Non-Contrast 4DCT to Detect Pulmonary Thromboembolic Events

• Sponsor: Thomas Guerrero (Other)
• Overall Status: Completed
• CT.gov ID: NCT03183063
• Collaborator: (none)
• Enrollment: 139
• Location: 1
• Arms: 3
• Actual Duration (Months): 24.4
• Patients Per Site Per Month: 5.7

Study Details

Study Description

Brief Summary

Deep vein thrombosis (DVT) occurs when a blood clot forms in a deep vein, typically in the lower extremities. Pulmonary embolism (PE) occurs when a DVT clot (or fragment) breaks free and travels through the heart to the pulmonary arteries (having to do with the lungs) and lodges in an artery causing a partial or complete blockage. PE is difficult to diagnose due to the non-specific signs and symptoms patients have with this condition such as a cough, shortness of breath, increased heart rate, blood tinged sputum, low oxygen levels.

The standard test to diagnose PE is the Pulmonary Computed Tomography Angiogram (CTA). This can be prohibitive with some patients due to the amount of radiation exposure as well as the complications associated with the need to use intravenous (IV) contrast. In this study the investigators are looking at an alternative method of diagnosing PE's in the Emergency Department where the investigators look at the breathing and blood flow to the lungs thru respiratory gated non-contrast CT (commonly called 4DCT).

The investigators hypothesize that respiratory induced blood mass change in the lungs will allow the identification of under-perfused lung regions.

Cohort 1: An anticipated15 participants will be enrolled with a diagnosis of PE by CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Respiratory induced blood mass change images will be issued from the 4DCT and compared to the SPECT/CT images.

Cohort 2: An anticipated 5 participants will be enrolled under the same criteria and study procedures as Cohort 1. The participants in Cohort 2 will have the addition of Bilevel Positive Airway Pressure (BiPAP) during the 4DCT imaging. This cohort will be used to compare the effect of airway pressure on 4DCT image.

Cohort 3: An anticipated 124 participants will be enrolled. Study procedure will be 4DCT only. Participants must be having or have had a CTA to rule in/out PE. This cohort of the study will be using 4DCT to compare negative CTA to positive CTA findings.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Thromboembolisms; Pulmonary Embolism	Device: 4DCT and SPECT/CT; Device: 4DCT with BiPAP and SPECT/CT; Device: 4DCT with CTA in suspected PE	N/A

Detailed Description

The standard test to diagnose PE is the Pulmonary Computed Tomography Angiogram (CTA). This can be prohibitive with some patients due to the amount of radiation exposure as well as the complications associated with the need to use intravenous (IV) contrast. CTA can detect acute PE with a sensitivity of 99 percent and specificity of 95 percent when combined with CT venography. In patients not medically eligible for CTA, the other option for diagnosis is a ventilation-perfusion (V/Q) single photon emission computed tomography (SPECT) scan. Though this is often prohibitive due to transport to Nuclear Medicine dept., prolonged test time, no test during off hours, etc. In this study the investigators are looking at an alternative method of diagnosing PE's in the Emergency Department where the investigators look at ventilation and perfusion images thru respiratory gated non-contrast CT (commonly called 4DCT).

Technetium-99 m macroaggregated albumin (99mTc-MAA) imaged with single photon emission computed tomography (SPECT) is considered the standard method for the quantitative determination of pulmonary perfusion. Magnetic resonance imaging (MRI) with contrast agents have been utilized experimentally to image the pulmonary vasculature and tissue perfusion. Quantification of SPECT images requires correction of the acquired data for attenuation and attenuation correction, which has lead to the development of SPECT/CT scanners. The low-dose CT can be utilized to evaluate the lung airway architecture, lung parenchyma, and pleural space in conjunction with the registered perfusion images rivaling CTA in sensitivity and specificity.

In a study comparing CT attenuation with SPECT perfusion defects, patients were found to have hypo-attenuated pulmonary regions corresponding to regions with decreased perfusion in 57 percent of acute pulmonary emboli and 88 percent of chronic emboli cases. In the same study, hyper-attenuated regions were found to correspond to regions with hyperperfusion. A method to measure pulmonary perfusion based on subtraction digital fluoroscopy without contrast has been reported. In that study, subtraction images were generated between chest projection images at systole and diastole generating an image representing the perfusion difference. These perfusion projection images were correlate with 99mTc-MAA scintigraphy. Thus, changes in the amount and distribution of pulmonary perfusion throughout the respiratory cycle can be expected and these changes may be apparent on dynamic CT.

Simon described a technique to calculate the change in fractional content of air within pulmonary tissue between anatomically matched CT regions based on a simple model that assumes the density changes were solely due to air content. The investigators successfully applied that model to inhale and exhale breath-hold CT image pairs as well as 4DCT images to create ventilation images. However, the amount of blood in the thorax and lungs varies with the respiratory cycle, thus violating the assumption of this model. The investigators found a cyclic variation in the apparent weight of the lung on 4DCT and others have reported respiratory induced variations in pulmonary perfusion of the lung on MRI. The pulmonary density changes found on 4DCT thus result from both changes in air and blood content.

4DCT derived ventilation images can also be inferred from the respiratory motion induced local tissue volume changes independent of the 4DCT density values. The Jacobian determinant of the deformation field, calculated from the result of images depicting different respiratory phases of the lungs, is used to estimate the local volume changes or ventilation. There is a discrepancy between the density based and the Jacobian based ventilation images suggesting a method to extract respiratory induced blood mass change from 4DCT images. The investigators hypothesize the respiratory induced blood mass changed (RIBMC) will only occur within perfused lung regions. Each image set will contain information representing the density change resulting from both ventilation and RIBMC. Extracting both ventilation and perfusion-like image from the 4DCT image intensities, referred to as Hounsfield Units (HU) is our goal.

The investigators found a cyclic variation in the apparent mass of the pulmonary parenchyma. The investigators hypothesize this variation is due to changes in pulmonary perfusion from respiratory-induced variation in cardiac output. The investigators hypothesize this respiratory induced blood mass change (RIBMC) will allow the identification of hypoperfused lung regions. The investigators did a preliminary study by creating 4DCT RIBMC images from cases with hypoxia induced vasoconstriction, patients with malignant airway constriction. The resulting images compare well with 99mTc-MAA SPECT images. It is unknown, however, if this process works to detect perfusion defects due to PE where the perfusion is obstructed and breathing normal.

In this study patients found to have new segmental, lobar or greater perfusion defects, will be imaged with 99mTc-MAA SPECT/CT and 4DCT to compare perfusion with RIBMC defects. This is a prospective imaging trial of 20 subjects diagnosed by CTA.

An anticipated 15 subjects will be enrolled into Cohort 1 and each will receive 99mTc-MAA SPECT/CT and two (2) 4DCT imaging scans (back-to-back) on the same day. This data will be analyzed for objectives 1, 4 and 5.

An anticipated 5 subjects will be enrolled into Cohort 2 and they will also receive 99mTc-MAA SPECT/CT and two (2) 4DCT imaging scans (back-to-back) on the same day, with the first one being obtained with normal breathing as previously done and the second one being obtained with positive pressure breathing via BiPAP. Cohort 2 results will be analyzed for objective 6 only. Respiratory induced blood mass change (RIBMC) images will be derived from the 4DCT images and quantitatively compared with the SPECT perfusion images.

Cohort 3. The objective of this cohort of the study is to collect and process the image data necessary to assess the sensitivity and specificity of our 4DCT. We will conduct a prospective imaging study of an anticipated 124 patients who present with symptoms leading to a clinical concern for PE and who subsequently undergo chest CTA for further evaluation. One 4DCT before or after the CTA is the only study imaging in this cohort. Data from this cohort will be analyzed for objectives 2 and 3.

Subjects will be followed for a period of 48 hours after imaging for any adverse effects to the 99mTc-MAA.

The Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) will be used to grade all treatment-related adverse events. All Adverse Event (AE) effects will be reported to the Principal Investigator, who will determine the course of action for the study participant and will determine whether the AE affects the study and requires changes to the protocol and/or informed consent form.

Study Design

• Study Type: Interventional
• Actual Enrollment: 139 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Patients will be imaged with SPECT/CT and 4DCT to compare perfusion with the respiratory induced blood mass changed (RIBMC) defect. Each patient will have both imaging studies performed on the same day. 15 subjects will be enrolled into Cohort 1 and will receive SPECT/CT and 4DCT imaging as described. After those are enrolled another 5 subjects will be enrolled into Cohort 2 and will receive SPECT/CT and 4DCT imaging as previously described with the first 4DCT being obtained with normal breathing and the second scan being obtained with positive pressure breathing via BiPAP. Cohort 3 will enroll 124 participants with clinical suspicion of PE, who will be or have had CTA imaging. 4DCT imaging will be performed for these study participants.Patients will be imaged with SPECT/CT and 4DCT to compare perfusion with the respiratory induced blood mass changed (RIBMC) defect. Each patient will have both imaging studies performed on the same day. 15 subjects will be enrolled into Cohort 1 and will receive SPECT/CT and 4DCT imaging as described. After those are enrolled another 5 subjects will be enrolled into Cohort 2 and will receive SPECT/CT and 4DCT imaging as previously described with the first 4DCT being obtained with normal breathing and the second scan being obtained with positive pressure breathing via BiPAP. Cohort 3 will enroll 124 participants with clinical suspicion of PE, who will be or have had CTA imaging. 4DCT imaging will be performed for these study participants.
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Novel Method to Detect Pulmonary Thromboembolic Events With Non-Contrast 4DCT
• Actual Study Start Date: Apr 12, 2017
• Actual Primary Completion Date: Apr 23, 2019
• Actual Study Completion Date: Apr 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4DCT and SPECT/CT Anticipated 15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for objectives 1, 4 and 5.	Device: 4DCT and SPECT/CT; Each patient will receive two 4DCT followed by SPECT/CT.
Experimental: 4DCT with BiPAP and SPECT/CT Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only.	Device: 4DCT with BiPAP and SPECT/CT; Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT
Experimental: 4DCT with CTA in suspected PE Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for objectives 2 and 3.	Device: 4DCT with CTA in suspected PE; Each patient will receive 4DCT before or after CTA for suspected PE

Outcome Measures

Primary Outcome Measures

1. Correlation of 4DCT Identified Perfusion With SPECT/CT Identified Perfusion [1 hour]

   A custom automated PE detection algorithm will delineate hypo-perfused regions of interest (ROIs) on SPECT perfusion and ROIs on respiratory induced blood mass change (RIBMC) via SPECT/CT. Spatial overlap between hypo-perfused ROIs on SPECT perfusion (standard) and ROIs on RIBMC will be assessed using Dice similarity coefficient (DSC). Spearman correlation will be reported.

2. Count of Participants With True Positive Detection of PE Using Contrast-free 4DCT Functional Imaging and SPECT/CT (Sensitivity) [48 hours]

   For each case, an automated PE detection algorithm will determine if functional deficits exist within CT-V and RIBMC. The patient will be classified as PE positive if the algorithm confirms the presence of two or more mismatched segmental or subsegmental defects between CT-V and RIBMC images. This CT-functional imaging (CT-FI) binary classification indicator will be acquired for each patient and compared to the result from the standard acquired CTA. Data will be reported as the count of participants determined to have PE by both imaging modalities (true positives, specificity).

3. Count of Participants With True Negative Detection of PE Using Contrast-free 4DCT Functional Imaging (Specificity) [48 hours]

   For each case, an automated PE detection algorithm will determine if functional deficits exist within CT-V and RIBMC. The patient will be classified as PE negative if the algorithm cannot confirm the presence of two or more mismatched segmental or subsegmental defects between CT-V and RIBMC images. This CT-functional imaging (CT-FI) binary classification indicator will be acquired for each patient and compared to the result from the standard acquired CTA. Data will be reported as count of participants determined not to have PE by both imaging modalities (true negatives, sensitivity).

Secondary Outcome Measures

1. Measure and Correlate the 4DCT Re-imaging Variance in Radiographic Tidal Volume of RIBMC Images [1 hour]

   We will repeat the 4DCT process, obtaining two sets of images, and measure the change in radiographic tidal lung volume on RIBMC between the first and second 4DCT using data from subjects in Cohort 1 (4DCT and SPECT/T). Results are reported as percentage difference between the two scans.

2. Measure and Correlate the 4DCT Re-imaging Variance in Parenchymal Lung Mass of RIBMC Images [1 hour]

   We will repeat the 4DCT process, obtaining two sets of images, and measure the change in radiographic parenchymal lung mass on RIBMC between the first and second 4DCT using data from subjects in Cohort 1 (4DCT and SPECT/T). Results are reported as percentage difference between the two scans.

Other Outcome Measures

1. Measure and Correlate the Airway Pressure Variance of RIBMC Images [1 hour]

   An automated PE detection algorithm will detect differences of hypo-perfused regions of interest (ROIs) on 4DCT and deficit ROIs on RIBMC with normal breathing versus positive pressure airway via BiPAP breathing using Dice similarity coefficient (DSC).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with segmental or lobar pulmonary emboli on CTA identified within the past 48 hours

• May have initiated anticoagulation therapy

• Patients must sign informed consent to enter this study

• Documented not pregnant if child-bearing age woman

Exclusion Criteria:

• Patients unable to tolerate two 15-minute (4DCT) and one 30-minute imaging sessions (SPECT/CT) in the same day

• Unable to sign informed consent due to cognitive impairment or health status

• Patients who are unstable from a respiratory status requiring ICU care

• Patients who receive tissue plasminogen activator

• Patients who are <18 years old

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	William Beaumont Hospital	Royal Oak	Michigan	United States	48073

Sponsors and Collaborators

• Thomas Guerrero

Investigators

• Principal Investigator: Thomas Guerrero, MD, PhD, Beaumont Health

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 29, 2018

More Information

Additional Information:

• Abstract on 4DCT ventilation imaging

Publications

None provided.

• Responsible Party: Thomas Guerrero, Vice Chair Translational Research, Radiation Oncology, William Beaumont Hospitals
• ClinicalTrials.gov Identifier: NCT03183063
• Other Study ID Numbers: 2017-018
• First Posted: Jun 9, 2017
• Last Update Posted: Jun 5, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Pulmonary Embolism; Embolism; Thromboembolism

Study Results

Participant Flow

Arm/Group Title	4DCT and SPECT/CT	4DCT With BiPAP and SPECT/CT	4DCT With CTA in Suspected PE
Arm/Group Description	Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for objective 1, 4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for objectives 2, 3 and 4. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Period Title: Overall Study
STARTED	20	4	115
COMPLETED	15	0	111
NOT COMPLETED	5	4	4

Baseline Characteristics

Arm/Group Title	4DCT and SPECT/CT	4DCT With BiPAP and SPECT/CT	4DCT With CTA in Suspected PE	Total
Arm/Group Description	Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed from this cohort for outcomes 1, 4, and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Data will be analyzed from this cohort for outcome 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. Patients will be compared with Cohort 1 (4DCT and SPECT/CT) for objective 4 only.	Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. 62 with positive CTA results for PE and 62 with negative CTA results for PE will be included. Data will be analyzed from this cohort for outcomes 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE	Total of all reporting groups
Overall Participants	15	0	115	130
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53.8	58.5	57.433
Sex: Female, Male (Count of Participants)
Female	4 26.7%	64 Infinity	68 59.1%
Male	11 73.3%	51 Infinity	62 53.9%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%	115 Infinity	130 113%

Outcome Measures

1. Primary Outcome

Title	Correlation of 4DCT Identified Perfusion With SPECT/CT Identified Perfusion
Description	A custom automated PE detection algorithm will delineate hypo-perfused regions of interest (ROIs) on SPECT perfusion and ROIs on respiratory induced blood mass change (RIBMC) via SPECT/CT. Spatial overlap between hypo-perfused ROIs on SPECT perfusion (standard) and ROIs on RIBMC will be assessed using Dice similarity coefficient (DSC). Spearman correlation will be reported.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

Correlation coefficients were only calculated using the 15 subjects with documented PE in Cohort 1 (4DCT and SPECT/CT). All subjects in Cohort 2 (4DCT with BiPAP and SPECT/CT were withdrawn. Subjects in Cohort 3 (4DCT with CTA in suspected PE) were not analyzed for this outcome.

Arm/Group Title	4DCT and SPECT/CT	4DCT With BiPAP and SPECT/CT	4DCT With CTA in Suspected PE
Arm/Group Description	Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for outcomes 1,4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for outcomes 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Measure Participants	15	0	0
Median (Full Range) [Spearman correlation]	0.45

2. Primary Outcome

Title	Count of Participants With True Positive Detection of PE Using Contrast-free 4DCT Functional Imaging and SPECT/CT (Sensitivity)
Description	For each case, an automated PE detection algorithm will determine if functional deficits exist within CT-V and RIBMC. The patient will be classified as PE positive if the algorithm confirms the presence of two or more mismatched segmental or subsegmental defects between CT-V and RIBMC images. This CT-functional imaging (CT-FI) binary classification indicator will be acquired for each patient and compared to the result from the standard acquired CTA. Data will be reported as the count of participants determined to have PE by both imaging modalities (true positives, specificity).
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

This outcome was analyzed for 51 subjects in Cohort 3 (4DCT with CTA in suspected PE) identified as PE positive by SPECT/CT. All subjects in Cohort 2 (4DCT with BiPAP and SPECT/T) were withdrawn. Subjects in Cohort 1 (4DCT and SPECT/CT) were not analyzed for this objective.

Arm/Group Title	4DCT and SPECT/CT	4DCT With BiPAP and SPECT/CT	4DCT With CTA in Suspected PE
Arm/Group Description	Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for outcomes 1,4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for outcomes 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE.
Measure Participants	0	0	51
Count of Participants [Participants]	40 266.7%

3. Primary Outcome

Title	Count of Participants With True Negative Detection of PE Using Contrast-free 4DCT Functional Imaging (Specificity)
Description	For each case, an automated PE detection algorithm will determine if functional deficits exist within CT-V and RIBMC. The patient will be classified as PE negative if the algorithm cannot confirm the presence of two or more mismatched segmental or subsegmental defects between CT-V and RIBMC images. This CT-functional imaging (CT-FI) binary classification indicator will be acquired for each patient and compared to the result from the standard acquired CTA. Data will be reported as count of participants determined not to have PE by both imaging modalities (true negatives, sensitivity).
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

This outcome was analyzed for 60 subjects in Cohort 3 (4DCT with CTA in suspected PE) identified as PE negative by CTA. All subjects in Cohort 2 (4DCT with BiPAP and SPECT/T) were withdrawn. Subjects in Cohort 1 (4DCT and SPECT/CT) were not analyzed for this objective.

Arm/Group Title	4DCT and SPECT/CT	4DCT With BiPAP and SPECT/CT	4DCT With CTA in Suspected PE
Arm/Group Description	Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. This data will be analyzed for outcomes 1,4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. This data will be analyzed for outcomes 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Measure Participants	0	0	60
Count of Participants [Participants]	57 380%

4. Secondary Outcome

Title	Measure and Correlate the 4DCT Re-imaging Variance in Radiographic Tidal Volume of RIBMC Images
Description	We will repeat the 4DCT process, obtaining two sets of images, and measure the change in radiographic tidal lung volume on RIBMC between the first and second 4DCT using data from subjects in Cohort 1 (4DCT and SPECT/T). Results are reported as percentage difference between the two scans.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

Data was analyzed from the 15 participants in Cohort 1 (4DCT and SPECT/CT). All subjects were withdrawn from Cohort 2 (4DCT with BiPAP and SPECT/CT). Data was not analyzed for this objective for subjects in Cohort 3 (4DCT with CTA in suspected PE).

Arm/Group Title	4DCT and SPECT/CT	4DCT With BiPAP and SPECT/CT	4DCT With CTA in Suspected PE
Arm/Group Description	Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for objectives 1, 4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT	Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for objectives 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Measure Participants	15	0	0
Median (Full Range) [percentage difference of volume]	14.84

5. Secondary Outcome

Title	Measure and Correlate the 4DCT Re-imaging Variance in Parenchymal Lung Mass of RIBMC Images
Description	We will repeat the 4DCT process, obtaining two sets of images, and measure the change in radiographic parenchymal lung mass on RIBMC between the first and second 4DCT using data from subjects in Cohort 1 (4DCT and SPECT/T). Results are reported as percentage difference between the two scans.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

Data was analyzed from the 15 participants in Cohort 1 (4DCT and SPECT/CT). All subjects were withdrawn from Cohort 2 (4DCT with BiPAP and SPECT/CT). Data was not analyzed for this objective for subjects in Cohort 3 (4DCT with CTA in suspected PE).

Arm/Group Title	4DCT and SPECT/CT	4DCT With BiPAP and SPECT/CT	4DCT With CTA in Suspected PE
Arm/Group Description	Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for objectives 1, 4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT	Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for objectives 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Measure Participants	15	0	0
Median (Full Range) [percentage difference of mass]	18.23

6. Other Pre-specified Outcome

Title	Measure and Correlate the Airway Pressure Variance of RIBMC Images
Description	An automated PE detection algorithm will detect differences of hypo-perfused regions of interest (ROIs) on 4DCT and deficit ROIs on RIBMC with normal breathing versus positive pressure airway via BiPAP breathing using Dice similarity coefficient (DSC).
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

Data from cohort 2 (4DCT with BiPAP and SPECT/CT) was to be analyzed for this outcome; however, all subjects were withdrawn. Data is not available from Cohorts 1 (4DCT and SPECT/CT) and 3 ($DCT with CTA in suspected PE) for this outcome measurement.

Arm/Group Title	4DCT and SPECT/CT	4DCT With BiPAP and SPECT/CT	4DCT With CTA in Suspected PE
Arm/Group Description	Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for objectives 1, 4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT	Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for objectives 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Measure Participants	0	0	0

Adverse Events

Time Frame	48 hours
Arm/Group Title	4DCT and SPECT/CT		4DCT With BiPAP and SPECT/CT		4DCT With CTA in Suspected PE
Arm/Group Description	Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for objectives 1, 4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.		Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT		Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for objectives 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
All Cause Mortality
	4DCT and SPECT/CT		4DCT With BiPAP and SPECT/CT		4DCT With CTA in Suspected PE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/4 (0%)		0/115 (0%)
Serious Adverse Events
	4DCT and SPECT/CT		4DCT With BiPAP and SPECT/CT		4DCT With CTA in Suspected PE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/4 (0%)		0/115 (0%)
Other (Not Including Serious) Adverse Events
	4DCT and SPECT/CT		4DCT With BiPAP and SPECT/CT		4DCT With CTA in Suspected PE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/4 (0%)		0/115 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.