surgical 
procedure. 
To obtain informed consent, study personnel will adhere to the following procedures: (1) 
present study information in a manner that is understandable to the patient; (2) discuss the 
study with the patient and answer any questions; (3) allow the patient an opportunity to 
discuss participation with their family; (4) confirm that the patient understands the risks 
and benefits of participating in the study and that their participation is voluntary; and (5) 
complete the consent process and obtain signatures from the patient and research team. 
The process of obtaining and documenting informed consent will be completed in 
accordance with Good Clinical Practice. 
Potential recruits are instructed that their participation is completely voluntary and that 
their medical care will not be altered in any way should they elect not to participate at 
any time prior to surgery. 
No advertisements or other promotional material will be used. No finder fees or 
recruitment incentives will be offered. 
There will be no honorarium or payment in association with this study.
14.0
Withdrawal of Subjects*
Participants will be removed from the protocol if:
1)
Concern for subscapularis tendon tear or insufficiency occurs.
2)
The subject withdraws consent.

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3)
The subject has an occurrence of a significant clinical event that precludes 
proceeding with surgery.
4)
Imaging cannot be completed for any reason
If a participant is withdrawn from the protocol, the PI will mark the data of this subject as 
"withdrawn" and will add a detailed explanation about the cause of withdrawal in the 
database. 
For subjects who withdraw after the intraoperative imaging, but prior to their first post 
operative appointment, we will follow-up to see if they still complete their clinical follow 
up at the 1-month interval, and provide them an opportunity to report any adverse events. 
We will acquire their follow up results to include these subjects in the statistical analysis 
portion that only involves the intraoperative image data and infection status.
15.0
Risks to Subjects*
The risks to subjects are minimal in relation to anticipated benefits and/or knowledge that 
might reasonably be expected from the results of this clinical trial.
Risk of ICG injection:  ICG (Indocyanine Green) will be administered intravenously 
twice: once before and once after the repair. ICG is FDA approved for human use in 
angiography for ophthalmology and cardiology applications and is given routinely to 
patients in these clinical settings. The risks are considered minimal and consist of nausea, 
vomiting, hives, increased heart rate in subjects with particular sensitivity to the dye. ICG 
does contain sodium iodide and patients with a history of allergy to iodides will be 
excluded. Anaphylactic or urticarial reactions are rare but have been reported in patients 
both with and without a history of allergy to iodides. Anaphylactic deaths have been 
reported following IGG administration during cardiac catheterization. Reported rates of 
mild, moderate and severe adverse reactions to ICG are 0.15%, 0.2% and 0.05%.  Every 
effort will be made to minimize this risk as much as possible.  It is the standard of care at 
this institution to obtain information related to allergies, sensitivities and past medical 
histories upon patient arrival.  Patients will also be monitored throughout their 
hospitalization, as is the standard of care, by everyone involved in their medical care for 
evidence of new or previously unknown reactions or sensitivities.  Additionally, at all 
times ICG fluorescence imaging assessments are taking place, both surgical and 
anesthesia staff will monitor patients closely for any adverse reaction to ICG. Surgical 
and anesthesia staff will also monitor patients for at least 30 minutes after all ICG 
fluorescence assessment procedures have been completed.  In the event of an unexpected 
allergic reaction, Dartmouth-Hitchcock Medical Center and all affiliated groups within 
this institution have procedures in place for managing patients with unknown or 
unexpected allergic reactions. If such a reaction were to occur, all standard of care 
treatments will be provided including but not limited to treatment with appropriate agents 

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imaging to guide total shoulder arthroplasty approach
V. 29Dec2021
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such as epinephrine, antihistamines and corticosteroids. Risk of infection from IV 
injection is also extremely rare but can occur. Pregnant women are excluded from the 
study. A pregnancy test is administered to women of child-bearing age.
Prolonged operating room time: Because the ICG fluorescence assessments will take 
place in the operating room, participation in this study may increase the amount of time 
spent under surgical anesthesia in the operating room.  For the average case, an additional 
10 minutes at most will be incurred.  However, the research staff will make every effort 
to minimize this risk by performing the assessment test while other required operative 
procedures are being performed.
Risk of confidentiality breach:  As with any protected health information, loss of 
privacy may lead to problems with insurability or social stigmatization.  The risk to 
subjects is low and members of the research team will make every effort to ensure that 
information is kept private and protected to the fullest extent possible. Any and all 
information will be stored and managed in a secure manner, following all applicable 
federal regulations and guidelines and according to institutional policies and practices.  
Any electronic information collected will be stored on password protected, HIPAA 
compliant computers maintained in private, locked offices within secure areas of 
Dartmouth-Hitchcock Medical Center with limited access.  Any non-electronic records 
collected will be stored likewise, as well.  Any discussions between patients and the 
research staff will be conducted in a private location.
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA). Risk of breach of confidentiality of the medical records and status of 
participants will be minimized. Databases which are used to store subject-sensitive 
information are password-protected and encrypted during file/data transfers from viewing 
terminals. Access will be limited to research team members who have undergone CPHS 
training at Dartmouth. Whenever possible and practical standard-of-care clinical data 
used in the research will be de-identified when under analysis.
16.0
Potential Benefits to Subjects*
Patients enrolling in this study will not benefit directly because no diagnostic or 
therapeutic decisions will occur based on the study, and thus, administration of the study 
is not intended to alter the surgical procedure. However, future patients may benefit from 
the knowledge gained from the study since this study may provide an objective, 
intraoperative, and real-time methodology to assess subscapularis tendon perfusion and 
potential for correlation to outcomes.
17.0
Data Management* and Confidentiality
Data Confidentiality:

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The use of PHI is necessary for the purposes of this research and the PI and 
investigational team will protect the confidentiality of the subjects through the following 
actions: 
Patients will be assigned a unique study identifier (study ID) based on the order in which 
they are recruited and a list of study IDs and the patients they correspond to (PHI) will be 
kept on a Dartmouth-Hitchcock secure server accessed by a DH laptop (the “H:/” drive). 
This is the only ‘key’ to matching patients and their corresponding study ID, and is only 
used to retrieve patient outcomes for the data analysis, and in the unlikely event that there 
is a reported adverse effect, to investigate the event.
A secured DH laptop will also store, in a separate document, a table containing the study 
date and anonymous study ID will be listed, along with any outcome information as it 
becomes available. This file will be kept separate from the file containing the study ID 
keys, to minimize the chance it will be inadvertently shared with unauthorized 
individuals.
The file containing the study IDs and which patients they correspond to (ID Key), will be 
destroyed once all outcomes have been recorded and/or the follow-up period has passed, 
unless required by the sponsor to maintain the information for an extended period of 
time. In that case, the ID Key will be destroyed at the earliest opportunity consistent with 
federal regulations.
Protected health information will not be reused or disclosed to any other person or entity, 
except as required by law, for authorized oversight of the research study, or for other 
research for which the use or disclosure of protected health information for which an 
authorization or opportunity to agree or object is not required by 45 CFR 164.512.
18.0
Provisions to Monitor the Data to Ensure the Safety of Subjects*
Since the PDD device does not meet the exempt criteria for an IDE, we request an 
abbreviated IDE determination from the IRB.  Kevin McGuire, MD will serve as 
an independent research monitor for this study. He has expertise consonant with 
the nature of the risks identified within the research protocol and meets all of the 
following criteria:
a) Is independent of the team conducting the research involving human 
subjects.
b) Can stop the research, remove individual subjects, and take steps to 
protect subjects until the IRB assesses the monitor’s report.

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c) Will promptly report observations and findings to the IRB or other 
designated official.
d) Has an IRB approved written summary of duties, authorities, and 
responsibilities based on specific risks or concerns about the research.
e) Has confirmed in writing his/her duties, authorities, and responsibilities
With regards to patient safety, ICG will be administered by an anesthetist in the operating 
room while they are being continuously monitored per anesthesia standard of care.  Post-
operatively, they are transferred to the Post-Anesthesia Care Unit (PACU) where they are 
monitored continuously by nursing staff supervised by anesthesiologists.  During this 
entire time vital signs (including temperature, pulse, respiratory rate and blood pressure) 
are collected as standard of care.  All clinical data will be reviewed for adverse events for 
a period of 30 minutes post-injection.
Day of surgery Procedures
Pre-
Infusion
0-30 
minutes 
post-
infusion
Pulse
X
X
Blood Pressure
X
X
Temperature
X
X
Respiratory Rate
X
X
Adverse Events
X
With regards to data monitoring, the program manager at D-H will be responsible for 
ensuring that all patient data is complete.  This will be monitored on a week-by-week 
basis and appropriate clinicians and/or research coordinators will be queried to complete 
incomplete patient data.
19.0
Provisions to Protect the Privacy Interests of Subjects
All identifying data will be kept in a restricted file on a secure DHMC server that can 
only be accessed by the PI and research coordinators. Participant data will also be entered 
in the "OnCore” database, which is a secure, password protected data collection system. 
Individual participants are assigned a random ID number within the OnCore database. 

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This database has restricted access, and the ability to view participant data is limited to 
specific members of the research team (e.g. PI and research coordinators). 
No information will be disclosed to others without written permission from the patient, 
except:     
• If necessary to protect the rights or welfare of the participant (for example, if the 
participant is injured and in need of emergency care); or    
 
• If required by law.
Any discussion between the patient and the research staff will be conducted in a private 
location. 
When the results of the research are published or discussed at conferences, no 
information will be included that would reveal participant identity. Authorized 
representatives of the D-HH IRB, Dartmouth College, and DHMC may need to review 
records of individual participants to ensure the accuracy of findings and to monitor the 
safety and welfare of study participants. The research imaging will not go into the 
patient’s medical record and will not be used for any clinical decision-making.
20.0
Compensation for Research-Related Injury
This is an imaging study with minimal risk. We do not anticipate any injury or sickness 
happen due to the study. If in any case subjects are injured or become ill as a result of 
research procedures, the subjects will be provided with medical treatment, but the 
following organizations do not plan to pay for this treatment.
•
Mary Hitchcock Memorial Hospital
•
Dartmouth-Hitchcock Clinic
•
Dartmouth-Hitchcock Medical Center 
•
Trustees of Dartmouth College
21.0
Economic Burden to Subjects
There are no additional costs that subjects will accrue in association with participating in 
this research.  All follow-up visits will be conducted during standard of care follow-up 
visits or over the phone.  Costs associated with the ICG and imaging device will be 
covered by the study and sponsor. They will not be billed to the patient.
22.0
Consent Process
To obtain informed consent, study personnel will adhere to the following procedures: 
(1) present study information in a manner that is understandable to the patient; (2) 
discuss the study with the patient and answer any questions; (3) allow the patient an 
opportunity to discuss participation with their family; (4) confirm that the patient 
understands the risks and benefits of participating in the study and that their participation 
is voluntary; and (5) complete the consent process and obtain signatures from the patient 
and research team. The process of obtaining and documenting informed consent will be 

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completed in accordance with Good Clinical Practice. If the research team member 
obtaining consent is at all unsure about the patient's ability to consent, s/he will consult 
with the study PI. 
Recognizing that consent is an ongoing process, the study team will encourage the 
participants to ask additional questions that may arise during the course of their 
participation in the study.
This study will not recruit non-English speaking subjects.  
This study will not involve any subject who is under age 18. 
The study team will comply with consent procedures outlined in SOP HRP-090. 
No cognitively impaired adults will be included in this study. 
No other vulnerable patient populations will be included in this study.
23.0
Process to Document Consent in Writing
To obtain informed consent, study personnel will adhere to the following procedures: (1) 
present study information in a manner that is understandable to the patient; (2) discuss the 
study with the patient and answer any questions; (3) allow the patient an opportunity to 
discuss participation with their family; (4) confirm that the patient understands the risks 
and benefits of participating in the study and that their participation is voluntary; and (5) 
complete the consent process and obtain signatures from the patient and research team.  
The process of obtaining and documenting informed consent will be completed in 
accordance with Good Clinical Practice, outlined by the SOP HRP-090. The signed 
consent form will be uploaded to DHMC EDH.
24.0
Setting
All consenting will be carried out in the outpatient clinic in the orthopedic department.  
Imaging for tendon perfusion will occur within the surgical suites at DHMC. All 
necessary patient follow-up with be conducted at the outpatient clinic. The data 
processing will be carried out by research staff within the administrative offices of the 
Orthopaedics Department located on level 5 of the Rubin building.   
25.0
Resources Available
The Department of Orthopaedics at DHMC, is a level 1 tertiary care academic medical 
center, and has a robust research infrastructure.  Research will be performed within the 
Orthopedic Surgery Department in the Rubin building, as well as in outpatient 

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Orthopaedic clinics.  All research personnel have been thoroughly trained and have been 
involved in multiple orthopaedic research studies. The Orthopaedic surgeons have 
weekly meetings to address any issues that arise during the process of care as well as any 
issues with ongoing research projects.   While the medical and psychological risks from 
the study are minimal, and we do not anticipate any medical or psychological resources 
being needed for subjects enrolled in this study, should the need arise, subjects will be 
treated in accordance with usual standard of care for any medical or psychological issues, 
including but not limited to medical management, counselling, and appropriate 
consultation/referral.  
All persons, including clinicians, faculty members, staff and students assisting with the 
research will receive instruction regarding the protocol, their duties and functions directly 
from the Principal Investigator.  Additionally all research staff are trained before 
engaging in any activities in accordance with Dartmouth- Hitchcock policies for 
conducting research under Good Clinical Practices and have completed Collaborative 
Institutional Training Initiative (CITI) research ethics and compliance training.
26.0
Multi-Site Research*
Not applicable. We will only be enrolling patients from Dartmouth-Hitchcock.
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