<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03261479</url>
  </required_header>
  <id_info>
    <org_study_id>2016P000864</org_study_id>
    <nct_id>NCT03261479</nct_id>
  </id_info>
  <brief_title>Validation of Thermal Imaging to Detect Pneumonia</brief_title>
  <official_title>Validation of Thermal Imaging to Detect Pneumonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are proposing a two-stage, prospective, cohort study of 138 subjects &gt; 28&#xD;
      days old and &lt; 18 years old with respiratory distress, already getting a chest x-ray as part&#xD;
      of their routine clinical care, who will get thermal pictures of their chest at the&#xD;
      Massachusetts General Hospital (MGH) Emergency Department, Pediatric Wards, and Pediatric&#xD;
      Intensive Care Unit. The thermal cameras will measure skin temperature, by taking a picture,&#xD;
      in a non-contact way. The investigators will recruit 138 patients using the FLIR ONE thermal&#xD;
      imaging camera for iPhone and the newly designed irPNA application. The FLIR ONE thermal&#xD;
      imaging camera will be attached to a study-designated iPhone which will only have the ability&#xD;
      to take pictures. This phone will not have the capability to make calls or use the internet.&#xD;
      The iPhone will be password protected, as encrypted by Partners regulations. Demographic and&#xD;
      diagnostic data will be collected from patient charts.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      I. BACKGROUND AND SIGNIFICANCE&#xD;
&#xD;
        1. Historical Background&#xD;
&#xD;
           Every day 16,000 children under the age of 5-years die. Although strides have been made&#xD;
           in early diagnosis and treatment of pneumonia, it still accounts for about 15% of deaths&#xD;
           of children under 5-years (1). Unfortunately care providers in low- and middle-income&#xD;
           countries (LMICs) are limited due to lack of resources and training. Chest x-rays are&#xD;
           especially difficult to obtain in these LMICs (14). Ironically, smartphones are readily&#xD;
           available. Since its development in 1960, Forward-Looking Infrared (FLIR) cameras have&#xD;
           made several technological strides. Notably they are now more affordable and compact,&#xD;
           attaching to smartphones. FLIR cameras now have the potential to aid in early diagnosis&#xD;
           and subsequent treatment of childhood pneumonia.&#xD;
&#xD;
           FLIR imaging was first developed in 1956 with military funding at the University of&#xD;
           Chicago. From the 1960s into the 1970s, FLIR technology was modified independently by&#xD;
           both the Air Force and Texas Instruments Inc. for use by military planes (2). Wendell&#xD;
           Smith first documented the use of thermal imaging in medical diagnosis in 1964. Smith&#xD;
           required 6 minutes to take each thermograph of the horses he was studying (3). Multiple&#xD;
           veterinary studies have been performed since then, and now thermal imaging has been&#xD;
           validated as a means to assess musculoskeletal injuries in animals (4,5).&#xD;
&#xD;
        2. Previous Clinical Studies Supporting the Proposed Research&#xD;
&#xD;
           Interestingly, very few clinical studies have been performed to validate the use of&#xD;
           thermal imaging in medical diagnosis for human diseases. The use of thermography to&#xD;
           diagnose lung disease was studied in Russia in 1976, 1981, and 1991 in three separate&#xD;
           studies, but these studies were neither controlled nor randomized (6-8). In 1970 Potanin&#xD;
           demonstrated through a case series that patients with pneumonia had increased overlying&#xD;
           chest temperatures and patients with pulmonary embolism had decreased overlying chest&#xD;
           temperatures (12). The most recent and impactful study evaluating pneumonia with thermal&#xD;
           imaging was a case series performed by Wiecek et al. (2001), which showed that patients&#xD;
           with pneumonia demonstrated a reduction in thermographic signal as they positively&#xD;
           responded to treatment (13). More modern studies have attempted to validate infrared&#xD;
           thermal imaging in measuring the size of brain tumors intra-operatively (9), screening&#xD;
           for fever in children (10), and predicting length of recuperation after burn injuries&#xD;
           (11), among others. However, there has not been a modern study validating thermal&#xD;
           imaging in diagnosing pneumonia.&#xD;
&#xD;
        3. Rationale behind Proposed Research and Potential Benefit to Society&#xD;
&#xD;
      Pneumonia is one of the primary contributors to under-five mortality worldwide. Imaging to&#xD;
      support the diagnosis of pneumonia can be very difficult to obtain in resource-limited&#xD;
      settings due to lack of equipment and trained staff. Easy-to-access imaging of pneumonia with&#xD;
      thermal imaging technology may allow practitioners to diagnose pneumonia earlier and more&#xD;
      accurately, which would lead to decreased morbidity and mortality. In LMICs where x-ray&#xD;
      availability is already limited in peripheral centers, excessive use of these facilities can&#xD;
      lead to consumption of limited medical resources. Validating thermal imaging in the diagnosis&#xD;
      of pneumonia would likely lead to cost savings, and obviation of side effects of&#xD;
      antimicrobials and excessive radiation.&#xD;
&#xD;
      II. SPECIFIC AIMS:&#xD;
&#xD;
        1. To determine whether the FLIR ONE camera can be used to detect differences in a&#xD;
           temperature spectrum that is clinically applicable. Temperature as measured by a&#xD;
           temporal artery thermometer on hospitalized patients can vary from less than 96°&#xD;
           Fahrenheit to over 104° Fahrenheit. The basis of the FLIR ONE camera and the irPNA&#xD;
           application is to detect asymmetry of temperatures. The investigators hope to&#xD;
           demonstrate that this technology has the capability to demonstrate this difference.&#xD;
&#xD;
        2. To validate thermal imaging with the FLIR ONE camera and irPNRA application as a&#xD;
           sensitive modality to diagnose pneumonia. The investigators hope to demonstrate that&#xD;
           there are few false negatives when using this modality to diagnose pneumonia.&#xD;
&#xD;
        3. To validate thermal imaging with the FLIR ONE camera and irPNRA application as a&#xD;
           specific modality to differentiate pneumonia from other pulmonary processes, such as&#xD;
           asthma, pulmonary embolism, and bronchiolitis. The investigators hope to demonstrate&#xD;
           that there are few false positives when using this modality to diagnose pneumonia.&#xD;
&#xD;
           III. SUBJECT SELECTION:&#xD;
&#xD;
             1. Inclusion/Exclusion Criteria&#xD;
&#xD;
                Inclusion criteria are 1) patients 28-days to 17-years of age, 2) who have&#xD;
                respiratory distress, and 3) who receive a chest x-ray. The investigators will&#xD;
                exclude patients with known chronic lung disease.&#xD;
&#xD;
             2. Source of Samples&#xD;
&#xD;
           The investigators will acquire consent from patients and parents in the Pediatric&#xD;
           Intensive Care Unit, (PICU) Pediatric Emergency Department (ED), and Pediatric Wards at&#xD;
           the Massachusetts General Hospital&#xD;
&#xD;
           IV. SUBJECT ENROLLMENT:&#xD;
&#xD;
             1. Methods of Enrollment&#xD;
&#xD;
                Trained clinical research staff will be present in the MGH PICU, pediatric wards,&#xD;
                and ED and identify potential subjects through providers. Additionally, the EPIC&#xD;
                electronic medical record system will be used by qualified research staff (research&#xD;
                assistants, coordinators, managers) to electronically identify patients who may be&#xD;
                potential candidates for the study. Subjects having a chest x-ray taken will be&#xD;
                approached for study participation. This study will not interfere with the&#xD;
                subject's medical care.&#xD;
&#xD;
                If a patient appears to be eligible, the patient's provider will first approach the&#xD;
                subject and ask if they are willing to be approached about a research study. If the&#xD;
                potential subject declines, no further attempts will be made to enroll the subject.&#xD;
                If the subject agrees to speak to someone about research, a study staff member will&#xD;
                approach him or her about participation.&#xD;
&#xD;
                Recruitment will not involve restrictions on socio-demographic factors including&#xD;
                ethnic characteristics. Recruitment will be devoid of any procedures, which could&#xD;
                be construed as coercive.&#xD;
&#xD;
             2. Procedures for Obtaining Informed Consent&#xD;
&#xD;
                At enrollment, in a private room, the investigator/designee will obtain written&#xD;
                informed consent from participants' parent(s) or guardian for this study. During&#xD;
                this encounter, the investigators will remind participants that they are free to&#xD;
                choose to take part in the research or not. The investigators will use a General&#xD;
                Consent Form for the parents/guardians of the patients. Children 14-17 can provide&#xD;
                assent by co-signing the General Template consent form when able. The investigators&#xD;
                will obtain Assent from the subjects verbally, when possible.&#xD;
&#xD;
             3. Treatment Assignment and Randomization&#xD;
&#xD;
           Treatments or changes in the health care plan will not be made based on this research.&#xD;
&#xD;
           V. STUDY PROCEDURES:&#xD;
&#xD;
             1. Study Parameters to be Measured&#xD;
&#xD;
                In addition to obtaining thermal images with the FLIR ONE camera, The investigators&#xD;
                will obtain several patient data points. These include 1) chief complaint, 2)&#xD;
                temporal artery temperature, 3) cutaneous temperature, 4) ambient temperature, 5)&#xD;
                respiratory rate, 6) oxygen saturation, 7) chest x-ray results and relevant data,&#xD;
                8) discharge diagnosis, and 9) disposition. Additional chest x-rays will not be&#xD;
                obtained, the investigators will use x-rays already procured as part of the patient&#xD;
                diagnosis and treatment approach and plan.&#xD;
&#xD;
             2. Drugs to be Used&#xD;
&#xD;
                None&#xD;
&#xD;
             3. Devices to be Used&#xD;
&#xD;
                FLIR ONE camera, attached to an encrypted iPhone. The investigators will also use&#xD;
                the irPNRA application on the iPhone designed by research team member Jim Lewis to&#xD;
                help direct the thermal imaging. The iPhone is encrypted by Partners regulations&#xD;
                and cannot connect to a phone network or the Internet. The iPhone will remain in&#xD;
                'airplane mode' at all times. Biomed has already investigated and approved these&#xD;
                devices.&#xD;
&#xD;
             4. Procedures/Surgical Interventions&#xD;
&#xD;
                None&#xD;
&#xD;
             5. Data to be Collected and when the Data is to be Collected&#xD;
&#xD;
           The investigators will obtain FLIR ONE thermal images within 4 hours of the subject's&#xD;
           chest x-ray. The investigators will also collect the following data: 1) chief complaint,&#xD;
           2) temporal artery temperature, 3) cutaneous temperature, 4) ambient temperature, 5)&#xD;
           respiratory rate, 6) oxygen saturation, 7) chest x-ray results and relevant data, 8)&#xD;
           discharge diagnosis, and 9) disposition. The vitals will be obtained at the time nearest&#xD;
           to the chest x-ray.&#xD;
&#xD;
           Patient data will be collected prior to being de-identified. The investigators will use&#xD;
           the patient name and medical record number to access their chart in the EMR. Then the&#xD;
           following data will be obtained from the chart: 1) chief complaint, 2) temporal artery&#xD;
           temperature, 3) cutaneous temperature, 4) ambient temperature, 5) respiratory rate, 6)&#xD;
           oxygen saturation, 7) chest x-ray results and relevant data, 8) discharge diagnosis, and&#xD;
           9) disposition. The x-rays will be obtained, uploaded to the LifeImage application,&#xD;
           de-identified, and then sent to the radiologist on our research team with the&#xD;
           appropriate study ID. The patient information will then be de-identified and replaced&#xD;
           with a study ID.&#xD;
&#xD;
           VI. BIOSTATISTICAL ANALYSIS:&#xD;
&#xD;
             1. Specific Data Variables to be Collected&#xD;
&#xD;
                The investigators will collect the following variables from the patient chart: 1)&#xD;
                chief complaint, 2) temporal artery temperature, 3) cutaneous temperature, 4)&#xD;
                ambient temperature, 5) respiratory rate, 6) oxygen saturation, 7) chest x-ray&#xD;
                results and relevant data, 8) discharge diagnosis, and 9) disposition.&#xD;
&#xD;
                The investigators will collect the following identifiers from the patient record&#xD;
                prior to de-identifying them: 1) name, 2) DOB, 3) age, 4) gender, and 5) MRN.&#xD;
&#xD;
                Interpretation of the x-rays will be blinded. The x-rays will be uploaded to&#xD;
                LifeImage, de-identified, and then sent to the radiologist on our research team.&#xD;
                The de-identified x-ray images will then be evaluated by the radiologist.&#xD;
&#xD;
             2. Study Endpoints&#xD;
&#xD;
                The investigators will assess for temperature asymmetry with the FLIR ONE thermal&#xD;
                camera with images taken of the chest. The investigators will compare these results&#xD;
                with the results of a chest x-ray taken within the last 12 hours.&#xD;
&#xD;
             3. Statistical Methods&#xD;
&#xD;
                The investigators will compare chest x-ray results to FLIR ONE thermal imaging&#xD;
                results. The investigators will use sensitivity and specificity calculations based&#xD;
                on the positive and negative results from those studies.&#xD;
&#xD;
             4. Power Analysis&#xD;
&#xD;
           Using the standard α = 0.05, sample size = 31, observed false positive (TI+|CXR-) rate&#xD;
           =0.38 and the observed false negative (TI-|CXR+) rate = 0.20, the power (β-1) for the&#xD;
           test applied to the overall population was calculated at 0.26. In order to achieve a&#xD;
           power of 0.80 with the conditions encountered in this study, The investigators would&#xD;
           require 138 patients.&#xD;
&#xD;
           VII. RISKS AND DISCOMFORT:&#xD;
&#xD;
             1. Complications of Surgical/Non-Surgical Procedures&#xD;
&#xD;
                None&#xD;
&#xD;
             2. Drug Side Effects and Toxins&#xD;
&#xD;
                None&#xD;
&#xD;
             3. Device Complications and Malfunctions&#xD;
&#xD;
                The FLIR ONE device is a thermal camera that attaches to an iPhone. Complications&#xD;
                of the device will not affect the patient. If it malfunctions, the investigators&#xD;
                will fix or replace it.&#xD;
&#xD;
             4. Psychosocial (non-medical) Risks&#xD;
&#xD;
                The risk of loss of confidentiality will be minimized by using study IDs on study&#xD;
                documentation to identify subjects. The list linking the study subjects to the&#xD;
                study IDs will be kept in a secure location, with access limited only to staff&#xD;
                directly involved with the research study.&#xD;
&#xD;
             5. Radiation Risks&#xD;
&#xD;
           There are no known radiation risks. As mentioned above, only x-rays obtained as part of&#xD;
           the patient diagnostic and treatment plans will be used. No additional x-rays will be&#xD;
           taken.&#xD;
&#xD;
           VIII. POTENTIAL BENEFITS:&#xD;
&#xD;
             1. Potential Benefits to Participating Individuals&#xD;
&#xD;
                Participants will not receive any direct benefit from their participation in the&#xD;
                study.&#xD;
&#xD;
             2. Potential Benefits to Society&#xD;
&#xD;
           Worldwide, pneumonia is one of the leading causes of mortality in children in the first&#xD;
           5 years of life. In both developed countries and resource poor settings, detection of&#xD;
           bacterial pathogens by culturing blood or other specimens is time consuming, lacks&#xD;
           sensitivity and ranges from difficult in the U.S. to impossible in the developing world.&#xD;
           In the U.S., the inability to determine which children have a bacterial infection&#xD;
           results in excessive use of antibiotics and increased risk of infection with multi-drug&#xD;
           resistant organisms. In the developing world, the consequences are delays in timely&#xD;
           initiation of antibiotic therapy and excessive referral of children for hospitalization&#xD;
           that overwhelms referral facilities. Regardless of setting, there is an urgent need for&#xD;
           point of care diagnostics to determine which children likely have bacterial pneumonia&#xD;
           and will benefit from administration of antibiotics.&#xD;
&#xD;
           Furthermore, aiding diagnosis of pneumonia with thermal imaging may obviate chest x-rays&#xD;
           as the primary diagnostic tool and reduce unnecessary exposure of patients to radiation.&#xD;
           In the PICU and the Wards, it is not uncommon that some patients require daily or even&#xD;
           more frequent chest x-rays. If The investigators are able to validate thermal imaging as&#xD;
           a tool to detect pneumonia, the investigators could potentially minimize the radiation&#xD;
           exposure of these patients.&#xD;
&#xD;
           IX. MONITORING AND QUALITY ASSURANCE:&#xD;
&#xD;
             1. Independent Monitoring of Source Data&#xD;
&#xD;
                Given the relatively small size of this study and the lack of an investigational&#xD;
                agent, there will not be a data and safety monitoring committee set up for the&#xD;
                purpose of evaluating data and safety of the participants. The principal&#xD;
                investigator, as well as the Partners IRB, shall provide oversight and review of&#xD;
                the study protocol throughout the duration of the study.&#xD;
&#xD;
             2. Safety Monitoring&#xD;
&#xD;
                There will be no official safety monitoring. The investigators anticipate the risks&#xD;
                of participation in this research study to be minimal.&#xD;
&#xD;
             3. Outcomes Monitoring&#xD;
&#xD;
                There will be no outcomes monitoring. Treatments or changes in the health care plan&#xD;
                will not be made based on this research.&#xD;
&#xD;
             4. Adverse Event Reporting Guidelines&#xD;
&#xD;
           The principal investigator will review all reports of safety or other concerns within 24&#xD;
           hours of being notified and communicate these to the IRB as per Partners IRB policy&#xD;
           &quot;Reporting Unanticipated Problems Including Adverse Events&quot;. The investigators will not&#xD;
           require a DSMB for this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Research stopped after lab-based data using mouse model did not support use of technology.&#xD;
  </why_stopped>
  <start_date type="Actual">April 13, 2016</start_date>
  <completion_date type="Actual">June 1, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Presence of pneumonia</measure>
    <time_frame>1 year</time_frame>
    <description>Compare identification of pneumonia in thermal image to x-rays read by study radiologists</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical diagnosis</measure>
    <time_frame>1 year</time_frame>
    <description>Compare identification of pneumonia in thermal image to diagnosis of clinical team</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">22</enrollment>
  <condition>Pneumonia</condition>
  <arm_group>
    <arm_group_label>Respiratory distress</arm_group_label>
    <description>Inclusion criteria are 1) subjects 28-days to 17-years of age, 2) who have respiratory distress, and 3) who receive a chest x-ray. We will exclude subjects with known chronic lung disease.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Thermal image</intervention_name>
    <description>We will take a non-invasive thermal image with the FLIR ONE thermal imaging camera that attaches to a study-designated iPhone.</description>
    <arm_group_label>Respiratory distress</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects evaluated in the emergency department, pediatric wards, or intensive care unit for&#xD;
        respiratory distress&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients 28-days to 17-years of age&#xD;
&#xD;
          -  respiratory distress&#xD;
&#xD;
          -  receive a chest x-ray&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  known chronic lung disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>28 Days</minimum_age>
    <maximum_age>17 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Ryan Carroll, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Physician</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ryan MD Carroll</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <last_update_submitted>November 10, 2020</last_update_submitted>
  <last_update_submitted_qc>November 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Ryan Carroll</investigator_full_name>
    <investigator_title>Assistant Pediatrician</investigator_title>
  </responsible_party>
  <keyword>pneumonia</keyword>
  <keyword>thermal imaging</keyword>
  <keyword>respiratory distress</keyword>
  <keyword>x-ray</keyword>
  <keyword>thermal</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03261479
org study id: 2016P000864
nct id: NCT03261479
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The investigators are proposing a two-stage, prospective, cohort study of 138 subjects > 28
      days old and < 18 years old with respiratory distress, already getting a chest x-ray as part
      of their routine clinical care, who will get thermal pictures of their chest at the
      Massachusetts General Hospital (MGH) Emergency Department, Pediatric Wards, and Pediatric
      Intensive Care Unit. The thermal cameras will measure skin temperature, by taking a picture,
      in a non-contact way. The investigators will recruit 138 patients using the FLIR ONE thermal
      imaging camera for iPhone and the newly designed irPNA application. The FLIR ONE thermal
      imaging camera will be attached to a study-designated iPhone which will only have the ability
      to take pictures. This phone will not have the capability to make calls or use the internet.
      The iPhone will be password protected, as encrypted by Partners regulations. Demographic and
      diagnostic data will be collected from patient charts.
I. BACKGROUND AND SIGNIFICANCE

        1. Historical Background

           Every day 16,000 children under the age of 5-years die. Although strides have been made
           in early diagnosis and treatment of pneumonia, it still accounts for about 15% of deaths
           of children under 5-years (1). Unfortunately care providers in low- and middle-income
           countries (LMICs) are limited due to lack of resources and training. Chest x-rays are
           especially difficult to obtain in these LMICs (14). Ironically, smartphones are readily
           available. Since its development in 1960, Forward-Looking Infrared (FLIR) cameras have
           made several technological strides. Notably they are now more affordable and compact,
           attaching to smartphones. FLIR cameras now have the potential to aid in early diagnosis
           and subsequent treatment of childhood pneumonia.

           FLIR imaging was first developed in 1956 with military funding at the University of
           Chicago. From the 1960s into the 1970s, FLIR technology was modified independently by
           both the Air Force and Texas Instruments Inc. for use by military planes (2). Wendell
           Smith first documented the use of thermal imaging in medical diagnosis in 1964. Smith
           required 6 minutes to take each thermograph of the horses he was studying (3). Multiple
           veterinary studies have been performed since then, and now thermal imaging has been
           validated as a means to assess musculoskeletal injuries in animals (4,5).

        2. Previous Clinical Studies Supporting the Proposed Research

           Interestingly, very few clinical studies have been performed to validate the use of
           thermal imaging in medical diagnosis for human diseases. The use of thermography to
           diagnose lung disease was studied in Russia in 1976, 1981, and 1991 in three separate
           studies, but these studies were neither controlled nor randomized (6-8). In 1970 Potanin
           demonstrated through a case series that patients with pneumonia had increased overlying
           chest temperatures and patients with pulmonary embolism had decreased overlying chest
           temperatures (12). The most recent and impactful study evaluating pneumonia with thermal
           imaging was a case series performed by Wiecek et al. (2001), which showed that patients
           with pneumonia demonstrated a reduction in thermographic signal as they positively
           responded to treatment (13). More modern studies have attempted to validate infrared
           thermal imaging in measuring the size of brain tumors intra-operatively (9), screening
           for fever in children (10), and predicting length of recuperation after burn injuries
           (11), among others. However, there has not been a modern study validating thermal
           imaging in diagnosing pneumonia.

        3. Rationale behind Proposed Research and Potential Benefit to Society

      Pneumonia is one of the primary contributors to under-five mortality worldwide. Imaging to
      support the diagnosis of pneumonia can be very difficult to obtain in resource-limited
      settings due to lack of equipment and trained staff. Easy-to-access imaging of pneumonia with
      thermal imaging technology may allow practitioners to diagnose pneumonia earlier and more
      accurately, which would lead to decreased morbidity and mortality. In LMICs where x-ray
      availability is already limited in peripheral centers, excessive use of these facilities can
      lead to consumption of limited medical resources. Validating thermal imaging in the diagnosis
      of pneumonia would likely lead to cost savings, and obviation of side effects of
      antimicrobials and excessive radiation.

      II. SPECIFIC AIMS:

        1. To determine whether the FLIR ONE camera can be used to detect differences in a
           temperature spectrum that is clinically applicable. Temperature as measured by a
           temporal artery thermometer on hospitalized patients can vary from less than 96°
           Fahrenheit to over 104° Fahrenheit. The basis of the FLIR ONE camera and the irPNA
           application is to detect asymmetry of temperatures. The investigators hope to
           demonstrate that this technology has the capability to demonstrate this difference.

        2. To validate thermal imaging with the FLIR ONE camera and irPNRA application as a
           sensitive modality to diagnose pneumonia. The investigators hope to demonstrate that
           there are few false negatives when using this modality to diagnose pneumonia.

        3. To validate thermal imaging with the FLIR ONE camera and irPNRA application as a
           specific modality to differentiate pneumonia from other pulmonary processes, such as
           asthma, pulmonary embolism, and bronchiolitis. The investigators hope to demonstrate
           that there are few false positives when using this modality to diagnose pneumonia.

           III. SUBJECT SELECTION:

             1. Inclusion/Exclusion Criteria

                Inclusion criteria are 1) patients 28-days to 17-years of age, 2) who have
                respiratory distress, and 3) who receive a chest x-ray. The investigators will
                exclude patients with known chronic lung disease.

             2. Source of Samples

           The investigators will acquire consent from patients and parents in the Pediatric
           Intensive Care Unit, (PICU) Pediatric Emergency Department (ED), and Pediatric Wards at
           the Massachusetts General Hospital

           IV. SUBJECT ENROLLMENT:

             1. Methods of Enrollment

                Trained clinical research staff will be present in the MGH PICU, pediatric wards,
                and ED and identify potential subjects through providers. Additionally, the EPIC
                electronic medical record system will be used by qualified research staff (research
                assistants, coordinators, managers) to electronically identify patients who may be
                potential candidates for the study. Subjects having a chest x-ray taken will be
                approached for study participation. This study will not interfere with the
                subject's medical care.

                If a patient appears to be eligible, the patient's provider will first approach the
                subject and ask if they are willing to be approached about a research study. If the
                potential subject declines, no further attempts will be made to enroll the subject.
                If the subject agrees to speak to someone about research, a study staff member will
                approach him or her about participation.

                Recruitment will not involve restrictions on socio-demographic factors including
                ethnic characteristics. Recruitment will be devoid of any procedures, which could
                be construed as coercive.

             2. Procedures for Obtaining Informed Consent

                At enrollment, in a private room, the investigator/designee will obtain written
                informed consent from participants' parent(s) or guardian for this study. During
                this encounter, the investigators will remind participants that they are free to
                choose to take part in the research or not. The investigators will use a General
                Consent Form for the parents/guardians of the patients. Children 14-17 can provide
                assent by co-signing the General Template consent form when able. The investigators
                will obtain Assent from the subjects verbally, when possible.

             3. Treatment Assignment and Randomization

           Treatments or changes in the health care plan will not be made based on this research.

           V. STUDY PROCEDURES:

             1. Study Parameters to be Measured

                In addition to obtaining thermal images with the FLIR ONE camera, The investigators
                will obtain several patient data points. These include 1) chief complaint, 2)
                temporal artery temperature, 3) cutaneous temperature, 4) ambient temperature, 5)
                respiratory rate, 6) oxygen saturation, 7) chest x-ray results and relevant data,
                8) discharge diagnosis, and 9) disposition. Additional chest x-rays will not be
                obtained, the investigators will use x-rays already procured as part of the patient
                diagnosis and treatment approach and plan.

             2. Drugs to be Used

                None

             3. Devices to be Used

                FLIR ONE camera, attached to an encrypted iPhone. The investigators will also use
                the irPNRA application on the iPhone designed by research team member Jim Lewis to
                help direct the thermal imaging. The iPhone is encrypted by Partners regulations
                and cannot connect to a phone network or the Internet. The iPhone will remain in
                'airplane mode' at all times. Biomed has already investigated and approved these
                devices.

             4. Procedures/Surgical Interventions

                None

             5. Data to be Collected and when the Data is to be Collected

           The investigators will obtain FLIR ONE thermal images within 4 hours of the subject's
           chest x-ray. The investigators will also collect the following data: 1) chief complaint,
           2) temporal artery temperature, 3) cutaneous temperature, 4) ambient temperature, 5)
           respiratory rate, 6) oxygen saturation, 7) chest x-ray results and relevant data, 8)
           discharge diagnosis, and 9) disposition. The vitals will be obtained at the time nearest
           to the chest x-ray.

           Patient data will be collected prior to being de-identified. The investigators will use
           the patient name and medical record number to access their chart in the EMR. Then the
           following data will be obtained from the chart: 1) chief complaint, 2) temporal artery
           temperature, 3) cutaneous temperature, 4) ambient temperature, 5) respiratory rate, 6)
           oxygen saturation, 7) chest x-ray results and relevant data, 8) discharge diagnosis, and
           9) disposition. The x-rays will be obtained, uploaded to the LifeImage application,
           de-identified, and then sent to the radiologist on our research team with the
           appropriate study ID. The patient information will then be de-identified and replaced
           with a study ID.

           VI. BIOSTATISTICAL ANALYSIS:

             1. Specific Data Variables to be Collected

                The investigators will collect the following variables from the patient chart: 1)
                chief complaint, 2) temporal artery temperature, 3) cutaneous temperature, 4)
                ambient temperature, 5) respiratory rate, 6) oxygen saturation, 7) chest x-ray
                results and relevant data, 8) discharge diagnosis, and 9) disposition.

                The investigators will collect the following identifiers from the patient record
                prior to de-identifying them: 1) name, 2) DOB, 3) age, 4) gender, and 5) MRN.

                Interpretation of the x-rays will be blinded. The x-rays will be uploaded to
                LifeImage, de-identified, and then sent to the radiologist on our research team.
                The de-identified x-ray images will then be evaluated by the radiologist.

             2. Study Endpoints

                The investigators will assess for temperature asymmetry with the FLIR ONE thermal
                camera with images taken of the chest. The investigators will compare these results
                with the results of a chest x-ray taken within the last 12 hours.

             3. Statistical Methods

                The investigators will compare chest x-ray results to FLIR ONE thermal imaging
                results. The investigators will use sensitivity and specificity calculations based
                on the positive and negative results from those studies.

             4. Power Analysis

           Using the standard α = 0.05, sample size = 31, observed false positive (TI+|CXR-) rate
           =0.38 and the observed false negative (TI-|CXR+) rate = 0.20, the power (β-1) for the
           test applied to the overall population was calculated at 0.26. In order to achieve a
           power of 0.80 with the conditions encountered in this study, The investigators would
           require 138 patients.

           VII. RISKS AND DISCOMFORT:

             1. Complications of Surgical/Non-Surgical Procedures

                None

             2. Drug Side Effects and Toxins

                None

             3. Device Complications and Malfunctions

                The FLIR ONE device is a thermal camera that attaches to an iPhone. Complications
                of the device will not affect the patient. If it malfunctions, the investigators
                will fix or replace it.

             4. Psychosocial (non-medical) Risks

                The risk of loss of confidentiality will be minimized by using study IDs on study
                documentation to identify subjects. The list linking the study subjects to the
                study IDs will be kept in a secure location, with access limited only to staff
                directly involved with the research study.

             5. Radiation Risks

           There are no known radiation risks. As mentioned above, only x-rays obtained as part of
           the patient diagnostic and treatment plans will be used. No additional x-rays will be
           taken.

           VIII. POTENTIAL BENEFITS:

             1. Potential Benefits to Participating Individuals

                Participants will not receive any direct benefit from their participation in the
                study.

             2. Potential Benefits to Society

           Worldwide, pneumonia is one of the leading causes of mortality in children in the first
           5 years of life. In both developed countries and resource poor settings, detection of
           bacterial pathogens by culturing blood or other specimens is time consuming, lacks
           sensitivity and ranges from difficult in the U.S. to impossible in the developing world.
           In the U.S., the inability to determine which children have a bacterial infection
           results in excessive use of antibiotics and increased risk of infection with multi-drug
           resistant organisms. In the developing world, the consequences are delays in timely
           initiation of antibiotic therapy and excessive referral of children for hospitalization
           that overwhelms referral facilities. Regardless of setting, there is an urgent need for
           point of care diagnostics to determine which children likely have bacterial pneumonia
           and will benefit from administration of antibiotics.

           Furthermore, aiding diagnosis of pneumonia with thermal imaging may obviate chest x-rays
           as the primary diagnostic tool and reduce unnecessary exposure of patients to radiation.
           In the PICU and the Wards, it is not uncommon that some patients require daily or even
           more frequent chest x-rays. If The investigators are able to validate thermal imaging as
           a tool to detect pneumonia, the investigators could potentially minimize the radiation
           exposure of these patients.

           IX. MONITORING AND QUALITY ASSURANCE:

             1. Independent Monitoring of Source Data

                Given the relatively small size of this study and the lack of an investigational
                agent, there will not be a data and safety monitoring committee set up for the
                purpose of evaluating data and safety of the participants. The principal
                investigator, as well as the Partners IRB, shall provide oversight and review of
                the study protocol throughout the duration of the study.

             2. Safety Monitoring

                There will be no official safety monitoring. The investigators anticipate the risks
                of participation in this research study to be minimal.

             3. Outcomes Monitoring

                There will be no outcomes monitoring. Treatments or changes in the health care plan
                will not be made based on this research.

             4. Adverse Event Reporting Guidelines

           The principal investigator will review all reports of safety or other concerns within 24
           hours of being notified and communicate these to the IRB as per Partners IRB policy
           "Reporting Unanticipated Problems Including Adverse Events". The investigators will not
           require a DSMB for this study.
observational model: Cohort
time perspective: Prospective
measure: Presence of pneumonia
time frame: 1 year
description: Compare identification of pneumonia in thermal image to x-rays read by study radiologists
measure: Clinical diagnosis
time frame: 1 year
description: Compare identification of pneumonia in thermal image to diagnosis of clinical team
arm group label: Respiratory distress
description: Inclusion criteria are 1) subjects 28-days to 17-years of age, 2) who have respiratory distress, and 3) who receive a chest x-ray. We will exclude subjects with known chronic lung disease.
intervention type: Diagnostic Test
intervention name: Thermal image
description: We will take a non-invasive thermal image with the FLIR ONE thermal imaging camera that attaches to a study-designated iPhone.
arm group label: Respiratory distress
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 28 Days
maximum age: 17 Years
last name: Ryan Carroll, MD
role: Principal Investigator
affiliation: Physician
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Ryan Carroll
investigator title: Assistant Pediatrician
mesh term: Pneumonia
sharing ipd: No