Non-Contrast 4DCT to Detect Pulmonary Thromboembolic Events
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | Cardiology, Cardiology, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 12/1/2018 |
| Start Date: | April 12, 2017 |
| End Date: | July 31, 2019 |
A Novel Method to Detect Pulmonary Thromboembolic Events With Non-Contrast 4DCT
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: 15 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: 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.
Cohort 3: 124 participants will be enrolled. Study procedure will be 4DCT only. Participants
must be having or have had a CTA to rule out PE. This cohort of the study will be using 4DCT
to compare negative CTA to positive CTA findings.
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: 15 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: 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.
Cohort 3: 124 participants will be enrolled. Study procedure will be 4DCT only. Participants
must be having or have had a CTA to rule out PE. This cohort of the study will be using 4DCT
to compare negative CTA to positive CTA findings.
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. 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. 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. Respiratory induced blood mass
change (RIBMC) images will be derived from the 4DCT images and quantitatively compared with
the SPECT perfusion images.
Subjects will be followed for a period of 48 hours after imaging for any adverse effects to
the 99mTc-MAA.
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 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.
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.
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. 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. 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. Respiratory induced blood mass
change (RIBMC) images will be derived from the 4DCT images and quantitatively compared with
the SPECT perfusion images.
Subjects will be followed for a period of 48 hours after imaging for any adverse effects to
the 99mTc-MAA.
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 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.
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.
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
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